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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
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
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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
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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
high-spin d6
7 6
Co high-spin d low-spin d
6 7
Ni high-spin d low-spin d
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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]
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Stability constants - ranges
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Stability Aspects: What governs
stability ?
1. charge effects
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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. F-
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Hard and Soft Acids and Bases
Hard Borderline Soft
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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 Irving-
Williams Series:
• High-spin M(II)
S,N X Y
complexes M
• Bidentate ligands
log K
N,O N,N
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Competition between protons and metal ions:
Conditional stability constants of the four most common zinc
logK’ ligands in proteins
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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
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Catalysis in Metalloenzymes
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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
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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
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
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
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