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.