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约翰逊教授和Jason Hein教授的工作。 分离手性分子作为纯的对映异构体仍然是合成化学的挑战。高度立体选择性反应（例如，手性催化剂或手性助剂）;然而，这些仅仅代表了反应的一个子集，并没有提供通用的解决方案。依靠物理分离的方法（例如，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来开发手性结晶方法。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。这些结果将用于指导耦合容器优先结晶方法的发展，该方法能够拆分外消旋体形成化合物，并为晶体诱导的不对称合成提供新的途径。 然而，许多药物仅以一种（“手性”）形式具有活性，并且这些分子的镜像（“对映异构体”）通常本身可能是有毒的。 因此，直接合成或更一般地分离两种对映异构体的方法是必不可少的。本研究将拓宽对手性分子之间分子间相互作用的理解，并为建立通用的、可靠的结晶手性分子的合成和分离方法迈出了第一步。手性分子作为单独的对映异构体的分离是精细化工和制药工业的关键目标。这项工作有可能大大扩展合成策略，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.