The Chemical Biology of Dinitrogen Trioxide

Dinitrogen trioxide (N2O3) mediates low-molecular weight and protein S- and N-nitrosation, with recent reports suggesting a role in the formation of nitrating intermediates as well as in nitrite-dependent hypoxic vasodilatation. However, the reactivity of N2O3 in biological systems results in an extremely short half-life that renders this molecule essentially undetectable by currently available technologies. As a result, evidence for in vivo N2O3 formation derives from the detection of nitrosated products as well as from in vitro kinetic determinations, isotopic labeling studies, and spectroscopic analyses. This review will discuss mechanisms of N2O3 formation, reactivity and decomposition, as well as address the role of sub-cellular localization as a key determinant of its actions. Finally, evidence will be discussed supporting different roles for N2O3 as a biologically relevant signaling molecule.