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

合作研究：GOALI：固态核磁共振波谱的灵敏度和分辨率增强

• 批准号: 1709972
• 负责人: Aaron Rossini
• 金额: $ 22.95万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709972&HistoricalAwards=false
• 关键词: Collaborative; Research; GOALI; Sensitivity; Resolution

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).

在化学系化学测量和成像项目的支持下，以及工业创新与合作司的共同资助下，肯塔基大学的 Eric Munson 教授和爱荷华州立大学的 Aaron Rossini 教授正在努力提高性能（尤其是固态核磁共振 (SSNMR) 光谱的灵敏度和分析速度，它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领域使用 SSNMR 的许多学科产生广泛影响。化学。产业合作通过促进正在开发的技术的快速传播和应用来增加价值。 它们还增强了工作的跨学科性质，为执行和展示这项研究的研究生和本科生（包括代表性不足群体的成员）提供了异常广泛的教育机会。 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，介绍固态 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； 3) 接触化学工程、食品科学和农业等其他学科，以强调如何利用核磁共振的新发展来解决他们的问题。目前正在采用三种方法来提高结晶和无定形有机化合物（例如活性药物成分）的 SSNMR 的灵敏度、分辨率和一般能力。 1) 已知动态核极化 (DNP) 可以将灵敏度提高几个数量级。 博士。 Munson 和 Rossini 正在通过研究非晶固体分散体中粒径和相分离的影响来优化这些效果。一个目标是建立一种识别和区分多态性的方法。 2) 机械魔角旋转 (MAS) SSNMR 探头可在液氮温度下运行，以降低此类实验的成本，同时保留或增强控制 MAS 转子中环境的能力。 与在 298 K 下工作的标准 NMR 探头相比，预计这将提高大约一个数量级的灵敏度，并提高射频性能。 3）该团队正致力于通过使用二维质子-碳异核核磁共振波谱（HETCOR）来提高SSNMR波谱的分辨率。

项目成果

Magic angle spinning dynamic nuclear polarization solid-state NMR spectroscopy of γ-irradiated molecular organic solids

• DOI: 10.1016/j.ssnmr.2022.101785
• 发表时间: 2022-04-08
• 期刊: SOLID STATE NUCLEAR MAGNETIC RESONANCE
• 影响因子: 3.2
• 作者: Carnahan, Scott L.;Chen, Yunhua;Rossini, Aaron J.
• 通讯作者: Rossini, Aaron J.

DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients

• DOI: 10.1002/mrc.4688
• 发表时间: 2018-07-01
• 期刊: MAGNETIC RESONANCE IN CHEMISTRY
• 影响因子: 2
• 作者: Zhao, Li;Pinon, Arthur C.;Rossini, Aaron J.
• 通讯作者: Rossini, Aaron J.

Fast Acquisition of Proton‐Detected HETCOR Solid‐State NMR Spectra of Quadrupolar Nuclei and Rapid Measurement of NH Bond Lengths by Frequency Selective HMQC and RESPDOR Pulse Sequences

快速采集质子检测到的四极核 HETCOR 固态 NMR 谱，并通过频率选择性 HMQC 和 RESPDOR 脉冲序列快速测量 NH 键长

• DOI: 10.1002/chem.202000390
• 发表时间: 2020
• 期刊: Chemistry – A European Journal
• 作者: Wijesekara, Anuradha V.;Venkatesh, Amrit;Lampkin, Bryan J.;VanVeller, Brett;Lubach, Joseph W.;Nagapudi, Karthik;Hung, Ivan;Gor'kov, Peter L.;Gan, Zhehong;Rossini, Aaron J.
• 通讯作者: Rossini, Aaron J.

Rapid Characterization of Formulated Pharmaceuticals Using Fast MAS 1H Solid-State NMR Spectroscopy

• DOI: 10.1021/acs.molpharmaceut.9b00343
• 发表时间: 2019-07-01
• 期刊: MOLECULAR PHARMACEUTICS
• 影响因子: 4.9
• 作者: Hirsh, David A.;Wijesekara, Anuradha V.;Rossini, Aaron J.
• 通讯作者: Rossini, Aaron J.

Characterization of Pharmaceutical Cocrystals and Salts by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy

通过动态核偏振增强固态核磁共振波谱表征药物共晶和盐

• DOI: 10.1021/acs.cgd.8b00203
• 发表时间: 2018
• 期刊: Crystal Growth & Design
• 影响因子: 3.8
• 作者: Zhao, Li;Hanrahan, Michael P.;Chakravarty, Paroma;DiPasquale, Antonio G.;Sirois, Lauren E.;Nagapudi, Karthik;Lubach, Joseph W.;Rossini, Aaron J.
• 通讯作者: Rossini, Aaron J.