AI 中文总结
本研究通过分子动力学探究将分子柔性纳入分子螺距框架的影响，评估两种药物对映体的剪切流分离潜力，预测10纳秒尺度下柔性对映体可线性分离，数小时内可达厘米级分离。
AI 中文摘要
对映异构体的机械分离是生产对映纯样品的合成方法的一种有吸引力的替代方案。产生溶液涡度的剪切流已被证明是分离从微米到纳米级手性物体的可行手段，这是由于手性物体与周围流体之间相互作用的张量性质。最近开发的分子螺距理论利用阻力张量来表征这些相互作用，并预测剪切诱导的药物样分子从其优化分子几何结构中的分离。我们开展了一项分子动力学研究，探究将分子柔性纳入分子螺距框架的影响，同时评估两种药物分子比卡鲁胺（Casodex）和孟鲁司特钠（Singulair）的对映体分离潜力。模拟显示，在真实溶剂环境中发生的构象变化会产生柔性诱导的螺距分布，不过这些分布受溶剂种类和剪切过程的影响较弱，产生的平均标量螺距值与优化气相结构的平均标量螺距值接近。尽管在分子尺度上存在平移扩散的相反作用，但柔性对映异构体的外消旋混合物在10纳秒时间尺度下表现出线性分离速率，我们预测在数小时内即可实现厘米级的分离。此外，我们还提供了用于产生层流剪切流的泰勒-库埃特（Taylor-Couette）装置的参数估计值，以及未来实验的相关考虑。
英文摘要
Mechanical separation of enantiomers is an attractive alternative to synthetic methods for producing enantiopure samples. Shear flow that produces solution vorticity has been shown to be a viable means for separating chiral objects on the micro- to nano-scale due to the tensorial nature of the interactions between chiral objects and the surrounding fluid. A recently-developed theory of molecular pitch characterizes these interactions using the resistance tensor and predicts the shear-induced separation of drug-like molecules from their optimized molecular geometries. We present a molecular dynamics study on the effects of incorporating molecular flexibility into the molecular pitch framework. We also evaluate the potential for enantiomeric separation of two drug molecules: bicalutamide (Casodex) and montelukast sodium (Singulair). Simulations reveal the emergence of flexibility-induced pitch distributions that result from conformational changes occurring in a realistic solvent environment. However, these distributions are weakly influenced by the solvent identity and the shearing process, producing mean scalar pitch values that are close to those from optimized gas phase structures. Despite the opposing effect of translational diffusion at the molecular scale, racemic mixtures of flexible enantiomers show linear rates of separation at the 10 ns timescale, and we predict that cm-scale separation can be achieved within hours. Additionally, we provide estimates for parameters of a Taylor-Couette device for generating laminar shear flow, as well as considerations for future experiments.
Journal refJ. Chem. Inf. Model. (2026) 66 (15), 9458-9467
