Visible-Light-Responsive Novel Ru(II)-Metallo-Antibiotics with Potential Antibiofilm and Antibacterial Activity.

Growing challenges with antibiotic resistance pose immense challenges in combating microbial infections and biofilm prevention on medical devices. Lately, antibacterial photodynamic therapy (aPDT) is now emerging as an alternative therapy to overcome this problem. Herein, we synthesized and characterized four Ru(II)-complexes, ., [Ru(ph-tpy)(bpy)Cl]PF (), [Ru(ph-tpy)(dpq)Cl]PF (), [Ru(ph-tpy)(dppz)Cl]PF (), and [Ru(ph-tpy)(dppn)Cl]PF () (where 4'-phenyl-2,2':6',2″-terpyridine = ph-tpy; 2,2'-bipyridine = bpy; dipyrido[3,2-f:2',3'-]quinoxaline = dpq; dipyrido[3,2-a:2',3'-]phenazine = dppz; and Benzo[I]dipyrido[3,2-a:2',3'-]phenazine = dppn), among which are novel. Octahedral geometry of the complexes with a RuNCl core was evident from the crystal structure of . showed an MLCT absorption band in the 450-600 nm region, useful for aPDT performances. Further, optimum triplet excited state energy and excellent photostability of made them good photosensitizers for aPDT. demonstrated enhanced antimicrobial activity on visible-light exposure (400-700 nm, 10 J cm), confirmed using different antibacterial assays. Mechanistic studies revealed that inhibition of bacterial growth was due to the generation of oxidative stress (via NADH oxidation and ROS generation) upon treatment with , resulting in destruction of the bacterial wall. performed best killing performance against both Gram-negative () and Gram-positive () bacteria when exposed to light. , when coated on a polydimethylsiloxane (PDMS) disk, showed long-term reusability and durable antibiofilm properties. Molecular docking confirmed the efficient interaction of with FabH (regulates fatty acid biosynthesis of ) and PgaB (gives structural stability and helps biofilm formation of ), resulting in probable downregulation. studies with healthy Wistar rats confirmed the biocompatibility of . This study shows that these lead complexes () can be used as potent alternative antimicrobial agents in low concentrations toward bacterial eradication with photodynamic therapy (PDT).