Reactions of pyrazolylborate-zinc-hydroxide complexes related to beta-lactamase activity

Simple beta-lactams and their hydrolysis products, the beta-amino acids, react with TpZn-OH under deprotonation. The latter become semibidentate carboxylate ligands with a NH...O hydrogen bond, and the former become N-bound beta-lactamide ligands. Likewise the antibiotic derivatives 6-aminopenicillanic acid and 7-aminocephalosporanic acid are incorporated as carboxylate ligands. beta-Lactams bearing nitrophenyl or acyl substituents at the nitrogen atoms are opened hydrolytically by TpZn-OH, and the resulting N-substituted beta-amino acids are attached to zinc by their carboxylate functions. Only with trifluoroacetyl as the N-substituent does the hydrolytic cleavage occur at the external amide bond, yielding the free beta-lactam and TpZn-trifluoroacetate. The kinetic investigation of the opening reactions has shown them to be of second order like all other TpZn-OH-induced hydrolytic cleavages, thereby supporting the four-center mechanism for the monozinc beta-lactamases.