Organometallic ruthenium (η⁶-p-cymene) complexes interfering with quorum sensing and biofilm formation: an anti-infective approach to combat multidrug-resistance in bacteria

Novel ruthenium arene complexes of flavonoid derivatives were synthesized and characterized. The structure of complex1was determined by single-crystal X-ray crystallography. Ruthenium complexes display strong DNA interactions. Zero-order relativistic approximation (ZORA) was employed for the B3LYP/DFT calculation to validate the structures of2and3. Frontier molecular orbital (FMO) analysis was performed for getting a trend of DNA binding propensity of the complexes. The ruthenium complexes1-3were tested against pathogens,viz. Pseudomonas aeruginosaPAO1,Chromobacterium violaceumATCC 12472, and methicillin-resistantS. aureus(MRSA). The ruthenium complexes exhibited potential acting as biofilm inhibitors and showed significant activity as quorum sensing inhibitors. Scanning electron microscopy (SEM) and confocal microscopy visualized biofilm inhibition, and a substantial reduction in microcolonies was observed. Furthermore, essential quorum sensing (QS) regulated functions that play a crucial role in biofilm formation were also studied,i.e., exopolysaccharide (EPS) production and swarming motility. A significant reduction was recorded at the tested sub-MICs.