Bio-Inorganic Chemistry

Lecture 4 Classifucation of
metals in biological system

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 Key points
• 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

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 CONTENT
• Historical Background
• ➢ Introduction
• ➢ Classification
• i. Elemental composition of biological systems
• ii. Essential elements and trace elements
• iii. Conditions for Essentiality
• iv. Elemental mass abundance in a 70 kg human
• ➢ Evolution of biological roles for essential metals
• ➢ Factors influencing the acquisition of metal ions by
biological systems
• ➢ Biological ligand
• Types of ligands in biological system
• ii. Hard and soft ligand
• iii. Chelate Effect
 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

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 Outline:
• Introduction/Historical Background
• Some General principes
-Inorganic elements in Organism: occurence and availability
-Biological functions of inorganic elements
- Biological ligands for metal ions
- Coordination Mode
• Spectroscopic Methods (Electronic spectra & magnetism)
• Electron-transfer proteins ( Cu/Fe proteins & some model
complexes)
• Oxygen transport in biology (Cu/Fe proteins & some model
complexes)
• Non-redox proteins (if time)
• Application: Medical Aspects
 General properties

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

Mo, Mn
Predominant +1 +2 +2 see Table 4
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+)
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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
6
high-spin d
7 6
Co high-spin d low-spin d
6 7
Ni high-spin d low-spin d

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 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
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 Oxidation states
+7 X
¡
+6 X
¡ X
l X
l
+5 ¡ X
l X
l
+4 ¡ ¡ X
l ¡ l
+3 ¡ X
l ¡ ¡ l ¡ ¡ l
+2 ¡ X
l X
l X
l ¡ ¡ ¡ ¡ ¡ ¡
+1 ¡ l l ¡
K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn

¡: common in chemistry
: Less common in chemistry
X : Not available to biology

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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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Function in Biology and Affects of Metal Deficiency in Humans
Elemental Composition of the Adult Human Body
Bulk or Constituent Elements:H, O, C, N, Ca, P, Na, K, S, Cl
Trace Elements:Mg, Si, F, Fe, Zn, B, Rb, Sr, Br, Cu
Ultra Micro Trace Elements:V, Li, Se, Mn, Ba, Ge, As, Ni, Mo,
Cd, I, Sn, Cr, Pb, Co
• ❖Essentiality of elements is defined by
• (1) A physiological deficiency appears when the element is
• removed from the diet
• (2) The deficiency is relieved by the addition of that element to
the diet
• (3) A specific biological function is associated with the element
• Consequences:
• ➢At lowest dosages organism does not survive.
• ➢In deficiency regions, the organism exists with less than
optimal functions.
• ➢After optimal dosage (plateau region), higher dosage cause
toxic effects
• in the organism eventually leading to lethality
 CLASSIFICATION
• ELEMENTAL COMPOSITION OF BIOLOGICALSYSTEMS
• Results of the chemical analysis of biological samples:
• practically all elements of the periodic table (min. 50-
70 element) can be detected in real biological samples
so far by the analytical instruments (Bertrand diagram).
Dose Response: Essential Elements
(Bertrand diagram)
ESSENTIAL ELEMENTS (CONDITIONS FOR ESSENTIALITY)
❖ Positive physiological response can be ascribed to their presence in the
case of several species.
❖ They occur in well defined concentration range in each species
❖ Deprival (from food) will results in reproducible and negative physiological
changes.
These effects can be reversible or at least reduced by addition of the given
element.
❖ Their deficiency and excess is connected with well defined diseseases.

❖ The biological presence of the element is connected with well defined

biochemical processes (Bertrand diagram).
• Difference between Essential and trace
elements?
• Essential elements:
• Required for maintenance of life, its absence
results in death or multifunctiong
• ▪ 30 elements are essential for life processes in
plants and animals
• Trace Elements:
• ▪Elements required in very small amount (in mg
or µg)
• ▪19 of the 30 elements are trace elements and
even out of these 12 are transition elements
• The following makes some elements essential:
• ➢ The element must have some unique chemical property that
an organism can use to its advantage and without which it can’t
survive.
• ➢ Adequate amounts of the element must be available in the
environment in an easily accessible form.
• ➢ Most living matter consists primarily of bulk elements—O,
C,H, N, and S They are the building blocks of the compounds
that make up our organs and muscles; they also constitute the
bulk of our diet.
• ➢ Six elements—Na, Mg, K, Ca, Cl, P are called
macrominerals and provide essential ions in body
• fluids and form the major structural components of the body.
• Remaining essential elements called trace elements and are
present in small amounts.
• TRACE ELEMENTS
• ➢It is difficult to detect low levels of some of the
essential elements,so the trace elements were
relatively slow to be recognized.
• ➢Many compounds of trace elements are toxic.
• ➢How can elements present in small amounts have
such large effects on the health of an organism?
• ➢Trace elements participate in an amplification
mechanism—they are essential components of larger
biological molecules that are capable of interacting
with or regulating the levels of relatively large amounts
of other molecules.
 Functions of Metals in Mammals
1)• Structure
– Hard material – bone and teeth
– Cell membranes
– DNA and RNA structure
– Protein, including enzyme conformation
2)• Charge carriers: Na+, K+, Ca2+
3)Electron transfer (Redox rxns) Fe, Cu, Mn, Mo, Ni, Co
4)• Metabolism: Degradation of organic molecules
5)• Activation of small molecules: O2, CO2
“ALL THINGS CAN BE POISONS”

It depends on: dosage, individual health, and way of

administration
Why does biology utilize
transition metals?
• Transition Metals are extremely good catalytic active sites in enzymes,
because they:
• – are stable in a variety of geometries and CN
• – have multiple coordination sites
• – Are stable in a variety of oxidation states
• – Are able to change the reactivity of ligands
• – Have “weak” coordinate bonds (where needed)
• – Are capable of stabilizing intermediates
• Why does it matter what ligands are attached to the metal ?
• • Tune Redox Properties
• • Assist in stabilization of multiple oxidation states of transition
• metals
• • Lability/Stability
 Principles of Bioinorganic Chemistry
Fundamental notions on protein chemistry:
Peptides and amino acids
Structure of proteins

The basics of coordination chemistry of transition metals

Peptides and amino acids
Structure of proteins
Nature of a transition metal
Geometrical and structural aspects

Coordination of proteins to transition metals

Coordination modes
Direct Coordination of amino acids
Coordination via cofactors

Useful techniques in bioinorganic chemistry

UV-visible spectroscopy
Vibrational spectroscopy (I.R., Raman)
EXAFS
EPR
Paramagnetic NMR
Mössbauer
 Transition Metals Relevant to
Bioinorganic Chemistry
• V, Mn, Fe, Co, Ni, Cu, Zn, Mo, & W
• Amino Acid Residues Commonly
Used as Ligands in Metalloenzymes
• • Cysteine, Histidine, Aspartic Acid,
Glutamic Acid, Methionine, Tyrosine,
Serine, & Lysine