Piano-stool type (η6-p-cymene)ruthenium(II) thiazole-derived motifs complexes: Synthesis, crystal structures, DFT studies, molecular docking and in-vitro binding studies with HSA and cytotoxicity

Two new ruthenium p-cymene complexes with thiazolyl ligands were synthesized and characterized. They were further evaluated for their HSA binding propensity using spectroscopic and computational studies. These complexes' cytotoxicity was carried out against human cancer cell lines and non-tumorigenic cells and compared with cisplatin. [Display omitted] Herein, two new p-cymene ruthenium(II) complexes [(η6-p-cymene)Ru (L1-OH) Cl] 1 and [(η6-p-cymene)Ru(L2-OH)Cl] 2 of thiazolyl-derived ligands i.e., (E)-2-(((5-methylthiazol-2-yl) imino) methyl) phenol (L1) and (E)-4-methyl-2-((5-methylthiazol-2-yl)imino) methyl)phenol (L2) have been designed and synthesized. The FT-IR, 1HNMR, 13C NMR spectroscopy and elemental analysis characterized both the ligands and the complexes. The representative molecular structures of the ligand L2 and complex 1 were determined by single X-ray crystallography. Moreover, the DFT studies were carried out to optimize the geometries and calculate the energies of the molecules by frontier molecular orbitals. Using multi-spectroscopic techniques and computational studies, these ruthenium arenes complexes 1 and 2 were investigated for the binding affinity towards human serum albumin (HSA). The results revealed the significantly good binding propensity of these complexes 1 and 2 towards HSA. The intrinsic binding studies exhibited the decerase in stern–volmer constant (Ksv) with increase in temperature. The mode of binding was also found to be static. The results obtained from extrinsic flouresence using ANS dye, ascertained the competitive binding inducing conformational alterations of HSA. Furrthermore, The cytotoxicity results displayed good IC50 values against HeLa cells compared to cisplatin, which is suggestive of the anti-cancer chemotherapeutic potential of complexes.