Transition Metals

1. Transition Metals

2. Periodic Table bulk elements for some species trace elements

3. 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

4. Other metal ions: less well defined and more obscure roles Fe, Cu, Mo:Electron-transfer Redox proteins and enzymes Oxygen carrying proteins Nitrogen fixation Zn:Metalloenzymes Structure promoters Lewis acid Not a redox catalyst!

5. 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)

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

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

9. Porphyrins • Fe • Oxygen Transport • Hemoglobin • 4 Fe containing globin units (2-alpha and 2-beta) • K increases with each O2 added • Fe(II) does not oxidize to Fe(III) • Non-aqueous or simultaneous Oxygen to two hemes. • Oxygen Storage • Myoglobin • 1 heme group

10. Porphyrin

11. Hemoglobin

12. Fe

13. Iron Environment in Myoglobin

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

15. Electron Transfer Chains

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

17. Periodic Table bulk elements for some species trace elements

18. Protection of DNA from O2- Cu(I), Cu(II) Plants Electron transfer Animals O2-carrying 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

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

20. Oxygen hemocyaninmollusks and arthropods

21. Copper-related Pathological Disorders 1. Wilson’s disease: Hereditary disfunction of ceruloplasmin Cu2+ 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

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

23. Mo HPO42- Uptake : MoO42- SO42- Molybdenium enzymes • Nitrogenase N2 NH3 • Aldehyde oxidases -CHO  -COOH • Nitrate reductase NO3-  NO2- • Sulfide oxidase SO32-  SO42- • Xanthin oxidase purin catabolism • Formate dehydrogenase H-COO-  CO2

24. Platinum Complexes in Cancer Therapy

25. NH3 Cl Cl NH3 Pt Pt Cl Cl NH3 NH3 Cis-dichlorodiammineplatinum (II) Trans-dichlorodiammineplatinum (II) inactive Blocking cell division Cl Cl Cl NH3 Cl NH3 Pt Pt NH3 Cl NH3 Cl Cl Cl Trans-tetrachlorodiammineplatinum (IV) Cis-tetrachlorodiammineplatinum (IV) inactive biologically active

26. NH3 Cl Pt NH3 NH3 Cl NH3 Pt Cisplatin N N HN N N N NH2 Platinum Complexes in Cancer Therapy

27. Protein Pt NH3 NH3 Pt NH3 NH3 Platinum Complexes in Cancer Therapy b a

28. Injection Blood Toxic side effect Cytostatic effect Plasma proteins Blood stream Other organs Kidney Tumor cells Liver Excretion

29. Activity of Pt(NH3)2X2 complexes (X = ligand)

30. a Pt-chelate complex (considerable antitumor activity)