Ctii F16 PDF

Chemical
Thinking
Volume II
University of Arizona
Chemical Thinking
Preface
The chemical thinking curriculum introduces an alternative way of conceptualizing the introduc-
tory chemistry curriculum for science and engineering majors. The curriculum has been designed
with the following goals in mind:
• Present chemistry as a powerful way of thinking rather than as a static body of knowledge
• Use essential questions in the discipline to guide the presentation and discussion of relevant
content
• Emphasize conceptual understanding of core concepts and ideas in chemistry
• Build student understanding through carefully designed learning progressions based on exist-
ing research in chemistry education
• Offer many opportunities for students to engage with core concepts and ideas through activi-
ties that ask them to analyze data, model chemical systems, and generate evidence-based
explanations
• Create opportunities for students to demonstrate and self-assess their understanding via the
application of their knowledge and skills in solving relevant integrated problems
• Engage students in thinking about important issues in four critical areas of interest for the
science and technology of the 21st century: energy sources, environmental issues, life and
medicine, and materials by design
• Take advantage of diverse educational tools that allow students to explore chemical ideas and
phenomena in interactive ways
The chemical thinking curriculum has been developed, tested, and implemented at the University
of Arizona. We thank all the students, instructors, and educational staff that had made it possible.
The project was initially funded by the National Science Foundation (DUE-0736844).
Vicente Talanquer
John Pollard
Chemical Thinking II
Contents
U5. How do we predict chemical change? 280
M1. Analyzing structure.....................................................................282
M2. Comparing free energies............................................................296
M3. Understanding mechanism.........................................................314
M4. Measuring rates..........................................................................328
U6. How do we control chemical processes? 350

M1. Characterizing interactions.........................................................352
M2. Influencing chemical equilibrium...............................................368
M3. Analyzing chemical stability.......................................................384
U7. How do we harness chemical energy? 412

M1. Controlling electron transfer......................................................414

U8. How do we synthesize substances? 434
M1. Analyzing processes....................................................................436
UNIT 5
How do we
predict
chemical
change?
Our ability to synthesize new chemical compounds or to con-
trol chemical processes depends on how well we can predict
the extent and rate of chemical reactions based on the analysis
of the composition and structure of the substances involved.
Our predictions may be enhanced by making use of experi-
mental information about key properties of the reactants and
products.
To predict the likelihood of a chemical reaction we need to

study the directionality, extent, mechanism, and rate of the
process. Of these four factors, directionality and extent are de-
termined by thermodynamic properties of the substances involved,
while mechanism and rate are associated with kinetic properties.
The central goal of this Unit is to help you identify and apply the
four different factors that help predict the likelihood of chemical
reactions. To illustrate these ideas, we will analyze processes that
may have played a central role in the origin of life on Earth.
280
Chemical Thinking
UNIT 5 MODULES
M1. Analyzing Structure
Comparing the thermodynamic stability of
reactants and products.
M2. Comparing Free Energies
Quantifying the directionality and extent of
chemical reactions.
M3. Understanding Mechanism
Analyzing the changes that lead from reactants
to products.
M4. Measuring Rates
Exploring changes in the concentration of re-
actants and products as a function of time.
281
282
Analyzing
Structure
There are multiple reasons to be interested in why and how chemical reactions oc-
U5: MODULE 1
cur. For example, we may want to predict whether a new polymers used to make
bottles will produce toxic substances by reacting with the
[Share Alike 3.0] via Wikimedia Commons

liquids they contain. We may be interested in predicting
whether the combustion products of a new type of gaso-
By Laitr Keiows (Own work)

line will react with other substances in the atmosphere.
We may want to identify the types of chemical reactions
that led to the formation of the basic components of life
on Earth. In all these cases, we want to determine the
extent to which a given chemical process occurs as well as
the rate at which the reaction proceeds. Some chemical
Rusting is a slow
processes may occur to a great extent (i.e., reactants are process but occurs to
almost completely converted into products) but at such slow rate that a great extent
the probability of observing the process will be very small. In other

cases, the extent of the reaction may be limited but the process could be so fast
that it is cost-effective for producing the substances that we want.
Chemists use a variety of approaches to predict the extent and rate of chemical
reactions. In Module 1, we will learn to recognize the compositional and structural
features of reactants and products that can be used to make qualitative predictions
about the direction in which chemical processes are likely to occur.
THE CHALLENGE Primitive Combinations

Nitrogen gas, N2(g), and hydrogen gas, H2(g), are suspected to be two im-
portant components of the primitive Earth. These two substances could have
reacted to form ammonia NH3(g) in the atmosphere.
• How would you go about predicting whether N2(g) and H2(g) will com-
bine to form NH3(g)?
• What factors must be considered when making this prediction?
Share and discuss your ideas with one of your classmates.
This module will help you develop the type of chemical thinking that is used
to answer questions similar to those posed in the challenge. In particular, the cen-
tral goal of Module 1 is to learn to predict reaction directionality based on the
relative thermodynamic stability of reactants and products.
Chemical Thinking U5 How do we predict chemical change? 283
Chemical Stability
Not every combination of substances will lead to the formation of new compounds
via a chemical reaction. How can we predict when a chemical process takes place?
One approach could be to compare the relative stability of reactants and products.
We might expect that chemical reactions will proceed in the direction in which
more stable substances are formed. However, for this strategy to work we need to
clearly define what we mean by “stability” and we need to identify the composi-
tional and structural features that can be used to evaluate the relative stability of
different substances.

In general, chemists distinguish between two types of chemical stability, called
By Einar Helland Berger (Own work)

thermodynamic stability and kinetic stability. Thermodynamic stability is a mea-
sure of how stable a system is with respect to changes in the surroundings, such as
changes in temperature and pressure, or to the addition of new components. The
greater the thermodynamic stability of a substance, the less likely it is to change
to a different state or to react with other substances. On the other hand, kinetic
stability is a measure of how long it would take for a system to reach a more stable
state without external intervention. Although the reaction between two substances
may be favored because it would lead to the formation of more thermodynami-
cally stable products, the process may take a long time to occur without external Figure 5.1 Mixtures of
common fuels (e.g., meth-
intervention because the reactants are kinetically stable (Figure 5.1). ane, wood, glucose) with
Kinetic stability is affected by the value of the activation energy Ea needed to oxygen tend to be thermo-
dynamically unstable but
initiate a process; this quantity determines the rate of the reaction but not its di- kinetically stable.
rectionality. On the other hand, thermodynamic stability is affected by energetic
and entropic factors:
• Energetic Factors influence the internal potential energy of a substance due to
interactions between its submicroscopic components (i.e., electrons, atoms, ions,
molecules);
• Entropic Factors influence the number of different configurations in which the
submicroscopic components of the substance may exist.
These two types of factors determine the directionality and extent of the chemical
process. In Module 1, we will focus our attention on the analysis of compositional
and structural features of chemical substances that can be used to judge their rela-
tive thermodynamic stability. This type of analysis is useful in making predictions
about the direction in which a chemical reaction may occur.
Directionality? LET’S THINK

Consider the following chemical processes:
2 H2(g) + O2(g) 2 H2O(l) 2 H2O(l) 2 H2(g) + O2(g)
• Which compositional and structural features of reactants and products may affect
which of these two processes is more likely to take place? Identify features that
can affect the potential energy of the molecules involved (energetic factors) as
well as the number of configurations they can adopt (entropic factors).
Share and discuss your ideas with a classmate, and clearly justify your reasoning.
284 MODULE 1 Analyzing Structure
Energetic Factors
Chemical substances in which their submicroscopic components interact strongly
tend to have low internal potential energies and to be more thermodynamically
stable. Thus, paying attention to compositional and structural features such as
bond strength (i.e., the strength of atom–atom interactions in molecular com-
pounds and ion–ion interactions in ionic compounds) and the type of intermo-
lecular forces (i.e., the strength of interactions between independent particles) may
help us predict relative thermodynamic stabilities To begin our analysis, let us
identify some useful patterns in the bond energies of different types of covalent
bonds.
LET’S THINK Bond Energies
Consider the bond energy (BE), expressed in kJ/mol, of the following types of bonds:
Bond BE (kJ/mol) Bond BE (kJ/mol) Bond BE (kJ/mol)

C–C 347 C–H 414 C–N 305
N–N 163 N–H 389 C–O 360
O–O 142 O–H 464 C–F 485
F–F 159 F–H 565 C–Cl 339
• How does the heterogeneity of a bond (i.e., whether the bond involves atoms of the
same or different types) affect bond strength?
• How would you use bond properties, such as bond length and bond polarity, to ex-
plain this effect?
• How could the analysis of the types of bonds in the molecules of different molecular
substances be used to predict relative stabilities?
Molecular compounds with stronger covalent bonds tend to be more ther-

modynamically stable than substances with weaker bonds because more energy
is needed to induce atomic rearrangements. In general, chemical bonds involving
atoms of the same type (A–A bonds) are weaker than bonds between atoms of
different types (A–B bonds). A–B bonds tend to be shorter and more polar than
A–A bonds, factors that increase the strength of atom–atom interactions and de-
crease the internal potential energy of the system. Thus, from an energetic point
of view, chemical reactions are more likely to proceed in the direction that leads to
the formation of molecules with the larger proportion of A–B bonds. Apply this
predictive rule cautiously, though, because some A–A bonds are strong (e.g., BE =
–436 kJ/mol for H–H) and there may be instances in which reactions that involve
breaking these types of bonds will not be energetically favored. We also need to
consider the strength of the intermolecular forces between particles in the system
and the number of configurations that different types of particles may adopt.
Initial Predictions LET’S THINK

It is likely that Earth’s atmosphere contained a considerable amount of Bond BE (kJ/mol)
H2(g) when the first life forms appeared. Given the information listed in H–H 436
the table to the right: F–F 159
Cl–Cl 243
• Analyze how thermodynamically favored it would have been for
H2(g) to react with other elementary substances such as O2(g), Br–Br 193
F2(g), Cl2(g), Br2(l), and I2(s) to form the associated binary com- I–I 151
pounds [i.e., H2O(l), HF(g), etc.] O=O 498
O–H 464
HINT: Write the balanced chemical equations for each potential reaction F–H 565
and compare the bond energies of reactants and products.
Cl–H 431
Share and discuss your ideas with a classmate, and clearly justify your Br–H 364
reasoning. I–H 297
Differences in the bond energy of reactants and products are responsible for
the absorption or release of energy during a chemical reaction. If the products of a
chemical process are made up of molecules with stronger bonds than those present
in the molecules of the reactants, the internal potential energy of the products will
be lower than that of the reactants and energy will be released during the reac- Ep
tion (exothermic process). Thus, reactions that lead to the formation of chemical
compounds with a larger proportion of A-B bonds than A-A bonds will likely be
exothermic (DHrxn< 0) (Figure 5.2). From the energetic point of view, chemical A2 + B2
processes will have a higher probability of occurring in the direction in which less
net energy needs to be invested for the reaction to happen. As a result, exothermic
Energy released
processes tend to be more energetically favored than endothermic processes. 2 AB
A secondary factor to consider is the strength of intermolecular forces between
particles in the system. The strength of the intermolecular interactions has an ef- Reactants Products
fect on the internal potential energy of substances. Molecules are closer to each
Reaction Path
other and interact more strongly in the solid and liquid states than in the gaseous
state. The internal potential energy of a substance is thus lower in the condensed Figure 5.2 Generic ener-
gy diagram for a reaction
phases and the formation of the liquid or the solid phase of a substance is more leading to the formation of
compounds with a larger
energetically favored than the formation of the gaseous phase. For example, the proportion of A–B bonds.
formation of liquid water H2O(l) from the reaction between H2(g) and O2(g) at
25 oC is more exothermic (DHrxn= –286 kJ/mol) than the formation of water va-
por H2O(g) (DHrxn= –242 kJ/mol). As we will see in the next section, this effect
competes with configurational factors that facilitate the formation of gases over
liquids and solids, particularly at high temperatures.
Directionality? LET’S THINK

• Which of these two processes is more likely to occur? Clearly justify your reasoning:
2 HCOOH(l) + O2(g) 2 CO2(g) + 2 H2O(g) | 2 CO2(g) + 2 H2O(l) 2 HCOOH(l) + O2(g)

The likelihood of chemical reactions involving ionic compounds depends on

r factors that influence the strength of ion–ion interactions. Ionic compounds con-
sists of positive ions (cations) and negative ions (anions) arranged in a crystalline
network, not of independent molecules. The strength of the interaction between
-+
anions and cations in the network is determined by Coulomb’s law (F= q1q2/r2),
and therefore it depends on the electric charge (q) of the ions and on their size
(Figure 5.3). Based on Coulomb’s law, the strength of ion–ion interactions should
increase when the charge of the ions is larger and their sizes are smaller. Stronger
Figure 5.3 The distance attractive interactions between neighboring anions and cations in an ionic lattice
(r) between charged par-
ticles is measured from lead to lower internal potential energies, thus increasing the thermodynamic sta-
center to center.
bility of the substance.
LET’S THINK Ionic Compounds
Ionic compounds, either in solid form or dissolved in water, are thought to have played several
important roles in the origin and evolution of life on Earth. Given their crystalline structure, the
surfaces of common rock-forming oxides and carbonates select and concentrate specific amino
acids and sugars, and they also increase the rate of a variety of chemical reactions.
• Consider the following ionic oxides present on Earth: Na2O, K2O, Al2O3, CaO, MgO. Ar-
range them in order of decreasing internal potential energy (or increasing thermodynamic
stability).
The energy released during the formation of a solid ionic network starting
from the cations (C+) and anions (A-) in the gas phase can be used to compare the
relative internal potential energy of different ionic compounds. This process can
be represented using the following generic chemical equation:
C+(g) + A-(g) CA(s)
-500 The energy released during this process (DHrxn) is

known as the lattice energy of the compound CA(s).
F- Cl- Br- I-
-600 The more negative the lattice energy of an ionic com-
Lattice Energy (kJ/mol)
K+ pound, the more energy will be required to separate

the ions that make up the system and the more ther-
-700
Na modynamically stable the compound can be expected
+
Li+
to be. Figure 5.4 illustrates the variation in the lattice
-800 energy for a set of binary ionic compounds involving
ions with different sizes. The experimental results in-
-900 cluded in this figure and its caption confirm our hy-
pothesis that relative ion sizes and charges can be used
-1000 to predict the relative thermodynamic stability of ionic
compounds.
-1100 Figure 5.4 Lattice energy for different sets of ionic compounds. The lattice
energy for compounds involving ions with a larger charge is much more
negative. For example, it is –2522 kJ/mol for MgCl2 and –2253 kJ/mol for
CaCl2.
Metallic Oxides LET’S THINK

Earth’s original atmosphere did not contain large amounts of oxygen. The action of UV radiation
on water molecules, combined with the production of oxygen by photosynthetic organisms, in-
creased dramatically the proportion of O2(g) in the atmosphere. Oxygen gas reacted with different
metals on Earth’s surface to produce a variety of ionic compounds, as in the following processes:
Chemical Reaction DHrxn (kJ/mol)
2 Fe(s) + 3/2 O2(g) Fe2O3(s) –824

Ti(s) + O2(g) TiO2(s) –944
Ca(s) + 1/2 O2(g) CaO(s) –635
Ba(s) + 1/2 O2(g) BaO(s) –548
• Apply the ideas discussed in this module to explain the observed differences in the heats
of reaction for these chemical processes. Discuss why some of these processes may be more
energetically favored than others.
Entropic Factors
The thermodynamic stability of chemical compounds does not depend only on
the potential energy of their submicroscopic components. We also have to take
into account the number of configurations in which these components may be
found. The larger the number of configurations that the atoms, ions, or molecules
that make up a substance can adopt in a given state, the smaller the probability
that random movements will lead them to a completely different state or to form
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M1/conf.html
new compounds when interacting with other systems. Thus, the larger the number
of configurations that the particles that make up a substance can adopt, the more
thermodynamically stable the substance should be expected to be.
Number of Configurations LET’S THINK

The simulations that can be opened by clicking on the image illustrate the be- CLICK TO PLAY
havior of the submicroscopic components of four different types of systems.
• Arrange these systems, from fewest to most, according to the number of

configurations that the particles in the system can adopt. The different
configurations represent different ways in which the particles may ar-
range in space or different manners in which energy may be distributed
among them.
Share and discuss your ideas with a classmate, and justify your reasoning.
In general, the larger the number of particles in a system, the more diverse
these particles are, and the greater the number of different types of interactions
among such particles, the larger the number of configurations in which the system
can exist. Particles in a system may adopt different configurations not only by
changing their positions in space, but also by adopting different configurations
in which the total energy is distributed in different ways among its components.
For example, a system may adopt two different sets of configurations in which the
total kinetic energy is the same but the energy distribution is rather different. In
some configurations all of the particles may be moving at similar medium speeds,
while in other configurations some particles may have high speeds while others
may have low speeds.
Physical scientists have been able to identify a measurable property of chemi-
cal substances that can be used to quantify the number of configurations that their
submicroscopic components can adopt at a certain temperature. This property is
known as the entropy of the substance and is represented by the letter S. The en-
tropy S of a system is related to the number of available configurations W through
the Boltzmann’s entropy equation:
(5.1) S = kB ln W
where kB is Boltzmann’s constant (kB = 1.380 x 10-23 J/K) and (ln) is the natural
logarithm. The entropy of a substance can be determined experimentally from its
heat capacity at different temperatures. Of particular interest is the value of the
standard molar entropy of formation Sfo , measured in J/(mol K) for the substance of
interest. This quantity is a measure of the different configurations that matter and
energy can take in one mole of the substance at 25 oC and 1 atm. The reported val-
ues of Sfo assume that the standard entropy of the perfect crystalline substance at T
= 0 K is equal to 0. According to Equation (5.1), this implies that at 0 K particles
can exist only in one configuration (the perfectly ordered solid).
The standard molar entropy of formation Sfo of chemical substances is affected
by a variety of factors, some of which depend on the composition and structure of
its individual molecules or ions (single particle level) while others are related to the
distribution and interactions of the many particles present in a mole of substance
(multiparticle level). These factors are summarized in the following table and their
effects will be explored and analyzed in the following activities.
Molecular Compounds
Single Particle Level Multiparticle Level
Molecular Mass State of Matter
Molecular Complexity Number of Particles
Ionic Compounds
Single Particle Level Multiparticle Level
Ion Mass State of Matter
Ion Charge
Ion Size
LET’S THINK State of Matter

The tables list the standard molar entropy of formation Sfo of a group of substances that played a
key role in the development of life on Earth.
Substance Sfo (J mol-1 K-1) Substance Sfo (J mol-1 K-1) Substance Sfo (J mol-1 K-1)
H2O(s) 41.0 C(s, diamond) 2.4 CO2(s) 51.1
H2O(l) 70.0 C(s, graphite) 5.7 CO2(aq) 117.6
H2O(g) 188.8 C(g) 158.1 CO2(g) 213.8
• According to these data, how does the state of matter affect the entropy of molecular com-
pounds? How would you explain these patterns using the ideas discussed in this module?
The following tables lists values of Sfo for important ionic compounds in our planet in different
states:
Substance Sfo (J mol-1 K-1) Substance Sfo (J mol-1 K-1)
NaCl(s) 72.1 NaNO3(s) 116.5
NaCl(aq) 115.5 NaNO3(aq) 205.4
• How would you explain the different effects on the entropy of dissolving a gaseous sub-
stance, such as CO2(g), in water and dissolving an ionic compound in this liquid?
As the data in the previous activity illustrate, the state of matter has a major
effect on the entropy of all types of chemical substances. In general, the more
configurations particles can adopt in any given state, the larger the entropy of the
substance in that phase. Given that temperature and pressure affect the state of
matter of chemical substances, we can expect these two variables to influence the
entropy values.
LET’S THINK Temperature Effects

The graph illustrates the effect of changing tempera-
ture on the entropy S of water.
• How would you explain the different effects that

Entropy
changing temperature has on the value of S at

different stages during the heating process?
Share and discuss your ideas with a classmate, and

clearly justify your reasoning. Temperature
LET’S THINK Molecular Mass
The table lists values of Sfo for substances in the same state of matter, Substance Sfo (J mol-1 K-1)
with similar molecular complexity, but different molecular mass.
H2(g) 130.7
• How would you explain the differences in standard molar en- N2(g) 191.6
tropy values? O2(g) 205.2
Cl2(g) 223.1
Share your ideas with a classmate and justify your reasoning.
LET’S THINK Molecular Complexity
The table lists values of Sfo for substances in the same state of matter,
with similar molecular mass, but different molecular complexity Substance Sfo (J mol-1 K-1)
N2(g) 191.6
• How would you explain the differences in standard molar en-
CO(g) 197.7
tropy values?
C2H4(g) 219.3
LET’S THINK Ionic Compounds
The tables to the right lists values of Sfo for a set of common ionic Substance Sfo (J mol-1 K-1)
compounds: LiF(s) 35.6
• Explain the differences in standard molar entropy values within NaF(s) 51.5
the fluorides, within the oxides, and between the fluorides and KF(s) 66.6
the oxides? What factors seem to have a dominant effect on the
value of the entropy of ionic compounds? Substance Sfo (J mol-1 K-1)
BeO(s) 13.8
Share your ideas with a classmate, and clearly justify
MgO(s) 27.0
your reasoning.
CaO(s) 38.1
Given that substances with higher values of entropy have a larger number of accessible configurations
at any given temperature, they should be more thermodynamically stable. Chemical reactions should then
be more likely to proceed in the direction that produces substances with higher entropy. If we were to
measure the difference in standard molar entropy between products and reactants DSorxn, we should expect
DSorxn > 0 for processes that are entropically favored. However, the same factors that result in high entropy
values often result in high internal potential energy values and thus DHrxn > 0. For example, the formation
of gases is favored entropically but disfavored energetically. The frequent competition between energetic
and entropic contributions to the thermodynamic stability of chemical substances means that we need to
devise reliable ways to quantify these two types of effects. This will be our central goal in Module 2.
FACING THE CHALLENGE CO2(g) + 4 H2(g) CH4(g) + 2 H2O(g)

CO(g) + 3 H2(g) CH4(g) + H2O(g)
Primordial Atmosphere N2(g) + 3 H2(g) 2 NH3(g)
The origin of life on Earth seems to have occurred
in a relatively short period of time in our plan- The first forms of life may have relied on these
et’s history. Experimental evidence suggests that types of chemical reactions as a source of energy.
the solar system is close to 4.65 billion years old. Methanogens, for example, are modern microbes
Life on Earth seems to have appeared between 3.9 that depend on the formation of methane, CH4,
and 3.8 billion years ago. The formation of life on in the first reaction above for their survival. These
Earth required the accumulation and organiza- organisms are strictly anaerobic and are believed to
tion of chemical compounds needed to sustain it. be evolutionarily ancient.
The synthesis and accumulation of these types of Geological evidence suggests that only low
substances would have depended on the prevailing levels of O2 existed in the atmosphere before 2.4
environmental conditions on the primitive Earth. billion years ago. The rise of oxygen in the atmo-
Unfortunately, little is sphere is somewhat linked
known with certainty to the development of
about the primordial at- organisms that produced
mospheric composition organic matter (represent-
of our planet. ed generically as CH2O)
H2, H2O, CH4, CO, through photosynthesis:
CO2, and NH3 are the
most abundant molecu- CO2 + H2O CH2O + O2
lar gases in our solar sys-
tem, and this was prob- Respiration and decay
ably the case during the processes reverse this
By NASA/Jenny Mottar
formation of our planet. chemical reaction on a
It is unlikely, however, that Earth kept much of time scale of 100 years, consuming over 99% of
its atmosphere during the formation process. It the oxygen produced by photosynthesis. However,
has thus been suggested that the primordial atmo- around 0.1-0.2% of the organic matter escapes the
sphere derived from outgassing (gases from volca- reconversion into CO2 and H2O through burial
nic emissions), at temperatures between 300 and in sediments. This process can eventually lead to
1500 oC. The chemical composition of the early a net accumulation of O2 in the atmosphere. This
mantle should have then determined the chemi- accumulation is possible as long as other thermo-
cal nature of the gases released during outgassing. dynamically favored processes in which oxygen is
As a result, the primordial atmosphere was likely consumed occur at a lower rate:
composed of mainly nitrogen, N2, and smaller
amounts of other gases such as CO, H2O, and H2. 4 FeO(s) + O2(g) 2 Fe2O3(s)
The amount of O2 is speculated to have been neg- C(s) + O2(g) CO2(g)
ligible. H2(g) + O2(g) 2 H2O(g)
The main components in the primordial atmo-
sphere could have reacted with each other to form Existing evidence suggests that there were two dis-
other chemical compounds. For example, the fol- tinct periods in the history of Earth in which O2
lowing processes proceed to a large extent due to amounts rose considerably. In each case, accumu-
the thermodynamic stability of the products: lation was due to the burial of chemical substances
that otherwise may have reacted with O2 to form
more thermodynamically stable products.
Let’s Apply
Chemistry on the Primitive Earth
Analysis of the thermodynamic stability of potential reactants and products is critical for build-
ing models and theories about the extent of the chemical reactions and the nature of the chemical
substances that led to and sustained the development of life on Earth.
ASSESS WHAT YOU KNOW
Methane Formation
The following chemical processes were likely involved in the formation of methane, CH4(g), in
Earth’s primordial atmosphere:
CO2(g) + 4 H2(g) CH4(g) + 2 H2O(g)

CO(g) + 3 H2(g) CH4(g) + H2O(g)
C(s) + 2 H2(g) CH4(g)
• Discuss whether each of these reactions would be product-favored or reactant-favored

based on a) energetic and b) entropic considerations.
• Build a diagram representing the potential energy (Ep) (vertical axis) and entropy (S)
(horizontal) axis of reactants and products. This diagram is equivalent to the PEC (po-
tential energy-number of configurations) diagram build in previous units.
Oxygen Sinks
The following chemical reactions represent processes that may have played an important role
in hindering the accumulation of oxygen, O2(g), in Earth’s atmosphere:
4 FeO(s) + O2(g) 2 Fe2O3(s)

4 FeS2(s) + 15 O2(g) + 8 H2O(l) 2 Fe2O3(s) + 8 H2SO4(aq)
C(s) + O2(g) CO2(g)
• Discuss whether each of these reactions would be product-favored or reactant-favored

based on a) energetic and b) entropic considerations.
(horizontal) axis of reactants and products. This diagram is equivalent to the PEC (po-
tential energy-number of configurations) diagram build in previous units.
Hydrogen Sources
Some models propose that H2(g) was a major component of Earth’s primordial atmo-
sphere. It is such a light gas, though, that most of it is assumed to have escaped from
Earth’s gravitational pull. The following table lists the heat of reaction (DHrxn) and the
difference in entropy DSorxn (difference in the standard molar entropy of products versus
reactants) at 25 oC for reactions that may have led to the formation of H2(g) on Earth:
Chemical Reaction DHrxn (kJ mol-1) DSorxn (J mol-1 K-1)
C(s) + 2 H2O(g) 2 H2(g) + CO2(g) 90.1 91.9

S(s) + 4 H2O(l) 3 H2(g) + H2SO4(aq) 233.9 98.5
2 FeO(s) + H2O(l) H2(g) + Fe2O3(s) 5.6 26.5
• Analyze each of the chemical reactions and justify the signs of DHrxn and DSorxn for
each of them. Discuss why some processes are more thermodynamically favored
than others.
Share and discuss your ideas with a classmate.
Amino acids
Amino acids were the first chemical compounds of biological interest produced in an
experiment simulating conditions on the primitive Earth. These substances have been
produced using an electrical discharge through different types of simple mixtures, such as
H2O/CH4/NH3/H2, H2O/CH4/N2/NH3, and CO/N2/H2. Ball-and-stick models of six
different amino acids are as follows:
Leucine Serine
Alanine
Glycine Proline Valine
• Based on your analysis of their composition and structure, arrange these amino
acids in order of increasing standard molar entropy.
Let’s Apply
Smelting
Chemical interactions between metals in the Earth’s crust and gases in our atmosphere led to the
formation of the wide variety of chemical compounds that make up the minerals that we routinely
mine today. Smelting is the industrial process used to extract metals such as silver, iron, copper, and
lead from these minerals using a combination of chemical reactions.
Common Minerals
The following chemical compounds are the major components of minerals from which the
widely used metals lead, iron, and silver are commonly extracted:
PbS (in galena) Fe2O3 (in Hematite) Ag2S (in argentite)
• Arrange these substances in order of a) decreasing internal potential energy (or more
negative lattice energy), and b) increasing standard molar entropy.
Iron Smelting
Iron is extracted from minerals containing Fe2O3(s) using coal (made mostly of carbon) and air
as source of oxygen. The process is carried out at high temperatures. The table lists the heat of
reaction (DHrxn) and the difference in entropy DSorxn (difference in the standard molar entropy
of products versus reactants) at 25 oC for the sequence of reactions that lead to the formation
of metallic iron:
Chemical Reaction DHrxn (kJ mol-1) DSorxn (J mol-1 K-1)
2 C(s) + O2(g) 2 CO(g) –221.0 178.8
3 Fe2O3(s) + CO(g) 2 Fe3O4(s) + CO2(g) –47.2 45.9
Fe3O4(s) + CO(g) 3 FeO(s) + CO2(g) 441.9 52.5
FeO(s) + CO(g) Fe(s) + CO2(g) –11.0 –17.41
• Analyze each of the chemical reactions and justify the signs of DHrxn and DSorxn for each
of them. Discuss why some processes are more thermodynamically favored than others.
Lead Smelting
Metallic lead is produced from galena (PbS) via the sequential processes of roasting and smelt-
ing:
a) In roasting the mineral is heated in the presence of air to convert the metallic sulfide into
the metallic oxide:
2 PbS(s) + 3 O2(g) 2 PbO(s) + 2 SO2(g)
b) In smelting the metal oxide is reacted with coal (carbon) to form the metal:
2 PbO(s) + C(s) 2 Pb(s) + CO2(g)

• Analyze the composition and structure of reactants and products in these two reactions
and then predict the signs of DHrxn and DSorxn in each case.
(horizontal) axis of reactants and products.
Metals and their Oxides
The following table lists the standard molar entropy of formation of several metals and of com-
mon metallic oxides found in minerals.
Fe(s) 27.3 Cu(s) 33.2 Al(s) 28.3
Ni(s) 29.9 Ag(s) 42.6 Sn(s) 51.2
Zn(s) 41.6 Hg(l) 75.9 Pb(s) 64.8
Fe3O4(s) 146.4 CuO(s) 42.6 Al2O3(s) 50.9
NiO(s) 38.0 Ag2O(s) 121.3 SnO(s) 57.2
ZnO(s) 43.7 HgO(s) 70.3 PbO(s) 68.7
• What main compositional and structural factors seem to determine the standard molar
entropy of formation of metals?
• What main compositional and structural factors seem to determine the standard molar
entropy of formation of metallic oxides?
• What accounts for the difference between the standard molar entropy of formation of a
metal and that of its associated oxide?
296
Comparing
Free Energies
The analysis of changes in the internal potential energy and the entropy of the
U5: MODULE 2
substances involved in a chemical reaction is useful in qualitatively predicting the

directionality of chemical reactions. However, given the often

competing effects between changes in internal potential en-
By Fidel Gonzalez (Own work)

ergy and entropy during chemical processes, we need to
find a systematic way to make reliable predictions. This
can be accomplished by carefully analyzing what hap-
pens to the entropy of both the chemical system and
its surroundings during a chemical process. Fortunately,
we can take advantage of a law of nature to derive useful
mathematical relationships to evaluate the directionality and
extent of chemical reactions based on available experimental in-
formation such as the heat of reaction and the change in molar entropies.
Most of our discussions in this module will focus on calculating the difference
in Gibbs Free Energy between products and reactants (DGrxn). As we will see, this
quantity depends on the heat of reaction DHrxn, the entropy difference DSrxn, and
the temperature T at which the chemical reaction takes place. The sign of DGrxn
will give us information about the directionality of the chemical process, while the
the ratio DGrxn/T can be used to quantitatively evaluate the extent of the conver-
sion of reactants into products.
THE CHALLENGE Chemical Origins

Glycine, C2H5NO2, is an important amino acid that could be potentially syn-
thesized using CH4(g), NH3(g), and H2O(l). The synthesis reaction leads to
an increase of entropy (DSrxn > 0) but the process is endothermic (DHrxn > 0).
• How would you decide whether this synthetic path is feasible and may
have led to the formation of glycine on the primitive Earth?
• How would temperature affect the likelihood of the reaction?
to answer questions similar to those posed in the challenge. In particular, the
central goal of Module 2 is to help you understand how to quantitatively deter-
mine the directionality and extent of chemical reactions.
2nd Law of Thermodynamics

The analysis of the many types of changes that occur in our world has allowed
physical scientists to identify common underlying characteristics. In particular,
changes that occur in isolated systems (systems that cannot exchange energy or
matter with their surroundings) are characterized by an increase in the total num-
ber of configurations available to the components of the system. In isolated sys-
tems, the random motion of particles are likely to lead to a more homogeneous
distribution of matter and energy. This means that whenever a change occurs in an Isolated Overall
isolated system, the total entropy of the system STOT increases. This experimental System
fact is known as the Second Law of Thermodynamics and it can be used to derive
useful relationships to quantitatively determine the directionality and extent of Surroundings
chemical reactions.
Let us consider a container with a mixture of reactants in which a chemical re-
action may take place. We will call this mixture the “system”. Our system is kept at System
constant temperature and pressure and can exchange energy with the environment
(i.e., energy can come in or out of the system). We will call “surroundings” that
part of the environment affected by the exchange of energy with the system. In Energy Exchange
this manner, the combination of our system and its surroundings can be thought
as an isolated system itself (Figure 5.5) in which the 2nd Law of Thermodynamics Figure 5.5 The combina-
applies. tion of the system plus
its surroundings can be
According to the 2nd Law, if a chemical reaction is going to take place in thought as an isolated sys-
tem in which the 2nd Law of
our system, the total entropy of the system plus its surroundings should increase. Thermodynamics applies.
This means, the difference between the total entropy after and before the process
should be positive (DSTOT > 0). This does not imply that the change of entropy
in the chemical system (DSsys) should also be larger than zero for the chemical
reaction to occur. DSsyscould be negative, as long as the associated change in the
entropy of the surroundings (DSsurr) is such that:
(5.2) DSTOT = DSsys + DSsurr > 0
This relationship implies that chemical reactions will proceed in the direction in
which DSTOT increases. Our task is then to figure out how to calculate this quantity
based on experimental information about the properties of reactants and products.
The Surroundings LET’S THINK

During a chemical reaction, a net amount of energy is either released to or absorbed
from the surroundings. This energy exchange affects the entropy of the surround-
ings as its particles gain or lose energy.
• How would you expect the entropy of the surroundings to change during an
exothermic process? How would it change during an endothermic process?
• Would you expect the value of DSsurr to depend on the temperature of the sur-
roundings?
298 MODULE 2 Comparing Free Energies
Gibbs Free Energy

To take advantage of the 2nd Law of Thermodynamics in predicting reaction di-
rectionality and extent, we need to find a way to determine the value of DSsys and
DSsurr for every process of interest. Given that we are considering chemical reac-
tions, the change of entropy of the system DSsys can be calculated by taking the dif-
ference between the total entropies of products and reactants. For a generic chemi-
cal reaction of the form: a A + b B c C + d D, DSsys would then be given by:
(5.3) DSsys = DSrxn = (cSC + dSD) - (aSA + bSB) = SSproducts - SSreactants
where Si represents the molar entropy of species “i” and the symbol “S” indicates
the sum over all reactants or products.
The change of entropy of the surroundings DSsurr is determined by the amount
of energy exchanged in the form of heat during the chemical reaction, DHrxn, and
the temperature of the surroundings T. In particular, if we assume that the effect
on the surroundings is rather small compared to its total entropy (i.e., the sur-
roundings are much larger than the system), DSsurr at constant temperature and
pressure can be estimated as:
(5.4) DSsurr = – DHrxn / T
According to this relationship, the change of entropy of the surroundings would

be positive for exothermic processes and negative for endothermic reactions. A
release of energy into the surroundings (DHrxn < 0) should result in an increase
in the number of configurations available to surrounding particles, while energy
absorption (DHrxn > 0) should limit the number of states in which these particles
may exist. Energy exchange at high T has a smaller impact on the entropy of the
surroundings as its particles already have access to many different states. On the
other hand, an energy transfer at low T should affect the entropy of the surround-
ings considerably as the number of available states is relatively small.
The combination of Eq. (5.2), (5.3), and (5.4) indicates that, at constant tem-
perature and pressure, chemical reactions proceed in the direction for which:
(5.5) DSTOT = DSsys + DSsurr = DSrxn – DHrxn / T > 0
LET’S THINK Types of Reactions
All chemical processes may be classified into one of four types based on the signs of DSrxn and DHrxn:
DSrxn > 0, DHrxn > 0 DSrxn > 0, DHrxn < 0 DSrxn < 0, DHrxn > 0 DSrxn < 0, DHrxn < 0
• Which of these processes can be expected to occur at all temperatures? Which processes
are unlikely to occur no matter what the temperature is? Which processes may occur at
some temperatures but not others?
• Build an Ep-S (PEC) diagram for each the four types of processes described above.
For chemical processes that take place at constant temperature and pressure, it
is common to calculate the difference in Gibbs free energy between products and
reactants, DGrxn, defined as:
(5.6) DGrxn = DHrxn - T DSrxn

DHrxn < 0, DSrxn < 0
This definition, together with the 2nd Law of Thermodynamics as expressed in
DGrxn
Eq. (5.5), imply that chemical reactions will occur in the direction for which DGrxn
is negative (DGrxn < 0), this is, in the direction in which the Gibbs free energy of
the system decreases. The definition of DGrxn allows us predict reaction directional- m = –DSrxn
ity and extent based solely on changes in properties of the system, without having
to consider the effects on the surroundings. The structure of Eq. (5.6), together T
with the condition DGrxn < 0, makes explicit the competition between energetic
(DHrxn) and entropic factors (DSrxn) in determining how thermodynamically favor- b = DHrxn
able a process is at a given temperature.
Based on Eq. (5.6) we can predict that processes for which DHrxn< 0 and
Figure 5.6 If we assume that
DSrxn > 0 are thermodynamically favored at all temperatures (DGrxn < 0 at all T). DHrxn and DSrxn do not change
with temperature (T), a graph
On the contrary, chemical reactions in which DHrxn> 0 and DSrxn < 0 will have a of DGrxn as a function of T is a
very small probability to occur at all T (DGrxn > 0 at all T). If DHrxn and DSrxn have straight line with a slope m equal
to –DSrxn and a y-intercept b equal
the same sign, there will be a temperature at which the process will become more to DHrxn. The directionality of the
reaction changes when DGrxn = 0.
or less favorable as the temperature varies. This particular temperature is deter-
mined by the condition DGrxn = 0 and can be estimated using Eq. (5.6), assuming
that the values of DHrxn and DSrxn do not change with temperature (Figure 5.6).
CO2(g) or CH4(g)? LET’S THINK

Hydrogen gas, H2(g), is suspected to have been an important component of the primordial atmo-
sphere. In a hydrogen-rich environment, CO2(g) may have been unstable and may have reacted to
form CH4(g). Is that a reasonable hypothesis?
• Using the information included in the following table, evaluate how thermodynamically
favorable the formation of CH4(g) from CO2(g) and H2(g) is at 25 oC.
Chemical Reaction DHrxn (kJ mol-1) DSrxn (J mol-1 K-1)
CO2(s) + 4 H2(g) CH4(g) + 2 H2O(l) –252.7 –410.3
Given the values of DHrxn and DSrxn one can expect that the above process will be more favorable
at some temperatures than others.
• Build a graph of DGrxn as a function of T. Use the graph to predict whether the formation of
CH4(g) is favored at low temperature or at high temperatures.
• Estimate the temperature at which CH4(g) becomes more thermodynamically favored than
CO2(g) in the presence of H2(g).
Standard Values
To facilitate the prediction of the thermodynamic likelihood of a wide variety
of chemical processes, chemical scientists have carried out a multitude of mea-
surements to determine the values of experimental properties that can be used
to calculate DSrxn, DHrxn, and DGrxn. These types of measurements are commonly
done under standard conditions: 25 oC and 1 atm, and the results are commonly
expressed per mole of substance. Thus, the measured quantities are referred to as
standard molar properties. In the following sections, we will discuss how to use
this valuable experimental information to calculate the quantities needed to pre-
dict reaction directionality and extent.
a) DSorxn
As discussed in the previous module, information about the value of the heat
capacity of a substance “A” at various temperatures can be used to determine its
standard molar entropy of formation Sfo[A] (J mol-1 K-1). The entropy change as
a result of a chemical reaction of the form: a A + b B c C + d D, carried out
under standard conditions can then be calculated by taking the difference between
the total entropy of the products minus that of the reactants:
(5.7) DSorxn = (c Sfo[C] + d Sfo[D]) - (a Sfo[A] + b Sfo[B])
LET’S THINK Entropy Change
Consider the formation of NH3(g) from the elemental substances: Substance Sfo (J mol-1 K-1)
H2(g) 130.7
3 H2(g) + N2(g) 2 NH3(g)
N2(g) 191.6
• Based on the nature of reactants and products, qualitatively NH3(g) 192.8
predict the sign of DSorxn for this process.
• Use the available data to determine the actual value of DSorxn for this process.
b) DHorxn
Measurements of the energy absorbed or released as heat during a chemical reac-

By Fidel Gonzalez (Own work)
tion can be done using an experimental technique known as calorimetry (Figure

5.7). In this approach, energy transferred as heat by a chemical system is measured
indirectly by quantifying changes in the temperature of a surrounding material.
One particularly useful calorimetric measurement is the heat released or absorbed
when one mole of a given substance is synthesized from its elementary compo-
nents under standard conditions (at 25 oC and 1 atm). The corresponding quan-
tity is known as the Standard Molar Enthalpy of Formation, DHfo (kJ/mol), of the
Figure 5.7 Bomb calo- chemical compound. The table on the next page illustrates the formation of well
rimeters such as the one
shown in this image are
used to measure heats of
known chemical substances and the associated DHfo values determined experi-
combustion. mentally.
Synthesis Reaction Substance DHfo (kJ/mol)

C(s, graphite) + O2(g) CO2(g) CO2(g) –393.5
H2(g) + 1/2 O2(g) H2O(l) H2O(l) –285.8
3/2 H2(g) + 1/2 N2(g) NH3(g) NH3(g) –45.9
C(s, graphite) + 2 H2(g) CH4(g) CH4(g) -74.6
Na(s) + 1/2 Cl2(g) NaCl(s) NaCl(s) –411.2
Mg(s) + 1/2 O2(g) MgO(s) MgO(s) –601.6
Notice that the elementary substances used for the synthesis reactions as rep-
resented in the table above are in their stable form at standard conditions (25
o
C, 1 atm). The value of DHfo for liquid water, for example, indicates that 285.8
kJ of energy are released every time that one mole of water is formed from the
needed stoichiometric amounts of hydrogen and oxygen gases. It is important to
realize that the same amount of energy will be absorbed when one mole of water
is decomposed into one mole of H2(g) and half a mole of O2(g). Thus the energy
needed to decompose a substance into elementary substance under standard con-
ditions is given by DHdo = –DHfo. We will take advantage of this symmetric rela-
tionship between heat of formation and heat of decomposition to calculate DHorxn
for any process.
Heat of Reaction LET’S THINK

Consider the following hypothetical data for these pair of generic chemical reactions:
A + B AB DHfo = –200 kJ/mol

B + C BC DHfo = –100 kJ/mol
• Use the above information to determine the standard heat of reaction DHorxn for the pro-
cess:
AB + C BC + A
• Discuss how you could generalize the calculation of DHorxn for any reaction using DHfo
values for reactants and products.
Information about the standard molar enthalpy of formation of the substances

involved in a chemical reaction can be used to predict the heat of reaction under stan-
dard conditions, DHorxn. To make this prediction, we can model chemical reactions as
processes in which all chemical compounds acting as reactants are first decomposed
into elementary substances that are then recombined to form the desired products.
Although it is unlikely that chemical reactions would actually proceed in this way,
the approach is based on the idea that, no matter what path a reaction follows,
the total energy transfer should be the same as long as we start with the same
amount of reactants and end with the same amount of products.
To illustrate this idea, let us predict the heat of reaction for a process likely
involved in the production of CO2(g) in our planet’s primordial atmosphere:
C(s, graphite) + 2 H2O(l) 2 H2(g) + CO2(g)

C(s) + 2 H2(g) + O2(g)
We can think of this reaction as occurring in two steps:
DECOMPOSITION
1) The decomposition of two moles of H2O(l) into
SYNTHESIS
– 2 x DHfo[H2O(l)] DHfo[CO2(g)] H2(g) and O2(g), and 2) The combination of elemen-
tary substances to form one mole of CO2(g) (Figure
5.8). The amount of energy involved in the first step is
-2 x DHfo[H2O(l)], and that associated with the second step
C(s) + 2 H2O(l) 2 H2(g) + CO2(g)
is simply DHfo[CO2(g)]. The standard heat of reaction for
DH o
rxn the reaction of interest should then be given by:
DHorxn = DHfo[CO2(g)] – 2 x DHfo[H2O(l)] = –393.5 + 2 x 285.8 = 178.1 kJ

Figure 5.8 Alternative reac-
tion path based on the de-
composition of reactants and
the synthesis of products.
In general, the standard heat of reaction DHorxn for any chemical process can
be calculated by taking the difference between the total standard enthalpies of
formation of the chemical compounds that are produced and the total standard
enthalpies of the chemical compounds that participate as reactants:
(5.8) DHorxn = SDHfo[product compounds] - SDHfo[reactant compounds]
Notice that no information is needed about the standard enthalpies of formation

of any elementary substance that are involved in the reaction. By convention, the
value of DHfo for any elementary substance in its stable state under standard conditions
is then taken to be equal to zero.
c) DGorxn
Once we know the values for DSorxn and DHorxn for a chemical reaction, we can use
the definition for the change in Gibbs free energy given in Eq. (5.6) to calculate
DGorxn for the process. This quantity can be used to predict the directionality and
extent of the chemical reaction (DGorxn < 0 for processes that are thermodynami-
cally favored under standard conditions). Eq. (5.6) can also be used to estimate
DGorxn(T) = DHorxn – T DSorxn at different temperatures if we assume that the values
of DSorxn and DHorxn remain constant at all temperatures (which is not necessarily
the case, but allows us to make reasonable predictions).
To facilitate the calculation of DGorxn at 25 oC and 1 atm for a chemical reac-
tion, chemical scientists have determined the Standard Molar Gibbs Free Energy of
Formation, DGfo (kJ/mol), of many chemical compounds. This quantity is a mea-
sure of the change in Gibbs free energy when a mole of the compound is formed
starting from its elementary components at standard T and P. The definition of
DGfo is similar to that of DHfo, and thus we can apply the ideas derived from Hess’s
Law to calculate DGorxn using DGfo values. In particular:
(5.9) DGorxn = SDGfo[product compounds] - SDGfo[reactant compounds],
where the DGfo for elementary substances is also taken to be equal to zero.
First Amino Acids LET’S THINK

One central question in the theories about the origin of life is how complex organic compounds
were synthesized from simpler molecules such as H2, N2, and CH4. Consider these two potential
paths in the synthesis of the amino acid, glycine (C2H5NO2):
2CO(g) + NH3(g) + H2(g) C2H5NO2(s) Substance DHfo Sfo DGfo

2CH4(g) + NH3(g) + 2H2O(l) C2H5NO2(s) + 5H2(g) (kJ mol-1) (J mol-1 K-1) (kJ mol-1)
H2(g) 0 130.7 0
• Calculate DSorxn, DHorxn, and DGorxn for each CH4(g) –74.6 186.3 –50.5
reaction.
CO(g) –110.5 197.7 –137.2
• Build graphs of DGorxn(T) as a function of T
NH3(g) –45.9 192.8 –16.4
and analyze the effect of temperature on the
extent of reaction. H2O(l) –285.8 70.0 –237.1
• Determine the temperature at which each reac- C2H5NO2(s) –528.4 103.5 –368.8
tion becomes product-favored.
Reaction Extent
Although the change in Gibbs free energy DGrxn allows us to predict the directionality of a
chemical reaction, the actual number tells us little about the final relative amounts of product
to reactants. Experimental results indicate that chemical reactions reach an “equilibrium”
state in which the concentration of products and reactants does not vary over time. In par-
ticular, it is found that, for a generic chemical reaction of the form:
aA+bB cC+dD
where A, B, C, and D are gaseous substances, the following ratios of the pressures of reactants
to products remain constant when chemical equilibrium is reached:
PCc PDd
(5.10) Kp =
PAaPBb
If A, B, C, and D are substances dissolved in a solvent, then the following ratio of their molar
concentrations (expressed using square brackets) remains constant at equilibrium:
(5.11) [C]c[D]d
KC =
[A]a[B]b
The quantities KP and KC evaluated at the equilibrium pressures or concentrations receive the
name of Equilibrium Constants, and they can be used to determine the reaction extent. In
general, chemical reactions for which KP >1 or KC > 1 can be thought as product-favored. The
larger the value of an equilibrium constant K, the larger the extent of the process.
LET’S THINK Directionality and Extent
Consider a generic chemical reaction of the form:
A(aq) B(aq)
• Express the equilibrium constant KC for this process.
Imagine that concentrations of A and B are measured as a function of time until the reaction reaches
chemical equilibrium. Depending on the chemical nature of A and B and on the temperature of the
system, these two types of experimental results are observed:
Concentration
Concentration
A B
Time Time
• Which of these two types of experimental results would you expect to observe in each of the
following cases? Predict whether Kc > 1 or Kc < 1 in each case:
DSrxn > 0, DHrxn > 0 at high T DSrxn > 0, DHrxn < 0 at all T
DSrxn < 0, DHrxn > 0 at all T DSrxn < 0, DHrxn < 0 at high T
• Based on your analysis, how is the sign of DGrxn (which determines reaction directionality)
related to whether Kc > 1 or Kc < 1?
The concentrations of reactants and products at chemical equilibrium, and

thus the value of the equilibrium constant KC or KP, depend on the chemical na-
ture of the substances involved as well as on the temperature of the system. For
example, reactions for which DGrxn < 0 (product-favored) at all temperatures can
be expected to have equilibrium constants KC, KP > 1, but the actual value of the
equilibrium constant will vary with temperature. However, the values of the equi-
librium constants KP or KC at any given temperature are independent of the initial
pressures or concentrations of the reactants and products in a chemical system.
Although the equilibrium pressures and concentrations of every species involved
in the reaction will differ depending on the initial conditions, the ratios of the
equilibrium pressures or concentrations as defined in Eq. (5.10) and Eq. (5.11),
respectively, will remain constant.
Equilibrium Constant LET’S THINK

The formation of molecular oxygen O2 in Earth’s atmosphere is affected by UV radia-
tion that breaks these molecules apart: O2(g) 2 O(g)
• Express the equilibrium constant Kp for this reaction.
Results from experiments carried out using different initial pressures of O2(g) at a high
constant temperature T are shown in the images below:
• Estimate the value of Kp for these two systems and compare your results.
• Discuss whether the value of Kp depends on the initial pressure of O2(g) and
O(g) in any given system.
During a chemical reaction, the amounts of reactants and products in the sys-
tem change as a function of time until reaching chemical equilibrium. However,
the concentration (i.e., number of particles per unit volume) of some substances
may remain constant during the process. Such is the case of pure solids and liquids
involved in the reaction The values of the equilibrium constants KP or KC at any Figure 5.9 Particulate rep-
resentation of the initial and
given temperature only depend on the equilibrium concentrations or pressures of equilibrium states of reactants
and products for the transfor-
those reactants and products whose concentrations actually change as a result of mation of A(s) into B(g).
the reaction. Consider, for example, the reaction represented in
A(s) B(g)
Figure 5.9 where a generic solid substance A(s) transforms into
the gaseous substance B(g). If the initial conditions are such
that the pressure of B(g) in the system is very low, we can expect
this pressure to increase as the reaction proceeds. Although A(s)
will be consumed in this process and its total amount in the
system will decrease, the concentration (density) of A particles
(i.e., number of A particles per unit volume) will not change.
Consequently, the value of the equilibrium constant KP will
only depend on the equilibrium pressure of the product:
KP = PB in this case.
Initial Equilibrium
LET’S THINK KP Expressions
Consider the two hypothetical routes for the synthesis of glycine analyzed previously:
2CO(g) + NH3(g) + H2(g) C2H5NO2(s)

2CH4(g) + NH3(g) + 2H2O(l) C2H5NO2(s) + 5H2(g)
• Express the equilibrium constants for following two reactions. Discuss whether the pressure
or concentration of solid and liquid substances should be included in the expressions.
The value of the equilibrium constant KP or KC is independent of the initial

pressures and concentrations of reactants and products, as well as of the external
pressure acting on the system. However, the value of KP or KC is affected by chang-
es in the temperature at which the chemical reaction takes place. The following
relationship expresses the effect of temperature on the equilibrium constant:
(5.12) K = exp [ –DGorxn(T)/ (RT) ]
where K represents either KP or KC, T is the temperature, R is the ideal gas constant
(R = 8.314 J mol-1 K-1), and DGorxn(T) is the standard change of Gibbs free energy
for the reaction at temperature T. Equation (5.12) indicates that for product-fa-
vored processes, where DGorxn(T) < 0, the equilibrium constant K > 1, while K < 1
when the reaction is reactant-favored. If we take DGorxn(T)= DHorxn – TDSorxn, the
dependence of the equilibrium constant on temperature can also be expressed as:
(5.13) K = exp [ – DHorxn / (RT) + DSorxn / R ]
This relationship suggests that the effect of changing temperature on the value of
the equilibrium constant is not the same for exothermic reactions as it is for en-
dothermic reactions. In the case of exothermic reactions (DHorxn < 0), K is always
a decreasing function of temperature with an asymptotic value at high T that may
be larger (DSorxn > 0) or smaller (DSorxn < 0) than one depending on the sign of
Figure 5.10 Variation of K as
a function of temperature T for DSorxn. For endothermic reactions (DHorxn > 0), K is always and increasing function
different types of reactions. of temperature as shown in Figure 5.10.
K DHorxn < 0, DSorxn < 0 K DHorxn < 0, DSorxn > 0 K DHorxn > 0, DSorxn < 0 K DHorxn > 0, DSorxn > 0
1 1 1 1
T T T T
Temperature Effects LET’S THINK
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M2/gibbs.html
Consider a simple isomerization reaction in aqueous solution of the form:
A(aq) B(aq).
CLICK TO PLAY
• Predict the effect of changing a) DHorxn , b)
DSorxn, and c) T on the value of the equilib-
rium constant KC for the reaction and on
the reaction extent (i.e., relative amount of
products to reactants at equilibrium).
• Once you made your predictions, click on
the image to the right to launch a simula-
tion that will allow you to verify your ideas.
This simulation allows you to see the effect
of independently changing the three main
variables that determine the value of KC.
According to Eq. (5.13), the equilibrium constant of endothermic reactions

increases as the temperature increases. On the other hand, the value of KP or KC
for exothermic reactions becomes smaller at higher temperatures. These effects are
independent of whether the entropy of the system increases or decreases as a result
of the chemical reaction. However, reactions where ∆Horxn < 0 and ∆Sorxn> 0 are
product-favored at all temperatures and K > 1 at all T. Similarly, reactions where
∆Horxn > 0 and ∆Sorxn< 0 are reactant-favored at all temperatures and K < 1 under
all circumstances. It is only for processes where ∆Horxn and ∆Sorxn are either both
negative or both positive that K values become larger or smaller than one when
changing temperature.
Different chemical reactions reach equilibrium states that have different pro-
portion of products and reactants in the system. For example, combustion reac-
tions tend to have very large K values under standard conditions:
CH4(g) + 2O2(g) CO2(g) + 2H2O(g) DGorxn = –800.9 kJ KP = 2.41 x 10140
The value of the equilibrium constant at 25 oC is so large that this reaction can be
assumed to go to completion. Given that ∆Horxn < 0 and ∆Sorxn> 0 in this process,
K > 1 at all temperatures. In these types of processes, we commonly use a single
arrow to represent the directionality of the reaction in the chemical equation.
Other processes have equilibrium constants that are not very large and the
value of KP or KC may vary considerably when changing the temperature. Con-
sider, for example, the reaction:
CO(g) + H2O(l) HCOOH(l) DGorxn = –12.9 kJ KP = 182

with ∆Horxn < 0 and ∆Sorxn< 0. This process is thermodynamically favored at 25 oC,
but the extent of the reaction decreases with increasing temperature. In cases like
this, it is better to represent the process using a double arrow connecting reactants
and products to indicate that the reaction achieves an equilibrium state in which
both reactants and products are present to a significant extent. The use of a single
or a double arrow in the representation of these types of chemical reactions may
change depending on reaction conditions.
In cases in which the value of the equilibrium constant K varies considerably
when changing temperature, it is convenient to derive an expression that facilitates
the comparison of its value at two different temperatures. This relationship can be
derived by using Eq. (5.13) to express the value of K at the two temperatures of
interest:
K1 = exp [ – DHorxn / (RT1) + DSorxn / R ]
K2 = exp [ – DHorxn / (RT2) + DSorxn / R ]
In writing these expressions, we have assumed that the values of DHorxn and DSorxn
do not vary with temperature. This is a reasonable assumption when the differ-
ence between the two temperatures is not large. We can calculate the ratio K2/K1
to determine how many times larger or smaller one equilibrium constant is with
respect to the other. This ratio can be expressed as:
K2 –DHorxn 1 1
(5.14) = exp ( [ – ]
K1 R T2 T1
Eq. (5.15) is known as the integrated Van’t Hoff equation. This relationship shows
that changes in the value of the equilibrium constant with temperature are solely
determined by the sign and magnitude of DHorxn.
Consider the reaction for the decomposition of molecular oxygen in the atmosphere:
O2(g) 2 O(g).
• Express Kp of the reaction.

• Calculate ∆Horxn and ∆Sorxn and predict the ef- Substance DHfo Sfo
fect of changing T on the value of KP. (kJ mol-1) (J mol-1 K-1)
• Qualitatively sketch a graph of KP as a func- O2(g) 0 205.2
tion of temperature.
O(g) 249 161
• Determine how many times larger or smaller is
KP at 50 oC than at 25 oC.
FACING THE CHALLENGE monia to form amines and amides. The resulting
protein-like compounds would form a hot soup
which would aggregate to form colloidal systems
Chemical Origins (coacervates,) from which the first heterotrophic
Chemical thinking has played a central role in the microorganisms evolved. Similar ideas were pro-
development of models and theories about the posed by J. B. S. Haldane around the same time.
origin of life in our planet. Although for many In 1953, Stanley Miller and Harold Urey pub-
years chemists thought that the worlds of the liv- lished the results of a classic experiment designed
ing and the nonliving followed different chemical to test Oparin’s and Haldane’s hypothesis that con-
rules, this idea was shattered in 1827 when Fried- ditions on the primitive Earth led to the synthesis
rich Whöler demonstrated that urea, a well known of organic compounds from simple inorganic pre-
organic compound produced by living organisms, cursors. In this experiment, a mixture of H2O(g),
could be synthesized in the CH4(g), NH3(g), and H2(g)
laboratory by heating an in- in a sealed flask was con-
organic substance, ammoni- nected to a container with
um cyanate. Later, in 1850, hot liquid water and ex-
Adolph Strecker would be posed to sparks to simulate
able to synthesize the amino lightning through a water-
acid alanine from a mixture vapor-rich atmosphere. Af-
of ammonia, hydrogen cya- ter two weeks of running
nide, and acetaldehyde. This the experimental system,
was followed by the synthe- Urey and Miller observed
sis of sugars by Butlerov us- the formation of various or-
ing formaldehyde. ganic compounds, including
During the first part of a large percentage of amino
the twentieth century, sev- By GYassineMrabetTalk (Own work) [Share Alike 3.0] via Wikimedia Commons
acids needed to make pro-
eral scientists developed diverse hypotheses about teins in living cells. One of the surprising results
the beginning of life in our planet. The dominant of the Miller-Urey experiment was that the pro-
view during this time was that the first forms of life cess did not yield a random mixture of chemical
were photosynthetic microorganisms that could fix compounds, but rather a relatively small number
CO2(g) in the atmosphere and use it in combina- of substances, most of them of biochemical sig-
tion with water to synthesize organic compounds nificance.
(autotrophic organisms). The Miller-Urey experiment inspired many
Alexander Oparin’s proposal about the origin others. For example, in 1960 Juan Oró reported
of life stood in sharp contrast with the prevalent the synthesis of adenine, a critical component of
ideas during his time. Oparin reasoned that since nuclei acids, from aqueous solutions of HCN and
heterotrophic microorganisms (those that do not NH3. However, there are numerous biochemicals
produce their own food) are metabolically simpler that do not appear to be prebiotically accessible.
than autotrophs, they should have evolved first. In Current theories about the origin of life suggest
his famous book “The Origin of Life” published in that it is unlikely that a single mechanisms was
1936, he proposed that hydrocarbons were formed responsible for the wide range of chemical com-
in our planet from the reaction of water vapor with pounds that may have been present on the primi-
carbon-metal compounds (carbides), in an atmo- tive Earth. The prebiotic soup was likely formed
spheric medium containing CH4(g), NH3(g), and by contributions from atmospheric synthesis,
H2O(g). The anaerobic fermentation of these hy- deep-sea hydrothermal vent synthesis, and exter-
drocarbons would yield alcohols, aldehydes, ke- nal delivery from sources such as comets, meteor-
tones, and so on, which would then react with am- ites, and interplanetary dust.
Let’s Apply
Chemical Origins
The mixture used by Miller and Urey in their famous experiment about the origin of life is one
of many that have been tested in an effort to better understand how complex organic molecules
could have been formed from simple inorganic compounds. Surprisingly, several of these mixtures
produce similar results. Why is that?
Primitive Mixtures
The following two mixtures have been tested as potential primitive sources of organic
molecules: 1) H2O(g), CH4(g), NH3(g), and H2(g); 2) CO(g), N2(g), and H2(g). Experi-
mental results indicate that the elemental composition (presence of C, H, N, O) of the
mixture is more relevant than the kinds of molecules used. This seems to be due to the
existence of chemical processes that transform one set of substances into the other:
CH4(g) + 2 H2O(g) CO2(g) + 4 H2(g) Substance DHfo Sfo

CO2(g) + H2(g) CO(g) + H2O(g) (kJ mol ) (J mol-1 K-1)
-1
H2(g) 0 130.7
2 NH3(g) N2(g) + 3 H2(g)
CH4(g) –74.6 186.3
• Calculate DH , DS , and DG for each of these
o
rxn
o
rxn
o
rxn CO(g) –110.5 197.7
three processes. Express and determine the value of
CO2(g) –393.5 213.8
KP for each reaction under standard conditions.
NH3(g) –45.9 192.8
• Estimate the values of DGorxn(T) and KP for each of
these processes at a) 100 oC and b) 1000 oC. These H2O(g) –241.8 188.8
values define the range of temperatures that were H2O(l) –285.8 70.0
common in the primitive Earth. Build graphs of
N2(g) 0 191.6
DGorxn(T) as a function of T to analyze the effect of
changing temperature. O2(g) 0 205.2
• Based on your results, discuss which compounds
of C, H, N, and O are more likely to exist at each temperature.
By NASA
Amino Acids
Experiments such as those carried out by Miller and Urey to test hypotheses about the origin of
life in our planet have led to the formation of different types of amino acids. A general chemical
reaction associated with the synthesis of many of these substances can be represented as:
n CO2(g) + NH3(g) + (2n-2+(m-3)/2) H2(g) CnHmNO2(s) + (2n-2) H2O(l)
• Calculate DHorxn, DSorxn, and DGorxn for the

synthesis of the four amino included in the Substance DHfo S fo
(kJ mol ) (J mol-1 K-1)
-1
table. Express and determine the value of KP

for each reaction under standard conditions. Glycine, C2H5NO2(s) –527.5 103.5
• Make graphs showing how DGorxn(T) and KP Alanine, C3H7NO2(s) –560.0 129.2
are expected to change with temperature in Proline, C5H9NO2(s) –507.6 164.1
the range from 25 oC to 200 oC.
Valine, C5H11NO2(s) –628.9 178.9
• Discuss how temperature affects the thermo-
dynamic likelihood of these reactions.
From mural at Page Museum
Other Paths
Other potential reactions for the synthesis of amino acids in the primitive Earth are illustrated
below for the case of glycine. Values of the associated equilibrium constants under standard
conditions are also provided:
2 CH4(g) + NH3(g) + 2 H2O(l) C2H5NO2(s) + 5 H2(g) KP = 6.14 x 10-40

2 CO(g) + NH3(g) + H2(g) C2H5NO2(s) KP = 3.25 x 1013
2 CH4(g) + NH3(g) + 5/2 O2(g) C2H5NO2(s) + 3 H2O(l) KP = 6.97 x 10164
• Determine the DGorxn for each of these processes.

• Discuss how you would expect DGorxn(T) and KP to change with increasing temperature.
• Although the third reaction in this set has a large KP at 25 oC, if the reactants are mixed
the process does not take place. How would you explain this phenomenon?
Let’s Apply
Producing and Sequestering CO2
Carbon dioxide (CO2) is a greenhouse gas that plays a vital role in regulating Earth’s surface tem-
perature. The current episode of global warming is attributed primarily to increasing CO2 emis-
sions due to human activities. More than 30% of the CO2 released by humans dissolves into
oceans, rivers and lakes, which contributes to ocean acidification. Major efforts are now dedicated
to finding ways to reduce CO2 production and to sequester (capture) it from the atmosphere.
CO2 Production
The following chemical reactions result in the formation of CO2(g) by human activities:
Fuel combustion by cars: 2 C8H18(l) + 25 O2(g) 16 CO2(g) + 18 H2O(l)

Steam reforming to produce H2(g): CH4(g) + 2 H2O(g) CO2(g) + 4 H2(g)
Iron smelting: 3 CO(g) + Fe2O3(s) 3 CO2(g) + 2 Fe(s)
• Which of these reactions would you predict to be exothermic?

• Which of these reactions would you expect to have a DSrxn > 0? Ep
• Which of these reactions would have a potential energy (Ep) - R
entropy (S) (PEC) diagram as that shown to the right? At what
temperature would these reactions be product-favored? P
• Which of these reactions would be product-favored at all
temperatures? Represent the variation of DGrxn as a function of S
temperature for these processes.
• Which of these reactions would have an equilibrium constant K > 1 only at low tem-
peratures?
Cement Production
Large quantities of CO2(g) are released into the atmo- Substance DHfo Sfo
sphere during the production of cement through the fol- (kJ mol ) (J mol-1 K-1)
-1
lowing chemical reaction: CaCO3(s) –1206.9 92.9

CaO(s) –635.1 38.2
CaCO3(s) CaO(s) + CO2(g)
CO2(g) –393.5 213.8
Cement Production
[CC by 3.0] via Wikimedia Commons

• Determine the standard enthalpy change DHorxn and the standard
By UK DFID (Own work)

entropy change DSorxn for the reaction used to produce cement.
• Estimate the temperature in oC at which the directionality of this
reaction is reversed.
• Express the equilibrium constant KC for the reaction.
• Sketch how the value of KC is expected to change as a function of
temperature for this reaction.

• Cement is produced at temperatures close to 1450 oC. What is the value of the
equilibrium constant KC for the reaction under such conditions?
CO2 Sequestration by the Oceans
It is estimated that about 1/3 of the

carbon dioxide released by combusting
hydrocarbons dissolves into the ocean 5
according to this process: 0
DGrxn(kJ)
50 100 150 200 250 300 T(K)

–5
CO2(g) CO2(aq) –10
–15
The DGrxn for this reaction as a function –20
of temperature is shown to the right.
• Infer the numerical values, signs, and units of DHrxn and DSrxn for the process.
• Justify the signs of DHrxn and DSrxn based on the analysis the changes in potential
energy and number of configurations when CO2 dissolves in water.
• Discuss wether this reaction is reactant-favored or product-favored at 25 oC.
• Sketch a graph that represents the variation of the equilibrium constant KC for
the reaction as a function of temperature.
• Sketch a graph that represents the concentrations of CO2(g) and CO2(aq) as a
function of time as the reaction reaches equilibrium at 25 oC.
• Carbon dioxide is a greenhouse gas and data shows that the global temperatures
are increasing with an increasing amount of CO2 in the atmosphere. Based on
the information provided, how could an increase in the ocean temperatures im-
pact the amount of CO2 in the atmosphere?
314
Understanding
Mechanism
We have discussed how to evaluate the thermodynamic stability of chemical sys-
U5: MODULE 3
tems and how to predict reaction directionality and extent. However, the values
of DGorxn or the equilibrium constant for a chemical process tell
us nothing about how long it will take for the reaction to hap-
pen. Thus, in this module we will shift our attention to issues
related to the kinetic stability of chemical systems. The rate of
a chemical reaction is influenced by a variety of internal and
external factors. The chemical composition and structure of the
species involved determine the value of the activation energy
needed to initiate the process, as well as the configuration ef-
fectiveness of collisions between reacting substances. Concen-
tration, temperature, and pressure affect the average rate at which Enzymes increase the rate
of specific reactions.
reacting particles collide.
To understand and predict the kinetic behavior of a chemical system, it is
important to explore how the reaction actually happens. This is, what sequence
of events, or mechanism, leads from reactants to products. Knowledge about the
mechanism of a chemical process allows us to better understand and control the
effect of variables such as concentration and temperature on the rate of reaction.
As we will see in Unit 8, it also helps us predict the likely structure of the products
of a chemical reaction.
THE CHALLENGE Mirror Images

Molecules of a given amino acid may exist in one of two forms, commonly
called D and L isomeric forms. The D form is the mirror image of the L form.
These types of molecules can transform into each other. The conversion pro-
cess involves a two-step mechanism.
• How would you expect the rate of conversion to depend on the concen-
tration of the amino acid and on the external temperature?
tral goal of Module 3 is to help you understand how to use information about
reaction mechanism to predict rates of reaction.
Reaction Mechanism
There are chemical processes that are thermodynamically favored but take too
long to happen. The reactant mixture in these types of cases tends to be kinetically
stable although thermodynamically unstable. Consider, for example, the following
two potential routes for the synthesis of the amino acid glycine on the primitive
Earth:
Figure 5.11 Schematic rep-
resentation of the change in
CH2O(g) + HCN(g) + H2O(l) C2H5NO2(s) DG o
rxn
= –154 kJ Gibbs free energy, DG, along
the two reaction paths for the
2 CH4(g) + NH3(g) + 5/2 O2(g) C2H5NO2(s) + 3 H2O(l) DG o
rxn
= –965 kJ synthesis of glycine.
Figure 5.11 shows a schematic representation of the changes in the

Gibbs free energy of the reacting mixtures, DG, as each of these DG
two reactions proceeds from reactants to products. As shown in
this figure, although the second process represented above is more
thermodynamically favored than the first one, it has such a large
free energy of activation that it is likely that the first process will
occur much faster and be a more common path for the synthesis 2 CH4(g) + NH3(g)
of glycine under standard conditions. + 5/2 O2(g)
Analyzing chemical systems from both the thermodynam-
ic and kinetic point of view is crucial in evaluating the actual
CH2O(g) + HCN(g) C2H5NO2(s)
chemical stability of substances. For example, the transformation
of diamond into graphite has a DGo = –2.9 kJ/mol, which makes + H2O(l)
it thermodynamically favored, but the activation energy for the
process is so high (Ea = 728 kJ/mol) that the process takes millions C2H5NO2(s) + 3H2O(l)
of years to occur without external intervention. From this perspec-
tive, diamond can be considered a chemically stable substance. Reaction Path
To better understand the kinetic behavior of chemical systems it is useful to
build models that describe how the reaction takes place at the submicroscopic
level. These models recognize that most chemical reactions involve a sequence of
steps in the path from reactants to products. This sequence of processes define the
mechanism of the reaction. In this mechanistic approach, the overall reaction is Bimolecular Step
viewed as the result of multiple elementary processes, or steps, occurring simulta-
neously across the system. The different elementary steps describe the likely order
in which chemical bonds are broken and formed during the reaction. The most
common elementary steps involve one of the following processes:
a) Unimolecular step, corresponding to the direct transformation of a
single molecule into another;
b) Bimolecular step, involving the collision of two particles of the same or
different type (Figure 5.12). Transition State
c) Termolecular step, involving the simultaneous collision of three particles
of the same or different types.
As a result of these types of processes, atomic rearrangements will lead to the for-
mation of new particles with different composition and structure. Some of these
particles may suffer additional transformations in other reaction steps and will
not be present in the final products. Such chemical species are known as reaction
intermediates.
Figure 5.12 Representation of a bimolecular step in-
volving the collision of two particles. During any type of
elementary step, there is only one transition state.
316 MODULE 3 Understanding Mechanism
LET’S THINK Molecularity
In chemistry, molecularity refers to the number of colliding particles that are involved in a single
reaction step. Determining the molecularity of a reaction step thus mean to identify whether the
process is unimolecular, bimolecular, etc.
• Determine the
molecularity of
each of the two A + A B + C
reaction steps
associated with
this reaction B C + E
mechanism.
• Identify the intermediate species in the mechanism and build a symbolic representation of
the overall reaction that this mechanism is modeling.
• Sketch the potential energy diagram for this reaction, showing the relative potential energy
of reactants, products, and intermediates. (Hint: Analyze the number and nature of the chemical
bonds broken and formed in each step of the mechanism).
• Discuss how you would expect the rate of each step to change when the concentration of
the reacting species in each step (i.e., A in the first step and B in the second step) is doubled.
Concentration Effects
If we know how many particles are involved in a reaction step (molecular-
ity), we can predict the rate of the process will vary with changes in the con-
centration of the reacting species. The rate of the reaction is a measure of how
the concentration of the reactants, or of the products that they form, changes
per unit time. To begin our analysis, let us consider a unimolecular process in
which a single particle A is involved. Imagine that we have nA moles of particles
of the reactant A in a given volume V; the molar concentration would then be
[A] = nA/V. For any reaction of this type, there is a probability k that a particle
will undergo a transformation in a given unit of time. The larger this probability,
the faster the rate of the reaction. The larger the concentration of A particles, the
larger the number of such particles that will be transformed per unit time. In fact,
we can expect the reaction rate to be directly proportional to [A]. Thus, the rate of
a unimolecular step can be expressed as:
(5.15) RATE = k [A] Unimolecular Process
The constant k in this expression is commonly called the rate constant for the
process. In this particular case, the rate constant has units of (1/time). Rates of
reaction are commonly expressed in units of concentration per unit time (e.g.,
molarity/second). Given that the rate of reaction is directly proportional to the
concentration of the reactant to the first power, we say that this is a “first order”
reaction.
In bimolecular processes, the rate of the reaction depends on the probability

that a collision between two particles A and B leads to a chemical transformation.
This probability, k, depends on factors such as the activation energy of the reac-
tion, the configuration effectiveness of the collision, and the temperature of the
system. The concentration of each of the colliding species will also affect the rate.
The higher the concentration of each of substance, the higher the likelihood that
their particles will collide and the faster the reaction rate. In this case, the relation-
ship between rate of reaction and concentration can be expressed as:
(5.16) RATE = k [A] [B] Bimolecular Process
The reaction rate depends on the product of the concentration of each species
because the likelihood of a collision depends on the product of the probability
of finding one particle of each type in the same location. Thus, if we double the
concentration of each reactant, the reaction rate increases four times. The rate con-
stant k for bimolecular processes has units of 1/(concentration x time).
A bimolecular process is said to be first order with respect to each reacting
species. However, overall, the process is a second order reaction. In general, the
relationship between the rate of a reaction and the concentration of each reactant
involved in the process is known as the Rate Law for the reaction. This rate law has
the following general form:
(5.17) RATE = k [A]a [B]b [C]c
where the exponents a, b, and c are the order of the reaction with respect to each
species (i.e, a = 1, first order; a = 2, second order, etc), and the overall reaction
order is given by the sum a+b+c.
Ozone Decomposition LET’S THINK

With the development of photosynthetic organisms on the primitive Earth, the amount of O2(g)
and O3(g) in the atmosphere increased considerably. The formation and decomposition of ozone
molecules was induced by UV radiation from the Sun. The two-step reaction mechanism for the
decomposition of O3(g) in the atmosphere can be represented as follows:
O3(g) O2(g) + O(g) Ep

O3(g) + O(g) 2 O2(g)
• Determine the molecularity of each step and identify all the reaction inter-
mediates;
• Express the rate law for each step in the mechanism. Determine the rate or-
der with respect to each species as well as the overall rate order for each step.
• Write the chemical equation that represents the overall process.
Reactants Products
The potential energy diagram for the overall reaction is shown to the right: Reaction Path
• Locate in the diagram the different reaction steps and the species involved in each of them.
Identify the fastest step in the decomposition process.
As we will discuss in Module 4, there are well established methods to de-

termine the rate law for an overall chemical reaction. This information can be
combined with results from other experimental techniques used to identify reac-
tion intermediates to propose a reaction mechanism. In the mechanistic model
of chemical reactions, the overall rate of the reaction is determined by the rate of
one or more of the individual steps. In particular, for reactions in which one of the
steps is considerably slower than the others, the overall rate of reaction in deter-
mined by the slowest step (Figure 5.13). The speed at which chemical species are
produced in this step sets the maximum speed at which the reaction can proceed.
The relationship between the rate law of the slowest step in a reaction mecha-
nism (rate determining step) and the rate law of the overall reaction is direct when
the slowest step is the first step in the mechanism. Consider, for example, the fol-
lowing hypothetical mechanism for an overall reaction of the type A C:
A + A B + C SLOW (Rate Determining Step)

B C FAST
The rate law for the first (bimolecular) step in the mechanism can be expressed
as: RATE1 = k1[A]2, where k1 is the associated rate constant. For the second step
we have: RATE2 = k2[B]. Given that the first step is the slowest in the mecha-
nism, the overall rate of the reaction should be equal to the rate of the first step:
RATE = k1[A]2. If the above mechanism is correct, the experimental determina-
tion of the reaction order for the overall reaction should indicate that the process
is second order with respect to the concentration of the reactant A.
The above example can also be used to illustrate the problems that we face
Figure 5.13 In this analogy, the
liquid passing through each filter in deriving the rate law for an overall reaction for which the slowest process in
represents a different reaction
step. The rate at which the flask the mechanism is not the first step. Imagine now that the first step in our ex-
is filled is determined by the
speed at which the liquid passes ample was faster than the second step. In this case, the overall rate law should be:
through the slowest filter. RATE = k2[B]. The problem with this relationship is that it is expressed in terms
of the concentration of the intermediate species B; a concentration that we cannot
easily determine and control. To derive a more useful rate law we need to express
[B] in terms of the concentrations of reactants, or of the reactants and products.
Finding this relationship is not always straightforward but it can be more easily
accomplished when we have a mechanism in which the reaction associated with
the first step reaches chemical equilibrium at a rate much faster than the rate of the
second step. In this case we can write:
FAST A + A B + C K = [B][C]/[A]2
SLOW B C (Rate Determining Step)
where K is the equilibrium constant for the first process. If we are able to deter-
mine the value of this constant, the concentration of the intermediate B can be
expressed as [B] = K[A]2/[C]. Thus, the overall rate of the reaction takes the form:
RATE = k2[B] = k2K[A]2/[C] = k[A]2/[C],
where the overall rate constant k = k2K. The experimental analysis of this reaction
should show a reaction rate that is second order with respect to A but also depends
on the inverse of the concentration of product C.
Dimerization LET’S THINK

Amino acids formed on the primitive Earth somehow combined to form dimers, trimers, and
eventually polymers (proteins). Consider the overall reaction for the dimerization of alanine
(Ala):
Experimentally, it is found that the rate law for this process can be expressed as: RATE = k[Ala]2.
Several possible mechanisms have been suggested for this reaction. Schematic representations of
two of them are shown below:
Ep Ep
Ala-Ala*
2 Ala Ala-Ala 2 Ala Ala-Ala

+ H2O + H2O
Reactants Products Reactants Products
Reaction Path Reaction Path
• Write the individual steps that correspond to each mechanism;

• Identify the molecularity of each step and the associated rate law;
• Evaluate which of the two mechanisms would fit the experimental result for the overall rate
law for the reaction;
• Propose a different reaction mechanism that involves a quick first step in which reacting
species reach chemical equilibrium, followed by a slow step. Evaluate whether this type of
mechanism would fit the experimental results for the overall rate law.
Temperature Effects
According to the kinetic model of chemical reactions, for a chemical process to
occur colliding particles must be oriented in a manner that allows reacting groups
to interact effectively. Additionally, colliding particles must have enough energy to
reach a transition state that leads to the formation of the new products. The energy
needed for colliding particles to adopt the structure of the transition state is the
activation energy, Ea, of the reaction. The larger the value of Ea, the less likely that
colliding particles will have enough energy to overcome the activation barrier and
the lower the rate of the reaction will be. Increasing the temperature of the system
leads to an increase in the average kinetic energy of the particles, increasing the
probability of favorable collisions and raising the reaction rate.
The effect of configuration effectiveness, activation energy, and temperature

on the rate of a reaction is represented in the value of the rate constant k in the
associated rate law. This constant is a measure of the probability that collisions will
lead to the formation of the transition state at a given temperature. This probabil-
ity can be calculated using Arrhenius equation expressed as:
(5.18) k = A exp ( –Ea / RT)
where the pre-exponential factor A is a measure of the frequency of collisions with

the proper configuration, and the term exp(-Ea/RT) is proportional to the frac-
tion of colliding particles with enough energy to react at a given temperature. In
general, we can assume that the frequency factor A and the activation energy Ea
are constants for a given chemical process, independent of the value of T. Conse-
quently, we can compare reaction rates at two different temperatures T1 and T2 by
calculating the ratio of the corresponding rate constants k1 and k2:
(5.19) k2 / k1 = exp ( –Ea/RT2) /exp ( –Ea/RT1) = exp[–Ea/R(1/T2– 1/T1)]
LET’S THINK First Amino Acids
The overall activation energy for the dimerization of alanine (Ala) that we studied in the previous
problem is close to 90 kJ/mol.
• Calculate how many times faster the dimerization of alanine is at a) 100 oC, and b) 400 oC,
than at 25 oC. These temperatures represent the range of values suspected to exist in high
pressure hydrothermal vents were life may have started in our planet.
Figure 5.14 The catalyst reduces Changing Mechanism

the overall activation energy by
changing the mechanism from a
single step to a two-step process. It has been suggested that one crucial step in the origin of life in our planet was the
synthesis of substances that could speed up the rate of certain chemical reactions.
Ep In chemistry, such substances are called catalysts and
they act by directly reducing the activation energy
Ea of a reaction or by changing the reaction mecha-
Uncatalyzed nism, which often results in lower activation barri-
ers (Figure 5.14). Catalyst may work by the action
of intermolecular forces on the reacting particles or
by actually forming chemical bonds with some spe-
cies. These interactions facilitate the formation of
a transition state that leads to the new products.
DH Catalyzed Some catalysts may be solid, but they could also
be species in solution. Catalysts participate in the re-
action but they are not consumed during the process.
Reaction Path
They can be separated at the end of the reaction.
Catalysts are of great importance for living organisms because many meta-
bolic processes would take too long in their absence. The substances that catalyze
reactions in biological systems are called enzymes, which tend to be proteins with
a composition and structure that varies depending on the process in which they
participate. Most enzyme-catalyzed reaction rates are million times faster than
those of the same uncatalyzed process. As is the case with all catalysts, enzymes
participate in the chemical reactions but are not consumed in the process, nor they
change the directionality and extent of a chemical reaction. However, enzymes
differ from most chemical catalyst in their high specificity for the processes that
they help accelerate. The action and high specificity of enzymes has been explained
using different models that we will explore in the following activities.
Lock and Key Model LET’S THINK

The process of enzyme catalysis begins with the binding of a substance, commonly called the
substrate, to the active site of the enzyme. The active site is a region of the enzyme that interacts
relatively strongly with the substrate. The binding process alters the electron distribution in the
substrate molecules and induces structural changes that facilitate their transformation. In the “Lock
and Key” model of enzyme action, the active site is assumed to have a unique geometric shape that
[Public domain] via Wikimedia Commons

is complementary to the shape of
By Jerry Crimson Mann (Own work)

the substrate molecule. The en-
zyme-substrate system is thought
to be analogous to a key-lock pair
in which the lock is the enzyme
and the key is the substrate. This
model explains the high specific-
ity of enzymes as only the correct key (substrate) can fit into the key hole (active site) of the lock
(enzyme). The reaction mechanism for enzymatic action in this model can be represented as:
Enzyme (E) + Substrate (S) Enzyme-Substrate Complex (ES) FAST

Enzyme-Substrate Complex (ES) Enzyme (E) + Product (P) SLOW
• Build a potential energy diagram representing the reaction path from reactants to products;
• Write the rate law for each individual step in the reaction mechanism, as well as the equilib-
rium constant for the first step. Use these relationships to derive the overall rate law for the
reaction in terms of concentrations that can be measured experimentally.
The overall rate law that you derived in the previous step is only valid at low concentrations of
substrate. At high concentrations, the reaction rate does not
change much with increasing [S} as shown in the graph. Maximum Rate (Vmax)
• Use the lock and key model to explain the flattening of Catalyzed
the reaction rate at high substrate concentrations.
• What is the order of the reaction under such conditions?
Uncatalyzed
LET’S THINK Induced Fit Model
The “Lock and Key” model provides an inaccurate description of the behavior of most enzymes.
The model has been modified to take into account changes in the structure of the enzyme as a result
of its interaction with the

substrate. In the “Induced
By Tim Vickers (Own work)

Fit Model” the initial in-
teractions between enzyme
and substrate are assumed
to be relatively weak, but
these interactions induce
conformational changes in
the enzyme that strengthen
the binding. The reaction mechanism for enzymatic action involves three steps represented by the
following set of generic chemical equations:
E + S ES FAST
ES EP SLOW
EP E + P FAST
• Build a potential energy diagram representing the reaction path from reactants to products;
• Write the rate law for each individual step in the reaction mechanism, as well as the equilib-
rium constant for the first step. Use these relationships to derive the overall rate law for the
reaction in terms of concentrations that can be measured experimentally.
• Compare the overall rate law predicted by the “Induced Fit Model” with that of the “Lock
and Key Model.” Discuss whether their predictions could be used to identify the best model
for enzymatic action.
Share your ideas with a classmate, and clearly justify your reasoning.
For a range of temperatures, the rate of an enzyme-catalyzed reaction increases as the temperature is
raised. A ten degree rise in temperature will increase the activity of most enzymes by 50 to 100%.
• Consider enzymes working at body temperature (37 oC).

Estimate the range of values for the activation energy of
reactions catalyzed by these types of enzymes.
Reaction Rate
The graph to the right depicts the effect of temperature on the

reaction rate of enzyme-catalyzed processes.
• Build an explanation for the effect of temperature on the

rate of reaction. Temperature
FACING THE CHALLENGE enzyme has chiral components, it will not interact
in the same way with the D or L isomers of a chiral
substance. This property enhances the selectivity
Mirror Images of the enzyme as a catalytic species.
How do we know if two molecules are identical? The origin in the asymmetry of the chiral-
In principle, they should have the same chemical ity of biologically molecules (homochirality) is
composition and structure. However, sometimes not well understood. Many chemical reactions
making this judgment is not so easy. Consider the in which chiral molecules are produced generate
two molecules shown in the image. Are they the the different enantiomers in the same proportion.
same? One way to answer this Additionally, enantiomers
question is to explore whether can transform into each other
the molecules are superimpos- through a chemical process
able; this is, if we can make one known as racemization. The
lay on top of the other having rate of interconversion varies
the same distribution of atoms. from substance to substance,
If we do that with the amino but for many naturally occur-
acids in the image, it turns that ring compounds the rate is not
the molecules are not identical. negligible. Thus, it is not clear
One is the mirror image of the other, like our two how living organisms developed to selectively use
hands, and they are not superimposable. They are and produce only one type of enantiomet.
said to be enantiomers or optical isomers. When There are several hypotheses about the origin
samples made up of these two types of molecules of homochirality of naturally occurring molecules
interact with polarized light, each of the samples in our planet. For example, analysis of amino acids
rotates the polarization plane in different direc- found in meteorites hitting our planet reveals the
tions. Pairs of enantiomers are often designated presence of preferentially one enantiomer. There
with the letters D and L to differentiate them. is evidence that certain type of radiation to which
Molecules that have at least one non-superim- these meteorites may have been exposed triggers
posable mirror image are said to be chiral. Molecu- the formation of optical isomers. These results sug-
lar chirality is caused by the presence gest that homochirality on Earth
of carbon atoms that are bonded to Achiral may have had an extraterrestrial
four different groups. If all carbons origin.
in a molecule are bonded two only However, there are other types
three or fewer different groups, the of processes that result in the pref-
molecule will be achiral and it will erential formation of one optical
not have enantiomers. Molecular isomer over the other. Stirring a
chirality is relevant to our discus- solution as it crystallizes leads to
sions in this module because many Chiral one chiral form almost exclusively
biologically active molecules are over the other. Similarly, boiling a
chiral and exist as only one type of enantiomer in supersaturated solution perturbs the crystallization
living organisms. For example, biologically active process, leading to the formation of a single chiral
amino acids are of type L but not D, while natu- phase. Once an enantiomeric imbalance is created,
rally occurring sugars are D but not L. it may be amplified and propagated by chemical
Chirality is of central importance for many processes that favor the formation of one type of
biological functions. Chiral molecules have most isomer over the other. Identifying the actual cause
of the same properties, but they interact different- of homochirality thus demands a careful analysis
ly with L and D enantiomers of other chiral sub- of the mechanisms behind these types of chemical
stances. Thus, for example, if the active site of an processes.
Let’s Apply
Racemization
Pure samples of L or D enantiomers eventually convert into a mixture of both forms. This process
is called racemization and the mixture that is formed is a racemic mixture. Racemization in vitro
or in vivo of some substances, such as chiral pharmaceutical drugs, may be a serious problem as
one enantiomer may be the one that triggers the response that we want and the other may induce
unwanted metabolic processes.
Amino Acids
The following potential energy diagram represents the racemization of the amino acid
alanine. The process is characterized by having DHorxn = 0 and DSorxn = 0.
Ep
L L- + H+ H+ + D- D
+ H+ H+ +
Reaction Path
• Represent the reaction mechanism for the racemization of alanine as a sequence

of steps. Determine the molecularity of each step and identify all reaction inter-
mediates.
• Establish the rate law for each reaction step and derive the rate law for the overall
racemization process. Determine the order of the reaction with respect to the con-
centration of the amino acid. Discuss how a change in concentration would affect
the rate of racemization.
• The activation energy for the first step of the racemization of alanine is close to
130 kJ/mol. Determine the temperature at which the rate of racemization would
be double than that corresponding to standard conditions.
• Given the nature of this process, describe what you would expect to happen to
a pure sample of L alanine as the time passes. What would be the value of ratio
[D]/[L] when the system reaches chemical equilibrium?
Thalidomide
Thalidomide is a drug introduced in the 1950s to treat morning sickness in pregnant women
and aid sleep. It was sold until 1961, when it was withdrawn from the market after being found
that the drug caused birth defects. The thalidomide molecule is chiral and each enantiomer has
a different effect in the human body. While the D isomer is a sedative, the L isomer can induce
malformations (teratogenic). Unfortunately, the rate of racemization is relatively high, taking
only a few hours for a pure sample of one of the enantiomer to generate a racemic mixture inside
the body. The interconversion process can be represented in the following way:

Chiral Carbon
Thalidomide-D Thalidomide-L
• Write each of the reaction steps associated with the above process. Determine the molecu-
larity of each step and identify all reaction intermediates.
• Build a potential energy diagram to represent the racemization process;
• Establish the overall rate law for the process and identify the order of the reaction with
respect to the concentration of thalidomide.
• Measurements of the rate constant for the racemization process at two different tempera-
tures generate the following values: k(15 oC) = 0.37 days-1; k(37 oC) = 0.30 hours-1. Use
this information to determine the activation energy for the racemization.
The rate of the racemization reaction in aqueous solution varies depending on the concentra-
tion of hydronium ion, H3O+ (which determines the acidity of the solution). If we represent the
D-thalidomide molecule using the symbol T(D)=O, the reaction mechanism for the first half of
the racemization process can be expressed as:
T(D)=O + H3O+ T(D)=OH+ + H2O FAST

T(D)=OH+ + H2O T(D)-OH + H3O+ SLOW
• Determine the molecularity of each step and identify all reaction intermediates.
• Establish the rate law for each step, as well as the equilibrium constant for the first
process. Use these relationships to find overall rate law for the process and identify the
order of the reaction with respect to the relevant species. Identify the overall order of the
reaction.
• The hydronium ion is said to “catalyze” the racemization process. Discuss any evidence
you have based on the analysis of the reaction mechanism to support such a claim. Build
an energy potential diagram that represents how the H3O+ ions may affect the reaction
path and speed up the process.
Let’s Apply
Photochemical Smog
Photochemical smog is a type of air pollution
produced when sunlight acts upon motor vehi-
cle exhaust gases, such as nitrogen oxides (e.g.,
NO, NO2) to form harmful substances such as
ozone (O3). The substances responsible for this

phenomenon participate in a reaction cycle that
determines the concentration of pollutants at dif-
ferent times during the day.
Ozone Formation
Nitrogen dioxide gas, NO2(g), is formed by chemical reactions involving N2(g) and O2(g) at
the high temperatures inside internal combustion engines in our cars. In the presence of sun-
light, NO2(g) reacts with O2(g) to generate O3(g) as described by the following overall reaction:
NO2(g) + O2(g) NO(g) + O3(g)
This chemical process occurs in two steps, as illustrated in the potential energy diagram.
In the second step of the Ep Ea = 306.5 kJ/mol Ea = 107 kJ/mol

process, the radical spe-
cies O reacts with O2. O + NO
In order for the process
to occur, the collision
O2 + M NO + O3 + M*
should involve a third
particle M that can ab-
sorb excess energy from NO2
the collision (e.g., N2). Reaction Path
• Write the chemical equations for each reaction step and determine the molecularity of
each of them. Identify all reaction intermediates.
• Express the rate law for each reaction step and derive the rate law for the overall process.
• The activation energy required to initiate the process is provided by sunlight. Calculate
the minimum frequency n of the radiation needed to start the reaction.
• Estimate how many times faster this reaction is at 30 oC versus 10 oC.
• Based on the information provided, evaluate whether this process can be expected to
occur to a large extent.
Ozone Consumption
Ozone formation is faster during the day due to the

action of sunlight on NO2 molecules. Thus, O3(g)
accumulates in the troposphere and its concentra-
tion peaks sometime in the afternoon. During the
night, ozone reacts with NO(g) according to the
PPB
following reaction:
NO(g) + O3(g) NO2(g) + O2(g)

This is a single-step process with an activation en-
Hour
ergy Ea = 12.5 kJ/mol and a DHrxn = –199.5 kJ/mol.
• Build potential energy diagram that represents the transformation of reactants to

products. Indicate on the diagram the activation energy and the heat of the reaction
for this process.
• Derive the rate law for this process.
• Estimate how many times slower this process is at 0 oC than at 25 oC.
Additional Reactions
The oxygen atoms gener- Chemical Reaction Rate Constant k

ated by the decomposi- (25 oC)
tion of NO2 molecules (molecules-1 cm3 s-1)
in the presence of light
NO2 NO + O• Varies: Light Intensity
are highly reactive and
interact with other sub- O• + H2O 2 OH• 2.0 x 10-10
stances to generate differ- CH4 + OH• H2O + CH3• 6.3 x 10-15
ent types of pollutants.
CH3• + O2 CH3O2• 1.8 x 10-12
Consider the following
sequence of reactions in- CH3O2• + NO NO2 + CH3O• 7.7 x 10-12
volving methane, CH4: CH3O• + O2 CH2O + HO2• 1.9 x 10-15
CH O + OH• HCO• + H O 9.0 x 10-12
• Analyze this reaction 2 2
mechanism. Identify HCO • + O 2

CO + HO 2
• 5.2 x 10-12
reactants, products, 2 HO2• H2O2 + O2 1.7 x 10-12
and reaction inter-
mediates. Derive the overall chemical equation for this process.
• Use the data to evaluate which step may determine the overall rate of reaction.
328
Measuring
Rates
Chemical models of the mechanism of a chemical reaction are useful in under-
U5: MODULE 4
standing the process, in predicting the effect of changing concentration and tem-
perature on reaction rates, and in devising strategies
to control the chemical reaction. However, to build
those models we need experimental information
about how the actual reaction proceeds as a function
Concentration
of time. The analysis of how the concentration of re-
actants or products changes with time can be used Product
to derive the order of the reaction with respect to
different species and to establish the rate law for the Reactant
process. Measurements of the rate of the reaction at
different temperatures can be used to calculate the
activation energy for the process. All these data, to- Time
gether with experimental studies about intermediate
species, are critical in making judgments about the kinetic stability of a chemical
system and in building hypotheses about reaction mechanisms.
The analysis of kinetic data demands a basic understanding of the mathemati-
cal relationships between concentration and time for chemical reactions with dif-
ferent rate orders. It also requires that we understand how experimental data can
be represented in different ways to elicit underlying trends. Developing these skills
is one of the central goal of this module.
THE CHALLENGE Many Options

Once formed, amino acids may undergo a variety of chemical reactions such
as decomposition, dimerization, and racemization. Which process dominates
may vary with temperature and pressure.
• What types of experimental measurements would you complete to de-

termine which chemical process dominates at various conditions?
This module will help you develop the type of chemical thinking used to an-
swer questions similar to those posed in the challenge. In particular, the central
goal of Module 4 to help you understand how to derive kinetic information
from changes in the concentration of reacting species as a function of time.
Reaction Rates
The analysis of the kinetic stability of biomolecules has been crucial in the evalu-
ation of different theories about the origin of life. For example, chemical species
needed for the synthesis of amino acids, such as CH4 and NH3, are abundant in
hydrothermal vent regions with temperatures between 60 oC and 400 oC. How Figure 5.15 Decarboxylation
of alanine into ethyl amine
could we determine how stable amino acids are under such conditions? From the and carbon dioxide.
thermodynamic point of view, we could try to determine the DGrxn for the decom-
position at various temperatures. So, for example, it is known that the
decomposition of alanine (Figure 5.15) is thermodynamically favored
under standard conditions. However, this process may take so long that
amino acids may combine to form proteins before decomposing.
Alanine Decomposition LET’S THINK

The kinetics of the decarboxylation of alanine has
been explored by measuring the concentration of 1.0
the amino acid, [Ala], as a function of time, t, in
0.8
aqueous solutions at various temperatures. The
[Ala] (mM)
data at T = 200 oC is shown in the graph, where 0.6
the concentration is expressed in milimoles per
liter (mM) and the time is measured in days. 0.4
0.2
• How would you use these data to calculate the
rate of the reaction at any given time? 0
0 6 12 18 24 30 36
t (days)
Experimental data for the concentration as a function of time for any reacting
species involved in a chemical reaction of the type A B can be used to calcu-
late the average rate of reaction between any two data points using this relationship:
(5.20) RATEAVERAGE = – D[A]/Dt = D[B]/Dt
Where D[X] is the difference in the concentration of species X between any two
times (D[X] = [X]2 - [X]1). The average rate of the reaction is a positive quantity
1.0
expressed in units of concentration per unit time that measures the average speed Rateinst = - D[Ala]/Dt
at which reactants are being consumed or products are being produced. For ex- 0.8
ample, in the case of the decarboxilation of alanine at 200 oC, the average rate of
[Ala] (mM)
0.6
the reaction between days 3 and 6 is: 0.4
D[Ala]
0.2 Dt
RATEAVERAGE = – ([Ala]2 – [Ala]1)/(t2– t1) = – (0.79 – 0.89)/(6 – 3) = 0.033 mM/day
0
0 6 12 18 24 30 36
The changes in the concentration of a reacting species as a function of time t (days)
can be more accurately described by calculating the instantaneous rate of reaction,
which is a measure of the instantaneous speed at which the substance is consumed Figure 5.16 The instantaneous rate at
a given time can be estimated by cal-
at any given time. The instantaneous rate is a measure of the slope of the tangent culating the slope of the tangent line.
line to the concentration versus time graph at any selected time. It can be esti-
mated using experimental results as shown in Figure 5.16.
330 MODULE 4 Measuring Rates
The instantaneous rate of reaction is mathematically defined as the derivative

of the concentration as a function of time:
(5.21) RATEINST= – d[A]/dt
As we will see in the next section, this relationship can be used to derive how the
concentration [A] changes as a function of time from experimental data.
LET’S THINK Kinetic Stability
The data tables included in this activity show the variation 150 oC 200 oC
of the concentration of alanine as a function of time for the Time [Ala] Time [Ala]
decarboxylation process at two different temperatures: 150 (years) (mM) (days) (mM)
o
C and 200 oC. 0 1 0 1
1 0.933 1 0.962
• Calculate the average rate of reaction between years 2
2 0.871 2 0.925
and 3, and between years 6 and 7 for T = 150 oC.
3 0.812 3 0.889
• Discuss how you would go about estimating the instan-
taneous rate of the reaction at year 4. 4 0.758 4 0.855
• How does the rate of reaction changes as the concentra- 5 0.707 5 0.823
tion of alanine in the system decreases? How would you 6 0.660 6 0.791
explain this result?
7 0.616 7 0.761
• How does the rate of reaction changes when raising the
8 0.574 8 0.732
temperature? How would you explain this result?
According to the kinetic model of chemical reactions, the reaction rate can be
expected to decrease as the concentration of reactants decreases and there are fewer
collisions between reacting particles. How fast the rate decreases as the concentra-
tion of reactants diminishes depends on the order of the reaction. Thus, we can
infer reaction orders by analyzing changes in concentration as a function of time.
LET’S THINK Data Analysis
A central goal of this module is to learn how to use kinetic experimental data for chemical reac-
tions to infer the associated rate law. Consider, for example, typical experimental data obtained in
the analysis of enzyme (E) catalyzed reactions: S + E P at high substrate Time [S]
(S) concentrations ([S] >> [E]). (min) (mM)
0 0.500
• How is the average rate of reaction changing over time?
5 0.413
• What is the rate law for this reaction?
10 0.326
• What is the rate order for this reaction?
15 0.239
20 0.152
Reaction Order and Integrated Rate Laws

The derivation of rate laws from experimental measurements can be systematized
by using mathematical procedures for data analysis. Consider generic chemical
reactions governed by rate laws of the form: RATEINST = k [A]m where k is the rate
constant for the reaction and m is the reaction order. Given the definition of in-
stantaneous rate of reaction, we can then write
m
(5.22) RATEINST = – d[A]/dt = k [A]
If we assume that m =1 (first order reaction), Eq. (5.22) indicates that the rate
at which [A] decreases over time is directly proportional to the actual value of [A].
This is the typical behavior of an exponential decay and it can be shown that [A]
decreases with time according to the following equation:
(5.23) [A] = [A]o exp ( – kt ) ln [A]
where [A]o is the concentration of species A at t = 0 and [A] is the concentration at

time t (this relationship can also be expressed as [A]2 = [A]1 exp [– k(t2 – t1)] where t
[A]1 and [A]2 are the concentrations at time t1 and t2, respectively). This expression ln [A]o
is known as the integrated rate law for a first order reaction.
Eq. (5.23) can be rewritten as ln [A] = ln [A]o – kt by taking the natural log-
arithm of both sides of the equation. The structure of this relationship suggests a
strategy to infer the reaction order and the value of the rate constant k from ex- m=–k
perimental data. The relationship has the general structure of the equation for a
straight line: y = b + mx if we make the following identifications:
Variables: y = ln [A] , x = t Constants: b = ln [A]o , m = – k Figure 5.17 Schematic representa-

tion of the variation of ln [A] as a func-
tion of time t in a first order reaction.
Thus, if a reaction is first order with respect to the measured concentration [A], a
plot of ln [A] versus time t should result in a straight line with a slope m = – k and
a y-intercept b = ln [A]o (Figure 5.17).
USEFUL TOOLS To linearize an equation it is convenient to:

a) Rearrange the equation to get a variable, or
a function of, it on the left side of the equation.
Linearizing equations is the process of modify- This becomes the y variable.
ing an equation to generate new variables that b) Regroup the right side of the equation to cre-
can be plotted to produce a straight line graph. ate a term containing the other variable, or a
The mathematical equation for a straight line function of it. This becomes the x variable.
has the form: c) Identify the constant term that multiply the x
y = b + mx variable (slope) and any additive constants that
are left over (y-intercept).
where x and y are variables, while b and m are Consider the equation: A = 4pr2. We can
constants. The constant b represents the y-in- linearize it by taking logarithms of both sides:
tercept of the line and m is its slope. We can
linearize an equation if we can get it in the form
ln A = ln (4pr2) or ln A = ln (4p) + 2 ln r
variable1 = constant1 + constant2 x variable2 A plot of ln A versus ln r will produce a straight
If this is possible, then a plot of variable1 versus line with b = ln (4p) and m = 2. In this particu-
variable2 should produce a straight line with a lar case, we could also simply plot A versus r2.
y-intercept equal to constant1 and a slope given The graph would be a straight line with a slope
by constant2. m = 4p and a y-intercept b = 0.
Let us apply the previous ideas to explore whether the decarboxyl-

ation of amino acids is a first order reaction. Data for the process at 150
o
C is presented in the table below. In this table we also include the values of
ln [Ala] needed to build the graph ln [Ala] versus t shown in Figure 5.18.
As we can see in this figure, ln [A} is a linear function of time which is in-
dicative of a first order reaction. The y-intercept is equal to zero given that
[A]o = 1 mM, and the slope of the line m = – k = – 0.0693 years-1. Thus, we can
express the rate law for the decarboxylation of alanine as:
Figure 5.18 Analysis of experi- RATEINST = 0.0693 [Ala]

mental data for the decarcoxyl-
ation od alanine to determine
whether the reaction is first
order with respect to [Ala]. This relationship indicates that the rate of the reaction is directly proportional
to the concentration of alanine and thus it
Time [Ala] ln [Ala] decreases as a function of time. The order
t (years)
(years) (mM) of the reaction is independent of tempera-
0 2 4 6
0 0 1 0 ture but the value of the rate constant k
will change as T increases or decreases.
- 0.1 1 0.933 –0.0694
Once the rate law of the reaction is de-
2 0.871 –0.138 rived, it can be used to predict the instan-
ln [Ala]
- 0.2
3 0.812 –0.208 taneous rate of the reaction at any concen-
- 0.3 tration of reactant. For example, the rate
4 0.758 –0.277
of the reaction when [Ala] = 0.7 mM is
- 0.4 ln [A] = – 0.0693 t 5 0.707 –0.347 equal to 0.0693 x 0.7 mM/year (i.e., the
- 0.5 6 0.660 –0.416 concentration [Ala] decreases at a rate of
0.0485 mM per year). Given that the reac-
tion is first order with respect to the con-
centration of the amino acid, the reaction rate decreases linearly with a decrease in
the value of [Ala].
LET’S THINK Data Analysis
http://www.chem.arizona.edu/tpp/chemthink/resources/U1_M1/graph.html
The rate of decarboxylation of alanine depends on temperature. The table in
200 oC
this activity provides information about changes in the concentration of the Time [Ala]
amino acid as a function of time at 200 oC. (days) (mM)
0 1
• Use the data provided to verify that the reaction is first order with respect
1 0.962
to [Ala] at 200 oC. Click on the graphing tool to plot the data.
• Determine the value of the rate constant k at this temperature. 2 0.925
• Use the integrated rate law for the process to calculate the time it will 3 0.889
take for the concentration of alanine to decrease from 1 mM to 0.5 mM. 4 0.855
• Calculate the time it will take for the concentration of alanine to de- 5 0.823
crease from 0.5 mM to 0.25 mM, and from 0.25 mM to 0.125 mM.
6 0.791
Based on your results, discuss how long it takes to halve the concentra-
tion of alanine. How would you explain this result?
CLICK TO PLAY
The integrated rate law for a chemical reaction expresses how the concentra-
tion of a relevant reacting species changes as a function of time. Thus, it can be
used to predict the time it will take for a reactant or product to reach a given
concentration, or to predict such concentration at a selected time. For a first order
reaction, the exponential decay of the concentration with time facilitates making
such predictions because the time required for the concentration of a reacting spe-
cies to be reduced in a certain fraction (e.g., a half, a quarter) is independent of the
actual concentration of the substance.
To illustrate this property of first order reactions, let us determine the time it
takes for any concentration [A]o of the reacting species to decrease to half its value
[A] = [A]o/2. Based on the integrated rate law for this type of process as expressed
in Eq. (5.23), we have:
Figure 5.19 At 150 oC, the concen-
tration of alanine is reduced by half
(5.24) ln [A]o/2 = ln [A]o – kt1/2 or t1/2 = ln (2) / k every ten years (t1/2 = 10 years).
where we have used the symbol t1/2 to represent the time

required to halve the concentration of the reacting spe- 1.0
cies. This quantity is commonly known as the half-life of
the process. According to Eq. (5.24), the half-life for a
first order reaction only depends on the value of the rate 0.75
constant k, which is a function of temperature but is in- [Ala] (mM)
1 half-life
dependent of concentration. This behavior is illustrated 0.5
in Figure 5.19 for the decarboxylation of alanine at 150
o
C. As we have seen, at this temperature the rate constant 2 half-lives
k = 0.0693 years–1. The half-life for the process is then: 0.25
3 half-lives
t1/2 = ln (2)/ k = ln (2) / 0.0693 = 10 years

0
0 10 20 30 40
The half-life of a substance during a first order decompo-
sition process is often used as an indication of its kinetic t (years)
stability.
Data Analysis LET’S THINK

The graph shown in this activity depicts the concentration [R] as a function of time t at three dif-
ferent temperatures (300 K, 330 K, 400 K) for a reaction of the form: 2 R P
• Which set of data corresponds to each temperature?

• What is the order of this reaction?
• What is the half life of the reaction at each tempera-
ture?
• Express the rate law for the reaction at each T.
• Determine the reaction rate when [R] = 0.5 at 400 K.
• Predict the value of [P] after 30 h at 330 K.
• Predict the time at which [R] = 0.125 M at 300 K.
Clearly justify your reasoning.

1 / [A] We can apply the same ideas and mathematical procedures just discussed to
generate the integrated rate law for second order reactions. In this case, we need to
m=k identify a function that satisfies the relationship: – d[A]/dt = k[A]2. Such a func-
tion can be expressed as:
t
(5.25) 1 / [A] = 1 / [A]o + kt
The structure of this relationship suggests that if a chemical reaction is second

1 / [A]o order with respect to [A], a graph of experimental data representing the inverse of
the concentration 1/[A] versus time t should yield a linear plot with a y-intercept
Figure 5.20 Representation of the
b = 1/[A]o and a slope m = k (Figure 5.20). Once the rate constant k is known, Eq.
variation of 1/ [A] as a function of (5.25) can be used to predict the value of [A] at any given time or to determine the
time t in a secondorder reaction.
time t it will take for this concentration to reach a certain value.
LET’S THINK Second Order Reactions
http://www.chem.arizona.edu/tpp/chemthink/resources/U1_M1/graph.html
Molecules of amino acids may react with each other to form dimers. The table lists data for the
dimerization of alanine at 200 oC:
Time [Ala]
• Use the data determine the rate order for the dimerization of alanine. (s) (mM)
Click on the graphing tool to plot the data.
14 0.150
• Determine the value of the rate constant k at this temperature.
15 0.0932
We can use the integrated rate law for a second order reaction to develop an 16 0.0692
expression for the half-life t1/2 for substances involved in this type of process: 17 0.0552
18 0.0460
• Derive an expression for t1/2 in a second order reaction. Compare your
result with that for a first order process. Discuss differences and similari- 19 0.0394
ties between the two expressions and evaluate the extent to which t1/2
for a second order reaction may be a useful quantity in making judgments
about kinetic stability.
CLICK TO PLAY
ln k Activation Energy
The type of data analysis discussed in the previous section can be used to derive the
values of the rate constant for a chemical reaction at different temperatures. Ac-
ln A cording to the kinetic model of chemical reactions, changes in the values of k are
determined by Arrhenius equation as introduced in Eq. (5.18). By taking natural
1/T logarithms of both sides of this equation, this relationship can be expressed as:

m = – Ea/R
(5.26) ln k = ln A – (Ea / R)(1 / T)
The structure of this equation suggests that if know the values of the rate constant
Figure 5.21 Schematic representa-
k at different temperatures T, then plotting (ln k) versus (1/T) should yield a linear
tion of the variation of ln k as a func- plot with y-intercept b = ln A and slope m = Ea / R (Figure 5.21). Given that the
tion of the inverse temperature (1/T)
according to Arhenius equation. value of R is well known, the activation energy Ea can be easily derived from the
experimental data.
Data Analysis LET’S THINK

These data listed in the table correspond to the decarboxylation of Temperature k
alanine at different temperatures. (K) (years-1)
323 1.17 x 10-8
• Use these data to calculate the activation energy for the
process Ea as well as the value of the pre-exponential factor A. 373 8.10 x 10-5
Click on the graphing tool to plot the data. 423 6.93 x 10-2
• Predict the value of the rate constant k at 623 K and calculate 473 1.42 x 101
the half-life of alanine at this temperature
523 1.06 x 103
Share and discuss your ideas with a classmate, and clearly justify 573 3.71 x 104
your reasoning.
Many chemical reactions do not occur in a single step but involve many
elementary processes. Thus, the activation energy determined from experimental
data is likely a measure of the height of the activation barrier for the rate deter-
mining step in the reaction mechanism. It is important to point out that many
chemical reactions satisfy Arrhenius equation only in a small range of tempera-
tures. Deviations are commonly observed when exploring reaction rates over wide
temperature intervals. In these cases, the plot of (ln k) versus (1 / T) is not linear,
which indicates that the value of the activation energy Ea depends on temperature.
The value of Ea at any given temperature can then be estimated by finding the
slope of the tangent line to the plotted curve at the corresponding value of 1/T.
Thermodynamics and Kinetics

Chemists frequently emphasize the distinction between the types of predictions
that can be made using thermodynamic data, such as DHorxn, DSorxn, and DGorxn,
and those that can be derived from kinetic data, such as k and Ea. Thermodynamic
data allow us to predict the directionality and extent of a reaction, but do not pro-
vide information about the time it will take for the process to reach chemical equi-
librium. On the other hand, kinetic data can be used to predict how much time
will be needed for the concentration of reactants and products to reach certain
values, but tell us little about reaction extent. The rate of a chemical reaction can
be altered by using catalysts that change the value of the activation energy Ea but
do not have any effect on the value of DGorxn, which determines reaction extent.
Although understanding the scope of thermodynamic and kinetic data is of
central importance when working with chemical systems, it is also critical to rec-
ognize the relationship that exists between these different descriptions of chemical
processes. To illustrate such connection, let us consider a simple unimolecular
reaction of the form A B that reaches chemical equilibrium after some time.
The rate law for the transformation of A into B (A B) can be expressed as
RATEA-B = kf [A], where kf is the rate constant for what we will identify as the for-
ward process. This constant is a measure of the probability of A transforming into
B at a given temperature. However, once B starts forming in the system, there
is a probability kb of B transforming back into A. The rate law for this backward
process (A B) is given by RATEB-A = kb [B].
Given that the rate of the forward and backward processes are proportional
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M4/eqab.html
to the concentration of different species, we can expect these rates to change as

the chemical reaction proceeds. If we start the process with pure substance A in a
container, the forward RATEA-B will be faster than the backward rate RATEB-A at the
beginning of the reaction. As time passes and A is consumed and B is produced,
CLICK TO PLAY the forward process will slow down while the backward reaction will speed up. At
some point, the rate at which A is consumed (or B is produced) in the forward
process will be equal to the rate at which A is produced (or B is consumed) in the
backward process. Thus, the concentration of all species will remain constant and
the system will reach chemical equilibrium (Figure 5.22). From the kinetic point
of view, chemical equilibrium is defined by the equality of the reaction rates for
the forward and backward processes: RATEA-B = RATEB-A, which in this example
corresponds to the condition
Figure 5.22 Click on the image to
run a simulation of an A <--> B ele- kf [A] = kb [B] or kf / kb = [B]/[A]
mentary reaction. You may change
the values of kf and kb to observe
the effect on the ratio of concen- This relationship implies that the ratio of concentration of products to reactants
trations at chemical equilibrium.
remains constant at chemical equilibrium. We have already defined this ratio as the
equilibrium constant K for the chemical reaction, which has a value determined
by the change in standard Gibbs free energy at temperature T, DGorxn(T) (see Eq.
(5.12)). Then, according to our analysis, the ratio of the kinetic rate constants for
the forward and backward processes for an elementary reaction is directly related
to the thermodynamic equilibrium constant for the reaction as expressed in the
following equation:
(5.27) kf / kb = K = exp ( – DGorxn(T) / RT )
Although most chemical reactions do not occur on a single step like the reac-
tion A B analyzed in the previous example, the equilibrium constant of more
complex processes can also be expressed in terms of the rate constants for the dif-
ferent elementary processes involved in the reaction mechanism
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M4/eqab2c.html
LET’S THINK Kinetics and Equilibrium
Consider an elementary process of the form: A + B 2C
• Express the rate laws for the forward and backward processes;
• Identify the relationship between the rate constants for the forward (kf ) and backward
(kb) processes and the concentrations of each species at chemical equilibrium;
• Imagine you start the reaction with equal concentrations of
each reactant [A]o = [B]o. Predict the ratio of concentrations
at equilibrium for chemical systems in which a) kf / kb = 1; b)
kf / kb = 2; c) kf / kb = 0.5.
• Use the simulation that you can launch by clicking on the im-
age to verify your predictions.
Share your ideas with a classmate and justify your reasoning. CLICK TO PLAY
FACING THE CHALLENGE tration of short peptides.

Autocatalytic species are chemical substanc-
es that catalyze their own synthesis. An example
Polymerization and Replication
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M4/bz.html
of an autocatalytic elementary step in a reaction
Although a variety of experiments have shown mechanism may take the form: A + B 2B.
that small organic molecules can form from the
CLICK TO PLAY
reaction between simple inorganic molecules such
CO2, H2O, and NH3, one of the unresolved is-
sues in moderns theories about the origin of life
is how small organic molecules then combined to
form complex polymers such as proteins, RNA,
and DNA. Analyses of reaction mixtures as those
generated in the Miller-Urey and Oró experiments
show that besides the synthesis of the basic com-
ponents of common biopolymers, such as amino
acids and nucleotides, the process also leads to the
Oscillating chemical reactions, such as the
formation of chemical compounds known to hin-
Belousov-Zhabotinsky reaction, involve
der polymerization processes. Additionally, poly- autocatalytic steps in their mechanism.
peptides (polymeric chains of amino acids) and
nucleic acids may break apart through their reac- One may speculate that as polymerized molecules
tion with water (hydrolysis). increased in length and complexity, some of them
Polymeric chains made up of 20-100 mono- may have adopted configurations that facilitated
meric units seem to be required to have any primi- their binding to other molecules. These molecules
tive catalytic and replication functions. However, may have worked as primitive catalysts for differ-
the polymerization of amino acids and nucleotides ent types of chemical reactions. As the variety of
are thermodynamically unfavorable processes. polymeric combinations increased, some of these
Some scientists have proposed that the selective molecules may have been able to catalyze their
adsorption of monomers onto mineral surfaces own self-replication. Although these self-replicat-
may have promoted their polymerization, a pro- ing molecules may have been scarce ar first, they
cess that has been confirmed in the laboratory. would have become increasingly more abundant
Once the polymers were formed, they may have given their ability to autocatalyze their own syn-
detached from the surface by thermal motion or thesis. Several known examples of self-replicating
by the action of concentrated salt solutions, a pro- molecular systems have been already discovered
cess that could have taken place in tidal regions and studied in the laboratory.
during evaporation or freezing of seawater. The appearance of the first molecular species
Hydrothermal vents may have been critical capable of replication, catalysis, and multiplication
sites for the formation of short polypeptides, as would have marked the origin of life and evolution
peptide bond formation becomes more thermody- in our planet. It is judged that the first “living”
namically favored at higher temperatures. Experi- molecular entities must have had the following
ments carried out with glycine and other amino properties: they could make imperfect copies of
acids under conditions similar to those present in themselves, to allow for the formation of more or
hydrothermal vents have led to the formation of less effective “mutant” molecules; they could facili-
molecules with up to 6 amino acid units. Howev- tate the replication of other molecules; and they
er, these amino acids rapidly decompose by hydro- could survive long enough to replicate before de-
lysis with water. To solve this problem, it has been composing. It is believed that the first molecules of
proposed that the development of autocatalytic these type may have had a structure similar to that
species may have helped sustain a steady concen- of RNA in modern living organisms.
Let’s Apply
Monomers or Dimers?
Amino acids formed in the primitive Earth may have been involved in a variety of chemical pro-
cess, such as decomposition, racemization, and dimerization. In fact, it is suspected that the forma-
tion of dimers, the first step in the polymerization process that leads to the formation of proteins,
may have helped amino acids accumulate and escape rapid decomposition at the high temperatures
that were common in our planet.
Dimerization Kinetics
Let us explore the dimeriza-

tion of alanine. The dimer-
ization process has the basic
structure: 2 A A2 + B.
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M4/dimer.html
• Click on the image below to launch the simulation of the dimerization of alanine.
The data that you can collect using this simulation can be used to determine the order of
the reaction, the values of the rate constant at different temperatures, and the activation
energy for the process.
CLICK TO PLAY
• Run the simulation at a constant temperature and
collect data for the concentration of alanine (mM) as a
function of time (s). Graph the data using the proper
selection of variables to determine the order of the re-
action and the value rate constant for the dimerization
process at the selected temperature.
• Repeat the process at different temperatures to obtain a collection of values for
the rate constant k as a function of temperature. Use these data to determine the
activation energy Ea for the reaction.
• Calculate the half-lives of a 1 M solution of alanine at 100 oC, 150 oC, and 200
o
C.
• Compare all your results for the dimerization of alanine with the equivalent
results for the decomposition (decarboxilation) of this amino acid generated
through the different activities in this module. Based on these results, identify
whether there is a range of temperature in which one could expect alanine to
dimerize before undergoing decomposition.
Hydrolysis Kinetics
Once an amino acid dimer is formed, it may react with water and get decomposed back into
the free amino acids: A2 + B 2 A. Processes in which chemical bonds are broken by in-
teraction with water molecules are generically known as “hydrolysis.” The kinetic study of the
hydrolysis of amino acid dimers and polymers at high temperatures and pressures is of central
importance to understand how proteins may have developed in the primitive Earth.
The following table shows experimental data for the hydrolysis of glycine

dimers (GG) at 120 oC and 265 atm:
t (h) 0 10 20 30 40 50
[GG] (mol/L) 0.020 0.0178 0.0158 0.0140 0.0125 0.0111
• Use these data to determine A) the order of the hydrolysis reaction, B) the value of the
associated rate constant kh, and C) the half-life in days of the GG dimers under the given
experimental conditions.
The following tables show data for the half-lives t1/2 of the GG dimers at different temperatures
and pressures:
P = 25 atm P = 265 atm

T (oC) t1/2 (h) T (oC) t1/2 (h)
100 2.40 x 103 100 1.75 x 102
160 2.90 x 10 160 2.15 x 10
220 1.03 220 5.17
280 7.51 x 10-2 280 1.58
• Use these data to determine the activation energy for the hydrolysis reaction at each of the
experimental pressures. Discuss how pressure affects the rate of hydrolysis.
The values for the equilibrium constant for the hydrolysis of GG dimers at 265 atm of pressure
are KC = 1.9 x 10-2 at 160 oC and KC = 4.8 x 10-2 at 220 oC.
• Use the information provided to determine the rate constants kd for the dimerization of
glycine at 160 oC and 220 oC at 265 atm.
• Estimate the value of the activation energy for the dimerization process, and discuss
whether GG dimers can be expected to form at the given conditions.
Let’s Apply
Drug Degradation
Many pharmaceutical drugs undergo chemical reactions that alter their chemical composition. The
rate of the degradation or decomposition processes depends on temperature and relative humidity.
Analyzing reaction kinetics is critical to estimate the shelf life of these pharmaceutical products.
Paracetamol
Paracetamol, or acetominophen, is a widely used over-the-counter

pain reliever and fever reducer (active component of Tylenol). Un-
der adverse storage conditions, this substance may decompose by
reacting with water. The data in the following table shows changes
in the amount of paracetamol (p-ac) present in a 200 mg commer-
cial tablet as a function of time at 15 oC and 75% relative humidity:
t (days) 0 50 100 150 200 250 300

p-ac (mg) 200 198.3 196.7 195.0 193.4 191.8 190.2
• Calculate the average rate of decomposition between 100 - 150 days and 250-300 after
production. Sketch how the amount of paracetamol changes over time.
• Use the data to determine A) the order of the decomposition reaction for paracetamol,
and B) the value of the rate constant k for the process at 15 oC and 75% humidity;
• Calculate the half-life t1/2 (in days) for the decomposition of paracetamol;
• The shelf life of a pharmaceutical drug is usually defined as the time it takes for 10% of
the drug to degrade (or the time it takes for the initial amount to decrease to 90%). Cal-
culate the shelf life (expressed in months) of paracetamol at 15 oC and 75% humidity.
The table shows the values of

T (oC) 25 37 45
the rate constants for the de-
composition of paracetamol k (days-1) 75% RH 1.92 x 10-4 2.17 x 10-4 2.42 x 10-4
at three different temperatures k (days-1) 100% RH 1.69 x 10-4 1.92 x 10-4 2.12 x 10-4
and two different relative hu-
midities (RH):
• Use these data to estimate the value of the activation energy Ea for the decomposition
process at different relative humidities. Compare your results and discuss how humidity
affects the rate of decomposition.
Where From?
reactants is kinetically stable. As we have seen
in this unit, kinetic stability depends on factors
such as concentration of reactants, temperature,
Where To? and activation energy of the process. Predictions

about the rate of a chemical reaction can be sim-
plified if we have a sense of the sequence of steps
that lead from reactants to products. Thus, the
The central goal of this determination and analysis of reaction mecha-
unit was to introduce nisms is a central activity for many chemical sci-
the qualitative and quan- entists. This work involves careful experimental
titative ways of thinking exploration of the nature of the intermediate spe-
used in chemistry to cies generated during a chemical reaction, as well
predict the direction- as analysis of how the concentrations of reactants
ality, extent, and rate and products change as a function of time under
of chemical processes. different conditions of temperature and pressure.
Thus, we analyzed how to use compositional and The intellectual and experimental tools dis-
structural cues to qualitatively compare the rela- cussed in this Unit are invaluable in the analy-
tive potential energy and entropy of reactants and sis and prediction of the properties and behavior
products. These types of comparisons are useful of reactive systems, from the hydrosphere to the
in predicting the likelihood of a chemical process. atmosphere in our planet, from single-celled to
However, actual experimental data can be used to multicellular organisms, from the combustion
quantify changes in the enthalpy and the entropy engines in our cars to the batteries that power
of a system, and quantitatively predict reaction our cell phones. In all these cases, understanding
extent based on the analysis of the sign and value change requires that we pay attention to the ther-
of the change in the Gibbs free energy due to the modynamic and kinetic factors that determine
reaction. the directionality, extent, and rate of any poten-
During our discussions, we emphasized that tial transformation.
the analysis of the thermodynamic stability of a In the following Unit of the textbook we will
chemical system demands that we pay close atten- seek to apply some of the ideas that we have dis-
tion to both energetic and entropic factors. Some cussed to develop strategies to control chemical
chemical processes mainly occur because random reactions. To simplify our task, we will focus our
atomic movements lead to states with lower po- attention on the study of chemical processes that
tential energy in which strong attractive inter- occur rapidly but often with limited extent. This
actions among particles limit further rearrange- will allow us to discuss issues related to thermo-
ments. Other processes happen because random dynamic control without having to worry about
particle motions take the system to a state with kinetic issues. We will leave for Unit 7 the analy-
so many different configurations (high entropy) sis of systems in which kinetic control is also rel-
that is unlikely that the system will revert back evant. However, before we
to its original state. In some cases, energetic and begun a new Unit, let
[Generic 2.0] via Flickr Commons
By Nina Matthews (Own work)
entropic factors act together in driving a chemi- us explore if “YOU

cal reaction. In other cases, these factors are in ARE READY” to ap-
competition and the final outcome depends on ply what you have
the working temperature. learned to the analy-
Although a chemical process may be favored sis of some interesting
from the thermodynamic point of view, it may systems.
take so long for it to happen that the mixture of
342 Are you Ready?
Are You Ready?

Many of the ideas discussed in this unit can be applied to the study of the directionality, extent, and rate of
physical changes. This is, transformations in which the chemical nature of the submicroscopic species that
make up the system (e.g., atoms, ions, molecules) does not change during the process.
Phase Changes
A change of state, such as melting or boiling, is a typical example of a physi-

cal transformation. During these types of processes, energy in the form of heat
is exchanged between the system and its surroundings and the entropy of the
system may increase or decrease. Consider, for example, the changes in enthalpy
(DH) and entropy (DS) when water melts or evaporates at different tempera-
tures under atmospheric pressure at sea level (1 atm):
H2O(s) H2O(l) H2O(l) H2O(g)
T DHfus DSfus T DHvap DSvap

(K) (kJ mol-1) (J K-1 mol-1) (K) (kJ mol-1) (J K-1 mol-1)
233.15 6.18 22.7 333.15 42.3 113.7
253.15 6.10 22.3 353.15 41.5 111.3
273.15 6.01 22.0 373.15 40.7 109.0
293.15 5.92 21.7 393.15 39.8 106.8
313.15 5.84 21.4 413.15 39.0 104.7
• Calculate the change in Gibbs free energy DG for each of these processes
at each of the given temperatures;
• Analyze the evolution of DG as the temperature increases. What do the
DG values indicate about the directionality of the phase transitions at dif-
ferent temperatures?
• The melting point of water is Tm = 273.15 K (0 oC) and its boiling point
is Tb = 373.15 (100 oC) at 1 atm of pressure. What is the value of DG for
each of the phase changes at the temperature of the transition? How do
you explain these results?
• Based on you analysis, establish a general relationship between the DH,
DS, and T for any substance at the point in which a phase transition can
be expected to occur.
Share and discuss your results with a classmate, and justify your reasoning.
via Wikimedia Commons
By Disdero (Own work)

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Physical Transformations
Dissolution
The extent to which a solute dissolves into a solvent can be predicted by evaluating the
change in Gibbs free energy DG for the process. Consider the values for DHosoln, DSosoln, and
DGosoln for the dissolution in water of various ionic compounds under standard conditions:
Dissolution Process DHosoln DSosoln DGosoln

(kJ mol-1) (J K-1 mol-1) (kJ mol-1)
NaCl(s) Na+(aq) + Cl-(aq) 3.8 42.9 –9.0
NaBr(s) Na+(aq) + Br-(aq) –0.6 52.4 –16.2
NaI(s) Na (aq) + I (aq)
+ -
–9.3 66.4 –29.1
NaNO3(s) Na+(aq) + NO3-(aq) 20.7 88.7 -5.7
MgCl2(s) Mg2+(aq) + 2 Cl-(aq) –159.9 –113.6 –126.0
AlCl3(s) Al3+(aq) + 3 Cl-(aq) –335.5 –264.8 –256.5
CaCO3(s) Ca (aq) + CO (aq)
2+
3
2-
–12.3 –201.7 47.7
ZnS(s) Zn2+(aq) + S2-(aq) 94.4 –145.5 137.8
Ca3(PO4)2(s) 3 Ca2+(aq) + 2 PO43-(aq) –62.4 –836.3 186.9
• Calculate the equilibrium constant for each of the above dissolution processes un-
der standard conditions. Based on the data available and your own results, discuss
which compounds can be expected to be soluble or insoluble in water;
• Analyze the data to evaluate how energetic and entropic factors affect the solubility
of these different compounds. For example, how does the charge of the ions seems
to affect the values of DHosoln and DSosoln? How does the size of the ions affect these
quantities? How would you explain these different effects?
• How would you use the data to justify the solubility rule that suggests that most
ionic compounds in which both cations and anions are multi-charged are likely to
be insoluble in water?
Consider the following thermodynamic data for AgCl(s) and AgBr(s):
Dissolution Process DHosoln DSosoln DGosoln

(kJ mol-1) (J K-1 mol-1) (kJ mol-1)
AgCl(s) Ag+(aq) + Cl-(aq) 65.7 33.8 55.6
AgBr(s) Ag+(aq) + Br-(aq) 84.8 47.1 70.8
• How would you explain the unexpected solubility properties of these compounds?
Share and discuss your results with a classmate, and clearly justify your reasoning.
344 Are you Ready?
Physical Transformations
Clathrates
Clathrates are ice-like systems in which methane or other gases are

caged by water molecules. On freezing, water molecules commonly
arrange in a hexagonal crystal structure. In the presence of sufficient
methane and other gases, water crystallizes in a cubic lattice that traps
gas molecules. Large deposits of methane clathrate have been found on
the ocean floors of our planet. The amount of carbon present in these
hydrates is estimated to be at least twice the amount found in all fossil
fuels on Earth. The study of methane clathrates have recently gained
much attention because their potential contribution to global warming
if they were to release methane, a greenhouse gas, into the atmosphere.
The rate constants of methane clathrate formation kf have been measured at different tem-
peratures at high pressure in the laboratory. The following table presents typical results.
• Use this information to estimate the activation energy T (K) kf

for the formation of methane clathrates at high pressure. 230 4.70 x 10-6
• The activation energy for the dissociation (destruction)
of the clathrate is close to 32 kJ/mol. Compare this value 240 1.03 x 10-5
with the activation energy for clathrate formation and 250 2.11 x 10-5
generate a hypothesis to explain the difference. 260 4.09 x 10-5
Zeolites and Thermodynamics
Zeolites are microporous crystalline solids commonly used as adsorbents and catalysts. Their po-
rous structure is generally made up of aluminum, silicon, and oxygen atoms (aluminosilicates)
and it can trap different types of cations such as Na+, K+, Mg2+, and Ca2+. Thus, these materials are
widely used in the water purification industry to eliminate undesired species. Consider the data
for the standard heat of adsorption DHoad and the standard entropy of adsorption DSoad for Cu2+,
Zn2+, and Cd2+ on a typical zeolite Z.
• How would you explain the positive values of DHoad and Ion DHoad DSoad
DSoad for the adsorption process (transfer of ions from solu- (kJ mol-1) (J mol-1 K-1)
tion to the zeolite surface)? Cu2+ 19 75
• Calculate the standard Gibbs free energy of adsorption DGoad
Zn2+ 20 77
for each of these ions and determine which adsorption pro-
cess is more thermodynamically favored. Cd2+ 23 82
Are You Ready?

Zeolites and Kinetics
The following tables show values of the rate constants for adsorption kad, measured in grams of zeolite Z per
milligram of adsorbed ion per minute (g mg-1 min-1), for Cu2+, Zn2+, and Cd2+ at different temperatures:
Cu2+ Zn2+ Cd2+

T (oC) kad T (oC) kad T (oC) kad
(g mg-1 min-1) (g mg-1 min-1) (g mg-1 min-1)
kad 30 1.35 x 10-2 30 1.31 x 10-2 30 9.70 x 10-3
M2+ + Z M2+-Z 40 1.45 x 10-2 40 1.41 x 10-2 40 1.42 x 10-2
kdes 50 2.60 x 10-2 50 2.43 x 10-2 50 2.14 x 10-2
60 3.28 x 10-2 60 2.86 x 10-2 60 2.01 x 10-2
• Use these data to estimate the activation energy of adsorption on the zeolite for each of the three ions.
• Based on the available data, sketch energy diagrams to represent the adsorption of each of the ions on
the zeolite. Discuss which of the adsorption processes is more kinetically favored.
• Use the information provided, together with your own results, to calculate the rate constants for de-
sorption kdes (transfer of ions from the zeolite to aqueous solution) for each of the three ions at 30 oC.
Zeolites as Catalysts
Zeolites can serve as catalysts for different chemical reactions. The associated reaction mechanisms typically
involve fast adsorption steps followed by a slow step in which the adsorbed species undergo the chemical
transformation into the product P. Consider the following two generic reaction mechanisms:
MECHANISM 1:
A + Z AZ Fast MECHANISM 2: A + Z AZ Fast
AZ P + Z Slow B + Z BZ Fast
AZ + BZ P + Z Slow
Let us call CA and CB the concentration of the different reacting species, CZ the concentration of empty
adsorbing sites on the zeolite, and CAZ and CBZ the concentration of zeolite sites occupied by species A and
B, respectively.
• Derive the overall rate law for each of these mechanisms in terms of CA, CB, and CZ. Assume that the
fast steps in the mechanisms reach equilibrium with associated equilibrium constants K1 and K2.
346 Are you Ready?
Are You Ready?

We have already discussed that ammonia, NH3, is one of the most important industrial chemical substances
in the world. Its industrial synthesis is accomplished taking advantage of our understanding of the thermo-
dynamic and kinetic factors that affect the chemical process.
Synthesis and Thermodynamics
Most industrial ammonia is produced by combining N2(g) and H2(g):
Synthesis Process DHorxn DSorxn

(kJ mol-1) (J K-1 mol-1)
1/2 N2(g) + 3/2 H2(g) NH3(g) –45.9 –99.1
• Justify the signs of DHorxn and DSorxn based on the analysis of the composition
and structure of reactants and products;
• Calculate the standard change in Gibbs free energy DGorxn for the reaction.
• Express the equilibrium constant for the process KP in terms of the pressures of
reactants and products. Calculate its value under standard conditions.
• The synthesis of ammonia is thermodynamically favored at some temperatures
but not others. Discuss whether the reaction will be favored at low or high
temperatures. Estimate the temperature at which the reaction goes from being
thermodynamically favored to thermodynamically unfavored.
Share and discuss your ideas and results with a classmate, and justify your reasoning.
Thermodynamics versus Kinetics
The activation energy for the synthesis of NH3(g) from H2(g) and N2(g) in the absence
of catalyst is high, Ea = 325 kJ/mol. The rate of the reaction may be increased by car-
rying out the synthesis at high temperatures.
• Use the data that has been provided to build an internal potential energy dia-
gram for the synthesis of ammonia;
• Determine how many times faster the reaction would be at 500 oC than at 25
o
C;
• Determine how many times smaller the equilibrium constant for the synthesis
reaction KP would be at 500 oC than at 25 oC.
• Evaluate the trade-offs associated with running the synthesis at high T.
Revisiting Ammonia
Catalysis
http://www.chem.arizona.edu/tpp/chemthink/resources/U5_M4/nh3.html
The synthesis of ammonia is typically carried out at high temperatures (300 - 550
o
C) and high pressures (150 - 250 atm)
CLICK TO PLAY
• Predict how an increase in pressure is
expected to affect A) the rate of the reac-
tion, B) the amount of NH3 produced the
reaction, and C) the equilibrium constant
KP for the process;
• Click on the image to launch a simula-
tion of the synthesis reaction. Use these
interactive tool to verify your predictions.
The reaction can be speeded up by using a catalyst that reduces the activation energy
of the process. The most popular catalysts are based on iron (Fe) and ruthenium
(Ru). The rate of reaction for the catalyzed process depends on the concentration of
nitrogen gas, N2(g), in the reactor:
• The following table shows the variation in the concentration of N2(g) as a

function of time for a reaction carried out at 500 oC and 200 atm. Use these
data to determine A) the order of the reaction with respect to N2(g) and
B) the value of the overall rate constant k for the synthesis process at the given
conditions.
t (s) 0 0.1 0.2 0.3 0.4 0.5 0.6

[N2(g)] (mol/L) 2.00 1.68 1.42 1.19 1.01 0.846 0.710
The rate constant for the synthesis reaction in the presence of a Fe-based catalysts has
been determined at various temperatures. The following table presents the results:
T (oC) 25 100 200 300 400

k (s-1) 3.24 x 10-9 2.32 x 10-6 5.81 x 10-4 2.11 x 10-2 2.64 x 10-1
• Use the data provided to determine the activation energy in the presence of
the Fe-based catalyst;
• Estimate how many times faster the reaction is in the presence of catalyst
compared to the reaction rate in its absence (Ea = 325 kJ/mol) at 500 oC.
348 Are you Ready?
Revisiting Ammonia
Mechanism
The following image depicts the reaction path for the synthesis of NH3 from N2 and
H2 over the surface of a ruthenium (Ru) catalyst. The symbol * denotes an empty
site on the catalyst and X* represents an adsorbed species.
Ep
• Describe the sequence of elementary steps that take place. Identify all the
intermediate species. Discuss how the catalyst provides a reaction path with a
lower effective activation energy. What processes decrease the internal poten-
tial energy of the reacting species?
• Identify the rate-limiting step in the process. Assuming that all of the steps
that only involve adsorption or desorption of species are fast and achieve
chemical equilibrium, derive the overall rate law for the synthesis reaction in
the presence of a catalyst. Use the following notation to represent the concen-
tration of relevant species: [N2], [H2], [*] (this symbol represents the concen-
tration of empty adsorption sites on the catalyst);
• Based on your results, discuss how doubling the concentration of [N2] and
[H2] by increasing the pressure should affect the rate of the reaction.
By ESA
Unit 5: Image Attributions

Module 1
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P280 & P281: Background
derivative from “The Origin of Life” poster: Lynn Margulis & Dorian Sagan; P282: Top right “Rust on iron” by Laitr Keiows (Own work) [Share
Alike 3.0] http://commons.wikimedia.org/wiki/File:Rust_on_iron.jpg; P283: Fig. 5.1 “Et baal” by Einar Helland Berger (Own work) [Share Alike
2.5] http://commons.wikimedia.org/wiki/File:Et_baal.jpg; P291: Center By NASA/Jenny/Mottar.
Module 2
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P296: Top right “AerialViewPho-
tochemicalSmogMexicoCity 2” by Fidel Gonzalez (Own work) [Share Alike 3.0] http://commons.wikimedia.org/wiki/File:AerialViewPhotochem
icalSmogMexicoCity_2.jpg; P300: Fig. 5.6 “Bombenkalorimeter mit bombe” by Harbor1 (Own work) [Generic 3.0] http://commons.wikimedia.
org/wiki/File:Bombenkalorimeter_mit_bombe.jpg; P309: Center “Miller-Urey experiment-en” by GYassineMrabetTalk (Own work) [Share Alike
3.0-2.5-2.0-1.0] http://commons.wikimedia.org/wiki/File:Miller-Urey_experiment-en.svg; P310: Bottom center By NASA; P311: Center photo-
graph of mural at Page Museum (La Brea Tar Pits); P313:Top right “A factory fit for the future” by UK Department for International Development
(DFID) (Own work) [CC by 3.0] https://commons.wikimedia.org/wiki/File:A_factory_fit_for_the_future_(8756741567).jpg
Module 3
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P321: Center right Derived from
“Competitive inhibition” by Jerry Crimson Mann (Own work) [Public domain] http://commons.wikimedia.org/wiki/File:Competitive_inhibi-
tion.svg; P322: Top right “Induced fit diagram” by Created by TimVickers (Own work) [Public domain] http://commons.wikimedia.org/wiki/
File:Induced_fit_diagram.svg; P323: Center “Chirality with hands” (Public domain) http://commons.wikimedia.org/wiki/File:Chirality_with_
hands.svg.
Module 4
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P341: Top left Derivative from
“The Origin of Life” poster: Lynn Margulis & Dorian Sagan; Bottom right “Day 139 - IF you Run, Jog or Cycle Look below O_O” by Nina Mat-
thews (Own work) [Generic 2.0] https://www.flickr.com/photos/21560098@N06/6722653055/in/set-72157627444093697/; P342 & P343:
Background “DeadSea3667”by Disdero (Own work) [Share Alike 2.5] http://commons.wikimedia.org/wiki/File:DeadSea3667.jpg; P348: Right
By ESA (European Space Agency).
General
Activity icons: Clip art from Microsoft Office; Molecular structures: Derived from online public software (Chemical Education Digital Library,
Jmol) and via Wikimedia Commons (Public domain images).
UNIT 6
How do we
control
chemical
processes?
Chemical thinking can be applied to devise strategies to control the
extent and rate of different types of chemical reactions. This control
can be achieved by various means such as selecting the proper reac-
tants, changing their concentrations, and modifying temperature
and pressure.
In this Unit we will apply our understanding of chemical reactions to

explore strategies to control an important type of chemical processes.
In particular, the central goal of Unit 6 is to analyze how to control
acid-base reactions in aqueous solutions. Acid-base reactions play a
critical role in many relevant systems, including our planet’s atmosphere,
hydrosphere, and lithosphere, human blood, and all cells in our bodies.
These types of reactions occur at a rather fast rate, which allows us to focus
on learning how to control reaction extent.
To illustrate the core ideas of Unit 6, we will explore the acid-base properties of
common pharmaceutical drugs looking to address questions such as:
How do acids and bases interact with water? How do we characterize acid and base strength?
How do we control the extent of acid-base reactions?

via Flickr Commons
[Generic 2.0]
350
Chemical Thinking
UNIT 6 MODULES
M1. Characterizing Interactions
Recognizing the types of interactions between
main components in a chemical system.
M2. Influencing Chemical Equilibrium
Determining and controlling the effect of differ-
ent factors on the extent of chemical reactions.
M3. Analyzing Chemical Stability
Analyzing energetic and entropic factors that af-
fect the stability of reactants and products.
351
352
Characterizing
Interactions
Many chemical processes in our surroundings and inside our bodies lead to chang-
U6: MODULE 1
es in chemical composition that may be beneficial or harmful for the systems

involved. To better explain, predict, and control these chemical
reactions chemists have devised strategies based on the careful

analysis of how different reactants interact with each other.
By kanenas.net (Own work)

The nature of these interactions depends on the composi-
tion and structure of the chemical compounds, but there
are classes of substances that tend to react in similar ways
with one another. Acids and bases are two prototypical ex-
amples of classes of chemical compounds that undergo simi-
lar types of transformations when interacting with each other. Fruits contain
Water behaves as an acid or as a base in the presence of different diverse acids
substances. Given that many systems of interest contain water, understanding and
controlling acid-base reactions in aqueous environments is of central importance
in many fields, from earth and environmental sciences to biochemistry. Acid-base
reactions tend to be quite fast, which facilitates their analysis because one can fo-
cus on the thermodynamic factors that influence reaction extent without worrying
about kinetic issues.
THE CHALLENGE Drug Problem
Many pharmaceutical drugs are acids or bases that react with wa-
ter, or with other acids and bases present in our bodies. These reactions
may alter the structure of drug molecules or their charge distribution.
• Why would it be important to control the acid-base reactions that drugs

undergo inside our body ? How could these reactions be controlled?
central goal of Module 1 is to help you understand the nature and effect of the
interactions between acids and bases.
Chemical Thinking U6 How do we control chemical processes? 353
Water as a Reactant
Many important chemical reactions occur in aqueous environments. When we
think about these processes, it is common to consider water as an inert solvent that
does not participate in the reactions. There are many chemical processes, however,
in which water is not only the solvent but actually reacts with the substances dis-
solved in it. In this Unit, we are particularly interested in exploring those reactions
that lead to the transfer of H+ ions, commonly referred to as “protons,” between
water molecules and the molecules of other chemical compounds. This proton
transfer is the result of the interaction between sites with partial negative (d–)
or partial positive (d+) charges in the water molecules, and molecular sites with
opposite charge in neighboring particles. Consider, for example, the interaction
between the water molecule and the acetic acid molecule represented in Figure
6.1. The interaction between the positive site in the OH group in the acetic acid
Figure 6.1 Proton transfer
molecule and the negative site (oxygen atom) in the water molecule may result in between an acetic acid and a
water molecule. In this case,
the transfer of one proton from the acid to water, resulting in the formation of a a water molecule gains a H+
ion and transforms into a hy-
hydronium ion (H3O+) and an acetate ion (CH3COO–): dronium ion H3O+.
– +
[ [
d+
d–
[ [
By convention, the arrow representing the chemical interaction between mole-
cules (red arrow in Figure 6.1) is drawn from the site with a partial negative charge
in one molecule to the site with a partial positive charge in the other molecule.
Notice that there are many other potential interactions between the acetic acid and
the water molecules that could result in proton transfer. For example, between the
oxygen atom in the carbonyl (C=O) group in the acetic acid molecule, which has
a negative partial charge, and a hydrogen atom in a water molecule , which has a
partial positive charge. In this case, the proton would move from the water to the
acetic acid molecule. However, this type of transfer is less likely to occur due to
unfavorable changes in the energy and entropy of the system.
In the reaction between acetic acid and water molecules, a proton is trans-
ferred from the acid to water. There are chemical compounds, however, in which
the interaction between molecules leads to proton transfer from water to the other
reactant. This type of interaction is illustrated in Figure 6.2 for the chemical reac-
tion between methyl amine (CH3NH2) and water. The outcome of this process is a Figure 6.2 Proton transfer
positive methyl ammonium ion (CH3NH3+) and a negative hydroxide ion (OH–). between water and a methyl
amine molecule. In this case,
Notice that in this case, proton transfer results from the interaction between a a water molecule loses a H+
ion and transforms into a hy-
nitrogen atom (d–) in the amine and a hydrogen atom (d+) in water: droxide ion OH–.
+ –
[ [
d–
d+
[ [
354 MODULE 1 Characterizing Interactions
LET’S THINK Proton Transfer
Analyze the composition and structure of the following molecules:
Lactic Acid Caffeine Alanine

• Predict how each of these molecules may interact with water. Which atoms in each molecule
are most likely to be involved in proton transfer? What would the outcome of the reaction
with water be?
Acids and Bases

Substances comprised of particles that transfer protons to water molecules are
known as Brønsted-Lowry acids (“acids” hereafter). As a result of the interaction
between acids and water, hydronium ions (H3O+) are formed. On the other hand,
substances made of particles that accept protons from water molecules are classi-
fied as Brønsted-Lowry bases (“bases” hereafter), and they lead to the formation of
hydroxide ions (OH–) in aqueous solution. In general, acids are known as proton
donors while bases are known as proton acceptors.
It is common to represent acids dissolved in water using the generic symbol
HA(aq), while bases are depicted as B(aq). A general chemical reaction between an
acid and water can then be represented in the following manner:
HA(aq) + H2O(l) A–(aq) + H3O+(aq)
This process is commonly known as “acid dissociation.” The extent of this reaction
depends on the composition and structure of the molecules of the acid HA, on
the acid’s concentration, and on the temperature of the system. Similarly, a general
chemical reaction between a base and water can be expressed as:
B(aq) + H2O(l) HB+(aq) + OH–(aq)
The position of this chemical equilibrium will be determined by the composition

and structure of base B, its concentration, and the temperature.
Most known acids and bases do not react with water to completion. This is,
not all the molecules of the acid donate a proton to a water molecule, and not all
molecules of a base accept a proton when dissolved in water. To understand and
control the extent to which proton transfer occurs we need to further explore the
properties of water as a reactant.
Acids or Bases? LET’S THINK

Many pharmaceutical drugs contain carboxylic groups (–COOH) that exhibit acidic behavior or
amine groups (–NH2, –NHR, –NR2) that exhibit basic behavior when interacting with water.
Salicylic
Acid
Ephedrine
• Predict and represent the structure of the products of the reaction between each of these two
drugs and water.
• Write the chemical equation between each of the drugs and water.
Water’s Autoionization
Water molecules interact strongly with one another due to their strong bond di-
poles and their overall molecular polarity. The attractive interaction between at-
oms with a positive partial charge (hydrogens) in one molecule and the atom with
a negative partial charge (oxygen) in another water molecule may result in proton
transfer between two molecules of water. As shown in Figure 6.3, as a result of Figure 6.3 Proton transfer
this transference one molecule becomes a hydroxide ion (OH–) while the other between two water molecules
results into a negative ion
molecule becomes a hydronium ion (H3O+): (OH–) and a positive ion (H3O+)
– +
[ [
d+
d–
[ [
This process, called the autoionization of water, is often represented in the follow-
ing manner in symbolic form:
(6.1) H2O(l) + H2O(l) OH–(aq) + H3O+(aq)
with an associated equilibrium constant:
(6.2) Kw = [OH–][H3O+]
Remember that the equilibrium constant expression does not include pure liquids
involved in a reaction as long as their concentrations is constant during the pro-
cess. The extent to which water autoionizes is very small and only a minimal frac-
tion of the water molecules undergo autoionization. Thus, for practical purposes
the concentration of water, [H2O], remains constant in this process.
The value of the autoinization equilibrium constant depends on temperature;

experiments indicate that at 25 oC Kw = 1.0 x 10–14. In pure water, the autoion-
ization process produces equal amounts of OH– and H3O+ ions (see Figure 6.3).
Consequently, according to Equation (6.2), we should have [OH–] = [H3O+] =
1.0 x 10–7 M in pure water at 25 oC. The molar concentration of H2O is close to
55.5 M under the same conditions, which confirms that only a very small fraction
of the water molecules autoionize (about one molecule per every 500 hundred
million molecules of water). As is the case for all chemical reactions that reach
equilibrium, autoionization is a dynamic process and particles in the system are
constantly undergoing change. Some water molecules autoionize, but simultane-
ously some H3O+ ions react with OH– ions to form water molecules. Overall, the
average concentration of H2O, OH–, and H3O+ remains constant.
LET’S THINK Thermodynamic Analysis

The autoionization of water represented in Equation (6.1) is an endothermic process with DHorxn =
+55 kJ per every two moles of water involved in the reaction. The change of entropy for the same
process is DSorxn = –80.5 J/K.
• Explain the signs of DHorxn and DoSrxn for the autoionization of water based on the changes
induced by the process at the molecular level.
• Predict whether the value of Kw increase or decrease when the temperature of water increases.
The concentrations of OH– ions and H3O+ ions change when acids or bases
dissolve in water. This is expected because acid molecules react with water mol-
ecules to produce more H3O+ ions and bases generate more OH– ions. The addi-
tion of an acid to pure water should make [H3O+] larger than 1.0 x 10–7 M, while
the addition of a base should make [OH–] larger than this same value. But what
happens to the concentration of OH– when an acid is added to water or to the
concentration of H3O+ ions when a base is added? Consider the case of an acid in
water. When the acid is added and more H3O+ ions are formed in solution, the
likelihood of them reacting with OH– ions to produce water increases. The back-
wards process in the autoionization equilibrium in Equation (6.1) becomes faster
than the forward process until chemical equilibrium is reestablished. At equilib-
rium, the concentration of [H3O+] ions will still be larger than 1.0 x 10–7 M but
the concentration of OH– ions will be smaller than 1.0 x 10–7 because some of
these hydroxide ions had been consumed. In fact, according to Equation (6.2),
By Datamax (Own work)
the product of concentrations [H3O+][OH–] should be equal to Kw as the concen-

tration of [H3O+] and [OH–] ions in water is always regulated by the autoionization
process. Similarly, the concentration of [OH–] will increase and the concentration
of [H3O+] will decrease when a base is added to water.
Although the concentrations of [H3O+] and [OH–] in pure water or in aque-
ous solutions of acids and bases are very small, they can be measured with great
precision using instruments that analyze the electrical properties of the solution
Figure 6.4 The concentration
of [H3O+] ions can be mea- (Figure 6.4). Small changes in the concentration of hydronium and hydroxide
sured with precision using
electronic devices.
ions often have a large impact on the properties of water and of the substances
dissolved in it.
[H3O+] and [OH–] LET’S THINK

The concentration of acetic acid (CH3COOH) in common vinegar is close to 1 M. Not all the
molecules of this acid react with water molecules and produce H3O+ ions. In fact, only around
four per every 1000 molecules of acetic acid dissociate.
• Estimate the concentrations of H3O+ and OH– ions in common vinegar at 25 oC.
• Estimate how many times greater or smaller these concentrations are than their correspond-
ing values in pure water at 25 oC.
pH Scale
When working with aqueous solutions of acids and bases it is common to express
the concentration of H3O+ and OH– ions using a logarithmic scale. In particular
the pH and the pOH of the solution are defined in the following way:
(6.3) pH = – log [H3O+]

(6.4) pOH = – log[OH–]
Figure 6.5 The pH scale often
expands from 0 (highly acidic
solutions) to 14 (highly basic
According to these definitions, the pH and pOH of pure water at 25 C are theno
solutions).
equal to:
pH = – log [H3O+] = – log (1.0 x 10–7) = 7

[H3O+]
pOH = – log [OH–] = – log (1.0 x 10–7) = 7
10–14
In general, given the value of the autoionization constant for water Kw, 10–13
as expressed in Equation (6.2), we should expect that: 10–12
By OpenStax College (Derivative) [Generic 3.0] via Wikimedia Commons

– log [H3O+] – log [OH–] = – log Kw 10–11
pH + pOH = 14 10–10
10–9
in any aqueous solution at 25 oC (when Kw = 1.0 x 10–14), no matter
10–-8
whether acids or bases are present in the system.
Pure water is considered to be a neutral environment from the ac- 10–7
id-base point of view, and thus the values pH = 7 or pOH =7 are used 10–6
as references in judging the acidity or the basicity of an aqueous solu-
10–5
tion. When an acid is added to water, the concentration of H3O+ ions
becomes greater than 1.0 x 10–7 and the pH of acidic solutions is then 10–4
lower than 7 (while pOH > 7). When a base is added to water, the 10–3
concentration of H3O+ is less than 1.0 x 10–7 and the pH of basic solu-
10–2
tions is then greater than 7 (while pOH < 7). As shown in Figure 6.5,
a great variety of products used in daily life are acidic or basic aqueous 10–1
solutions. The sour taste of many fruits is due to the presence of ac- 100
ids such as citric acid, while the characteristic smell of many cleaning
products is due to the presence of ammonia (a basic compound).
LET’S THINK Antiacid?

The pH of milk of magnesia, a product used as an “antiacid” in the treatment of heartburn, is close
to 10.5. The pH of the fluid in a human stomach is close to 2.0.
• What is the concentration of H3O+ ions in a human stomach? What is the concentration of
OH– ions in milk of magnesia?
The autoionization of water is not thermodynamically favored (Kw << 1). Consequently, the reverse
process, the reaction between H3O+ and OH– to form water, is strongly favored.
• What would you expect to happen at the molecular level when equal amounts of milk of mag-
nesi and stomach fluid are mixed?
• Estimate the final pH of this mixture.
Reaction Extent
Not all acids or bases react to the same extent with water. A few chemi-
cal compounds react to completion and generate as many H3O+ ions or
OH– ions as particles of the substance are added to water (Figure 6.6).
These types of chemical compounds are labeled as “strong” acids or bases.
Examples of strong acids include hydrochloric acid (HCl), hydrobromic
–
acid (HBr), hydroiodic acid (HI), and nitric acid (HNO3). The chemical
+
reaction between any of these strong acids and water can be represented
–
in the following general manner:
–
+
+
– –
+
– The equilibrium constant Ka associated with this reaction is very large
(Ka >>1).
+ +
Chemical compounds that are strong bases tend to be ionic substanc-
es comprised of OH– ions (hydroxides) that fully dissolve in water. That is
Figure 6.6 When a strong the case of sodium hydroxide (NaOH) and potassium hydroxide (KOH).
acid, like HCl, is added to wa-
ter, it reacts to completion
The dissolution in water of these strong bases is often represented as shown below:
(i.e., it fully dissociates).
XOH(s) + H2O(l) X+(aq) + OH–(aq)
Most chemical substances with acid-base properties, however, do not react

with water to completion. In fact, in most cases the extent of the reaction with
water is pretty small, with equilibrium constants that are typically smaller than 1
x 10–3. These types of chemical compounds are labeled as “weak” acids or bases.
Carboxylic acids (characterized by the presence of the carboxyl functional group
–COOH), such as acetic acid or citric acid, are weak acids, while amines (–NH2,
–NHR, –NR2) are weak bases, including ammonia NH3. The acid-base properties
of many substances is due to the presence of carboxyl or amine groups.
The extent of the reaction between a weak acid or a weak base with water is
determined by the value of the equilibrium constant for the process. For weak
acids that react as described by the following chemical equation:
the equilibrium constant Ka, also called the acid dissociation constant, can be
expressed as:
[A–(aq)] [H3O+(aq)]
(6.5) K =
a
[HA(aq)]
where the concentration of water is assumed to remain constant in the process.
Typical values of Ka for different weak acids are listed in the table at the bottom
of this page. In all these cases, the small value of the equilibrium constant indicates
that only a very small fraction of the molecules of each substance will dissociate to
generate H3O+ ions when reacting with water (Figure 6.7). Given the small values
of Ka for weak acids, it is common to represent these values using a logarithmic
scale. Similarly to how concentrations of H3O+ and OH– are expressed, the pKa of Figure 6.7 When a weak
a weak acid is defined as: acid, like HF, is added to wa-
ter, only a small fraction of the
molecules dissociate.
(6.6) pKa = -log Ka
Given this definition, the smaller the value of Ka (or the weaker the acid), the
larger the value of the pKa for that substance.
The same type of procedure is applied to define and represent the equilibrium
constant Kb for the reaction of weak bases with water:
In this case, the equilibrium constant is expressed as
(6.7) [HB+(aq)] [OH–(aq)]

Kb =
[B(aq)]
and the associated pKb is defined as:
(6.8) pKb = -log Kb
Weak Acids Weak Bases

Substance Ka pKa Substance Kb pKb
HF – Hydrofluoric Acid 7.2 x 10–4 3.14 CH3NH2 – Methylamine 4.4 x 10–4 3.36
HNO2 – Nitrous Acid 4.0 x 10–4 3.39 NH3 – Ammonia 1.8 x 10–5 4.75
HCOOH – Formic Acid 1.8 x 10–4 3.75 CH3COO– – Acetate ion 5.6 x 10–10 9.25
CH3CH2OCOOH – Lactic Acid 1.4 x 10–4 3.86 C6H5NH2 – Aniline 3.8 x 10–10 9.42
C6H5COOH – Benzoic Acid 6.5 x 10–5 4.19 NO2– – Nitrite ion 2.5 x 10–11 10.61
CH3COOH – Acetic Acid 1.8 x 10–5 4.75 F– – Fluoride ion 1.4 x 10–11 10.86
LET’S THINK Comparing Strengths
Among the weak acids listed in the table on page 369, hydrofluoric acid (HF) is the strongest acid.
On the other hand, the fluoride ion (F–) is the weakest base of those included in the same table.
• Analyze the reactions between HF and water and between F– and water, and explain the rela-
tive difference in strength between these acid-base pair.
Conjugate Pairs
When an acid or a base react with water, protons are transferred between the react-
ing species. As a result of this process, new chemical species are formed in solution.
For an acid, the associated product has one less proton and it is said to be “depro-
tonated.” For a base, the associated product has one more proton and it is said to
be “protonated.” These new substances also have acid-base properties because they
may react with water by gaining or losing a proton. Consider the reaction between
acetic acid (CH3COOH) and water:
CH3COOH(aq) + H2O(l) CH3COO–(aq) + H3O+(aq)
The acetate ion (CH3COO–) formed through this reaction may react with water
and reform acetic acid, behaving as a base:
CH3COO–(aq) + H2O(l) CH3COOH(aq) + OH–(aq)
In general, the product of the deprotonation of an acid is a chemical base known

as the “conjugate base” of the original acid. The pair CH3COOH/CH3COO– is
said to be a conjugate acid-base pair. Similarly, when a base like ammonia (NH3)
reacts with water:
NH3(g) + H2O(l) NH4+(aq) + OH–(aq)
the associate product, ammonium ions (NH4+), may react with water as an acid
to reform NH3:
NH4+(aq) + H2O(l) NH3(aq) + H3O+(aq)
The product of the protonation of a base is a chemical acid known as the “con-
jugate acid” of the original base. The pair NH4+/NH3 is another example of a
conjugate acid-base pair.
The stronger an acid, the less likely that its conjugate base will react with water
and gain protons back. Protonation and deprotonation are opposite processes, and
the more one of these processes is thermodynamically favored the more the other
process is disfavored. Strong acids, such as HCl, have extremely weak bases, such
as Cl–.
Water molecules also undergo changes when reacting with acids or bases.
When water reacts with an acid, it gains protons and behaves as a proton-acceptor
(or a base). The product of the reaction H3O+ may then act as a proton-donor (or
an acid) when reacting with other substances. Thus, the pair H3O+/H2O can be
thought of as a conjugate acid-base pair. Similarly, when water reacts with a base, it
loses protons and behaves as a proton-donor (or an acid). The product of the reac-
tion OH– may thus act as a proton-aceptor (or a base) when reacting with other
substances. Consequently, the pair H2O/OH– is another example of a conjugate
acid-base pair. In general, when an acid or a base reacts with water, the following
two conjugate acid-base pairs can be identified:
Acid Conjugate Base

Base Conjugate Acid
Base Conjugate Acid

Acid Conjugate Base
Conjugate Acid-Base Pairs LET’S THINK

The solubility and physiological activity of many pharmaceutical drugs strongly depends
on their acid-base properties. Consider the molecular structure of the following drugs:
Ibuprofen Methamphetamine Lidocaine

C13H18O2 C10H15N C14H22N2O
• Predict whether each of these substances will behave as an acid or as a base when
reacting with water.
• Determine the structure and chemical formula of the conjugate base or acid for
each of these substances.
• Represent the chemical equations for the reactions of each of these substances with
water and identify all the conjugate acid-base pairs involved in each process.
Aqueous solutions of acids and bases are comprised of different chemical spe-
cies that are in constant interaction with each other. In an acid’s solution, for
example, we have the acid HA and its conjugate base A–, we also have water H2O,
and hydronium ions H3O+ and hydroxide ions OH–. At chemical equilibrium,
which is reached very fast in these types of systems, the concentration of each of
these species will be determined by the equilibrium constants of the following
chemical reactions between components:
[A–(aq)] [H3O+(aq)]
HA(aq) + H2O(l) A–(aq) + H3O+(aq) Ka =
[HA(aq)]
[HA(aq)] [OH–(aq)]
A (aq) + H2O(l)
–
HA(aq) + OH (aq)
– Kb =
[A–(aq)]
2 H2O(l) H3O+(aq) + OH–(aq) Kw = [H3O+(aq)] [OH–(aq)]
The analysis of these relationships indicates that they are not independent
from each other. For example, if we multiply Ka times Kb we get:
[A–(aq)] [H3O+(aq)] [HA(aq)] [OH–(aq)]

(6.9)
Ka x Kb = x = Kw
[HA(aq)] [A–(aq)]
or, by using the definitions of pKa and pKb in Equations (6.6) and (6.8):
(6.10) pKa + pKb = pKw
where pKw = –log Kw = 14 at 25 oC. The relationship between pKa and pKb as
expressed in Equations (6.9) or (6.10) confirms that the stronger an acid is (larger
Ka, smaller pKa) the weaker its conjugate base would be (smaller Kb, larger pKb),
and vice versa. A weak acid or base, however, always has a weak conjugate pair.
LET’S THINK An Anesthetic
Procaine (C13H20N2O2) is a local anesthetic used primarily

to reduce the pain from penicillin injection, and it is also
used in dentistry. For basic drugs such as procaine, it is
common to report the value of the pKa of their conjugate
acid instead of the pKb of the actual base. The pKa of the
conjugate acid of procaine has a value close to 8.
• Predict the structure of the conjugate acid of procaine.

• Calculate the Kb and pKb of procaine.
• Discuss which species, procaine or its conjugate acid, is stronger in terms of their acid-base
reactivity with water.
Share and discuss you ideas with a classmate, and clearly justify your reasoning.
FACING THE CHALLENGE cally charged species will be more likely to dissolve
in water and less likely to move across nonpolar
environments. Given that drug molecules will en-
Drugs in Our Body counter different chemical environments as they
Most drugs in the market are chemical com- distribute throughout our body, drug designers
pounds that behave as weak acids or bases when need to carefully analyze the acid-base properties
added to water. For example, common over-the- of the compounds that they synthesize to predict
counter- analgesics such as aspirin and ibuprofen how they will behave once ingested.
are weak acids, while stronger narcotic analgesic The intracellular fluid is considerably more
such as morphine and oxy- acidic than the cellular plasma.
codone are weak bases. The The distribution of drugs in-
acid-base properties of drugs side and outside cells may thus
are determined by the nature be different for acid and basic
of key functional groups (e.g., drugs. Basic drug molecules are
carboxyl, amine) present in the more likely to exist as ions in
molecules of these substances. acidic medium than acid drug
When acid or basic drugs molecules are. The intracellu-
react with water, the particles lar concentration of weak bases
of the conjugate acid-base should thus be higher than the
pairs that are formed have concentration of weak acids.
a different electrical charge In general, basic drugs tend to
than the original species. For be more active than acid drugs
example, the conjugate bases because of these differences in
of carboxylic acids have nega- By psyberartist (Own work) [Generic 2.0] via Flickr Commons intracellular concentrations.
tive charge (anions), while the conjugate bases of The charge distribution in drug molecules also
amines have positive charge (cations). The extent affects how these molecules interact with the active
to which these charged species will be produced site of the protein receptors that a drug is designed
depends on the pKa of the drugs and on the con- to target. The presence or absence of charge in key
centration of H3O+ and OH– ions already present areas of drug molecules will affect the strength to
in the medium in which drugs are dissolved. For which these particles can bind to protein recep-
example, if the pH of the medium is low (i.e., the tor sites. Low binding strength may lead to drug
concentration of H3O+ is high), like in stomach inactivity while too strong of a binding may result
fluids, it is less probable that acidic drug molecules in high toxicity.
will dissociate to form more H3O+. Thus, the drug Changes in the pH of urine induced by differ-
will most likely exist in its neutral form. On the ent types of food may have a profound influence
other hand, basic drug molecules are more likely on the facility with which acid and basic drugs are
to be protonated and acquire a positive charge excreted. Weak acids are more easily excreted in
when the concentration of H3O+ is high. In gen- highly alkaline urine where their molecules will
eral, the pH of the medium has a critical effect on be mostly ionized, and weak bases in acidic urine
the proportion of ionized and unionized acid or where most molecules will be protonated. The
basic drug molecules present in a system. elimination of potentially toxic drugs may thus be
The electrical charge of drug molecules has a accelerated by adjusting the urinary pH. Chang-
strong influence on the absorption, distribution, ing the pH of urine often facilitates the detection
metabolism, excretion, and toxicity of the drugs. of recreational drugs. Amphetamines, for example,
The electrical charge affects the solubility of the may be more easily detected in acidic urine where
drug in water and in cell membranes, which are molecules of the drugs are protonated and thus are
mainly comprised of nonpolar substances. Electri- more soluble in water.
Let’s Apply
Drug Properties
Over 70% of the drugs in the market have acid-base properties. Of these, close to 60% are weak
bases, around 25% are weak acids, and the rest exhibit both acid and base behavior (amphoteric).
Most of the basic drugs contain amine groups and the pKa of their conjugate acids is close to 9. The
strongest acid drugs tend to be carboxylic acids with pKa values close to 4, and the weakest acid
drugs tend to be barbiturates with pKa values close to 8.
Analgesics
Analgesics are pharmaceutical drugs used to relieve pain (pain killers). They include different
types of drugs, from non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibu-
profen to opioid drugs such as morphine and oxycodone. The molecular structures, chemical
formulas, and pKas of aspirin and morphine are shown below, where main functional groups
with acid-base properties are highlighted:
Morphine
Aspirin C17H19NO3
C7H6O3 pKa = 8.2
pKa = 3.5
Morphine
is extracted
from
• Predict whether each of these drugs will behave as an acid or as a base when reacting opium
with water. Make a drawing to represent how each drug molecule will interact with a poppies
water molecule.
• Write the chemical formula of the conjugate acid or base of
each of these substances, and calculate their associated pKb. By Me (Own work) [Public domain]
• Discuss what information the values of pKa and pKb (or Ka and
Kb) convey for eah of these substances. Identify the strongest
species in each conjugate acid-base pair.
• Write the chemical equation that represents the reaction of
each of these drugs with water.
• Identify all the conjugate acid-base pairs involved in each of
the reactions.
• Express the equilibrium constant for the reaction of aspirin with water.
Drug Absorption
In the stomach, where the pH of the gastric juice is close to 2, drugs such as morphine
and aspirin mainly exist in their acid form. Their structure under these conditions influ-
ences how fast the drugs are absorbed through the stomach walls.
• Which of these two drugs will be absorbed at a faster rate through stomach cell
membranes?

Aspirin Tablets
When a 500 mg tablet of Aspirin is dissolved in a glass of water, the pH is close to 2.8.
When two 500 mg tablet of Aspirin are dissolved in the same amount of water, the pH
is close to 2.5
• How would you explain this result? Why does the pH decrease? Why is the change
in pH so small when the amount of aspiring is doubled?
Other Analgesics
Other over-the-counter analgesics include ibuprofen and acetominophen (or paracetamol),

substances that behave like acids when reacting with water:
Ibuprofen Acetominophen
C13H18O2 C8H9NO2
pKa = 4.5 pKa = 4.5
• Compare the acid-base properties of aspirin, ibuprofen, and acetominophen.

Which is the strongest acid? Which substance has the strongest conjugate base?
Let’s Apply
Acidic Atmosphere
The atmosphere of our planet contains a variety of acidic substances. Understanding the acid-base
properties of these chemical compounds is of central importance to predict and control their in-
teractions.
Atmospheric Acids
Consider the following molecular structures of acids formed in Earth’s atmosphere:
Nitric Acid Carbonic Acid Sulfuric Acid

HNO3 H2CO3 H2SO4
• Predict how each of these acids may interact with water. Make a drawing to represent
how each of the acid molecules will interact with a water molecule.
• Draw the molecular structure of the conjugate bases of each of these acids.
• Write the chemical equation that represents the reaction of each of the acids with water.
• Identify all conjugate acid-base pairs in each of the processes.
• Carbonic acid, H2CO3, and sulfuric acid, H2SO4, are examples of polyprotic acids,
which are substances comprised of molecules that may donate more than one proton to
water molecules. Draw the molecular structure of the bases that would form when each
of these acids donates two protons to water molecules.
• Nitric acid is a strong acid (Ka >> 1). Draw a molecular representation of a solution of
nitric acid in water (no need to represent water molecules).
Carbonic acid is a weak acid. The pKa for the dissociation of a first proton is 3.6, while the pKa
for the dissociation of the second proton, represented by this chemical equation, is 6.3:
HCO3–(aq) + H2O(l) CO32–(aq) + H3O+(aq)
• Provide a reasonable explanation for the difference in the pKa values for the first and
second dissociations.
Sulfuric Acid
Sulfuric acid, H2SO4, is not only an important atmospheric component but also a widely
used chemical compound with multiple industrial applications. Each molecule of this di-
protic acid may donate up to two protons to water molecules. The pKa for the first disso-
ciation has a negative value (strong acid) while the pKa for the second dissociation is 1.9.
• Write the chemical equations that represent the first and the second dissociations
of sulfuric acid in water.
• Express the equilibrium constants for each of the dissociation processes.

• A solution of sulfuric acid with a pH close to –0.6 is used as electrolyte in car bat-
teries. What is the concentration of H3O+ ions in these types of solutions?
Acid Rain Effect of acid rain on statues
The rain in our planet tends to be acidic due to the

presence of H2CO3, HNO3, and H2SO4. Rain that
is derived from the Atlantic Ocean can have a pH
as high as 5.6; rain that comes across the continent
from the west can have a pH as low as 3.8.
• How many times larger is the concentration

of H3O+ ions in the most acidic rain versus in
the less acidic rain?
Share and discuss your ideas with a classmate, and By Nino Barbieri (Own work) [Generic 2.5]
clearly justify your reasoning.
Ammonia Effects
Ammonia, NH3, is a gaseous basic compound (pKb = 4.7) widely used in the production
of fertilizers. This substance can react with nitric acid and sulfuric acid in the atmosphere:
HNO3(aq) + NH3(g) NO3–(aq) + NH4+(aq)

HSO4(aq) + NH3(g) HSO4–(aq) + NH4+(aq)
• Discuss how these reactions may affect the pH of rainwater.
368
Influencing
Chemical
Equilibrium
The extent to which acids or bases react with water, or with each other, is in-
U6: MODULE 2
fluenced by the chemical composition and structure of the substances

involved, their concentrations, and the temperature of the system.
We can thus control the extent of acid-base reactions by changing
different variables. In particular, the concentration of different
species at chemical equilibrium can be controlled by chang-
ing the initial concentrations of reactants, and the concen-
trations of H3O+ or OH– ions in aqueous solution. The anal-
ysis of how these changes affect chemical equilibrium is the
central focus of Module 2.
The chemical composition and structure of reactants and
products, together with the temperature at which the chemi-
cal reaction takes place, determine the value of the equilibrium
constant for the process. However, the initial concentrations of
different species in solution also affect the final concentrations at which chemical
equilibrium is reached. Understanding the influence of concentration on acid-base
equilibrium is critical in many areas, from pharmacology to environmental science
to proteomics.
THE CHALLENGE Proteomics

Proteomics refers to the large-scale study of the composition, structure,and
function of the proteins in different organisms.
• Why and how do you think the structure and function of proteins are
affected by changes in the concentration of H3O+ or OH– in their sur-
roundings, or by the temperature of the system?
tral goal of Module 2 is to help you understand how to use the concentration of
different species to control the extent of acid-base reactions.
Concentration Effects
The initial concentrations of acids or bases in solution affect the final concentra-
tions of all the species in the system. To understand this effect, let us first consider
the case of a simple acid of the form HA reacting with water as represented by the
following chemical equation:
According to Eq. (6.5) in Module 1, the equilibrium constant for this dissociation
process can be expressed as:
[A–(aq)] [H3O+(aq)]
Ka =
[HA(aq)]
Imagine that Co represents the initial molar concentration of the acid before it dis-
sociates by reacting with water. How can we predict the concentrations of the acid
HA, its conjugate base A–, and H3O+ ions at equilibrium?
The prediction of all equilibrium concentrations can be simplified by explic-
itly listing the initial concentrations of all species in solution and the changes that
are expected to occur as a result of the reaction. For this purpose, it is convenient
to build a table, also called ICE table, with the following structure:

Initial Co – 0 1x10-7 M
Change –x – +x +x
Equilibrium Co – x – x x
The first row in this table includes the initial concentrations of all species; the sec-
ond row lists the unknown change “x” in these concentrations due to the chemical
reaction, and the third row includes the equilibrium concentrations calculated by
adding the first two rows. In this case, when x moles per liter of HA dissociate in
water the same amount of A– and H3O+ are produced per liter of solution. Notice
that in the ICE table above we have neglected the change in water concentration,
which is expected to be very small under most common situations. Similarly, we
assumed that the initial concentration of the conjugate base A– is zero and that
the concentration of H3O+ ions due to the auto-ionization of water is negligible in
comparison with the concentration of H3O+ ions that results from the dissociation
of the acid (x). This is, we expect that x >> 1 x 10-7 M.
If the acid HA is strong, it will fully dissociate in water and x = Co. A solution
of an strong acid should then have a pH = –log Co. If the acid HA is weak, however,
x < Co and at chemical equilibrium we should have:
(6.11) [A–(aq)] [H3O+(aq)] x2

Ka = =
[HA(aq)] (Co – x)
If we know the values of Ka and Co for the acid HA, this expression can be used to
calculate x, and thus the concentration of all species at equilibrium.
370 MODULE 2 Influencing Chemical Equlibrium
For many weak acids we can expect proton transfer to occur to a little extent.
In those cases in which x is much smaller than Co (x << Co), Eq. (6.11) can be
further simplified to yield:
x2
(6.12) Ka = or x = (KaCo)1/2
Co
Thus, pH = -log (x) = – log [(KaCo)1/2] for a weak acid. This relationship is com-
monly used to estimate pH when the value of x is smaller than 5% of Co (or x <
0.05 Co). This will be the case whenever the ratio Co/Ka is larger than 400.
LET’S THINK Drug pH
Phenobarbital (C12H12N2O3) is a weak acid (pKa = 7.4) used as a sedative

and anticonvulsant. This drug is insoluble in water; the concentration of
saturated aqueous solutions of this compound is close to 1 g/L.
• Estimate the pH of a saturated solution of phenobarbital.

• Compare the pH of a saturated solution of this pharmaceutical drug
with the pH of a diluted solution with 1/10th of the concentration at
saturation. Explain the difference in pH values.
• Calculate the ratio of the equilibrium concentrations of the conjugate base to the acid ([A–]/
[HA]) for the saturated and the diluted solutions. Build a reasonable explanation for the
change in the value of this concentration ratio with decreasing or increasing initial acid con-
centration Co.
Based on Eq. (6.12), we can predict that higher initial concentrations Co of

the weak acid will yield higher concentrations of both conjugate base A– and H3O+
ions at equilibrium ([A–(aq)] = [H3O+(aq)] ~ (KaCo)1/2). Thus, higher concentra-
tions of the weak acid will yield lower values of the pH. However, the pH of the
solution also depends on the Ka for the weak acid. Thus, we can control the pH of
an aqueous solution by varying both the concentration and the chemical nature
of the acid.
LET’S THINK Drug Comparison
Aspirin (C9H8O4; pKa = 3.5) and Ibuprofen (C13H18O2; pKa = 4.9) are over-the-counter acidic
drugs used for relieving pain and reducing fever. Consider a 300 mg tablet of Aspirin and a 600
mg tablet of Ibuprofen.
• Which of these tablets will generate a more acidic solution when dissolved in 250 mL of wa-
ter? Estimate the pH of each solution and analyze the accuracy of your estimations. Discuss
what could be done to generate more accurate values.
• In which of these two solutions would the acid be dissociated to a greater extent?
There are situations in which the dissociation of the acid is not negligible com-
pared to its initial concentration Co (i.e., x > 0.05 Co). In these cases, the value of
“x” can be found using the following relationship:
x2
(6.13)
Ka = x2 + Kax – KaCo = 0
(Co – x)
Applying the quadratic formula we have:
– Ka + (Ka2 + 4 KaCo)1/2
(6.14) x=
2
This relationship can be used to calculate the pH of aqueous solutions of weak
acids (pH = – log (x)) as long as x >>1 x 10-7 M.
The pH of aqueous solutions of basic compounds can be calculated by follow-
ing a procedure similar to that used for acids. In this case, the corresponding ICE
table takes the form:

Initial Co – 0 1x10-7 M
Change –y – +y +y
Equilibrium Co – y – y y
Co represents the initial concentration of the base and “y”is the moles per liter of
the base that react with water. If the base B is strong, then y = Co and pOH = –log
Co. The pH of a solution of a strong base is then given by pH = 14 –log Co. If the base
B is weak, at chemical equilibrium we should have::
[HB+(aq)] [OH–(aq)] y2
Kb = =
[B(aq)] (Co – y)
For aqueous solutions of a weak base in which y < 0.05Co (or Co/Kb > 400), we
can estimate y = [OH–] = (KbCo)1/2. Under these conditions, pOH = – log [(KbCo)1/2]
for a weak base, with pH = 14 – pOH. Otherwise, y = [OH–] = (–Kb + [Kb2 +
4KbCo)1/2])/2 according to Eq. (6.14). The value of the equilibrium constant Kb
can always be derived from data for the Ka of the conjugate acid, as Kb = Kw/Ka
according to Eq. (6.9).
Soluble Salts LET’S THINK

Due to the poor solubility of its acid form, phenobarbital (pKa = 7.4) is often adminis-
tered as a sodium salt of its conjugate base (NaC12H11N2O3) which is over 100 times more
soluble than the acid.
• Estimate the pH of a saturated solution of sodium phenobarbital (100 g/L).
Equilibrium Shifts
Once chemical equilibrium is established in an aqueous solution of an acid or a
base, the concentration of the different species in the system will remain constant.
These concentrations can be altered, however, by making changes to the solution
such as adding more reactants or products, evaporating the solvent, or changing
the temperature. Predicting how the solution will respond to these changes is of
central importance to control the chemical system. These predictions can be made
by paying attention to changes in the rate of the different chemical processes tak-
ing place in the system (kinetic argument) or by analyzing changes in concentra-
tion ratios between reactants and products (thermodynamic argument). In this
section, we illustrate how to build both types of arguments.
Consider, for example, an aqueous solution in which the following chemical
equilibrium has been established:

This equilibrium can be perturbed by adding an extra amount of acid HA into
the system. How would that affect the concentration of each species in solution?
Kinetic Argument: Given that the forward dissociation of HA and the backward
reaction between the conjugate base A– and hydrogen ions H3O+ take place in a
single step (proton transfer from one species to another), the reaction rates for
each of these processes can be expressed as:
RATEf = kf [HA] [H2O] Forward Reaction

RATEb = kb [A–] [H3O+] Backward Reaction
Where kf and kb are the rate constants for these two processes. At equilibrium
the forward and backward rates are equal. Adding more HA will cause [HA] to
increase. As a result, the forward rate will become greater than the backward rate
and the concentration of products A– and H3O+ will also increase in system (more
product is formed). When equilibrium is reestablished, all concentrations [HA],
[A–], and [H3O+] will thus have greater values than in the initial condition. In
general, perturbations that cause the forward rate to increase lead to the formation
of more product. If the perturbation causes a greater backward rate, then more
reactant will be formed.
LET’S THINK Your Arguments
Consider the following acid-base reaction taking place in gas phase: HCl(g) + NH3(g) NH4Cl(s)
• Use kinetic arguments to predict how chemical equilibrium will be affected when the follow-
ing changes are made to the system:
a) The volume of the container is reduced; b) More HCl(g) is added at constant volume;
c) More NH3(g) is added at constant pressure; d) More NH4Cl(s) is added into the container.
Thermodynamic Argument: At chemical equilibrium, the concentration of all

species in solution satisfy the relationship defined by the equilibrium constant Ka:
[A–(aq)]eq [H3O+(aq)]eq
Ka =
[HA(aq)]eq
The subindex “eq” has been added to all the concentrations in the expression above
to emphasize that they represent concentration values at chemical equilibrium.
When more HA is added into the solution, the concentration [HA] will in-
crease. If we calculate the ratio of the concentrations of products to reactants im-
mediately after HA has been added, its value will be different from Ka. The con-
centration ratio calculated when the system is not at equilibrium is known as the
reaction quotient and it is represented using the symbol “Q”:
[A–(aq)] [H3O+(aq)]
(6.15) Q
Q=
[HA(aq)]
Ka
In the particular case in which more HA is added to the solution, we can expect More
Q to have an initial value smaller than Ka (Q < Ka) given that [HA(aq)] appears in Q < Ka product is
formed
the denominator of Eq. (6.15). The value of Q will vary as a function of time as
the reaction mixture reaches a new equilibrium state (see Figure 6.8). When the
solution reaches equilibrium again, the value of Q should be equal to Ka. For this Time
to happen, the concentrations of the products [A–(aq)] and [H3O+(aq)] should
increase and the concentration of the reactant [HA(aq)] should decrease from Figure 6.8 The value
of reaction quotient Q
its value after the addition. In general, when a perturbation in a chemical system changes as equilibrium is
results in Q < Ka more product will form. On the other hand, a perturbation that reestablished in a system
(at equilibrium Q = Ka).
causes Q > Ka will lead to the formation of more reactant.
As illustrated by the example above (addition of HA to a solution of the acid at

equilibrium), the kinetic and thermodynamic arguments lead us to the same con-
clusion. Learning how to build both types of arguments is very useful in predicting
equilibrium shifts due to diverse changes made to a chemical system.
Your Arguments LET’S THINK

Imagine that you have a 0.15 M aqueous solution of aspirin (pKa = 3.5) in equilibrium:
• Write the chemical equation for the reaction of aspirin (HA) and water.
• Estimate the pH of the solution.
• Predict what will happen to the concentration of each species in solution and to the pH of
the mixture when the following changes are made:
a) More conjugate base A– is added to the solution; b) More aspirin (HA) is added to the
solution; c) More OH– is added to the solution; c) More water is added to the solution.
Present both kinetic and thermodynamic arguments to justify each of your predictions.
In each case, build a graph similar to that shown in Figure 6.8 to show the expected evo-
lution of the reaction quotient Q as a function of time.
pH Effects
In many important situations, acids or bases of interest dissolve in solutions that
are already acidic or basic (i.e., the pH of the solution is different from 7). This
is the case, for example, of drugs that we ingest and then dissolve in the stomach
fluid (pH ~ 2) or reach our intestines (pH ~ 6). When this happens, we may be
interested in predicting or controlling how the existing concentration of H3O+ or
OH– ions in solution affects the concentrations of the other acid or basic species.
As it is always the case for chemical systems in equilibrium, we can use relevant
equilibrium constant expressions to analyze such concentration effects.
Consider the case of an acid HA that is added to a solution with a fixed pH.
The generic expression of the equilibrium constant for the dissociation of this acid,
Ka as represented below, can be written in terms of the pH of the solution by fol-
lowing this sequence of mathematical steps:
[A–(aq)] [H3O+(aq)]
Ka =
[HA(aq)]
[A–(aq)] [H3O+(aq)]
– log Ka = – log [ [HA(aq)]
]
[A–(aq)]
pKa = – log [ [HA(aq)]
] + pH
[A–(aq)]
(6.16) pH = pKa + log [ [HA(aq)]
]
Where we applied the definitions pH = – log[H3O+(aq)] and pKa = – log Ka. Equa-
tion (6.16) is a re-expression of the equilibrium constant relationship that can be
used to calculate acid/base concentration ratios at any given pH. This particular
way of expressing the equilibrium dissociation constant of an acid is known as the
Henderson-Hasselbalch equation.
LET’S THINK Relative Abundance
Acetic acid (CH3COOH; pKa = 4.8) is a weak acid and ethylamine (CH3CH2NH2; pKb = 3.3) is a
weak base.
• Draw the structure of the dominant molecular species of each of these substance in aqueous
solutions with a fixed a) pH = 2.0, and b) pH = 8.0. Use kinetic or thermodynamic arguments
to explain the change in relative abundance with pH.
When comparing the concentrations of an acid and its conjugate base (or a
base and its conjugate acid) in an aqueous solution with a given pH, it is useful to
calculate the percent of dissociation of the acid a defined in the following manner:
[A–(aq)]
(6.17) a= x 100
[A–(aq)] + [HA(aq)]
The percent dissociation a is a measure of the fraction the substance that has
dissociated (or that exists in its conjugate base form A– in solution). The percent
dissociation can be expressed in terms of the pH of the solution and the pKa of the
acid by combining Eqs. (6.16) and (6.17):
(6.18) 1 Figure 6.9 Variation in the

a= x 100 percent of HA and A– in solu-
1 + [HA(aq)]/ [A–(aq)] tion as a function of pH for
an acid with pKa = 4.0. How
would you explain these
results using a kinetic or a
We can use Eq. (6.18) to calculate the percent of A– in solution at any pH, as thermodynamic argument?
well as the percent of the substance that remains in acid form (%HA
= 100 – a). The change in these two quantities with pH is illustrated 100
a = % species
in Figure 6.9 for a substance with pKa = 4. As shown in this image, HA A–
80
the substance mostly exists in its acid form ([HA] > [A–]) when pH
60
< pKa and it is mostly dissociated ([A–] > [HA]) for pH > pKa. The
concentrations of the acid and its conjugate base have the same value 40
when pH = pKa. The following activity illustrates the importance of 20

predicting which species is dominant under different pH conditions. 0
0 1 2 3 4 5 6 7 8 9 10
1 pH
a= x 100
1 + 10(pKa – pH)
Acid or Base Form? LET’S THINK

The tables list data for different types of pharmaceutical drugs:
• Predict which form of the drug (HA or A–; B or HB+) is

dominant in the following physiological environments in our DRUG pKa
digestive system: a) stomach (pH = 2), b) duodenum (pH = Aspirin (HA) 3.5
6.0), and c) jejunum (pH = 7.5). Justify your reasoning.
• Predict the region of the body in which each drug is more Phenobarbital (HA) 7.4
likely to be absorbed (i.e., go through cell membranes com-
Ephedrine (B) 9.6
prised of non-polar molecules). Justify your prediction.
Our analysis indicates that if we are able to fix the pH of a solution, then we
can control the relative concentrations of the acid and base in a conjugate pair.
According to equations (6.16) and (6.18), the acid form in the conjugate pair HA
will be dominant (more abundant) at pH values lower than its pKa while the base
form A– will be dominant at pH values larger than the pKa (Figure 6.10)
pKa
more HA more A– Figure 6.10 Regions where
the acid HA and base A–
forms in a conjugate pair are
dominant (more abundant)
as a function of pH.
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 pH
Buffer Solutions
Fixing the pH of a solution to a constant value that does not change when other
acids or bases are added into the system is impossible. However, it is possible to
prepare solutions that undergo minimal changes of pH when other substances are
added in small or moderate amounts. These solutions often contain a mixture of
a weak acid HA and its conjugate weak base A–, and are known as “buffer” solu-
tions. Buffer solutions are used to keep the pH at a nearly constant value in a
wide variety of chemical applications. These types of solutions can also be found
in many natural systems and are critical in sustaining life on Earth. The structure
of important biological molecules such as proteins is very sensitive to variations in
pH and their functioning as enzymes typically occurs in buffered environments.
The response of a buffer solution HA/A– to the addition of other acids or bases
depends on the initial concentrations of HA (CA) and A– (CB) in the system. When
any other acid HB is added to the buffer, the acid HB reacts with the base in the
buffer pair A– and produces more HA:
Figure 6.11 When an acid
HB is added to the buffer so-
lution, it reacts with the base HB(aq) + A–(aq) B–(aq) + HA(aq)
A–. This reaction partially
neutralizes the effect of acid
HB on the pH of the mixture.
Similarly, when a base B– is added to the buffer, the acid in the buffer pair HA is
consumed and the concentration of A– increases:
B–(aq) + HA(aq) HB(aq) + A–(aq)

HB A –
HA B –
In any case, the buffer partially neutralizes the effect

of the acid or base that are added, reducing poten-
tial changes in the concentration of H3O+ and OH–
ions in the system (Figure 6.11). For a buffer to be
effective, the acid HA and the base A– in the buffer
pair should be present in appreciable amounts so
that they are not fully consumed when the added
acids or bases react with them.
A buffer solution containing a mixture of the
conjugate acid-base pair HA/A– has a pH that can be
calculated using Henderson-Hasselbalch equation:
pH = pKa + log ([A–]/[HA]) (where Ka is the acid dissociation constant for HA).
Notice that pH = pKa when the buffer is prepared using equal concentrations of
the acid and its conjugate base.
LET’S THINK Buffer pH
Imagine that you use 0.6 moles of HCN (pKa = 9.2) and 0.5 moles of NaCN to prepare two dif-
ferent buffer solutions. In one case you add these amounts to a beaker with 100 mL of H2O. In
the other case, you add the same amounts to another beaker with 200 mL of H2O.
• Which of the two buffer solutions will have a lower pH?
Many natural and artificial solutions have buffering properties. In particular,

there are a variety of acid-base buffer systems in our body that help regulate blood
pH and the pH inside and outside different types of cells. In the laboratory, artifi-
cial buffers can be prepared using a variety of strategies. These buffers are used to
control the extent and rate of many chemical processes.
Buffering Effect LET’S THINK

One of the most important natural buffers includes the acid-base pair H2PO4–/HPO42– (pKa =
7.1). The graph included in this activity shows how the pH of this phosphate buffer changes with
the percentage of the base (HPO42–) in solution.
• Based on the graph, decide which

of the following solutions would
be the best buffer: a) 80% HA and
20% A–; b) 60% HA and 40% A–;
c) 50% HA and 50% A–.
• Discuss how the graph would be
different for another buffer pair,
such as H3PO4/H2PO4– (pKa =
2.16).
• What ratio [A–]/[HA] would be best
to use to prepare a buffer with the
pair H3PO4/H2PO4–.
• Discuss whether it would be pos-
sible to prepare a buffer solution
using a mixture of a strong acid, such as HCl, and its conjugate pair.
• Discuss the implications of your analysis for the preparation of buffer solutions that can
best resist changes in pH when other acids or bases are added to them.
Buffer Preparation LET’S THINK

Buffers can be prepared by directly combining the acid/base pair or by inducing reactions that
generate them in solution. Imagine that you wanted to prepare the following set of buffers con-
taining equal concentrations of the acid and its conjugate base:
a) Buffer solution of HNO2 and NO2–. The substances available to complete the task include:
H2O, HNO2, KNO2, HCl, NaOH.
b) Buffer solution of NH4+ and NH3. The substances available to complete the task include:
H2O, NH4Cl, NH3, HCl, NaOH.
• Propose at least two different strategies to prepare each targeted buffer.
[ShareALike 2.0] via Flickr Commons
Buffers play a central role in oxygen and carbon dioxide transport and de-
By Ton Haex (Own work)
livery in our blood. Human blood is slightly basic with a pH between 7.35 and
7.45. Any deviations from this pH range can have serious effects on enzymatic
activity. Death may occur if the blood pH rises over 7.8 or falls below 6.8. Lungs
and kidneys help regulate the pH using a buffer system involving carbonic acid
(H2CO3) and bicarbonate ions (HCO3–).
LET’S THINK Carbonic Acid-Bicarbonate Buffer
The major chemical equilibria involved in the regulation of blood pH are:
CO2(g) CO2(aq)
CO2(aq) + H2O(l) H2CO3(aq)
H2CO3(aq) + H2O(l) HCO3–(aq) + H3O+(aq)
CO2(g) is a product of cellular respiration and is carried by blood from different organs in our
body to the lungs where it is eliminated when we exhale.
• What should happen to the pH of blood when CO2(g) dissolves in this fluid? What
should happen to blood pH when we exhale? Use kinetic and thermodynamic argu-
ments to justify your answers.
• When blood pH rises above 7.45, people develop a condition called alkalosis. One way
to treat this condition is to breathe into a paper bag where CO2(g) accumulates. Use
kinetic and thermodynamic arguments to explain how this treatment works.
LET’S THINK Hemoglobin

Hemoglobin (Hb) transports oxygen in the blood. The binding of O2 to
Hb involves the following exothermic process:

HbH+ + O2 + H2O HbO2 + H3O+
Blood coming from the lungs is rich in HbO2. When you do exercise, the
temperature of your body increases, and the concentration of O2 in active
tissues decreases while the concentration of CO2 increases.
• Build kinetic and thermodynamic arguments to explain how the

changes in the concentrations of O2 and CO2 in active tissues will
affect the delivery of O2 by blood coming from the lungs.
FACING THE CHALLENGE depends on the extent to which acidic side chains
are deprotonated and basic side chains are proton-
ated. The overall charge of a protein can thus be
Protein Separation controlled by varying the pH of its surroundings.
Proteins are biological macromolecules that per- The isoelectric point (pI) of a protein is de-
form a vast array of functions in living organisms, fined as the pH at which the macromolecule car-
from transporting molecules across cell membranes ries no electrical charge (the protein is electrically
to catalyzing cellular processes. The proteome in- neutral). The pI value depends on the composition
cludes all the proteins produced or modified by a and structure of each specific protein and thus it is
system, such as a cell, a tissue, or an entire organ- used as a differentiating characteristic in the sepa-
ism. A proteome’s composition depends on cellu- ration of proteins by isoelectric focusing (IEF).
lar and environmental conditions, and thus may In IEF the proteins to be separated are applied
change over time. In recent years, proteomics has to a polyacrilamide gel matrix or strip prepared
emerged as an effort to provide with a fixed and stable pH gradi-
techniques for the global char- ent (i.e., the pH varies across the
acterization of entire proteomes. gel strip). An electric field is ap-
The analysis of proteins on plied to the gel and charged pro-
a large or a small scale critically teins migrate through the pH
depends on the availability of gradient towards the negative
appropriate separation methods. or positive electrodes. The pH
Finding a separation technique across the gel is set up to increase
that can respond to the diversity from the positive electrode (an-
of proteins in a cell, tissue, or ode) to the negative electrode
organism can be quite challeng- (cathode) in the system. Pro-
ing. Some of the most powerful teins that travel through regions
separation methods, such as iso- with a pH below their pI will be
electric focusing (IEF) or elec- positively charged (their basic
trofocusing, are based on dif- groups will be protonated) and
ferences in the electrical charge migrate towards the cathode. As
of proteins in different environ- they migrate through a gradient
ments. Such electrical charge IEF Gel Characteristic Banding Pattern, FDA of increasing pH, their charge
may be controlled or manipulated by changing the will decrease until each of them reaches the pH
pH of the system. region that corresponds to their specific pI value.
Proteins are natural polymeric chains of dif- At that point, the protein’s overall charge will be
ferent amino acids. The side chains of some amino zero and the protein will stop moving. As a result,
acid residues in proteins have acid-base properties. proteins separate into sharp stationary bands posi-
Of the twenty-one amino acids used to synthe- tioned according to their different pIs. Colored or
size proteins in our bodies, two of them (Aspartic fluorescent dyes are commonly used to detect the
Acid, Glutamic Acid) include functional groups in position of the different protein bands on the gel
their side chains that behave like weak acids and (see image on this page).
three of them (Arginine, Hystidine, Lysine) have IEF is capable of very high resolution, leading
side chains with weak base properties. Depending to the separation into different bands of proteins
on pH, the acidic side chains may be electrically that differ in pI values by as little as 0.01. IEF is
neutral or have a negative charge due to the lost of often the first step in two-dimensional electropho-
a proton. On the other hand, the basic side chains resis, a separation technique in which proteins are
may be neutral or have a positive charge due to the first separated by their pI, and then further sepa-
gain of a proton. The overall charge of the protein rated by their molecular weight.
Let’s Apply
Amino Acids and Proteins
The chemical structure of amino acids and proteins in our body is rather sensitive to changes in
the concentration of surroundings species, such as H3O+ ions, and to variations in temperature.
Consequently, protein function strongly depends on pH and temperature.
Dominant Species pKa ~ 9.5

On average, the pKa of amino and carboxylic groups in
amino acids have the values shown on the image.
pKa ~ 2
• Predict which of the following species is most
likely to be found inside cells in our bodies where
the average pH is 7.4.
% Charged Residues
Consider a segment of a protein with the composition shown below:
pKb = 3.2 pKa = 10.1 pKa = 8.3 pKa = 3.9 pKa ~ 16 pKb ~ 14.5
Given the pKa or pKb of the amino acid residues shown in the image:
• Estimate the percent of each of the residues that will be present in charged form, either
protonated (+) or deprotonated (–), inside human cells where the average pH is 7.4
Protein Folding
The presence of charged groups in a protein helps the macromolecule to

fold due to ion-ion interactions and ion-dipole interactions between resi-
dues. Protein folding can be represented as a chemical process:
Unfold Fold.
• Build a potential energy diagram for the folding process. Clearly indicate which state,
unfolded or folded, has a lower potential energy.

The unfolded form of a protein is favored at higher temper- Folded
Biological Activity
atures. The unfolded protein loses its biological function Unfolded
(the protein is said to be denaturalized).

Denaturalization
• How would you explain the effect of temperature on

folding using kinetic and thermodynamic arguments? Temperature
Protein Separation
Isoelectric focusing (IEF) is used to separate complex mixtures of proteins. This

technique relies on the use of a gel matrix with a fixed and stable pH gradient
(review “Facing the Challenge” on page 403). Chemical compounds known as
Immobilines are commonly used to fix the pH in different regions of the gel.
• If someone uses the Immobiline 4-acrylamido butyric acid (pKa = 4.6) to

create the region of the gel with a pH = 3.3. Calculate the concentration of
the aqueous solution of this Immobiline that should be prepared.
• A 1.58 x 10-3 M aqueous solution of the Immobiline N,N-dimethylamino-
ethyl acrylamide (pKb = 5.5) is being used to prepare the gel. Calculate the
pH that this solution will generate.
• How would the acid-base equilibrium in the above solution be affected if
the solution is left in an open container and some of the water evaporates?
How would the pH of this solution change? Use both kinetic and thermo-
dynamic arguments to make your predictions.
• Increasing the temperature of an IEF gel plate produces pH increments in
the acidic region of the plate (where pH < 7). How would you explain this
phenomenon using a kinetic or a thermodynamic argument?
Let’s Apply
pH Indicators
There are chemical compounds with acid-base properties that change color when reacting with
water. The acid form of these substances, often represented as HInd, has a different color from the
base form, represented as Ind–:
HInd(aq) + H2O(l) Ind–(aq) + H3O+(aq)
The color of a solution of these types of substances depends on the percent of the molecules pres-
ent in acid or base form, and thus varies with the pH of the system. These types of compounds
are thus commonly used as pH indicators to visually detect changes in the pH of a solution. The
following table lists relevant information for common laboratory pH indicators:
Indicator pKa Low pH color Transition pH High pH color

Thymol Blue 1.7 Red 1.2 – 2.8 Yellow
Bromophenol Blue 4.0 Yellow 3.0 – 4.6 Purple
Methyl Red 5.0 Red 4.2 – 6.3 Yellow
Phenol Red 8.0 Yellow 6.8 – 8.2 Red
Phenolphtalein 9.6 Colorless 8.3 – 10.0 Pink
Phenol Red
Phenol red (C19H14O5S) is a pH indicator frequently used in cell biology laboratories. Its solu-
bility in water is 0.77 g/L.
• Calculate the pH of a saturated aqueous solution of phe-

nol red.
• Determine the percent dissociation of phenol red in the
saturated solution.
• Determine the color of a saturated solution of phenol red.
• Determine the value of the concentration ratio HInd
[Ind ]/HInd] at the high end of the transition pH (when a
–
solution of the indicator turns red).

• Predict what would happen to the value of the concentration ratio [Ind–]/[HInd] at the
high end of the transition pH when water is added to the solution. Would you expect
the solution to become more yellowish or more reddish? Justify your predictions using
both kinetic and thermodynamic arguments.
Phenophtalein
Phenophtalein (C20H14O4) is one of the most commonly used pH

indicators in school chemistry laboratories.
• Build a graph showing how the percent dissociation of phe-

nolphtalein changes as a function of pH in the range from
pH = 7 to pH =13. HInd
• Determine the value of the concentration ratio [In–]/[HInd]
at the low and high pH ends of the color transition range for this indicator.
• A solution of phenophtalein is colorless at low pH values and turns pink when

NaOH is added to the system. Predict how the presence of OH– ions affects the
chemical equilibrium of this pH indicator. Use both kinetic and thermodynamic
arguments to explain the effect of the hydroxide ions.
Mixtures
It is common to prepare mixtures of pH indicators that display a variety of color over a

wide range of pH values. That is the case of the so called “universal” indicators. Imagine
that you prepared a pH indicator mixture using bromophenol blue and phenophtalein.
• Using a pH scale from pH = 0 to pH =14, indicate the expected color of the solu-
tion in different pH ranges.
• Identify the form of each indicator, HInd or In–, that would be dominant in each
of the pH regions with a different color.
• Assuming that the dissociation reactions of both indicators are exothermic, de-
scribe what should happen to the different color ranges when the temperature of
the mixture is increased. Do the color ranges become wider, narrower, or do not
change? Use kinetic and thermodynamic arguments to build your predictions.
Natural Indicators
Natural compounds, such as cyanidin present in berries and red cabbage, may be used as
pH indicators. Consider the three different forms of cyanidin shown below:
• Propose different strategies to change the color (red, violet, blue) of a solution of
cyanidin. Justify your reasoning using kinetic and thermodynamic arguments.
384
Analyzing
Chemical Stability
We can control acid-base reactions by changing the initial concentrations of re-

U6: MODULE 3
actants and products. Reaction extent, however, is also determined by the chemi-
cal composition and structure of the particles involved which affect their inter-
actions. Energetic and entropic factors influence the extent to
which proton transfer occurs among interacting particles
and determine the final equilibrium state. The transfer of
protons from acids to bases leads to changes in charge
distribution within and across interacting particles, and
these changes affect the chemical stability of individual
particles and of the solution as a whole. The formation
of anions and cations has a major effect on polar water
molecules that interact strongly with them. These strong in-
teractions reduce the potential energy of the system, but also de-
crease the likelihood of water molecules adopting different configurations, reduc-
ing the total entropy. The balance of these competing effects determines reaction
directionality and extent, and thus acid and base strength. Learning to identify
compositional and structural features that influence acid and base strength is thus
critical in predicting and controlling acid-base reactions.
THE CHALLENGE Food Additives

Many food additives are chemical compounds with acid-base properties that
are used to alter or control the pH of different types of foods.
• How do you think the composition and structure of an acidic or a basic

food additive may influence its function and the sensations it produces
when ingested?
tral goal of Module 3 is to help you identify and evaluate compositional and
structural features that influence acid and base strength.
Thermodynamic Stability
In Module 1 of Unit 5 we learned how to identify compositional and structural
features of reactants and products to qualitatively predict reaction directional-
ity. These features allowed us to infer the signs, positive or negative, of potential
changes in the enthalpy (DH) and entropy (DS) of the reacting system. A simi-
lar type of chemical thinking can be applied to qualitatively predict the relative
strength of different acids and bases. In this case, however, we need to take into
account how the transformation of reactants into products affects charge distri-
bution within and across species, as well as the interactions among the various
components in the system. Consider, for example, the reaction of a generic acid
HA with water as represented in Figure 6.12. Proton transfer from a HA molecule
to a H2O molecule requires energy (DH > 0) as the H–A bond needs to be broken
and attractive interactions between HA and surrounding solvent molecules will be
disrupted. On the other hand, the formation of A– ions will likely lead to energy
release as electrons adopt lower potential energy states and the negative ions more Figure 6.12 Expected changes
strongly interact with water. These strong interactions may restrict the mobility of in enthalpy and entropy dur-
ing the reaction of an acid with
water molecules, reducing the total entropy of the system. water.
Losing solvent interactions Charge redistribution Attracting solvent particles

DH > 0 DH < 0 DH < 0
Breaking bond Ordering solvent particles Forming bond

DH > 0 DS < 0 DH < 0
Which of the changes in enthalpy and entropy depicted in Figure 6.12 are
larger may vary from one acid to another. Despite this complexity, analysis of the
behavior of different substances suggests that reasonable predictions can often be
made by analyzing the structure and interactions of the base present in the system,
either the conjugate base (A–) that is formed when an acid reacts with water or the
base directly added to a solution. In particular, analysis of the stability of the ions
or molecules of the base and of their interactions with water (energy and entropy
factors) can be used to explain and predict patterns in acid and base strength.
Ion Stability LET’S THINK

Conjugate acids and bases are often charged particles. The stability of these ions depends on
the type of electric charge (+ or –) they have, the types of atoms that hold the charge, and the
charge density. Which of the following systems would you predict to be more stable?
• A negative charge on a more electronegative atom or on a less electronegative atom.

• A negative charge on a smaller or a larger atom.
• A negative charge localized on a single atom or distributed among various atoms.
386 MODULE 3 Analyzing Chemical Stability
Acid Strength: Major Features

The conjugate base of an acid molecule of the generic form HA is a negative ion
A–. The extent to which HA molecules transfer protons to water molecules often
depends on the stability of the A– ions, and on the strength of the interactions be-
tween A– ions and surrounding water molecules. Losing a proton induces changes
in how electrons distribute among the different atoms that comprise a molecule.
This change is illustrated in Figure 6.13 where we show the electrostatic potential
maps for a molecule of acetic acid (CH3COOH) and its conjugate base, the ac-
etate ion (CH3COO–). How the negative charge ends distributed in the ions of the
conjugate base affects their stability and interactions with other particles.
The stability and the strength of the interactions of ions formed in solution de-
pends on their charge density, or the degree to which ion charge is concentrated in
a given area or volume. In general, the lower the charge density of a negative ion,
the greater its stability because electron repulsions within the particle are reduced.
On the other hand, the higher the charge density of an ion the stronger its inter-
actions with surrounding water molecules. The formation of such ions may thus
cause a large decrease in the potential energy of the system (DH < 0). The higher
the charge density, however, the greater the ordering effect of such ions on the ori-
entation of water molecules. This restriction in the number of configurations that
water molecules may adopt causes a decrease in the total entropy of the solution
(DS < 0). Keeping in mind these competing factors is useful in making sense of the
Figure 6.13 Electrostatic relative strength of weak acids as measured experimentally.
potential maps for the
acid CH3COOH and its con-
jugate base CH3COO–.
The major compositional and structural features that influence acid strength
can be inferred by carefully analyzing experimental data, identifying trends or pat-
terns in the behavior of different classes of substances, and looking for reasonable
explanations based on energetic and entropic arguments. We will follow this ap-
proach throughout this module as we explore the acid-base properties of different
types of chemical compounds. The results of this analysis will allow us to predict
reaction directionality for chemical processes involving acids and bases.
Feature 1. The type of atom holding the charge

When an acid HA loses a proton, the conjugate base that is formed has a nega-
tive charge that is often localized on a single atom. Charge density, which affects
the stability and interactions of the A– ions, depends on the type of atom holding
the negative charge. The following activity includes some experimental data that
can help us identify common patterns of behavior.
LET’S THINK Acid Strength 1a
Consider the pKa values of the following substances, which may behave as weak acids:
Compound CH4 NH3 H2O HF
pKa 48 38 15.7 3.1
• Write the formula of the conjugate base in each case. Analyze the composition and structure
of each ion and propose a reasonable explanation for the observed trend in acid strength.
Hydrogen fluoride (HF) is the strongest acid among the chemical substances
included in the previous activity. In fact, the dissociation constant for methane
(CH4) and ammonia (NH3) is so small that these compounds are not thought as
acids in aqueous solutions (in general, substances with a pKa > 15 will not behave
as acids in water). The conjugate bases of each of these substances have a negative
charge localized on an atom in the second row in the periodic table (i.e., C, N, O, Figure 6.14 Recognizing
differences in atomic size
and F). These atoms differ both in their size and electronegativity. Size differences, and electronegativity is
however, are comparatively smaller than differences in electronegativity (Figure useful in predicting relative
acid strength
6.14). While the volumes of a carbon atom and a nitrogen atom, for example,
differ in less than ten percent, the electronegativity of nitrogen is twenty
percent higher than that of carbon. Paying attention to differences in size Electronegativity increases at a greater
rate than atomic size decreases
and electronegativity is important because these factors influence charge
smaller rate than atomic size increases

density and the stability of negative ions. The smaller the atomic size, the
Electronegativity decreases at a
6 7 8 9
higher the charge density; the higher the electronegativity, the lower the C N O F
potential energy of electrons localized on an atom. 15 16 17
How can we make sense of the increasing acid strength from CH4 to P S Cl
HF as indicated by their pKa values? These experimental results suggest 34 35
that the F– ions are more thermodynamically stable than the ions OH–, Se Br
NH2–, and CH3– (i.e., the F– ions are more likely to form). Charge density 53
can be expected to be higher in the F– ions, which will lead to stronger I
interactions with water (DH < 0) but stronger ordering effects (DS < 0).
These effects, however, should be similar for the other ions as atomic size
differences are not very large. Stabilization of the negative charge on the more
electronegative fluorine atoms should be much larger though. Experimental data
suggest that the electronegativity effect is dominant when comparing atoms in the
same row of the periodic table. HF is a stronger acid because fluoride ions F– are
more stable, and thus more likely to form, than OH–, NH2–, and CH3– ions.
Let us now compare the acid strength of a different set of chemical com-
pounds that also differ in the type of atom holding the negative charge when the
conjugate base is formed.
Acid Strength 1b LET’S THINK

Consider the pKa values of these substances, which behave like acids when dissolved in water:
Compound HF HCl HBr HI
pKa 3.1 -7 -9 -10
The experimental data presented in the previous activity indicates that hydro-
gen iodide (HI) is the strongest acid in this series. In fact, HF is the only weak
acid in this group as the dissociation constants for the other three compounds
(i.e., HCl, HBr, and HI) are much larger than one. The data suggest that the large
I– ions are more thermodynamically stable than the smaller F–, Cl–, and Br– ions,
and they are thus more likely to form in aqueous solutions.
How do we make sense of the trend in acid strength for HF, HCl, HBr, and
HI? Differences in atomic sizes seem to be dominant in this case. Changes in
atomic size between atoms in the same column but consecutive rows in the peri-
odic table are quite large, and more significant than associated changes in electro-
negativity (Figure 6.14). Charge density decreases considerably from the conju-
gate base F– through the conjugate base I–. The large I– ions interact less strongly
with water than any of the other ions. Although these weaker interactions have
a smaller stabilizing effect from the energetic point of view, they impose fewer
restrictions on the configurations that water molecules can adopt. We should then
assume that differences in entropic effects are responsible for the observed trend in
acid strength. Despite the fact that F– ions may be more energetically stable than I–
ions, experimental results suggests that changes in the entropy of water may have
a major impact on the extent to which the dissociation process occurs.
In general, proton transfer is more likely to involve hydrogen atoms attached
to the most electronegative atoms (when comparing atoms in the same row in the
periodic table) or the largest atoms (when comparing atoms in the same column
in the periodic table) in a molecule. These more reactive hydrogens are often called
the most acidic protons in a molecule. Energetic factors strongly affect acid strength
when comparing acidic protons attached to atoms in the same row of the periodic table,
while entropic factors have a larger effect when comparing acidic protons bonded to
atoms in the same periodic family.
LET’S THINK Most Acidic Protons
Consider potential pharmaceutical drugs with the following structures (where

the symbol R is used to represent the rest of the molecule).
• Identify the most acidic proton in the represented molecules.
Feature 2. Charge delocalization

There are many weak acids in which the negative charge in the conjugate base
is not localized on a single atom. The bonding structure in the molecules of these
substances allows electrons to be delocalized among several atoms, affecting acid
strength.
Acid Strength 2 LET’S THINK

Consider the pKa values for the following dissociation processes:
+ H2O(l) + H3O+(aq) pKa = 15.9
+ H2O(l) + H3O+(aq) pKa = 4.8
• How would you explain the difference in pKa values?
Electrons in molecules are in constant movement but tend to be localized

around single atoms or between two atoms (bonding electrons). There are mol-
Figure 6.15 Different
ecules and molecular ions, however, in which some valence electrons are delocal- representations of elec-
tron delocalization in the
ized in a larger area or volume through resonance. In particular, when a lone pair acetate ion
of electrons in an atom and a bonding pair of electrons in a double bond are
located one single bond away from each other, like in the acetate
ion in Figure 6.15, delocalization through resonance occurs and
the two pairs of electrons end distributed in a larger space. Electron
delocalization is often represented using curved arrows that indicate
the flow of electrons in the molecule or ion, and using dotted lines
to highlight the delocalization region (Figure 6.15). As discussed in
Module 3 of Unit 2, electron delocalization through resonance is
also commonly represented by drawing the different Lewis struc- O
tures in which valence electrons are distributed according to the oc-
tet rule. None of these individual structures, however, corresponds
to the actual structure of the molecule or ion.
Delocalization lowers the kinetic energy and the potential en- O
ergy of the electrons which are less constrained and can get farther
away from each other. Additionally, delocalization leads to lower charge density as
electrical charge is distributed over a larger space. The corresponding ions have a Figure 6.16 Substance
A can be expected to
weaker disrupting effect on the configurations of water molecules, decreasing their be a stronger acid than
substance B. Why?
negative impact on the entropy of the system. Electron delocalization is thus a sta-
bilizing effect that increases the probability that the negative ions will be formed. O
From this perspective, chemical compounds that have conjugate bases comprised
of ions that can be stabilized through resonance are likely to be stronger acids than A
substances in which resonance does not occur. The stabilizing effect due to delo- OH
calization is more pronounced when electrons are delocalized around atoms that
are highly electronegative (e.g., O, N), as this decreases the potential energy of the
anions. or around atoms with a relatively big size (e. g., S), as this further decreases B
charge density (Figure 6.16). OH

Consider potential pharmaceutical drugs with the following structures (where the symbol R is
used to represent the rest of the molecule).
Feature 3. Bond polarization

Acid strength is also affected by the presence of nearby atoms or groups of at-
oms in a molecule that stabilize or destabilize the negative charge in the conjugate
base. To understand the effect of this compositional and structural feature, let us
again analyze some experimental data.
LET’S THINK Acid Strength 3
Consider the pKa values of the following weak acids:
pKa = 0.70 pKa = 2.9 pKa = 4.8 pKa = 5.0
If we take the pKa for acetic acid (CH3COOH) as a reference in our analysis
in the previous activity, the available data indicate that the substitution of hydro-
gen atoms by chlorine atoms in the methyl group (–CH3) increases acid strength,
while the substitution of hydrogens by methyl groups (or other alkyl groups com-
prised of carbon and hydrogen atoms) decreases acid strength. This phenomenon,
known as the inductive effect, can be explained by paying attention to the effect of
different substituents on bond polarity.
The presence of highly electronegative atoms in a molecule, such as F, O, Cl,

and N, causes bonds to be polar, with the electronegative atoms acquiring a par-
tial negative charge and the atoms bonded to them (typically carbon) acquiring
a partial positive charge. The polarization of a bond affects charge distribution in
neighboring chemical bonds. Carbons with a partial positive charge will attract
electrons towards them, polarizing the other bonds that they form. The overall
effect is a transfer of negative charge towards the region where the electronegative
atoms are located. This inductive effect reduces the charge density on the negative
ion that forms after proton transfer, stabilizing the anion and reducing its con-
straining effect on the configurations of water molecules. As a result, the conjugate
base is more thermodynamically stable and acid strength increases.
The presence of alkyl groups in the vicinity of the negatively charged area in
the conjugate base has an opposite effect to that of electronegative atoms. In this
case, the negative charge of the anion becomes more localized and charge density
increases. The conjugate base is then destabilized and acid strength decreases. In
general (Figure 6.17), electron withdrawing atoms or groups of atoms (highly
electronegative) tend to stabilize anions by withdrawing negative charge but they Figure 6.17 Electronega-
tive atoms are said to with-
destabilize cations (as electron withdrawing increases positive charge density). On draw negative charge while
alkyl groups are said to in-
the other hand, electron donating groups (such as alkyl groups) tend to destabilize ject negative charge.
anions but they stabilize cations (alkyl groups are easily polarizable and electrons
can be pulled towards the positive charge, helping to stabilize it).
Most Acidic Protons LET’S THINK

Consider potential pharmaceutical drugs with the following structures (where the symbol R is
used to represent the rest of the molecule).
The three major compositional and structural features discussed in this section
have a strong influence on acid strength. It is then important to carefully analyze
each of them when qualitatively comparing the acid strength of weak acids. Some
of these features, however, have a greater effect than others. In general, the type of
atom holding the negative charge has a stronger effect on acid strength than charge
delocalization, and charge delocalization has a stronger influence than bond polar-
ization. As we will learn in the next section, these three features also play a role in
determining base strength but their influence is based on the effect that they have
on the ability of base molecules to accept protons.
• Select the most acidic proton among the two hydrogen atoms highlighted in each molecule:
• Identify the most acidic proton in each of these nine molecules:
Base Strength: Major Features

The extent to which a base reacts with water, or with other acids, depends on the
likelihood of base molecules B accepting protons. In order for proton transfer to
H–OH
occur, a base molecule should form a new chemical bond with the transferred hy-
drogen ion. Proton transfer is thus likely to involve atoms that have lone electron
R–NH2
pairs, such as N and O, and can covalently bond to hydrogen (Figure 6.18). In
general, the more available the lone electrons pairs are to interact with the hydro-
gen ion, the stronger the base can be expected to be. Consequently, any compo-
sitional or structural features that reduce electron density around the accepting
atom (basic center), or hinder its ability to form a new bond, will weaken the base. Figure 6.18 The accessibil-
On the other hand, any features that increase electron density around the basic ity of the lone electron pair
on the nitrogen of amines
center will make the base stronger. To better understand these ideas, analyze the affects their base strength.
experimental data included in the next activity.
Base Strength LET’S THINK

Consider the pKb values of the following pairs of weak bases:
pKb = 16.2 pKb = 3.36
• How would you explain the difference in base strength? Consider the effect of the major
compositional and structural features discussed in the previous section.
pKb = 9.42 pKb = 3.36
pKb = 3.27 pKb = 3.36 pKb = 4.50
The experimental data included in the previous activity suggests that com-
positional and structural features that: a) stabilize lone electron pairs in the basic
Figure 6.19 Electron de- center of a molecule, b) make these lone pairs less available, or c) decrease electron
localization through reso- density on the basic center, make the base weaker. The lone electron pairs may be
nance weakens this base
(aniline). more stable if they belong to a more electronegative atom in which electrons tend
to occupy lower energy states. If the lone electron pairs are one bond away from a
double bond, electron delocalization may
occur through resonance, which will limit
the availability of those electrons to form a
new bond (Figure 6.19). The presence of
electron withdrawing electronegative at-
oms or groups of atoms in the vicinity of
the basic center will likely weaken the base, while the presence of alkyl groups will
strengthen the base by injection of electron density (inductive effect).
Base strength may also be weakened by the presence of too many alkyl groups
pKb = 3.27 directly attached to the atom holding the lone electron pair. These alkyl groups
may hinder this basic center from approaching hydrogen atoms in other mol-
ecules, reducing the likelihood of proton transfer. This phenomenon is known as
steric hindrance and it is responsible for the typically lower base strength of tertiary
pKb = 4.19 amines compared to that of secondary amines, despite the expected presence of a
larger inductive effect (Figure 6.20).
Many bases are negatively charged species, such as F–, OH–, and CH3COO–,
Figure 6.20 Steric hin- that are the conjugate pairs of neutral acids (e.g., HF, H2O, CH3COOH). The
drance makes tertiary stronger the conjugate acid, the weaker the associated base. Stronger acids generate
amines typically weaker
than secondary amines. more stable anions when they dissociate in water and these more stable species are
less likely to accept protons back. The more stable the anion and the less disruptive
of water molecule configurations, the weaker a base it will be.
LET’S THINK Most Basic Center
Consider a potential pharmaceutical drug with the structure

shown on the image (where the symbol R is used to represent
the rest of the molecule).
• Identify the most basic center in this molecule.
LET’S THINK Higher pH
The two bases shown on the image are added to different

containers with 100 mL of water each.
• Which of the two solutions will have the highest pH?

Acid-Base Reactions
Acids (proton-donors) can react with bases (proton-aceptors) by proton transfer.
Analysis of the relative strength of acids and bases in water helps to qualitatively
predict the directionality and extent of chemical reactions between these types of
substances. Strong acids and strong bases can be expected to react with each other
to a great extent, but predicting reaction extent in processes involving weak acids
and weak bases demands careful consideration of the stability of the different spe-
cies in solution.
Chemical reactions between acids and bases proceed in the direction that leads
to the formation of the most stable species because once these species are formed,
they are less likely to react to generate the original reactants. The most stable spe-
cies are the weakest acids and bases in solution. The stronger the acid and base that
react with each other, or the weaker the conjugate acid and base that are produced,
the greater the reaction extent. Consequently, we can predict reaction directional-
ity and extent by comparing the strength, or the stability, of the reacting acid and
base with those of their conjugate pairs.
Reaction Extent LET’S THINK

Consider the following acid-base reactions:
HCl(aq) + CH3CH2NH2(aq) Cl–(aq) + CH3CH2NH3+(aq)
HF(aq) + NH3(aq) F–(aq) + NH4+(aq)
HBr(aq) + (CH3CH2)2NH(aq) Br–(aq) + (CH3CH2)2NH2+(aq)
• Rank these acid-base reactions in order from less to more product-favored.
Reaction Directionality LET’S THINK

NH2–(aq) + H2O(l) NH3(aq) + OH–(aq)
F–(aq) + HCl(aq) HF(aq) + Cl–(aq)
CH4(g) + F–(aq) CH3–(aq) + HF(aq)
H2S(g) + F–(aq) HS–(aq) + HF(aq)
• Predict whether each of these processes will be product-favored or reactant favored.
LET’S THINK Reaction Directionality
• Predict whether each of these processes will be product-favored or reactant favored.
FACING THE CHALLENGE cules of carboxylic acid also affects the intensity of
the sour taste response. Weak acids, such as acetic
acid and citric acid, can taste more sour than solu-
Sour Taste tions of hydrochloric acid (a strong acid) with the
Food additives are chemical substances added to same pH. Solutions of different carboxylic acids
food for a variety of purposes, such as preserving that taste equally sourly often have different pH.
flavor, enhancing taste, changing texture, modify- These results suggest that the actual composition
ing color, or delaying decomposition by chemical and structure of each carboxylic acid plays a criti-
or biological processes. Many of these additives are cal role in determining sour taste intensity.
chemical compounds extracted from natural sourc- The chemical mechanism that triggers a sour
es that have been used for centuries to preserve and taste response is not well understood. Some experi-
improve food taste. These natural additives include ments suggest that molecular polarity is an impor-
salt, sugar, vinegar, and citric acid. Other additives tant factor to consider. Less polar acid molecules
are synthetic chemical compounds developed by seem to induce a more intense sour taste sensation
the food industry, such as than more polar particles.
food colorants and artificial Acids that contain several
sweeteners. carboxylic groups tend to
Many food additives taste less sour than mono-
have acid-base properties protic acids at the same con-
and are used, among other centration. It has been sug-
things, to change and regu- gested that acid molecules
late food pH. Acidic addi- should be able to go through
tives, in particular, are used the cell membrane and reach
to enhance flavors and as the cell interior to trigger a
preservatives and antioxi- taste response. This would
dants. Their presence tends explain the relationship be-
to inhibit microbial growth. tween molecular polarity and
Common additives in this By Steven Depolo (Own work) [Generic 2.0] via Flickr Commons sour taste, as less polar undis-
group include acetic acid, benzoic acid, citric acid, sociated molecules should be able to more easily
fumaric acid, lactic acid, malic acid, and tartaric diffuse through the non polar cell membrane than
acid. Basic additives, such as calcium carbonate more polar acid molecules.
and calcium oxide, are often used to neutralize ac- Sour taste intensity seems to be directly related
ids and increase pH. to the total molar concentration of the undisso-
Most acidic food additives are carboxylic acids ciated carboxylic acid plus the concentration of
with pKa values in the range from 3 to 5. They free H3O+ ions. Different mechanisms have been
are thus weak acids that barely dissociate in wa- proposed to explain the action of these different
ter. Acidic food additives are characterized by their species. Results from experiments with mice sug-
sour taste and food scientists have invested signifi- gest that specific ion channels in taste buds are
cant efforts trying to figure out the chemical basis involved in sour taste perception. It has not been
of the sour taste response. Although it is generally determined, however, whether the sour taste re-
accepted that sour taste depends on pH and on sponse requires that H3O+ ions and carboxylic acid
the chemical nature and concentration of the car- molecules enter the receptor cells or may operate
boxylic acid, it is not yet possible to predict and from the surface of the cells.
modify with precision sour taste intensity in foods. In addition to their taste qualities, some acids
Sour taste cannot be explained solely on the also impart olfactory sensations. Solutions of a va-
basis of the concentration of H3O+ ions in solu- riety of strong and weak acids can be detected by
tion. The concentration of undissociated mole- nasal inhalation.
Let’s Apply
Acids and Bases in the Body
Acids and bases in our body play central roles in many metabolic functions and physiological pro-
cesses. From how our stomach digests food to how our moods are regulated, molecules that exhibit
acid-base properties are everywhere.
Metabolic Intermediates
The citric acid cycle, also known as the Krebs cycle, is a series of chemical reactions used by
all aerobic organisms to generate energy from the combustion of carbohydrates, fats, and pro-
teins. The conjugate bases of the following acids play a central role in the Krebs cycle:

Oxoloacetic Acid Malic Acid Succinic Acid
• Identify the most acidic proton in each of these molecules.

• Which of these acids is likely to be the weakest? Which of them is the strongest?
Neurotransmitters
Neurotransmitters are chemical substances that transmit signals across a synapse from one neu-
ron (brain cell) to another neuron. Major neurotransmitters in our body include the following
bases:
Methyltyramine Norepinephrine Epinephrine
• Identify the most basic center in each of these molecules.

• Which of these bases is likely to be the weakest? Which of them is the strongest?
Nucleobases
Nucleobases are structural units of DNA and RNA. The structure and pKb of the main basic
center (indicated by an arrow) in three of these metabolites are shown below:
Adenine Cytosine Guanine

pKb = 9.9 pKb = 9.6 pKb = 10.7

• Build a reasonable explanation for the differences in pKb values for these substances
based on the analysis of the three structural features discussed in this module.
Amino Acids
Amino acids are the monomers that make up proteins. They are characterized by the presence
of a carboxylic acid group, a primary amine group, and a side chain with a composition and
structure that varies from one amino acid to another. Consider the amino acids shown below:
Tyrosine Aspartic Acid Alanine
Cysteine Serine Lysine
• Identify the most acidic proton in the side chain of each amino acid.
• Rank these amino acids in order of decreasing acid strength of their side chains.
• Discuss how the presence of the amino group in all amino acids may affect the acid
strength of the carboxyl group, and how the carboxyl group may affect the base strength
of the amino group.
Let’s Apply
More About Drugs
The acid-base properties of pharmaceutical drugs can be usually inferred by careful analysis of their
molecular composition and structure.
Barbiturates
Barbiturates are acidic drugs that act as central nervous system depressants (sedatives, anesthet-
ics). They are derivatives of barbituric acid. Consider these three examples:
Barbituric Acid Barbital Pentobarbital

pKa = 4.1 pKa = 7.9 pKa = 8.1
• Explain the relative high acidity of the hydrogen atom bonded to nitrogen in these three
compounds.
• Build a reasonable explanation for the differences in pKa values for these substances
based on the analysis of the three structural features discussed in this module.
Basic Drugs
Over three quarters of all drugs are weak bases. Consider these examples:
Demerol Ephedrine Benzocaine
• Identify the most basic center in these molecules.

• Rank these drugs in order of increasing base strength. Justify your reasoning.
Amphoteric Drugs
Amphoteric compounds may behave as acids or as bases depending on the substances

with which they interact. Their molecules have at least one acidic group and at least one
basic group. Consider these examples:
Mesalazine Sulfadiazine Lisinopril

• Identify the most acidic proton and the most basic center in these molecules.
Drug Interactions
Given that some drugs are acids and some are bases, they may react with each other.
Consider the following potential reaction involving drugs with different functionalities:
• Predict whether these reactions will be product-favored or reactant-favored.
Drug Modifications Melphalan
Consider this amphoteric chemotherapy drug:
• Propose at least three modifications to the struc-

ture of this drug that would increase either its acid
strength or its basic strength. Justify your reasoning.
Let’s Apply
Chocolate Chemistry
Cocoa beans are naturally tart and acidic because of the presence of a wide variety of organic acids.
This acidity is an advantage since it causes the proteins in baked goods to set rapidly.
Chocolate Acids
Many different types of organic acids can be found in chocolate. Below you can see the mo-
lecular structure of three of them:
Vanillic Acid Butyric Acid Gallic Acid
• Rank the above acids from weakest to strongest.

• Which main factor determines de difference in acid strength between these substances?
• The Ka values for the three weakly acidic protons in vanillic acid are Ka1 = 4.9 x 10-5, Ka2
= 1.6 x 10-9, and Ka3 = 1 x 10-49. Associate these values with the corresponding protons.
• Ammonia (NH3) is used in the chocolate industry to control acidity. Represent the reac-
tion between vanillic acid and ammonia and infer the directionality of the process.
Theobromine is an alkaloid found in chocolate. It is a stimulant

similar to caffeine, although it has stronger cardiac effects. This
compound can be highly poisonous to other animals (this sub-
stance is the reason why dogs should not eat chocolate).
• Despite having several nitrogen atoms in its structure,

theobromine is an extremely weak base in water. Provide a
reasonable explanation for this behavior.
• Propose and draw one structural modification to the molecule of theobromine that
would transform the substance into a stronger base.
• Theobromine actually behaves like a weak acid in water. Draw the line structure of the
conjugate base of theobromine and explain how resonance stabilizes this ion. Use ener-
getic and entropic arguments.
Where From?
be easily shared to form a covalent bond with a
nearby proton.
We can control the extent of acid-base reac-
Where To? tions by carefully selecting the reactants that we

use. However, we can also control these processes
by changing the concentrations of reactants and
In this Unit, we sought products in the system. Increasing the concentra-
to characterize the dif- tion of the product of the dissociation of an acid,
ferent factors that con- for example, will reduce the extent to which the
trol the directionality acid dissociates. Similarly, removing the product
and extent of chemical from the system will increase the extent to which
reactions. We focused proton transfer occurs. Given that the products
our attention on a very of the reaction between acid and bases with water
important class of re- are H3O+ and OH– ions, respectively, the extent
actions that occur rapidly in aqueous solution, to which an acid dissociates or a base is proton-
and thus can be analyzed without much concern ated in water can be controlled by changing the
about kinetic issues. These acid-based reactions concentrations of such ions. This is, by changing
involve the transfer of one or more protons (H+ the pH = –log [H3O+] or the pOH = –log [OH–]
ions) from one molecule to another. Water plays of the solution.
a central role in these types of processes both as a Although the pH or pOH of an aqueous
solvent and a reactant. system always changes when an acid or a base
Many substances have acid-base properties is added to the solution, the magnitude of this
and their molecules participate in proton transfer change can be minimized using buffers. Buffering
when dissolved in water. The molecules of acids solutions are prepared by mixing similar amounts
lose one or more protons (proton donors) when of a weak acid and its conjugate base. When an-
interacting with the molecules of bases (proton other acid or base is added to this solution, the
acceptors) which bond to those H+ ions. The components of the buffer react with them, reduc-
extent to which the molecules of an acid lose ing their effect on the concentration of H3O+ and
their acidic protons when interacting with mol- OH– ions.
ecules of a base depends on the composition and The concepts and ideas about chemical reac-
structure of both types of molecules. In general, tions introduced in Units 5 and 6 have important
proton transfer is more likely to occur when the applications in diverse areas of modern science
process results in the formation of more thermo- and technology. In Unit 7, we will apply these
dynamically stable (less reactive) species. concepts and ideas to the exploration of electro-
When the molecules of an acid lose a proton, chemical devices that are used to harness chemi-
ions with a negative charge (anions) are formed. cal energy. In Unit 8, . we will take advantage of
The thermodynamic stability of these anions this knowledge to analyze prototypical examples
depends on the nature of the atom holding the of chemical processes used in the synthesis of
negative charge, and on the extent to which that new chemical com-
charge is delocalized among nearby atoms. In pounds Units 7
By Hedgehog Fibres (Own work)
general, the acids that dissociate to a larger extent and 8 have been
(stronger acids) produce low-charge density an- designed for you to
ions with a lower potential energy and a weaker apply what you have
disruptive effect on the hydrogen-bonding net- learned abut “chemi-
work of water. The molecules of strong bases con- cal thinking.” Are
tain atoms holding lone electron pairs that can you ready?
Are You Ready?

Psychoactive drugs, also called psychotropic drugs, are chemical substances that change brain function and
alter perception, mood, or consciousness. These types of drugs may be used for therapeutic purposes, but
some of the most well known substances in this group are used for recreational purposes, cause addiction,
and considered illegal in many countries. As is the case with many drugs, most psychotropics have acid-base
properties that affect how they are delivered and consumed, and their effects on our bodies.
GHB
g-Hydroxybutyric acid (GHB, C4H8O3) is a central nervous

depressant used as intoxicant (street name: G, Liquid X, Home
Boy) or as date rape drug. It has also therapeutic uses in the
treatment of depression and alcoholism. The line structure of
this drug is shown to the right.
• Identify the most acidic and the least acidic protons in GHB.
GHB is a weak acid that reacts with water according to the following chemical equation:
GHB(aq) + H2O(l) GB–(aq) + H3O+(aq) Ka = 2.0 x 10–5 DHrxno = –0.4 kJ/mol
Adulterated (spiked) drinks containing GHB have a concentration of GHB close to 0.1 M.
• Estimate the pH of drinks adulterated with GHB.

• Discuss how the pH of the adulterated drink would change if its temperature is increased
or decreased.
• The soft drinks to which GHB is commonly added have a relatively constant pH close to
3. When GHB is added to these drinks, which form of the drug, its acid or basic form is
dominant? What is the percentage of GHB versus GB– in solution?
GHB is used most commonly as a sodium salt (NaGB) or as a potassium salt (KGB). These salts
may be prepared using NaOH or KOH to induce the following acid-base reaction:
GHB(aq) + OH–(aq) GB–(aq) + H2O(l)
• Discuss whether the above reaction is product-favored or reactant-favored.

• Discuss what would happen to a) the concentration and b) the total amount of GHB in so-
lution if more water was added to the above reaction after it reached chemical equilibrium.
Psychoactive Drugs
LSD
Lysergic acid diethylamide (LSD) is mainly used as a recreational

drug, but recent research has shown it to be beneficial in the treat-
ment of post-traumatic stress disorder (PTSD). LSD is non-addictive
but it often induces acute adverse reactions such as anxiety, paranoia,
and delusions. The line structure of LSD is shown to the right.
• Identify the most basic nitrogen in the molecule of LSD and

discuss why the other nitrogen atoms are significantly less basic.
• Identify the most acidic proton in the molecule of LSD.
LSD is a weak base that reacts with water to produce the conjugate acid LSDH+. The graph below
shows the percent of LSD in solution as a function of pH.
• Estimate the pKa of LSDH+ and the pKb of LSD.

• As the drug reaches different parts of the body, it
will adopt its protonated (LSDH+) or its proton-
ated (LSD) form. Discuss which form will be
more abundant in the different regions of the
body listed in the table below.
• Drugs cross biological membranes primarily in
their uncharged form. In which region of the
body will LSD be more rapidly absorbed?
Body Region Mouth Stomach Intestine Blood Jejunum

pH 7 2 6 7.4 8
Imagine that you wanted to investigate LSD absorption in the lab. For that purpose, you want to
prepare a solution that mimics the pH conditions in the Jejunum.
• Which of the following acid-base pairs would you use to buffer your solution?
CH3COOH/CH3COO– (Ka = 1.8 x 10–5) H2PO4–/HPO42– (Ka = 6.3 x 10–8)
HF/F– (Ka = 6.8 x 10–4) H3PO4/H2PO4– (Ka = 1.1 x 10–2)
• Describe the specific chemical compounds you would use, the amounts you would measure,
and the steps that you would follow to prepare the buffer with the desired pH.
• Calculate the percentage of LSD present in such a buffer.
Are You Ready?

Cocaine
Cocaine (C17H21NO4) is an addictive recreational drug that

act as a stimulant and appetite suppressant. This drug is a
weak base with a pKb close to 5.5. The line structure of the
cocaine molecule is shown to the right.
• Predict the structure of the conjugate acid of cocaine (Coc-H+)

• Calculate the Ka and pKa of the conjugate acid.
• Discuss which species, cocaine or its conjugate acid, is stronger in terms of their acid-base
reactivity with water.
The base form of cocaine (also called “freebase”) is practically insoluble in water. Thus, the co-
caine extracted from coca plants is treated with a solution of sulfuric acid (H2SO4) to produce
a water soluble product.
• Discuss how the treatment with sulfuric acid leads to the formation of a water soluble
product. What is the chemical formula of such product?
Cocaine crystals trafficked around the world are commonly the chloride salt of the acid form
of cocaine (Coc-H+). When this substance is mixed with sodium bicarbonate (NaHCO3) to
prepare “crack” cocaine, the following chemical reaction may take place:
Coc-H+(aq) + HCO3–(aq) Coc(s) + H2CO3(aq)
The pKa of carbonic acid (H2CO3) is close to 6.4. Given the pKa for Coc-H+ that you calculated:
• Predict whether the chemical reaction as represented above is product-favored or reac-

tant-favored
Carbonic acid is unstable in water and rapidly decomposes into CO2(g) and H2O(l). Conse-
quently, the reaction between Coc-H+(aq) and HCO3–(aq) is better represented as:
Coc-H+(aq) + HCO3–(aq) Coc(s) + CO2(g) + H2O(l)
• How does the formation of CO2(g) in this reaction may affect the position of the chemical
equilibrium?
Psychoactive Drugs
Most Used Psychotropics
The molecular structures of other psychoactive drugs widely used around the world are
shown below:
Heroin Methamphetamine
Caffeine Nicotine
MDMA THC
• Identify the major basic or acidic centers in each of these molecules.

• Which of these molecules have the most basic centers?
• Which of these drugs have the most acidic protons?
• What is the structure of the conjugate acid or base of each of these molecules?
• Which of these drugs will react with hydrochloric acid to produce soluble salts
(hydrochlorides)?
• Propose a simple structural modification that would decrease the basicity of the
basic drugs or the acidity of the acidic drugs in this group?
Are You Ready?

Food additives are chemical substances added to food to preserve flavor, enhance taste, change texture,
modify color, or delay decomposition. Many of these substances have acid-base properties and are used,
among other things, to change and regulate food pH. Acidic additives are used to enhance flavors and as
preservatives and antioxidants. Basic additives are often used to neutralize acids and increase pH.
Citric Acid
Citric acid (H3C6H5O7) is the most common

acidulant used by the beverage industry. It is a
triprotic acid with a first dissociation constant
Ka = 7.4 x 10–4. The equilibrium constants for
the second and third dissociations are much
smaller. Consequently, we can approximate
the behavior of citric acid by that of a monoprotic acid.
• Which of the hydrogens represented in the line structure of citric acid is likely
to be the most acidic?
The pH of common lemon-flavored sodas is close to 3. If the only acid used to acidu-
late these beverages is citric acid,
• Estimate the molar concentration of citric acid in these sodas.

• Estimate the grams of citric acid added to a 355 mL (12 oz) soda can.
Citric acid is naturally present in fresh lemon, lime, and Juice C (g/L)
orange juices.
Lemon 48
• Use the information listed in the table to estimate the Lime 46
pH of the different juices. Orange 9
Phosphoric Acid
Phosphoric acid (H3PO4) is used to acidulate colas. It is also a

triprotic acid with a first dissociation constant Ka = 7.1 x 10–3.
• Build a reasonable argument to explain why phosphoric

acid is a stronger acid than citric acid.
Food Additives
Buffer Solutions
pH control is critical for ensuring the physical, chemical, and biological stability
of foods. Buffer solutions are thus often used to maintain optimal pH values. For
example, the chemical aspartame is used as an artificial sweetener in diet sodas.
Kinetic studies of aspartame decomposition show that this substance is more
stable at pH values close to 3. To maintain this pH, two main types of buffers are
used. A citric acid/citrate buffer (H3C6H5O7/H2C6H5O7–, Ka = 7.4 x 10–4), and a
phosphoric acid/biphosphate buffer (H3PO4/H2PO4–, Ka = 7.1 x 10–3).
• Determine the ratio of base to acid concentrations ([A–]/[HA]) needed to

maintain a pH = 3 using each of the buffers. Does aspartame have
• If aspartame is most stable when the total concentration of the buffer is acid-base properties?
close to 0.1 M ([A–] + [HA] = 0.1), what specific concentrations of base
and acid should be used when preparing each buffer solution?
Acidulants
Acidulants are acidity regulators used to lower food pH. Some of the acidulants
used by the food industry include:
Tartaric Acid Succinic Acid Lactic Acid
• Identify the most acidic proton in each of these molecules.

• Arrange these carboxylic acids in order of increasing acid strength. Investi-
gate the pKa of these substances to verify your hypothesis.
• Given the compositions and structure of these acidulants, draw the line
structure of another substance that could be used as an acidity regulator.
Predict the relative acidity of this substance compared with that of the sub-
stances above.
Are You Ready?

Basic Additives
Chemical compounds such as calcium carbonate (CaCO3) and calcium oxide (CaO) are used
as acidity regulators too. CaCO3(s) undergoes this chemical reaction in acidic medium:
CaCO3(s) + 2 H3O+(aq) Ca2+(aq) + CO2(g) + H2O(l)
• How does this chemical process affect the pH of the solution where it takes place?
• Express the equilibrium constant for this reaction. Analyze how changes in the amount
of CaCO3(s), pressure of CO2(g), and concentration of Ca2+ ions in the system would
affect this equilibrium. Discuss what would happen to the pH of the system if water
evaporates from the food product. Use kinetic and thermodynamic arguments to jus-
tify your reasoning.
Calcium oxide participates in the following chemical equilibria:
CaO(s) + H2O(l) Ca(OH)2(aq)

Ca(OH)2(s) + 2 H3O+(aq) Ca2+(aq) + 4 H2O(l)
• How do these chemical processes affect the pH of the solution where they take place?
• These reactions are exothermic. Discuss how changes in temperature will affect the pH
of a food system in which CaO(s) is present. Use kinetic and thermodynamic argu-
ments to justify your reasoning.
Share your ideas with a classmate.
Neutralizers
The production of some foods and beverages is based on

fermentation processes that generate carboxylic acids such

By Paul Wilkinson (Own work)
as acetic acid and lactic acid. The pH of these systems is

often controlled by adding ammonia (NH3, pKb = 4.7).
• Represent the acid-base reaction between a generic

carboxylic acid (R–COOH, pKa ~ 4) and ammonia.
Discuss whether this reaction can be expected to be
product-favored or reactant favored.

Module 1
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P350 & P351: Background “Day
139 - IF you Run, Jog or Cycle Look below O_O” by Nina Matthews (Own work) [Generic 2.0] https://www.flickr.com/photos/21560098@
N06/6722653055/in/set-72157627444093697/; P352: Top right By kanenas.net (Own work) [Generic 2.0] https://www.flickr.com/photos/
kanenas-net/sets/72157625888567777; P356: Fig. 6.4 “PH Meter” by Datamax (Own work) [Public domain] http://commons.wikimedia.org/
wiki/File:PH_Meter.jpg; P357: Fig. 6.5 Derivative from “216 pH Scale-01” by OpenStax College (Own work) [Generic 3.0] http://commons.
wikimedia.org/wiki/File:216_pH_Scale-01.jpg; P363: Center “rossy glasses, crimson pills” by psyberartist (Own work) [Generic 2.0] https://www.
flickr.com/photos/psyberartist/2447542822/; P364: Bottom right “Slaapbol R0017600” by Me (Own work) [Public domain] http://commons.
wikimedia.org/wiki/File:Slaapbol_R0017600.JPG; P367: Center right “Pollution - Damaged by acid rain” by Nino Barbieri (Own work) [Generic
2.5] http://commons.wikimedia.org/wiki/File:Pollution_-_Damaged_by_acid_rain.jpg.
Module 2
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P78: Upper right “Corpus blood
stream” by Ton Haex [ShareAlike 2.0] https://www.flickr.com/photos/zjootsuite/2358124682/in/pool-; P379: Center “IEF Banding” from Fed-
eral Drug Administration (FDA).
Module 3
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P397: Center “Airheads Extreme
Sweet Sour Belts Candy Macros” Steven Depolo (Own work) [Generic 2.0] https://www.flickr.com/photos/stevendepolo/4573521344/; P403:
Upper left “Day 139 - IF you Run, Jog or Cycle Look below O_O” by Nina Matthews (Own work) [Generic 2.0] https://www.flickr.com/
photos/21560098@N06/6722653055/in/set-72157627444093697/; Lower right by Hedgehog Fibres [Generic 2.0] https://www.flickr.com/pho-
tos/29825916@N05/8722484981/in/album-72157606929752112/; P404 & P405: Background “CB RGB Retro Psychedelic Persona: J’y suis
L’Art!” by Cairo Braga (Own work) [ShareAlike 2.0] https://www.flickr.com/photos/cairobraga/sets/72157624845539372; P406 & P407: Back-
ground “Cannabis Plant” by BruceBlaus Own work) [3.0 Unported] http://commons.wikimedia.org/wiki/File:Blausen_0159_Cannabis_Plant.
png; P410: Bottom right “Cheese stall, Borough Market, London SE1” by Paul Wilkinson (Own work) [Generic 2.0] https://www.flickr.com/
photos/77992023@N08/galleries/72157634917281414/#photo_8326115428
General
UNIT 7
How do we
harness chemical
energy?
The core concepts, ideas, and methodologies introduced

in previous Units of this course can be applied to design,
implement, and evaluate strategies to harness energy from
chemical reactions. The proper selection of materials and
conditions critically depends on the analysis of diverse fac-
tors that may influence the directionality, extent, and rate
of different chemical processes.
Modern devices used to harness chemical energy often rely

on reactions that result in the transfer of electrons from one
system to another. These batteries transform chemical en-
ergy into electrical energy and are used to power watches, cell
phones, tablet computers, and electric cars in modern times.
The current challenge is to produce devices that can store energy
in large amounts per unit mass and that can deliver that energy in
short periods of time.
The central goal of Unit 7 is to create opportunities for you to apply

the knowledge developed in this course to the analysis of electrochemical
processes and devices used to harness energy.
By Avda (Own work) [Share Alike 3.0]
412
Chemical Thinking
UNIT 7 MODULES
M1. Controlling Electron Transfer

Analyzing thermodynamic, kinetic,and practical
aspects of electrochemical systems.
413
414
Controlling
Electron Transfer
Most of the energy used by modern societies results from the transformation of
U7: MODULE 1
chemical energy into thermal, electrical, or light energy. The major proportion of
[Public Domain] via Wikimedia Commons

that energy is generated by combustion of fossil fuels rich in
hydrocarbons that react with oxygen in the atmosphere
By KyloDeel (Own work)

and produce carbon dioxide and water in a very exother-
mic process. Concerns with the role that CO2 has on
global warming and climate change on Earth has sparked
interest in the development of more durable and power-
ful batteries and fuel cells. These devices transform chemical
energy into electrical energy without generating greenhouse gases.
The design of electrical batteries and fuel cells demands a very good under-
standing of the thermodynamics and kinetics of the processes that take place inside
these devices. The challenges that scientists and engineers face to improve energy
storage and delivery are not small. Chemical reactions inside batteries and fuel
cells involve substances in different states of matter that should interact effectively
over time and under different conditions. Rechargeable batteries require chemical
reactions that can be reversed without major deterioration of components. Reac-
tants and products should be contained within the device at all times and any heat
produced by internal processes should be quickly dissipated to avoid damaging the
battery and major hazards. In Unit 7 we will explore how chemical thinking can
be used to face some of these challenges.
THE CHALLENGE Bio-Batteries

The understanding of how plants and animals store and use energy has guided
the development of bio-batteries that mimic biological systems.
• Which biochemical processes for energy storage do you know?

• What are some potential advantages and disadvantages of bio-batteries
compared to conventional batteries?
central goal of Module 1 is to help you apply your knowledge in the analysis of
electrochemical processes used to harness chemical energy.
Chemical Thinking U7 How do we harness chemical energy? 415
Analyzing Electron Distribution

Chemical reactions result from interactions between regions with different elec-
tron density in the reacting particles. These interactions often lead to the breaking
of some chemical bonds and to the formation of new ones. In these processes,
valence electrons are redistributed between some atoms and their potential energy
changes. The chemical reactions commonly used to generate energy in modern
societies are exothermic processes in which energy is released due to the movement
of electrons from high to low potential energy states. Thus, identifying
chemical species in which electrons occupy states with different potential
energies can help us select combination of reactants that will react exo-
thermically with each other.
Electrons are negatively charged particles that are attracted to centers
with a partial or net positive electric charge. Electrical forces thus induce
movement of electrons from regions with a partial or net negative charge
to areas with a partial or net positive charge. From an energetic perspec-
tive, the potential energy of electrons is higher in areas with a partial or net nega- Figure 7.1 In this reaction,
tive charge and lower in regions with a more positive partial or net charge (Figure electrons in the double bond
(higher potential energy)
7.1). Transfer of electrons should then spontaneously occur from high potential move towards the chlorine
atom where they occupy
energy states to low potential energy states, but these processes often face kinetic lower potential energy states.
activation barriers that need to be overcome for the transfer to happen.
We can identify areas of partial positive or negative charge in molecules by
analyzing their composition and structure. Difference in electronegativity may be
used to infer partial charges in different atoms. This approach, however, has limi-
tations as it does not make explicit how many electrons are transferred between
reactants and how they are redistributed during a chemical reaction.
Electron Transfer and Redistribution LET’S THINK

Consider the addition reaction
represented to the right:
• Assign partial charges to all + HBr

the atoms in reactants and
products.
• Describe the major changes in electron density that you observe.
• Evaluate whether you can determine how many electrons were transferred in this process
and how they were redistributed.
• Highlight advantages and disadvantages to this approach to analyze electron transfer.
Analysis of the partial charges on different atoms in reactants and products

provides qualitative information about changes in electron density as a result of a
chemical reaction. However, chemists have developed other strategies that facili-
tate the identification of electron-rich and electron-poor sites in molecules and
provide more insights into how electrons are transferred or redistributed in chemi-
cal reactions.
416 MODULE 1 Controlling Electron Transfer
A useful strategy to analyze electron distribution in molecules and ions is to

calculate the oxidation state (or oxidation number) of each atom present in the
system. The oxidation state indicates the total number of valence electrons that
an atom would gain or lose when forming chemical bonds if we assumed that
bonding electrons belong to the most electronegative atom in each bond. Thus,
the oxidation state represents the charge of the atoms if we assumed that all bonds
are ionic. The oxidation state is often a fictitious quantity but it provides useful
information about electron distribution in chemical species.
To calculate the oxidation state (OS) of an atom in a system we take the dif-
ference between the number of valence electrons in the isolated atom and the
number of valence electrons in the bonded atom (assuming ionic bonding):
OS = Number of valence electrons in the isolated atom

– Number of valence electrons in the bonded atom
Let us apply this relationship to calculate the oxidation state of all atoms in a
molecule of ethanol CH3CH2OH. If we assign the different valence electrons to
the most electronegative atom in each bond and split bonding electrons equally
between atoms of the same type, as shown in Figure 7.2, the oxidation state for
each atom in the molecule can be calculated as:
OS(H) = 1 – 0 = +1
OS(O) = 6 – 8 = –2
1 2
OS(C1) = 4 – 7 = –3
OS(C2) = 4 – 5 = –1
Figure 7.2 Assignation The number of valence electrons in the isolated atoms can be inferred from their
of valence electrons to
different atoms in the position in the periodic table. The number of valence electrons in the bonded state
ethanol molecule assum-
ing ionic bonding. is determined by counting the electrons assigned to each atom based on relative
electronegativity values (Figure 7.2). Notice that the carbon atoms in ethanol do
not have the same oxidation states, making explicit the presence of an electron-
poor site (C2) in this molecule. However, the oxidation states determined above do
not correspond to actual electric charges on any of the atoms.
LET’S THINK Oxidation State
Determine the oxidation state of each

atom in the species shown to the right:
• What major patterns do you observe?

• What is the relationship between the
oxidation states and the net charge of
a molecule or ion?
Clearly justify your ideas.

The determination of the oxidation states of many molecules and ions reveals
some basic patterns that simplify the calculation of this quantity for any atom in
any molecular species. These simplifying rules are listed below:
a) Elementary Substances: The oxidation state of atoms present in the par-

ticles of elementary substances, such as He(g), O2(g), Na(s) or He(g) is always
zero. For example, in the case of the molecule of Cl2 (Figure 7.3):
OS(Cl) = 7 – 7 = 0 Figure 7.3 Assignation of va-

lence electrons to the atoms
in the Cl2 molecule.
b) Monoatomic Ions: The oxidation state of monoatomic ions present in
ionic compounds or as free ions in solution, such as Na+, Cl–, Mg2+, S2–, is the same
as the net charge of the ion. Thus:
OS(Al3+) = +3
c) Reference Atoms: The oxidation state of some atoms is generally a fixed

number in many chemical compounds. These values can be used to infer the oxi-
dation states for other atoms present in the same chemical species:
OS(Alkali Metals: Li, Na, K ..) = +1

OS(Alkaline Earth Metals: Mg, Ca, Sr ..) = +2
OS(H) = +1
OS(O) = –2
OS(F) = –1
d) Net Charge: The algebraic sum of the oxidation states of all the atoms pres-
ent in a molecule or ion should be equal to the net charge of the chemical species.
If the molecule has no charge, the algebraic sum of the oxidation states should be
equal to zero. If the particle is a polyatomic ion, the algebraic sum of the oxida-
tion states should be equal to the charge of the ion. Consider, for example, the
molecule of ethanol CH3CH2OH in Figure 7.2:
Net Charge = SOS = 6 x OS(H) + OS(C1)+ OS(C2)+ OS(O)
Net Charge = SOS = 6 x (+1) + (–3) + (–1) + (–2) = 0
Basic Rules LET’S THINK

The following chemical species are commonly used in the synthesis or transformation of alcohols:
H2 H2CrO4 KMnO4 NaOCl
The following species are polyatomic ions present in different electric batteries:
OH– SO42– NO3– NH4+
• Determine the oxidation state of each atom in these different chemical species.
Oxidation-Reduction (REDOX) Reactions

When different chemical species interact with each other, electrons may be trans-
ferred from one atom to another. In this process, the oxidation state of some at-
oms may change as some bonds get broken and new bonds are formed. Chemical
reactions that result in changes in the oxidation state of participating atoms are
classified as oxidation-reduction reactions or redox reactions.
LET’S THINK Electron Transfer
Consider the chemical reaction for the incomplete combustion of methanol (CH4O):
CH4O + O2 CO + 2 H2O
• Assign oxidation states to each atom in the reactants and products.

• Use your results to identify which atoms lost electrons and which atoms gained electrons
during the reaction.
Redox reactions tend to be exothermic reactions due to the movement of electrons

from higher to lower potential energy states, and thus may be used to harness
chemical energy. The following two chemical reactions are typical examples of
these types of processes (oxidation states for each atom are shown):
-4 +1 0 +4 -2 +1 -2
CH4 C H4 + 2 O 2 C O2 + 2 H2 O
C CH4
Oxidized Reducing 0 0 -3 +1
Agent 3 H2 + N2 2 N H3
+ In the first of these reactions, the combustion of methane (CH4), the oxidation
state of carbon atoms increases from –4 to +4, while the oxidation state of oxy-
O2 gen atoms decreases from 0 to –2. These changes indicate a transfer of electrons
O 2 O2 Oxidizing
Reduced (or electron density) from carbon atoms to oxygen atoms during the combustion
Agent process. In the synthesis of ammonia (NH3) represented by the second reaction,
electron transfer occurs from hydrogen atoms to nitrogen atoms.
During a redox reaction, the atoms that lose electrons or electron density are
CO2 said to be oxidized during the process. We can recognize oxidized atoms because
their oxidation state increases (it becomes less negative or more positive). In gen-
eral, the term “oxidation” refers to the loss of electrons. On the other hand, the atoms
+ that gain electrons or electron density are said to be reduced. We can recognize
reduced atoms because their oxidation state decreases (it becomes less positive
2 H2O or more negative). In general, the term “reduction” refers to the gain of electrons.
Consequently, during the combustion of CH4 carbon atoms are oxidized and oxy-
Figure 7.4 Oxidized and re- gen atoms are reduced. The two reactants that exchange electrons during a redox
duced atoms, and oxidizing
and reducing agents. reactions are commonly named the oxidizing agent and the reducing agent. The
oxidizing agent holds the atoms that gain electrons during the process (i.e., the at-
oms that are reduced), while the reducing agent holds the atoms that lose electrons
as a result of the reaction (i.e., the atoms that are oxidized). In the combustion of
methane, O2 is the oxidizing agent and CH4 is the reducing agent (Figure 7.4).
Redox Reactions LET’S THINK

Consider the following exothermic reactions :
H2 + 2 O2 2 H2O
HCl + NH3 NH4Cl
CH4 + 2 H2O CO2 + 4 H2
C2H4 + H2 C2H6
• In each case, determine whether the process can be classified as a redox reaction. Identify
the oxidized and reduced atoms, and the oxidizing and reducing agents in redox reactions.
Many redox reactions used in electric batteries to generate energy involve me-
tallic and ionic species that react readily when in contact with each other. For
example, when metallic zinc is added to an aqueous solution of a copper(II) salt,
the following exothermic and product-favored reaction takes place:
Zn(s) + Cu2+(aq) Zn2+ (aq) + Cu(s)
Analysis of the oxidation states of reactants and products indicates that zinc atoms
are oxidized and copper ions are reduced in this process. Moreover, the change in
oxidation states reveals that every zinc atom loses two electrons and every copper
ions gains two electrons. It is common to represent the oxidation and reduction
processes as the following separate half reactions:
Zn Zn2+ + 2 e– OXIDATION
Cu2+ + 2 e– Cu REDUCTION
[Sahre Alike 3.0] via Wikimedia Commons

Each half-reaction represents the chemical species involved in electron transfer and
By Toby Hudson (Own work)

the number of electrons that are exchanged between them. By convention, elec-
trons are represented in the product side in the oxidation half reaction and in the
reactant side in the reduction half reaction. The number of electrons exchanged
is always the same, as the electrons lost by the oxidized atoms are gained by the
reduced atoms. For example, consider the reaction that takes place when metallic
copper is in contact with an aqueous solution of a silver(I) salt (Figure 7.5):
Cu(s) + 2 Ag+(s) Cu2+(s) + 2 Ag(s)
In this case, the half reactions can be expressed as:

Figure 7.5 Oxidation of
metallic copper in a solution
Cu Cu 2+
+ 2e –
OXIDATION of silver nitrate.
2 Ag+ + 2 e– 2 Ag REDUCTION
These half reactions reveal that each copper atoms provides the number of elec-
trons needed to reduce two silver ions. Notice that in this case the copper atoms
are the oxidized species, which suggests that the direction of electron transfer de-
pends on the nature of the chemical species in interaction.
LET’S THINK Half-Reactions
Consider the following unbalanced redox reactions:
Al(s) + Cu2+(aq) Al3+(aq) + Cu(s)

Zn(s) + H+(aq) Zn2+(aq) + H2(g)
Al(s) + Br2(l) Al3+(aq) + Br–(aq)
• Write the corresponding half reactions for each process. Identify the atoms that are oxidized
and reduced, and the minimum number of each species involved in electron exchange.
Electrochemical Devices
The electron transfer that takes place during some redox reactions can be used to
generate an electric current. Electrochemical devices are systems designed to con-
trol the transformation of chemical energy into electrical energy. These types of
devices often include three basic parts:
I. A chemical system that undergoes “oxidation”: A An+ + ne-

II. A chemical system that undergoes “reduction”: B + me-
m+
B
III. A mechanism to allow and control charge transfer.
These three parts must be connected to each other to allow a controlled transfer
of electrons from the system where the oxidation takes place to the system where
the reduction occurs.
LET’S THINK An Electrochemical Cell
The image to the right depicts the basic com-

ponents of a galvanic or voltaic cell, a pro-
totypical electrochemical device. Although (–) Na2SO4 paste (+)
the specific chemical substances used in Anode Cathode
Sodium Ions Sulfate Ions
the cell may vary, as well as the manner in
which different components are linked to
each other, the underlying structure is pres-
ent in most electrical batteries.
• Identify the three basic components of

the electrochemical device.
• Describe and represent in detail the
processes that are taking place in each
of the main components of the system.
In an electrochemical cell, the systems that undergo oxidation and reduction

are physically separated from each other to avoid the direct transfer of electrons High Electric Potential
between them. Instead, they are connected via an external circuit that controls the ++++++++++++
flow of electrons from the reducing agent to the oxidizing agent. Electrons spon-
taneously move from high to low potential energy states. The potential energy of
charged particles is determined by the electric potential (V) at the place where they + –
are located. The potential energy of positive charges decreases as they move from
regions where the electric potential is higher or more positive to regions where the
electric potential is lower or more negative. Conversely, the potential energy of ––––––––––––
Low Electric Potential
negatively charged particles, such as electrons, decreases as they move from areas
with a low or negative electric potential to regions with a higher or more positive Figure 7.6 Movement of
electric potential (Figure 7.6). charge due to a difference in
electric potential.
The two main systems that comprise an electrochemical cell, also called half
cells, have different electric potentials. The half cell that contains the oxidizing
agent has the higher or more positive electric potential and is associated with the
“cathode” of the cell (Figure 7.7). The half cell that contains the reducing agent has
the lower or more negative electric potential and is associated with the “anode.”
The difference in electric potential from the anode to the cathode is the electric
voltage of the cell (DV) and it drives the flow of electrons from one electrode to the
other. The electric voltage DV depends on the chemical nature and concentration
of the species in the cell, and on temperature. DV
DV
decreases as electrons transfer from anode to cath-
ode and eventually becomes zero.
When electrons are allowed to move from the
anode to the cathode through the external circuit
By Shamsher Singh (Own work)

via UC Davis ChemWIki
of an electrochemical cell, a charge unbalance is
created. The anode becomes slightly more positive
and the cathode becomes slightly more negative.
This affects the distribution of ions in the aque-
ous solutions of the electrochemical cell. Negative
ions are repelled by the cathode and attracted by
the anode, while positive ions are pulled towards
the cathode and move away from the anode. This
flow of ions allows the oxidation and reduction processes to continue as the posi- Figure 7.7 Major components
tive ions formed in the anode as a result of the oxidation (Cu2+ in Figure 7.7) are of an electrochemical cell
continuously dispersed throughout the system, and the positive ions involved in
the reduction reaction (Ag+ in Figure 7.7) are pulled towards the reduction site.
Charge Transfer LET’S THINK

Consider the electrochemical cell depicted in Figure 7.7:
• Carefully analyze the flow of charge in this electrochemical device. Discuss how electric
charge is transferred through the external circuit and through the salt bridge.
• Analyze whether the salt bridge is necessary for the electrochemical cell to work. Think of
other arrangements that could be used to replace the salt bridge.
Electrochemical Cell Potentials

The voltage DV of an electrochemical cell determines the maximum amount of
electrical energy that the device may generate. DV is a measure of the chemical en-
ergy transformed into electrical energy per unit of electric charge that flows from
the anode to the cathode. The voltage DV is often expressed in volts (V) which
are a measure of the joules (J) of energy per coulomb of charge transferred. An
electrochemical cell with a DV = 2.5 V, for example, will produce 2.5 J of energy
when 1 C of charge flows through its external circuit.
Given that the magnitude of the electric charge of a single electron is very
small when expressed in coulombs |qe| = 1.602 x 10–19 C, it is common to express
and calculate the energy transformed by an electrochemical cell per mole of elec-
trons transferred. The magnitude of this amount of charge is known as Faraday’s
constant F and it is equal to:
Ep F = Na|qe| = 6.022 x 1023 x 1.602 x 10–19 = 9.647 x 104 C/mol

n e-
where Na is Avogadro’s number. If “n” moles of electrons are transferred from the
anode to the cathode in an electrochemical cell with a voltage DV, the amount
DG = – nFDV
of energy involved is then given by the product nFDV. This quantity is equal in
magnitude to the decrease in potential energy of the electrons transferred from the
anode to the cathode (Figure 7.8). This change in potential energy is a measure
of the decrease in the Gibbs free energy DG of the electrochemical cell when “n”
Anode Cathode
moles of electrons flow from the anode to the cathode:
Figure 7.8 Change in
free energy due to elec- (7.1) DG = – n F DV
tron transfer.
The negative sign in this expression accounts for the decrease in the potential en-
ergy of the system. This relationship highlights the importance of determining the
value of DV for any electrochemical cell of interest as this quantity can be used to
predict the maximum amount of electrical energy that device can produce.
LET’S THINK A Reference Cell
Consider the following information:
When an electrochemical device with the two half cells Ag(s)|Ag+(aq) (1 M) and H2(g)|H+(aq)
(1 M) is built, the following processes take place and a DV is established
Anode: H2 2 H+ + 2 e- Cathode: Ag+ + e- Ag DV = 0.80 V
When an electrochemical device with the two half cells Zn(s)|Zn2+(aq) (1 M) and H2(g)|H+(aq)
(1 M) is built, the following processes take place and a DV is established:
Anode: Zn Zn2+ + 2 e- Cathode: 2 H+ + 2 e- H2 DV = 0.76 V
• What would you expect to happen when an electrochemical cell is built using the half cells
Ag(s)|Ag+(aq) (1 M) and Zn(s)|Zn2+(aq) (1 M). What would DV be? Justify your reasoning.
The two electrodes in an electrochemical cell typically have different electric

potentials. The electric potential of the cathode is higher than the electric potential
of the anode and DV is a measure of such difference. If we build a set of electro-
chemical cells that have one half cell in common and measure their associated volt-
ages, we can use these data to infer the DV for any electrochemical cell built with
any pair of half cells in the set. For example, consider these data:
Electrochemical Cell A: H2(g)|H+(aq) (1 M) || Cu(s)|Cu2+(aq) (1 M)

Anode: H2 2 H+ + 2 e-
V
Cu|Cu2+
Cathode: Cu2+ + 2 e- Cu DV = 0.34 V
0.34 V
H2|H+
Electrochemical Cell B: Zn(s)|Zn2+(aq) (1 M) || H2(g)|H+(aq) (1 M)
Anode: Zn Zn2+ + 2 e- 0.76 V
Cathode: 2 H+ + 2 e- H2 DV = 0.76 V
e-
Zn|Zn2+
These data suggest that the Cu(s)|Cu2+(aq) half cell has an electric potential that
is 0.34 V higher than that of the H2(g)|H+(aq) half cell, while the Zn(s)|Zn2+(aq) Figure 7.9 Relative elec-
half cell has an electric potential that is 0.76 V lower than that of the H2(g)|H+(aq) tric potential V of differ-
ent half cells. When free,
half cell. Consequently, an electrochemical cell built with the copper and zinc half electrons move from re-
gions of low to high elec-
cells should have these characteristics (Figure 7.9): tric potential.
Electrochemical Cell C: Zn(s)|Zn2+(aq) (1 M) || Cu(s)|Cu2+(aq) (1 M)

Anode: Zn Zn2+ + 2 e-
Cathode: Cu2+ + 2 e- Cu DV = 0.34 + 0.76 = 1.1 V
The DV measured using the H2(g)|H+(aq) half cell as a reference can be used
to define an standard reduction potential Eored for any given redox pair A|An+. The
magnitude of Eored is equal to the voltage DV of the electrochemical cell comprised
of the half cells A|An+ and H2(g)|H+(aq) under standard conditions: 25 oC of tem-
perature, 1 M concentrations for all aqueous solutions, and 1 atm of pressure for
all gaseous substances. The sign of Eored depends on whether the half cell A|An+ acts
as the cathode (Eored > 0) or as the anode (Eored < 0) when paired with
Standard Reduction Potentials
the reference system. The standard reduction potentials for common
redox pairs are listed in the table to the right. By definition, the value of Reduction Half-Reaction Eored (V)
Eored for the reference H2(g)|H+(aq) system is equal to zero. F2 + 2 e- 2 F– +2.87
The standard reduction potentials can be used to calculate the volt-
age, commonly called the standard cell potential Eocell of electrochemi- Cl2 + 2 e- 2 Cl –
+1.36
cal cells formed using any combination of redox pairs. The value of Eocell Ag+ + e- Ag +0.80
is given by the difference between the E red for the half cell where reduc-
o
I2 + 2 e- 2 I– +0.54
tion takes place (cathode) and the Eored for the half cell where oxidation
More Oxidizing
occurs (anode): Cu2+ + 2 e- Cu +0.34

H+ + 2 e- H2 0.0
(7.2) DV = E cell = E red (cathode) – E red (anode)
o o o
Pb + 2 e-
2+
Pb –0.13
Systems with a more positive value of Eored involve stronger oxidizing Zn2+ + 2 e- Zn –0.76
agents than systems with the less positive or more negative standard Al3+ + 3 e- Al –1.66
reduction potentials. The relative position of different redox pairs in the Mg + 2 e-
2+
Mg –2.37
scale can be used to predict which species undergo reduction (cathode)
Li+ + e- Li –3.05
and oxidation (anode) when connected in an electrochemical cell.
LET’S THINK Design your Own Devices
Based on the information presented in previous pages:
• Design an electrochemical cell that will produce a standard cell potential close to 2.0 V.
• Determine what half reactions will take place in the cathode and the anode of your cell.
• Make a drawing of the electrochemical cell showing the chemical processes that are taking
place in each half cell and how charge is being transferred from one half cell to the other.
• Determine the amount of electrical energy that your electrochemical cell will be produce per
mole of reducing agent consumed in the anode.
The values of the reduction potentials Ered and the associated Ecell for an electro-
chemical device depend on the temperature and the concentration of all species
present in the system. For a reduction half reaction of the generic form:
Oxidizing Species + n e- Reducing Species
the effects on the reduction potential Ered are determined by the following relation-
ship, known as Nernst equation:
RT [Red]
(7.3) Ered = Eored – ln
nF [Ox]
In this equation, Eored is the standard reduction potential for the redox pair under
consideration, T is the temperature, and [Red] and [Ox] are the concentrations (or
pressures) of the reducing and oxidizing species, respectively.
Consider now the generic electrochemical cell: Red1|Ox1 || Red2|Ox2

Anode: Red1 Ox1 + n e-
Cathode: Ox2 + n e- Red2 DV = Ecell = Ered(cat) – Ered(an)
with an overall redox reaction: Red1 + Ox2 Ox1 + Red2
If we apply Nernst equation to calculate the reduction potentials Ered for the anode
and the cathode, the cell potential Ecell is given by:
RT [Red2][Ox1] RT
(7.4) Ecell = Eocell – ln = Eocell – ln Q
nF [Ox2][Red1] nF
where Q is the reaction quotient for the overall reaction. As discussed in Unit 6,
Q = K at equilibrium, where K is the equilibrium constant for the process. When
chemical equilibrium is reached Ecell = 0 and no net charge is transferred between
the half cells.
What are the Effects? LET’S THINK

Analyze the implications of (7.4):
• How does Ecell vary as the redox reaction proceeds and reactants are consumed?
• How does Ecell change with increasing or decreasing temperature?
• If Ecell = 0 and Q = K when the redox reaction reaches equilibrium, how is K related to Eocell?
Electrochemical Cell Kinetics

The voltage of an electrochemical cell Ecell determines the amount of energy that
the device can produce per unit of charge transferred from the anode to the cath-
ode. The electric power of the cell, however, depends on both Ecell and the rate at
which the charge is being transferred between electrodes as measured by the elec-
tric current “i”. The magnitude of the electric current i is determined by the rate
of the chemical reactions taking place in the half cells. Let us explore the effect of
different factors on such reaction rate.
Reaction Rate LET’S THINK

The rate of reaction in an electrochemical cell depends on the various factors listed below:
a) Temperature of the system b) The activation energy of the reaction

c) The porosity of the electrodes d) The solvation of ions in solution
e) The concentration of ions at the interface f ) The rate of ion diffusion in solution
• Discuss and explain how each of these factors may affect reaction rate and, thus, the magni-
tude of the electric current generated by an electrochemical cell.
In the types of electrochemical cells analyzed in Unit 8, the chemical re-

++++++++++++
actions taking place at the electrodes typically involve metal dissolution and +
deposition, as well as gas evolution. When the device is set up, the reactants –
can be expected to be plentiful and the electric current will be determined +
by the rate at which electrons are transferred between metal atoms and ions
at the electrode/solution interface. As the reaction proceeds and reactants
are consumed, the availability of ions at the electrode/solution interface will –
–
decrease, slowing down the overall process (Figure 7.10). The rate at which +
ions diffuse from the bulk of the solution to the surface of the electrode will
affect the rate of the reaction. Increasing temperature will increase the diffu-
sion rate and thus the electric current. The formation of films at the metal – +
surfaces, such as metal oxide films, often increases the resistance to charge
Figure 7.10 Submicrosco-
transfer and decreases electric current. pic representation of an
electrode/solution interface.
Once an electric current is established in an electrochemical cell, conditions in

each half cell start to change. For example, positive ions produced by the oxidation
in the anode start accumulating near this electrode. In the other hand, the concen-
tration of positive ions near the cathode decreases as the reduction half reaction
takes place. These changes affect the value of the voltage (Ecell) across the electro-
chemical cell. In particular, we can expect the electric potential of the anode to
increase due to the accumulation of positive charge in its vicinity and the electric
potential of the anode to decrease due to the depletion of positive ions near that
electrode. The faster the reaction, the greater the electric current but also the larger
the decrease of the cell potential Ecell = Ered(cathode) – Ered(anode).
Ecell at i = i1 The relationship between electric current i
and the reduction potential Ered of the electrodes
i is represented in Figure 7.11 for a Cu|Cu2+ (1 M)
Cu Cu2+ + 2e- || Ag|Ag+ (1 M) electrochemical cell. By conven-
tion, the anodic current is defined to be positive
i1 (electron flow out of the anode) and the cathodic
current is taken to be negative (electron flow into
0.34 0.80 Ered (V) the electrode). Thus, on the current “i” axis in Fig-
–i1 ure 7.11 anodic current is plotted upward and ca-
thodic current downward. The greater the electric
Ag + e- Ag
+ current, the larger the drop in the cell potential Ecell
and the lower the amount of energy that the device
generates per unit of charge transferred from the
Ecell at i = 0
anode to the cathode. Consequently, the design of
efficient electrochemical devices demands creating
Figure 7.11 Relationship conditions in which the decrease of the cell potential is minimal when an electric
between electric current i
and cell potential Ecell in a current is actually circulating through the system. This requires lowering all types
Cu|Cu2+ || Ag|Ag+ cell. of energetic barriers that hinder the transfer and movement of electrons and ions
in different parts of the electrochemical cell.
LET’S THINK i-Ecell Relationship
The graph shown to the right depicts the relation-

ship between electric current i and cell potential Ecell at i = i1
Ecell for an electrochemical device under two differ-
ent conditions represented by the solid and dotted i
lines, respectively.
i1
• Discuss and explain which set of i-Ecell data
–i1 Ered (V)
corresponds to:
a) A cell working at high versus low tempera
ture;
b) A cell with more porous versus less porous Ecell at i = 0
electrodes;
c) A cell in which ions diffuse rapidly versus slowly.
• Discuss what other factors may affect the i-Ecell relationship and how they may influence it.
FACING THE CHALLENGE Hydrogen ions H+ migrate to the cathode through

the porous separator, where they participate in the
reduction reaction
Bio-Batteries
A bio-battery is an electrochemical device that gen- O2 + 4 H+ + 4 e– 2 H2O
erates electricity from organic compounds, such as
sucrose, glucose, and fructose. The batteries rely Due to the selective reactivity of the enzymes at
on biocatalysts to increase rates of oxidation and each electrode, no cross reaction occurs between
facilitate electron transfer. The biocatalysts can be the anode and the cathode.
enzymes or microorganisms that help process the Currently, the are no bio-battery templates
organic fuels. In passive bio-batteries, the reactive that allow the mass production of miniature devic-
substances are absorbed into the system by natural es with a size in the order of 1 cubic centimeter, as
diffusion. In active devices, the reactants are in- needed for physiological sensors. Electron flow in
jected into the electrochemical cell. In the future, current devices is too slow, mostly due to the diffi-
miniature bio-batteries culty of establishing ef-
could be used to power fective contact between
microsensors implanted Glucose Glucanolactone enzymes and electrodes.
within a human patient Anode Enzyme stability is also
Enzymes
to monitor blood pres- Anode
a critical issue as these
Anode
sure, temperature, and Mediators bio-catalysts are very
the concentration of sensitive to changes in
different metabolites. Electrolyte temperature and pH.
The chemical reac- Enzymes used in
e– H+
tions in a bio-battery bio-batteries are ex-
Separator
can proceed by direct Cathode tracted from micro-
electron transfer be- organisms an immo-
tween the biocatalysts Cathode bilized onto carbon
Mediators
(enzymes) and the elec- Cathode
nanotubes that are used
trodes. However, it is Enzymes
O2 H2O as electrodes. Nano-
common to use “me- materials provide large
diators” that reduce the surface areas for the
kinetic barrier for electron transfer. Many of these attachment of enzymes, increasing the concentra-
mediators are vitamin molecules, such as vitamin tion of biocatalyst and improving battery power
C and vitamin K3. Direct transfer systems are density. Additionally, nanostructured materials ex-
more desirable as they simplify the construction hibit great potential for stabilizing enzyme activity.
of the batteries. Carbon nanotubes, however, seem to induce the
A bio-battery typically includes an anode denaturation of some proteins by dehydration.
containing the carbohydrate to be oxidized, car- An important advantage of bio-batteries over
bohydrate-digesting enzymes, and a mediator. other types of electrochemical devices is the pos-
The cathode contains oxygen, oxygen-reducing sibility of instant recharge. If the organic fuel is
enzymes, and a mediator. The two half cells are readily available in the surroundings, these batter-
divided by a porous separator. When using glucose ies can continuously refuel. They are also a clean
as a fuel, the oxidation at the anode can be repre- and renewable energy source fueled by inexpen-
sented as follows: sive materials, including different types of waste.
Unfortunately, existing prototypes are not yet
Glucose Glucanolactone + 2 H+ + 2 e– competitive in terms of energy storage and power
density.
Let’s Apply
[Public Domain] via Wikimedia Commons

Hydrogen Fuel Cell
By Dervisoglu (Own work)

Fuel cells are electrochemical devices in which reactants are con-
tinuously supplied to the system to sustain the redox reaction.
In a hydrogen fuel cell, for example, hydrogen gas and oxygen
gas from air are used to produce energy. The overall reaction
that takes place in the hydrogen fuel cell can be represented as:
H2(g) + 1/2 O2(g) H2O(l).
Oxidation-Reduction
Consider the overall chemical reaction in a hydrogen fuel cell: H2(g) + 1/2 O2(g) H2O(l)
• Determine the oxidation state of each atom in the reactants and products.
• Identify the oxidized and reduced atoms in the process.
• Identify the oxidizing agent and reducing agent in the reaction.
• Determine the number of electrons exchanged per molecule of H2 consumed.
Thermodynamic Analysis DHof (kJ/mol) Sof (J/(mol K)

H2(g) 0 130.6
The table to the right lists relevant thermody-
namic information for reactants and products in O2(g) 0 205.0
a hydrogen fuel cell. H2O(l) –285.8 69.95
• Qualitatively predict the signs of DHrxn and DSrxn for the overall reaction in a hydrogen
fuel cell. Predict the effect of changing temperature T on the extent of the reaction.
• Verify your predictions using thermodynamic data to calculate DHorxn and DSorxn.
• Calculate the DGorxn and 25 oC and 70 oC (typical temperature at which a hydrogen fuel
cell operates). Build a graph showing how DGorxn changes as a function of T.
According to Equation (7.1): DGorxn = – nFEocell, where Eocell is the cell potential generated by a
fuel cell at standard pressures (1 atm).
• Estimate the value of Eocell at 25 oC and 70 oC. Build a plausible explanation for the
change of Eocell with temperature.
Cell Potential and Energy Output
The table to the right lists the standard reduc-

Standard Reduction Potentials
tion potentials for redox pairs relevant to the
operation of fuel cells under acidic or basic (al- Reduction Half-Reaction Eored (V)
kaline) conditions.
O2 + 4 H+ + 4 e- 2 H2O +1.23
• Express the half reactions taking place in O2 + 2 H2O + 4 e- 4 OH– +0.40
the anode and the cathode of hydrogen 2 H+ + 2 e- H2 0
fuel cell working under acidic conditions.
2 H2O + 2 e- H2 + 2 OH–
–0.83
• Express the half reactions taking place

in the anode and the cathode of hydrogen fuel cell working under basic (alkaline)
conditions.
• Determine Eocell for each of these fuel cells and compare your result with the value
obtained using the DGorxn from thermodynamic data.
• Estimate the maximum amount of energy that each of these fuels cell produces per
mol of hydrogen consumed under standard conditions.
• Express the Nernst equation for these fuel cells in terms of the temperature of the
system and the pressure of the gases used as reactants. Qualitatively analyze this rela-
tionship and determine the best conditions to maximize energy output.
Fuel Cell Kinetics
Given that reactants are in the gas phase in hydrogen fuel cells, inert metal electrodes are
used as surfaces where electron transfer takes place. The nature of the electrodes used af-
fects the relationship between the electric current i established in the system and the cell
potential Ecell of the device.
The graph to the right represents i-Ecell

data for hydrogen fuel cells with two i Pt Au
different types of electrodes.
• Which type of electrode would i1

Ered (V)
be best to use?
0.0 1.23
• When a current is established, –i1
the change in Ered is greater in
the cathode than in the anode.
Propose a plausible explanation Au Pt
for this result.
• How would you expect temperature to affect the value of Ecell when an electric cur-
rent flows through the fuel cell?
Let’s Apply
Electric Batteries
Different types of batteries have been developed in the past 150 years. Some of them are commonly
used to power small electric devices, cell phones and laptop computers, and electric systems in
regular combustion cars. Let us explore the characteristics of the most used batteries.
Alkaline Battery
[Sahre Alike 3.0] via Wikimedia Commons

Alkaline batteries are portable electrochemical systems
By Aney (Own work)

that can be rechargeable or not rechargeable. They ac-
count for over 80% of all manufactured batteries in the
US. The following chemical reactions take place in the
electrodes of this type of battery:
Zn(s) + 2 OH– (aq) ZnO(s) + H2O(l)

2 MnO2(s) + H2O(l) Mn2O3(s) + 2 OH–(aq)
• Assign oxidation states to the atoms in these half reactions. Complete each of the half
reactions by representing the number of electrons lost or gained in each case.
• Identify which of these reactions takes place in the anode of the alkaline cell and which
reaction occurs in the cathode.
• Write the overall chemical reaction for the alkaline battery.
An alkaline battery generates a standard cell potential close to 1.5 V.
• How much energy does an alkaline battery produce per gram of zinc consumed?
An aqueous solution of potassium hydroxide (KOH) is used as electrolyte in alkaline batteries.

This solution creates a basic environment.
• Express the Nernst equation for the battery. Analyze

how the cell potential varies with pH, and discuss the
implications of your results for battery performance.
20 oC
The graph shows how the cell potential (Ecell) of an alkaline 0 oC

battery decreases as a function of time when the battery –20 oC
produces the same current i at three different temperatures.
• How would you justify these results?

Lead-Acid Battery
The lead–acid battery was developed more than 150 years ago. It
is a low cost rechargeable battery that provides the high current
required by automobile starter motors. Lead–acid battery sales ac-
count for over 40% of the value from batteries sold worldwide.
The following chemical reactions take place in the electrodes of this
type of battery:
PbO2(s) + 3 H+(aq) + HSO4–(aq) PbSO4(s) + 2 H2O(l)

Pb(s) + HSO4–(aq) PbSO4(s) + H+(aq)
• Assign oxidation states to each atom in these half reactions. Complete each of the
half reactions by representing the number of electrons lost or gained in each case.
• Identify which of these reactions takes place in the anode of the lead–acid battery
and which reaction occurs in the cathode.
• Draw a schematic diagram of a lead–acid battery showing the chemical composition
and structure of each half cell, as well as the flow of electric charge throughout the
system.
The standard reduction potentials in the cathode and anode of a lead–acid battery are
Eored = 1.685 V and Eored = –0.356 V, respectively.
• Calculate the standard cell potential for this battery.
A typical car battery does not run under standard conditions. The concentration of sulfuric
acid (H2SO4; a strong acid that completely dissociates into HSO4– ions in aqueous solu-
tion) is close to 5 M and the pH is close to 0.
• Write the overall chemical reaction for the alkaline battery.

• Express the Nernst equation for a lead–acid battery and calculate its actual cell po-
tential.
• Express the Nernst equation for the battery as a function of pH. Make a graph of cell
potential versus pH and discuss its implications for cell voltage and power.
The graph sketches how the reduction potentials of the

cathode and the anode in a lead–acid battery change
when a given current i is established across the battery i
10 oC –10 oC
at two different temperatures. i1
–i1 Ered (V)

• Explain why starting a car is more difficult under
cold weather conditions.
Let’s Apply
Lithium-Ion Battery
Lithium-ion batteries are often used in con- Anode Cathode

sumer electronics. They are one of the most
popular types of rechargeable batteries for LixC6 Li1-xCoO2
portable devices, such as watches, cell phones,

and laptop computers. This type of battery
takes advantage of the ability of Li+ ions to
be reversibly inserted and removed from cer-
tain solids. The image represents the internal
Li+
structure of this type of battery.
The half cell reactions in the lithium-ion battery are:
ANODE: LixC6 x Li+ + x e- + C6

CATHODE: Li1-xCoO2 + x Li+ + x e- LiCoO2
where LixC6 represents graphite (C6) intercalated with x moles of Li+ ions, and LiCoO2 repre-
sents lithium cobalt (III) oxide. When x moles of Co3+ ions are oxidized to Co4+, x moles of Li+
ions are released from the solid and Li1-xCoO2 is produced. This process is reversible for x < 0.5.
• Analyze the information provided and generate a detailed explanation of how the lithi-
um-ion battery works. Discuss what happens in each half cell as electrons are transferred
from the anode to the cathode, and Li+ diffuse between the two cells.
• A lithium-ion battery can be recharged. Discuss why this is possible and how it can be
done. Analyze the distribution and movement of Li+ ions between the two half cells
when the battery is charging and when it is discharging.
A lithium-ion battery generates a standard cell poten-

tial close to 3.7 V. As shown in the graph, this volt-
0.2 mA
age depends on temperature and the value of the elec-
tric current i (measure din milliampere, mA) flowing
through the system. 2.0 mA
20 mA
• Analyze the data represented in the graph and
build a kinetic argument to justify the behavior
of the lithium-ion battery under different condi-
tions.

Module 1
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P412 & P413: Background
“Berlin Potdamer Platz” by Avda (Own work) [Share Alike 3.0] http://commons.wikimedia.org/wiki/File:Berlin_-_Potsdamer_Platz_-_E-Mo-
bility-Charging.jpg; P414: Upper right “Lithium Battery CR2032” by KyloDee (Own work) [Public Domain] http://commons.wikimedia.
org/wiki/File:Battery-lithium-cr2032.jpg; P419: Middle right by Toby Hudson (Own work) [Share Alike 3.0] http://commons.wikimedia.org/
wiki/File:Precipitation_of_Silver_on_Copper_1.jpg; P421: Middle right by Shamsher Singh (Own wok) http://chemwiki.ucdavis.edu/Analyti-
cal_Chemistry/Electrochemistry/Voltaic_Cells; P428: Upper right by Dervisoglu (Own work) [Public domain] http://commons.wikimedia.org/
wiki/File:Solid_oxide_fuel_cell_protonic.svg; P430: Upper right “Alkaline batteries” by Aney (Own work) [Share Alike 3.0] http://commons.
wikimedia.org/wiki/File:Alkali_battery_5.jpg
General
UNIT 8
How do we
synthesize
substances?
The core concepts, ideas, and methodologies introduced in

previous Units of this course can be applied to design, imple-
ment, and evaluate strategies to synthesize new chemical
substances. The proper selection of reactants and reaction con-
ditions critically depends on the analysis of diverse factors that
may influence the directionality, extent, and rate of different
chemical processes.
Modern chemical synthesis not only relies on our understanding

of how composition and structure affects how chemical substanc-
es interact with each other, but also on the practical knowledge ac-
cumulated over many years about the physical and chemical properties
of diverse classes of substances. Creative and productive syntheses result
from the artful combination of theoretical and practical knowledge.
The central goal of Unit 8 is to create opportunities for you to apply

the knowledge developed in this course to the analysis of important
synthetic processes.
By Hedgehog Fibres (Own work) [Generic 2.0]
via Flickr Commons
434
Chemical Thinking
UNIT 8 MODULES
M1. Analyzing Processes

Analyzing thermodynamic, kinetic, and practi-
cal aspects of synthetic processes.
435
436
Analyzing
Processes
The synthesis of new chemical substances is one of the central aims of the chemical
U8: MODULE 1
enterprise. Many of these new compounds have practical applications, including

pharmaceutical drugs, food preservatives, cosmetics, synthetic
fibers, plastics, and insecticides. Although not every new

By Shawn Campbell (Own work)
substance synthesized in a chemical lab has a direct ap-
plication in some aspect of our lives, their development
provides useful information about synthetic methods
that may be used later to create other useful chemical
compounds. This feedback cycle has made chemistry
the most productive of all sciences in terms of developing
products that have shaped the world we live in.
Chemists are often in search of synthetic methods to produce desired products
in high yields and with low environmental impact. This search requires careful
consideration of the nature of reactants, reaction conditions, and targeted prod-
ucts. The accumulation of knowledge about how different classes of substances
react has been critical for the advancement of the synthetic enterprise. This knowl-
edge, combined with a deep understanding of how chemical composition and
structure affect the extent and rate of chemical processes, has led to the synthesis
of over 90 million different substances at an average rate of production of one new
substance every four seconds.
THE CHALLENGE Green Chemistry

The synthesis of chemical substances demands the evaluation of costs and
benefits. In recent years, chemists have focused their efforts on the design of
synthetic strategies that minimize hazards and maximize reaction efficiency.
• What factors may affect the “greenness” of a chemical synthesis?

• How can knowledge about the thermodynamics and kinetics of chemi-
cal processes help us design “greener” synthetic methods?
central goal of Unit 8 is to help you apply your knowledge in the analysis of
synthetic pathways with important applications.
Chemical Thinking U8 How do we synthesize substances? 437
Identifying Interactions
Ideally, chemists would like to devise strategies to synthesize new chemi-
cal substances using methods that are fast, produce very high yields of the
targeted product, demand simple reaction conditions, require readily avail-
able starting materials, and generate inoffensive byproducts. To accomplish
these goals, they need to have a deep understanding of the thermodynamic
and kinetic factors that affect diverse chemical processes as well as a vast
knowledge about the chemical reactivity of different classes of substanc-
es. This knowledge is often organized in terms of the types of functional
groups (e.g., hydroxyl, carbonyl, carboxyl, amine) present in the molecules
of available reactants and targeted products, and in terms of the reaction
mechanisms involved in particular transformations (e.g., bimolecular sub-
stitution, unimolecular elimination).
Most chemical syntheses involve the addition, elimination, substitu-
Figure 8.1 Different
tion, or rearrangement of functional groups to transform reactants into reaction conditions
products. Thus, recognizing how different functional groups interact with and reagents may be
used to transform a
each other or with different types of reagents is critical in synthetic chemis- given reactant into
different products.
try (Figure 8.1). These interactions are often driven by the presence of un-
even distributions of charge in the molecules present in a reaction mixture. Mol-
ecules could be polar, for example, and have regions with partial negative or partial
positive charges. Other molecules could include double or triple bonds between
carbon atoms, which have a larger electron density than single bonds. The
presence of particular functional groups influences how electron density
is distributed in molecules and affects how they interact with each other.
Many synthesis reactions result from interactions between electron-
rich centers in a molecule and electron-poor centers in another mol-
ecule. Thus, it is important to recognize their presence in different par-
ticles. In general, areas of a molecule that have a partial negative charge
Figure 8.2 Which
or a large electron density are identified as nucleophilic centers. On the other are the nucleophilic
and electrophilic cen-
hand, areas of a molecule that have a partial positive charge or a low electron ters in this molecule?
density are identified as electrophilic centers (Figure 8.2). Chemical reactions result
from the motion of electrons from nucleophilic to electrophilic centers.
Nucleophilic or Electrophilic? LET’S THINK

Consider these molecules:
• Identify all the potential nucleophilic and electrophilic centers in these particles.
438 MODULE 1 Analyzing Processes
When different types of molecules or ions are mixed, multiple interactions

may occur between different nucleophilic and electrophilic centers. Some of these
interactions may be stronger than others or may more easily induce structural
changes, such as the formation or breaking of chemical bonds. In bond-forming
interactions, the particle holding the nucleophilic center is said to act as the nu-
cleophile while the particle holding the electrophilic center acts as the electrophile.
Nucleophiles are species that have a pair of electrons that can be shared to form
a new chemical bond. Electrophiles are species capable of accepting the pair of
electrons from the nucleophile.
LET’S THINK Nucleophiles or Electrophiles?
Consider the following pairs of particles:
• For each of these six pairs: a) identify the major nucleophilic or electrophilic center in
each particle, and b) decide which species will likely act as either the electrophile or the
nucleophile when they interact with each other.
Many synthesis reactions are initiated by the interaction between a nucleophile

and an electrophile. The outcome of such interactions are often intermediate spe-
Figure 8.3 Representation cies with nucleophilic or electrophilic character that engage in further interactions.
of a reaction mechanism us-
ing curved arrows. The reaction mechanisms thus involve several steps from starting materials to final
products. Chemists represent such mechanisms in pictorial ways, using curved
arrows to highlight the interactions between
the different nucleophiles and electrophiles in
each step of the process. These curved arrows
Bond forming are always drawn from the nucleophilic center
(or electron-rich site) to the electrophilic cen-
ter (or electron-poor site) of the interacting
Bond breaking Bond forming species. The arrows indicate the direction in
which electrons are moving as the result of the
interaction between particles. They represent
the direction in which electrons move when
a bond is formed or when a bond is broken
(Figure 8.3).
Curved Arrows LET’S THINK

Consider the reaction mechanism represented below:
• Identify the nucleophile and the electrophile in each step of this mechanism.
• Describe in your own words the meaning of each arrow represented in the mechanism.
• Analyze how the electric charge of each species changes in each step of the mechanism, and
explain these changes based on bond formation or bond breaking.
• This mechanism has three steps. Represent each of them as separate processes, including all
species involved as reactants and products.
Consider the following one-step chemical reaction:
• Identify the nucleophile and the electrophile in this process.

• Draw curved arrows to represent movement of electrons in the mechanism, and explain in
your own words what the arrows represent in terms of bond formation or breaking.
• This process is an acid-base reaction. What role is the acid playing in the mechanism, the
electrophile or the nucleophile? What is the role of the base?
Consider the acid and base included in the image to the right:
• Predict the products of this acid-base reaction by draw-

ing curved arrows to represent bond formation and
bond breaking due to interactions between reactants.
Successful chemical syntheses demand careful analysis of thermody-

namic, kinetic, and practical factors that affect chemical processes. Careful Thermodynamic
consideration of the nature of reactants and products is necessary to make Analysis
predictions about reaction extent, and how such extent may be affected
when external (e.g., temperature, pressure) or internal (e.g., pH, nature of
the solvent) conditions are varied. Analyses of reaction mechanisms provide CHEMICAL
insights into how to better control the outcome. Paying attention to practi- SYNTHESIS
cal aspects such as availability, cost, and safety of the substances involved is
critical to ensure the feasibility of the synthesis. On the next pages, we will Kinetic Practical
work on a set of activities that illustrate the type of chemical thinking that Analysis Analysis
guides the synthesis of new chemical products.
A Focus on Functional Groups

The physical and chemical properties of substances are often determined by the
nature of the functional groups present in their molecules. Consequently, the
synthesis of new compounds often involves changing the identity or position of
functional groups in the starting materials. To illustrate this idea, we will analyze
synthesis reactions used to produce alcohols through the introduction of hydroxyl
groups (–OH) bonded to saturated carbon atoms (Figure 8.4). The best known al-
cohol is ethanol (CH3CH2OH), present in alcoholic beverages and also used as an
antiseptic and as an automotive fuel. However, there are a variety of other alcohols
with many different uses, including antifreeze for cars, and solvents for perfumes
Figure 8.4 Molecule of isopro-
panol or isopropyl alcohol, for- and cosmetics. Let us consider the synthesis of isopropanol (CH3CHOHCH3), a
mally known as 2-propanol.
compound used as an antiseptic and as an industrial solvent.
Thermodynamic Analysis
A synthetic process can be analyzed from a thermodynamic perspective to evaluate

the extent to which the reaction will occur under different conditions. This analy-
sis requires knowledge about the composition and structure of the reactants and
products involved in the process, as well as information about their physical and
chemical properties. Consider, for example, the most common synthetic route for
the production of isopropanol as represented in two different forms below:
H3O+
CH3CHCH2(g) + H2O(l) CH3CH(OH)CH3(l)
Figure 8.5 Representation of
the hydration of propene.
H3O+
+ H2O
In this process, propene, an unsaturated hydrocarbon, is hydrated under acidic

conditions to produce the alcohol. Given the nature of the reactants and products,
we can expect the extent of this process to be affected by different factors, such as
temperature, pressure, and pH. We can apply the type of chemical thinking intro-
duced in Unit 5 to qualitatively analyze these effects.
LET’S THINK Qualitative Predictions
Analyze the reactants and products in the hydration of propene (Figure 8.5):
• Predict the sign of DHrxn based on the composition and structure of reactants and products.
• Predict the sign of DSrxn based on the nature of reactants and products.
• Discuss how DGrxn can be expected to change with temperature and identify the conditions
under which the synthesis of isopropanol will occur to a large extent.
• Discuss how an increase in pressure may affect the relative concentration of reactants and
products at equilibrium. Build both thermodynamic and kinetic arguments.
• Predict whether propene and isopropanol can be expected to be soluble in water and discuss
how that may affect the synthesis of the product and its isolation.
To transform qualitative predictions into quantitative calculations on reac-

tion extent under different conditions, we need actual data about the physical and
chemical properties of reactants and products, such as the boiling points of the
compounds (Tb ), their solubility in water (sol), and their standard enthalpy (DHof
) and entropy (Sof ) of formation. Relevant information for the synthesis of isopro-
panol is listed in the following table.
Tb (K) sol (M) DHof (kJ/mol) Sof (J/(mol K)

CH3CHCH2(g) 225.6 1.45 x 10-5 20.41 266.9
H2O(l) 373.1 -- –285.8 69.95
CH3CHOHCH3(l) 355.8 miscible –317.9 180.5
Quantitative Predictions LET’S THINK

Use the experimental data for chemical compounds involved in the synthesis of isopropanol to
characterize the extent of the reaction under different conditions and verify your qualitative predic-
tions.
• Calculate DHorxn and DSorxn at 25 oC for the hydration of propene and determine whether the
reaction is product favored under such conditions.
• Express the equilibrium constant K for the reaction and calculate its value at 25 oC.
• Determine the temperature (in Kelvins) at which the reaction becomes reactant favored.
The industrial synthesis of isopropanol is carried out at high temperatures and pressures. For ex-
ample, the production reactor in one common process is kept at 180 oC (453 K) and 40 atm of
pressure. Propene is the only substance in the gas phase under such conditions.
• Estimate the value of the equilibrium constant KP for the reaction at 180 oC.
• Discuss why the industrial process is likely carried out under such conditions.
• During the synthetic process, isopropanol is extracted out of the reaction vessel as it forms.
Discuss why this is done.
• Discuss how the addition of more water into the reaction vessel would affect reaction extent.
Kinetic Analysis
In the design and implementation of a chemical synthesis, chemical scientists and

engineers need also to consider the effect of different factors on the rate of the
process. The experimental determination of rate orders and rate constants at dif-
ferent temperatures, pressures, and pH, together with the chemical analysis of
the composition and structure of reaction intermediates is critical to infer the
reaction mechanism. Knowledge about the reaction mechanism provides insights
into strategies to control and modify the process to, for example, increase the rate
of the reaction and avoid the formation of undesirable byproducts. The following
activity is designed for you to engage in this type of analysis.
LET’S THINK Reaction Mechanism
The reaction mechanism for the hydration of propene is represented below:
Analyze the mechanism:
• Identify the nucleophile and the electrophile in each step.

• Describe in your own words the meaning of each arrow represented in the mechanism.
• Represent the different steps in the mechanism as separate processes (include all species that
participate as reactants and products in each step).
• Identify all acid-base reaction steps in the mechanism. Analyze the relative strength of the
acids and bases involved to evaluate the directionality of each step.
• Infer the role that H3O+ plays in the reaction.
• Infer which process is likely to be the slowest step in the mechanism.
Use the results of your analysis to:
• Sketch the energy diagram for the reaction.

• Infer the rate law for the process.
• Predict the effect of changing pressure on the rate of reaction.
• Predict the effect of changing pH on the rate of reaction.
• Estimate how many times faster this reaction is at 180 oC, the temperature at which the
industrial synthesis is carried out, than at room temperature (25 oC). Experimental data
indicate that the activation energy of this reaction is close to 85 kJ/mol.
• Evaluate which factors, temperature, pressure, and pH, can be expected to have opposite ef-
fects on reaction extent and reaction rate. Discuss how these results can be used to determine
the best conditions to carry out the targeted synthesis.
Many synthetic processes produce byproducts as a result of alternative reaction pathways. Con-
sider, for example, the following alternate mechanism in the hydration of propene:
• Generate a reasonable argument to explain why this alternative mechanism is much less
probable (for all practical purposes, the potential byproduct does not form).
Practical Analysis
Chemical syntheses need to be carefully planned to reduce costs and risks while
trying to maximize reaction yields and quality of products. The costs and risks
involved in a chemical synthesis are multiple. There are always economical, safety,
and environmental considerations to take into account. The chemical industry is
one of the most productive enterprises in the world, but it is also one of the most
regulated given the catastrophic effects that mistakes, accidents, or malpractice
may have on workers, surrounding communities, and the environment. Analysis
of practical aspects of a synthesis are also critical in research labs where experimen-
tation with new substances and synthetic methods is common.
Making Decisions LET’S THINK

The following tables list information about propene and isopropanol, the two main chemical
compounds involved the chemical synthesis under analysis:
Propene (CH3CHCH2)
At room temperature and atmospheric pressure, propene is a colorless gas with a weak
unpleasant smell. Propene is often produced from fossil fuels such as petroleum and natural
gas. Propene is the second most important starting product in the petrochemical industry
with a world wide production of around 80 million tonnes per year. Propene is considered
a volatile organic compound (VOC) but it is not listed by the U.S. Environmental Protection
Agency (EPA) as a hazardous air pollutant. The compound has low acute toxicity from inhala-
tion. The flashpoint of propene is –108 oC (the flashpoint is the lowest temperature at which
a substance can vaporize to form an ignitable mixture in air near the surface of the liquid).
Isopropanol (CH3CHOHCH3)
At room temperature and atmosphere pressure, isopropanol is a colorless, volatile, flamma-
ble liquid with a strong odor and highly miscible in water. Isopropanol vapor is denser than air
with a lower flammability level of 2.2%. The substance has been reported to form peroxides,
which may explode upon concentration. Isopropanol is a skin irritant and poisoning can occur
from ingestion, inhalation, or absorption. Its flashpoint is 11.7 oC.
Given the information provided, together with your knowledge about the syn-
thetic process used to produce isopropanol through the hydration of propene:
• Discuss what potential problems and hazards may be present during the
synthesis of isopropanol and how they could be a) prevented, b) ad-
dressed if they happen.
• Given the properties of reactants and products, discuss how you propose
to carry out the synthesis. For example, how would you ensure efficient
contact between reactants? How would you isolate the product?
LET’S THINK Synthesis of Ethylene Glycol
Ethylene glycol (HOCH2CH2OH) is primarily used in the manufacture of polyester fibers and
polyethylene terephthalate polymer (PET) used in bottling. A small percent is used to produce anti-
freeze formulations and other industrial products. Ethylene glycol is synthesized using ethylene oxide
(C2H4O) and water under acidic or basic conditions:
H3O+ or OH–
+ H2O
The table lists Tb (K) sol (M) DHof (kJ/mol) Sof (J/(mol K)
relevant physical
properties for the C2H4O(g) 283.8 miscible –52.6 243
substances involved H2O(l) 373.1 -- –285.8 69.95
in this reaction.
HOCH2CH2OH(l) 470.4 miscible –460 166.9
The reaction mechanisms for the synthesis of ethylene glycol under acidic and basic conditions are
presented below. The activation energies for the rate limiting step in each of the processes are shown.
Ea ~ 75 kJ/mol
Ea ~ 93 kJ/mol
Ethylene Oxide Ethylene Glycol

Additional relevant
Ethylene oxide is a flammable, carci- Ethylene glycol is a moderately toxic
information for reactants nogenic, irritating, and anaesthetic liquid with a sweet taste. Acute ex-
and products is included gas with a misleadingly pleasant posure by ingesting large quantities
in this table. aroma (the gas is already toxic at the causes depression, cardiopulmonary
concentrations it can be smelled). Its effects and renal damage. Its flash-
flashpoint is –20 oC. point is 111 oC.
• Use the information provided to complete a thorough thermodynamic, kinetic, and practical
analysis of the synthesis of ethylene glycol under acidic and basic conditions.
• Based on your analyses, generate a reasonable argument to support which conditions (e.g., tem-
perature, pressure, pH) are likely to be best in the synthesis of the targeted product.
A Focus on Structural Changes

Besides paying attention to the types of functional groups that need to be trans-
formed to produce a targeted compound, chemical synthesis also benefits from
analyzing the structural changes that need to be induced in the reactant mol-
ecules. The most common structural changes involve the substitution, addition,
elimination, or rearrangement of atoms in the molecules of the starting materials.
Understanding how these structural changes occur helps chemists devise strategies
to induce such changes and control them. To illustrate this type of thinking, let us Figure 8.6 In a substitution
analyze the case of substitution reactions involving the exchange of one functional reaction a functional group X
is replaced by another Y.
group for another (Figure 8.6).
Substitution reactions result from the interaction between a nucleophile and
an electrophile. The electrophile, sometimes called the “substrate” in a substitution
reaction, must contain a group capable of separating from the molecule (leaving
group). The leaving group is often comprised of electronegative atoms that can po-
larize the electrophile via induction, creating an electrophilic carbon center where
the nucleophile interacts (Figure 8.7):
Electrophilic Leaving Group
Center
d+ d- H2O Figure 8.7 The chloride ion
H3C–Cl + OH –
H3C–OH + Cl – Cl– serves as leaving group in
this substitution reaction.
Electrophile Nucleophile
(substrate)
Halogenated organic compounds, such as CH3Cl in the reaction above, are com-
monly used as electrophiles in substitution reactions. The halogen anions Cl–, Br–,
and I– are good leaving groups. In any case, the feasibility of a substitution reaction
in a synthetic route can be determined by completing thermodynamic, kinetic,
and practical analyses as we did before.
Thermodynamic Analysis LET’S THINK

The reaction between methyl chlo- Tb (K) sol (M) DHof S of
ride (CH3Cl) and hydroxide ions (kJ/mol) (J/(mol K)
(OH–) in water to produce metha-
nol (CH3OH) represented in Figure
CH3Cl(g) 225.6 1.05 x 10-1 –83.68 234..4
8.7 is a typical example of a substi- OH–(aq) -- -- –229.9 –10.5
tution reaction. Relevant thermody-
CH3OH(l) 355.8 miscible –238.4 127.2
namic data for reactants and prod-
ucts are listed in the table: Cl–(aq) -- -- –167.4 55.1
• Qualitatively predict whether the reaction will be product or reactant favored.

• Use your data to verify your prediction. Calculate the value of the equilibrium constant for
this reaction at 25 oC.
• Discuss the effect of increasing temperature on the extent of the reaction.
The kinetics of substitution reactions have been studied extensively. These in-
vestigations have revealed that the rate of reaction and the reaction mechanism
may dramatically vary when changing the nature of reactants, both the electro-
phile and the nucleophile, and the solvent in which the reaction takes place. Let
us explore these different effects.
LET’S THINK Kinetic Analysis: Electrophile Structure
The kinetics of substitution reactions can be studied by comparing the rate of reaction soon after
the reaction begins (initial rates of reaction). The tables below list data for two different reactions
involving the same nucleophile (OH–) but different electrophiles (E):
CH3Cl + OH– CH3OH + Cl– (CH3)3CCl + OH– (CH3)3COH + Cl–
Trial Initial Initial Initial Rate Trial Initial Initial Initial Rate
[E] [OH–] (M/s) [E] [OH–] (M/s)
1 0.001 1.0 4.9 x 10–7 1 0.01 0.001 5.9 x 10–6
2 0.002 1.0 9.8 x 10–7 2 0.02 0.001 1.18 x 10–5
3 0.001 2.0 9.8 x 10–7 3 0.01 0.002 5.9 x 10–6
4 0.002 2.0 1.96 x 10-6 4 0.02 0.002 1.18 x 10-5
• Analyze the data and infer the rate order of each reaction with respect to each reactant.
• Calculate the rate constant and express the rate law for each reaction.
• Compare the rate laws and propose a reasonable explanation for the difference.
The two different reaction

mechanisms, SN1 and SN2, SN1 Loss of E-N Interaction
shown to the right have Leaving Group
been proposed to explain
the experimental data:
• Compare and contrast

each mechanism, high- SN2 E-N Interaction
Loss of
lighting major differ- Leaving Group
ences and similarities
(e.g., number of steps,
molecularity).
• Determine which of these mechanisms corresponds to each of the substitution reactions
represented above. Clearly justify your claims using available data.
• For each reaction, represent the different steps in the mechanism as separate processes (in-
clude all species that participate as reactants and products in each step).
• Sketch the energy diagram for each reaction.
• Identify structural factors of the electrophile that may determine which reaction mechanism
is most likely to take place.
• Based on your analysis, predict how the rate of reaction, the reaction mechanism, and the
rate law may vary for this set of electrophiles: CH3Br, CH3CH2Br, (CH3)2CHBr, (CH3)3CBr.
The two types of mechanisms that a substitution reaction may follow,

SN1 and SN2, determine not only the rate of reaction and its dependence on
the concentration of the nucleophile, but also the nature of the products
that are formed when the electrophilic center on the substrate is a “chiral”
center. As discussed in Module 3 of Unit 5, a chiral center involves an atom
that has four different substituents which can be arranged in two different
configurations, one being the mirror image of the other. This leads to the
existence of optical isomers (Figure 8.8) that differ in some physical and
Figure 8.8 These optical isomers
chemical properties. are mirror images of each other.
Change of Configuration LET’S THINK

Consider the following experimental results:
a) When the following substitution reaction is carried out, the substrate and the targeted product
have different configurations. Only one of the two potential optical isomers is formed and the reac-
tion is said to proceed with inversion of configuration:
Me = CH3
Et = CH3CH2
b) When the following substitution reaction is carried out, the analysis of the products reveals the
presence of a 1:1 mixture of the two possible optical isomers. The reaction is said to produce race-
mization (generation of a mixture of optical isomers):
Me = CH3
Et = CH3CH2
Pr = CH3CH2CH2
• Analyze the two reactions represented above and generate a plausible explanation for the dif-
ferent outcomes. (HINT: Consider how each of the reaction mechanisms, SN1 and SN2, may affect
the configuration of the products that are formed).
• Discuss which of the two reaction mechanisms, SN1 or SN2, allows for better control over the
configuration of the products.
Consider the substitution reaction represented to the right.
• Make a prediction about the likely mechanism of the

reaction.
• Predict and represent the structure of the products.
As we have seen in the previous activities, the molecular structure of the elec-
trophile has a big impact on the rate of substitution reactions, on the mechanism
of the reaction, and on the nature of the product. The rate of substitution is also
affected by the nature of the leaving group present in the electrophile.
LET’S THINK Kinetic Analysis: The Leaving Group
The rate of substitution reactions varies from one type of leaving group to another. Common leav-
ing groups are listed below arranged in order of increasing rate of substitution as measured experi-
mentally in different reaction systems:
NH2– < CH3O– < OH– < Cl– < Br– < I–
Differences in reaction rates for these different leaving groups can be quite large. For example, the
rate of substitution for an electrophile such as CH3I can be 100 times faster than for CH3Cl.
• Propose a reasonable explanation for the trend in increasing rate of substitution for the leav-
ing groups represented above. (HINT: Consider energetic and entropic factors that may facilitate
the detachment of a leaving group and its stability in the surrounding solvent).
The type of nucleophile used in a substitution reaction can also affect the rate
of reaction. This effect, however, is more constrained than that of the electrophile
given the different mechanisms that substitution reactions may follow.
LET’S THINK Kinetic Analysis: The Nucleophile
The rate of some substitution reactions also depends on the type of nucleophile that is used. The
strength of a nucleophile is a measure of how fast it reacts to produce the substitution product. The
table below shows the ratio of the rate of SN2 substitution of different nucleophiles dissolved in
water to the reaction rate when the nucleophile is actually water:
H2O F– Cl– Br– OH– I– CN–

1 1 x 102 5 x 102 3.2 x 103 1.6 x 104 5.0 x 104 1.2 x 105
• Propose a reasonable explanation for the trend in increasing rate of substitution for the
nucleophiles represented above. (HINT: Consider energetic and entropic factors that may facilitate
the attachment of the nucleophile and its stability in the surrounding solvent).
• The rate of substitution reactions that proceed via a SN1 mechanism is not affected by either
the concentration or the strength of the nucleophile. How would you explain this?
• Discuss whether the use of strong or weak nucleophiles can be expected to influence the
mechanism of a substitution reaction.
The rate of a substitution reaction is also affected by the nature of the solvent
used to carry out the process. Substitution reactions involve polar or ionic species,
either as nucleophiles or as intermediate carbocations in the case of SN1 reactions
that will interact to different degrees with different solvents. Strong interactions
with solvent molecules will decrease the likelihood of interactions between the
nucleophile and the electrophile, reducing the rate of SN2 reactions. Strong in-
teractions with the solvent, however, help stabilize the formation of carbocations
in SN1 reactions increasing the rate of these types of processes. In general, experi-
mental data indicate that SN2 reactions are significantly slower in solvents made up
of polar molecules that can form hydrogen bonds (polar protic solvents, like H2O
and CH3CH2OH) than in solvents made up of polar molecules that cannot form Figure 8.9 Common polar
hydrogen bonds (polar aprotic solvents, like CH3CN and DMSO) (Figure 8.9). aprotic solvents: Acetonitrile
(CH3CN) and Dimethylsulfox-
This trend is reversed for SN1 reactions that tend to be faster in polar protic than ide (DMSO, CH3SOCH3).
in polar aprotic solvents.
Practical Analysis LET’S THINK

Substitution reactions are commonly used in synthetic chemistry to introduce desired functional
groups into molecules. However, from an environmental perspective, these types of reactions may
not be as efficient and environmentally friendly as others. One way to measure reaction efficiency
is by calculating the “atom economy” of a reaction. Atom economy is a measure of the propor-
tion of the mass of the reactants that ends up as mass of the targeted product:
Molar Mass Targeted Product

Atom Economy = x 100%
Molar Mass of all Reactants
Substitution reactions have a lower atom economy than other types of reactions, such as addi-
tion and rearrangement, because they always generate other products (the leaving group). These
other products are waste that needs to be disposed or treated in some manner, increasing the
environmental impact of the process. Additionally, substitution reactions often demand the use
of solvents to mix the reactants, some of which are volatile organic compounds (VOCs) that may
pose health and environmental hazards.
Imagine that you wanted to synthesize the compound shown to the right
(cyclohexanecarbonitrile). You have access to sodium cyanide (NaCN) and a
variety of solvents: H2O, CH3CH2OH, CH3COCH3, and CH3SOCH3.
• What compound would you use as a substrate (electrophile) to carry out

the reaction?
• What solvent would you use?
• How would your choice of substrate and solvent influence the mechanism
that the reaction follow and the rate of the reaction?
• Write the overall chemical equation the reaction and calculate its atom economy.
• How would your choices impact the environmental effects of your proposed synthesis?
LET’S THINK Integrating Ideas
The use of substitution reactions in the synthesis of new compounds demands a careful consideration
of structural, thermodynamic, kinetic, and practical factors. The following problems demand the
integration of these understandings:
Imagine that someone proposes the reaction represented to

the right to introduce a thiol group (–SH) in a molecule:
• Predict and represent the likely mechanism that the

reaction would follow and identify the products of the
reaction.
• Discuss whether the above reaction could generate a chiral product.
• The above reaction is endothermic. Predict whether the reaction can be expected to be product
favored at any temperature. If not, suggest a different substrate that may be used.
• Represent the rate law for the reaction and discuss how the reaction rate will be affected by the
concentration of the nucleophile and the electrophile.
• Discuss what would happen to the rate of the reaction if the solvent is changed from DMSO to a
greener solvent such as ethanol. Determine which solvent would be a better choice.
• Calculate the atom economy for this reaction.
Imagine that you wanted to carry out the reaction repre-

sented to the right to introduce a nitrile group (–CN) and
produce a single chiral product:
• Predict and represent the mechanism that the reaction

will have to follow.
• The above reaction is exothermic. Predict the effect of increasing temperature on reaction extent
and rate.
• Represent the rate law for the reaction and discuss how the reaction rate will be affected by the
concentration of the nucleophile and the electrophile.
• Discuss what solvent you would propose to use to facilitate the desired process. Evaluate the
potential problems associated with your choice.
• Calculate the atom economy for this reaction.
The formation of the product shown to

the right is very slow when water (H2O)
is used as the nucleophile but very fast
when OH– is the nucleophilic species.
• Propose a reasonable explanation

for the difference in rates of reaction based on the analysis of the reaction mechanism.
FACING THE CHALLENGE 7. Use renewable feedstocks: Use starting materi-

als (also known as feedstocks) that are renewable
rather than depletable.
Green Chemistry 8. Avoid chemical derivatives: If possible, avoid
Green chemistry is a philosophy and approach using blocking or protecting groups or any tempo-
to practicing chemistry based on the design of rary modifications.
products and processes that reduce or eliminate 9. Use catalysts, not stoichiometric reagents:
the use or generation of hazardous substances. Minimize waste by using catalytic processes. Cata-
Also known as sustainable chemistry, this practi- lysts are effective in small amounts and can carry
cal philosophy seeks to prevent pollution and re- out a single reaction many times. They are prefer-
duce the consumption of natural resources. Green able to stoichiometric reagents, which are used in
chemistry applies across the life cycle of a chemical excess and carry out a reaction only once.
product, including its design, manufacture, use, 10. Design chemicals and products to degrade
and disposal. This approach to thinking and do- after use: Design chemical products to break
ing chemistry applies at down to innocuous sub-
the research laboratory stances after use so that
Atom
and industrial levels. The Economy they do not persist and
focus is on minimizing Safety Prevent accumulate in the envi-
Control Waste
the hazard and maximiz- ronment.
ing the efficiency of any 11. Analyze in real time
Quality Benign
chemical choice. Control Design to prevent pollution:
Green chemistry is Green Monitor and control
guided by 12 basic prin- Chemistry processes in real time to
ciples (Source: EPA): Catalyst Reduced minimize or eliminate
Efficiency Toxicity
1. Maximize atom the formation of hazard-
economy: Design pro- ous byproducts.
Renewable Fewer
cesses to maximize the Feedstocks Ancillaries 12. Minimize the po-
Energy
incorporation of starting Efficiency tential for accidents:
materials into the final Use and produce chemi-
product. cal substances seeking to
2. Prevent waste: Design products and processes minimize potential chemical accidents including
to prevent waste that needs to be treated or cleaned fires, explosions, and toxic releases to the environ-
up. ment.
3. Design less hazardous chemical syntheses: Green chemistry is part of a major effort to
Design synthetic processes that use and generate reduce the health and environmental impact of
substances with little or no toxicity to humans and all types of chemical activities. In particular, green
the environment. chemistry is considered a powerful tool for evalu-
4. Design safer chemicals and products: Design ating the impact of the development and use of
chemical products that are effective yet have little nanomaterials. The fast development of nanotech-
or no toxicity. nology in recent years has made people concerned
5. Use safer solvents and reaction conditions: about the lack of a regulatory framework to as-
Avoid or reduce the use of ancillary substances sess and control the risks of nanotechnology and
(e.g., solvents, separation agents). If they are need- its products. However, claims about the virtues
ed, use safer ones. of green chemistry are not without controversy.
6. Increase energy efficiency: Minimize energy There are some who argue that green chemistry is
requirements. Conduct synthetic processes at no more than a public relations label used by some
room temperature and pressure whenever possible. chemical industries to improve their image.
Let’s Apply
Making Alkenes
Alkenes are hydrocarbons made up of molecules that contain at least one carbon-to-carbon double
bond. They are used as starting materials for producing many different compounds. Alkenes are
often prepared in the laboratory by the reaction between alkyl halides and basic substances, as il-
lustrated by the following process:
CH3CH2OH(l)
(CH3)3Br(l) + CH3CH2O– (CH3)2CCH2(g) + CH3CH2OH(l) + Br–
In this example, tert-butyl bromide (CH3)3Br (t-BuBr) reacts with the strong base ethoxide
CH3CH2O– (EtO–), producing the alkene isobutylene (IB), ethanol CH3CH2OH (EtOH), and
the bromide ion Br–. This reaction is carried out using dry ethanol as a solvent.
Analyze the reactants and products in the synthesis of isobutylene (IB):
• Predict the signs of DHrxn and DSrxn based on the composition and structure of reactants
and products.
• Discuss how DGrxn can be expected to change with temperature and identify the condi-
tions under which the synthesis of IB will occur to a large extent.
• Discuss how an increase in pressure may affect the relative concentration of reactants
and products at equilibrium. Build both thermodynamic and kinetic arguments.
Trial Initial Initial Rate

Kinetic Analysis: Rate Laws (25 oC) [t-BuBr] [EtO–] (M/s)
1 0.02 0.01 1.7 x 10–8
The tables list data for initial reaction rates for the syn-
thesis of IB at low and high concentrations of EtO–: 2 0.04 0.01 3.4 x 10–8
3 0.02 0.02 1.7 x 10–8
• Analyze the data and infer the rate order of the 4 0.04 0.02 3.4 x 10-8
reaction with respect to each reactant at low and Trial Initial Initial Rate
high concentrations of the base. (25 oC) [t-BuBr] [EtO–] (M/s)
• Calculate the rate constant and express the rate 1 0.02 1 6.0 x 10–7
law under both conditions.
2 0.04 1 1.2 x 10–6
• Compare tee rate laws and propose a reasonable
explanation for the difference. 3 0.02 2 1.2 x 10–6
4 0.04 2 2.4 x 10-6
Kinetic Analysis: Reaction Mechanism
The two different reaction mechanisms, E1 and E2, shown below have been proposed to
explain the experimental data for the synthesis of IB at different concentrations of the base:
:
:
:
: –
:
:
+
: :
:
:
E1

:
– : –
:
:
: : :
:
:
:
:
:
E2
• Compare and contrast each mechanism, highlighting major differences and similarities
(e.g., number of steps, types of steps, molecularity).
• Determine which of these mechanisms corresponds to each of the reaction conditions
(i.e., low and high base concentration) analyzed in the previous activity. Clearly justify
your claims using available data.
• For each reaction, represent the different steps in the mechanism as separate processes
(include all species that participate as reactants and products in each step). Identify the
rate limiting step in each case.
• Sketch the energy diagram for each reaction mechanism.
Kinetic Analysis: Reaction Conditions
Experimental results indicate that different experimental conditions favor different reaction
mechanisms in the formation of alkenes using alkyl halides treated with a basic substance:
Favor E1 Favor E2
Low Concentrations of Base High Concentrations of Base
Weak Bases (H2O, CH3CH2OH) Strong Bases (OH–, CH3CH2O–)
Strongly Polar Protic Solvents Weakly Polar Protic or Aprotic Solvents
• Build reasonable arguments to explain why each of the reaction conditions listed in the
table favors one mechanism over the other. Consider the composition and structure of
reactants, intermediates species, and solvent molecules in your explanations.
Let’s Apply
Making Polymers
Polymers are macromolecules composed of a large number of repeating units (monomers). More
than 200 billion pounds of synthetic polymers are produced in the US every year. They are used in
multiple applications, including clothing, plastic containers, and construction materials.
Different types of alkenes are used as monomers in
the production of a variety of polymers. Consider the
generic polymerization reaction shown in the image,
where “n” represents the number of monomers that
combine to form a molecule of the polymer.
• Analyze the represented polymerization reaction and discuss Bond BE (kJ/mol)

whether the process is exothermic or endothermic. Use the
data for bond energies (BE) to guide your thinking.
C–H 414
C–C 347
• Discuss whether entropy of the reaction mixture can be ex-
pected to decrease during polymerization. C=C 611
• Based on your analysis of energetic and entropic factors, identify the conditions of tem-
perature and pressure that will favor the formation of the polymer.
Kinetic Analysis
Synthetic polymers are commonly formed
via cationic addition polymerization in
which the reaction is initiated by a small
+ +
amount of acid HA. A generic mechanism
for the reaction is shown:.
• Identify the nucleophile and the elec-

trophile in each represented step.
Polymer
• Describe the meaning of each arrow +
represented in the mechanism.

• Describe the sequence of steps that lead to the formation of the polymer.
• Discuss what could be added to the system to stop (terminate) the polymerization.
Cationic Addition
The monomers represented to the right are used to
produce two important polymers, polyisobutylene
and polystyrene, via cationic addition.
• Draw the first three steps in the mechanism

that leads to the formation for each polymer.
Isobutylene Styrene
• Represent the structure of each polymer us-
ing bracket notation.

The monomers represented to the right do not
react via cationic polymerization to form a poly- CN
meric material.
• Build an argument to explain the lack of re-

activity of each of these monomers based on
Ethylene Acrylonitrile
their molecular structure and the mechanism
for cationic polymerization.
Condensation
Some polymers are synthesized using reactions in which the combination of molecules of
monomers results in the loss of a small molecule, such as H2O, CO2 or HCl. The mecha-
nism for one of such condensation reactions is represented below:
: :
–
: : : :
: :
:
–
: :
:
: :
+
:
+
: :
:
• Identify the nucleophile and the electrophile in each represented step.

• Represent the different steps in the mechanism as separate processes
• Use the represented mechanism as a guide to propose a mechanism for the forma-
tion of the polymer Nylon 6,6 using hexamethylenediamine and adipoyl chloride.
The overall reaction is shown below:
Let’s Apply Na+
Making Soap
Soaps are chemical compounds comprised of amphiphilic molecules with a polar
group on one end of the molecule and a nonpolar group on the other end (car-
boxylate ions). Most soaps are produced from fats and oils made of triglycerides,
using strong bases such as sodium hydroxide to hydrolyze these substances.
The hydrolysis of a generic
triglyceride molecule in a
basic solution is represented
to the right. The products in- 3 OH– 3
–
clude three carboxylate ions
and one molecule of glycerol.
• Analyze the chemical reaction and discuss whether it can be expected to be exothermic
or endothermic.
• Discuss how the entropy of the system may change as a result of the process.
• Identify the best conditions of temperature and pressure to carry out the reaction.
Kinetic Analysis
The mechanism for the hydrolysis of one of the ester groups in a triglyceride is shown below:
: : : :– : :
:
– : :
:OH
: :
–
:
: :
: :
: :
–
:
: :
: :
:
:
:
:
• Identify the nucleophile and the electrophile in each step of the mechanism.
• Represent each step in the mechanism as a separate process.
• Experimental information indicates that the rate of hydrolysis depends on the concen-
trations of both the triglyceride and the base. Use this information to identify the rate
limiting step in the mechanism and sketch the energy diagram for the reaction.
• Identify and discuss similarities and differences between this mechanism and an SN2
mechanism for substitution reactions.

Module 1
Most of the images in this module have been generated by the authors (Own work). Other attributions include, P434 & P435: Background by
Hedgehog Fibres (Own work) [Generic 2.0] https://www.flickr.com/photos/29825916@N05/8722484981/in/set-72157606929752112; P436:
Upper right “do you think there’s something wrong with the American diet?” by Shawn Campbell (Own work) [Generic 2.0] https://www.flickr.
com/photos/thecampbells/3367105978/in/set-72157614124894156;
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Chemical

U6. How do we control chemical processes? 350

U7. How do we harness chemical energy? 412

To predict the likelihood of a chemical reaction we need to

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By Laitr Keiows (Own work)

the probability of observing the process will be very small. In other

THE CHALLENGE Primitive Combinations

Share and discuss your ideas with one of your classmates.

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By Einar Helland Berger (Own work)

Directionality? LET’S THINK

2 H2(g) + O2(g) 2 H2O(l) 2 H2O(l) 2 H2(g) + O2(g)

LET’S THINK Bond Energies

Bond BE (kJ/mol) Bond BE (kJ/mol) Bond BE (kJ/mol)

Molecular compounds with stronger covalent bonds tend to be more ther-

Initial Predictions LET’S THINK

Directionality? LET’S THINK

2 HCOOH(l) + O2(g) 2 CO2(g) + 2 H2O(g) | 2 CO2(g) + 2 H2O(l) 2 HCOOH(l) + O2(g)

The likelihood of chemical reactions involving ionic compounds depends on

LET’S THINK Ionic Compounds

C+(g) + A-(g) CA(s)

-500 The energy released during this process (DHrxn) is

K+ pound, the more energy will be required to separate

Metallic Oxides LET’S THINK

Chemical Reaction DHrxn (kJ/mol)

2 Fe(s) + 3/2 O2(g) Fe2O3(s) –824

Number of Configurations LET’S THINK

• Arrange these systems, from fewest to most, according to the number of

LET’S THINK State of Matter

LET’S THINK Temperature Effects

• How would you explain the different effects that

changing temperature has on the value of S at

Share and discuss your ideas with a classmate, and

LET’S THINK Molecular Mass

LET’S THINK Molecular Complexity

LET’S THINK Ionic Compounds

FACING THE CHALLENGE CO2(g) + 4 H2(g) CH4(g) + 2 H2O(g)

CO2(g) + 4 H2(g) CH4(g) + 2 H2O(g)

• Discuss whether each of these reactions would be product-favored or reactant-favored

4 FeO(s) + O2(g) 2 Fe2O3(s)

• Discuss whether each of these reactions would be product-favored or reactant-favored

Chemical Reaction DHrxn (kJ mol-1) DSorxn (J mol-1 K-1)

C(s) + 2 H2O(g) 2 H2(g) + CO2(g) 90.1 91.9

ASSESS WHAT YOU KNOW

Share and discuss your ideas with a classmate.

Glycine Proline Valine

PbS (in galena) Fe2O3 (in Hematite) Ag2S (in argentite)

Chemical Reaction DHrxn (kJ mol-1) DSorxn (J mol-1 K-1)

2 C(s) + O2(g) 2 CO(g) –221.0 178.8

3 Fe2O3(s) + CO(g) 2 Fe3O4(s) + CO2(g) –47.2 45.9

Fe3O4(s) + CO(g) 3 FeO(s) + CO2(g) 441.9 52.5

FeO(s) + CO(g) Fe(s) + CO2(g) –11.0 –17.41

ASSESS WHAT YOU KNOW

Metals and their Oxides

substances involved in a chemical reaction is useful in qualitatively predicting the

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By Fidel Gonzalez (Own work)

THE CHALLENGE Chemical Origins

Share and discuss your ideas with one of your classmates.

2nd Law of Thermodynamics

(5.2) DSTOT = DSsys + DSsurr > 0