^•H Atom and ^•OH Radical Reactions with 5-Methylcytosine

Abstract

The reactions between either a hydrogen atom or a hydroxyl radical and 5-methylcytosine (5-MeCyt) are studied by using the hybrid kinetic energy meta-GGA functional MPW1B95. *H atom and *OH radical addition to positions C5 and C6 of 5-MeCyt, or *OH radical induced H-abstraction from the C5 methyl group, are explored. All systems are optimized in bulk solvent. The data presented show that the barriers to reaction are very low: ca. 7 kcal/mol for the *H atom additions and 1 kcal/mol for the reactions involving the *OH radical. Thermodynamically, the two C6 radical adducts and the *H-abstraction product are the most stable ones. The proton hyperfine coupling constants (HFCC), computed at the IEFPCM/MPW1B95/6-311++G(2d,2p) level, agree well with B3LYP results and available experimental and theoretical data on related thymine and cytosine radicals.

Kinetics of deamination and Cu(II)/H 2 O 2 /Ascorbate-induced formation of 5-methylcytosine glycol at CpG sites in duplex DNA

“…We found that the yield of single-nucleobase lesions is ∼100 times more than intrastrand cross-links when methyl-CpG-bearing DNA was treated with Fenton-type reagents (11). A recent theoretical study on 5-methylcytosine predicted that the addition of • OH radical to the double bond is more facile than hydrogen atom abstraction from the 5-methyl group (12), which is in agreement with the scarce experimental data (13). It has not been examined how efficiently the mdCg can be formed relative to the methyl group oxidation products in duplex DNA.…”

“…Previous experimental data obtained for poly(dG-mdC) upon exposure to γ rays (13) and theoretical calculations at the mononucleoside level (12) indicated that the hydroxyl radical can attack 5-methylcytosine at the C5 = C6 double bond and the 5-methyl group, with preference being on attack at the double bond to yield 5-methylcytosine glycol. The latter can deaminate to afford thymine glycol.…”

Transient and steady-state photolysis of p-nitroaniline in aqueous solution

“…When O 2 cooperates with • OH, peroxide is formed when O 2 adds to the nitro substituted hydroxylcyclohexadienyl radicals. Most of the ring cleavages come from these peroxide compounds producing alcohols, aldehydes and acids [30][31][32][33]. As a result, a more prominent degradation pathway is engendered leading to the final evolution of CO 2 and NO 3 − [34 -37].…”

Understanding hydrogenation of the adenine‐thymine base pairs and their anions: A density functional study

“…It has shown the H-atom addition prefers the C8 position of guanine, which has been demonstrated both experimentally and theoretically [29,40]. The hydrogenated cytosine has also been the target of the DFT study [41][42][43][44][45] and EPR/ENDOR experiments [46,47]. The formed hydrogenated radicals would undergo a fast proton rearrangement to form more thermodynamically stable species, which may induce DNA lesions and interstrand crosslinks after trapping electrons.…”