Tautomers of One‐Electron‐Oxidized Guanosine

The reaction of hydroxyl radical (OH•) with DNA accounts for about half of radiation-induced DNA damage in living systems. Previous literature reports point out that the reaction of OH• with DNA proceeds mainly through the addition of OH• to the C=C bond of the DNA bases. However, recently it has been reported that the principal reaction of OH• with dGuo (deoxyguanosine) is the direct hydrogen atom abstraction from its exocyclic amine group rather than addition of OH• to the C=C bond. In the present work, these two reaction pathways of OH• attack on guanine (G) in the presence of water molecules (aqueous environment) are investigated using the density functional theory (DFT) B3LYP method with 6-31G* and 6-31++G** basis sets. The calculations show that the initial addition of the OH• at C4=C5 double bond of guanine is barrier free and the adduct radical (G-OH•) has only a small activation barrier of ca. 1 – 6 kcal/mol leading to the formation of a metastable ion-pair intermediate (G•+---OH−). The formation of ion-pair is a result of the highly oxidizing nature of the OH• in aqueous media. The resulting ion-pair (G•+---OH−) deprotonates to form H2O and neutral G radicals favoring G(N1-H)• with an activation barrier of ca. 5 kcal/mol. The overall process from the G(C4)-OH• (adduct) to G(N1-H)• and water is found to be exothermic in nature by more than 13 kcal/mol. (G-OH•), (G•+---OH−), and G(N1-H)• were further characterized by the CAM-B3LYP calculations of their UV-visible spectra and good agreement between theory and experiment is achieved. Our calculations for the direct hydrogen abstraction pathway from N1 and N2 sites of guanine by the OH• show that this is also a competitive route to produce G(N2-H)•, G(N1-H)• and H2O.

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“…The preferred stability of G(N 1 -H) • over G(N 2 -H) • has also been found in earlier theoretical and experimental studies. 9a,19, 20 …”

Section: Resultsmentioning

confidence: 99%

Hydroxyl Radical (OH^•) Reaction with Guanine in an Aqueous Environment: A DFT Study

2011

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“…þ . These questions have been treated by a number of authors employing both theory and experiment [142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158] without definitive conclusions. Recently, electron spin resonance (ESR) and the B3LYP/6-31G(d) level of theory have been used to identify the preferred site of deprotonation from guanine radical cation (G .…”

Section: -144mentioning

confidence: 99%

“…Similar conclusions were also drawn by Naumov and Sonntag 158 using UV-visible spectral properties and DFT study recently. Chatgilialoglu et al 155,156 also studied the tautomers of one-electron-oxidized guanosine using UV-visible spectral properties and the DFT method. Based on DFT results, they proposed the presence of a transient species G (N2-H) .…”

Section: Interestingly G(n1-h)mentioning

confidence: 99%

Theoretical Modeling of Radiation‐Induced DNA Damage

Kumar

Sevilla

2009

Radical and Radical Ion Reactivity in Nucleic Acid Chemistry

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“…20 From ESR and pulse radiolysis experiments it is found that the G •+ deprotontes either from its N1 or N2 site to form neutral radicals • G N1 and • G N2 , respectively. 10,20,21 The transiently formed • G N1 and • G N2 in DNA disrupt the normal hydrogen bonding pattern with its complementary hydrogen bonded cytosine and results in the formation of slipped hydrogen bonded but still based paired structure. 10,11b,,22 In this work, we initially investigated the reaction of • G N1 and • G N2 with the neutral cytosine base to form the radicals G N1 (N1-N3)C • and G N2 (N2-N3)C • , respectively, see Table 1.…”

Section: Resultsmentioning

confidence: 99%

Formation of N–N Cross-Links in DNA by Reaction of Radiation-Produced DNA Base Pair Diradicals: A DFT Study

2011

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This study employs DFT (density functional theory) to investigate the formation of hydrazine like (N-N) cross-linked structures between DNA base pair diradicals that are likely to result from the interaction of high linear energy transfer (LET) radiation such as ion-beam radiation with DNA. In our calculations, we generated the guanine (G), cytosine (C), adenine (A) and thymine (T) radicals by removing one hydrogen atom from an N-H bond involved in the normal base pairing. The radical species formed are those that naturally result from one electron oxidation of the bases followed by deprotonation. N-N cross-links between G and C or A and T diradicals were studied using the BHandHLYP, B3LYP, M06 and M06-2X density functionals and 6-31G* basis set. From a comparison to several test cases performed with the G3B3 method which gives thermodynamically reliable values, we found that calculations employing the BHandHLYP/6-31G* method predict the best estimates of bonding energies for hydrazine like structures. Our study shows that the N-N cross-link formed between guanine radical and a neutral cytosine is endothermic in nature but can form metastable structures. However, the reactions between two DNA base radicals (diradical) to form several N-N cross-linked structures are found to be highly exothermic in nature. The N-N cross-links formed between various G-C, G-G, and C-C diradicals have binding energies in the range ca. −54 to −68 kcal/mol, −41 to −47 kcal/mol and −67 to −75 kcal/mol, respectively, while A-T, A-A and T-T have binding energies −80 kcal/mol, −60 kcal/mol and −98 kcal/mol, respectively. In all purine-pyrimidine N-N cross-linked structures, the highest occupied molecular orbital (HOMO) is found to be localized on the purine moiety and LUMO on the pyrimidine moiety.

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Tautomers of One‐Electron‐Oxidized Guanosine

Cited by 66 publications

References 19 publications

Hydroxyl Radical (OH^•) Reaction with Guanine in an Aqueous Environment: A DFT Study

Hydroxyl Radical (OH^•) Reaction with Guanine in an Aqueous Environment: A DFT Study

Theoretical Modeling of Radiation‐Induced DNA Damage

Formation of N–N Cross-Links in DNA by Reaction of Radiation-Produced DNA Base Pair Diradicals: A DFT Study

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Tautomers of One‐Electron‐Oxidized Guanosine

Cited by 66 publications

References 19 publications

Hydroxyl Radical (OH•) Reaction with Guanine in an Aqueous Environment: A DFT Study

Hydroxyl Radical (OH•) Reaction with Guanine in an Aqueous Environment: A DFT Study

Theoretical Modeling of Radiation‐Induced DNA Damage

Formation of N–N Cross-Links in DNA by Reaction of Radiation-Produced DNA Base Pair Diradicals: A DFT Study

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Product

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Hydroxyl Radical (OH^•) Reaction with Guanine in an Aqueous Environment: A DFT Study

Hydroxyl Radical (OH^•) Reaction with Guanine in an Aqueous Environment: A DFT Study