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).

在化学测量和成像计划中的化学划分和工业创新和合作伙伴关系司的支持下，来自肯塔基大学的埃里克·蒙森教授和爱荷华州立大学的埃里克·蒙森（Eric Munson）正在努力提高稳定性核能共鸣的敏感性和速度分析的敏感性和速度分析（SSSSSNMR）的效果（尤其是分析）的表现（SSSSNMR）。 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来增加价值。 他们还提高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，并介绍了这项研究。 为了进一步扩大这种影响，Munson/Rossini团队是1）为研究生和博士后提供短课程，以解决固态NMR及其在药品和材料科学上的应用； 2）建立一项访问科学家计划，以启用学生，工业代表和政府机构的成员，以了解正在开发的先进技术； 3）接触其他学科，例如化学工程，食品科学和农业，以突出如何使用NMR的新发展来解决他们的问题。正在采用三种方法来提高晶体和无定形有机化合物（例如活性药物成分）的SSNMR的敏感性，分辨率和一般能力。 1）已知动态核极化（DNP）通过数量级来提高灵敏度。 博士。芒森（Munson）和罗西尼（Rossini）正在通过研究粒径和相位分离在无定形固体分散体中的影响来优化这些效果。一个目的是建立一种识别和区分多态性形式的方法。 2）机械魔术角旋转（MAS）SSNMR探针在液体氮温度下可操作，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。 可以预计，与在298 K下运行的标准NMR探针相比，这将提供敏感性的数量级，并提高了射频性能。 3）该团队正在努力通过使用二维质子碳异核NMR光谱法（HETCOR）来改善SSNMR光谱的分辨率。

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.