Development of Cyclometalated Iridium(III) Complexes of 2‐Phenylbenzimidazole and Bipyridine Ligands for Selective Elimination of Gram‐Positive Bacteria

Herein, we have reported a series of cationic aggregation‐induced emission (AIE) active iridium(III) complexes (Ir1‐Ir5) of the type [Ir(C N)2(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. A series of cationic AIE‐active iridium(III) complexes derived from cyclometalating 2‐phenylbenzimidazole derivatives and N N donor 2,2’‐bipyridine ligands have been synthesized and used as bacterial imaging and killing agents. The complexes selectively and efficiently eradicate Gram‐positive bacteria through ROS generation, cell membrane depolarization and cell wall disruption.