Unless otherwise stated, all images in this file have been reproduced from:

1. Unless otherwise stated, all images in this file have been reproduced from: Blackman, Bottle, Schmid, Mocerino and Wille,Chemistry, 2007 (John Wiley)     ISBN: 9 78047081 0866

2. CHEM1002 [Part 3] Dr Michela Simone Lecturer BSc (I Hons), MSc, D.Phil. (Oxon), MRSC, MRACI Weeks 8 – 13 Office Hours: Monday 3-5, Friday 4-5 Room: 412A (or 416) Phone: 93512830 e-mail:michela.simone@sydney.edu.au

3. Summary of Last Lecture • Complexes III • Transition metal atoms of the first transition series have electron configuration [Ar]4sx3dy where x + y is the group number • For the cations, the electronic configuration is [Ar]3dz where z = group number – oxidation number • These electrons occupy the ten d-orbitals and, if this leads to unpaired electrons, the complex is paramagnetic • Complexes in which the 3dorbitals are not empty, half full or full are coloured due to excitations of the electrons

4. Complexes IV • Lecture 15 • Metals in Biological Processes • Essential Elements • Toxic Elements • Medicinal Uses • Blackman Chapter 13 • Lecture 16 • Chemical Kinetics • Rate of Reaction • Rate Laws • Reaction Order • Blackman Chapter 14, Sections 14.1 - 14.3

5. The Biological Periodic Table essential medicinal archaea toxic

6. Metal ions in biology fall into three groups: Essential elements e.g.Na+, K+, Mg2+, Ca2+, Fe2+/3+, Cu+/2+, Zn2+ Toxic elements e.g.Pb2+, Hg2+, Be2+ Elements used in medicine e.g.Li+, Pt2+ Metal Ions in Biology

7. Essential Elements

8. Essential Elements - Na+ and K+ • Maintaining the Na+ and K+ concentrations requires a pumpingsystem and a lot of energy (ATPase) Outer membrane Na+, K+ pump Inner membrane (inside of the cell)

9. Iron – Oxygen Transport/Storage • Square planar coordination of Fe by porphyrin ligand • Oxygen binds reversibly to the free coordination site of Fe

10. O2 Transport Complexes • In humans, transport system (haemoglobin) and storage system (myoglobin) are both Fe(II) complexes: myoglobin haemoglobin affinity of myoglobin > affinity of haemoglobin affinity of haemoglobin increases as O2 pressure grows – cooperative effect muscle lungs

11. Haemoglobin and Myoglobin - Structures • Haemoglobin consists of 4 haem groups, myoglobin consists of 1 haem group: distal histidine residue proximal histidine residue

12. Haemoglobin and Myoglobin - Function weak H-bond? enforcedbending distal histidine residue distal histidine residue proximal histidine residue proximal histidine residue partial prevention of (irreversible) CO attachment

13. Haemoglobin – Cooperative Effect • Unoxygenated protein contain Fe(II) d6: • Ion has is too large to fit in haemring and actually sits slightly below it • Oxygenated protein contains smallerFe(III) d5 which fits into ring • The motion of the proximal group is transferred through protein structure to the next deoxygenated haem group decreasing its activation energy for O2 attachment proximal histidine residue

14. Carbonic Anhydrase • Zn2+-OH2 is acidic: • N3Zn-OH2 N3Zn-OH + H+ • Metal is bonded to "OH-" which is a good nucleophile • Binds CO2 reversibly for transfer from muscles to lungs • CO2 + OH- CO32-

15. Essential Trace Element Trace and Toxic Elements • Lack or shortage of a trace element is damaging to health, as is an excess. • Low concentrations of toxic metals may be tolerated but at even moderate concentrations they damage health.

16. Ca5(PO4)3(OH)(s) Lead in the Body • Pb2+ has approximately the same size and charge as Ca2+ - it can substitute for Ca in biological systems especially bone and teeth. • Many poisons act due to have the same size/charge ratio as an essential molecule/ion PbCa4(PO4)3(OH)(s) remove as [Pb(EDTA)]2-

17. Pt Anti-Cancer Drugs

18. Two mice with solid Sarcoma-180 tumors Untreated died day 21 tumor 3 g. Bottom mouse treated with cis-[PtCl2(NH3)2] on day 8. Tumor completely regressed by day 14. Died of old age 3 years later.

19. Pt Anti-Cancer Drugs • All Pt(II) complexes are square planar • trans-diamminedichloroplatinum • inactive • cis-diamminedichloroplatinum • very active

20. Pt Anti-Cancer Drugs • cis-Pt(NH3)2 bonds to two N-bases in the DNA • causes DNa helix to "kink" preventing it from replicating • trans-Pt(NH3)2 cannot bind to DNA

21. Summary: Biological Periodic Table • Learning Outcomes - you should now be able to: • Identify essential, toxic and medicinal elements • Explain functioning of metals in body • Relate medicinal uses to function of element • Think about consequences for drug design (for example: why cis-PtCl2(NH3)2 is active but trans form is not) • Next lecture: • Reaction kinetics

22. Practice Examples Hemochromatosis or “iron overload” is a potentially fatal disorder in which excess iron is deposited in the bodily organs as insoluble hydrated iron(III) oxide. It can be treated by administration of desferioxamine B (Desferal), a natural substance isolated from fungi. Desferal Desferal is taken over 8-12 hour periods up to six times per week.A value of logK = 30.6 is associated with the following equilibrium: Fe3+ + LH3+FeL+ + 3H+ where LH3+ = Desferal Briefly describe the chemical basis for the use of Desferal in iron overload therapy.

23. Practice Examples en = ethylenediamine = NH2CH2CH2NH2