Electron Transfer from Nucleobase Electron Adducts to 5-bromouracil. Is Guanine an Ultimate Sink for the Electron in Irradiated DNA?

Abstract

Electron transfer to 5-bromouracil (5-BrU) from nucleobase (N) electron adducts (and their protonated forms) has been studied by product analysis and pulse radiolysis. When an electron is transferred to 5-BrU, the ensuing 5-BrU radical anion rapidly loses a bromide ion; the uracilyl radical thus formed reacts with added t-butanol, yielding uracil. From the uracil yields measured as the function of [N]/[5-BrU] after gamma-radiolysis of Ar-saturated solutions it is concluded that thymine and adenine electron adducts and their heteroatomprotonated forms transfer electrons quantitatively to 5-BrU. Like the electron adduct of adenine, those of cytosine and guanine are rapidly protonated by water. The (protonated) electron adduct of guanine does not transfer an electron to 5-BrU, and in the case of the (protonated) cytosine electron adduct only partial electron transfer is observed. The results can be modelled if the protonated electron adduct (protonated at N(3) or at the amino group) of cytosine, CH., which can transfer its electron to 5-BrU (k approximately 2 x 10(7) dm3 mol-1 s-1) is transformed in a slow tautomerization reaction (k approximately 2.5 x +/- 10(3) s-1) into another form C'H. (possibly protonated at C(6) or C(5)) which does not transfer an electron to 5-BrU. There is also electron transfer from the electron adduct of thymine to cytosine and guanine which serve as electron sinks. The rate constant of electron transfer from the thymine electron adduct to cytosine is about 250 times greater than that of the reverse reaction. The heteroatom-protonated electron-adduct of thymidine transfers an electron to 5-BrU more slowly (k = 2.3 x 10(7) dm3 mol-1 s-1) than the electron-adduct itself (k = 7.2 x 10(8) dm3 mol-1 s-1). Phosphate buffer-induced protonation of the electron-adduct of thymine at carbon (C(6)) prevents electron transfer to 5-BrU. Such phosphate catalysis is also observed as an intramolecular process (k approximately 2 x 10(4) s-1) with thymidine-5'-phosphate but not with the 3'-phosphate. Phosphate-induced protonation at carbon also reduces transfer efficiency for the electron adducts of dinucleoside phosphates such as dTpdT and dTpdA. The data raise the question whether in DNA the guanine moiety may act as the ultimate sink of the electron in competition with other processes such as protonation at C(6) of the thymine electron adduct.

Do Solvated Electrons (eaq–) Reduce DNA Bases? A Gaussian 4 and Density Functional Theory-Molecular Dynamics Study

“…The optimized result for T-6H 2 O •- (Figure 2) appears in direct contrast with the experimental fact that all DNA bases react at diffusion controlled rates with e - aq . 1-7,32-35,53-57 The unpaired electron spin distribution shown in Figure 2 appears anomalous since the stable position for the electron is actually on the thymine not in the water cavity as shown in the Figure. However, this metastable state converts to the stable molecular arrangement when molecular dynamics induces the electron transfer as described below.…”

“…However, pulse radiolysis experiments clearly show that guanine (as a nucleobase, nucleoside, or in oligomers) reacts with e - aq at near diffusion controlled rates. 2,7,53-57 Therefore, reaction of e - aq with guanine is both kinetically and thermodynamically accessible.…”

Radiation-induced reduction of quinoxalin-2-one derivatives in aqueous solutions

“…These are the sites where protonation by water will probably occur preferentially since protonation is likely to occur first at a heteroatom but ultimate protonation may take place at carbon atoms (Hissung et al, 1981). Since quinoxalin-2-ones being (to some extent) structurally similar to purines and hypoxanthines, it can be reasonably assumed that radical anions derived from them are also rapidly protonated as in the case of adenine Hissung et al, 1981;Visscher et al, 1987), guanine Nese et al, 1992), hypoxanthine (Aravindakumar et al, 1994), methyl derivative of xanthine (Rao et al, 1995), inosine (Aravindakumar et al, 1994), and 2'-deoxyinosine (Rao et al, 1996). This mechanism is apparently a general one for electron adducts of heterocyclic compounds Novais and Steenken, 1986).…”

The deprotonated guanine-cytosine base pair

“…Mindful of this present limitation, many researchers are looking for different materials with desirable properties in the microscale to nanoscale size range. Knowledge of the electronic characteristics of DNA and its components can be useful in tailoring its charge transport properties (16,28). Fig.…”