1c: Bioinorganic Chemistry:

Inorganic Chemistry in Living

Systems

Prof. Madhab Chandra Das

Department of Chemistry
High Pressure Lab (Ground Floor)
Ph: 03222-282894
Email: mcdas@chem.iitkgp.ac.in
 Bioinorganic Chemistry
• “Bioinorganic Chemistry“ is at the gate-way of
inorganic chemistry and biochemistry, i.e. it
describes the mutual relationship between
these two sub-disciplines, with focus upon the
function of inorganic “substances“ in living
systems, including the transport, speciation
and, eventually, mineralisation of inorganic
materials.
Bio elements?
Metals in biology
 Metal Binding Bio-Groups

functional groups like

-COOH, -OH, -SH, NH2
CONH2 in peptide bond
 Human body

75% Hem-iron 25% Non-hem-iron

 Hemoglobin  Rubredoxins
 Myoglobin  Ferredoxins
 Cytochromes
 Oxidases, P-450

Fe(II) and Fe(III): Uptake: ~ 1 mg/day

 PORPHYRIN:
A STRONG METAL BINDING GROUP

Fairly rigid
N

N M-N bond length:

H
N 196 pm - Ni(II)
H 210 pm - Fe(II)
N
 Iron(II)-protoporfirin IX-complex (HEM)
Heme B
CH2
Heme A...Cyt a
Heme B...Cyt b, Hb, Mb H3C CH
Heme C...Cyt c

HC CH
N
H3C
CH3

N Fe N

H2C CH
N
HC CH
CH2 CH2
OOC

H2C CH3

H2C COO
 Oxygen Carrier
It is believed all free O2 on earth has been formed by photosynthesis

• The problem: Oxygen is required by cells

throughout organisms for respiration.
• But…
– Diffusion of oxygen through tissues is ineffective.
– Oxygen has low solubility in aqueous solutions.
• To solve this problem, we need a carrier
molecule that can transport oxygen from the
lungs to tissues where the oxygen is needed.
 Biological oxygen carrier
• Binds oxygen reversibly
– Efficiently pick up oxygen in the lungs (high
capacity and fast binding)
– Efficiently release oxygen in tissues where it is
needed
– No side reactions
• Metals are better candidates for reversible oxygen
binding than organic molecules.
• But … reaction of "free" metals with oxygen can be
irreversible and can also lead to production of
dangerous free radicals.
• Dioxygen Transport
– respiration uniquely performed by metalloproteins
– hemoglobin/myoglobin (Fe)
• 1Fe : 1 O2
– hemocyanins (Cu) in mollusks and arthropods
• 2Cu : 1 O2
hemerythrin (Fe) in marine invertebrates (e.g. worms)
• 2Fe : 1 O2
– in each, O2 molecule binds to the metal reversibly.
– note: nature uses different metals in different organisms
to carry out identical function.
The solution: Hemoglobin
• Approx tetramer of Mb
• Hemoglobin has four heme (iron-
porphyrin) groups that bind oxygen.
• four heme groups are bound to 4 protein
chains (2 & 2 with 141 & 146 aminio
acids)
• The protein surrounding the hemes plays
important roles.
• Prevents side-reactions like irreversible
heme oxidation
• Enhances selectivity for O2 binding
(relative to CO for example)
• Tetramer allows cooperativity making
hemoglobin efficient.
• Found in red blood cells 150 g Hb/lit of
human blood
Myoglobin Hemoglobin
Porphyrin bound iron: Heme Group
Heme Protiens: Hemoglobin

Hemoglobin (Hb)
N

N Transport O2
Fe
from lung
N
to tissues and transfer O2
N to Mb which store it for
oxdn of food staffs
 Before Oxygen BINDS
O
HISTIDINE
H
HO N
H2N
N
PORPHYRIN

N
N N Fe(II)
Fe
N
Before Oxygen BINDS

92 pm – pseudo-octahedral
Square pyramidal
 Superoxide

HS d6 LS d5

Antiferromagnetically coupled: diamagnetic

 Hemoglobin dynamics
Oxygen binding triggers local conformational changes:

Fig. 5-11

Tensed st Relaxed St
The shift in the iron tugs on the His, which moves helix F