Solid-state 17O NMR study of α-D-glucose: exploring new frontiers in isotopic labeling, sensitivity enhancement, and NMR crystallography

J. Shen, V. Terskikh, J. Struppe, A. Hassan, M. Monette, I. Hung, Z. Gan, A. Brinkmann, and G. Wu*,
Chem. Sci. 13, 2591-2603, (2022).
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We report synthesis and solid-​state 17O NMR characterization of α-D-glucose for which all six oxygen atoms are site-​specifically 17O-labeled. Solid-​state 17O NMR spectra were recorded for α-D-glucose/NaCl/H2O (2/1/1) cocrystals under static and magic-​angle-​spinning (MAS) conditions at five moderate, high, and ultrahigh magnetic fields: 14.1, 16.4, 18.8, 21.1, and 35.2 T. Complete 17O chemical shift (CS) and quadrupolar coupling (QC) tensors were determined for each of the six oxygen-​containing functional groups in α-D-glucose. Paramagnetic Cu(II) doping was found to significantly shorten the spin-​lattice relaxation times for both 1H and 17O nuclei in these compounds. A combination of the paramagnetic Cu(II) doping, new CPMAS CryoProbe technology, and apodization weighted sampling led to a sensitivity boost for solid-state 17O NMR by a factor of 6–8, which made it possible to acquire high-​quality 2D 17O multiple-​quantum (MQ) MAS spectra for carbohydrate compounds. The unprecedented spectral resolution offered by 2D 17O MQMAS spectra permitted detection of a key structural difference for a single hydrogen bond between two types of crystallographically distinct α-D-glucose molecules. This work represents the first case where all oxygen-​containing functional groups in a carbohydrate molecule are site-​specifically 17O-labeled and fully characterized by solid-​state 17O NMR. Gauge Including Projector Augmented Waves (GIPAW) DFT calculations were performed to aid 17O and 13C NMR signal assignments for a complex crystal structure where there are six crystallographically distinct α-D-glucose molecules in the asymmetric unit.