Introduction to Statistical

Thermodynamics
 Introduction
• Thermodynamics is often regarded as too abstract to be
relevant to biochemists:
– emphasis on heat engines.
– abstract concepts of energy and entropy.
• However, this abstractness makes Thermodynamics an
ideal tool for addressing biological systems.
– such systems are often not ‘well-defined’.
• Example: Energetics of Protein Denaturation
– Temp-dependence of Keq:
• Yields the enthalpy change, ∆Ho during denaturation.
• so-called ‘van’t Hoff analysis’.
– knowledge of protein structure or composition unnecessary.
 Outline
• Here, we briefly review some basic ideas from thermodynamics:
– Lecture 6:
• Heat, Work, and Energy
• The 1st Law of Thermodynamics.
– Lecture 7:
• Entropy, Free Energy, and Equilibrium.
• The 2nd Law of Thermodynamics.
• Useful for understanding macromolecular structure.
– structure discussed in terms of distributions over accessible states.
– Free energies will relate to equilibrium probabilities of occupation.
• Prerequisite for Statistical Thermodynamic modeling (Unit 4).
 Overview
• Biochemical systems typically contain huge numbers of
molecules:
– Size Avagadro’s
 Number (6.023 x 1023 molecules).
– These systems are extremely complex.
– Explicit modeling often beyond the capability of physical chemistry.
• However…a Thermodynamic analysis:
– independent of the specific details of molecular structure.
• nevertheless, provides detailed predictions.
• essentially exact, for many-particle systems.
– represents a statistical analysis…
• Statistical thermodynamic predictions represent ensemble averages.
 Points to Remember

• Thermodynamic predictions yield average quantities:

– conceptually, the most likely behavior.
• Predictions exact only for systems with a very large
number of particles.
– systems with a small number of particles may deviate.
• e.g.: protein copy number is often small.
• Predictions apply to systems at equilibrium.
– need to (separately) investigate times to equilibrium.
• Thermo. provides no information about rates.
– thermodynamics means ‘equilibrium thermodynamics’.
 Fundamental Quantities
• We first define and discuss some fundamental quantities:
1. The System.
2. The State of a System.
3. Heat, q.
4. Work, w.
5. Internal Energy, E.
6. Enthalpy, H = E + PV.
• These quantities will allow us to state the 1st Law of
Thermodynamics.
 The ‘System’
• Def. (System): A part of the universe chosen for study.
• Essentially, we divide the universe into 2 parts:
– system of interest;
– the rest of the universe = the ‘surroundings’.
– our system will have a definite spatial boundary.
 ‘System’ Characteristics
• Very abstract notion…but with definite characteristics:
• Definite boundaries in space.
• May be open or closed with respect to transfer of matter.
– constraint on exchange of particles?
• May, or may not be thermally isolated from the
surroundings.
– constraint on exchange of heat?
– If insulated, system is called adiabatic.
• note the absence of a notion of time…
– result: cannot discuss rates.
 Thermodynamic ‘State’ of a System
• At equilibrium, system assumed to occupy one of a set of
abstract, thermodynamic states.
– no precise meaning away from equilibrium.
• Each state unique; defined by the values of state variables:
– e.g.: two out of three of {temperature, pressure, volume}…
• plus the masses and identities of component chemical substances.
• System state determines system properties:
– provides a complete (macroscopic) specification of the system.
• Such properties will be of two types:
– extensive properties – require specification of amount of substance;
• e.g., volume, total energy.
– intensive properties – independent of system size.
• e.g., density, viscosity…require less information.
 Changes of System State
• Thermodynamics is concerned with:
– equilibrium distributions over accessible states.
– mean values of the properties of this distribution.
• …Also concerned with changes b/w equilibrium states.
– i.e., system traversal from an initial to a final state.
– focus: resulting change in some macroscopic system property.
• A change of state may be either reversible or irreversible.
– Reversible changes take a path near to equilibrium.
• resulting system changes can be accurately predicted.
– Irreversible changes deviate from equilibrium.
• resulting system changes cannot be accurately predicted.
• however, generally bounded by equilibrium values.
 The Transfer of Energy:
‘Heat’ vs. ‘Work’
• Heat, q
– energy transferred into a system due to a temperature difference
between the system and its surroundings.
– positive heat = heat absorbed by a system (+ energy flows in).
• Work, w
– any other exchange of energy between a system and surroundings.
• e.g.: volume change vs. external pressure, electrical work, etc.
– positive work = work done by a system (+ energy flows out).
• Neither q or w is a system property or state variable:
– have meaning only with respect to some energy transfer.
• Why differentiate between the two?
– transferring heat transfers entropy…while doing work does not.
 Internal Energy

• Internal Energy, E:
– the total energy within the system.
– includes energies which change during a chemical process:
• kinetic energy: translational, vibrational, and rotational;
• energy of chemical bonding (covalent bonds);
• energy of non-bonding interactions b/w molecules.
• E is a function of system state (a state variable).
– specifying a system’s state fixes its E.
• how the system attained the state irrelevant.
– E values defined relative to an arbitrary standard state:
• which has been defined to have zero energy.
 Enthalpy, H

• System Enthalpy is the sum of:

– the internal energy (E).
– the product of system volume, and the external pressure
exerted on our system (PV).
H = E + PV
• H is also a function of system state (state variable).
– each state characterized by a unique value of H.
– changes between states A and B yield a well-defined
enthalpy change, ∆H = HB-HA.
• ∆H independent of the intermediate set of conformations.
– also referred to as the ‘path’.
 The Heat Capacity
• The heat capacity, C of a given substance:
– the heat input required to raise the temperature of a given mass of
a substance by 1 Κο:
C = mc = ∆Q/∆T.
• depends on m, the mass of the substance (an extrinsic property).
• c = specific heat (heat capacity/gram…an intrinsic property).
– C refers to the molar heat capacity (an intrinsic property).
• C depends on the manner in which heating occurs:
– constant volume: C = Cv.
– constant pressure: C = Cp.
– in general, Cv <= Cp.
– For an ideal gas, CP - CV = R.
 First Law of Thermodynamics

• The 1st Law is a statement of Conservation of Energy…

– in terms of heat, work, and internal energy.
– For a change in state, the 1st Law states:
∆E = q-w
• For small changes, we use differential symbols for q,w:
dE = dq – dw
– slashes indicate that q and w do depend on path.
• In this treatment, slashes will generally be omitted.
– E is a state variable, so that dE does not depend on path.
• dE is an exact differential.
• The 1st Law completely general.
– does not rely on assumptions, such as reversibility (equilibrium).
 PdV Work
• PdV work refers to:
– work involving only a change of system volume, dV…
– in response to an external pressure, P.
• If only PdV work is done, dw = PdV, and
– the 1st Law becomes:
dE = dq - PdV
• Similarly we can write for dH:
dH = d(E + PV)
= dE + PdV + VdP
= (dq - dw )+ PdV + VdP
= dq + VdP
 Measuring ∆E
• These two expressions help to relate system variable
changes to a measurable quantity:
– a change in temperature, ∆T.
• For state changes at constant volume:
dE = dq – pdV = dq
– heat absorbed at constant volume, qV measures
dE.
– for a finite change, ∆E = qV.
• Since C = ∆q/∆T, we have:
∆E = Cv ∆T = mcv ∆T.
• A constant-volume calorimeter:
– ∆E = qV accompanying a chemical reaction, measured by ∆T.
 Measuring ∆H
• For state changes at constant pressure:
dH = dq + VdP = dq
– for a finite change, ∆H = qp.
– heat absorbed at constant pressure, qP
measures ∆H.
• Since C = ∆q/∆T, we have:
∆H = Cp ∆T = mcp ∆T.
– facilitates measuring ∆H b/w 2 states:
• choose a path at constant pressure…
• and measure ∆T.
• A constant-pressure calorimeter shown at right:
– ∆H accompanying a chemical reaction measured by ∆T.
 The Difference between ∆E and ∆H
• In general, ∆E and ∆H will differ slightly for the same
change of state.
– in biological systems, we generally have ~ constant pressure.
– consider an infinitesimal change of state, at constant pressure…
dH = dE + PdV + VdP
= dE + PdV.
• The difference is thus the work done to enforce the change in system
volume, dV.
• In biological systems, volume change generally small…
– since most occur in liquid or solid (rather than gas).
• Essentially incompressible.
– thus, we often neglect the difference b/w ∆E and ∆H.
 Molecular Interpretation

• Together, the 1st Law and the concept of a state variable:

– allow some very general conclusions.
– we could now apply the 1st Law to many different conditions…
• combinations of constant P, V, and T.
• Our focus however, is a molecular interpretation:
– how do ∆E, ∆H relate to the behavior of atoms and molecules?
• In particular, if we add energy to the system…
– can we predict where has the energy has gone?
• into kinetic energy….translation and rotation.
• for a complex biopolymer: vibrational energy, intermolecular
interactions.
– How is the energy distributed ?
 Statistical Thermodynamics –
The Ensemble
• Concern: behavior of a large number of molecules.
– or, the mean behavior of 1 particle over a long time.
• We therefore take a statistical view:
– we consider an ‘ensemble’ at equilibrium:
• O(1023) identically prepared copies of our biopolymer.
– we then investigate the ensemble distribution:
• how members are distributed over particle states.
• each overall distribution = 1 system state.
• Here, thermodynamic ‘state’:
– refers to the state of our system of N particles.
• not equal to particle state.
– e.g., system energy is the sum over all particle energies.
E = Σi Ei.
 The Most Probable Distribution
• Generally, our system will be constrained…
– constraints will vary, depending our system of interest.
– For the ‘microcanonical ensemble’, we have:
• constant total energy (E).
• constant total number of particles (N).
– Each distribution which satisfies our constraints is called accessible.
• What is the most probable distribution, at equilibrium?
– this system state will be useful:
• it will help characterize mean particle behavior.
– mean properties = ensemble averages.
• averages taken over all particle states…
• correspond to macroscopic observables.
 The Fundamental Assumption
• Fundamental Assumption of Statistical Thermodynamics:
– For a particle in an isolated system, each particle state equally likely…
• isolated means constant E, N.
– Implied: Each elementary distribution equally likely.
• such an elementary distribution referred to as a system microstate.
• in a system microstate, each particle assigned a distinct energy.
• Each system state is a macroscopic state:
– only the total number of particles in each particle-state is specified.
– each system state = a sum over a set of equivalent microstates.
• The most probable system state:
– ensemble distribution with the largest number of distinct ways to arrange
the particles over the particle states.
 Example

• Consider a simple system:

– 6 particles (N = 6);
– distributed over 6 quantum ‘states’, i = {1,…,6}.
• here, particle state i has energy, εi = i*ε …
– where ε is the energy of the ‘ground state’.
– Let the total (system) energy be constrained: E = 10ε.
• Many distributions consistent with this constraint.
– let ni denote the number of particles in particle state i;
• system state then an ordered list: (n1, n2, n3, n4, n5, n6).
– three such distributions are shown on the next slide…
 Example (cont.)

• Each can be achieved in a number of particle

arrangements….
– State a (5, 0, 0, 0, 1, 0) can be achieved in 6 ways.
– State b (3, 2, 1, 0, 0, 0) can be achieved in 60 ways.
– State c (2, 4, 0, 0, 0, 0) can be achieved in 15 ways.
 System State Degeneracy, W
• The number of ways, W of arranging N particles…
– n1 in one group;
– n2 in a second group, etc.
is given by …

• The most probable distribution will maximize W.

– subject to our constraints:
• N = constant; E = constant.
 The Boltzmann Distribution

• For a large number of particles, W maximized when:

ni = n1exp[-α(εi-ε1)];
• ni = number of particles in particle state, i.
• εi = energy of particle state, i.
• state i = 1 is the particle state of lowest energy (ground state).
• Referred to as the Boltzmann distribution :
– the most probable distribution at constant system N, E.
• …for a system of particles at equilibrium.
– constant given by, α = 1/(kBT).
• kB = R/NA is the Boltzmann constant.
• T = absolute temperature.
 Particle State Degeneracy, gi

• The Boltzmann distribution, as written describes:

– a distribution of the N particles of our system over particle states…
• Assumption: each particle state has a unique energy.
– however, many particle states may have the same energy;
• these are energetically equivalent…and thus, can be grouped.
– more appropriate: distribution over particle energy levels.
• Let’s redefine i to refer to the ith energy level.
– So, for the ‘new’ degenerate levels, we have ni’ = gini,
• Substituting into the Boltzmann distribution we get:

ni ’ /gi= (n1 ’ /g1)exp[-(εi-ε1)/kBT];

• Now, ni ’ = tot. number of particles in energy level i (we re-defined ni).
• gi = degeneracy of the ith energy level.
– For convenience, we now drop the primes on n from here on…
 The Partition Function
• Summing over all energy levels, i yields the total particle
number:
N = Σi ni = (n1/g1)Σi gi exp[-(εi-ε1)/kBT]

• Then the probability that a randomly selected particle will be

found in state i is:

• Here the denominator is the partition function:

• very useful for calculating system average quantities.

 Conclusion
• In this Lecture, we have discussed:
– The concepts of system and equilibrium state…
• Identified several state variables (e.g., P, V, T, E, and H),
• Distinguished between reversible and irreversible changes of state.
– The relationship between heat (q), work (w), and internal energy (E):
• The 1st Law of Thermodynamics.
– The concept of an Ensemble,
• And identified the Boltzmann distribution as the most probable distribution of
ensemble members, at equilibrium.
• In Lecture 7, we will:
– re-express system degeneracy in terms of a macroscopic quantity:
• the Entropy, S.
– This concept will enable us to formulate the 2nd Law of Thermodynamics,
• to identify the conditions for equilibrium,
• and to convert the Boltzmann distribution to a more familiar form.
 Midterm Test Postponed

• The Midterm is postponed until next class:

– Thursday, Dec. 20th (next class)
– Same material (does not include today’s lecture material)

• The test format has also changed:

– Mainly a short answer format