The role of a beta-proton transfer donor in the degradation of benzylpenicillin

Abstract

[eng] The thiolysis mechanism of benzylpenicillin has been determined by 1H NMR and HPLC. The degradation of benzylpenicillin was accelerated when the thiol used presented a -group capable of acting as a general acid catalyst, such as -monothioglycerol, 2-mercaptoethanol and mercaptoethylamine. With these thiols, after the formation of the thioester, an intramolecular acyl transfer reaction occurs at a pH far below the pKa of the group acting as a general acid catalyst, which shows that the proton transfer has already occurred, probably in a concerted mechanism with the nucleophilic attack. Rate constants were calculated. The system can be taken as a simple model of the general acid catalyst in serine and cysteine proteases.