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Bioinorganic chemistry
Or How “Organic” is Inorganic?
Evolution of life essential elements
Earth solidified ~ 4 billion years ago
81 stable elements
Elements of the living organism:
1. Elements with large concentration: 11 elementsH, C, N, O, Na, Mg, P, S, Cl, K, Ca
2. Elements with small concentration : 7 elementsMn, Fe, Co, Cu, Zn, I, Mo
3. Elements of a few species: 7 elementsB, F, Si, V, Cr, Se, Sn
bulk elements
trace elements
some species
Periodic Table
Effect
Lack of element(Death)
Deficiency(Disease)
Optimal supply Excess (Disease)
Toxic dose(Death)
Conc
Concentration and physiological effect
Metals
Metals essential for life:
The role for most is uncertain
Na, K, Mg, Ca
V, Cr, Mn, Fe Co, Ni, Cu, Zn
Mo, W
Metal content of a human body (70 kg)
Metal content of a human body (70 kg)
Functions of “inorganic elements”–– summary
General roles of metal ions in biology
Na, K:Charge carriersOsmotic and electrochemical
gradientsNerve function
Mg, Ca: Enzyme activatorsStructure promotersLewis acidsMg2+: chlorophyll,
photosynthesisCa2+: insoluble phosphates
Alkali metals
Terrestrial distribution:
Li Na K Rb Cs Fr0.060 nm 0.133 nm ionic radii
0.095 nm
Distribution in vivo:(Li) Na K (Rb)
Role: Na+
• Extracellular fluid• Osmotic balance „sodium pump”• Acid-base balance• Conformation of proteins
nucleic acids• Electrical impulse of nerve system
Mg2+
3Na+ic + 2K+
ec + ATP4- + H2O 3Na+ec + 2K+
ic + ADP3- + HPO42- + H+
K+
• Enzyme activator • Conformation of proteins
RNA (replication)
• Secretion of gastric acid• Transmembrane potentials!
Complexes of alkali metals (Na+, K+)
Cyclic antibiotics: Valinomycin Monactin Nonactin
polyetherscryptands
synthetic
The valinomycin-potassium complex
H D-Val
L
L-Val
H
D-Val
LL-Val
H
D-Val
L
L-Val
O
O
O
O
O
OK+
The nonactin-potassium complex
O
CH3 O
CH3
H3C
O
CH3
O
CH3
O CH3
O
H3C
O
CH3
O O
O O
K
Macrocyclic ligands
O
O
O
OO
O
N
O O
N
O O
O O
O
O
CH2 CH2 O
CH2 CH2 O4
4
N
O O
N
O O
O OM
n+
+ M
n+
Alkaline Earth Metals
Terrestrial distribution:Be Mg Ca Sr Ba Ra
Distribution in vivo:Mg Ca
Be, Ba TOXIC!
Sr (not particularly toxic)90Sr accumulates in bones
Alkaline Earth Metals
Mg2+
• Plants chlorosis CHLOROPHYLL
• nervous system (tetany)• active transport (intracellular)• enzyme activator (e.g. ATP-ase)• Ca2+ antagonist
Ca2+
Inhibits Mg2+-activated enzymes Extracellular: clotting (10-3M)
Ca2+
prothrombin thrombin-fibrinogen-fibrin
Mg
NH3C
CHCH2
N
R
CH2 CH3
CH3
N
OH3COOC
N
H3C
O
O
O
P
OO
OOP
O
O
O
OH OH
OO
O
R R
M2+
OH
M2+ M2+
O
R
Chlorophyll
The mechanism of the phosphate hydrolysis
Proteins - LigandsProteins - Ligands
Transition MetalsTransition Metals
Other metal ions: less well defined and more obscure roles
Zn: Metalloenzymes
Structure promoters
Lewis acid
Not a redox catalyst!
Fe, Cu, Mo: Electron-transfer
Redox proteins and enzymes
Oxygen carrying proteins
Nitrogen fixation
Fe(II), Fe(III):
• Essential for ALL organisms
• In plants: iron deficiency
• In human body: 4-5 g
• Uptake: ~ 1 mg/day
In human body
75% Hem-iron
Hemoglobin Myoglobin Cytochromes Oxidases, P-450
25% Non-hem-iron
Rubredoxins Ferredoxins
Cu(I), Cu(II)
Plants Electron transferAnimals O2-carrying
Protection of DNA
from O2-
Cu-proteins and enzymes
Cytochrome oxidase O2 H2O
Tyrosinase, phenol oxidase ox. of phenols
Ceruloplasmin Fe(II) Fe(III)
Blue proteins Electron transfer
Superoxide dismutase Elimination of O2-
Hemocyanin O2 transport
Superoxide Dismutase
SOD-Cu2+ + O2.- SOD-Cu1+ + O2
SOD-Cu1+ + O2.- + 2H+ SOD-Cu2+ + H2O2
Role of Zn2+ :
deficiency:
• disturbances of repr. system
• dwarfism
• skin lesions
• skeletal abnormalities
Zn – metalloenzymes: 80!Zn activated enzymes: 20!
(Cys – X – Cys)7
x=nonaromatic amino acid
Zn Zn Zn
(H2O)(1-2) (H2O)(1-2)
S
SS
SS(N)S(N)
N
N
N
O
O
C
Function of Zn in metalloenzymes
1. Structure-promoter
2. Substrate binder
3. Lewis acid
Outlined structure of apoferritin
Iron(II)-protoporfirin IX-complex (HEM)
N
NHC
N
CH
NHC CH
H3C CH
CH2
CH3
CH
CH2
CH3H2C
H2C
H2C
CH2
OOC
COO
H3C
Fe
Myoglobin Hemoglobin
Catalytic cycle of P-450 enzymesS
Fe
H2O
III
S
FeIII
RH
RH
Fe
S
II
S
Fe
O
ORH
III
S
Fe
O
ORH
III
S
Fe
O
R H
IV
RHH2O
e-
3O2e-
H2O
2 H+
H2OROH
+ AO
+ A
O
Zn
O
NHN N
NH
CH2
H2C
CNC
HH H
C
O
H2C
CH2
His-69
Glu-72
His-196
Zink(II) in the active centre of
carboxipeptidase-A
O Zn
S
S
N
C
CH3
H
H
(Cys)
(His)
(Cys)
The active centre of the alcohol
dehydrogenase
Coordination environment of the copper centre in azurin
Cu
His
His O
L
HisO
Cu
His
His
His
Cu
His
His
His
Cu
His
His
His
I I II II
+ 3O2
- 3O2
Reversible oxygenation of hemocyanin
Structure of dimetal center in Cu-Zn superoxide dismutase
A tour of hemocyanin
Fe S
S Fe
SFe
S Fe
S Fe
Fe S
FeS
Fe SS
S
S
MoS
Supposed structure of Fe-S-Mo cofactor of nitrogenase
3 NADH + 3H+
3 NAD+
3 Ferredoxin(oxidized)
3 Ferredoxin(reduced)
Fe protein(reduced)
Fe protein(oxidized)
Fe protein(oxidized)
Fe protein(reduced)
12 ATP
12 ATP
12 ADP + 12 Pi
Fe-Mo protein(oxidized)
Fe-Mo protein(reduced)
Fe-Mo protein(oxidized)
N2
2 NH3
6 H+
12 ATPN2
The supposed reaction mechanism of dinitrogenase
Coordination environment of the Cr3+
center in the glucose tolerance factor
N
Cr
N
L
L L
L
COOH
HOOC
Approx. 30 µgRequired daily
