The inducing NO-vasodilation by chemical reduction of coordinated nitrite ion in cis-[Ru(NO₂)L(bpy)₂]⁺ complex

The synthesis of [Ru(NO₂)L(bpy)₂]⁺ (bpy = 2,2′-bipyridine and L = pyridine (py) and pyrazine (pz)) can be accomplished by addition of [Ru(NO)L(bpy)₂](PF₆)₃ to aqueous solutions of physiological pH. The electrochemical processes of [Ru(NO₂)L(bpy)₂]⁺ in aqueous solution were studied by cyclic voltammetry and differential pulse voltammetry. The anodic scan shows a peak around 1.00 V vs. Ag/AgCl attributed to the oxidation process centered on the metal ion. However, in the cathodic scan a second peak around −0.60 V vs. Ag/AgCl was observed and attributed to the reduction process centered on the nitrite ligand. The controlled reduction potential electrolysis at −0.80 V vs. Ag/AgCl shows NO release characteristics as judged by NO measurement with a NO-sensor. This assumption was confirmed by ESI/MS⁺ and spectroelectrochemical experiment where cis-[Ru(bpy)₂L(H₂O)]²⁺ was obtained as a product of the reduction of cis-[Ru^II(NO₂)L(bpy)₂]⁺. The vasorelaxation observed in denuded aortic rings pre-contracted with 0.1 μmol L⁻¹ phenylephrine responded with relaxation in the presence of cis-[Ru^II(NO₂)L(bpy)₂]⁺. The potential of rat aorta cells to metabolize cis-[Ru^II(NO₂)L(bpy)₂]⁺ was also followed by confocal analysis. The obtained results suggest that NO release happens by reduction of cis-[Ru^II(NO₂)L(bpy)₂]⁺ inside the cell. The maximum vasorelaxation was achieved with 1 × 10⁻⁵ mol L⁻¹ of cis-[Ru^II(NO₂)L(bpy)₂]⁺ complex.