Antibiotic resistance to clinically employed beta-lactam antibiotics currently poses a very serious threat to the clinical community. The origin of this resistance is the expression of several beta-lactamases that effectively hydrolyze the amide bond in beta-lactam compounds. These beta-lactamases are classified into two major categories: serine beta-lactamases and metallo-beta-lactamases. The metalloenzymes use one or two zinc ions in their active sites to catalyze the hydrolysis of all classes of beta-lactam antibiotics, including carbapenems. As there is no clinically useful inhibitor for the metallo-beta-lactamases, it is important to understand the mechanism by which these enzymes catalyze the hydrolysis of antibiotics. In this regard, the development of synthetic analogues will be very useful in understanding the mechanism of action of metallo-beta-lactamases. This review highlights some important contributions made by various research groups in the area of synthetic analogues of metallo-beta-lactamases, with major emphasis on the role of dinuclear Zn(II) complexes in the hydrolysis of beta-lactam antibiotics.

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.

The phosphotriesterase (PTE) activity of a series of binuclear and mononuclear zinc(II) complexes and metallo-beta-lactamase (mbetal) from Bacillus cereus was studied. The binuclear complex 1, which exhibits good mbetal activity, shows poor PTE activity. In contrast, complex 2, a poor mimic of mbetal, exhibits much higher activity than 1. The replacement of Cl(-) ligands by OH(-) is important for the high PTE activity of complex 2 because this complex does not show any catalytic activity in methanol. The natural enzyme mbetal from B. cereus is also found to be an inefficient catalyst in the hydrolysis of phosphotriesters. These observations indicate that the binding of beta-lactam substrates at the binuclear zinc(II) center is different from that of phosphotriesters. Furthermore, phosphodiesters, the products from the hydrolysis of triesters, significantly inhibit the PTE activity of mbetal and its functional mimics. Although the mononuclear complexes 3 and 4 exhibited significant mbetal activity, these complexes are found to be almost inactive in the hydrolysis of phosphotriesters. These observations indicate that the elimination of phosphodiesters from the reaction site is important for the PTE activity of zinc(II) complexes.

Bio-based nanocomposites of poly (butylene adipate-co-terephthalate) (PBAT)/silver oxide (Ag 2 O) were prepared by the composite film casting method using chloroform as the solvent.The prepared Ag 2 O at different ratios (1, 3, 5, 7, and 10 wt%) is incorporated in the PBAT.The PBAT nanocomposite films were subjected to structural, thermal, mechanical, barrier, and antimicrobial properties. The electron micrographs indicated uniform distribution of Ag 2 O in the PBAT matrix. However, the images indicated agglomeration of Ag 2 O particles at 10 wt% loading. The thermal stability of the nanocomposite films increased with Ag 2 O content.The tensile strength and elongation of the composite films were found to be higher than those of PBAT and increased with Ag 2 O content up to 7 wt%. The PBAT-based nanocomposite films showed the lower oxygen and water vapor permeability when compared to the PBAT film.Antimicrobial studies were performed against two food pathogenic bacteria, namely, Klebsiella pneumonia and Staphylococcus aureus.

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