Development and Reactivity of Nitrosyl Ruthenium Complexes with Possible Action as Metallopharmaceuticals.
Nitric Oxide; Nitrosyl Complexes; Ruthenium; Plasmid DNA.
Nitric oxide (NO) is a signaling molecule involved in several biological processes, including blood pressure regulation, neurotransmission, immune responses, antibacterial activity and anticancer activity. For this reason, nitrosyl complexes have been investigated as NO donors in an attempt to improve the medicinal applications of this molecule that depends on modulation to interact or act on potential molecular targets. In this context, this paper aims to develop new nitrosyl ruthenium complexes of the system [Ru(bpy)(L)(NO2)(NO)](PF6)2, where L = 1,10’- phenanthroline and 1,10’-phenanthroline-5,6- dione, bpy = 2,2’-bipyridine and NO2- = nitrite, capable of acting as nitric oxide releasers in biological systems. The compounds were obtained from precursor cis-[Ru(bpy)(L)Cl2] complexes in water and ethanol, with the addition of sodium nitrite ligand and 4 mol.L-1HTFA. In the infrared technique, in KBr pellets, the complexes exhibited modes at 1938 and 1942 cm-1 associated with nNO+ with phenanthroline and phendione, respectively, indicating the coordination of the nitric oxide ligand. Through the UV-Vis technique, in acetronitrile, it was possible to identify intraligand bands of the type π → π* in the ultraviolet region as well as charge transfer transitions from ruthenium to polypyridine ligands around 450 nm. Cyclic voltammograms obtained in NaTFA 0,1 mol.L-1 and pH 3.5 showed a potential of 122 mV for the complex with phenanthroline and 158 mV for phendione, both referring to the NO+/0 redox couple. Regarding to UV-Vis reactivity, the complex showed evidence of NO release with glutathione and cysteine due to the generation of intermediate products at 450 and 380 nm as well as the formation of the aquo complex at 450 nm. In turn, in square wave voltammetry, the reaction of the complexes with glutathione, histidine and methionine showed qualitative signs of NO release, due to the appearance of processes in the range of 150 and 550 mV characteristic of the redox pairs NO+/0 and Ru2+/3+, respectively. Finally, the pBR322 plasmid DNA cleavage tests with the complex containing phenanthroline did not show activity even with up to 60 µM of this compound in the dark. However, under blue light irradiation (460 nm) the complex showed the ability to cleave DNA, changing its structure from form I (supercoiled) to form II (open circular) with a cut in one strand.