Zinc complexes with 1,2,4-triazole functionalized amino acid derivatives: Synthesis, structure and beta-lactamase assay

Naik, Anil Damadar [UCL] Beck, Josephine [UCL] Dirtu, Marinela Maria [UCL] Bebrone, Carine [Univ Liege] Tinant, Bernard [UCL] Robeyns, Koen [UCL] Marchand-Brynaert, Jacqueline [UCL] Garcia, Yann [UCL]

Coordinating abilities of 4R-1,2,4-triazole derivatives (R = glycine ethyl ester (L1), glycine (L2), diethylamino malonate (L3), methionine (L4) and diethyl aminomethylphosphonate (L5)) towards Zn-II ions have been studied in solution, in solid state and versus three zinc-beta-lactamases. The crystal structure of [Zn-3(L-4)(6)(H2O)(6)] (6) is described; it is the first crystal structure involving a 1,2,4-triazole functionalized methionine. It forms a trinuclear complex with central zinc octahedrally coordinated by only L4, whereas terminal zinc ions coordination sphere is completed by three water molecules. L4 exhibits a dual functionality of a bridging bidentate ligand as well as an anion. A dense hydrogen bonding network connects these trinuclear entity into a 3D supramolecular network. The Zn-II ions in 6 are held at equidistance (3.848 angstrom) which coincidently matches with the corresponding Zn center dot center dot center dot Zn distance in the binuclear zinc enzyme from Bacillus cereus (3.848 and 4.365 angstrom). Among L1-L5 screened for beta-lactamase assay, L4 shows modest inhibition for BcII enzyme. (C) 2010 Elsevier B.V. All rights reserved.