Theoretical Investigations on the Thermal Decomposition Mechanism of 5-Hydroxy-6-hydroperoxy-5,6-dihydrothymidine in Water

Chen, Zeqin; Yang, Xue

doi:10.1021/jp100933d

Cited by 17 publications

(22 citation statements)

References 46 publications

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“…Additional water molecules or the use of continuum models are likely to further lower these barriers, as was shown for the acid-catalyzed hydrolysis of formamide. [51][52][53] For example, at B3LYP/6-31þG(d) (results not included) the overall barriers, 178, 159, and 152 kJ mol -1 , for the reaction of Gua with 2H 2 O, 3H 2 O, and 4H 2 O, respectively, are lower than with a single water (227 kJ mol -1 ). These overall activation energies are, however, still higher than for the reaction with H 2 O/OH -.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Study of the Deamination Reaction of Guanine: A Computational Study

et al. 2011

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The mechanism for the deamination of guanine with H(2)O, OH(-), H(2)O/OH(-) and for GuaH(+) with H(2)O has been investigated using ab initio calculations. Optimized geometries of the reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-31+G(d) levels of theory. Energies were also determined at G3MP2, G3MP2B3, G4MP2, and CBS-QB3 levels of theory. Intrinsic reaction coordinate (IRC) calculations were performed to characterize the transition states on the potential energy surface. Thermodynamic properties (ΔE, ΔH, and ΔG), activation energies, enthalpies, and Gibbs free energies of activation were also calculated for each reaction investigated. All pathways yield an initial tetrahedral intermediate and an intermediate in the last step that dissociates to products via a 1,3-proton shift. At the G3MP2 level of theory, deamination with OH(-) was found to have an activation energy barrier of 155 kJ mol(-1) compared to 187 kJ mol(-1) for the reaction with H(2)O and 243 kJ mol(-1) for GuaH(+) with H(2)O. The lowest overall activation energy, 144 kJ mol(-1) at the G3MP2 level, was obtained for the deamination of guanine with H(2)O/OH(-). Due to a lack of experimental results for guanine deamination, a comparison is made with those of cytosine, whose deamination reaction parallels that of guanine.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Study of the Deamination Reaction of Guanine: A Computational Study

et al. 2011

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“…Our stability ordering is also consistent with the previous reports from experiments and theoretical calculations. [ 23,24 ] The unpaired electron densities are populated mainly on both O a and distal O b , and their values are presented in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…[ 23 ] The relevant DFT B3LYP together with 6‐31+G(d,p) and 6‐311++G(2d,p) basis sets gave the range of the activation barriers from 33.4 to 133.3 kcal/mol. [ 24 ] These facts show that the elimination of the oxidation products could contain some radical intermediates.…”

Section: Introductionmentioning

confidence: 99%

A theoretical study towards understanding the origin of DNA oxidation products

Zhao

Jiang

Wang

et al. 2020

J of Physical Organic Chem

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Reactivity of thymine peroxy radical in DNA and its fate under oxygen‐less condition are studied at DFT B3LYP and M06‐2X functionals together with 6‐31+G(d,p) and aug‐cc‐pVTZ basis sets. The irreversible reaction between OH free radical‐induced C6‐yl and O2 molecule leads to the two main conformers. The spaciously accessible H2′ on the sugar can be abstracted by C6‐peroxy with the estimated barriers of 15.7–21.0 kcal/mol, dependent on various theoretical methods and the conformers. The calculations show that C6‐peroxy has a highly more reactivity towards C (sp3)‐H abstraction reactions than its relative C6‐yl, which is a counter‐intuitive case. Based on the classical Arrhenius rate formula, we find that the vertical electron affinities and proton affinities of the H‐atom acceptors are strongly relevant to electron transfer rate and proton transfer rate, respectively, in the C‐H abstraction reactions. The formed hydroperoxide with the C6‐OaObH2′ constituent can ultrafastly transfer ObH2′ to C2′ radical of the same sugar with a very low barrier (approximately 1.6 kcal/mol) and very strong exothermicity. The results show that the formed hydroperoxide product is too unstable so that it could be quickly transformed into other species and thus is very hard to be experimentally observed. Afterwards, H2′ can be again abstracted by C6‐oxyl radical to result in formation of thymine glycol. The parallel C5‐C6 bond scission reaction leads to formation of the precursor to 5‐hydroxy‐5‐methylhydantion. The two competitive reactions have very low or even negative barriers, dependent on the used functional. Thus, the new radical reaction paths to formation of both thymine glycol and 5‐hydroxy‐5‐methylhydantion are discovered under oxygen‐less condition, which is different from the previously suggested paths under high oxygen concentration surroundings. The influences of the relevant side reactions on formation of the two oxidation damage biomarker molecules are also discussed.

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“…Owning to the similarity in structure to OH-mediated thymine hydroperoxides, the optimum pathway for the decomposition of thymine hydroperoxides, was¯rstly taken into account for 5-OH-6-OOH-DHC in our present calculation, which, as per our previous work, 39 mainly involves the dehydration of C6 hydroperoxyl group, giving rise to the formation of 6-amino-5-hydroxy-5H-pyrimidine-2,4-dione, 2. The optimized geometries and important bond lengths for all the stationary points of pathway A are shown in Fig.…”

Section: Pathway Amentioning

confidence: 99%

“…In such cyclic transition states, the orbits required for the bond dissociation and formation are deformed so much that a large amount of deformation energy is substantially needed. Our previous work on the decomposition of thymidine hydroperoxides and hydrolyzes of nucleosides suggests that the presence of explicit water molecules may bring the barrier down by a few more Kcal/mol because water can act not only as a solvent but as a catalyst, 22,39 where it can donate or accept a proton to promote long-range proton transfer. Then, it is of great interest whether the activation energy of this step can be reduced by the contribution of an extra water molecule.…”

Section: Pathway Amentioning

confidence: 99%

Mechanisms for the Decomposition of Hydroxyl-Radical-Induced Cytosine Hydroperoxides: A Computational Study

Chen

Yang

2013

J. Theor. Comput. Chem.

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Hydroxyl-radical-induced damage to cytosine leads to a multitude of base modi¯cations, which contribute to the natural processes of aging, mutagenesis and carcinogenesis. The stable products resulting from the main hydroxyl-radical-induced cytosine hydroperoxide, 5-hydroxy-6hydroperoxyl-5,6-dihydrocytosine (5-OH-6-OOH-DHC), have been mapped out in the present work for the¯rst time using ab initio calculations. Optimized geometries of all stationary structures in the gas phase were determined at the MP2 and B3LYP using the 6-31G(d) basis set and at the B3LYP/6-311þþG(d,p) levels of theory. Energies were also determined at the G3MP2 level of theory. Meanwhile, full optimization of all stationary points were also performed in aqueous solution at the B3LYP/CPCM/6-31G(d) level of theory to evaluate the solvent e®ect. Three distinct possible pathways, pathways AÀC, were evaluated. For pathway C, four channels, channels DÀG, were characterized in turn. In each pathway, both the direct and the water-mediated processes were considered. The calculated results clearly manifest that (i) pathway C is kinetically favored over pathways A and B and is the most energetically feasible decomposition process of 5-OH-6-OOH-DHC; (ii) for pathway C, channels D, E and G are energetically feasible mechanisms and 6,7-dihydroxy-[1,3,5]triazepane-2,4-dione, 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine, and biuret therefore are predicted to be the kinetically favored decomposition products of 5-OH-6-OOH-DHC; (iii) channel G may be kinetically favored over channels D and E and have the highest possibility to occur; (iv) the thermal decomposition of 5-OH-6-OOH-DHC can be signi¯cantly promoted by the presence of one explicit water molecule. Apart from characterizing the experimental products well, the main striking result of the present DFT computational study is the identi¯cation of a new theoretical optimum decomposition product, i.e. 6,7-dihydroxy-[1,3,5]triazepane-2,4-dione. The data and insights presented here have elucidated the chemical properties of 5-OH-6-OOH-DHC in free radical reactions and should facilitate to assess their mutagenic features.

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Theoretical Investigations on the Thermal Decomposition Mechanism of 5-Hydroxy-6-hydroperoxy-5,6-dihydrothymidine in Water

Cited by 17 publications

References 46 publications

Mechanistic Study of the Deamination Reaction of Guanine: A Computational Study

Mechanistic Study of the Deamination Reaction of Guanine: A Computational Study

A theoretical study towards understanding the origin of DNA oxidation products

Mechanisms for the Decomposition of Hydroxyl-Radical-Induced Cytosine Hydroperoxides: A Computational Study

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