Collaborative Research: GOALI: Sensitivity and Resolution Enhancement in Solid-State NMR Spectroscopy

在化学系化学测量和成像项目的支持下，以及工业创新和合作伙伴关系部的共同资助下，来自肯塔基州大学的Eric Munson教授和来自爱荷华州州立大学的Aaron Rossini教授正在努力提高性能（特别是分析的灵敏度和速度）的固态核磁共振（SSNMR）光谱，化学分析中最强大的工具之一。 在与Revolution NMR，LLC的John Heinrich博士的合作中，该团队专门针对制药行业感兴趣的物质的分析，尽管目标改进将在几乎所有化学领域使用SSNMR的许多学科中产生广泛的影响。工业合作通过促进正在开发的技术的快速传播和应用而增加价值。 他们还加强了工作的跨学科性质，为研究生和本科生（包括代表性不足的群体的成员）提供了非常广泛的教育机会，执行和提出这项研究。 为了进一步扩大这种影响，Munson/Rossini团队1）为研究生和博士后提供短期课程，解决固态NMR的基础知识及其在制药和材料科学中的应用; 2）建立访问科学家计划，使学生，工业代表和政府机构成员能够学习正在开发的先进技术;以及3）接触其他学科，如化学工程、食品科学和农业，以突出如何利用NMR的新发展来解决他们的问题。三种方法被用来提高灵敏度，分辨率，和结晶和无定形有机化合物（如活性药物成分）的SSNMR的一般能力。1)已知动态核极化（DNP）以数量级增加灵敏度。 Munson博士和Rossini博士正在研究无定形固体分散体中粒度和相分离的影响，以优化这些效果。一个目的是建立一种鉴定和区分多态形式的方法。2)机械魔角旋转（MAS）SSNMR探针可在液氮温度下操作以降低这些类型的实验的成本，同时保持或增强控制MAS转子中的环境的能力。 预计与在298 K下操作的标准NMR探针相比，这将提供灵敏度的大约一个数量级的增加，以及改进的射频性能。3)该团队正在努力通过使用二维质子碳杂原子NMR光谱（HETCOR）来提高SSNMR光谱的分辨率。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, and co-funding from the Division of Industrial Innovation and Partnerships, Professors Eric Munson from the University of Kentucky and Aaron Rossini from Iowa State University are striving to improve the performance (especially the sensitivity and speed of analysis) of solid-state nuclear magnetic resonance (SSNMR) spectroscopy, one of the most powerful tools for chemical analysis. In collaborations with Dr. John Heinrich of Revolution NMR, LLC, the team is specifically targeting analysis of substances of interest to the pharmaceutical industry, although the target improvements will have wide-ranging impact across the many disciplines that use SSNMR in almost all fields of chemistry. The industrial collaborations add value by promoting rapid dissemination and application of the technologies being developed. They also enhance the interdisciplinary nature of the work, providing exceptionally broad educational opportunities for the graduate and undergraduate students (including members of underrepresented groups) performing and presenting this research. To expand this impact even further, the Munson/Rossini team is 1) providing short courses for graduate students and postdocs, addressing the basics of solid-state NMR and its applications to pharmaceutical and material science; 2) establishing a visiting scientist program to enable for students, industrial representatives, and members of government agencies to learn the advanced techniques being developed; and 3) reaching out to other disciplines, such as chemical engineering, food science, and agriculture to highlight how new developments in NMR can be used to solve their problems. Three approaches are being employed to improve the sensitivity, resolution, and general capabilities of SSNMR of crystalline and amorphous organic compounds (such as active pharmaceutical ingredients). 1) Dynamic nuclear polarization (DNP) is known to increase sensitivity by orders of magnitude. Drs. Munson and Rossini are working to optimize these effects by studying the impact of particle size and phase separation in amorphous solid dispersions. One aim is to establish a means of identifying and differentiating polymorphic forms. 2) A mechanical magic-angle spinning (MAS) SSNMR probe operable at liquid nitrogen temperatures to lower the cost of these kinds of experiments while retaining or enhancing the ability to control the environment in the MAS rotor. It is anticipated that this will provide about an order of magnitude increase in sensitivity compared to a standard NMR probe operating at 298 K, as well as improved radiofrequency performance. 3) The team is working to improve the resolution of SSNMR spectra by using two-dimensional proton-carbon heteronuclear NMR spectroscopy (HETCOR).