Synthesis, characterization and investigation of the antibacterial activity of cationic complexes of Ru(II)-p-cymene phosphine with weakly-coordinating acetonitrile ligands

The synthesis and characterization of ruthenium(II)-arene triarylphosphine complexes, [Ru(η⁶-p-cymene)(PAr₃)(NCCH₃)Cl][PF₆], where Ar = (3,5-^tBu₂C₆H₃-) (L1), (3,5-Me₂C₆H₃-) (L2), (4-MeO-3,5-Me₂C₆H₂-) (L3) and (4-MeOC₆H₄-) (L4), are described. The structures have been confirmed by IR and ³¹P NMR spectroscopy and by single crystal X ray diffraction studies. The redox behavior of the complexes has been investigated by voltammetry in CH₃CN, with stability over a wide potential window ΔE ≅ 2.7 V. The antibacterial properties of the complexes have been studied against a Gram-positive and a Gram-negative strain. Complex 2 exhibits strong activity against S. aureus (MIC 25 µmol L^-1, IC₅₀ 13.5 µmol L^-1) and notably potent activity against MRSA (MIC 12.5 µmol L^-1, IC₅₀ 8.52 µmol L^-1). Complex 3 also demonstrates activity against S. aureus (MIC 25 µmol L^-1, IC₅₀ 15.9 µmol L^-1) and MRSA (IC₅₀ 11.04 µmol L^-1), though its MIC against MRSA is >100 µmol L^-1. By contrast, complex 4 is inactive. The interactions of 2 and 4 with phospholipid monolayers were investigated by the Langmuir monolayer method, in a system that simulates the Staphylococcus aureus cell membrane. Complex 2 interacts with and disrupts the organization of these monolayers, and this result possibly indicates that cell membrane rupture causes the antibacterial effect.