Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts
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- 作者：Amitava Adhikary ; Anil Kumar ; Alicia N. Heizer ; Brian J. Palmer ; Venkata Pottiboyina ; Yong Liang ; Stanislaw F. Wnuk ; Michael D. Sevilla
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：February 27, 2013
- 年：2013
- 卷：135
- 期：8
- 页码：3121-3135
- 全文大小：752K
- 年卷期：v.135,no.8(February 27, 2013)
- ISSN：1520-5126
文摘
In this work, addition of OH鈥?/sup> to one-electron oxidized thymidine (dThd) and thymine nucleotides in basic aqueous glasses is investigated. At pHs ca. 9鈥?0 where the thymine base is largely deprotonated at N3, one-electron oxidation of the thymine base by Cl2鈥⑩€?/sup> at ca. 155 K results in formation of a neutral thyminyl radical, T(鈭扝)路. Assignment to T(鈭扝)路 is confirmed by employing 15N substituted 5鈥?TMP. At pH 鈮?ca. 11.5, formation of the 5-hydroxythymin-6-yl radical, T(5OH)路, is identified as a metastable intermediate produced by OH鈥?/sup> addition to T(鈭扝)路 at C5 at ca. 155 K. Upon further annealing to ca. 170 K, T(5OH)路 readily converts to the 6-hydroxythymin-5-yl radical, T(6OH)路. One-electron oxidation of N3-methyl-thymidine (N3-Me-dThd) by Cl2鈥⑩€?/sup> at ca. 155 K produces the cation radical (N3-Me-dThd鈥?) for which we find a pH dependent competition between deprotonation from the methyl group at C5 and addition of OH鈥?/sup> to C5. At pH 7, the 5-methyl deprotonated species is found; however, at pH ca. 9, N3-Me-dThd鈥? produces T(5OH)路 that on annealing up to 180 K forms T(6OH)路. Through use of deuterium substitution at C5鈥?and on the thymine base, that is, specifically employing [5鈥?5鈥?D,D]-5鈥?dThd, [5鈥?5鈥?D,D]-5鈥?TMP, [CD3]-dThd and [CD3,6D]-dThd, we find unequivocal evidence for T(5OH)路 formation and its conversion to T(6OH)路. The addition of OH鈥?/sup> to the C5 position in T(鈭扝)路 and N3-Me-dThd鈥? is governed by spin and charge localization. DFT calculations predict that the conversion of the 鈥渞educing鈥?T(5OH)路 to the 鈥渙xidizing鈥?T(6OH)路 occurs by a unimolecular OH group transfer from C5 to C6 in the thymine base. The T(5OH)路 to T(6OH)路 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).