Metallo-β-lactamase and phosphotriesterase activities of some zinc(II) complexes

Abstract

Metallo-β-lactamases (mβ l) and phosphotriesterase (PTE) are zinc(II) enzymes, which hydrolyze the β -lactam antibiotics and toxic organophosphotriesters, respectively. In the present work, we have synthesized a few asymmetric phenolate-based ligands by sequential Mannich reaction and their corresponding zinc(II) complexes. These zinc(II) complexes were studied for their mβl and PTE activities. It is shown that the zinc(II) complexes can hydrolyze oxacillin, the β-lactam antibiotic, at much higher rates as compared to the hydrolysis of p-nitrophenyl diphenylphosphate (PNPDPP), the phosphotriester. Among the complexes studied, the binuclear asymmetric complex 1 having a water molecule coordinated to one of the zinc(II) ions exhibits much better mβl activity than the mononuclear complexes. However, the mononuclear zinc(II) complexes having labile chloride ions exhibit significant PTE activity, which can be ascribed to the replacement of chloride ions by hydroxide ions during hydrolysis reactions.