A highly positively charged Ru(II) complex with photo-labile ligands for selective and efficient photo-inactivation of intracellular Staphylococcus aureus.

Due to the protection afforded by host cells, intracellular Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), poses a significantly greater challenge to eliminate compared to the extracellular counterparts. It is highly desirable to develop novel antibacterial agents which are capable of selectively and efficiently eradicating intracellular bacteria, including drug-resistant strains, while being less prone to induce bacterial resistance. In this work, two Ru(II) complexes (Ru1 and Ru2) with photo-labile ligands were designed and synthesized. Both Ru1 and Ru2 could covalently bind to DNA after photo-induced ligand dissociation. Compared to Ru1, the incorporation of a triphenylamine group adorned with two positively charged cationic pyridine units significantly boosts the DNA binding constant, bacterial binding/uptake level, and subsequently, the antibacterial activity of Ru2. Ru2 could selectively photo-inactivate intracellular S. aureus and MRSA, being more efficient than vancomycin both in vitro and in vivo. Interestingly, after 20 days' treatment at sublethal concentrations, S. aureus cells exhibited no obvious drug resistance towards Ru2 upon irradiation. Such appealing results may provide new sights for developing novel antibacterial agents against intractable intracellular pathogens and also prevalent drug resistance.