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

Metallo-β-lactamases (mβl) 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.

In this paper, metallo-β-lactamase and phosphotriesterase activities of some zinc(II) complexes are described. It is shown that the complexes having asymmetric phenolate-based ligand systems are better mimics of metallo-β-lactamase than phosphotriesterase. The binuclear zinc(II) complex 1 having water molecule exhibits high metallo-β-lactamase activity. On the other hand, the mononuclear zinc(II) complexes 2 and 3 having labile chloride ions exhibit significant phosphotriesterase activity.Figure optionsDownload as PowerPoint slideHighlights
► Zn(II) complexes exhibit metallo-β-lactamase (mβl) and phosphotriesterase (PTE) activities.
► A binuclear Zn(II) complex exhibits high mβl activity.
► Mononuclear complexes having chloride ligands exhibit high PTE activity.
► Replacement of the metal-bound labile chloride ions by hydroxide ions is important for the PTE activity.