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 [(η(5)-C(5)Me(5))(2)Rh(2)(μ-dhnq)Cl(2)] (1) and [(η(5)-C(5)Me(5))(2)Ir(2)(μ-dhnq)Cl(2)] (2) (dhnqH(2) = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of [(η(5)-C(5)Me(5))M(μ-Cl)Cl](2) (M = Rh, Ir) with dhnqH(2) in the presence of CH(3)COONa. 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 AgCF(3)SO(3), affords the corresponding tetranuclear metalla-rectangles [(η(5)-C(5)Me(5))(4)M(4)(μ-dhnq)(2)(μ-L)(2)](4+) (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, (1)H and (13)C 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 IC(50) values in the low micromolar range.