Reactivity of Nucleic Acid Sugar Radicals

Chatgilialoglu, Chryssostomos

doi:10.1002/9780470526279.ch4

Cited by 15 publications

(24 citation statements)

References 111 publications

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“…and (ii) The formation of C 5′ + by the oxidation reaction with K 3 Fe(CN) 6 and the rate constant of the reaction was reported to be ca. 10 9 M −1 s −1 27,88. …”

Section: Resultsmentioning

confidence: 99%

“…The cross-link formation or sugar ring fragmentation is not unusual and has been found experimentally. 27,28,33 C 1′ and C 3′ cations were found to retain their parent neutral sugar radical structure and radical site becomes planar, i.e., the sum of the angles centering C 1′ and C 3′ atoms is 360 deg., see Figures S2 and S3 in the SI. Except for C 2′ + , the optimization of C 1′ + , C 3′ + , C 4′ + and C 5′ + in solution are found to retain their parent sugar radical structure, Figure S2 and S3 in the SI.…”

Section: Resultsmentioning

confidence: 99%

“…which readily reacts with DNA bases and the sugar phosphate backbone to produce base and sugar radicals. 1,27,28,29,30–33 The dominant reaction of OH • is the addition reaction at C 4 , C 5 and C 8 atoms of purines and C 5 and C 6 atoms of pyrimidines. 34–38 OH • reacts with the sugar moiety by hydrogen abstraction and produce C 1′ • , C 2′ • , C 3′ • , C 4′ • and C 5′ • sugar radicals.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

One-Electron Oxidation of Neutral Sugar Radicals of 2′-Deoxyguanosine and 2′-Deoxythymidine: A Density Functional Theory (DFT) Study

2012

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One electron oxidation of neutral sugar radicals has recently been suggested to lead to important intermediates in the DNA damage process culminating in DNA strand breaks. In this work, we investigate sugar radicals in a DNA model system to understand the energetics of sugar radical formation and oxidation. The geometries of neutral sugar radicals C1′•, C2′•, C3′•, C4′• and C5′• of 2′-deoxyguanosine (dG) and 2′-deoxythymidine (dT) were optimized in the gas phase and in solution using the B3LYP and ωB97x functionals and 6-31++G(D) basis set. Their corresponding cations (C1′+, C2′+, C3′+, C4′+ and C5′+) were generated by removing an electron (one-electron oxidation) from the neutral sugar radicals and their geometries were also optimized using the same methods and basis set. The calculation predicts the relative stabilities of the neutral sugar radicals in the order C1′• > C4′• > C5′• > C3′• > C2′•, respectively. Of the neutral sugar radicals, C1′• has the lowest vertical ionization potential (IPvert) ca. 6.33 eV in the gas phase and 4.71 eV in solution. C2′• has the highest IPvert ca. 8.02 eV in the gas phase and the resultant C2′ cation is predicted to undergo a barrierless hydride transfer from the C1′ site to produce the C1′ cation. One electron oxidation of C2′• in dG is predicted to result in a low lying triplet state consisting of G+• and C2′•. The 5′,8-cyclo-2′-deoxyguanosin-7-yl radical formed by intramolecular bonding between C5′• and C8 of guanine transfers spin density from C5′ site to guanine and this structure has IPvert 6.25 eV and 5.48 eV in the gas phase and in solution.

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“…and (ii) The formation of C 5′ + by the oxidation reaction with K 3 Fe(CN) 6 and the rate constant of the reaction was reported to be ca. 10 9 M −1 s −1 27,88. …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

One-Electron Oxidation of Neutral Sugar Radicals of 2′-Deoxyguanosine and 2′-Deoxythymidine: A Density Functional Theory (DFT) Study

2012

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“…After abstraction of a hydrogen atom from 2-deoxyribose, the fate of the carbon-centered radical depends upon the environment. There are several studies focused on the selective generation of these species to obtain quantitative data [10,11,12]. The C5′ radical has a very peculiar behavior with respect to the other positions of 2-deoxyribose, since its corresponding peroxyl radical does not generate an abasic site and leads to the formation of unique cyclic base–sugar adducts, the purine 5′,8-cyclo-2′-deoxynucleosides (cPu).…”

Section: Introductionmentioning

confidence: 99%

5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance

Chatgilialoglu

Ferreri

Geacintov

et al. 2019

Cells

Self Cite

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Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols.

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“…1 – 4 One electron oxidation of the sugar-phosphate backbone creates an electron loss center (hole) which upon deprotonation forms a sugar radical and these are the immediate precursors of radiation-induced frank DNA-strand breaks produced via the electron-loss (oxidative) pathway. 1, 4 – 13 Hole transfer from the sugar-phosphate backbone to a DNA base creates a base cation radical which prevents formation of sugar radicals via deprotonation (scheme 1). 5 – 7, 11, 12, 14 – 19 Our recent work 14 has shown that, for successful formation of a sugar radical (for example, C5′•), a very rapid (< 10 -12 s) deprotonation must occur from the one-electron oxidized sugar-phosphate backbone before a competitive backbone-to-base hole transfer can occur (scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Formation of S–Cl Phosphorothioate Adduct Radicals in dsDNA S-Oligomers: Hole Transfer to Guanine vs Disulfide Anion Radical Formation

et al. 2013

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In phosphorothioate containing dsDNA-oligomers (S-oligomers), one of the two non-bridging oxygen atoms in the phosphate moiety of sugar-phosphate backbone is replaced by sulphur. In this work, electron spin resonance (ESR) studies of one-electron oxidation of several S-oligos by Cl2•− at low temperatures are investigated. Electrophilic addition of Cl2•− to phosphorothioate with elimination of Cl− leads to the formation of a 2-center three-electron σ2σ*1 bonded adduct radical (-P-S∸Cl). In AT S-oligomers with mutiple phosphorothioates, i.e., d[ATATAsTsAsT]2, -P-S∸Cl reacts with a neighboring phosphorothioate to form the σ2σ*1 bonded disulphide anion radical ([-P-S∸S-P-]−). With AT S-oligomers with a single phosphorothioate, i.e., d[ATTTAsAAT]2, reduced levels of conversion of -P-S∸Cl dsDNA [-P-S∸S-P-]− are found. For guanine containing S-oligomers containing one phosphorothioate, -P-S∸Cl results in one-electron oxidation of guanine base but not of A, C, or T thereby leading to selective hole transfer to G. The redox potential of -P-S∸Cl is thus higher than that of G but is lower than those of A, C, and T. Spectral assignments to -P-S∸Cl and [-P-S∸S-P-]− are based on reaction of Cl2•− with the model compound diisopropyl phosphorothioate. The results found for d[TGCGsCsGCGCA]2 suggest that [-P-S∸S-P-]− undergoes electron transfer to the one-electron oxidized G healing the base but producing a cyclic disulfide bonded backbone with a substantial bond strength (50 kcal/mol). Formation of -P-S∸Cl and its conversion to [-P-S∸S-P-]− is found to be unaffected by O2 and this is supported by the theoretically calculated electron affinities and reduction potentials of [-P-S-S-P-] and O2.

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Reactivity of Nucleic Acid Sugar Radicals

Cited by 15 publications

References 111 publications

One-Electron Oxidation of Neutral Sugar Radicals of 2′-Deoxyguanosine and 2′-Deoxythymidine: A Density Functional Theory (DFT) Study

One-Electron Oxidation of Neutral Sugar Radicals of 2′-Deoxyguanosine and 2′-Deoxythymidine: A Density Functional Theory (DFT) Study

5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance

Formation of S–Cl Phosphorothioate Adduct Radicals in dsDNA S-Oligomers: Hole Transfer to Guanine vs Disulfide Anion Radical Formation

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