OH Radical-Induced Charge Migration in Oligodeoxynucleotides

Abstract

Using the technique of pulse radiolysis with spectrophotometric detection, OH radical (•OH)-induced electron transfer by intramolecular processes was studied in aqueous solutions containing either equimolar binary mixtures of deoxynucleosides or di- and oligodeoxynucleotides at pH 7.4. The time-resolved optical absorbance changes in mixtures of monodeoxynucleosides did not reveal significant electron transfer, indicating the lack of intermolecular electron transfer induced by •OH. Of the dinucleotides studied, only 2‘-deoxyadenylyl-(3‘→5‘)-2‘-deoxyguanosine (dApdG) shows •OH-induced intramolecular electron transfer. This reaction involves electron transfer from guanine to the adenine radical, which results from dehydration of its C(4)−•OH adduct and was monitored at 400 nm. The rate-determining step of electron transfer is the dehydration of the C(4)−•OH adduct of adenine. With the single-stranded oligodeoxynucleotides, dAGA, dAAGAA, and dAAGTA, the spectral changes with time are consistent with electron transfer occurring from guanine, but to only one of the possible neighboring adenine radicals produced by dehydration of the adenine C(4)−•OH adduct. In contrast, •OH interactions with dATGAA and dATGTA do not induce electron transfer from guanine to the adenine radical produced by dehydration of the C(4)−•OH adduct. These results indicate that the dehydrated adenine radical 5‘ to the guanine is preferentially involved in the electron-transfer process.

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

“… The efficiency of DMPO trapping of this radical may be due to the more sterically accessible exocyclic NH 2 -derived adduct and/or product stability (the exocyclic adduct has an intact aromatic ring). This trapped radical may assume significance in DNA as this redox–neutral radical may be relatively stable [52], leading to A(adenine)-mediated hole migration to adjacent bases[53]. It has been predicted by hole-trapping researchers that the adenine radical cation contributes to the hole-transfer (HT) process through A/T sequences and exists as a real chemical intermediate [54-58].…”

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2′-Deoxyadenosin- N6-yl Radical

“…7 Although direct formation of neutral purine radicals by H-atom abstraction by hydroxyl radicals during γ-radiolysis is generally agreed to be unfavorable, a sequential addition-elimination process (such as through 2 ) can produce these species. 8,9 The neutral purine radicals are also decomposition products of chloramines (e.g. 3 ) that are formed upon reaction with hypochlorite produced by myeloperoxidase as part of the inflammatory response.…”

“…19,20 Generation of dA• from 1 may quench hole migration in DNA, yet this radical has also been proposed to oxidize dG in dinucleotides and DNA. 9,13 The reactivity of dA• is underexplored. Its reaction with molecular oxygen has been reported to be as little as 5 × 10 2 M −1 s −1 7 .…”

DNA Damage Emanating From a Neutral Purine Radical Reveals the Sequence Dependent Convergence of the Direct and Indirect Effects of γ-Radiolysis

“…13 Knowledge of dA• reactivity has mostly been obtained from pulse radiolysis experiments on the nucleoside or dinucleotides containing dA. 4,14–17 These experiments established that dA• oxidizes dG, likely via a proton coupled electron transfer in which the first step is endothermic (−0.16 V) but the overall reaction is thermodynamically favorable (0.13 V) and has been observed in similar systems in DNA (eqn. 1).…”