从dnp增强的固态核磁共振中获得天然同位素丰度的药物的完整共振分配

IF 1.8 3区 化学 Q4 CHEMISTRY, PHYSICAL Solid state nuclear magnetic resonance Pub Date : 2022-06-01 DOI:10.1016/j.ssnmr.2022.101794
Renny Mathew , Ivan V. Sergeyev , Fabien Aussenac , Lydia Gkoura , Melanie Rosay , Maria Baias
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引用次数: 0

摘要

固体动态核极化增强魔角旋转(DNP-MAS)核磁共振测量与密度泛函数理论(DFT)计算相结合,可以在不需要同位素富集的情况下实现复杂药物分子的全共振分配。DNP极大地增强了核磁共振信号,从而使以前难以处理的二维相关核磁共振谱在自然丰度上成为可能。使用从DFT计算的输入,在这里我们描述了复杂有机分子的结构解析过程的显著改进。此外,我们证明了一系列二维相关实验,包括15N-13C TEDOR, 13C-13C不充分/SARCOSY, 19F-13C HETCOR和1H-13C HETCOR,可以在合理的实验时间内以自然同位素丰度获得,从而实现西格列汀(用于治疗2型糖尿病的药物)的完整共振分配。
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Complete resonance assignment of a pharmaceutical drug at natural isotopic abundance from DNP-Enhanced solid-state NMR

Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including 15N–13C TEDOR, 13C–13C INADEQUATE/SARCOSY, 19F–13C HETCOR, and 1H–13C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.

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来源期刊
CiteScore
5.30
自引率
9.40%
发文量
42
审稿时长
72 days
期刊介绍: The journal Solid State Nuclear Magnetic Resonance publishes original manuscripts of high scientific quality dealing with all experimental and theoretical aspects of solid state NMR. This includes advances in instrumentation, development of new experimental techniques and methodology, new theoretical insights, new data processing and simulation methods, and original applications of established or novel methods to scientific problems.
期刊最新文献
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