Virtual Free Radical School Iron Chelation in Biology

Virtual Free Radical School Iron Chelation in Biology Alvin L. Crumbliss Department of Chemistry Duke University Box 90346 Durham, NC 27708 -0346 Telephone: (919) 660 -1540 Fax: (919) 660 -1605 E-mail: alvin. crumbliss@duke. edu Website: http: //www. chem. duke. edu/%7 Ealc/labgroup/ Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 1

Iron Chelation in Biology Tutorial Guide Introduction: Biological Iron Coordination Chemistry Panels 3, 4 & 5 Chelation and Solubility Chelation and Redox Potential Panel 6 Panel 7 Common Iron Ligands in Biology Chelate Stability Definitions Panel 8 Panel 9 Chelation and Redox Control Oxidation State Influence on Chelate Stability Panels 10, 11 & 12 Panel 13 Iron Chelation and Transport Panels 14, 15 &16 Influence of p. H on Chelate Stability Panel 17 Influence of Chelate Stability on E 0 Influence of Chelation on Kinetics Panel 18 Panel 19 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 2

Introduction: Biological Iron Coordination Chemistry Common oxidation states: +2, +3 3 Common coordination numbers: 4, 5, 6 Iron in Biology 1 st coordination shell; immediate chemical environment Society For Free Radical Biology and Medicine Crumbliss 3 References [1, 2]

Introduction: Biological Iron Coordination Chemistry 4 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 4 References [1, 2]

Introduction: Biological Iron Coordination Chemistry The first coordination shell Prevents hydrolysis/precipitation Influences molecular recognition Controls redox potential Controls mobility 5 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 5

Iron Chelation and Solubility Fe insoluble due to hydrolysis Strong chelators prevent hydrolysis and precipitation 6 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 6

Iron Chelation and Redox Potential Fe(III/II) redox potential varies significantly with ligands in 1 st coordination shell e. g. Desferal 7 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 7

Common Iron Ligands in Biology (II) (I) (IV) (VIII) 8 (IX) Iron in Biology (VI) (V) Society For Free Radical Biology and Medicine (VII) Crumbliss 8

Iron Chelate Stability Definitions 9 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss References 9[3, 4, 5, 6]

Iron Chelation and Redox Control Why is it important? 10 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 10 Reference [6]

Iron Chelation and Redox Control Why is it important? 11 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 11 [6] Reference

Iron Chelation and Redox Control Why control E 0? 12 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 12 Reference [6]

Oxidation State Influence on Chelate Stability Thermodynamics Kinetics Fe(OH 2)63+ + *OH 2 +e - Iron in Biology Fe(OH 2)5(*OH 2)3+ + OH 2 -e- Fe(OH 2)62+ 13 t 1/2 = 4 ms + *OH 2 t 1/2 = 0. 2 s Society For Free Radical Biology and Medicine Fe(OH 2)5(*OH 2)2+ + OH 2 Crumbliss 13 References [7, 8, 9, 10, 11]

Iron Chelation and Transport 14 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 14 Reference [7]

Iron Chelation and Transport 15 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 15 References [4, 5, 6]

Iron Chelation and Transport desferrioxamine B Fe(III)-enterobactin complex 110 = 1049 ; p. Fe = 35. 5 enterobactin 16 Iron in Biology ferrioxamine B complex 110 = 1030. 2 ; p. Fe 16 = 26. 6 Society For Free Radical Biology and Medicine Crumbliss References [4, 5, 6]

Influence of p. H on Fe(III)-Chelate Stability (I) (II) 17 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 17 [9, 12] Reference

Influence of Fe(III)-Chelate Stability on E 0 18 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss References 18 [6, 10, 13, 14]

Influence of Fe(III)-Chelation on Kinetics k 1 = 1. 8 M-1 s-1 k 2 = 8. 1 x 102 M-1 s-1 19 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 19 [5, 15] Reference

References 20 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 20

References Acknowledgements 21 Iron in Biology Society For Free Radical Biology and Medicine Crumbliss 21