Synthesis, characterization, and in vitro evaluation of novel ruthenium(II) eta6-arene imidazole complexes

Ten complexes of general formula [Ru(eta6-arene)Cl2(L)], [Ru(eta6-arene)Cl(L)2][X], and [Ru(eta6-arene)(L)3][X]2 (eta6-arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole, N-vinylimidazole, N-benzoylimidazole; X = Cl, BF4, BPh4) have been prepared and characterized by spectroscopy. The structures of five representative compounds have been established in the solid state by single-crystal X-ray diffraction. All the new compounds were assessed by the same in vitro screening assays applied to [imidazole-H][trans-RuCl4(DMSO)(imidazole)] (NAMI-A) and [Ru(eta6-arene)Cl2(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compounds. It was found that the new compounds show essentially the same order of cytotoxicity as the RAPTA compounds toward cancer cells. Several of the compounds were selective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that are used to model healthy human cells. Thus, two of the compounds, [Ru(eta6-p-cymene)Cl(vinylimid)2][Cl] (vinylimid = N-vinylimidazole) and [Ru(eta6-benzene)(mimid)3][BF4]2 (mimid = N-methylimidazole), have been selected for a more detailed in vivo evaluation.