Reactions of Amine and Peroxynitrite: Evidence for Hydroxylation as Predominant Reaction and New Insight into the Modulation of CO2

Abstract

Peroxynitrite is related to numerous diseases including cardiovascular diseases, inflammation, and cancer. In order to expand the understanding for the toxicology of peroxynitrite in biological system, the reactions of amine (morpholine as a probe) with peroxynitrite and the modulation of CO2 were investigated by using DFT methods. The results strongly indicate that the hydroxylation of amine by peroxynitrous acid ONOOH, which was previously overlooked by most studies, is predominant relative to the widely reported nitration and nitrosation in the absence of CO2. The product N-hydroxylamine is proposed to be mainly generated via nonradical pathway (two-electron oxidation). The modulation of CO2 exhibits two main functions: (1) inhibition of hydroxylation due to the promoted consumption of peroxynitrite via fast reaction of CO2 with ONOO¯ to form ONOOCO2¯; (2) dual effect (catalysis and inhibition) of CO2 toward nitration and nitrosation. As a new insight, amine does react with CO2 and produce inert amine carbamate R2NCOO¯. This reaction has the potential to compete with the reaction of CO2 and ONOO¯, which leads to inhibition of nitration and nitrosation. The concentration of CO2 could be a critical factor determining the final effect, catalysis or inhibition. As a new finding, HCO3¯ is probably an effective catalyst for the reaction of amine and CO2. Moreover, further studies on how the different types of the amine might affect the outcome of the reactions would be an interesting topic.