The Effect of a Photoactivated Ruthenium Nitrocomplex [RuCl(NO2)(dppb)(4,4-2 Mebipy)] on the Viability of Eukaryotic and Prokaryotic Cells, Including Bacterial Biofilms

Antimicrobial resistance (AMR) is a critical global public health problem. Many bacterial pathogens use biofilm formation as their main pathogenicity mechanism, a practical tactic for surviving in natural settings and colonized host tissues. Research using ruthenium(II) complexes has demonstrated antibacterial action linked to photodynamic therapy, an alternate method of microbial control. Thus, in this work, the photosensitive nitro complex [RuCl(NO2)(dppb)(4,4-Mebipy)] (I) was prepared and the X-ray structure was determined. Then, we investigated the antibacterial and antibiofilm activities, antibiotic-associated effects, and cytotoxicity. The results showed that complex I exhibited promising antimicrobial activity with MIC values ranging from 4 to 256 µg/mL and MBC from 4 to 32 µg/mL. The antimicrobial activity of this nitro complex was significantly enhanced with blue light irradiation, as confirmed by agarose gel electrophoresis of the pBR322 DNA, which must be related to the DNA cleavage promoted by the photorelease of NO. A synergistic effect against Staphylococcus aureus and Staphylococcus epidermidis strains was observed when combined with ampicillin, which exhibited FICI values from 0.186 to 0.311. Interestingly, complex I associated with tetracycline showed a synergistic effect only on Escherichia coli. Regarding biofilms, the irradiated complex I showed antibacterial activity against biofilm formation and mature biofilms. Furthermore, SEM and confocal analyses revealed changes in cell morphology and damage to the wall and plasma membrane. Complex I presented a percentage of hemolysis between 2 and 4%, and no cytotoxic effect was observed against murine dermal fibroblasts. In conclusion, the photoactivated ruthenium(II) complex showed antibacterial and antibiofilm activity against relevant bacteria.