Reactive Nitrogen Species Reactivities with Nitrones: Theoretical and Experimental Studies

摘要

Reactive nitrogen species (RNS) such as nitrogen dioxide (^•NO2), peroxynitrite (ONOO^–), and nitrosoperoxycarbonate (ONOOCO2^–) are among the most damaging species present in biological systems due to their ability to cause modification of key biomolecular systems through oxidation, nitrosylation and nitration. Nitrone spin traps are known to react with free radicals and non-radicals via electrophilic and nucleophilic addition reactions, and have been employed as reagents to detect radicals using electron paramagnetic resonance (EPR) spectroscopy, and as pharmacological agents against oxidative stress-mediated injury. This study examines the reactivity of cyclic nitrones such as 5,5-dimethylpyrroline N-oxide (DMPO) with, ^•NO2, ONOO^–, ONOOCO2^–, SNAP and SIN-1 using EPR. The thermochemistries of nitrone reactivity with RNS, and isotropic hfsc's of the addition products were also calculated at the PCM(water)/B3LYP/6-31+G**//B3LYP/6-31G* level of theory with and without explicit water molecules in order to rationalize the nature of the observed EPR spectra. Spin trapping of other RNS such as azide (^•N3), nitrogen trioxide (^•NO3), amino (^•NH2) radicals, and nitroxyl (HNO) were also theoretically and experimentally investigated by EPR spin trapping and mass spectrometry. This study also shows other spin traps such as AMPO, EMPO and DEPMPO can react with radical and non-radical RNS, thus, making spin traps suitable probes as well as antioxidants against RNS mediated oxidative damage.