Reactivities of hydroxyl and perhydroxyl radicals toward cytosine and thymine: A comparative study

Abstract

As the hydroxyl (OH) and perhydroxyl (OOH) radicals are known to play important roles in biological systems, their reactions with cytosine and thymine were studied. Addition reactions of these radicals at different sites of cytosine and thymine, and hydrogen abstraction reactions by each of the two radicals from the different sites of the two molecules were studied at the B3LYP/6‐31G(d,p), B3LYP/AUG‐cc‐pVDZ and BHandHLYP/AUG‐cc‐pVDZ levels of density functional theory. Effect of solvation in aqueous media on the reactions was studied at all these levels of theory using single point energy calculations using the polarizable continuum model. The present study shows that whereas the OH radical would abstract H atoms from the various sites of cytosine and thymine efficiently, the OOH radical would have poor reactivity in this regard. The OH radical is also predicted to be much more reactive than the OOH radical with regard to addition reactions at the C5 and C6 sites of both thymine and cytosine, though the OOH radical is also predicted to have significant reactivity in this respect. © 2012 Wiley Periodicals, Inc.

Insight into the Mechanism of the Initial Reaction of an OH Radical with DNA/RNA Nucleobases: A Computational Investigation of Radiation Damage

“…For thymine we find the same order of addition C 6 >C 5 and almost the same order for abstraction H 7 >H 1 >H 3 >H 6 as ref. 6 with the only difference being the order of H 3 and H 6 . Our calculated overall rate constants agree exceptionally well with the experimental ones in ref.…”

“…Our calculated abstraction energies agree with those of ref. 6 being of the order H 42 >H 41 >H 5 >H 6 . We guess that the rate constants for the addition reactions in cytosine will somewhat resemble those found for thymine and uracil, due to the resemblance in geometry.…”

“…A thorough review of the interactions of electrons with nucleobases has been done by Schaefer and co‐workers,5 but no such unifying review has been found for the interactions of the nucleobases with the OH radical. Of earlier investigations into the reactions of the bases with the OH radical one can mention that calculations of the energetic barriers for the reaction between the OH radical and the pyrimidine nucleobases, have shown that addition is the more favourable reaction type through addition onto carbon positions C 5 or C 6 depending on the nucleobase in question 6–8. These studies conclude that in cytosine the preference for addition reactions decreases in the series C 5 >C 6 >C 4 , while for thymine the preference decreases in the series C 6 >C 5 .…”

Communication: Electronic UV-Vis transient spectra of the ·OH reaction products of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active space self-consistent field second-order perturbation (CASPT2//CASSCF) theory

“…[1][2][3][4][5][6][7] It is well known that these reactions yield modified nucleobases which may cause mutations in DNA/RNA sequences and/or cell reproduction inability. 8 It has been demonstrated both experimentally 2,3,5,9 and theoretically [10][11][12][13] that addition to the C5-C6 double bond is the most favored mechanism in pyrimidine nucleobases. Using differential redox properties of the C5OH and C6OH radical adducts, 14 estimated values of the C5OH:C6OH ratios were determined during the 1980s decade.…”

DFT study of adenine‐uracil base pair damage by OH radical

“…Base pairs are the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. However, DNA and RNA are vulnerable to damage under the action of reactive oxygen species in normal metabolites in organisms . Especially, OH radical, which has an extremely short lifetime, generates abundantly in cell and plays a vital character for DNA and RNA damage .…”