Sei sulla pagina 1di 48

Bio-Inorganic Chemistry

Lecture 1:
Basic Principles and Concepts

1
2
3
Overview
a) Synopsis of important properties of metal ions
b) Geometries and electronic structures of metal ions in
Biological System
c) Thermodynamics: complex stability and site selectivity
• Stability constants
• Charge
• Ionic radii
• HSAB principle
• Irving-Williams Series
• Other effects
• pKa values and the competition of metals with protons

d) Properties important for catalysis


• Lewis acidity
• Redox potentials and electron transfer rates
• Ligand exchange rates

e) Effect of metal environment created by protein


4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
General properties

Characteristics Na+, K+ Mg2+, Ca2+ Zn2+, Ni 2+ Fe, Cu, Co,


Mo, Mn
Predominant +1 +2 +2
oxidation state
stability of very low low or high high (except
complexes medium Fe2+ and
Mn2+,
medium )
preferred O O N, S N, S
donor atoms (sometimes
O for high
oxidation
states)
mobility in high medium low to low to
biological medium(esp. medium
systems Zn) (Fe2+ and
Mn2+)
22
23
24
Geometries
Metal ion Preferred geometries in small high-

spin complexes with O and N donors

Cu(II), d9 tetragonal > 5-coord. > tetrahedral


Mn(III) d4
Cu(I) d10 linear, trigonal planar, or tetrahedral

Co(II) d7 octahedral > tetrahedral>others

Zn(II) d10 tetrahedral > octahedral > 5-coord.

Fe(III), d5
Co(III), d6 Causes: see Ligand-field
theory and steric factors
Cr(III), d3 octahedral > others
Mn(II), d5
Ni(II) d8
25
Oxidation states
+7 
X
+6 
X l
X l
X
+5  l
X l
X
+4   l
X  l
+3  X
l   l   l
+2  X
l l
X l
X      
+1  l l 
K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn

: common in chemistry
l: Less common in chemistry
X : Not available to biology

26
Common spin states for some metal ions
Table: Common spin states for some metal ions
Metal M2+ M3+
Mn high-spin d5 high-spin d4
Fe low-spin or high-spin d5
high-spin d6
7 6
Co high-spin d low-spin d
6 7
Ni high-spin d low-spin d

27
Stability aspects: Thermodynamics
of metal binding
• Important for Understanding of:
– Metal uptake and distribution
– Specificity of metal binding (bio)molecules
– Catalysis by metalloenzymes
– Interactions of metals with nucleic acids

28
Stability constants
L + M LM

[LM]
K=
[L] [M]

Often expressed as log K:


e.g.: K = 1015  log K = 15

The dissociation constant Kd is K-1  log Kd = -15

29
Stability constants - ranges

Rough rule of thumb:


• Strong complexes: log K > 10
• Weak complexes log K < 4

30
Stability Aspects: What governs
stability ?
1. charge effects

• Rule of thumb: The higher the charge of


the cation, the more stable the complex
• Biophysical reason: Charge recombination
is favourable
• But see later: HSAB principle

31
2. Ionic radii
• Ionic radii are dependent on:
– position in periodic system
– charge (the higher, the smaller)
– coordination number (the higher, the larger)
• If covalence (due to differences in
electronegativity), steric hindrance etc.
would not operate, z/r (charge/radius)
would dictate order of stabilities
• In reality: seldom observed, only with very
small ligands, e.g. F-
32
Hard and Soft Acids and Bases
Hard Borderline Soft

Acids: Fe2+, Co2+, Ni2+, Cu+, Ag+, Au+, Pt2+,


H+, Na+, K+, Mg2+, Cu2+, Zn2+ Pb2+, Hg2+, Cd2+
Ca2+, Cr3+, Fe3+, Co3+

Bases: Ar-NH2, Imidazole RS-, RSR


NH3, RNH2, H2O, OH-
, O2-, ROH, RO-,
RCO2-, PO43-

33
• See Handout
Hard and Soft Acids

34
Stability Aspects:
The Irving-Williams Series
• Stability order for high-spin divalent metal ion
complexes
• Always peaks at Cu(II)
• Mn(II) always
the minimum
• Underlying
reasons:
a) ionic radii
b) LFSE Zn(II)

35
Stability Aspects: Interplay between HSAB
principle and the Irving-
Williams Series:

• High-spin M(II)
S,N X Y
complexes M
• Bidentate ligands
log K

• Trend more pronounced


the softer the ligand
O,O

N,O N,N

Figure from Sigel and


Fe Cu McCormick, Acc. Chem. Res. 36
3, 201 (1970).
Competition with protons
• Both metal ions and H+ are positively charged
and have an affinity for bases
• The actual concentration of a complex ML
therefore depends on [M], [L], and [H+]
• Low pH  high [H+]: ML complexes dissociate
 Effective (or apparent or conditional) stability
constants

37
Competition between protons and metal ions:
Conditional stability constants of the four most common zinc
logK’ ligands in proteins
10
Zn-Cys
9
Calculated with:
Cys (S,N)
8 logK’ =
7
Zn-His
His (N,N)
logK + logKa –
6 Asp (N,O) log (Ka+[H+])
5 Glu (N,O) Zn-Asp and
Zn-Glu and values for logK for the 1:1
4 Zn(aa) complexes (taken from the
IUPAC stability constants database).
3
-logKa (= pKa):
2
Cys: 8.5
1 His: 6-7
Asp/Glu: 4
00 2 4 6 8 10 12 38
pH
Other contributions to stability
• Chelate effect
• Preferred coordination geometry
• Dielectric constant of the medium:
Interiors of proteins can be very different
from water – usually more hydrophobic 
lower dielectric constant: Enhances charge
recombination and therefore complex
formation

39
Catalysis in Metalloenzymes

40
Properties of metal ions exploited for
enzymatic catalysis
• Lewis acidity: affinity for electrons OR'
2+ d-
- polarisation of substrates: Zn O d+ + OH-
R
- facilitation of attack by external base
- increasing attacking power of bound base
- pKa values of coordinated ligands are lowered
E.g.: aquo-ions: pKa usually 9-10
in zinc enzymes as low as 7.
• Orienting the substrate and stabilising it in a
conformation conducive to reaction
• Redox activity
41
Lewis acidity: Effect on pKa of
bound ligands

NB: Hydrolysis of
aquocomplexes

42
From Lippard and Berg
Importance of redox chemistry in
biological systems
• Electron transfer reactions: Energy generation for life is
based on flow of electrons - e.g. from “fuel” to O2
(respiration)

http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter9/animations.h

43
Standard reduction potentials (pH 0)
Species E0 (V)
Cu2+/Cu+ +0.153
Fe3+/Fe2+ +0.771
Oxidising power
Mn3+/Mn2+ +1.51
increases
Co3+/Co2+ +1.842
O2 /O2– – 0.33
O2 + H+/ HO2 – 0.13
NB: Redox potentials of metal
ions are highly dependent on
O2 + 2H+ / H2O2 +0.281
environment and coordinated
O2 + 4H+ / 2H2O +0.815
ligands
O2– + 2H+ / H2O2 +0.89
OH + H+ / H2O +2.31

H+/H2 (pH 7): -0.4 V Biology (ie chemistry in water)


O2/OH- (pH 7): +0.8 V is limited to this range.
44
Kinetic aspects
• Water exchange rates
Expressed as lifetime of complexes
Useful to characterise reactivity in
ligand exchange reactions

inert labile

45
Proteins tune the properties of
metal ions
• Co-ordination number:
– The lower the higher the Lewis acidity
• Co-ordination geometry
– Proteins can dictate distortion
– Distortion can change reactivity of metal ion
• Weak interactions in the vicinity: second shell
effects
– Hydrogen bonds to bound ligands
– Hydrophobic residues: dielectric constant can change
stability of metal-ligand bonds

• We’ll look at these in more detail later (lectures on zinc,


46
copper, and iron enzymes)
47
Summary
• The behaviour of metal ions in biological
systems can be understood by combining
the principles of coordination chemistry with
a knowledge of the special environment
created by biomolecules

48

Potrebbero piacerti anche