The triphenylphosphonium appended Schiff base ligands and their half-sandwich Ru(II) complexes: DNA binding, Anticancer and antioxidant properties

In this study, three novel Schiff base ligands (HL1TPP-HL3TPP), each incorporating a lipophilic triphenylphosphonium (TPP+) moiety, and their corresponding half-sandwich Ru(II) complexes were synthesized and structurally characterized. The anti-proliferative activities of these compounds were evaluated using the MTS assay on one healthy cell line [HUVEC - Human Umbilical Vein Endothelial Cells] and three cancer cell lines [H2452 (mesothelioma), YKG-1 (glioblastoma), and OUMS (chondrosarcoma)]. All compounds-except for [Ru (eta 6-p-cymene)(L1TPP)(Cl)]PF6-exhibited lower IC50 values against the YKG-1 cell line compared to HUVEC, suggesting selective cytotoxicity. Notably, [Ru(eta 6-p-cymene)(L2TPP)(Cl)]PF6 demonstrated the most potent anticancer activity on the YKG-1 line, with an IC50 value of 12.46 mu g/mL. The DNA-binding interactions of the ligands and their Ru(II) complexes were explored via spectroscopic and viscosity-based techniques, revealing a consistent groove-binding mode for all compounds. Additionally, comprehensive computational analyses were conducted to better understand the structural and biological properties of the synthesized molecules. Geometry optimizations, HOMO-LUMO energy calculations, ionization energy, electron affinity, global hardness, and chemical potential values were obtained using density functional theory (DFT) at the B3LYP/LANL2DZ level. Molecular electrostatic potential (MEP) surfaces were also generated to visualize the electronic distribution. These electronic and physicochemical parameters provided insights into the compounds' stability, reactivity, and potential bioactivity.