Synthesis, Molecular Structure, and Anticancer Activity of Cationic Arene Ruthenium Metallarectangles

Cationic arene ruthenium-based tetranuclear complexes comprising rectangular structures have been obtained from the dinuclear arene ruthenium complexes [Ru2(arene)2(OO∩OO)2Cl2] (arene = p-cymene, hexamethylbenzene; OO∩OO = 2,5-dihydroxy-1,4-benzoquinonato, 2,5-dichloro-1,4-benzoquinonato) by reaction with pyrazine or bipyridine linkers (N∩N = pyrazine, 4,4′-bipyridine, 1,2-bis(4-pyridyl)ethylene) in methanol in the presence of AgO3SCF3, forming tetranuclear cations of general formula [Ru4(arene)4(N∩N)2(OO∩OO)2]4+. All complexes were isolated in good yield as triflate salts and were characterized by NMR and IR spectroscopy and studied by cyclic voltammetry. The cytotoxicities of the water-soluble compounds of the 4,4′-bipyridine and 1,2-bis(4-pyridyl)ethylene series have been established using ovarian A2780 cancer cells. The large rectangles incorporating 1,2-bis(4-pyridyl)ethylene linkers are ca. 5 times more cytotoxic (IC50 ≤ 6 μM) than the 4,4′-bipyridine-containing cations (IC50 ≥ 30 μM). Structural characterization by X-ray diffraction of two representative compounds, i.e., the triflate salts of [Ru4(hexamethylbenzene)4(4,4′-bipyridine)2(2,5-dihydroxy-1,4-benzoquinonato)2]4+ and [Ru4(hexamethylbenzene)4(1,2-bis(4-pyridyl)ethylene)2(2,5-dichloro-1,4-benzoquinonato)2]4+, reveals differently sized cavities, different flexibilities, and different packing arrangements, suggesting a correlation between these structural properties and the observed cytotoxicities.