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

来自肯塔基大学的Eric Munson教授和来自爱荷华州立大学的Aaron Rossini教授在化学系化学测量和成像项目的支持下，以及来自工业创新和合作伙伴关系部门的共同资助下，正在努力提高固态核磁共振（SSNMR）光谱的性能（特别是分析的灵敏度和速度），这是化学分析最强大的工具之一。该团队与Revolution NMR， LLC的John Heinrich博士合作，专门针对制药行业感兴趣的物质进行分析，尽管目标改进将对几乎所有化学领域中使用SSNMR的许多学科产生广泛的影响。工业合作通过促进正在开发的技术的迅速传播和应用来增加价值。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来执行和展示这项研究。为了进一步扩大这种影响，曼森/罗西尼团队正在1)为研究生和博士后提供短期课程，介绍固态核磁共振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；3)接触其他学科，如化学工程、食品科学和农业，以突出核磁共振的新发展如何用于解决他们的问题。三种方法被用来提高晶体和非晶态有机化合物（如活性药物成分）的灵敏度、分辨率和一般能力。1)已知动态核极化（DNP）可以提高几个数量级的灵敏度。Drs。Munson和Rossini正致力于通过研究非晶固体分散体中颗粒大小和相分离的影响来优化这些效应。目的之一是建立一种识别和区分多态形式的方法。2)设计一种可在液氮温度下操作的机械魔角旋转（MAS） SSNMR探针，以降低此类实验的成本，同时保留或增强MAS转子对环境的控制能力。与工作在298k的标准核磁共振探针相比，预计这将提供大约一个数量级的灵敏度提高，并改善射频性能。3)利用二维质子-碳异核磁共振波谱（HETCOR）技术提高ssmr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).