Synthesis, X-ray structure determination, cytotoxicity and interactions with 9-methylguanine, of ruthenium(II) η6-arene complexes

•Ruthenium η6-arene complexes were synthesized and structurally characterized.•The complexes were cytotoxic against various cancer cell lines, with IC50 < 1 μM.•9-methylguanine coordinates to ruthenium through N7.•The aromatic ring systems of the ligands provide strong shielding on 9MeG H8.

Ruthenium η6-arene compounds of the general formula [(η6-arene)Ru(L)Cl](PF6), (1)PF6–(4)PF6, (η6-arene is benzene (bz) or p-cymene (cym), L is 2-(2′-pyridyl)quinoxaline (pqx) or 2-(2′-pyridyl)benzo [g]quinoxaline (pbqx)) and [(η6-cym)Ru(L)(9MeG)](PF6)2, (L is 2-(2′-pyridyl)quinoxaline (pqx), 2-(2′-pyridyl)benzo [g]quinoxaline (pbqx), 2,2′-bipyridine (bpy), 9MeG is 9-methylguanine), (5)(PF6)2–(7)(PF6)2, were synthesized and characterized by spectroscopic and analytical techniques. The molecular structures of the complexes (1)–(4), determined by single-crystal X-ray analysis of the hexafluorophospate salts, are also reported. In (5)(PF6)2–(7)(PF6)2, the nucleobase 9MeG binds to ruthenium through N7. Based on 1H NMR spectroscopy, a strong shielding effect between the aromatic ring system of the quinoxaline or benzo[g]quinoxaline moiety of the ligands pqx and pbqx and the H8 of 9MeG was observed. The complexes (1)–(4) are highly cytotoxic as chloride salts, against various cancer cell lines, with their IC50 values observed at less than 1 μΜ.

Graphical abstractAt the complexes with the general formula [(η6-cym)Ru(L)(9MeG)](PF6)2 a strong shielding effect between the aromatic ring system of the chelating ligands L and the H8 of 9MeG, was observed. Figure optionsDownload full-size imageDownload as PowerPoint slide