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.