Chemical Radiation Studies of 8‐Bromo‐2′‐deoxyinosine and 8‐Bromoinosine in Aqueous Solutions

Russo, Marialuisa; Jiménez, Liliana; Mulazzani, Quinto G.; D’Angelantonio, Mila; Guerra, Maurizio; Miranda, Miguel A.; Chatgilialoglu, Chryssostomos

doi:10.1002/chem.200600040

Cited by 15 publications

(30 citation statements)

References 55 publications

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“…Recently, Chatgilialoglu and colleagues have carried out a series of further mechanistic studies of cyPudNs formation [15][16][17][18][19][20]. In addition to discovering better synthetic routes for cyPudNs, these studies have yielded a number of important mechanistic insights into the stereochemistry and energetics of cyPudNs formation, including the determination of a rate constant for the cyclization reaction (1.6 × 10 5 /s) [20].…”

Section: Cyclopurine Deoxynucleosides: Chemistry Formation and Strumentioning

confidence: 99%

The 8,5′-cyclopurine-2′-deoxynucleosides: Candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair

2008

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It is a commonly held view that oxidatively induced DNA lesions are repaired by the base excision repair (BER) pathway, whereas DNA lesions induced by UV light and other "bulky" chemical adducts are repaired by the nucleotide excision repair (NER) pathway. While this distinction is generally accurate, the 8,5'-cyclopurine deoxynucleosides represent an important exception, in that they are formed in DNA by the hydroxyl radical, but are specifically repaired by NER, not by BER. They are also strong blocks to nucleases and polymerases, including RNA polymerase II in human cells. In this review, I will discuss the evidence that these lesions are in part responsible for the neurodegeneration that occurs in some XP patients, and what additional evidence would be necessary to prove such a role. I will also consider other DNA lesions that might be involved in XP neurologic disease. Finally, I will also discuss how our recent studies of these lesions have generated novel insights into the process of transcriptional mutagenesis in human cells, as well as the value of studying these lesions not only for a better understanding of NER but also for other aspects of human health and disease.

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Section: Cyclopurine Deoxynucleosides: Chemistry Formation and Strumentioning

confidence: 99%

The 8,5′-cyclopurine-2′-deoxynucleosides: Candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair

2008

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“…Indeed, DFT calculations at the B1B95/6-31þ(λ=0.7)G** level show that the π radical anion of 10 (R = Me) is unstable and tends to lose Br -, as previously found for the corresponding radical anion of 8-bromo-2 0 -deoxyadenosine 1 and 8-bromo-2 0 -deoxyinosine. 2 The rate constant for the reaction of e aq -with 11 was found to be (4.9 ( 0.1) Â 10 9 M -1 s -1 at pH 7.6, which is 3 times slower than its protonated form 10. The optical absorption spectrum obtained after the reaction of e aq -with 11 at pH 7 is shown in Figure 3 (black circles).…”

Section: Section Biophysical Chemistrymentioning

confidence: 97%

One-Electron Reduction of 8-Bromoisoguanosine and 8-Bromoxanthosine in the Aqueous Phase: Sequential versus Concerted Proton-Coupled Electron Routes

Chatgilialoglu

D’Angelantonio

Kaloudis

et al. 2009

J. Phys. Chem. Lett.

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The reactions of hydrated electrons (e aq -) with 8-bromoisoguanosine and 8-bromoxanthosine were studied by pulse radiolysis techniques and addressed computationally by means of hybrid meta DFT calculations at the B1B95/6-31þG** level. The one-electron oxidized purine derivative is formed either by oxidation of the corresponding purine with SO 4•-or by reduction of the corresponding 8-bromopurine with e aq -at pH 7. The reactivity of 8-bromoxanthosine depends on its protonation state. In agreement with the experimental findings, DFT calculations suggest that the reaction of the e aq -/H þ couple with 8-bromoisoguanosine and 8-bromoxanthosine (monoanion) involves sequential electron-transfer-proton-transfer (ET-PT) and concerted electron-proton-transfer (EPT) pathways, respectively. SECTION Biophysical ChemistryO ur understanding of the one-electron reduction of 8-bromopurines 1 has been improved in recent years (Scheme 1). The nature of the substituents X and Yat positions 6 and 2 of the nitrogenous six-member ring plays an important role in the reaction outcome. 8-Bromo-2 0 deoxyadenosine (X = NH 2 , Y = H) 1 and 8-bromo-2 0 -deoxyinosine (X = O, Y = H) 2 were found to capture hydrated electrons and rapidly lose bromide ions to give the corresponding σ-type radicals 2 as expected for delocalized halide (Cl, Br) π anion radicals. 3 Radical translocation to the sugar moiety affords C5 0 radicals and allows for the detailed study of these species. On the other hand, electron transfer (ET) to 8-bromoguanine (X = O, Y = NH 2 ) 4,5 and 8-bromo-2-aminoadenine (X = Y = NH 2 ) 6 derivatives was found to give radical anion 3, which undergoes a fast protonation at C8 by proton transfer (PT) from solvent to afford the complex 4. This mechanism is similar to the step-by-step ET-PT reactions observed in pulse radiolysis of adenine 7 and guanine 8 nucleosides. The successive debromination allowed studying for the first time the tautomerization of one-electron-oxidized guanosine. 4,5 This Letter reports on the reactivity of 8-bromoisoguanosine (X = NH 2 , Y = O) and 8-bromoxanthosine (X = Y = O) as well as on the dynamics of the proton-coupled electron-transfer (PCET) reactions, [9][10][11] in particular, on the sequential electron-transfer-proton-transfer (ET-PT) versus concerted electron-proton-transfer (EPT) mechanism. 9,10Radiolysis of neutral water leads to e aq -(0.27), HO • (0.28), and H • (0.062), where the values in parentheses represent the radiation chemical yields in units of μmol J -1 . The reactions of e aq -with the substrates were studied in O 2 -free solutions containing 0.25 t-BuOH. With this amount of t-BuOH, HO • and H • are scavenged efficiently. 12 The optical absorption spectrum obtained after the reaction of e aq -with 8-bromoisoguanosine (5) at pH 7 is shown in Figure 1 (black circles). The time profile of the formation of this transient at 340 nm (upper inset) or the disappearance of e aq -at 720 nm (lower inset) leads to the same pseudo-first-order rate constant (k obs ), indicating that if any interm...

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“…From theoretical considerations the behavior of 8-bromopurine derivatives with respect to hydrated electrons can be attributed to differences in the energy gap between the π*-and σ*-radical anions. [26,30] …”

Section: Generation Of One-electron Oxidized 2'-deoxyguanosine Tautomersmentioning

confidence: 98%

“…[26] Pulse radiolysis revealed that one-electron reductive cleavage of the C-Br bond gives the C(8) radical followed by a fast translocation of the radical site to the sugar moiety. Selective generation of a C(5') radical occurs in the 2'-deoxyriboderivative which undergoes 5',8-cyclization, with a rate constant of 1.4 × 10 5 s -1 .…”

Section: Purine 5'8-cyclonucleosidesmentioning

confidence: 99%

DNA Damage and Radical Reactions: Mechanistic Aspects, Formation in Cells and Repair Studies

Cadet¹,

Carell²,

Cellai³

et al. 2008

Chimia

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Several examples of oxidative and reductive reactions of DNA components that lead to single and tandem modifications are discussed in this review. These include nucleophilic addition reactions of the one-electron oxidation-mediated guanine radical cation and the one-electron reduced intermediate of 8-bromopurine 2'-deoxyribonucleosides that give rise to either an oxidizing guanine radical or related 5',8-cyclopurine nucleosides. In addition, mechanistic insights into the reductive pathways involved in the photolyase induced reversal of cyclobutadipyrimidine and pyrimidine (6-4) pyrimidone photoproducts are provided. Evidence for the occurrence and validation in cellular DNA of • OH radical degradation pathways of guanine that have been established in model systems has been gained from the accurate measurement of degradation products. Relevant information on biochemical aspects of the repair of single and clustered oxidatively generated damage to DNA has been gained from detailed investigations that rely on the synthesis of suitable modified probes. Thus the preparation of stable carbocyclic derivatives of purine nucleoside containing defined sequence oligonucleotides has allowed detailed crystallographic studies of the recognition step of the base damage by enzymes implicated in the base excision repair (BER) pathway. Detailed insights are provided on the BER processing of non-double strand break bistranded clustered damage that may consist of base lesions, a single strand break or abasic sites and represent one of the main deleterious classes of radiation-induced DNA damage.

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Chemical Radiation Studies of 8‐Bromo‐2′‐deoxyinosine and 8‐Bromoinosine in Aqueous Solutions

Cited by 15 publications

References 55 publications

The 8,5′-cyclopurine-2′-deoxynucleosides: Candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair

The 8,5′-cyclopurine-2′-deoxynucleosides: Candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair

One-Electron Reduction of 8-Bromoisoguanosine and 8-Bromoxanthosine in the Aqueous Phase: Sequential versus Concerted Proton-Coupled Electron Routes

DNA Damage and Radical Reactions: Mechanistic Aspects, Formation in Cells and Repair Studies

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