Controlled nitric oxide photo-release from nitro ruthenium complexes: The vasodilator response produced by UV light irradiation

Preliminary pharmacological studies of various nitric oxide (NO) photo-releasing agents are reported based on the flash-photolysis studies of the nitro ruthenium complexes cis-[RuII(NO2)L(bpy)2]+ (bpy = 2,2′-bipyridine and L = pyridine, 4-picoline and pyrazine) and [RuII(NO2)(bpy)(terpy)]+ (terpy = terpyridine) in physiological medium. The net photoreactions under these conditions are two primary photoproducts, in (I) there is RuII–NO2 photoaquation, where the photoproducts are RuII–H2O plus NO2- and (II) homolytic dissociation of NO from a coordinated nitrito to derive the RuII–OH2 specie and NO. Based on photochemical processes, the nitro ruthenium complexes were incorporated in water in oil (W/O) microemulsion and used in the vasorelaxation induced experiment. Denuded rat aortas were contracted with KCl and nitro ruthenium complexes in microemulsion were added. Perfusion pressures were recorded while arteries were irradiated at 355 nm The time to reach maximum relaxation was longer for [RuII(NO2)(bpy)(terpy)]+ complex (ca. 50 min, n = 6) than for cis-[Ru(NO2)L(bpy)2]+ with L = py and 4-pic complex (ca. 28 min, n = 6) and cis-[Ru(NO2)(bpy)2 (pz)]2+ complex (ca. 24 min, n = 5).

The synthesis, physical chemistry, photochemical and pharmacological properties of cis-[RuII(NO2)L(bpy)2]+ (bpy = 2,2′-bipyridine and L = pyridine, 4-picoline and pyrazine) and [RuII(NO2)(bpy)(terpy)]+ (terpy = terpyridine) in physiological medium are reported. The photolysis at 355 nm light irradiation of nitro ruthenium complexes produces cis-[RuIII(OH)L(bpy)2]2+ or [RuIII(OH)(bpy)(terpy)]2+ and nitric oxide, which causes vasorelaxation in denuded rat aortic rings.Figure optionsDownload as PowerPoint slide