Zhang Ru Bo, Zhang Ke, Eriksson Leif A
School of Science and the Institute for Chemical Physics, Beijing Institute of Technology, Beijing 100081, China.
Chemistry. 2008;14(9):2850-6. doi: 10.1002/chem.200701324.
Low-energy electrons (LEE) are well known to induce nucleic acid damage. However, the damage mechanisms related to charge state and structural features remain to be explored in detail. In the present work, we have investigated the N1-glycosidic and C3'-O(P) bond ruptures of 3'-UMP (UMP=uridine monophosphate) and the protonated form 3'-UMPH with -1 and zero charge, respectively, based on hybrid density functional theory (DFT) B3 LYP together with the 6-31+G(d,p) basis set. The glycosidic bond breakage reactions of the 3'UMP and 3'UMPH electron adducts are exothermic in both cases, with barrier heights of 19-20 kcal mol(-1) upon inclusion of bulk solvation. The effects of the charge state on the phosphate group are marginal, but the C2'-OH group destabilizes the transition structure of glycosidic bond rupture of 3'-UMPH in the gas phase by approximately 5.0 kcal mol(-1). This is in contrast with the C3'-O(P) bond ruptures induced by LEE in which the charge state on the phosphate influences the barrier heights and reaction energies considerably. The barrier towards C3'-O(P) bond dissociation in the 3'UMP electron adduct is higher in the gas phase than the one corresponding to glycosidic bond rupture and is dramatically influenced by the C2'-OH group and bulk salvation, which decreases the barrier to 14.7 kcal mol(-1). For the C3'-O(P) bond rupture of the 3'UMPH electron adduct, the reaction is exothermic and the barrier is even lower, 8.2 kcal mol(-1), which is in agreement with recent results for 3'-dTMPH and 5'-dTMPH (dTMPH=deoxythymidine monophosphate). Both the Mulliken atomic charges and unpaired-spin distribution play significant roles in the reactions.
低能电子（LEE）可诱导核酸损伤，这是众所周知的。然而，与电荷状态和结构特征相关的损伤机制仍有待详细探索。在本工作中，我们基于杂化密度泛函理论（DFT）B3 LYP以及6 - 31 + G(d,p)基组，分别研究了带有 - 1和零电荷的3'-单磷酸尿苷（UMP = 尿苷单磷酸）及其质子化形式3'-UMPH的N1-糖苷键和C3'-O(P)键断裂情况。在两种情况下，3'UMP和3'UMPH电子加合物的糖苷键断裂反应都是放热的，考虑到溶剂化作用后，势垒高度为19 - 20 kcal mol(-1)。磷酸基团上电荷状态的影响较小，但在气相中，C2'-OH基团使3'-UMPH糖苷键断裂的过渡结构不稳定，降低了约5.0 kcal mol(-1)。这与低能电子诱导的C3'-O(P)键断裂形成对比，在C3'-O(P)键断裂中，磷酸基团上的电荷状态对势垒高度和反应能量有显著影响。在气相中，3'UMP电子加合物中C3'-O(P)键解离的势垒高于相应的糖苷键断裂势垒，并且受到C2'-OH基团和溶剂化作用的显著影响，溶剂化作用使势垒降低至14.7 kcal mol(-1)。对于3'UMPH电子加合物的C3'-O(P)键断裂，反应是放热的，势垒甚至更低，为8.2 kcal mol(-1)，这与最近关于3'-脱氧胸苷单磷酸（dTMPH）和5'-脱氧胸苷单磷酸（dTMPH）的研究结果一致。Mulliken原子电荷和未成对自旋分布在反应中都起着重要作用。
