Ultrafast 1H MAS NMR Crystallography for Natural Abundance Pharmaceutical Compounds

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Abstract
Magic angle spinning (MAS) NMR is a powerful method for the study of pharmaceutical compounds, and probes with spinning frequencies above 100 kHz enable 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 1H-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-13C,15N histidine and also for the significantly larger, natural product Posaconazole, an anti-fungal compound investigated at natural abundance. Our results illustrate the power for characterizing organic molecules, enabled by exploiting the increased 1H resolution and sensitivity at MAS frequencies above 100 kHz.
Funding Information
  • National Institute of General Medical Sciences (P30GM110758, P50AI150481)

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