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

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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).