Stability of the Guanine Endoperoxide Intermediate: A Computational Challenge for Density Functional Theory

详细信息    查看全文

• 作者：Raymond Gr眉ber ; Antonio Monari ; Elise Dumont
• 刊名：Journal of Physical Chemistry A
• 出版年：2014
• 出版时间：December 11, 2014
• 年：2014
• 卷：118
• 期：49
• 页码：11612-11619
• 全文大小：310K
• ISSN：1520-5215

文摘

The addition of singlet molecular oxygen ¹O₂ onto guanine is a most important and deleterious reaction in biological damage. We assess the efficiency of density functional theory for evaluating the respective stabilities of two intermediates that can form upon ¹O₂ addition: a charge-separated adduct with a peroxide anion at the C8 position of guanine, and the corresponding cyclic endoperoxide across the 4,8-bond, of the imidazole ring. The reference post Hartree鈥揊ock SCS-MP3/aug-cc-pVTZ//MP2/DZP++ level of theory provides an unambiguous assignment in favor of the endoperoxide intermediate, based on implicitly solvated structures, by 鈭?.0 kcal路mol^鈥?. This value is taken as the reference for a systematic and extended benchmarck performed on 58 exchange--correlation functionals. While B3LYP remains commonly used for studying oxidative DNA lesions, we prove that the stability of the peroxide anion is overestimated by this functional, but also by other commonly used exchange-correlation functionals. The significant error (ca. +3 kcal路mol^鈥? over a representative set of 58 functionals) arises from overdelocalization but also from the description of the dynamic correlation by the density functional. The significantly improved performance of several recently proposed functionals, including range-separated hybrids such as LC-BLYP, is outlined. We believe that our results will be of great help to further studies on the versatile chemistry of singlet oxygen-induced DNA damage, where complex reaction mechanisms are required to be depicted at a quantum level.