1-(2-Picolyl)-substituted 1,2,3-triazole as novel chelating ligand for the preparation of ruthenium complexes with potential anticancer activity

Abstract

The 1,4-disubstituted 1,2,3-triazole ligand prepared by click chemistry 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole (ppt) was investigated as novel chelating ligand for Ru(II) complexes with potential antitumor activity. The preparation and structural characterization, mainly by NMR spectroscopy in solution and by X-Ray crystallography in the solid state, of four new Ru(II) complexes is reported: two isomeric Ru-dmso compounds, trans,cis-[RuCl₂(dmso-S)₂(ppt)] (1) and cis,cis-[RuCl₂(dmso-S)₂(ppt)] (2), and two half-sandwich Ru-[9]aneS₃ coordination compounds, [Ru([9]aneS₃)(dmso-S)(ppt)][CF₃SO₃]₂ (3) and [Ru([9]aneS₃)Cl(ppt)][CF₃SO₃] (4). In all compounds ppt firmly binds to ruthenium in a bidentate fashion through the pyridyl nitrogen atom and the triazole N2, thus forming a puckered six-membered ring. The chemical behavior in aqueous solution of the water-soluble complexes 3 and 4 was studied by UV-Vis and NMR spectroscopy and compared to that of the previously described organometallic analogue [Ru(η⁶-p-cymene)Cl(ppt)][Cl] (5) in view of their potential antitumor activity. Compounds 3–5 were tested also in vitro for cytotoxic activity against two human cancer cell lines, one sensitive and one resistant to cisplatin, in comparison with cisplatin. Compound 4, the one that aquates faster, was found to be more cytotoxic than cisplatin against human lung squamose carcinoma cell line (A-549).