Thermodynamics of Peroxynitrite and Its CO<sub>2</sub> Adduct

Merényi, Gábor; Lind, Johan

doi:10.1021/tx970101j

Cited by 102 publications

(86 citation statements)

References 40 publications

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“…However, this interpretation was questioned, particularly the assumptions concerning the entropy of hydration of ONOO Ϫ (38). It is instructive to review the known structural features of peroxynitrite before considering the possible decomposition mechanisms in more detail.…”

Section: Discussionmentioning

confidence: 99%

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution

Khan

Kovacic

Kolbanovskiy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The mechanism of decomposition of peroxynitrite (OONO ؊ ) in aqueous sodium phosphate buffer solution at neutral pH was investigated. The OONO ؊ was synthesized by directly reacting nitric oxide with superoxide anion at pH 13. The hypothesis was explored that OONO ؊ , after protonation at pH 7.0 to HOONO, decomposes into 1 O2 and HNO according to a spin-conserved unimolecular mechanism. Small aliquots of the concentrated alkaline OONO ؊ solution were added to a buffer solution (final pH 7.0 -7.2), and the formation of 1 O2 and NO ؊ in high yields was observed. The 1 O2 generated was trapped as the transannular peroxide (DPAO2) of 9,10-diphenylanthracene (DPA) dissolved in carbon tetrachloride. The nitroxyl anion (NO ؊ ) formed from HNO (pKa 4.5) was trapped as nitrosylhemoglobin (HbNO) in an aqueous methemoglobin (MetHb) solution. In the presence of 25 mM sodium bicarbonate, which is known to accelerate the rate of decomposition of OONO ؊ , the amount of singlet oxygen trapped was reduced by a factor of Ϸ2 whereas the yield of trapping of NO ؊ by methemoglobin remained unaffected. Because NO3 ؊ is known to be the ultimate decomposition product of OONO ؊ , these results suggest that the nitrate anion is not formed by a direct isomerization of OONO ؊ , but by an indirect route originating from NO ؊ .nitrosylhemoglobin ͉ diphenylanthracene endoperoxide P eroxynitrite is a potent oxidant formed by the near diffusioncontrolled reaction of nitric oxide (NO ⅐ ) and superoxide ion (O 2 Ϫ ) (1). Both nitric oxide and superoxide are produced by activated macrophages (2, 3), neutrophils (4), and endothelial cells (5, 6). There is evidence that peroxynitrite is formed in significant concentrations in vivo (7-9) and may contribute to an increased risk for cancer (10), artherosclerosis (11), stroke (12), and other diseases (13). Peroxynitrite is a stable anion in alkaline solution (pKa of 6.8); however, once protonated, it decomposes rapidly with a half-life of less than 1 s at physiological pH at 37°C (14), generating reactive species that readily react with biomolecules such as lipids (15), amino acids (16), and DNA (17). Central to the question of the biochemistry of peroxynitrite is the mechanism of decomposition and the identity of the reactive species, a subject of intense research and controversy (18-21). Speculations about the decomposition mechanisms are largely based on kinetic and thermodynamic considerations (22). It has been shown that bicarbonate ion enhances the rate of disappearance of peroxynitrite, leading to the proposal of a nitrosoperoxycarbonate anion adduct, with a distinctly different chemistry from that of OONO Ϫ (19). We reported previously that the mere acidification of an aqueous peroxynitrite solution resulted in chemiluminescence at 1,270 nm characteristic of the deactivation of singlet oxygen (23). By comparing the intensity of this emission to that of 1 O 2 generated by the reaction of hydrogen peroxide (H 2 O 2 ) with hypochlorite anion (OCl Ϫ ), which is known to be stoichiometric (24), it wa...

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Section: Discussionmentioning

confidence: 99%

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution

Khan

Kovacic

Kolbanovskiy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…The mechanism of decomposition involves the homolytic cleavage of its peroxo-bond producing hydroxyl radical (OH) and nitrogen dioxide (NO 2 ) in a solvent cage from which ~30 % of the radicals escape and can be trapped at high target concentration, while the rest recombine to produce nitrate ( Fig. 1) [45,46]. The reactions depending on the products of homolysis are first order in peroxynitrite and zero order in target, i.e the presence of the target does not affect the rate of peroxynitrite decay.…”

Section: The Hydroxyl Radical/nitrogen Dioxide Pathwaymentioning

confidence: 99%

Nitrogen monoxide and oxidative stress: composition and intensity of cellular oxidative bursts cocktail. A study through artificial electrochemical synapses on single human fibroblasts

Trujillo¹,

Naviliat²,

Álvarez³

et al. 2000

Analusis

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Peroxynitrite1 is a powerful oxidant produced in biological systems from superoxide (O 2˙-) and nitric oxide (˙NO). Peroxynitrite has been implicated in a host of disease states, including neurodegenerative disorders [1], chronic inflammation and autoimmune diseases [2,3], ischemia-reperfusion injury [4] and septic shock [5].The chemistry of peroxynitrite is complex and highly pHdependent [6,7]. Not only peroxynitrite anion (ONOO -) and its conjugated acid, peroxynitrous acid (ONOOH) (pK a = 6.8) are potent oxidants by themselves [8,9] but also they can lead to the production of secondary reactive species. Moreover, peroxynitrite is capable of nitrating aromatics [10] in a process that can be enhanced by metal centres and CO 2 [11].Despite of being a reactive and short-lived species, which precludes its direct isolation or measurement, peroxynitrite detection and quantitation can be achieved with the use of detector molecules as well as molecular footprints that take advantage of oxidation and nitration reactions. A good detector molecule should be sensitive and outcompete the multiple reactions that peroxynitrite can undergo in biological systems. Moreover, both detector molecules and footprints should be specific, in order to discriminate between the reactions of peroxynitrite from those of other species, including its precursors ˙NO and O2 -, and other ˙NO or O˙2 --derived oxidants. None of the detection systems used until now fulfil all these requisites, and a subtle knowledge of the biological chemistry of peroxynitrite is required in order to choose and utilise the best approach in different biochemical or biological systems. Peroxynitrite formationAlthough several possible routes lead to peroxynitrite formation, the main one in biology arises from the radicalradical combination reaction of ˙NO[12] and O˙2 - [13,14] NOThis is a diffusion-controlled reaction with a second order rate constant (k 2 ) that has been independently determined as 4. 1 The term peroxynitrite refers to the sum of peroxynitrite anion (ONOO-) and peroxynitrous acid (ONOOH). IUPAC recommended names for peroxynitrite anion, peroxynitrous acid, nitroso-peroxocarboxylate (ONOOCO 2 -) and nitric oxide are oxoperoxynitrate (1-), hydrogen oxoperoxynitrate, 1-carboxylato-2-nitrosodioxidane and nitrogen monoxide respectively.

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“…A lthough Mahoney (1) had demonstrated as early as in 1970 that the decomposition of ONOOH yields about 30% ⅐ NO 2 and ⅐ OH free radicals, a great confusion ensued during the next two decades because of misinterpretations of inconclusive experiments, sometimes stimulated by improper thermodynamic estimations (2)(3)(4)(5)(6)(7). Fortunately, by the end of the nineties, the radical mechanism was readopted after judicious experiments in several laboratories (8)(9)(10)(11).…”

mentioning

confidence: 99%

The decomposition of peroxynitrite does not yield nitroxyl anion and singlet oxygen

Merényi

Lind²,

Czapski³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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In a recent article [Khan, A. U., Kovacic, D., Kolbanovsky, A., Desai, M., Frenkel, K. & Geacintov, N. E. (2000) Proc. Natl. Acad. Sci. USA 97, 2984 -2989], the authors claimed that ONOO ؊ , after protonation to ONOOH, decomposes into 1 HNO and 1 O2 according to a spin-conserved unimolecular mechanism. This claim was based partially on their observation that nitrosylhemoglobin is formed via the reaction of peroxynitrite with methemoglobin at neutral pH. However, thermochemical considerations show that the yields of 1 O2 and 1 HNO are about 23 orders of magnitude lower than those of ⅐ NO2 and ⅐ OH, which are formed via the homolysis of ONOOH. We also show that methemoglobin does not form with peroxynitrite any spectrally detectable product, but with contaminations of nitrite and H 2O2 present in the peroxynitrite sample. Thus, there is no need to modify the present view of the mechanism of ONOOH decomposition, according to which initial homolysis into a radical pair, [ONO ⅐ ⅐ OH] cage, is followed by the diffusion of about 30% of the radicals out of the cage, while the rest recombines to nitric acid in the solvent cage.A lthough Mahoney (1) had demonstrated as early as in 1970 that the decomposition of ONOOH yields about 30% ⅐ NO 2 and ⅐ OH free radicals, a great confusion ensued during the next two decades because of misinterpretations of inconclusive experiments, sometimes stimulated by improper thermodynamic estimations (2-7). Fortunately, by the end of the nineties, the radical mechanism was readopted after judicious experiments in several laboratories (8-11). Additional insight gained during these later investigations allowed the pH dependence of the product yield of peroxynitrite decomposition to be explained, i.e., the decomposition of peroxynitrite in acidic solutions yields nitrate as a final product, but as the pH is raised, O 2 and nitrite in a 1:2 ratio are formed at the expense of nitrate, reaching ca. 40% O 2 at pH 9 (12, 13). The slowly returning faith in the radical model was disturbed recently by Khan et al. (14), who reported that the decomposition of peroxynitrite at neutral pH forms high yields of NO Ϫ and 1 O 2 . In this work, the authors claim that nitrosylhemoglobin (HbNO) is formed via the reaction of peroxynitrite with methemoglobin (MetHb) at neutral pH. They also report that the decomposition of peroxynitrite in the presence of 9,10-diphenylanthracene (DPA) forms substantial amounts of the transannular peroxide of DPA. Because DPA is considered a specific reagent for Materials and MethodsMaterials. All chemicals were of analytical grade and were used as received. Solutions were prepared with distilled water, which was purified further by using a Milli-Q water purification system from Millipore. Bovine MetHb (Sigma) was purified by passing through a Sephadex G-25 column and using 100 mM phosphate buffer (pH 7) as the eluant. The concentration of MetHb was determined from its absorption at 406 nm by using ϭ 154 mM Ϫ1 ⅐cm Ϫ1 (15). Fresh solutions of peroxynitrite were prepared before use ...

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Thermodynamics of Peroxynitrite and Its CO₂ Adduct

Cited by 102 publications

References 40 publications

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution

Nitrogen monoxide and oxidative stress: composition and intensity of cellular oxidative bursts cocktail. A study through artificial electrochemical synapses on single human fibroblasts

The decomposition of peroxynitrite does not yield nitroxyl anion and singlet oxygen

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Thermodynamics of Peroxynitrite and Its CO2 Adduct

Cited by 102 publications

References 40 publications

The decomposition of peroxynitrite to nitroxyl anion (NO − ) and singlet oxygen in aqueous solution

The decomposition of peroxynitrite to nitroxyl anion (NO − ) and singlet oxygen in aqueous solution

Nitrogen monoxide and oxidative stress: composition and intensity of cellular oxidative bursts cocktail. A study through artificial electrochemical synapses on single human fibroblasts

The decomposition of peroxynitrite does not yield nitroxyl anion and singlet oxygen

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Thermodynamics of Peroxynitrite and Its CO₂ Adduct

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution

The decomposition of peroxynitrite to nitroxyl anion (NO ⁻ ) and singlet oxygen in aqueous solution