RUI: NMR Crystallography of Co-crystals

RUI：共晶的 NMR 晶体学

• 批准号: 1464948
• 负责人: Manish Mehta
• 金额: $ 31.8万
• 依托单位: Oberlin College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464948&HistoricalAwards=false
• 关键词: RUI; NMR; Crystallography; Co; crystals

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.

化学系的化学结构、动力学和机制（CSDM-A）项目将资助奥伯林学院的Manish Mehta教授研究共晶的形成——两种或两种以上的分子晶体，它们在固态下保持分子特性。这些结构非常有趣，因为它们提供了一种控制物质体积性质的新方法。例如，药物物质的性质如溶解度和生物利用度可以通过与赋形剂共结晶而改变。共晶通常是通过机械化学（例如，将共形成的固体磨在一起）制成的，而其他共晶则是通过简单的混合粉末自发形成的。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加强对这些机制的理解。从这些研究中获得的见解将有助于在未来设计和合成具有所需性能的共晶材料。参与的本科生将获得实验设计和执行的实践经验，并在同行评审的期刊上撰写论文。诸如此类的经历有助于为感兴趣的本科生准备STEM学科的研究生学习。在这项工作中，PI和他的本科研究团队应用核磁共振晶体学工具，利用实时原位固态核磁共振（ssNMR）研究共晶的合成结构及其形成。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像（用中子衍射和从头计算补充单晶核磁共振数据）；(3)利用显微镜和单晶x射线衍射（scXRD）检查单晶反应动力学。基于核磁共振的策略提供了动力学数据，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）。第二个目标是利用中子衍射和单晶核磁共振研究模型共晶系统中的氢键合子结构（包括评估质子位移张量及其在晶体框架中的取向）。从广义上讲，这些研究有望帮助建立核磁共振晶体学和晶体工程学之间的桥梁。