Synthesis of antibacterial ruthenium complexes modified with 4-chlorobiphenyl derivatives and their application in postoperative wound infection

The rapid global emergence of drug-resistant bacteria has led to a critical shortage of effective treatments, necessitating the development of novel antibacterial agents. To address this urgent need, we rationally synthesized three polybipyridine ruthenium complexes, RuL-1, RuL-2 and RuL-3 , by employing 4-chlorobenzene-modified o -phenanthroline derivatives as the principal ligand (L=4′-chlorinated-biphenyl-1H- imidazo[4,5- f ][1,10]phenanthroline). The introduction of the 4-chlorobiphenyl moiety was intended to enhance membrane interaction and improve antibacterial potency. The in vivo and in vitro antibacterial activities studies demonstrated that three ruthenium complexes exhibited significant antibacterial activity, with RuL-1 displaying a particularly low minimal inhibitory concentration (MIC) of 1 μg/mL. Notably, RuL-1 has a robust capacity to block the acquisition of drug resistance in Staphylococcus aureus ( S. aureus ) and reduced bacterial virulence factor secretion by 37%. Mechanistic studies further revealed that RuL-1 induced depolarization of the membrane potential of S. aureus , promoted intracellular reactive oxygen species generation, and disrupted bacterial outer membrane integrity. More importantly, a mouse infection model further confirmed that RuL-1 exhibited strong therapeutic efficacy against postoperative incision infections. Collectively, these results demonstrate that 4-chlorobiphenyl-modified ruthenium complexes are promising candidates for combating bacterial resistance and treating wound infections.