Synthesis, characterization, interactions with the DNA duplex dodecamer d(5 '-CGCGAATTCGCG-3 ')(2) and cytotoxicity of binuclear eta(6)-arene-Ru(ii) complexes

The novel binuclear.6-arene-Ru(II) complexes with the general formula {[(eta(6)-cym)Ru(L)](2)(mu-BL)}(PF6)(4), and their corresponding water soluble {[(eta(6)-cym)Ru(L)](2)(mu-BL)}Cl-4, where cym = p-cymene, L = 2,2'bipyridine (bpy) and 1,10-phenanthroline ( phen), BL = 4,4'-bipyridine (BL-1), 1,2-bis(4-pyridyl)ethane (BL-2) and 1,3-bis(4-pyridyl)propane (BL-3), were synthesized and characterized. The structure of {[(.6cym)Ru(phen)]2(mu-BL-1)}(PF6) (4) was determined by X-ray single crystal methods. The interaction of {[(eta(6)cym)Ru(phen)](2)(mu-BL-i)}Cl-4 (i = 1, 2, 3; (4), (5) and (6) correspondingly) with the DNA duplex d(5'CGCGAATTCGCG-3') (2) was studied by means of NMR techniques and fluorescence titrations. The results show that complex (4) binds with a K-b = 12.133 x 10(3) M-1 through both intercalation and groove binding, while (5) and (6) are groove binders (K-b = 2.333 x 10(3) M-1 and Kb = 3.336 x 103 M-1 correspondingly). Comparison with the mononuclear complex [(eta(6)-cym)Ru( phen)( py)]2+ reveals that it binds to the d(5'CGCGAATTCGCG-3') (2) with a K-b value two orders of magnitude lower than (4) (K-b = 0.158 x 103 M-1), indicating that for the binuclear complexes both ruthenium moieties participate in the binding. The complexes were found to be cytotoxic against the A2780 and A2780 res. cancer cell line with a selectivity index (SI) in the range of 3.0-5.9.