Transition Metals Transition Metals

bulk elements trace elements for some species Periodic Table

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

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

Biochemical Reactivity Promotion of Appropriate Geometry Change acid/base character Change Redox potentials Change ionic concentration Formation of Unique species Formation of structural materials Activation of small molecules (NO)

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

Porphyrins Fe Fe  Oxygen Transport Hemoglobin  4 Fe containing globin units (2-alpha and 2-beta)  K increases with each O 2 added  Fe(II) does not oxidize to Fe(III)  Non-aqueous or simultaneous Oxygen to two hemes.  Oxygen Storage Myoglobin  1 heme group

Porphyrin

Hemoglobin

Fe

Iron Environment in Myoglobin

Cytochromes, Peroxidases, and Catalases Cytochrome P-450 Cytochrome P-450  Oxidation catalyst Peroxidases/Catalases Peroxidases/Catalases  Decomposition of organic peroxides.

Electron Transfer Chains

Other Fe Compounds Ferritin / Transferrin Ferritin / Transferrin  Iron storage in spleen, liver and marrow.  Mw  445,000 (4,300 Fe atoms)

bulk elements trace elements for some species Periodic Table

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

Oxygen hemocyanin mollusks and arthropods

1. Wilson’s disease: Hereditary disfunction of ceruloplasmin Cu 2+ accumulates in liver, brain: dementia, liver failure Administration: Cu-specific chelate 2. Menke’s „kinky hair” syndrome: Hereditary disfunction of intracellular copper transport Copper deficiency symptoms: disturbances in the mental and physical development Therapy: intravenously administered copper compounds 3. Acute copper deficiency Insufficient oxygen utilization in brain 4. Mutations in the copper dependent superoxide dismutase Copper-related Pathological Disorders

Ni(II) Ni-containing enzymes of bacteria Urease(Vesicle) CO-dehydrogenase Hydrogenases Membranes

Mo HPO 4 2- Uptake :MoO42- SO 4 2- Molybdenium enzymes NitrogenaseN 2  NH 3 Aldehyde oxidases-CHO  -COOH Nitrate reductaseNO 3 -  NO 2 - Sulfide oxidaseSO 3 2-  SO 4 2- Xanthin oxidasepurin catabolism Formate dehydrogenaseH-COO -  CO 2

Platinum Complexes in Cancer Therapy

NH 3 Cl Pt Cis-dichlorodiammineplatinum (II) Blocking cell division NH 3 Cl Pt Trans-dichlorodiammineplatinum (II) inactive Cis-tetrachlorodiammineplatinum (IV) biologically active NH 3 Cl Pt Cl Trans-tetrachlorodiammineplatinum (IV) inactive NH 3 Cl Pt Cl

N N HN NH 2 N N N Pt NH 3 Cisplatin NH 3 Cl Pt Platinum Complexes in Cancer Therapy

a b NH 3 Pt NH 3 Protein Platinum Complexes in Cancer Therapy

Injection Blood Toxic side effectCytostatic effect Plasma proteinsBlood stream KidneyTumor cells Other organs Liver Excretion

Activity of Pt(NH 3 ) 2 X2 complexes XActivity NO 3 - toxic H2OH2O Cl - antitumor Br - antitumor I-I- inactive SCN - inactive NO 2 - inactive CN - inactive (X = ligand)

a Pt-chelate complex (considerable antitumor activity)