ISONIAZID STABILIZED TUNGSTEN TRICARBONYL COMPLEX: A NEW CO-RELEASING MOLECULE WITH ANTIBACTERIAL ACTIVITY

Abstract

Transition metal carbonyl complexes substituted with biologically active ligand can act as CO-releasing molecules which have beneficial roles including antimicrobial activity. Careful choices of ancillary ligand such as isoniazid help in eliminating issues of toxicity that may arise from drug substrates. Substitution reaction of tungsten hexacarbonyl with isoniazid in the presence of trimethylamine N-oxide under nitrogen atmosphere was carried out at ambient temperature for 72 hrs. The product was characterized using spectroscopic techniques and the CO release profile as well as the antibacterial activity evaluated. The successfully prepared substituted carbonyl complex was found to contain three CO ligands arranged in cis position with C3V symmetry in a facial geometry. fac-[W(INH)3(CO)3] released CO in solution at a rate of 3.4 x 10-2 s-1 following first order kinetics and a likely dissociative mechanism. The tricarbonyl complex displayed impressive bacteriostatic property against S. aureus, E. coli, and P. aeruginosa with activity comparable to the standard ampicillin drug used as control. The compound exhibited the highest bactericidal activity against Gram-negative P. aeruginosa inspiring hope of its application as potential antibiotic capable of tackling antibiotic resistant strains. Keywords: antibacterial, CO-RMs, isoniazid, tungsten carbonyl, decarbonylation