Nitrosilo complexos de rutênio: síntese, caracterização, reatividade e ação frente ao DNA plasmidial

Abstract

Nitric oxide (NO) is a signaling molecule involved in several biological processes, including the regulation of blood pressure, neurotransmission, immunological responses, antibacterial activity and anticancer activity. For this reason, nitrosyl complexes have been investigated as NO donors in order to improve the biological applications of this molecule that depends on modulating the structure of the complexes to interact or act on potential molecular targets. In this context, this paper aims to develop new ruthenium nitrosyl complexes of the system [Ru(bpy)(L)(NO2)(NO)](PF6)2, where L: the ligands 1,10’-phenanthroline (phen), 1,10’- phenanthroline-5,6-dione (phendione) and bpy = 2,2’-bipyridine, capable of acting as nitric oxide releasers in biological systems. The compounds were obtained from the cis- [Ru(bpy)(L)Cl2] precursor complexes in water and ethanol, with the addition of the sodium nitrite ligand in 4 mol L-1 HTFA. Trough the infrared technique, in KBr pellets, the complexes exhibited vibrational modes at 1941 and 1944 cm-1 associated with NO+ with phenanthroline and phendione, respectively, indicating the coordination of nitric oxide. Through the UV-Vis technique, in acetonitrile, it was possible to identify intraligand bandas of π → π* character in the ultraviolet region as well as MLCT type charges transfer transitions from ruthenium to polypyridine ligands around 450 nm. The cyclic voltammograms obtained in 0.1 mol L -1 NaTFA and pH = 3.5 showed a half-wave potential of 122 mV for the complex with phenanthroline and 133 mV for the complexe with phendione, both referring to the redox couple NO+/0. Regarding UV-Vis reactivity, the complex with phenanthroline showed evidence of NO release in the presence of glutathione and cysteine due to the generation of intermediate products at 450 and 380 nm as well as the formation of the aqua complex at 450 nm. On the other hand, the compound with phendione compared to these reducers did not follow the same mechanism. In square wave voltammetry, the reaction of the compounds with glutathione, histidine and methionine showed qualitative signs of NO release, due to the appearance of processes in the range of 100-150 and 500-700 mV characteristic of the redox pairs NO+/0 and Ru3+/2+ , respectively. Finally, (pBR322) plasmid DNA cleavage tests revealed that in the dark the complexes do not exhibit activity even with up to 60 µM of the compounds. However, under blue light irradiation (463 nm) and in the presence of glutathione, the complexes showed cleavage activity, therefore altering their Form I (supercoiled) structure between Forms II (open circular) and III (linear form).