Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles

The neutral dinuclear complexes [(eta(5)-C5Me5)(2)Rh-2(mu-dhnq)Cl-2] (1) and [(eta(5)-C5Me5)(2)Ir-2(mu-dhnq)Cl-2] (2) (dhnqH(2) = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of (eta(5)-C5Me5)M(mu-Cl)Cl (M = Rh, Ir) with dhnqH(2) in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4'-bipyridine or 1,2-bis(4-pyridyl) ethylene), in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles (eta(5)-C5Me5)(4)M-4(mu-dhnq)(2)(mu-L)(2) (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4'-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridyl) ethylene, M = Rh, 7; M = Ir, 8). All complexes were isolated as their triflate salts and were fully characterized by infrared, H-1 and C-13 NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3-8 was evaluated against the human ovarian A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range.