Peroxynitrite: The Basics

WILLEM H. KOPPENOL

1.1 History

1.1.1 Before 1990

In this section, I will focus on the early discovery of peroxynitrite, its ability to nitrate aromatic compounds, its sensitivity to carbon dioxide and early determination with permanganate.

More than a 100 years ago, Baeyer and Villiger proposed that a "Nitrosopersäure" (ROONO) was formed as an intermediate in reactions of nitrite, ethyl nitrite, and amyl nitrite (R1ONO) with hydrogen peroxide and ethyl hydroperoxide (R2OOH). They came to the conclusion that an adduct between R1ONO and R2OOH was formed that yielded R1OH and R2ONO2. Had a direct oxidation of the nitrite taken place, R1ONO2 and R2OH would have been the products. In the case of the reaction between nitrous acid and hydrogen peroxide, nitrate (NO3-) is ultimately formed and the accompanying formula shows an adduct between peroxynitrous acid and water. Although they did not provide direct evidence for the structure of peroxynitrous acid, we may credit them with the discovery of this reactive species. In 1907, Raschig prepared a solution of bromide in hydrogen peroxide and one of bromide in nitrous acid. Both solutions stayed clear, but upon mixing, dibromine was formed as deduced from the reddish-brown color and the smell. He assumed that two hydrogen peroxide molecules reacted with one nitrous acid and proposed the formula HNO4 and the name "Übersalpetersäure"; apparently he was not aware of the publication of Baeyer and Villiger. In 1922, Trifonow explored the properties of the short-lived product of the reaction between nitrous acid and hydrogen peroxide for analytical purposes. He concluded that "naszente Persalpetersäure" (nitric acid in statu nascendi) is capable of oxidizing aniline and nitrating aromatic compounds. He proposed using these reactions for the detection of nitrite and aromatic compounds due to the intensively colored products. In 1929, Gleu and Roell reported that the reaction of azide with ozone results in a deep orange–red solution that smells of hypochlorite and sometimes nitrogen dioxide. Although stable in alkaline solution, the color disappears rapidly upon neutralization by addition of hydrogen carbonate, or by lowering of the pH. In spite of considerable efforts, they were unable to isolate the new unstable compound, but their experiments allowed them to exclude hydrogen peroxide as the oxidant, and they concluded that they were dealing with peroxynitrous acid. Gleu and Hubold described in their paper of 1935 a simple synthesis of peroxynitrite from hydrogen peroxide and nitrite at low pH: one mixes nitrite and hydrogen peroxide, adds acid followed by base within 2 s. If done correctly, the deep yellow color of peroxynitrite is observed. Use of a quenched-flow reactor improves the yield. Kortüm and Finckh showed in 1941 that the absorption maximum of peroxynitrite anion (ONOO-) in the UV ultraviolet range is close to that of NO3-, but the intensity is about 15 times higher and the band is much broader. The initiation of the polymerization of methyl acrylate and the hydroxylation and nitration of aromatic compounds by peroxynitrous acid, reported in 1952 by Halfpenny and Robinson, was rationalized in terms of homolysis of the O–O bond in ONOOH. However, in 1954, Anbar and Taube studied the reactions of peroxynitrite labeled with two O18, and found doubly labeled NO3- as a product of intramolecular rearrangement of peroxynitrite and, in the presence of an excess of unlabeled nitrite, singly labeled nitrite and nitrate as products of O18 transfer from peroxynitrite to nitrite, a result that is not easily explained by homolysis. The first kinetics study of peroxynitrous acid involving its isomerization to NO3- appeared in 1962 and the second in 1969. The latter gives a pKa of 6.6 and a rate of isomerization of 0.10 s-1, obtained at a temperature of 1 °C and an ionic strength of 0.5 M. It also mentioned that peroxynitrite vanishes quickly in the presence of carbonate or borate. Formation of peroxynitrite from nitrate in solution by ultraviolet light was demonstrated in 1964. The same study also showed that permanganate oxidized peroxynitrite. Hughes and Nicklin reported in 1968 the extinction coefficient of peroxynitrite at 302 nm of 1670 [+ or -] 50 M-1 cm-1, which is within the error of that obtained by Bohle and coworkers in 1994 with pure tetramethylammonium peroxynitrite, 1705 [+ or -] 10 M-1 cm-1. Blough and Zafiriou made a very important observation in 1985 of a yellow color after mixing a mostly anaerobic alkaline solution of superoxide with that of nitrogen monoxide. They concluded that superoxide and nitrogen monoxide react to form peroxynitrite. As nitrogen monoxide was identified in 1987 as an "endothelium-derived relaxing factor", and SOD extends the life of nitrogen monoxide, the finding of Blough and Zafiriou could be relevant to physiology!

We see that a few properties and reactions that have been discovered can be used to quantitate peroxynitrite: its yellow color, its ability to nitrate aromatic compounds and the reduction of purple permanganate to green manganate. An excellent review on the "older" chemistry of peroxynitrite by Edwards and Plumb appeared in 1993. It also discusses the role of peroxynitrite in atmospheric chemistry.

From 1901 until 1990, ca. 40 papers on peroxynitrite appeared. Since then, the number of publications has sharply increased to well over 12 000 as a recent search (November 2014) on the Web of...