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

The thiolysis mechanism of benzylpenicillin has been determined by H-1 NMR and HPLC. The degradation of benzylpenicillin was accelerated when the thio l used presented a beta -group capable of acting as a general acid catalyst , such as alpha -monothioglycerol, 2-mercaptoethanol and mercaptoethylamine . With these thiols, after the formation of the thioester, an intramolecula r acyl transfer reaction occurs at a pH far below the pK(a) of the group ac ting as a general acid catalyst, which shows that the proton transfer has a lready occurred, probably in a concerted mechanism with the nucleophilic at tack. Rate constants were calculated. The system can be taken as a simple m odel of the general acid catalyst in serine and cysteine proteases. (C) 200 1 Elsevier Science B.V. All rights reserved.