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

We report synthesis and solid-state O-17 NMR characterization of alpha-d-glucose for which all six oxygen atoms are site-specifically O-17-labeled. Solid-state O-17 NMR spectra were recorded for alpha-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 O-17 chemical shift (CS) and quadrupolar coupling (QC) tensors were determined for each of the six oxygen-containing functional groups in alpha-d-glucose. Paramagnetic Cu(ii) doping was found to significantly shorten the spin-lattice relaxation times for both H-1 and O-17 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 O-17 NMR by a factor of 6-8, which made it possible to acquire high-quality 2D O-17 multiple-quantum (MQ) MAS spectra for carbohydrate compounds. The unprecedented spectral resolution offered by 2D O-17 MQMAS spectra permitted detection of a key structural difference for a single hydrogen bond between two types of crystallographically distinct alpha-d-glucose molecules. This work represents the first case where all oxygen-containing functional groups in a carbohydrate molecule are site-specifically O-17-labeled and fully characterized by solid-state O-17 NMR. Gauge Including Projector Augmented Waves (GIPAW) DFT calculations were performed to aid O-17 and C-13 NMR signal assignments for a complex crystal structure where there are six crystallographically distinct alpha-d-glucose molecules in the asymmetric unit.