Dataset Information

?-Radical to ?-Radical Tautomerization in One-Electron-Oxidized 1-Methylcytosine and Its Analogs.

ABSTRACT: In this work, iminyl ?-radical formation in several one-electron-oxidized cytosine analogs, including 1-MeC, cidofovir, 2'-deoxycytidine (dCyd), and 2'-deoxycytidine 5'-monophosphate (5'-dCMP), were investigated in homogeneous, aqueous (D2O or H2O) glassy solutions at low temperatures by employing electron spin resonance (ESR) spectroscopy. Upon employing density functional theory (DFT) (DFT/B3LYP/6-31G* method), the calculated hyperfine coupling constant (HFCC) values of iminyl ?-radical agree quite well with the experimentally observed ones, thus confirming its assignment. ESR and DFT studies show that the cytosine iminyl ?-radical is a tautomer of the deprotonated cytosine ?-cation radical [cytosine ?-aminyl radical, C(N4-H)(•)]. Employing 1-MeC samples at various pHs ranging from ca. 8 to 11, ESR studies show that the tautomeric equilibrium between C(N4-H)(•) and the iminyl ?-radical at low temperature is too slow to be established without added base. ESR and DFT studies agree that, in the iminyl ?-radical, the unpaired spin is localized on the exocyclic nitrogen (N4) in an in-plane pure p-orbital. This gives rise to an anisotropic nitrogen hyperfine coupling (Azz = 40 G) from N4 and a near isotropic ?-nitrogen coupling of 9.7 G from the cytosine ring nitrogen at N3. Iminyl ?-radical should exist in its N3-protonated form, as the N3-protonated iminyl ?-radical is stabilized in solution by over 30 kcal/mol (?G = -32 kcal/mol) over its conjugate base, the N3-deprotonated form. This is the first observation of an isotropic ?-hyperfine ring nitrogen coupling in an N-centered DNA radical. Our theoretical calculations predict that the cytosine iminyl ?-radical can be formed in double-stranded DNA by a radiation-induced ionization-deprotonation process that is only 10 kcal/mol above the lowest energy path.

SUBMITTER: Adhikary A

PROVIDER: S-EPMC4562692 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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π-Radical to σ-Radical Tautomerization in One-Electron-Oxidized 1-Methylcytosine and Its Analogs.

Adhikary Amitava A Kumar Anil A Bishop Casandra T CT Wiegand Tyler J TJ Hindi Ragda M RM Adhikary Ananya A Sevilla Michael D MD

The journal of physical chemistry. B 20150813 35

In this work, iminyl σ-radical formation in several one-electron-oxidized cytosine analogs, including 1-MeC, cidofovir, 2'-deoxycytidine (dCyd), and 2'-deoxycytidine 5'-monophosphate (5'-dCMP), were investigated in homogeneous, aqueous (D2O or H2O) glassy solutions at low temperatures by employing electron spin resonance (ESR) spectroscopy. Upon employing density functional theory (DFT) (DFT/B3LYP/6-31G* method), the calculated hyperfine coupling constant (HFCC) values of iminyl σ-radical agree ...[more]

PMID: 26237072

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Project description:In this work, addition of OH(-) to one-electron oxidized thymidine (dThd) and thymine nucleotides in basic aqueous glasses is investigated. At pHs ca. 9-10 where the thymine base is largely deprotonated at N3, one-electron oxidation of the thymine base by Cl(2)(•-) at ca. 155 K results in formation of a neutral thyminyl radical, T(-H)·. Assignment to T(-H)· is confirmed by employing (15)N substituted 5'-TMP. At pH ? ca. 11.5, formation of the 5-hydroxythymin-6-yl radical, T(5OH)·, is identified as a metastable intermediate produced by OH(-) addition to T(-H)· at C5 at ca. 155 K. Upon further annealing to ca. 170 K, T(5OH)· readily converts to the 6-hydroxythymin-5-yl radical, T(6OH)·. One-electron oxidation of N3-methyl-thymidine (N3-Me-dThd) by Cl(2)(•-) at ca. 155 K produces the cation radical (N3-Me-dThd(•+)) for which we find a pH dependent competition between deprotonation from the methyl group at C5 and addition of OH(-) to C5. At pH 7, the 5-methyl deprotonated species is found; however, at pH ca. 9, N3-Me-dThd(•+) produces T(5OH)· that on annealing up to 180 K forms T(6OH)·. Through use of deuterium substitution at C5' and on the thymine base, that is, specifically employing [5',5"-D,D]-5'-dThd, [5',5"-D,D]-5'-TMP, [CD(3)]-dThd and [CD(3),6D]-dThd, we find unequivocal evidence for T(5OH)· formation and its conversion to T(6OH)·. The addition of OH(-) to the C5 position in T(-H)· and N3-Me-dThd(•+) is governed by spin and charge localization. DFT calculations predict that the conversion of the "reducing" T(5OH)· to the "oxidizing" T(6OH)· occurs by a unimolecular OH group transfer from C5 to C6 in the thymine base. The T(5OH)· to T(6OH)· conversion is found to occur more readily for deprotonated dThd and its nucleotides than for N3-Me-dThd. In agreement, calculations predict that the deprotonated thymine base has a lower energy barrier (ca. 6 kcal/mol) for OH transfer than its corresponding N3-protonated thymine base (14 kcal/mol).

Dataset Information

?-Radical to ?-Radical Tautomerization in One-Electron-Oxidized 1-Methylcytosine and Its Analogs.

Publications

π-Radical to σ-Radical Tautomerization in One-Electron-Oxidized 1-Methylcytosine and Its Analogs.

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