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. Slide 2/23 e CHEM1002 [Part 2] A/Prof Adam Bridgeman (Series 1) Dr Feike Dijkstra (Series 2) Weeks 8 – 13 Office Hours: Monday 2-3, Friday 1-2 Room: 543a e-mail: adam.bridgeman@sydney.edu.au e-mail: feike.dijkstra@sydney.edu.au

3. Slide 3/23 e Complexes III Transition metal atoms of the first transition series have electron configuration [Ar]4s x 3d y where x + y is the group number For the cations, the electronic configuration is [Ar]3d z 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 3d orbitals are not empty, half full or full are coloured due to excitations of the electrons Summary of Last Lecture

4. Slide 4/23 e 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 Complexes IV

5. Slide 5/23 e The Biological Periodic Table essential toxic archaeamedicinal

6. Slide 6/23 e Metal Ions in Biology Metal ions in biology fall into three groups:  Essential elements e.g. Na +, K +, Mg 2+, Ca 2+, Fe 2+/3+, Cu +/2+, Zn 2+  Toxic elements e.g. Pb 2+, Hg 2+, Be 2+  Elements used in medicine e.g. Li +, Pt 2+

7. Slide 7/23 e Na + K+K+ Mg 2+ Ca 2+ Ionic radius, Å1.161.520.861.14 Charge/radius ratio0.860.662.321.75 Coordination number66-86 Preferred donorsOON,OO Concentration (mmol/kg) Intracellular11922.50.1 Extracellular15251.52.5 Seawater460105210 Essential Elements

8. Slide 8/23 e Essential Elements - Na + and K + Na +, K + pump Outer membrane Inner membrane (inside of the cell) Maintaining the Na + and K + concentrations requires a pumping system and a lot of energy (ATPase)

9. Slide 9/23 e Iron – Oxygen Transport/Storage Oxygen binds reversibly to the free coordination site of Fe Square planar coordination of Fe by porphyrin ligand

10. Slide 10/23 e O 2 Transport Complexes In humans, transport system (haemoglobin) and storage system (myoglobin) are both Fe(II) complexes: myoglobin haemoglobin muscle lungs affinity of myoglobin > affinity of haemoglobin affinity of haemoglobin increases as O 2 pressure grows – cooperative effect

11. Slide 11/23 e Haemoglobin and Myoglobin - Structures Haemoglobin consists of 4 haem groups, myoglobin consists of 1 haem group: proximal histidine residue distal histidine residue

12. Slide 12/23 e Haemoglobin and Myoglobin - Function proximal histidine residue distal histidine residue weak H- bond? proximal histidine residue distal histidine residue enforced bending partial prevention of (irreversible) CO attachment

13. Slide 13/23 e Unoxygenated protein contain Fe(II) d 6 : Ion has is too large to fit in haem ring and actually sits slightly below it Oxygenated protein contains smaller Fe(III) d 5 which fits into ring Haemoglobin – Cooperative Effect proximal histidine residue The motion of the proximal group is transferred through protein structure to the next deoxygenated haem group decreasing its activation energy for O 2 attachment

14. Slide 14/23 e Carbonic Anhydrase Zn 2+ -OH 2 is acidic:  N 3 Zn-OH 2 N 3 Zn-OH + H + Metal is bonded to "OH - " which is a good nucleophile Binds CO 2 reversibly for transfer from muscles to lungs  CO 2 + OH - CO 3 2-

15. Slide 15/23 e Trace and Toxic Elements Essential Trace Element 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. Slide 16/23 e Ca 5 (PO 4 ) 3 (OH)(s) Pb 2+ has approximately the same size and charge as Ca 2+ - 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 remove as [Pb(EDTA)] 2- Lead in the Body PbCa 4 (PO 4 ) 3 (OH)(s)

17. Slide 17/23 e Pt Anti-Cancer Drugs

18. Slide 18/23 e Two mice with solid Sarcoma-180 tumors Untreated died day 21 tumor 3 g. Bottom mouse treated with cis-[PtCl 2 (NH 3 ) 2 ] on day 8. Tumor completely regressed by day 14. Died of old age 3 years later.

19. Slide 19/23 e Pt Anti-Cancer Drugs  cis-diamminedichloroplatinum  very active All Pt(II) complexes are square planar  trans-diamminedichloroplatinum  inactive

20. Slide 20/23 e Pt Anti-Cancer Drugs cis-Pt(NH 3 ) 2 bonds to two N-bases in the DNA causes DNa helix to "kink" preventing it from replicating trans-Pt(NH 3 ) 2 cannot bind to DNA

21. Slide 21/23 e 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-PtCl 2 (NH 3 ) 2 is active but trans form is not) Next lecture: Reaction kinetics

22. x 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: Fe 3+ + LH 3 + FeL + + 3H+ where LH 3 + = Desferal Practice Examples Desferal  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. Briefly describe the chemical basis for the use of Desferal in iron overload therapy.

23. Slide 23/23 x Practice Examples  Compounds of d-block elements are frequently paramagnetic. Using the box notation to represent atomic orbitals, account for this property in compounds of Ni 2+.  Complete the following table. FormulaO.N.CN3dn3dn Species in water K 3 [FeF 6 ] [Cr(NH 3 ) 5 (OH 2 )]Cl 3 [Zn(en)Cl 2 ] en = ethylenediamine = NH 2 CH 2 CH 2 NH 2