Ru3

Three novel Ru(II)‐based photoantibiotics, viz., [Ru(phtpy)(N,N,N)2](PF6)2, where N,N,N = 4′‐phenyl‐2,2′:6′,2″‐terpyridine (phtpy, Ru1), 4‐([2,2′:6′,2′′‐terpyridin]‐4′‐yl)‐N,N‐dimethylaniline (NMe2tpy, Ru2), trifluoromethylphenyl)‐2,2′:6′,2′′‐terpyridine (CF3tpy, Ru3) were developed with excellent photostability for visible light‐activated antibacterial activities and infective wound healing. Ru1‐Ru3 exhibited an absorption in the 400–600 nm range, beneficial for antibacterial photodynamic therapy (aPDT) application. Upon visible light exposure (400‐700 nm), Ru1‐Ru3 inhibited bacterial growth of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis), due to the effects of oxidative stress via ROS generation and photo‐oxidation of NADH. Ru3 was identified as a lead antibiotic that further showed antibiofilm activities against E. coli under visible light exposure. Ru3 was found to be biocompatible against rat red blood cells and human embryonic kidney cells. Ru3 + light promoted rapid healing of infected wounds within 9 days in an E. coli‐induced rat model, highlighting its potential future use in healthcare.

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)₂ (bpm)] (PF₆)₂ (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.