Pj. Coupe et Dlh. Williams, Formation of peroxynitrite at high pH and the generation of S-nitrosothiols from thiols and peroxynitrous acid in acid solution, J CHEM S P2, (9), 2001, pp. 1595-1599
Citations number
23
Categorie Soggetti
Physical Chemistry/Chemical Physics
Journal title
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
The formation of peroxynitrite from hydrogen peroxide and S-nitrosothiols a
t high pH is shown to involve reaction of the hydroperoxide anion. Kinetic
measurements over a pH range 10-13 yield a value close to,the literature va
lue for the pK(a) of hydrogen peroxide and give a quantitative measure of t
he reactivity of. the hydroperoxide ion. S-Nitrosothiols are formed in high
yield when peroxynitrous acid reacts with thiols when the thiol is in very
large excess, within the pH range 2.7-3.7. Kinetic measurements have shown
that reaction occurs by rapid oxidation of the thiol to the disulfide, wit
h release of nitrite ion, which at these pH. values is sufficiently protona
ted to effect nitrosation of the thiol, which is in large excess. Quantitat
ive yields of RSNO can be obtained when there is a very large excess [thiol
], when the spontaneous decomposition of peroxynitrous acid cannot compete.
The individual kinetic results are fully first order and analysis of the r
esults yields values for the third-order rate constants k (in rate = k [RSH
][HNO2][H+]) which are in acceptable agreement with the values in the liter
ature for the direct - nitrosation of thiols with nitrous acid. Results wer
e obtained for three thiols [glutathione (GSH), cysteine (Cys) and cysteine
ethyl ester], confirming the generality of the reaction. At higher pH valu
es the yield of RSNO drops off sharply as nitrous acid becomes deprotonated
. A separate experiment with stoichiometric-concentration ratios of thiol a
nd peroxynitrous acid in acid solution gave high yields of nitrous acid: At
higher acidities (>0.3 mol dm(-3)) S-nitrosothiols are still formed, but n
ow there are clearly two sequential first-order processes which can be fitt
ed to a two exponential model. One reaction is believed to be nitrous acid
nitrosation, following oxidation of the thiol as before, whilst the other r
eaction, which is also acid catalysed, is interpreted as nitrosation via:a
protonated form of peroxynitrous acid as recently reported in the literatur
e; which can compete with the isomerisation of peroxynitrous acid to nitrat
e anion, when the thiol is at high concentration.