羟基加成反应对A-T碱基对结构和质子转移过程的影响

Effect of Hydroxylation on Structures and Proton Transfer of A-T Base Pairs

应用密度泛函理论在B3LYP/6-31++G(d,p)//B3LYP/6-31G(d,p)水平上对羟基化碱基对A-T的结构进行了研究,经计算共得到8种稳定的羟基化加成产物,其能量的相对顺序为8OHA-T<A-T6OH<A-T5OH<2OHA-T<4OHA-T<5OHA-T<A-T2OH<A-T4OH(数字表示羟基加成进攻的原子在腺嘌呤或胸腺嘧啶中的编号),这与其加成反应前后结构变化的大小密切相关.当羟基对腺嘌呤端进行加成时,A-T间的相互作用能略有增加,而当羟基对胸腺嘧啶进行加成时,A-T之间的相互作用能略有减小.另外,还以能量较低的加成产物8OHA-T和A-T6OH为例对羟基化碱基对中A和T之间的质子转移过程进行了研究,结果表明羟基化产物中A与T之间的质子转移机理由未加成前的分步双质子转移变为协同双质子转移,且其势垒低于未加成的A-T发生第一步(决速步骤)质子转移的势垒.

The structures and proton transfer processes of hydroxylated A-T base pairs were theoretically studied at the B3LYP/6-31＋＋G（d,p）//B3LYP/6-31G（d,p） level. Our calculations revealed that hydroxyl radical could react with A-T at different positions to form eight stable adducts. The order of these adducts in energy is 8OHA-T〈A-T6OH〈A-T5OH2OH〈A-T4OH〈A-T5OH〈A-TA-T2OH〈A-T4OH （the number denotes the label of the atom in the A/T which is attacked by hydroxyl）, which relates well with their structural changes upon the addition of hydroxyl radical. The interaction energy between A and T would increase slightly when hydroxyl radical reacts with the adenine, but it would decrease when the radical reacts with thymine. To study the proton transfer processes of the hydroxylated A-T base pairs, the most stable adducts, 8OHA-T and A-T6OH, were selected to give calculations. The calculated results indicate that the proton transfer processes of 8OHA-T and A-T6OH follow the concerted mechanism, which is different from the stepwise mechanism of A-T. What is more, its energy barrier is lower than the corresponding energy of the latter＇s first step （rate-determining step）.