Peroxynitrous acid: controversy and consensus surrounding an enigmatic oxidant

Abstract

The isomerisation of ONOOH to NO(3)(-) and H(+), some oxidations and all hydroxylations and nitrations of aromatic compounds are first-order in ONOOH and zero-order in the compounds that are modified. These reactions are widely believed to proceed via homolysis of ONOOH into HO˙ and NO(2)˙ to an extent of ca. 30%. We review the evidence pro and contra homolysis in studies that involve (1) thermochemical considerations, (2) isomerisation to NO(3)(-) and H(+), (3) decomposition to NO(2)(-) and O(2), (4) HO˙ scavenger studies, (5) deuterium isotope effects, (6) (18)O-scrambling studies, (7) electrochemistry, (8) CIDNP NMR, and (9) photolysis. Our conclusion is that homolysis may be involved to a minor extent of ca. 5%. The initiation of ONOOH isomerisation may be visualised as an out-of-plane vibration of the terminal HO-group relative to the nitrogen. At ONOO(-) concentrations exceeding 0.1 mM and near neutral pH, disproportionation to NO(2)(-) and O(2) occurs; such disproportionations are typical for peroxy acids. For oxidation and nitration of organic substrates, we favour a mechanism involving initial formation of an adduct between the compound to be oxidised or nitrated and ONOOH.

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

“…This modification can be generated through several pathways that include the reaction with ROS and RNS like ONOO − and NO 2 • [225–227] (Figure 2). NO • generated by NOS can react with O 2 •− to form ONOO − that, at acidic pH, is present as protonated form (ONOOH) which is believed to decompose into HO • and NO 2 • to an extent of ~30% [10]. Generally, tyrosine oxidation is a two-step process with the formation of a tyrosine radical, generated by different oxidative steps, followed by the reaction with NO 2 • .…”

“…Upon activation, neutrophils produce various ROS via myeloperoxidase (MPO) and RNS via inducible nitric oxide synthase (iNOS). MPO catalyzes the H 2 O 2 -dependent formation of hypochlorous acid (HClO) while iNOS produces nitric oxide (NO • ), which then reacts with O 2 •− to form peroxynitrite (ONOO − ) [10]. NOX associated with cell membrane catalyzes the generation of superoxide radicals that play a physiological role in cancer invasion, hypoxia, and integrin signaling [11–13].…”

Nitric oxide, antioxidants and prooxidants in plant defence responses

“…The exact pathway of ONOO − and ONOOH (peroxynitrous acid) decay to NO − 2 and NO − 3 at neutral pH is still debated (Table 3). It was suggested that ONOOH isomerises to NO − 3 and H + either directly or indirectly via the radical intermediates NO 2 and OH (Goldstein and Merenyi, 2008; Koppenol et al, 2012). The peroxynitrite anion on the other hand yields the RNS NO 2 , NO, and N 2 O 3 during its degradation to NO − 2 (Goldstein and Merenyi, 2008).…”

Reactive nitrogen species in cellular signaling

“…OH) 24,26 with an efficiency of approximately 30%, though these values are controversial. 48,50,51 The hydroxyl radical is reactive enough to remove electrons from nearly any biological molecule, for instance the reaction with tyrosine creates a tyrosyl radical which can then react with nitrogen dioxide to form nitrotyrosine. In addition, peroxynitrite directly reacts with CO 2 yielding nitrosoperoxycarbonate (ONOOCO 2 À), which decomposes into nitrogen dioxide and the carbonate radical (…”