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

We report synthesis and solid-state 17 O NMR characterization of α-d-glucose for which all six oxygen atoms are site-specifically 17 O-labeled. Solid-state 17 O NMR spectra were recorded for α-d-glucose/NaCl/H 2 O (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 17 O 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 1 H and 17 O 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 17 O NMR by a factor of 6-8, which made it possible to acquire high-quality 2D 17 O multiple-quantum (MQ) MAS spectra for carbohydrate compounds. The unprecedented spectral resolution offered by 2D 17 O 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 17 O-labeled and fully characterized by solid-state 17 O NMR. Gauge Including Projector Augmented Waves (GIPAW) DFT calculations were performed to aid 17 O and 13 C NMR signal assignments for a complex crystal structure where there are six crystallographically distinct α-d-glucose molecules in the asymmetric unit.