One-bond 13C-13C spin-coupling constants in saccharides: a comparison of experimental and calculated values by density functional theory using solid-state 13C NMR and X-ray crystallography.

Methyl aldohexopyranosides were 13C-labeled at contiguous carbons, crystallized, and studied by single-crystal X-ray crystallography and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy to examine the degree to which density functional theory (DFT) can calculate one-bond 13C-13C spin-coupling constants (1JCC) in saccharides with sufficient accuracy to permit their use in MA'AT analysis, a newly-reported hybrid DFT/NMR method that provides probability distributions of molecular torsion angles in solution (Zhang et al., J. Phys. Chem. B, 2017, 121, 3042-3058; Meredith et al., J. Chem. Inf. Model., 2022, 62, 3135-3141). Experimental 1JCC values in crystalline samples of the doubly 13C-labeled compounds were measured by solid-state 13C NMR and compared to those calculated from five different DFT models: (1) 1JCC values calculated from single structures identical to those observed in crystalline samples by X-ray crystallography (all atom refinement); (2) 1JCC values calculated from the single structures in (1) but after Hirshfeld atom refinement (HAR); (3) 1JCC values calculated from the single structures in (1) after DFT-optimization of hydrogen atoms only; and (4 and 5) 1JCC values calculated in rotamers of torsion angle θ2 (C1-C2-O2-O2H) or ω (C4-C5-C6-O6) from which either specific or generalized parameterized equations were obtained and used to calculate 1JCC values in the specific θ2 or ω rotamers observed in crystalline samples. Good qualitative agreement was observed between calculated 1JCC values and those measured by solid-state 13C NMR regardless of the DFT model, but in no cases were calculated 1JCC values quantitative, differing (over-estimated) on average by 4-5% from experimental values. These findings, and those reported recently from solution NMR studies (Tetrault et al., J. Phys. Chem. B 2022, 126, 9506-9515), indicate that improvements in DFT calculations are needed before calculated 1JCC values can be used directly as reliable constraints in MA'AT analyses of saccharides in solution.