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Tetranuclear Coordination Assemblies Based on Half-Sandwich Ruthenium(II) Complexes: Noncovalent Binding to DNA and Cytotoxicity

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journal contribution
posted on 03.08.2009 by Fátima Linares, Miguel A. Galindo, Simona Galli, M. Angustias Romero, Jorge A. R. Navarro, Elisa Barea
The reaction of [(cymene)RuCl2]2 with K2Hoxonate (H3oxonic = 4,6-dihydroxy-2-carboxy-1,3,5-triazine acid) in methanol leads to the formation of the dinuclear half-sandwich ruthenium(II) complex [(cymene)2Ru2(μ-Hoxonato)Cl2] (1a). Removal of the chloride ligands of 1a by treatment with AgCF3SO3 yields [(cymene)2Ru2(μ-Hoxonato)(CF3SO3)2] (1b), which, upon posterior reaction with N,N′-linkers (L = 4,4′-bipyridine (4,4′-bpy), 4,7-phenantroline (4,7-phen)), gives rise to the formation of the tetranuclear open boxes [(cymene)4Ru4(μ-Hoxonato)2(μ-N,N′-L)2](CF3SO3)4 (2a, L = 4,4′-bpy; 2b, L = 4,7-phen). These systems have been characterized by 1H NMR, UV−vis, and ESI-MS. The single-crystal structures of the dinuclear precursor 1a and of the clathrate 2b⊂4,7-phen have been determined. The interaction of these systems with cysteine, mononucleotides, and calf-thymus DNA has been studied by means of 1H NMR, UV−vis, circular dicroism, competitive binding assays, and atomic force microscopy imaging. The results show that the robust tetracationic ruthenium(II) cyclic systems 2a and 2b do not give ligand exchange reactions toward biorelevant ligands. Nevertheless, these systems are able to noncovalently bind to DNA, probably at the surface of the major groove, inducing significant conformational changes in this biomolecule. It is also interesting to note that compounds 2a and 2b, in spite of only giving supramolecular interactions with biomolecules, exhibit antitumor activity, particularly toward the human ovarian cancer cell line A2780cisR, showing acquired resistance to cisplatin, with respective 4.6 and 8.3 microM IC50 values.