Theoretical Evidence for the Antibacterial and Antioxidant Potentials of a New Molybdenum Tricarbonyl Complex

Abstract

The development of low energy light-activated therapeutics with precise targets is currently receiving pronounced attention.  Here we report the evaluation of a novel mer-tricarbonylmolybdenum(0) complex with benzyl isonicotinoyl hydrazone (BIH) as ancillary ligands. The complex is a photoactive carbon monoxide-releasing molecule (PhotoCORM) with dual action. Spectroscopic characterization (IR, NMR) and the elemental analysis results confirmed a meridional octahedral geometry tricarbonyl complex with a para substitution pattern for the coordinating pyridinic nitrogen atom of the ancillary ligand. FTIR spectral analysis strongly suggested that the para substitution mode of the ligand attenuated metal-to-ligand π-backbonding, resulting in the weakening of the Mo-C bond. Time-dependent density functional theory (TD-DFT) calculations showed that a highly allowed Metal-to-Ligand Charge Transfer (MLCT) in the visible light region (λ_max = 587.45 nm) initiated the photolysis process. Experimental evidence supported that upon irradiation, the complex undergoes dissociation at a rapid rate (k = 9.7x10^-2 s^-1). Released CO is successfully delivered to biological heme sites as confirmed by carbonmonoxy myoglobin (MbCO) formation. In silico molecular docking simulation with SwissDock program demonstrated that possible release of hydrazone ancillary ligand may effectively target the active site of keap1 (PDB: 4L7B) and those of essential bacterial proteins; LasR (PDB: 3IX3), MRSA PBP2a (PDB:5M18) and E. coli DNA Gyrase (PDB: 6F86). In vitro antibacterial assay carried out to validate the theoretical broad-spectrum activity of the ligand, and the CO poisoning of the heme indicates significant growth inhibition against S aureus, E. coli, and P. aeruginosa in a dose-dependent manner. These results highly suggest this novel photoCORM as a promising synergistic antimicrobial agent.