Ruthenium(III) chloride complex with a tridentate bis(arylimino)pyridine ligand: Synthesis, spectra, X-ray structure, 9-ethylguanine binding Pattern, and in vitro cytotoxicity

The synthetic, spectroscopic, structural, and biological studies of a bis(arylimino)pyridine Ru(III) chloride compound containing the ligand, 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine are reported. The bis(arylimino)pyridine ligand, with three donor nitrogen atoms, was synthesized by condensation of 2,6-pyridinedicarboxaldehyde with 2,4,6trimethylaniline. The Ru(III) complex, with formula [RUCl3(L1)](H2O) (RuL1), where L1 = 2,6-bis(2,4,6trimethylphenyliminomethyl)pyridine, was structurally determined on the basis of analytical and spectroscopic (IR, UV-vis, ESI-MS) studies. A straightforward strategy to fully characterize the paramagnetic compound using advanced H-1 NMR is reported. This new complex is a prototype for a series of new anticancer Ru(Ill) and Ru(II) compounds with improved cytostatic properties; likely to be modified in a desirable manner due to the relatively facile ligand modification of the bis(imino)pyridines and their molecular architecture. The present Ru(III) complex is the first example of this family of Ru(III)/Ru(II) anticancer compounds with the aimed physicochemical characteristics. Although the ligand itself is moderately active in selected cell lines (EVSA-T and MCF-7), the activity of the [Ru(L1)CI3] complex has increased significantly for a broad range of cancer cell lines tested in vitro IC50 values = 11 similar to 17 mu M). Reaction of the RuL1 species with the DNA model base 9-ethylguanine (9EtGua) was found to produce in a redox reaction the species trans-[Ru(II)(L1)(9EtGua)(2)(H2O)](CIO4)(2) (abbreviated as RuL1-9EtGua), which was studied in solution and also in the solid state, by X-ray crystallography. The structure comprises the as yet unknown trans-bis(purine)Ru(II) unit.