Ketone-Catalyzed Decomposition of Peroxynitrite via Dioxirane Intermediates

Yang, Dan; Tang, Yeung‐Chiu; Chen, Jian; Wang, † Xue-Chao; Bartberger, Michael D.; Houk, K. N.; Olson, Leif P.

doi:10.1021/ja984358v

Cited by 64 publications

(87 citation statements)

References 49 publications

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“…6 at pH 9.8. These results are in agreement with the observation of Yang et al [21] that nitrite is oxidized quantitatively by the intermediate dimethyldioxirane.…”

supporting

confidence: 94%

“…Adducts similar to the 1-carboxylato-2-nitrosodioxidane anion have been proposed for aldehydes [20] and other carbonyl compounds [21], and could similarly enhance formation of nitrated products. That peroxynitrite reacts with formaldehyde was first reported in 1929 (Scheme 1).…”

mentioning

confidence: 99%

“…For the reaction of peroxynitrite and acetone, we proposed the formation of an adduct as intermediate (Scheme 3) [29]. In 1999, it was reported that activated ketones can act as catalysts for the isomerization of peroxynitrite, and dioxiranes were suggested as intermediates [21].…”

mentioning

confidence: 99%

“…As expected, peroxynitrite does not react with the deactivated carbonyl compounds N,N-dimethylacetamide, l-alanylalanine, and methyl acetate. With more electrophilic compounds like propionaldehyde or methyl pyruvate, the reaction proceeds faster (530 m À1 s À1 [20] and 1.3 Â 10 4 m À1 s À1 [21], resp.). Thus, although peroxynitrite reacts with carbonyl compounds, these reactions, unlike that with carbon dioxide, cannot be relevant under physiological conditions.…”

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confidence: 99%

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Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Tibi

Koppenol

2000

HCA

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Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday Peroxynitrite (ONOO À , oxoperoxonitrate(1 À)), an isomer of nitrate that oxidizes and nitrates biomolecules, is likely to be formed in vivo from the reaction of superoxide with nitrogen monoxide. To determine whether flavonoids scavenge peroxynitrite as postulated in the literature, we studied the reactions of peroxynitrite with phenol, hydroquinone, catechol, and the flavonoid monoHER. These reactions are first-order with respect to peroxynitrous acid and zero-order with respect to the organic compounds, and proceed as fast as the isomerization of peroxynitrous acid to nitrate. In vivo, a large fraction of all peroxynitrite is likely to react with carbon dioxide to form an unstable adduct, the 1-carboxylato-2-nitrosodioxidane anion (ONOOCO À 2 ). The presence of phenolic compounds did not influence the rate of disappearance of this adduct, which was ca. 4 Â 10 2 s À1 . On the basis of these kinetic studies, it can be concluded that flavonoids are not scavengers of peroxynitrite. The products from the reaction of peroxynitrite with hydroquinone (benzene-1,4-diol) and catechol (benzene-1,2-diol) are para-benzoquinone and ortho-benzoquinone, respectively; no nitrated products were found. In a subsequent reaction, ortho-quinone reacted with nitrite, a common contaminant of peroxynitrite preparations to form 1,2-dihydroxy-4-nitrobenzene. We also investigated whether carbonyl compounds could redirect the reactivity of peroxynitrite toward nitration, as carbon dioxide does. The reaction with acetone is first-order with respect to peroxynitrite and first-order with respect to the carbonyl compound. The rate constant is 1.8 m À1 s À1 at neutral pH and 208; peroxynitrite does not react with the carbonyl compounds dimethyl acetamide, lalanylalanine, or methyl acetate. It is not likely that the carbonyl compounds or the mono-, di-, or polyphenolic compounds can scavenge peroxynitrite in vivo.

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“…6 at pH 9.8. These results are in agreement with the observation of Yang et al [21] that nitrite is oxidized quantitatively by the intermediate dimethyldioxirane.…”

supporting

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Tibi

Koppenol

2000

HCA

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“…), pyruvate (k 2 ) 88 M -1 s -1 , pH 7.4, 37°C), and 3-methylacetoacetone (k 2 ) 166 M -1 s -1 , pH 7, 25°C) (24)(25)(26). Hence, these reactions have been considered of negligible biological relevance.…”

Section: Introductionmentioning

confidence: 99%

Radical Acetylation of 2′-Deoxyguanosine and l-Histidine Coupled to the Reaction of Diacetyl with Peroxynitrite in Aerated Medium

Massari

Fujiy

Dutra

et al. 2008

Chem. Res. Toxicol.

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Diacetyl, like other alpha-dicarbonyl compounds, is reportedly cytotoxic and genotoxic. A food and cigarette contaminant, it is related with alcohol hepatotoxicity and lung disease. Peroxynitrite is a potent oxidant formed in vivo by the diffusion-controlled reaction of the superoxide radical anion with nitric oxide, which is able to form adducts with carbon dioxide and carbonyl compounds. Here, we investigate the nucleophilic addition of peroxynitrite to diacetyl forming acetyl radicals, whose reaction with molecular oxygen leads to acetate. Peroxynitrite is shown to react with diacetyl in phosphate buffer (bell-shaped pH profile with maximum at 7.2) at a very high rate constant ( k 2 = 1.0 x 10 (4) M (-1) s (-1)) when compared with monocarbonyl substrates ( k 2 < 10 (3) M (-1) s (-1)). Phosphate ions (100-500 mM) do not affect the rate of spontaneous peroxynitrite decay, but the H 2PO 4 (-) anion catalyzes the nucleophilic addition of the peroxynitrite anion to diacetyl. The intermediacy of acetyl radicals is suggested by a three-line spectrum ( a N = a H = 0.83 mT) obtained by EPR spin trapping of the reaction mixture with 2-methyl-2-nitrosopropane. The peroxynitrite reaction is accompanied by concentration-dependent oxygen uptake. Stoichiometric amounts of acetate from millimolar amounts of peroxynitrite and diacetyl were obtained under nonlimiting conditions of dissolved oxygen. In the presence of either l-histidine or 2'-deoxyguanosine, the peroxynitrite/diacetyl system afforded the corresponding acetylated molecules identified by HPLC-MS ( n ). These studies provide evidence that the peroxynitrite/diacetyl reaction yields acetyl radicals and raise the hypothesis that protein and DNA nonenzymatic acetylation may occur in cells and be implicated in aging and metabolic disorders in which oxygen and nitrogen reactive species are putatively involved.

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Reactions of Aldehydes and Ketones and Their Derivatives

Murray¹

Organic Reaction Mechanisms• 1999

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Ketone-Catalyzed Decomposition of Peroxynitrite via Dioxirane Intermediates

Abstract: Ketones are found to be catalysts for the decomposition of peroxynitrite. Kinetics, product studies, and B3LYP transition-state calculations together provide consistent evidence for a mechanism involving the formation of dioxirane intermediates.

Cited by 64 publications

References 49 publications

Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Radical Acetylation of 2′-Deoxyguanosine and l-Histidine Coupled to the Reaction of Diacetyl with Peroxynitrite in Aerated Medium

Reactions of Aldehydes and Ketones and Their Derivatives

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