γ-Radiolysis of 1,3-Dimethyluracil in N<sub>2</sub>O-Saturated Aqueous Solutions

Al-Sheikhly, M.; Sonntag, Clemens von

doi:10.1515/znb-1983-1214

Cited by 40 publications

(37 citation statements)

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“…1,2,4–12 However, under acidic conditions (pH 3), 5-hydroxy-1,3-dimethyluracilyl-C6 (C5-OH adduct) radical has been reported to convert to the corresponding 6-hydroxy-1,3-dimethyluracilyl-C5 (C6-OH adduct) radical. 1,5–9,11,12 Thus, the conversion of T(5OH)• to T(6OH)• observed in this work appears to be thermodynamically controlled.We note that ESR studies of addition of water molecules to one-electron oxidized halopyrimidines in 5.3 M H 2 SO 4 glasses on annealing at 155 to 165 K show formation of C6-OH adduct radical most likely from C5-OH adduct radical to C6-OH adduct radical conversion. 66 …”

Section: Discussionsupporting

confidence: 49%

“…1,5–9,11,12 Our theoretical and experimental work with dThd and thymine nucleotides suggests unimolecular conversion of T(5OH)• to T(6OH)• occurs under alkaline conditions at 170 K. However, we cannot also eliminate some contribution of a catalytic action of OH − by concerted addition to T(5OH)• and elimination to form T(6OH)•.…”

Section: Discussionmentioning

confidence: 83%

“…For example, a combination of pulse radiolysis, ESR with flow systems, and product analyses study has reported that in aqueous solution, under acidic conditions (pH 3) at room temperature the 5-hydroxy-1,3-dimethyluracilyl-C6 (C5-OH adduct) radical of 1,3-dimethyluracil converts to the corresponding 6-hydroxy-1,3-dimethyluracilyl-C5 (C6-OH adduct) radical. 1, 2, 5–11,12 …”

Section: Introductionmentioning

confidence: 99%

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Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

et al. 2013

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In this work, addition of OH− to one-electron oxidized thymidine (dThd) and thymine nucleotides in basic aqueous glasses is investigated. At pHs ca. 9–10 where the thymine base is largely deprotonated at N3, one-electron oxidation of the thymine base by Cl2•− at ca. 155 K results in formation of a neutral thyminyl radical, T(−H)•. Assignment to T(−H)• is confirmed by employing 15N substituted 5'-TMP. At pH ≥ ca. 11.5, formation of the 5-hydroxythymin-6-yl radical, T(5OH)•, is identified as a metastable intermediate produced by OH− addition to T(−H)• at C5 at ca. 155 K. Upon further annealing to ca. 170 K, T(5OH)• readily converts to the 6-hydroxythymin-5-yl radical, T(6OH)•. One-electron oxidation of N3-methyl-thymidine (N3-Me-dThd) by Cl2•− at ca. 155 K produces the cation radical (N3-Me-dThd•+) for which we find a pH dependent competition between deprotonation from the methyl group at C5 and addition of OH− to C5. At pH 7 the 5-methyl deprotonated species is found; however, at pH ca. 9, N3-Me-dThd•+ produces T(5OH)• that on annealing up to 180 K forms T(6OH)•. Through use of deuterium substitution at C5' and on the thymine base, i.e., specifically employing [5',5”-D,D]-5'-dThd, [5',5”-D,D]-5'-TMP, [CD3]-dThd and [CD3,6D]-dThd, we find unequivocal evidence for T(5OH)• formation and its conversion to T(6OH)•. The addition of OH− to the C5 position in T(−H)• and N3-Me-dThd•+ is governed by spin and charge localization. DFT calculations predict that the conversion of the “reducing” T(5OH)• to the “oxidizing” T(6OH)• occurs by a unimolecular OH group transfer from C5 to C6 in the thymine base. The T(5OH)• to T(6OH)• conversion is found to occur more readily for deprotonated dThd and its nucleotides than for N3-Me-dThd. In agreement, calculations predict that the deprotonated thymine base has a lower energy barrier (ca. 6 kcal/mol) for OH transfer than its corresponding N3-protonated thymine base (14 kcal/mol).

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

et al. 2013

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“…data reported in Ref. 44). However, this does not rule out such a reaction in DNA where another base is in close proximity.…”

Section: Pyrimidines and Alkyl Radicalsmentioning

confidence: 79%

The Chemistry of Free-Radical-Mediated DNA Damage

Sonntag

1991

Physical and Chemical Mechanisms in Molecular Radiation Biology

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In the living cell, ionizing radiation can cause DNA damage by the direct effect (ionization of DNA) and the indirect effect (reaction of radicals formed in the neighborhood of DNA with DNA, e.g., OH, e~q' H, protein-and glutathione-derived radicals). Properties of the base radical cations have been studied in model systems using S04 radical to oxidize the nucleobases in aqueous solution. The pK a values of some nucleobase radical cations are reported, so are the ensuing reactions of the thymidine radical cation with water. The products of reactions are compared with those formed by OH radical attack. The reaction of e~q with the nucleobases yields radical anions. Protonation at heteroatom sites and at carbon are discussed, and some recent results regarding the electron transfer to adjacent nucleobases as well as to 5-bromouracil are reported. A brief account is given on the reaction of carbon-centered radicals with the nucleobases. These reactions may mimic the reactions of protein-derived radicals with DNA. Glutathione is present in cells at rather high concentrations and is expected to act as an H-or electron-donor in repairing radiation-induced DNA damage (chemical repair). As thiyl radicals are known to also undergo the reverse reaction, i.e., H-abstraction from suitable solutes, some experiments are reported which probe this type of reaction with dilute DNA solutions.In some polynucleotides radical transfer from the base radical to the sugar moiety occurs with the consequence of strand breakage and base release. Some currently held mechanistic concepts are discussed.Attention is drawn to some important open questions which should be addressed in the near future.

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“…-H + CH 3 1 1,3-Dimethyluracil (1,3-DMU) is a simple model system for the pyrimidine component in the nucleic acids (for review see von Sonntag and Schuchmann (1986)) whose OH-induced reactions are well known (Al-Sheikhly and von Sonntag 1983) . Its radical cation is most conveniently generated by reacting solvated electrons (and H atoms) from the radiolysis of water (reaction 3) with peroxodisulphate (reaction 4) .…”

Section: Introductionmentioning

confidence: 99%

The SO⁻·₄-induced Chain Reaction of 1,3-dimethyluracil with Peroxodisulphate

Schuchmann

Deeble

Olbrich

et al. 1987

International Journal of Radiation Biology and Related Studies

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The sulphate radical SO4(.-) reacts with 1,3-dimethyluracil (1,3-DMU) (k = 5 X 10(9) dm3 mol-1 s-1) thereby forming with greater than or equal to 90 per cent yield the 1,3-DMU C(5)-OH adduct radical 4 as evidenced by its absorption spectrum and its reactivity toward tetranitromethane. Pulse-conductometric experiments have shown that a 1,3-DMU-SO4(.-) aduct 3 as well as the 1,3-DMU radical cation 1, if formed, must be very short-lived (t1/2 less than or equal to 1 microsecond). The 1,3-DMU C(5)-OH adduct 4 reacts slowly with peroxodisulphate (k = 2.1 X 10(5) dm3 mol-1 s-1). It is suggested that the observed new species is the 1,3-DMU-5-OH-6-SO4(.-) radical 7. At low dose rates a chain reaction is observed. The product of this chain reaction is the cis-5,6-dihydro-5,6-dihydroxy-1,3-dimethyluracil 2. At a dose rate of 2.8 X 10(-3) Gys-1 a G value of approximately 200 was observed ([1,3-DMU] = 5 X 10(-3) mol dm-3; [S2O8(2-)] = 10(-2) mol dm-3; [t-butanol] = 10(-2) mol dm-3). The peculiarities of this chain reaction (strong effect of [1,3-DMU], smaller effect of [S2O(2-)8]) is explained by 7 being an important chain carrier. It is proposed that 7 reacts with 1,3-DMU by electron transfer, albeit more slowly (k approximately 1.2 X 10(4) dm3 mol-1 s-1) than does SO4(.-). The resulting sulphate 6 is considered to hydrolyse into 2 and sulphuric acid which is formed in amounts equivalent to those of 2. Computer simulations provide support for the proposed mechanism. The results of some SCF calculations on the electron distribution in the radical cations derived from uracil and 1-methyluracil are also presented.

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γ-Radiolysis of 1,3-Dimethyluracil in N₂O-Saturated Aqueous Solutions

Cited by 40 publications

References 0 publications

Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

The Chemistry of Free-Radical-Mediated DNA Damage

The SO⁻·₄-induced Chain Reaction of 1,3-dimethyluracil with Peroxodisulphate

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γ-Radiolysis of 1,3-Dimethyluracil in N2O-Saturated Aqueous Solutions

Cited by 40 publications

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Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

The Chemistry of Free-Radical-Mediated DNA Damage

The SO−·4-induced Chain Reaction of 1,3-dimethyluracil with Peroxodisulphate

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γ-Radiolysis of 1,3-Dimethyluracil in N₂O-Saturated Aqueous Solutions

The SO⁻·₄-induced Chain Reaction of 1,3-dimethyluracil with Peroxodisulphate