Organic polyoxides

Plesniar, Boo

doi:10.1002/9780470771730.ch16

Cited by 5 publications

(3 citation statements)

References 110 publications

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“…UV exposure can generate 1 O 2 , as does visible light in the presence of suitable (exogenous or endogenous) sensitizers (7). 1 O 2 is also formed during dimerization reactions of peroxyl radicals, via the Russell mechanism, and hence is a common intermediate in many peroxidation reactions (8). 1 O 2 reacts with a broad spectrum of biological molecules including DNA, cholesterol, lipids, and amino acids and proteins (9), and it has been postulated that damage caused thereby plays a role in the development of cataract, sunburn and some skin cancers (10,11).…”

Section: Introductionmentioning

confidence: 99%

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

Wright¹,

Bubb²,

Hawkins³

et al. 2007

Photochemistry and Photobiology

106

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Singlet oxygen (1O2) is generated by a number of enzymes as well as by UV or visible light in the presence of a sensitizer and has been proposed as a damaging agent in a number of pathologies including cataract, sunburn, and skin cancers. Proteins, and Cys, Met, Trp, Tyr and His side chains in particular, are major targets for 1O2 as a result of their abundance and high rate constants for reaction. In this study it is shown that long‐lived peroxides are formed on free Tyr, Tyr residues in peptides and proteins, and model compounds on exposure to 1O2 generated by both photochemical and chemical methods. The yield of these species is significantly enhanced in D2O and decreased by azide. Nuclear magnetic resonance and mass spectroscopic analysis of reaction mixtures, or materials separated by high‐performance liquid chromatography, are consistent with the initial formation of an (undetected) endoperoxide that undergoes rapid ring‐opening to give a hydroperoxide situated at the C1 ring‐position (i.e. para to the phenolic group). In the presence of a free α‐amino group (e.g. with free Tyr), rapid ring‐closure occurs to give an indolic hydroperoxide that decays into the corresponding alcohol, 3a‐hydroxy‐6‐oxo‐2,3,3a,6,7,7a‐hexahydro‐1H‐indole‐2‐carboxylic acid. Hydroperoxides that lack a free α‐amino group (e.g. those formed on 3‐(4‐hydroxyphenyl)propionic acid, N‐Ac‐Tyr and Tyr‐containing peptides) are longer‐lived, with half‐lives of hours to days. These species undergo slow decay at low temperatures to give the corresponding alcohol. Their rate of decay is enhanced at 37°C, or on exposure to UV light or metal ions, and gives rise to reactive radicals, via cleavage of the peroxide bond. These radicals have been characterized by electron paramagnetic resonance spin trapping. These studies demonstrate that long‐lived Tyr‐derived peroxides are formed on proteins exposed to 1O2 and that these may promote damage to other targets via further radical generation.

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Section: Introductionmentioning

confidence: 99%

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

Wright¹,

Bubb²,

Hawkins³

et al. 2007

Photochemistry and Photobiology

106

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“…As a reactive species in oxidation reactions1, 2a it is important and ubiquitous. It can be generated in the troposphere by ozone photolysis,2b, 3 or by the oxidation and combustion of hydrocarbons (autoxidation) 2c, 4a. It can also be prepared in the laboratory by chemical (and photochemical) techniques 2a, 2d, 5a.…”

Section: Introductionmentioning

confidence: 99%

The ¹Δ_g Dioxygen Ene Reaction with Propene: A Density Functional and Multireference Perturbation Theory Mechanistic Study

Maranzana¹,

Ghigo²,

Tonachini³

2003

Chemistry A European J

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This study aims to determine whether a balance between concerted and non-concerted pathways exists, and in particular to ascertain the possible role of diradical/zwitterion or peroxirane intermediates. Three non-concerted pathways, via 1) diradical or 2) peroxirane intermediates, and 3) by means of hydrogen-abstraction/radical recoupling, plus one concerted pathway (4), are explored. The intermediates and transition structures (TS) are optimized at the DFT(MPW1K), DFT(B3LYP) and CASSCF levels of theory. The latter optimizations are followed by multireference perturbative CASPT2 energy calculations. (1) The polar diradical forms from the separate reactants by surmounting a barrier (deltaE(++)(MPW1K)=12, deltaE++(B3LYP)=14, and deltaE(++)(CASPT2)=16 kcal mol(-1) and can back-dissociate through the same TS, with barriers of 11 (MPW1K) and 8 kcal mol(-1) (B3LYP and CASPT2). The diradical to hydroperoxide transformation is easy at all levels (deltaE(++)(MPW1K)<4, deltaE(++)(B3LYP)=1 and deltaE(++)(CASPT2)=1 kcal mol(-1)). (2) Peroxirane is attainable only by passing through the diradical intermediate, and not directly, due to the nature of the critical points involved. It is located higher in energy than the diradical by 12 kcal mol(-1), at all theory levels. The energy barrier for the diradical to cis-peroxirane transformation (deltaE(++)=14-16 kcal mol(-1)) is much higher than that for the diradical transformation to the hydroperoxide. In addition, peroxirane can very easily back-transform to the diradical (deltaE(++)<3 kcal mol(-1)). Not only the energetics, but also the qualitative features of the energy hypersurface, prevent a pathway connecting the peroxirane to the hydroperoxide at all levels of theory. (3) The last two-step pathway (hydrogen-abstraction by (1)O(2), followed by HOO-allyl radical coupling) is not competitive with the diradical mechanism. (4) A concerted pathway is carefully investigated, and deemed an artifact of restricted DFT calculations. Finally, the possible ene/[pi2+pi2] competition is discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Singlet Oxygen–mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

Wright

Bubb

Hawkins

et al. 2002

Photochem Photobiol

195

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Singlet oxygen (1O2) is generated by a number of enzymes as well as by UV or visible light in the presence of a sensitizer and has been proposed as a damaging agent in a number of pathologies including cataract, sunburn, and skin cancers. Proteins, and Cys, Met, Trp, Tyr and His side chains in particular, are major targets for 1O2 as a result of their abundance and high rate constants for reaction. In this study it is shown that long-lived peroxides are formed on free Tyr, Tyr residues in peptides and proteins, and model compounds on exposure to 1O2 generated by both photochemical and chemical methods. The yield of these species is significantly enhanced in D2O and decreased by azide. Nuclear magnetic resonance and mass spectroscopic analysis of reaction mixtures, or materials separated by high-performance liquid chromatography, are consistent with the initial formation of an (undetected) endoperoxide that undergoes rapid ring-opening to give a hydroperoxide situated at the C1 ring-position (i.e. para to the phenolic group). In the presence of a free alpha-amino group (e.g. with free Tyr), rapid ring-closure occurs to give an indolic hydroperoxide that decays into the corresponding alcohol, 3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indole-2-carboxylic acid. Hydroperoxides that lack a free alpha-amino group (e.g. those formed on 3-(4-hydroxyphenyl)propionic acid, N-Ac-Tyr and Tyr-containing peptides) are longer-lived, with half-lives of hours to days. These species undergo slow decay at low temperatures to give the corresponding alcohol. Their rate of decay is enhanced at 37 degrees C, or on exposure to UV light or metal ions, and gives rise to reactive radicals, via cleavage of the peroxide bond. These radicals have been characterized by electron paramagnetic resonance spin trapping. These studies demonstrate that long-lived Tyr-derived peroxides are formed on proteins exposed to 1O2 and that these may promote damage to other targets via further radical generation.

show abstract

Organic polyoxides

Cited by 5 publications

References 110 publications

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

The ¹Δ_g Dioxygen Ene Reaction with Propene: A Density Functional and Multireference Perturbation Theory Mechanistic Study

Singlet Oxygen–mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

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Organic polyoxides

Cited by 5 publications

References 110 publications

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

Singlet Oxygen-mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

The 1Δg Dioxygen Ene Reaction with Propene: A Density Functional and Multireference Perturbation Theory Mechanistic Study

Singlet Oxygen–mediated Protein Oxidation: Evidence for the Formation of Reactive Side Chain Peroxides on Tyrosine Residues¶

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The ¹Δ_g Dioxygen Ene Reaction with Propene: A Density Functional and Multireference Perturbation Theory Mechanistic Study