Cytotoxicity of ruthenium(II) piano-stool complexes with imidazole-based PN ligands

A series of p-cymene ruthenium(II) complexes with imidazol-2-yl phosphines as PN ligands was prepared. Depending on the number of imidazolyl substituents in the ligands Ph3−nP(im)n {1–3: n = 1–3, im = imidazol-2-yl (a), 1-methylimidazol-2-yl (b)} different coordination modes were observed: κP, κ2N,N or κ3N,N,N. The complexes were tested for their cytotoxicity in different cancer cell lines. Most of the compounds were found to be non-toxic; The compounds [(p-cymene)Ru(1a)Cl2] (4a) shows cytotoxicity towards A2780sens and Hct116 cells in the μM range but not in H4IIE cells. The cytotoxicity is decreased upon introduction of a methyl group as [(p-cymene)Ru(1b)Cl2] (4b) shows only modest toxicities in the cell lines investigated. The κP compound [(p-cymene)Ru(2a)Cl2] (5a) shows selective toxicity in H4IIE cells after 72 h whereas the κ2N,N compound [(p-cymene)Ru(2a)Cl]OTf (5a′) showed no toxicity in the cell lines investigated which again.

Cytotoxicity profiles of a series of p-cymene ruthenium(II) complexes with imidazol-2-yl phosphines were determined in different cancer cell lines. The PN ligands can adopt different coordination modes. Most complexes are non-toxic, two show cytotoxicity towards H4IIE cells in the μM range and one shows some selectivity vs. different cell lines.Figure optionsDownload as PowerPoint slideHighlights
► p-Cymene ruthenium(II) with imidazole-based PN ligands were prepared.
► Polyimidazolyl ligands show κP-, κ2N,N- and κ3N,N,N-chelating coordination modes.
► The Ru(II) complexes show moderate cytotoxicity.
► The cytotoxic activities of the complexes increase with their lipophilicity.