物理化学学报 >> 2013, Vol. 29 >> Issue (11): 2321-2331.doi: 10.3866/PKU.WHXB201310082

理论与计算化学 上一篇    下一篇

脯氨酸硫酯自然化学连接反应中的轨道相互作用

张琪1, 于海珠2, 石景1   

  1. 1 中国科学技术大学化学系, 合肥 230026;
    2 北京科技大学高分子科学与工程系, 北京 100083
  • 收稿日期:2013-06-07 修回日期:2013-10-07 发布日期:2013-10-30
  • 通讯作者: 石景 E-mail:shijing@ustc.edu.cn
  • 基金资助:

    国家自然科学基金(21272223, 21202006)资助项目

Orbital Interactions in Native Chemical Ligation Reaction of Proline Thioesters

ZHANG Qi1, YU Hai-Zhu2, SHI Jing1   

  1. 1 Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. China;
    2 Department of Polymer Science and Engineering, University of Science and Technology Beijing, Beijing 100083, P. R. China
  • Received:2013-06-07 Revised:2013-10-07 Published:2013-10-30
  • Contact: SHI Jing E-mail:shijing@ustc.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21272223, 21202006).

摘要:

采用密度泛函理论(DFT)方法(M06//B3LYP)对脯氨酸硫酯在自然化学连接(NCL)反应中低反应活性的现象进行了详细的理论研究. 通过对脯氨酸和丙氨酸硫酯NCL反应的具体反应路径(Path-Pro 和Path-Ala)分别进行计算发现, 两个分子的反应路径均先后经历外源硫醇-硫酯交换、硫酯-硫酯交换、分子内S→N酰基化重排三个主要步骤. 两者的决速步骤均为第一步骤. 其中Path-Pro 的总能垒较高, 即脯氨酸硫酯的反应活性较低, 这与实验结果一致. 对两路径的决速步骤进一步考察, 发现脯氨酸中αN上的羰基对反应中心羰基的n→π*相互作用使得脯氨酸硫酯的LUMO轨道能量升高, 相应羰基C与S(芳基硫醇)原子之间的相互作用较小, 从而使得反应能垒升高.

关键词: 自然化学连接反应, 脯氨酸, n→π*相互作用, 机理, 密度泛函理论

Abstract:

A systematic theoretical study was carried out to investigate the origin of the relatively low reactivity of peptide-prolyl-thioesters in the native chemical ligation (NCL) reaction. Mechanistic calculations were performed on the two NCL reactions of peptide-prolyl-thioester (Path-Pro) and peptidealanyl-thioester (Path-Ala). The results show that both include three steps: intermolecular thiol-thioester exchange, transthioesterification, and a final intramolecular S→N acyl migration. The calculations indicate that the first step is the rate determining step of both pathways. Path-Pro is kinetically disfavored, so the peptide-prolyl-thioester is found to be less reactive in NCL reaction. This conclusion is consistent with the experimental observations. Further examination of the rate determining steps of these two pathways shows that the n→π* interaction of proline αN carbonyl increases the LUMO orbital energy of peptidyl-prolylthioester, decreases the interaction energy between proline carbonyl and the sulphur atom in aryl thiol, and finally increases the total energy barrier.

Key words: Native chemical ligation, Proline, n→π* interaction, Mechanism, Density functional theory

MSC2000: 

  • O643