Tuning the reaction products of ruthenium and ciprofloxacin for studies of DNA interactions

Abstract

This work presents two potential metallo-drugs, the ionic (C17H19FN3O3)3[RuCl6] · 3H2O (1) and the coordination [Ru(C17H17FN3O3)3] · 4H2O (2) compounds, obtained by the combination of ruthenium(III) and ciprofloxacin in different synthetic conditions. The ESI MS spectrum of 1 displayed a main peak at m/z = 994.6, assigned to the gaseous phase adduct (ciprofloxacin)3 · H+, while 2 featured peaks at m/z 1093.3 and 547.1 ascribed to [Ru(C17H17FN3O3)3 · H+–4H2O]+ and [Ru(C17H17FN3O3)3 · 2H+–4H2O]2+. Thermal analysis corroborated the proposed water content for both complexes. Absorption spectra of the compounds in aqueous medium are dominated by ciprofloxacin transitions in the UV region but displayed weak bands in the visible region, assigned to ligand field transitions. The cyclic voltammograms of 2 exhibited a quasi-reversible process ascribed to the Ru(II)/(III) redox pair at −0.25 V (vs. SHE) while 1 displayed this process at −0.11 V, showing that the central ruthenium ion is stabilized in the (III) oxidation state by the coordination to the hard oxygen atoms of ciprofloxacin. The solubility of 1 is pH dependent (as well as free ciprofloxacin) while 2 is fully water soluble and stable under physiological pH for at least 48 h. The compounds are also stable under incubation conditions (stomach pH and 37°C) without significant pH lowering. An interaction study of 2 with ct-DNA showed a value of K b = 2.47 (±0.89) × 104 mol−1 L for the intrinsic binding constant.