A new family of Ru(ii) complexes with a tridentate pyridine Schiff-base ligand and bidentate co-ligands: synthesis, characterization, structure and in vitro cytotoxicity studies

Abstract

Starting from the Ru(III) complex, [RuCl₃(L1)](H₂O) (L1: 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine), the chemical reactivity and cytotoxic activity of a new family of Ru(II) complexes with a number of bidentate co-ligands have been studied. The synthesis of the Ru(II)-bis(arylimino)pyridine complexes with the co-ligands 1,10-phenanthroline (phen), 2,2′dipyridyl-(bpy), 2-(phenylazo)pyridine (azpy), 2-(phenylazo)-3-methylpyridine (3mazpy), 2-(tolylazo)pyridine (tazpy), and 2-picolinate (pic) is reported. These new six complexes, with L1 and different bidentate N donor co-ligands, have been designed to allow the binding of a monodentate chloride ligand, which would be easily hydrolysed in vitro. Elemental analysis and several spectroscopic techniques (IR, UV-Vis, 1D and 2D ¹H NMR and ESI-MS) have been used for the characterization of the new Ru(II) compounds. In addition, the crystal structure of the chlorido(2-picolinato)(2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine)ruthenium(II) was solved and shows a slightly distorted octahedral geometry for the Ru(II) centre with the tridentate L1 ligand coordinated in a planar mer fashion, with the bidentate ligand in a perpendicular orientation and a monodentate chloride, trans to the coordinating oxygen of the picolinate ion. The in vitro cytotoxic properties of these new Ru(II) complexes in comparison with the parent, starting Ru(III)-compound (IC₅₀ values = 11–17 μM) appear to be encouraging for a broad range of cancer cell-lines tested (IC₅₀ values = 0.4–10 μM). Some of them show better cytotoxic effects than cisplatin on a straight comparison with the same cancer cell lines. The cytotoxicity data are discussed in the light of structure–activity relationships and these ruthenium(II) compounds could well be promising next generation candidates worth further investigation.