RUI: Thermodynamics and NMR Crystallography of Organic Crystal Forms

RUI：有机晶型的热力学和核磁共振晶体学

• 批准号: 2100582
• 负责人: Manish Mehta
• 金额: $ 42.24万
• 依托单位: Oberlin College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2100582&HistoricalAwards=false
• 关键词: RUI; Thermodynamics; NMR; Crystallography; Organic

In this project, funded by the Chemical Structure Dynamics and Mechanisms-A (CSDM-A) program of the Chemistry Division, Professor Manish Mehta of Oberlin College is using experimental methods of physical chemistry to study the stability of organic co-crystals, the molecular basis of plastic and elastic crystals, and the creation of crystals that will allow existing techniques to determine their structures to a new level of accuracy. Co-crystals have proved to be a useful formulation for some medicinal compounds, one that allows control over factors such as solubility and biological effectiveness, yet their stability is poorly understood. The PI and his research team are building two custom instruments that will enable measurements of physical properties to determine that stability. His team is also investigating the structural characteristics of an unusual class of bendable organic crystals. If success, these studies will add to our understanding of the connection between structure and stability, and this will inform the design of new compounds. The research is being performed by college students as part of a course taught by the PI. Undergraduate participants in this research are gaining hands-on experience with modern experimental methods, acquiring skills in written and oral communication, and eventually are expected be undergraduate coauthors on peer-reviewed publications.This project concerns organic crystal forms and is divided into two main thrust areas. The first goal is to determine three key thermodynamic quantities necessary to understand the relative stability of crystal forms: the enthalpy of formation via bomb calorimetry, standard molar entropy via heat capacities using low-temperature calorimetry, and the enthalpy of sublimation via the Knudsen effusion mass-loss method. These three quantities are being combined to yield the Gibbs energy of formation, which determines overall thermodynamic stability. The study focuses a set of molecular targets chosen for their structural homology; included are common functional groups and ubiquitous supramolecular synthons. This course-based undergraduate research is being performed as part of a thermodynamics course taught by the PI. In the second thrust area, the PI and his research team are investigating elastic and plastic molecular crystals by using solid-state NMR to detect subtle changes when the crystals are subjected to mechanical strain. The team will attempt to detect the effects of isotope substitution on organic crystalline structure. Students are gaining hands-on experience with cutting-edge techniques which will prepare them for advanced study in the chemical sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在这个由化学系化学结构动力学和机制(CSDM-A)计划资助的项目中，奥伯林学院的Manish Mehta教授正在使用物理化学的实验方法来研究有机共晶体的稳定性，塑料和弹性晶体的分子基础，以及晶体的创建，这将使现有的技术能够将确定其结构的精度提高到一个新的水平。事实证明，共晶体对一些药物化合物是一种有用的配方，这种配方允许控制溶解度和生物有效性等因素，但人们对其稳定性知之甚少。PI和他的研究团队正在建造两种定制的仪器，这将使物理属性的测量能够确定稳定性。他的团队还在研究一类不寻常的可弯曲有机晶体的结构特征。如果成功，这些研究将增加我们对结构和稳定性之间联系的理解，这将为新化合物的设计提供信息。这项研究是由大学生进行的，作为PI教授的一门课程的一部分。这项研究的本科生参与者正在获得现代实验方法的实践经验，获得书面和口头交流的技能，最终有望成为同行评议出版物的本科生合著者。该项目涉及有机晶体形式，分为两个主要领域。第一个目标是确定理解晶型相对稳定性所必需的三个关键热力学参数：用弹式量热法测定生成热焓，用低温热量法测定标准摩尔熵，用努森渗透质量损失法测定升华能。这三个量结合在一起，产生吉布斯生成能，这决定了整体热力学稳定性。这项研究集中了一组分子靶标，这些靶标是因为它们的结构同源性而选择的；包括常见的官能团和普遍存在的超分子合成子。这项以课程为基础的本科研究是作为PI教授的热力学课程的一部分进行的。在第二个推进区域，PI和他的研究团队正在使用固态核磁共振来研究弹性和塑性分子晶体，以检测晶体受到机械应变时的细微变化。该团队将尝试检测同位素替代对有机晶体结构的影响。学生们正在获得尖端技术的实践经验，这将为他们在化学科学方面的高级研究做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

The Effects of Humidity on Spontaneous Cocrystallization: A Survey of Diacid Cocrystals with Caffeine, Theophylline, and Nicotinamide

湿度对自发共结晶的影响：二酸与咖啡因、茶碱和烟酰胺共晶体的调查

• DOI: 10.1007/s10870-022-00922-8
• 发表时间: 2022
• 期刊: Journal of Chemical Crystallography
• 影响因子: 0.8
• 作者: Davies, Riley D.;Vigilante, Nicolas J.;Frederick, Aaron D.;Mandala, Venkata S.;Mehta, Manish A.
• 通讯作者: Mehta, Manish A.