Bruker Biospin Corporation , 15 Fortune Drive , Billerica , Massachusetts 01821 , United States.
Department of Chemistry and Biochemistry , University of Delaware , Newark , Delaware 19716 , United States.
Mol Pharm. 2020 Feb 3;17(2):674-682. doi: 10.1021/acs.molpharmaceut.9b01157. Epub 2020 Jan 13.
Magic angle spinning (MAS) NMR is a powerful method for the study of pharmaceutical compounds, and probes with spinning frequencies above 100 kHz enable an atomic-resolution analysis of sub-micromole quantities of fully protonated solids. Here, we present an ultrafast NMR crystallography approach for structural characterization of organic solids at MAS frequencies of 100-111 kHz. We assess the efficiency of H-detected experiments in the solid state and demonstrate the utility of 2D and 3D homo- and heteronuclear correlation spectra for resonance assignments. These experiments are demonstrated for an amino acid, U-C,N-histidine, and also for the significantly larger, natural product Posaconazole, an antifungal compound investigated at natural abundance. Our results illustrate the power for characterizing organic molecules, enabled by exploiting the increased H resolution and sensitivity at MAS frequencies above 100 kHz.
魔角旋转（MAS）NMR 是研究药物化合物的强大方法，旋转频率高于 100 kHz 的探头能够对亚毫摩尔数量的完全质子化固体进行原子分辨率分析。在这里，我们提出了一种超快 NMR 晶体学方法，用于在 MAS 频率为 100-111 kHz 下对有机固体进行结构表征。我们评估了固态中 H 检测实验的效率，并证明了 2D 和 3D 同核和异核相关谱对于共振分配的实用性。这些实验是针对氨基酸 U-C,N-组氨酸进行的，也针对天然产物泊沙康唑（一种研究自然丰度的抗真菌化合物）进行了演示。我们的结果说明了通过利用 MAS 频率高于 100 kHz 时增加的 H 分辨率和灵敏度，对有机分子进行表征的强大功能。
