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 [Ru-2(arene)(2)(OO boolean AND OO)(2)Cl-2] (arene = p-cymene, hexamethylbenzene; OO boolean AND OO=2,5-dihydroxy-1,4-benzoquinonato, 2,5-dichloro-1,4-benzo-quinonato) by reaction with pyrazine or bipyridine linkers (N boolean AND N = pyrazine, 4,4'-bipyridine, 1,2-bis(4pyridyl)ethylene) in methanol in the presence of AgO3SCF3, forming tetranuelcar cations of general formula [Ru-4(arene)(4)(N boolean AND N)(2)(OO boolean AND 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 mu M) than the 4,4'-bipyridine-containing cations (IC50 >= 30 mu M). Structural characterization by X-ray diffraction of two representative compounds, i.e., the triflate salts of [Ru-4(hexamethylbenzene)(4)(4,4'-bipyridine)(2)(2,5-dihydroxy-1,4-benzoquinonato)(2)](4+) and [Ru-4(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.