Development of Cyclometalated Iridium(III) Complexes of 2‐Phenylbenzimidazole and Bipyridine Ligands for Selective Elimination of Gram‐Positive Bacteria
Aryan Gautam, Ajay Gupta, Puja Prasad, Pijus K. Sasmal
Abstract
(N N)]Cl, wherein C N is a cyclometalating 2-phenylbenzimidazole ligand with varying alkyl chain lengths and N N is a 2,2'-bipyridine ligand attached to bis-polyethylene glycol chains, for the treatment of bacterial infections. The AIE phenomenon of the complexes leveraged for detecting bacteria by fluorescence microscopy imaging that displayed a strong red emission in Gram-positive bacteria. The antibacterial activity of the complexes assessed against Gram-positive methicillin-sensitive S. aureus, methicillin-resistant S. aureus, E. faecium and E. faecalis and Gram-negative E. coli and P. aeruginosa bacteria of clinical interest. The complexes Ir2-Ir4 exerted potent antibacterial activity towards Gram-positive strains with low minimum inhibitory concentrations (MICs) values in the range of 1-9 μM, which is comparable to clinically approved antibiotic vancomycin. In contrast, these complexes were found to be inactive towards Gram-negative bacterial strains (MICs >100 μM). The mechanism of antibacterial activity of the complexes implies that ROS generation, membrane depolarization and rupture are responsible for bacterial cell death. Further, the complexes Ir1-Ir3 were found to be low-toxic against human red blood cells and human embryonic kidney (HEK293) cells, indicating their potential for use as antibacterial agents.