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.

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，无需同位素富集即可实现复杂药物分子的完全共振分配。DNP 显着增强了 NMR 信号，从而使以前难以处理的二维相关 NMR 光谱在自然丰度下成为可能。使用来自 DFT 计算的输入，我们在此描述了对复杂有机分子的结构解析过程的重大改进。此外，我们证明了一系列二维相关实验，包括¹⁵ N– ¹³ C TEDOR、¹³ C– ¹³ C INADEQUATE/SARCOSY、¹⁹ F–¹³ C HETCOR 和¹ H– ¹³ C HETCOR 可以在合理的实验时间内以天然同位素丰度获得，从而使用于治疗 2 型糖尿病的药物西格列汀完全共振。