Synthesis, characterization, interactions with the DNA duplex dodecamer d(5′-CGCGAATTCGCG-3′)2 and cytotoxicity of binuclear η6-arene-Ru(ii) complexes

Abstract

The novel binuclear η⁶-arene-Ru(II) complexes with the general formula {[(η⁶-cym)Ru(L)]₂(μ-BL)}(PF₆)₄, and their corresponding water soluble {[(η⁶-cym)Ru(L)]₂(μ-BL)}Cl₄, 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 {[(η⁶-cym)Ru(phen)]₂(μ-BL-1)}(PF₆)₄ was determined by X-ray single crystal methods. The interaction of {[(η⁶-cym)Ru(phen)]₂(μ-BL-i)}Cl₄ (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 × 10³ M⁻¹ through both intercalation and groove binding, while (5) and (6) are groove binders (K_b = 2.333 × 10³ M⁻¹ and K_b = 3.336 × 10³ M⁻¹ correspondingly). Comparison with the mononuclear complex [(η⁶-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 × 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.