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 elements H, C, N, O, Na, Mg, P, S, Cl, K, Ca 2.Elements with small concentration : 7 elements Mn, Fe, Co, Cu, Zn, I, Mo 3.Elements of a few species: 7 elements B, F, Si, V, Cr, Se, Sn

bulk elements trace elements some species Periodic Table

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: Na, K:Charge carriers Osmotic and electrochemical gradients Nerve function Mg, Ca: Mg, Ca:Enzyme activators Structure promoters Lewis acids Mg 2+ : chlorophyll, photosynthesis Ca 2+ : insoluble phosphates

Alkali metals Terrestrial distribution: LiNaKRbCsFr nm0.133 nmionic radii nm Distribution in vivo: (Li)NaK(Rb)

Na + Role: Na + Extracellular fluid Osmotic balance „sodium pump” Acid-base balance Conformation of proteins nucleic acids Electrical impulse of nerve system Mg 2+ 3Na + ic + 2K + ec + ATP 4- + H 2 O 3Na + ec + 2K + ic + ADP 3- + HPO H +

K+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 cryptands synthetic

The valinomycin-potassium complex

The nonactin-potassium complex

Macrocyclic ligands

Alkaline Earth Metals Terrestrial distribution: Be MgCaSrBaRa Distribution in vivo: MgCa Be, Ba TOXIC! Sr (not particularly toxic) 90 Sr accumulates in bones

Alkaline Earth Metals Mg 2+ Plants chlorosis CHLOROPHYLL nervous system (tetany) active transport (intracellular) enzyme activator (e.g. ATP-ase) Ca 2+ antagonist Ca 2+ Inhibits Mg 2+- activated enzymes Extracellular: clotting (10 -3 M) Ca 2+ prothrombin thrombin-fibrinogen-fibrin

Chlorophyll The mechanism of the phosphate hydrolysis

Proteins - Ligands Proteins - Ligands

Transition Metals Transition Metals

Other metal ions: less well defined and more obscure roles Zn: Zn: Metalloenzymes Structure promoters Lewis acid Not a redox catalyst! Fe, Cu, Mo: 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 % Non-hem-iron Rubredoxins Ferredoxins

Cu(I), Cu(II) Plants Electron transfer Animals O 2 -carrying Protection of DNA from O 2 - Cu-proteins and enzymes Cytochrome oxidaseO 2 H 2 O Tyrosinase, phenol oxidaseox. of phenols CeruloplasminFe(II) Fe(III) Blue proteinsElectron transfer Superoxide dismutaseElimination of O 2 - HemocyaninO 2 transport

Superoxide Dismutase SOD-Cu 2+ + O 2.-  SOD-Cu 1+ + O 2 SOD-Cu 1+ + O H +  SOD-Cu 2+ + H 2 O 2

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

Zn – metalloenzymes: 80! Zn – metalloenzymes: 80! Zn activated enzymes: 20! (Cys – X – Cys) 7 x=nonaromatic amino acid Zn (H 2 O) (1-2) S S S SS(N) N N N O O C

Function of Zn in metalloenzymes 1.S tructure-promoter 2.S ubstrate binder 3.L ewis acid

Outlined structure of apoferritin

Iron(II)-protoporfirin IX-complex (HEM)

MyoglobinHemoglobin

Catalytic cycle of P-450 enzymes RH H2OH2O e-e- 3O23O2 e-e- H2OH2O 2 H + H2OH2O ROH + AO + A

Zink(II) in the active centre of carboxipeptidase-A The active centre of the alcohol dehydrogenase

Coordination environment of the copper centre in azurin

Reversible oxygenation of hemocyanin Structure of dimetal center in Cu-Zn superoxide dismutase A tour of hemocyanin

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 ADP + 12 P i Fe-Mo protein (oxidized) Fe-Mo protein (reduced) Fe-Mo protein (oxidized) N2N2 2 NH 3 6 H + 12 ATP N2N2 The supposed reaction mechanism of dinitrogenase

Coordination environment of the Cr 3+ center in the glucose tolerance factor Approx. 30 µg Required daily