Bioinorganic chemistry is a highly interdisciplinary field that studies the roles of metals and metalloids in biological systems. Key points: - 11 elements make up the majority of living organisms by mass, including H, C, N, O, Na, Mg, P, S, Cl, K, and Ca. Metals like Fe, Cu, Zn, Mo, and Mn also play important roles. - Metals are essential for life, serving as enzyme activators, charge carriers that maintain osmotic gradients, and components of oxygen-carrying and electron transfer proteins. However, both deficiency and excess of metals can cause disease. - Transition metals Fe, Cu, and Mo are important for electron

1. Bioinorganic chemistry
Introduction

2. Bioinorganic chemistry as a highly interdisciplinary
research field
Inorganic chemistry
biochemistry
(micro-) biology
physiology physics
pharmacology toxicology
Bioinorganic chemistry

3. Evolution of life essential elements
Earth solidified ~ 4 billion years ago
81 stabile elements
Elements of the living organism:
1. Elements in large scale: 11 elements
H, C, N, O, Na, Mg, P, S, Cl, K, Ca
2. Elements in small scale: 7 elements
Mn, Fe, Co, Cu, Zn, I, Mo
3. Elements of a few species: 7 elements
B, F, Si, V, Cr, Se, Sn

4. bulk eliments
trace eliments
for some species
Periodic Table

5. Effect
Lack of element
(Death)
Deficiency
(Disease)
Optimal supply Excess
(Disease)
Toxic dose
(Death)
Conc
Concentration and physiological
effect

6. Metals

7. Metals essential for life:
 The role for most is uncertain
 Na, K, Mg, Ca
 V, Cr, Mn, Fe Co, Ni, Cu, Zn
 Mo, W

8. General roles of metal ions in biology
Na, K: Charge carriers
Osmotic and electrochemical gradients
Nerve function
Mg, Ca: Enzyme activators
Structure promoters
Lewis acids
Mg2+: chlorophyll, photosynthesis
Ca2+: insoluble phosphates

9. Alkali metals
Terrestrial distribution:
Li Na K Rb Cs Fr
0.060 nm 0.133 nm ionic radii
0.095 nm
Distribution in vivo:
(Li) Na K (Rb)

10. 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- + HPO4
2- + H+

11. 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
polyethers synthetic
cryptands

12. The valinomycin-potassium complex
H D-Val
L
L-Val
H
D-Val
L
L-Val
H
D-Val
L
L-Val
O
O
O
O
O
O
K+

13. The nonactin-potassium complex
O
CH3 O
CH3
H3C
O
CH3
O
CH3
O CH3
O
H3C
O
CH3
O O
O O
K

14. Macrocyclic ligands
O
O
O
O
O
O
N
O O
N
O O
O O
O
O
CH2 CH2 O
CH2 CH2 O
4
4
N
O O
N
O O
O O
M
n+
+ M
n+

15. 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

16. 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
Alkaline Earth Metals

17. Mg
N
H3C
CH
CH2
N
R
CH2 CH3
CH3
N
O
H3COOC
N
H3C
O
O
O
P
O
O
O
O
P
O
O
O
OH OH
O
O
O
R R
M2+
OH
M2+ M2+
O
R
Chlorofill
The mechanism of the phosphate hydrolysis

18. Transition Metals

19. 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

20. Fe(II), Fe(III):
 Essential for ALL organisms
 In plants: iron deficiency
 In human body: 4-5 g
 Uptake: ~ 1 mg/day

21. In human body
75% Hem-iron
 Hemoglobin
 Myoglobin
 Cytochromes
 Oxidases, P-450
25% Non-hem-iron
 Rubredoxins
 Ferredoxins

22. Cu(I), Cu(II)
Plants Electron transfer
Animals 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

23. Superoxide Dismutase
SOD-Cu2+ + O2
.-  SOD-Cu1+ + O2
SOD-Cu1+ + O2
.- + 2H+  SOD-Cu2+ + H2O2

24. Role of Zn2+ :
deficiency:
 disturbances of repr. system
 dwarfism
 skin lesions
 skeletal abnormalities

25. 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
S
S
S
S(N)
S(N)
N
N
N
O
O
C

26. Function of Zn in metalloenzymes
1. Structure-promoter
2. Substrate binder
3. Lewis acid

27. Outlined structure of apoferritin

28. Iron(II)-protoporfirin IX-complex
(HEM)
N
N
HC
N
CH
N
HC CH
H3C CH
CH2
CH3
CH
CH2
CH3
H2C
H2C
H2C
CH2
OOC
COO
H3C
Fe

29. Myoglobin Hemoglobin

30. Catalytic cycle of P-450 enzymes
S
Fe
H2O
III
S
Fe
III
RH
RH
Fe
S
II
S
Fe
O
O
RH
III
S
Fe
O
O
RH
III
S
Fe
O
R H
IV
RH
H2O
e-
3O2
e-
H2O
2 H+
H2O
ROH
+ AO
+ A

31. O
Zn
O
N
HN N
NH
CH2
H2
C
C
N
C
H
H H
C
O
H2
C
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

32. Coordination environment of the
copper centre in azurin

33. Cu
His
His O
L
His
O
Cu
His
His
His
Cu
His
His
His
Cu
His
His
His
I I II II
+ 3
O2
- 3
O2
Reversible
oxygenation of
hemocyanin
Structure of dimetal centre in Cu-Zn superoxide dismutase

34. Fe S
S Fe
S
Fe
S Fe
S Fe
Fe S
Fe
S
Fe S
S
S
S
Mo
S
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 ATP
N2
The supposed reaction mechanism of dinitrogenase

35. Coordination environment of the Cr3+
centre in the glucose tolerance factor
N
Cr
N
L
L L
L
COOH
HOOC