Metallocarbonyl complexes of bromo‐ and dibromomaleimide: synthesis and biochemical application

Abstract

Bromomaleimides react with cysteine residues to form thiomaleimides that can be further cleaved with TCEP (tris(2‐carboxyethyl)phosphine) to regenerate the cysteine derivatives. Herein we report the preparation of new organometallic Fe complexes containing monobromo and dibromo maleimide ligands. Both of these complexes were characterised by X‐ray diffraction. Organometallic bromomaleimide derivatives were reacted with the thiol‐containing biomolecules: cysteine ethyl ester hydrochloride, glutathione and papain. These cysteine‐containing molecules underwent a substitution reaction with metallocarbonyl bromo‐ or dibromo maleimide complexes, followed by an addition reaction to the thio‐maleimide double bond if thiol was added in excess. The metallocarbonyl mono‐bromomaleimide complex was shown to inhibit the peptidase activity of the enzyme papain. The resulting papain–maleimide product could be cleaved by addition of TCEP to regenerate the catalytically active enzyme. Copyright © 2012 John Wiley & Sons, Ltd.