Green-light-activated Os(II) metallo-photoantibiotics for antibacterial therapy and infected wound healing

Abstract

The emergence of antibacterial resistance and persistent bacterial biofilms challenges conventional antibacterial therapies for infected wounds, while antibacterial photodynamic therapy offers a promising alternative. To address these challenges and explore the unknown potential of Os(II) complexes as photo-antibiotics for infected wound cure, here we developed three NIR-emissive Os(II) metallo-photo-antibiotics viz., [Os(OH-phtpy)(thiophene-tpy)](PF6)2 (Os1), [Os(OH-phtpy)(pyrrole-tpy)](PF6)2 (Os2), [Os(OH-phtpy)(furan-tpy)](PF6)2 (Os3). Os1-Os3 exhibit green-light absorption, indicating their potential for photo-triggered catalytic antibacterial applications. SC-XRD analysis of Os2 confirms the distorted octahedral geometry of the Os(II)N6 core. Computational studies provide insight into their excited-state energy levels. Under green-light (50.4 J cm-2, 525 nm), Os1-Os3 efficiently inhibit the growth of Bacillus subtilis, Escherichia coli, and Staphylococcus aureus by inducing oxidative stress through ROS generation and catalytic NADH photo-oxidation (TOF up to 31.2 h-1). Os1 emerges as the lead candidate, exhibiting potent light-activated antibiofilm activity against mature E. coli. Os1 also demonstrates biocompatibility in HEK-293 (Human Embryonic Kidney) cells, rat RBCs, and the in ovo chicken egg model. Furthermore, in an E. coli-infected rat wound model, Os1 + green-light irradiation accelerates wound healing, as evidenced by histological evaluation and biomarker analyses. Overall, these findings underscore the potential of Os(II) metallo-photo-antibiotics for light-triggered therapy of infected wounds. Antimicrobial resistance poses a significant global health challenge, limiting the efficacy of conventional antibiotics. Here, the authors explore Os(II) polypyridyl complexes for antibacterial photodynamic therapy, highlighting their strong spin-orbit coupling and long-lived excited states, which enhance reactive oxygen species generation, offering a promising strategy to combat resistant bacterial infections.