Ruthenium(II)-Arene Metallacycles: Crystal Structures, Interaction with DNA, and Cytotoxicity

A series of 24, 26-membered Ru-2(II) metallamacrocycles containing 1-{3-[(1H-imidazol-1-yl)methyl]benzyl}-1Himidazole (m-bib) and 1-{4-[(1H-imidazol-1-yl)methyl]benzyl}1H-imidazole (p-bib) ligands have been synthesized and characterized. X-ray crystal structures of [Ru-2(eta(6)-p-cymene)(2)(m-bib)(2)Cl-2](CF3SO3)(2) (2), [Ru-2(eta(6)-p-cymene)(2)(m-bib)(2)Cl-2](SbF6)(2) (3), [Ru2(eta(6)-p-cymene) 2(m-bib)(2)I-2]I-2 (6), and [Ru2(eta(6)-p-cymene)(2) (p-bib)(2)Cl-2](CF3SO3)(2) (8) were determined and found to exhibit chair-like conformations. In general, the complexes exhibited little or moderate anti-proliferative activity towards cancer cells [human lung cancer cells (A549),breast adenocarcinoma cells (MCF-7), cervical epithelioid carcinoma cells (HeLa)] as well as normal liver cells (L02), except [Ru-2(eta(6)-p-cymene)(2)(p-bib)(2)Cl-2](NO3)(2) (10) (IC50 = 16.7 mu M), which had activity comparable with the anticancer drug cisplatin (IC50 = 15.8 mu M). Gel electrophoresis studies suggested that the complexes can interact with DNA and induce DNA condensation.