Division of Science, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates.
Bruker Biospin Corporation, 15 Fortune Drive, Billerica, MA, USA.
Solid State Nucl Magn Reson. 2022 Jun;119:101794. doi: 10.1016/j.ssnmr.2022.101794. Epub 2022 Apr 11.
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 N-C TEDOR, C-C INADEQUATE/SARCOSY, F-C HETCOR, and H-C 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.
固态动态核极化增强魔角旋转（DNP-MAS）NMR 测量与密度泛函理论（DFT）计算相结合，可在无需同位素富集的情况下，对复杂药物分子进行完整的共振分配。DNP 极大地增强了 NMR 信号，从而使以前在自然丰度下难以处理的二维相关 NMR 光谱成为可能。在此，我们使用 DFT 计算的输入，描述了复杂有机分子结构阐明过程的重大改进。此外，我们证明可以在合理的实验时间内，在自然同位素丰度下获得一系列二维相关实验，包括 N-C TEDOR、C-C INADEQUATE/SARCOSY、F-C HETCOR 和 H-C HETCOR，从而能够对用于治疗 2 型糖尿病的药物西他列汀进行完整的共振分配。
