Reactions of Pyrazolylborate-Zinc-Hydroxide Complexes Related to (beta)-Lactamase Activity

Simple (beta)-lactams and their hydrolysis products, the (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 Tp*Zn-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 Tp*Zn-trifluoroacetate. The kinetic investigation of the opening reactions has shown them to be of second order like all other Tp*Zn-OH-induced hydrolytic cleavages, thereby supporting the four-center mechanism for the monozinc (beta)-lactamases.