Drug Design & Discovery Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, Shanghai 201203 P. R. China.
J Phys Chem B. 2010 Jan 21;114(2):1221-4. doi: 10.1021/jp911103f.
To explore the nature of electron attachment to the guanine-centered DNA fragments in the presence of a polarizable medium, theoretical investigation of electron attachment to the guanine-related DNA single-strand fragments deoxyguanosine-3'-monophosphate (dGp), deoxyguanosine-5'-monophosphate (pdG), and deoxyguanosine-3',5'-diphosphate (pdGp) were performed using density functional theory with the polarizable continuum model. The electron distributions for the radical anions of pdGp in aqueous solution are extraordinarily different from those in the gas phase. In solution, the excess electron can covalently bind either to the base (forming pdG(-)p) or to the 3'-phosphate in the radical anion (forming pdGp(-)). The significant electron detachment energies found for these radical anions suggest that both pdG(-)p and pdGp(-) are electronically stable species in aqueous solution and are expected to be initiators in electron attachment-induced DNA damage in nature. In the presence of the polarizable medium, the base-centered radical anion pdG(-)p is more stable than the phosphate-centered structure. By comparison with electron attachment to the monophosphated nucleotide models pdG and dGp, the existence of the phosphate-centered radical pdGp(-) in pdGp is attributed to the cooperative influence of the two phosphate groups and the polarizable medium.
为了探究在极化介质存在下电子与鸟嘌呤中心 DNA 片段的结合性质，使用极化连续模型的密度泛函理论对鸟嘌呤相关的 DNA 单链片段脱氧鸟苷-3'-单磷酸(dGp)、脱氧鸟苷-5'-单磷酸(pdG)和脱氧鸟苷-3',5'-二磷酸(pdGp)的电子俘获进行了理论研究。pdGp 在水溶液中的自由基阴离子的电子分布与气相中的电子分布截然不同。在溶液中，多余的电子可以共价键合到碱基上(形成 pdG(-)p)或自由基阴离子中的 3'-磷酸上(形成 pdGp(-))。这些自由基阴离子具有显著的电子脱附能，表明 pdG(-)p 和 pdGp(-)在水溶液中都是电子稳定的物种，预计在自然界中电子俘获诱导的 DNA 损伤中是引发剂。在极化介质存在下，碱基中心的自由基阴离子 pdG(-)p 比磷酸中心结构更稳定。与单磷酸核苷酸模型 pdG 和 dGp 的电子俘获相比，pdGp 中存在磷酸中心自由基 pdGp(-)归因于两个磷酸基团和极化介质的协同影响。
