Synthesis, structure, spectral, redox properties and anti-cancer activity of Ruthenium(II) Arene complexes with substituted Triazole Ligands

Abstract Three versatile half-sandwich ruthenium(II) p-cymene complexes bearing substituted triazole ligands exhibit promising cancer cell growth inhibition activity towards A549 lung adenocarcinoma and MDA-MB-231 breast adenocarcinoma cells. In this context, the triazole based phthalimide protected new ligand (2-(3, 5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-yl) isoindoline-1,3-dione) (L1) was prepared. Three ruthenium(II) p-cymene complexes [Ru(η6-p-cymene)(L1)Cl]Cl: [1]Cl, L1: (2-(3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione), [Ru(η6-p-cymene)(L2)Cl]Cl: [2]Cl and [Ru(η6-p-cymene)(L2)Cl](PF6): [2](PF6), L2 (2,2′-(4-(1H-pyrrol-1-yl)-4H-1,2,4-triazole-3,5-diyl) dipyridine) have been successfully synthesized and characterized by different spectral and analytical tools. Pyrrole protected substituted ruthenium complexes [2]Cl and [2](PF6) have been successfully identified structurally by single-crystal X-ray diffraction studies and confirmed the successful anion exchange. The redox properties of the ligands and the targeted metal complexes have been carefully examined. Cellular staining, live-cell imaging and MTT assay have been performed for all the complexes. We have demonstrated that our synthesized ruthenium(II) p-cymene complexes are capable of inducing significant cytotoxicity in A549 lung cancer cell lines, with an IC50 values of 6.56 ± 0.31 µM, 4.74 ± 0.2 µM and 13.67 ± 0.64 µM and in MDA-MB-231 breast cancer cell lines with an IC50 values of 1.13 ± 0.046 µM, 0.36 ± 0.016 µM and 11.32 ± 0.49 µM for [1]Cl, [2]Cl and [2](PF6) respectively.