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.
Gross
Florian
F
Institut für Anorganische und Analytische Chemie der Universität Freiburg, Albertstrasse 21, D-79104 Freiburg, Germany.
Vahrenkamp
Heinrich
H
D000596:Amino Acids / Q000737:chemistry; D001881:Borates / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry
D000596:Amino Acids; D001881:Borates; D009942:Organometallic Compounds; D011720:Pyrazoles; D047090:beta-Lactams; D001618:beta-Lactamases; D015032:Zinc