One-bond C-C spin-coupling constants in saccharides: a comparison of experimental and calculated values by density functional theory using solid-state C NMR and X-ray crystallography.

Methyl aldohexopyranosides were C-labeled at contiguous carbons, crystallized, and studied by single-crystal X-ray crystallography and solid-state C nuclear magnetic resonance (NMR) spectroscopy to examine the degree to which density functional theory (DFT) can calculate one-bond C-C spin-coupling constants () in saccharides with sufficient accuracy to permit their use in ' analysis, a newly-reported hybrid DFT/NMR method that provides probability distributions of molecular torsion angles in solution (Zhang , , 2017, , 3042-3058; Meredith , , 2022, , 3135-3141). Experimental values in crystalline samples of the doubly C-labeled compounds were measured by solid-state C NMR and compared to those calculated from five different DFT models: (1) values calculated from single structures identical to those observed in crystalline samples by X-ray crystallography (all atom refinement); (2) values calculated from the single structures in (1) but after Hirshfeld atom refinement (HAR); (3) values calculated from the single structures in (1) after DFT-optimization of hydrogen atoms only; and (4 and 5) values calculated in rotamers of torsion angle (C1-C2-O2-O2H) or (C4-C5-C6-O6) from which either specific or generalized parameterized equations were obtained and used to calculate values in the specific or rotamers observed in crystalline samples. Good qualitative agreement was observed between calculated values and those measured by solid-state C NMR regardless of the DFT model, but in no cases were calculated values quantitative, differing (over-estimated) on average by 4-5% from experimental values. These findings, and those reported recently from solution NMR studies (Tetrault , . B , , 9506-9515), indicate that improvements in DFT calculations are needed before calculated values can be used directly as reliable constraints in ' analyses of saccharides in solution.