Consecutive reaction mechanism for the formation of spore photoproduct in DNA photolesion.
Consecutive reaction mechanism for the formation of spore photoproduct in DNA photolesion.
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DOI：
10.1021/jp305915e
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发表时间：
2012-09
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影响因子：
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通讯作者：
Qian Du;Hongmei Zhao;D. Song;Kunhui Liu;Hongmei Su
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文献类型：
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作者：
Qian Du;Hongmei Zhao;D. Song;Kunhui Liu;Hongmei Su
我们用密度泛函理论和含时密度泛函理论研究了TpT二核苷酸在S（0）、S（1）和T（1）态沿着态形成DNA光致裂解产物-孢子光致产物（SP）的势能分布.结合自旋密度分析，可以建立SP形成的连续机制。详细的反应途径已被揭示。所有单独通过S（1）、T（1）或S（0）进行的绝热反应途径在能量上都是不可行的，而涉及T（1）和S（0）状态的非绝热途径对应于最低能量路径，并且是最有利的能量。非绝热途径受T（1）态氢原子转移步骤的速率限制，势垒为14.2 kcal mol（-1）（本体溶液中为11.9 kcal mol（-1）），而随后的C5-CH（2）键形成朝向最终SP形成容易发生在通过单线态-三线态相互作用从T（1）到S（0）的系间穿越之后的S（0）中。结果为实验观察到的TpT的3 '-T甲基氘取代后的动力学同位素效应提供了理论依据。
We have explored the potential energy profiles of TpT dinucleotides toward formation of a DNA photolesion product, spore photoproduct (SP), along the S(0), S(1), and T(1) states, by means of density functional theory and time-dependent density functional theory. Together with the spin density analysis, the consecutive mechanism for the SP formation can be established. The detailed reaction pathways have been revealed. All the adiabatic reaction pathways proceeding though S(1), T(1), or S(0) alone are shown to be energetically infeasible, while the nonadiabatic pathway involving both the T(1) and S(0) states corresponds to the lowest-energy path and is the most favorable in energy. The nonadiabatic pathway is rate-limited by the step of the hydrogen atom transfer proceeding in the T(1) state with a barrier of 14.2 kcal mol(-1) (11.9 kcal mol(-1) in bulk solution), whereas the subsequent C5-CH(2) bond formation toward the final SP formation occurs readily in S(0) after intersystem crossing from T(1) to S(0) via the singlet-triplet interaction. The results provide a rationale for the experimentally observed kinetic isotope effect after deuterium substitution at the 3'-T methyl group of TpT.