Liang Guoming, Bao Xiaoguang, Gu Jiande
College of Chemistry, Chongqing Normal University, Chongqing 400047, China.
J Comput Chem. 2008 Dec;29(16):2648-55. doi: 10.1002/jcc.21009.
To evaluate the possibility of the decomposition of 2-deoxyribose moiety of thymidine induced by low energy electrons (LEE) attachment, the transition states and the energy barriers of the bond breaking processes of the ribose of the nucleoside have been studied theoretically by applying the density functional theory with the double zeta basis sets (DZP++). The energy barriers for the breakage of the C-C bonds (C(1')-C(2'), C(2')-C(3'), C(3')-C(4'), and C(4')-C(5')) of the ribose group of the radical anion of thymidine are found to be high (ca. 42-57 kcal/mol). The total energies of the C-C bond-broken products are significantly higher than that of the radical anion dT(-). The decomposition of dT(-) through the C-C bond rupture is unlikely to take place. The rupture of the C(1')-O(4') bond of dT(-) needs an activation energy as low as 10.4 kcal/mol. However, the reversed reaction (C(1')-O(4') bond formation) needs the activation energy low as 0.3 kcal/mol. Therefore, the intermediate product LM1(C1')-(O4') is unlikely to be stable and the C(1')-O(4') bond-broken is not favored. The activation energy of the C(4')-O(4') bond rupture process amounts to 20.5 kcal/mol. The total energy of the C(4')-O(4') bond broken product is about 6.5 kcal/mol lower than that of the reactant dT(-). The subsequent N1-glycosidic bond breaking process is found to have a very low energy barrier. Therefore, the LEE-induced base release through the C(4')-O(4') bond rupture might be a possible pathway.
为了评估低能电子（LEE）附着诱导胸苷2-脱氧核糖部分分解的可能性，通过应用具有双ζ基组（DZP++）的密度泛函理论，从理论上研究了核苷核糖键断裂过程的过渡态和能垒。发现胸苷自由基阴离子核糖基团的C-C键（C(1')-C(2')、C(2')-C(3')、C(3')-C(4')和C(4')-C(5')）断裂的能垒很高（约42-57千卡/摩尔）。C-C键断裂产物的总能量明显高于自由基阴离子dT(-)的总能量。通过C-C键断裂使dT(-)分解不太可能发生。dT(-)的C(1')-O(4')键断裂需要低至10.4千卡/摩尔的活化能。然而，逆向反应（C(1')-O(4')键形成）需要低至0.3千卡/摩尔的活化能。因此，中间产物LM1(C1')-(O4')不太可能稳定，且C(1')-O(4')键断裂不受青睐。C(4')-O(4')键断裂过程的活化能为20.5千卡/摩尔。C(4')-O(4')键断裂产物的总能量比反应物dT(-)的总能量低约6.5千卡/摩尔。随后的N1-糖苷键断裂过程具有非常低的能垒。因此，通过C(4')-O(4')键断裂由LEE诱导的碱基释放可能是一条可行的途径。
