Biomimetic Models for Cysteine Proteases. 1. Intramolecular Imidazole Catalysis of Thiol Ester Solvolysis: A Model for the Deacylation Step

Article abstract of DOI:10.1021/ja00307a043

The solvolysis of 2-<2-(acetylthio)phenyl>-4,5-dimethylimidazole (3) has been studied in ethanol-water solution as a model for the thiol ester intermediates occurring during the catalytic cycle of cysteine proteases.Additionally the solvolyses of N-acetyl-4,5-dimethyl-2-phenylimidazole (4) and benzenethiolacetate (5) were studied as reference compounds.At neutrality, a plateau in the pH-log k_obsdprofile for solvolysis of 3 is seen due to the participation of imidazole.Evidence is given that the mechanism in this region is intramolecular general-base-catalyzed solvent attack on the thiol ester by imidazole.At pHs greater than 10, specific-base-catalyzed solvolysis of the thiol ester becomes predominant.There is no kinetic importance of an S-to-N acyl transfer during the course of solvolysis.The relevance of these results to the chemical mechanism of cysteine proteases is discussed.