Peroxynitrite is stable, but its acid, HOONO, either rearranges to form nitrate or oxidizes nearby biomolecules. We report here the reactions ofHOONO with methionine and the methionine analog 2-keto-4-thiomethylbutanoic acid (KTBA). These oxidations proceed by two competing mechanisms. The first yields the sulfoxide; the second-order rate constants, k2, for this process for methionine and .KTBA are 181 ± 8 and 277 ± 11 M-l s'1, respectively, at pH 7.4 and 25WC. In the second mechm, methionine or KTBA undergoes a one-electron oxidation that ultimately gives ethylene. We propose that the one-electron oxidant is an activated form of peroxynitrous acid, HOONO*, that is formed in a steady state mechanism. The ratios of the second-order rate constants for the ethylene-producing reaction (kl) and the first-order rate constant to produce nitric acid (kN) for methionine and KTBA, kl/kN, are 1250 ± 290 and 6230 ± 1390 M-, respectively.Both ceric and peroxydisufate ions also oxidize KTBA to ethylene, confirming a one-electron transfer mechanism. The yields of neither MetSO nor ethylene are affected by several hydroxyl radical scavengers, suggesting that a unimolecular homolysis of HOONO to HO and NO2 is not involved in these reactions. HOONO* gives hydroxyl radical-like products from various substrates but displays more selectivity than does the hydroxyl radical; thus, HOONO* is incompletely trapped by typical HO scavengers. However, a mechanism involving dissociation of HOONO* to caged radicals cannot be ruled out at this time.Nature's use of *NO as a biological signal molecule is remarkable from many perspectives, not the least of which is the fact that NO is a toxin. Paradoxically, the toxicity of NO involves oxidation reactions, but nitric oxide itself is only a weak oxidant. However, nitric oxide can be converted to a potent oxidant by reaction with superoxide to produce the peroxynitrite ion (-O0-N=O) and its conjugate acid, peroxynitrous acid (HOO-N=O) (1), as shown in Eqs. 1 and 2. Peroxynitrite* is capable of oxidizing thiols (2)
Peroxynitrite is a versatile and important biological oxidant that
is produced from the reaction of nitric
oxide and superoxide radicals. Two mechanisms have been proposed
to rationalize oxidation reactions of peroxynitrite.
One assumes that HO−ONO can homolize to form the hydroxyl
radical and nitrogen dioxide, and that the hydroxyl
radical is the proximate oxidant in peroxynitrite systems. The
second argues this homolysis is too slow to occur at
ordinary temperatures and suggests an excited species, HOONO*, is the
proximate oxidant. If the radical mechanism
is correct, then peroxynitrite should disappear more slowly in solvents
of higher viscosity. This is true because for
free radical initiators undergoing single-bond homolysis: (1) cage
return is substantial and more of the cages would
return to re-form HO−ONO as the viscosity of the medium increases;
and (2) diffusion from the radical cage competes
effectively with other cage processes. We have studied the
disappearance of peroxynitrite at pH 5 and 7 in buffers
with and without dioxane (as a control) or up to 30 wt % of the
poly(ethylene glycol) (PEG) polymers, PEG 3350
and PEG 8000. These polyethers produce substantial changes in
viscosity, raising the viscosity from about 0.89 to
about 17 mPa·s. The rate constant for diffusion should decrease
by about 10- to 20-fold as the viscosity increases
in this interval, and the rate of diffusion from the solvent cage would
be predicted to vary accordingly. However,
at pH 5, where most of HOONO is undissociated, no change in the rate of
disappearance of peroxynitrite is observed
with increasing viscosity. At pH 7, a small increase in the
observed rate constant is found, but it is likely due to
the
greater concentration of the undissociated HOONO in the
ether-containing solvents resulting from a pK
a
shift. Thus,
we conclude that the viscosity test does not support a free radical
mechanism for the unimolecular decomposition of
peroxynitrite.
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