Chemiluminescent Aldehyde and -Diketone Reactions Promoted by Peroxynitrite
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- 作者：Fernanda S. Knudsen ; Carlos A. A. Penatti ; Leandro O. Royer ; Karine A. Bidart ; Marcelo Christoff ; Denise Ouchi ; and Etelvino J. H. Bechara
- 刊名：Chemical Research in Toxicology
- 出版年：2000
- 出版时间：May 2000
- 年：2000
- 卷：13
- 期：5
- 页码：317 - 326
- 全文大小：203K
- 年卷期：v.13,no.5(May 2000)
- ISSN：1520-5010
文摘
Peroxynitrite is shown here to promote the aerobic oxidation of isobutanal (IBAL) and3-methyl-2,4-pentanedione (MP) in a pH 7.2 phosphate buffer into acetone plus formate andbiacetyl plus acetate, respectively. These products are expected from dioxetane intermediates,whose thermolysis is known to be chemiluminescent (CL). Accordingly, the extent of total oxygenuptake by IBAL at different concentrations parallels the corresponding CL maximumintensities. The pH profile based on oxygen uptake data for the MP reaction matches thetitration curve of peroxynitrous acid (pKa ~ 7), indicating that peroxynitrite anion is theoxidizing agent. Energy transfer studies with IBAL and the 9,10-dibromoanthracene-2-sulfonateion, a triplet carbonyl detector, indicates that triplet acetone (
= 19 
s) is the energy donor.It is postulated that IBAL- or MP-generated triplet carbonyls are produced by the thermolysisof dioxetane intermediates, which are formed by the cyclization of 
-hydroperoxide intermediates produced by insertion of dioxygen into the IBAL or MP enolyl radicals, followed by theirreduction. Accordingly, EPR spin-trapping studies with 3,5-dibromo-4-nitrosobenzenesulfonicacid (DBNBS) and 2-methyl-2-nitrosopropane (MNP) revealed the intermediacy of carbon-centered radicals, as expected for one-electron abstraction from the enol forms of IBAL or MPby peroxynitrite. The EPR data obtained with IBAL also reveal formation of the isopropylradical produced by competitive nucleophilic addition of ONOO- to IBAL, followed by homolyticcleavage of this adduct and 
-scission of the resulting Me2CHCH(O-)O
. Superstoichiometricformation of fragmentation products from IBAL or MP attests to the prevalence of anautoxidation chain reaction, here proposed to be initiated by one-electron abstraction by ONOO-from the substrate. This work reveals the potential role of peroxynitrite as a generator ofelectronically excited species that may contribute to deleterious and pathological processesassociated with excessive nitric oxide and aldehyde production.
= 19 s) is the energy donor.It is postulated that IBAL- or MP-generated triplet carbonyls are produced by the thermolysisof dioxetane intermediates, which are formed by the cyclization of -hydroperoxide intermediates produced by insertion of dioxygen into the IBAL or MP enolyl radicals, followed by theirreduction. Accordingly, EPR spin-trapping studies with 3,5-dibromo-4-nitrosobenzenesulfonicacid (DBNBS) and 2-methyl-2-nitrosopropane (MNP) revealed the intermediacy of carbon-centered radicals, as expected for one-electron abstraction from the enol forms of IBAL or MPby peroxynitrite. The EPR data obtained with IBAL also reveal formation of the isopropylradical produced by competitive nucleophilic addition of ONOO- to IBAL, followed by homolyticcleavage of this adduct and -scission of the resulting Me2CHCH(O-)O. Superstoichiometricformation of fragmentation products from IBAL or MP attests to the prevalence of anautoxidation chain reaction, here proposed to be initiated by one-electron abstraction by ONOO-from the substrate. This work reveals the potential role of peroxynitrite as a generator ofelectronically excited species that may contribute to deleterious and pathological processesassociated with excessive nitric oxide and aldehyde production.