Interfaces and chirality: Molecular dynamics simulations of enantioseparations

一个“手性”分子有一个孪生子，孪生子是一个镜像--就像右手的倒影是左手一样。 分子孪生体被称为对映异构体，在化学合成中，它们经常一起产生。 许多药物都有镜像，但像立普妥和普拉替尼这样的药物都是以单一对映体（只有一种）出售的。 为什么？为什么？对于许多药物，活性存在于一种对映体中，而另一种对映体可能具有完全不同的效果。 这种差异是分离对映体在药物开发中以及农业化学品、食品添加剂、香水和其他产品的生产中非常重要的原因。 实验技术已经发展到分离对映异构体，这些方法使用第三个手性分子-选择剂-与每个对映异构体配对。 这些对是不同的，理想情况下，差异足够大，可以实现分离。 拟议的工作适用于分子动力学模拟，以解决有关的问题，对映体的分离。 在接下来的五年里，我们将：1）设计和测试新的表面结合手性选择剂，目标是确定那些随着溶剂的变化而可预测地改变其性质的手性选择剂。 这些选择剂将提供控制和改善手性分离的简单手段。2)将研究施加场时手性选择剂的有效性，以深入了解实验。 3)无定形二氧化硅表面经常出现在分离对映体的实验中，我们将仔细研究这些表面。 4)手性分子会影响其所处的环境，我们将研究手性在有序流体中的传递。 五名博士生，一名博士后研究员和几名本科生将在拟议的研究计划过程中接受手性系统分子动力学模拟的专业培训。 高性能计算在经济、医学、科学和其他领域中越来越重要。 所有学员将熟悉高性能计算和最先进的并行编程。

A "chiral" molecule has a twin, and the twin is a mirror image - just like the reflection of a right hand is a left hand. Molecular twins are called enantiomers and in a chemical synthesis, they are often produced together. Many pharmaceuticals have mirror images but drugs such as Lipitor and Plavix are sold as single enantiomers (only one of the twins). Why? For many drugs, activity resides with one enantiomer and the other may have an entirely different effect. This difference is the reason why separating enantiomers is important in drug development, and for the production of agrichemicals, food additives, perfumes, and other products. Experimental techniques have been developed to separate enantiomers and these methods use of a third chiral molecule - a selector - that pairs up with each of the enantiomers. The pairs are different and, ideally, the difference is big enough that a separation can be achieved. The proposed work applies molecular dynamics simulations to address questions relevant to the separation of enantiomers. In the next five years, we will: 1) design and test new surface-bound chiral selectors with the goal of identifying ones that predictably alter their properties with changes in solvent. These selectors will provide a simple means to control and improve a chiral separation. 2) The effectiveness of a chiral selector when a field is applied will be studied to gain insight into experiments. 3) Amorphous silica surfaces are often present in experiments that separate enantiomers and we will look closely at these surfaces. 4) Chiral molecules impact their environment and we will study the transfer of chirality in ordered fluids. Five doctoral students, one postdoctoral researcher, and several undergraduate students will receive specialized training in molecular dynamics simulations of chiral systems during the course of the proposed research program. High performance computing is increasingly important in economics, medicine, science, and other areas. All trainees will become familiar with high performance computing and state-of-the-art parallel programming.