title: Structural studies on tazobactam.
abstract: Tazobactam (3, C10H12N4O5S) is an effective inhibitor of bacterial beta-lactamases. It crystallizes with unit cell dimensions a = 10.230 (2) A, b = 14.396 (2) A, and c = 17.291 (2) A in space group P2(1)2(1)2(1). Compared to the related inhibitor sulbactam (2), which lacks the triazole ring, crystalline tazobactam exhibits very similar beta-lactam geometry and the same S(1) envelope conformation of the thiazolidine ring. However, in both independent molecules of 3 a triazole ring nitrogen atom accepts an intermolecular hydrogen bond; similar interaction by this moiety of 3 with a hydrogen-bond donor on the enzyme, which is impossible for 2, could account for its enhanced inhibitory power. Semiempirical molecular orbital calculations show pronounced negative potential there. Molecular mechanics supports the hypothesis that the carboxyl group can rotate freely and the triazole ring can "flip".
authors.affiliation: Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
authors.forename: C A
authors.initials: CA
authors.lastname: Toomer
authors.forename: C H
authors.initials: CH
authors.lastname: Schwalbe
authors.forename: N S
authors.initials: NS
authors.lastname: Ringan
authors.forename: P A
authors.initials: PA
authors.lastname: Lambert
authors.forename: P R
authors.initials: PR
authors.lastname: Lowe
authors.forename: V J
authors.initials: VJ
authors.lastname: Lee
mesh_terms: D003198:Computer Simulation; D008956:Models, Chemical; D008968:Molecular Conformation; D010397:Penicillanic Acid / Q000737:chemistry* / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
chemical_list: D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam