CHED 623

Synthesis and characterization of iron complexes as potential enzyme inhibitors

Stephen U. Dunham and Jason T. Gatlin. Chemistry, Colby College, 5763 Mayflower Hill, Waterville, ME 04901-8857, fax: 207-872-3804,

A wide range of drugs work via binding to and inhibiting enzymes. Methods for design and synthesis of these drugs include rational drug design of known inhibitors, high throughput screening of molecular libraries, and combinatorial synthesis of new molecules.

An alternative approach to increased chemical diversity could be obtained by taking advantage of the unique orientation of ligands around metal ions. In order to use this approach, one part of a ligand must bind to the metal ion, while the other part of a ligand interacts with the enzyme. Additional diversity could be obtained by synthetic modifications of functional groups that interact with the enzyme. Reactions of Fe(III) with various substituted catechols and salicylates have been followed by UV/Visible spectroscopy and HPLC. Iron complexes have been assayed for activity by inhibition of enzymes with chromogenic substrates.