RUI: NMR Crystallography of Co-crystals

有了这个奖项，化学系的化学结构，动力学和机制（CSDM-A）计划资助奥伯林学院的Manish Mehta教授研究共晶体的形成-分子晶体，涉及两个或多个物种，在固态下保持其分子身份。这些结构是非常有趣的，因为它们提供了一种新的方法来控制物质的整体性质。例如，药物物质的性质如溶解度和生物利用度可以通过使药剂与赋形剂共结晶来改变。共晶通常使用机械化学（例如，将共形成的固体研磨在一起），而其它的通过简单地混合粉末自发形成。Mehta博士试图通过结合固态磁共振、X射线和中子衍射以及计算方法来增强对这些机制的理解。从这些研究中获得的见解应该有助于为未来具有所需性能的共晶材料的设计和合成提供信息。参与的本科生在实验设计和执行方面获得实践经验，并在同行评议的期刊上发表论文。在这项工作中，PI和他的本科生研究团队应用NMR晶体学工具，使用真实的时间原位固体NMR（ssNMR）研究共晶体的合成子结构及其形成。他们（1）研究共晶形成的动力学;（2）创建合成子结构的详细图片（用中子衍射和从头计算补充单晶NMR数据）;（3）使用显微镜和单晶X射线衍射（scXRD）检查单晶反应动力学。基于NMR的策略提供动力学数据，包括检测固态反应过程中可能出现的任何瞬态中间体（液体或固体）。第二个目标是使用中子衍射和单晶NMR（包括评估质子位移张量及其在晶格中的取向）研究模型共晶系统中的氢键合成子结构。从广义上讲，这些研究有望帮助弥合NMR晶体学和晶体工程社区。

With this award, the Chemical Structure, Dynamics, and Mechanisms (CSDM-A) Program of the Division of Chemistry is funding Professor Manish Mehta at Oberlin College to study the formation of co-crystals - molecular crystals that involve two or more species which retain their molecular identity in the solid state. These structures are of great interest, as they provide a new way to control bulk properties of substances. For example, properties of pharmaceutical substances such as solubility and bioavailability may be altered by co-crystallizing the agent with an excipient. Co-crystals are often made using mechanochemistry (e.g., grinding the co-forming solids together), while others form spontaneously by simply mixing powders. Dr. Mehta seeks to enhance the understanding of these mechanisms using a combination of solid-state magnetic resonance, X-ray and neutron diffraction, and computational methods. The insight gleaned from these studies should help to inform the design and synthesis of co-crystalline materials with desired properties in the future. Participating undergraduate students receive hands-on experience in experimental design and execution and in drafting manuscripts for publication in peer-reviewed journals. Experiences such as these help to prepare interested undergraduates for graduate study in the STEM disciplines.In this work, the PI and his undergraduate research team apply the tools of NMR crystallography to study the synthon structure of co-crystals and their formation using real time in situ solid-state NMR (ssNMR). They (1) investigate the kinetics of co-crystal formation; (2) create a detailed picture of the synthon structure (complementing single-crystal NMR data with neutron diffraction and ab initio calculations); and (3) examine single-crystal reaction dynamics using microscopy and single-crystal X-ray diffraction (scXRD). The NMR-based strategy provides kinetic data, including detection of any transient intermediates (liquid or solid) that might arise in the course of the solid-state reaction. A second goal is to investigate the hydrogen bond synthon structure in model co-crystal systems using neutron diffraction and single-crystal NMR (including assessment of proton shift tensors and their orientation in the crystal frame). Broadly construed, these studies are expected to help bridge the NMR crystallography and crystal engineering communities.