Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Molecules. 2018 Oct 18;23(10):2680. doi: 10.3390/molecules23102680.
The distinct pharmacodynamic and pharmacokinetic properties of enantiopure sulfoxide drugs have stimulated us to systematically investigate their chiral separation, stereochemical assignment, and chiral recognition mechanism. Herein, four clinically widely-used sulfoxide drugs were chosen and optically resolved on various chiral stationary phases (CSPs). Theoretical simulations including electronic circular dichroism (ECD) calculation and molecular docking were adopted to assign the stereochemistry and reveal the underlying chiral recognition mechanism. Our results showed that the sequence of calculated mean binding energies between each pair of enantiomers and CSP matched exactly with experimentally observed enantiomeric elution order (EEO). It was also found that the length of hydrogen bond might contribute dominantly the interaction between two enantiomers and CSP. We hope our study could provide a fresh perspective to explore the stereochemistry and chiral recognition mechanism of chiral drugs.
具有独特药效动力学和药代动力学性质的手性砜药物激发我们系统地研究了它们的手性分离、立体化学归属和手性识别机制。在此，选择了四种临床广泛使用的砜药物，并在各种手性固定相（CSP）上进行了光学拆分。采用理论模拟，包括电子圆二色性（ECD）计算和分子对接，对手性进行了归属并揭示了潜在的手性识别机制。我们的结果表明，每对对映异构体与 CSP 之间计算得到的平均结合能的顺序与实验观察到的对映体洗脱顺序（EEO）完全吻合。还发现氢键的长度可能主要贡献于两个对映异构体与 CSP 之间的相互作用。我们希望我们的研究能够为探索手性药物的立体化学和手性识别机制提供新的视角。
