posted on 2023-11-17, 21:13authored byXinrui Yang, Depeng Zhang, Rui Liu, Lu Wang, Jing-yao Liu, Zhigang Wang
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.