inorganic chemistry

1. 1
Key points from last lecture
• Many “inorganic” elements are essential for
life
• Organisms make economic use of available
resources, but also have developed
mechanisms to accumulate certain elements
• Despite the low amount of metal ions present
in living systems, they are enormously
important for virtually all life processes
• Both deficiency and overload/excess lead to
illness

2. 2
Bio-Inorganic Chemistry
Lecture 2:
Basic Principles and Concepts

3. 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. 4
General properties
Characteristics Na+
, K+
Mg2+
, Ca2+
Zn2+
, Ni2+
Fe, Cu, Co,
Mo, Mn
Predominant
oxidation state
+1 +2 +2 see Table 4
stability of
complexes
very low low or
medium
high high (except
Fe2+
and
Mn2+
,
medium )
preferred
donor atoms
O O N, S N, S
(sometimes
O for high
oxidation
states)
mobility in
biological
systems
high medium low to
medium(esp.
Zn)
low to
medium
(Fe2+
and
Mn2+
)

5. 5
Geometries
Metal ion Preferred geometries in small high-
spin complexes with O and N donors
Cu(II),
Mn(III)
d9
d4
tetragonal > 5-coord. > tetrahedral
Cu(I) d10
linear, trigonal planar, or tetrahedral
Co(II) d7
octahedral > tetrahedral>others
Zn(II) d10
tetrahedral > octahedral > 5-coord.
Fe(III),
Co(III),
Cr(III),
Mn(II),
Ni(II)
d5
d6
d3
d5
d8
octahedral > others
Causes: see Ligand-field
theory and steric factors

6. 6
+7 
+6  l l
+5  l l
+4   l l
+3  l   l   l
+2  l l l      
+1  l l 
K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn
Oxidation states
X
X X X
X
X
X
X
X
X
X

: common in chemistry
l: Less common in chemistry
X : Not available to biology

7. 7
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 d6
high-spin d5
Co high-spin d7
low-spin d6
Ni high-spin d6
low-spin d7

8. 8
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

9. 9
Stability constants
L + M LM
Often expressed as log K:
e.g.: K = 1015  log K = 15
The dissociation constant Kd is K-1  log Kd = -15
[M]
[L]
[LM]
=
K =

10. 10
Stability constants - ranges
Rough rule of thumb:
• Strong complexes: log K > 10
• Weak complexes log K < 4

11. 11
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

12. 12
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-

13. 13
Hard and Soft Acids and Bases
Hard Borderline Soft
Acids:
H+, Na+, K+, Mg2+,
Ca2+, Cr3+, Fe3+, Co3+
Fe2+, Co2+, Ni2+,
Cu2+, Zn2+
Cu+, Ag+, Au+, Pt2+,
Pb2+, Hg2+, Cd2+
Bases:
NH3, RNH2, H2O, OH-
, O2-, ROH, RO-,
RCO2
-, PO4
3-
Ar-NH2, Imidazole RS-, RSR
• See Handout

14. 14
Hard and Soft Acids

15. 15
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)

16. 16
Stability Aspects: Interplay between HSAB
principle and the Irving-
Williams Series:
O,O
N,N
N,O
S,N
Cu
Fe
Figure from Sigel and
McCormick, Acc. Chem. Res.
3, 201 (1970).
X Y
M
log
K
• High-spin M(II)
complexes
• Bidentate ligands
• Trend more pronounced
the softer the ligand

17. 17
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

18. 18
Zn-Cys
Zn-His
Zn-Asp and
Zn-Glu
Calculated with:
logK’ =
logK + logKa –
log (Ka+[H+])
and values for logK for the 1:1
Zn(aa) complexes (taken from the
IUPAC stability constants database).
-logKa (= pKa):
Cys: 8.5
His: 6-7
Asp/Glu: 4
logK’
0
1
2
3
4
5
6
7
8
9
10
0 2 4 6 8 10 12
Competition between protons and metal ions:
Conditional stability constants of the four most common zinc
ligands in proteins
pH
Asp (N,O)
Glu (N,O)
Cys (S,N)
His (N,N)

19. 19
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

20. 20
Catalysis in Metalloenzymes

21. 21
Properties of metal ions exploited for
enzymatic catalysis
• Lewis acidity: affinity for electrons
- polarisation of substrates:
- 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
Zn
2+
OR'
R
O OH-
+
d+
d-

22. 22
Lewis acidity: Effect on pKa of
bound ligands
NB: Hydrolysis of
aquocomplexes
From Lippard and Berg

23. 23
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

24. 24
Oxidising power
increases
H+/H2 (pH 7): -0.4 V
O2/OH- (pH 7): +0.8 V
Species E0
(V)
Cu2+
/Cu+
+0.153
Fe3+
/Fe2+
+0.771
Mn3+
/Mn2+
+1.51
Co3+
/Co2+
+1.842
O2 /O2
–
– 0.33
O2 + H+
/ HO2 – 0.13
O2 + 2H+
/ H2O2 +0.281
O2 + 4H+
/ 2H2O +0.815
O2
–
+ 2H+
/ H2O2 +0.89
OH + H+
/ H2O +2.31
NB: Redox potentials of metal
ions are highly dependent on
environment and coordinated
ligands
Biology (ie chemistry in water)
is limited to this range.
Standard reduction potentials (pH 0)

25. 25
Kinetic aspects
• Water exchange rates
Expressed as lifetime of complexes
Useful to characterise reactivity in
ligand exchange reactions
inert labile

26. 26
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,
copper, and iron enzymes)

27. 27
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