胸腺嘧啶二醇脱氧核苷单分子糖苷键断裂的理论研究

摘要

采用理论计算方法对cis-(5S,6R)胸腺嘧啶二醇脱氧核苷(dTg)单分子糖苷键断裂的热力学和动力学性质进行了研究.在气相中,所有稳定点的几何构型都采用B3LYP/6-31+G(d,p)方法进行全优化,并利用导电极化连续模型对气相优化构型进行单点计算确定水的溶剂效应,作者主要考虑了直接断裂和抽氢断裂两条路径.计算结果表明:两条反应机理均涉及较高的活化能,从而说明单分子分解并不能促进糖苷键的断裂,该研究为生物体内这一重要反应提供了更多有用的信息.%The thermodynamic and kinetic properties for the unimolecular N -glycosidic bond cleavage in cis - (5S,6R) - 5,6 - dihydroxy - 5,6 - dihydrodeoxythymidine (dTg) were studied by computational techniques.Optimized structures for all of the stationary points in the gas phase were investigated using the B3LYP/6 -31 + G (d, p)method.The solvent effect of water solution on the processes was assessed at the gas - phase geometry optimization by means of the conductor - like polarized continuum model.Two mechanisms were investigated, including the direct cleavage and abstraction cleavage.The calculated results show that both processes involve large energy barriers, suggesting that the cleavage of the N - glycosidic bond via unimolecular decomposition is not feasible.Our results emphasize the significant roles of the nucleophile and enzyme, and have provided more valuable information about this important biological reaction.