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

Simple beta-lactams and their hydrolysis products, the P-amino acids, react with Tp(*)Zn-OH under deprotonation. The latter become semibidentate carboxylate ligands with a (NHO)-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 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 -lactamases.