Ruthenium(II)-Arene Complexes: Biomolecular Binding, Thermodynamic Insights, and Selective Cytotoxicity

Two novel dimeric ruthenium-(II)-arene complexes, PNRP and PNRB, incorporating a planar π-conjugated PNN ligand and different arene moieties (p-cymene and benzene, respectively), were synthesized and characterized. These complexes were designed to explore the role of arene identity in modulating biomolecular interactions and redox-mediated cytotoxicity. Comprehensive physicochemical and spectroscopic studies confirmed the structural integrity and solution stability of both complexes. Binding interactions with calf thymus DNA and human serum albumin were investigated using absorption and fluorescence spectroscopy, with thermodynamic parameters (ΔG°, ΔH°, ΔS°) determined from temperature-dependent binding studies. The results indicated spontaneous and moderately strong binding driven primarily by hydrophobic and electrostatic interactions. Viscosity analysis and guanine binding further supported partial intercalation. Cellular assays in A549 lung carcinoma and HEK293 normal kidney cells demonstrated that both complexes exhibit notable cytotoxic activity, with PNRB showing enhanced selectivity (IC₅₀ = 31.37 μM; SI = 7.58). Reactive oxygen species (ROS) generation was confirmed via fluorescence microscopy, suggesting oxidative stress as a contributing mechanism. Overall, the study highlights arene-dependent modulation of biological response in Ru-(II) complexes and supports the development of redox-active, π-conjugated metal-based agents as selective anticancer therapeutics.