Zn(II) and Cd(II) complexes of cephalosporin: Solvent-free and solution-based syntheses, characterization and <i>in vitro</i> antimicrobial evaluation

Abstract

Rapid increase of microbial resistance to antibiotics is fast becoming a global concern. To overcome this alarming problem, the discovery of novel active compounds against new targets is a matter of urgency. Herein, solvent-free and solution-based synthesized Zn(II) and Cd(II) complexes of cephalosporin derivatives (cefixime and cefuroxime) have been described and compared. The complexes were characterized by solubility, melting point and conductivity measurements, infrared spectroscopy, UV/Visible and metal analysis. The complexes were either milky, yellow or brown in colour and had high decomposition temperatures (187-315˚C). The complexes were all air stable and generally soluble in dimethyl sulfoxide but insoluble in n-hexane. The molar conductivity values (10.3 – 16.6 Scm² mol^-1) for both solvent-free and solution-based complexes were found to below indicative of the complexes being non-electrolytic. The coordination of the metal ions to the ligands occurred through oxygen of the three C═O in the ligands as it was evident from infrared spectroscopic analysis. The UV-Visible spectra for all the complexes formed showed a five-coordinate geometry around the ligands and two aqua molecules. In general, the characterization has evidenced the identical nature of the complexes obtained via the two synthesis techniques. The antimicrobial screening was carried out against four Gram-positive (Staphylococcus aureus, S. pyogen, Methicillin-resistance Staphylococcus aureus (MRSA) and Bacillus subtilis), four Gram-negative (Klebsiella pneumoniae, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) bacteria and one fungus (Candida albicans). The results revealed that both ligands showed activity against all the micro-organisms tested except Pseudomonas aeruginosa and Streptococcus pyogene in the case of the ligand cefuroxime. Compared to the ligands, the other complexes were also more active against the micro-organisms. At all test concentrations, the complex [Cd(CFU)Cl²] showed increased activity against all tested micro-organisms. Similar results were reported for cefixime complexes which showed significantly enhanced antimicrobial and antifungal activities against microbial strains as compared to free ligand cefixime.