Rigid dinuclear ruthenium-arene complexes showing strong DNA interactions

Six novel dinuclear Ru(II)-arene complexes [Ru-2(eta(6)-p-cymene)(2)(1,3-bib)(2)Cl-2] x(2)center dot Solvent (X = Cl-, I- (2), NO3- (3), BF4- (4), PF5- (5), CF3SO3- (6); 1,3-bib = 1,3-di(1H-imidazol-1-yl) benzene) were synthesized and fully characterized by FT-IR, H-1 NMR, ESI-MS, Elemental Analysis (EA) and Powder X-ray Diffraction (PXRD). Single crystal X-ray diffractions studies showed that 3 and 4 have rigid bowl-like structures, where one counter-anion (NO3- for 3 and BF4- for 4) was trapped inside the cavity to balance the charge, respectively. Even complexes 1-6 showed only moderate or little anti-proliferative activity toward cancer cells, strong interactions with DNA molecules through intercalation, however, were confirmed by UV-Vis, CD and fluorescence spectroscopy. Apoptosis and cell cycle arrest studies for complex 2 with cancer A549 cells indicated concentration-dependent late apoptosis and the G1/G0 phase arrest. Interactions with the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) might explain the relatively low antiproliferative potency of these complexes. This class of rigid dinuclear cations hold potential as DNA-targeting anticancer agents if their uptake and delivery could be under controlled.