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 (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 four different DFT models: (1) 1JCC values calculated from a single structure identical to that observed in crystalline samples by X-ray crystallography; (2) 1JCC values calculated from the same single structure in (1) but allowing all C–H bonds to optimize during the DFT calculations; and (3 and 4) 1JCC values calculated in rotamers of torsion angle theta 2 (C1–C2–O2–O2H) or omega (C4–C5–C6–O6) from which either specific or generalized parameterized equations were obtained and used to calculate 1JCC values in the specific theta 2 or omega rotamer 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 on average by 4–5% from experimental values. Calculated 1JCC values were consistently larger than experimental values. These findings, and those reported in recent solution NMR studies (Tetrault et al., J. Phys. Chem. B 2022, in press), indicate that improvements in DFT calculations are needed before calculated 1JCC values can be used as reliable constraints in MA’AT analyses of saccharides in solution.