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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
1
Bio-Inorganic Chemistry
Lecture 2:
Basic Principles and Concepts
2
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
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•
•
•
•
•
•
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
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General properties
Characteristics Na+, K+
Mg2+, Ca2+
Zn2+, Ni 2+
Predominant
+1
oxidation state
stability of
very low
complexes
+2
+2
low or
medium
high
preferred
donor atoms
O
O
mobility in
biological
systems
high
medium
Fe, Cu, Co,
Mo, Mn
see Table 4
high (except
Fe2+ and
Mn2+,
medium )
N, S
N, S
(sometimes
O for high
oxidation
states)
low to
low to
medium(esp. medium
Zn)
(Fe2+ and
Mn2+)
4
Geometries
Preferred geometries in small high-
Metal ion
spin complexes with O and N donors
Cu(II),
d9
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
Cr(III),
d3
Mn(II),
d5
Ni(II)
d8
tetragonal > 5-coord. > tetrahedral
octahedral > others
Causes: see Ligand-field
theory and steric factors
5
Oxidation states
+7
+6
+5
+4
+3
+2
+1

X
l
X
l



K
Ca
Sc
Ti




X
l
X
X
l

X
X
l
l
X
l
X

l

l
X
l
l
X



V
Cr
Mn
Fe


l
l
l
Co
Ni



Cu

Zn
: common in chemistry
l: Less common in chemistry
X : Not available to biology
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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
Co
Ni
high-spin d
6
high-spin d
7
high-spin d
6
low-spin d
6
low-spin d
7
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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
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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
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Stability constants - ranges
Rough rule of thumb:
• Strong complexes: log K > 10
• Weak complexes log K < 4
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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
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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. F12
Hard and Soft Acids and Bases
Hard
Borderline
Soft
Acids:
Fe2+, Co2+, Ni2+,
H+, Na+, K+, Mg2+,
Cu2+, Zn2+
Ca2+, Cr3+, Fe3+, Co3+
Cu+, Ag+, Au+, Pt2+,
Pb2+, Hg2+, Cd2+
Bases:
Ar-NH2, Imidazole
NH3, RNH2, H2O, OH, O2-, ROH, RO-,
RCO2-, PO43-
RS-, RSR
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• See Handout
Hard and Soft Acids
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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)
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Stability Aspects: Interplay between HSAB
principle and the IrvingWilliams Series:
• High-spin M(II)
complexes
• Bidentate ligands
log K
S,N
X
Y
M
• Trend more pronounced
the softer the ligand
O,O
N,O
N,N
Fe
Cu
Figure from Sigel and
McCormick, Acc. Chem. Res.
3, 201 (1970).
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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
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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)
logK’ =
logK + logKa –
log (Ka+[H+])
8
7
6
5
Zn-His
His
(N,N)
Asp (N,O)
Glu (N,O)
Zn-Asp and
and values for logK for the 1:1
Zn-Glu
Zn(aa) complexes (taken from the
IUPAC stability constants database).
4
3
-logKa (= pKa):
Cys: 8.5
His: 6-7
Asp/Glu: 4
2
1
00
2
4
6
pH
8
10
12
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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
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Catalysis in Metalloenzymes
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Properties of metal ions exploited for
enzymatic catalysis
• Lewis acidity: affinity for electrons
- polarisation of substrates:
Zn
2+
- facilitation of attack by external base
- increasing attacking power of bound base
dO
OR'
d+ + OHR
- 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
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Lewis acidity: Effect on pKa of
bound ligands
NB: Hydrolysis of
aquocomplexes
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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
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Standard reduction potentials (pH 0)
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
H+/H2 (pH 7): -0.4 V
O2/OH- (pH 7): +0.8 V
Oxidising power
increases
NB: Redox potentials of metal
ions are highly dependent on
environment and coordinated
ligands
Biology (ie chemistry in water)
is limited to this range.
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Kinetic aspects
• Water exchange rates
Expressed as lifetime of complexes
Useful to characterise reactivity in
ligand exchange reactions
inert
labile
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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)
26
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
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