CH450 INORGANIC CHEMISTRY

Mentor: Dr. Kabaso Kalebaila

Email: kkalebai@gmail.com
School of Mathematics and Natural Sciences
Chemistry Department
BIOINORGANIC CHEMISTRY
Bioinorganic chemistry is concerned with the roles of
inorganic elements in biological processes.

Coordination Complexes in Living Systems

 Biologically Important Elements:
Biodistribution of Metal Ions
Which “inorganic” elements are important biologically?

1. Bulk biological elements: H, C, N, O, P, S, Cl (as PO43-,

SO42-, Cl-)
2. Bulk metal ion nutrients: Na, Mg, K, Ca
3. Essential elements for a wide range of bacteria, plants,
animals
4. Transition metals: V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo
5. Non-Metals: (B), F, (Si), Se I, F.

 99% of human body is comprised of 11 elements

Periodic Distribution of Biologically Important Elements

Why have certain elements been "selected"

for use in biological systems?
 Biological roles for essential metals
Why have certain elements been "selected" for use in biological systems?

 Lighter elements are more abundant in general and therefore

utilized more: 3d metals, rather than 4d, are used as catalytic
centers in metalloenzymes.

 Why has Mo (4d) rather than Cr (3d) been utilized more

biologically?:

• Although Mo is rare in the earth’s crust, Mo is the most abundant

transition metal in sea water as MoO4 has fairly high solubility in
water.

 Despite the high abundance of Si, Al and Ti (the 2nd, 3rd and 10th
most abundant elements on earth). Why are they are not utilized
biologically?:
• Because of the insolubility of their naturally occurring oxides
(SiO2, Al2O3, TiO2) under physiological conditions- aerobic
environment.
 The most important ions
• Ion • Role:
• Ca2+ • 1.5-2% of body mass, bones, teeth
• Mg2+ • Bones and teeth, intracellular activity
• Fe2+ • Hemoglobin, O2 transfer
• Cu2+ • Cofactor in enzymes
• Zn2+ • Cofactor in enzymes,growth, healing
• Co3+ • In vitamin B12
• Na+ • Water balance, nerve impulses, fluids
• K+ inside and outside cells
 Biochemical Classification of Metallobiomolecules
O2 binding/transport: Myoglobin (Fe)
Hemoglobin (Fe)
Hemerythrin (Fe)
Hemocyanin (Cu)

Hydrolases: Carbonic anhydrase (Zn)

Carboxypeptidase (Zn)

Oxido-Reductases: Superoxide dismutase (Cu, Zn, Mn, Ni)

Catalase, Peroxidase (Fe)

Cytochrome oxidase (Fe, Cu)

Isomerases: B12 coenzymes (Co)

Aconitase (Fe-S)
 Biocoordination compounds:
Role metal center in biomolecules
Transition Metal Complexes in
Biological Molecules
• Metal ion complexes are used in humans
for the transport and storage of oxygen,
as electron-transfer agents, as catalysts,
and as drugs.
 Biocoordination compounds:
Role metal center in biomolecules
 Metal ions can have structural roles, catalytic roles, or both.

 Metals that have catalytic roles will be present at the active

site of the biomolecule: a metalloprotein

 Reactivity of a metalloprotein dependent on electronic structure

and oxidation state of metal.

 Electronic structure and oxidation state of metal is determined

by its coordinated ligands and molecular geometry, which is
provided by the architecture of the protein surrounding the
metal.
 Importance of the electronic structure
of the metal center

 Electronic structure and spin state of a metal center:

a. controls its chemical reactivity as a redox center (i.e.
its efficiency at accepting or donating electrons)

b. permits its investigation and characterization through

electronic and magnetic analysis etc.

 Electronic structure of a metal center defines its chemical

reactivity as a Lewis acid (electron-pair acceptor) which
enables it to bind ligands (O2, N2, CO ..) for transport,
activation and reaction.
 Transition Metal Complexes in
Biological Molecules
Why do we need to eat d metals?
 Some critical enzymes in our cells are metalloproteins, giant
biomolecules which contain a metal atom
These metalloproteins control key life processes such as respiration
and protect cells against disease

Hemoglobin is a metalloprotein which contains an iron atom and

transports O2 through out living systems

Vitamin B12, which prevents pernicious anemia, contains a Co atom

which gives the vitamin a red color
In general, metal ion complexes are used in humans for the
transport and storage of oxygen, as electron-transfer agents, as
catalysts, and as drugs.
 Biological Ligands in Living Systems
Ligands that surround metal center in living systems.

MACROCYCLIC LIGANDS
TETRAPYRROLES
 most common, best known bioinorganic compounds
 partially unsaturated, tetradentate, macrocyclic ligands
 stable, rigid, planar or nearly planar ring system
 deprotonated forms bind metal ions tightly and size selectively
 extensive conjugation leads to very intense colors (pigments of
life) and potentially to redox activity
 study of structure/function and organic synthesis of these
complexes led to several Nobel prizes
 Biological Ligands in Living Systems
TETRAPYRROLES
 Biological Ligands in Living Systems
Porphyrins:
 Are a group of heterocyclic macrocycle organic compounds:
containing four interconnected pyrrole groups.
 Macrocyclic tetrapyrrole in a 18-π aromatic ring system
 The parent porphyrin is porphin, and substituted porphines are
called porphyrins
Four-fold coordination, binds majority of metals (Mg, Zn, Cu, Fe …)
C

C

porphin, M = 2H, Mg, Zn et al.

 The Heme Complexes:
Iron Complexes of Porphyrins

Biological Importance of Iron

• Plays a central role in almost all living cells.

• Component of hemoglobin and myoglobin.
• Involved in the electron-transport chain.
 Regulation of iron absorption & transport.
Iron for synthesis of heme, Fe-S centers & other
non-heme iron proteins is obtained from:
 the diet
 release of recycled iron from macrophages of old &
damaged erythrocytes.
There is no mechanism for iron excretion.
 Iron is significantly lost only by bleeding.
 Small losses occur from sloughing of cells of skin
(shedding or casting off dead tissue).
The Heme Complex
 Hemes: Iron Complexes of Porphyrins

Hemes are iron based contained porphyrins

Several different types of hems depending of functional groups
bound at meso carbons
 Hemes: Iron Complexes of Porphyrins

Hemes are iron based contained porphyrins

Several different types of hems depending of functional groups
bound at meso and beta carbons
 Hemoglobin
• Oxygen binds to hemoglobin by cooperative binding i.e the
binding of oxygen increases the affinity for more oxygen to by to
hemoglobin
• A single red blood cell can carry up to a billion molecules of
oxygen from the lungs.
• Each hemoglobin has two α chains and two β chains, each with a
heme complex near the center: four heme groups.
• Each hemoglobin molecule can complex with four O2 molecules.
• Hemoglobin carries oxygen from lungs to tissue cells.
 Hemoglobin as oxygen carrier
• In each hemoglobin molecule there are four
heme groups
• Heme = Fe2+ surrounded by phorphyrin group,
four N act as ligands.
• As O2 carrier: O2 binds to Fe2+ as a ligand
• Reversible process
• CO and CN– bind irreversible to Fe2+
 Reversible addition of O2 to hemoglobin

As a result of cooperative binding, almost all of the hemoglobin is

saturated with oxygen after it passes through the lungs.

The increased affinity of hemoglobin results from a conformational

change, or a change in the structure of hemoglobin when the oxygen
binds.
BINDING OF O2 BY HAEMOGLOBIN
 Myoglobin, Mb
• Single strand or chain with the Fe2+ ion is coordinated to four
nitrogen atoms in the porphyrin of the heme and on nitrogen from the
protein chain.
• This leaves a 6th coordination position (the W) available for an
oxygen molecule.
• Mb has a higher affinity for oxygen than does hemoglobin: whereas
hemoglobin transports oxygen, myoglobin's function is to store
oxygen.
 Other Heme Enzymes Porphyrins:
Apart from hemoglobin and myoglobin other metalloproteins
such as catalase and peroxidases exist in living organisms
(bacteria, plants, and animals).

• Oxygen, is not only essential for energy metabolism and

respiration, but it has been implicated in many diseases and
degenerative conditions
• Common human disorders as ageing, arthritis, cancer, involve of
partially reduced forms of oxygen.
• When O2 undergoes reduction, several reactive intermediates
are formed, like superoxide (O2– ), hydrogen peroxide (H2O2),
and the extremely reactive hydroxyl radical (.OH): collectively
termed as the reactive oxygen species (ROS).
O2 +e- → O2¯+e- → H2O2+e-→ .OH+e-→ H2O
 Other Heme Enzymes Porphyrins:
Catalase
 A common enzyme in organisms that are exposed to oxygen
 Contains four porphyrin heme (iron) groups that allow the
enzyme to react with the hydrogen peroxide
 Helps to protect cells from oxidative damage by reactive oxygen
species (ROS) such as catalytic decomposition of hydrogen peroxide to
water and oxygen
 One catalase molecule converst millions of hydrogen peroxide
molecules to water and oxygen each second.
Without catalase, toxic substances could attack and mutate DNA.
Commercial catalases also are used to break down hydrogen peroxide
in wastewater.
 Catalase
Catalase is a form of protein.
Proteins are large, globular molecules made of amino acid subunits.
These amino acids are arranged in a chain to form the protein
molecule.
All proteins (and enzymes) have a specific shape: dependent on how
the amino acids chains are folded together. The folded and twisted
segments in this image represent the amino acids chains.

Hydrogen peroxide enters the active site of the protein that contains heme group
 Hydrogen peroxide interacts with the amino acids and a hydrogen ion is transferred
from one oxygen atom to the other.
The free oxygen atom coordinates to the heme, liberating water molecule and
intermediate Fe(IV)=O.
 Fe(IV)=O reacts with a second hydrogen peroxide molecule to reform Fe(III)-E and
produce water and oxygen.
 Other Heme Enzymes Porphyrins:
Peroxidase
Haem peroxidases (or heme peroxidases) are haem-containing
enzymes that use hydrogen peroxide as the electron acceptor to
catalyse a number of oxidative reactions.
Fe3+ + H2O2 [Fe4+=O]R' (Compound I) + H2O
[Fe4+ O]R' + substrate --> [Fe4+=O]R (Compound II) + oxidised substrate
[Fe4+ O]R + substrate --> Fe3+ + H2O + oxidised substrate
 The Non-Heme Porphyrins:
Zinc protoporphyrin (ZPP) is a compound found in red blood cells
when heme production is inhibited by lead and/or by lack of iron.
 Instead of incorporating a ferrous ion, to form heme, the
immediate precursor of heme, incorporates a zinc ion, forming ZPP.

Clinical determination of zinc protoporphyrin in red cells is used

as a screening test for lead poisoning and for iron deficiency
 Biological Ligands in Living Systems
TETRAPYRROLES
 Non-Pophyrins: Mg Complexes of Chlorins
CHLORINS – CHLOROPHYLL a

N N

Mg
Chlorophyll
N N
(C55H72N4O5Mg)

O COOMe O

Chlorophyll contains a magnesium enclosed in a chlorin and is vital in

photosynthesis.
The magnesium ion is not directly involved in the photosynthetic function and can
be replaced by other divalent ions with little loss of activity.

The photon is absorbed by the chlorin ring, whose electronic structure.

Non-Porphyrins: Co Complexes of Corrins
CORRINS – VITAMIN B12

Involved in many important biological processes, including the production of red

blood cells

Vitamin B12 (Co[C62H88N13O14P])CN