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

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Cationic arene ruthenium-based tetranuclear complexes comprising rectangular structures have been obtained from the dinuclear arene ruthenium complexes [Ru 2 (arene) 2 ( OO ∩ OO ) 2 Cl 2 ] (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 AgO 3 SCF 3, forming tetranuclear cations of general formula [Ru 4 (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 (IC 50 ≤ 6 μM) than the 4,4′-bipyridine-containing cations (IC 50 ≥ 30 μM). 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.