title: Antibiotic resistance: mono- and dinuclear zinc complexes as metallo-beta-lactamase mimics.
abstract: Biomimetic systems containing one or two zinc(II) ions supported by phenolate ligands were developed as functional mimics of metallo-beta-lactamase. These complexes were shown to catalytically hydrolyze beta-lactam substrates, such as oxacillin and penicillin G. The dinuclear zinc complex 1, which has a coordinated water molecule, exhibits high beta-lactamase activity, whereas the dinuclear zinc complex 2, which has no water molecules, but labile chloride ligands, shows a much lower activity. The high beta-lactamase activity of complex 1 can be ascribed to the presence of a zinc-bound water molecule that is activated by being hydrogen bonded to acetate substituents. The kinetics of the hydrolysis of oxacillin by complex 1 and the effect of pH on the reaction rates are reported in detail. In addition, the kinetic parameters obtained for the synthetic analogues are compared with those of the natural metallo-beta-lactamase from Bacillus cereus (BcII). To understand the role of the second metal ion in hydrolysis, the syntheses and catalytic activities of two mononuclear complexes (3 and 4) that include coordinated water molecules are described. Interestingly, the mononuclear zinc complexes 3 and 4 also exhibit high activity, supporting the assumption that the second zinc ion is not crucial for the beta-lactamase activity.
authors.affiliation: Department of Inorganic and Physical Chemistry Indian Institute of Science, Bangalore 560 012, India.
authors.forename: A
authors.initials: A
authors.lastname: Tamilselvi
authors.forename: Munirathinam
authors.initials: M
authors.lastname: Nethaji
authors.forename: G
authors.initials: G
authors.lastname: Mugesh
mesh_terms: D001409:Bacillus cereus / Q000201:enzymology; D040761:Biomimetic Materials; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D006868:Hydrolysis; D062385:Hydroxybenzoates; D009942:Organometallic Compounds; D013379:Substrate Specificity; D015032:Zinc; D001618:beta-Lactamases / Q000737:chemistry / Q000502:physiology*
chemical_list: D062385:Hydroxybenzoates; D009942:Organometallic Compounds; D001618:beta-Lactamases; C017616:phenolic acid; D015032:Zinc