Yang Xinrui, Zhang Depeng, Liu Rui, Wang Lu, Liu Jing-Yao, Wang Zhigang
Institute of Atomic and Molecular Physics, Jilin University, Changchun 130012, China.
Normal School, Shenyang University, Shenyang 110044, China.
J Phys Chem Lett. 2023 Nov 30;14(47):10592-10598. doi: 10.1021/acs.jpclett.3c02757. Epub 2023 Nov 17.
Quantum mechanical tunneling (QMT) can play an important role in light element-related chemical reactions; however, its influence on racemization is not fully understood. Herein, we demonstrate that the role of QMT is decisive for rapid racemization of the well-known thalidomide molecule in aqueous environments, increasing the reaction rate constants of the most likely racemization pathways by 87-149 times at approximately body temperature and achieving good agreement between theoretical calculations and experimental observations. In addition, the kinetic isotope effect values fit well with those of previous experiments. These results are attributed to enhanced tunneling probability due to the alteration of potential barriers for proton transfer reactions via water bridges. This work highlights the significance of the QMT effect in racemization and its potential impact on drug safety, providing a fundamental perspective for understanding chirality-related issues in biological systems.
量子力学隧穿（QMT）在与轻元素相关的化学反应中可发挥重要作用；然而，其对消旋作用的影响尚未完全明晰。在此，我们证明了QMT对于著名的沙利度胺分子在水性环境中的快速消旋起决定性作用，在大约体温下将最可能的消旋途径的反应速率常数提高了87 - 149倍，并使理论计算与实验观测结果达成良好一致。此外，动力学同位素效应值与先前实验结果吻合良好。这些结果归因于通过水桥改变质子转移反应的势垒而增强的隧穿概率。这项工作突出了QMT效应在消旋中的重要性及其对药物安全性的潜在影响，为理解生物系统中与手性相关的问题提供了一个基本视角。
