RESUMO
Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1-4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l-valine) and characterized by 1H NMR, 13C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1-4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.
Assuntos
Óxido Nítrico , Rutênio , Humanos , Rutênio/química , Óxido Nítrico/metabolismo , Células HeLa , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Isomerismo , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios XRESUMO
Iron-sulfur cluster conversion and nitrosyl modification are involved in regulating their functions and play critical roles in signaling for biological systems. Hereby, the photo-induced dynamic process of (Me4N)2[Fe2S2(NO)4] was monitored using time-resolved electron paramagnetic resonance (EPR) spectra, MS spectra and cellular imaging methods. Photo-irradiation and the solvent affect the reaction rates and products. Spectroscopic and kinetic studies have shown that the process involves at least three intermediates: spin-trapped NO free radical species with a gav at 2.040, and two other iron nitrosyl species, dinitrosyl iron units (DNICs) and mononitrosyl iron units (MNICs) with gav values at 2.031 and 2.024, respectively. Moreover, the [Fe2S2(NO)4]2- cluster could bind with ferritin and decompose gradually, and a binding state of dinitrosyl iron coordinated with Cys102 of the recombinant human heavy chain ferritin (rHuHF) was finally formed. This study provides insight into the photodynamic mechanism of nitrosyl iron - sulfur clusters to improve the understanding of physiological activity.