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.