Theoretical and Experimental Investigation of Homo-Chiral and Hetero-Chiral Interactions in the Solid Phase

该奖项支持加州大学默塞德分校的Erin Johnson和Jason Hein教授的工作。作为纯对映体的手性分子的分离仍然是合成化学的一个挑战。高度立体选择性反应(如：手性催化剂（或手性助剂）已被开发；然而，这些只是反应的一个子集，并不能提供一般的解决方案。依赖于物理分离的方法(例如：对映选择性结晶（对映选择性结晶）具有更广泛应用的潜力。手性化合物相平衡的理论和实验相结合的研究将被用于允许发展的选择性结晶方法。这种方法将使用密度泛函理论结合交换空穴偶极矩色散模型来预测同手性和异手性晶体形式之间的能量差异。这些结果将用于指导耦合容器优先结晶方法的发展，能够分解形成外消旋体的化合物，并为晶体诱导不对称合成提供新的途径。大多数化学反应产生的产物都是它们的镜像。然而，许多药物仅以一种（“手性”）形式起作用，并且通常这些分子的镜像（“对映体”）本身可能是有毒的。因此，直接合成或更一般地分离这两种对映体的方法是必不可少的。这项研究将扩大对手性分子之间分子间相互作用的理解，并代表着建立晶体手性分子合成和分离的通用、可靠方法的第一步。分离手性分子作为单个对映体是精细化工和制药工业的关键目标。这项工作有可能极大地扩展合成策略，以产生100%对映体纯度的分子。

This award supports the work of Professors Erin Johnson and Jason Hein at the University of California-Merced. Isolation of chiral molecules as pure enantiomers remains a challenge for synthetic chemistry. Highly stereoselective reactions (eg. chiral catalysts or chiral auxiliaries) have been developed; however, these represent only a subset of reactions and do not offer general solutions. Methods relying on physical separations (eg. enantioselective crystallizations) have the potential to be more broadly applicable. A combined theoretical and experimental study of the phase equilibria of chiral compounds will be employed to allow development of enatioselective crystallization methods. This approach will use density-functional theory combined with the exchange-hole dipole moment dispersion model to predict energy differences between homochiral and heterochiral crystal forms. These results will be used to guide the development of a coupled-vessel preferential crystallization method, capable of resolving racemate-forming compounds and providing a new approach to crystal-induced asymmetric synthesis.Most chemical reactions produce products in their mirror images. However, many drugs are active in only one ("chiral") form, and often the mirror images ("enantiomers") of these molecules can themselves be toxic. Thus methods for either direct synthesis, or more generally, for separation of the two enantiomers is essential. This study will broaden the understanding of intermolecular interactions between chiral molecules and represents a first step toward establishing general, reliable methods for the synthesis and separation of crystalline chiral molecules. Isolation of chiral molecules as individual enantiomers is a critical goal for the fine-chemical and pharmaceutical industries. This work has the potential to greatly expand synthetic strategies to produce molecules of 100% enantiomeric purity.