One-Bond ¹³C-¹H and ¹³C-¹³C Spin-Coupling Constants as Constraints in MA'AT Analysis of Saccharide Conformation

MA'AT analysis uses ensembles of redundant experimental NMR spin-coupling constants, parametrized J-coupling equations obtained from density functional theory (DFT) calculations, and circular statistics to produce probability distributions of molecular torsion angles in solution and information on librational motions about these angles (Meredith et al., J. Chem. Info. Model. 2022, 62, 3135-3141). Current DFT methods give nearly quantitative two- and three-bond J_HH, J_CH, and ¹J_CC values for use in MA'AT analysis of saccharides. In contrast, the accuracy of DFT-calculated one-bond ¹J_CH and ¹J_CC values is more difficult to determine, preventing their use in MA'AT modeling. This report describes experimental and computational studies that address this problem using two approaches (Strategies 1 and 2). Differences [¹J_CH^calc - ¹J_CH^exp] (Strategy 1) ranged from -1.2 to 2.5 Hz, giving an average difference of 0.8 ± 1.7 Hz. Percent differences ranged from -0.8% to 1.6%, giving an average % difference of 0.5 ± 1.1%. In comparison, [¹J_CH - ¹J_CH^exp] (Strategy 2) ranged from -1.8 to 0.2 Hz, giving an average difference of -1.2 ± 0.7 Hz. Percent differences ranged from -1.2% to 0.1%, giving an average % difference of -0.8 ± 0.5%. Strategy 1 gave an average difference of 2.1 Hz between calculated and experimental ¹J_CC values, with an average % difference of 5.1 ± 0.2%. Calculated ¹J_CC values were consistently larger than experimental values. Strategy 2 also gave calculated ¹J_CC values that were larger than the experimental values, with an average difference of 2.3 ± 0.6 Hz, and an average % difference of 5.6 ± 1.6%. The findings of both strategies are similar and indicate that ¹J_CH values in saccharides can be calculated nearly quantitatively, but ¹J_CC values appear to be consistently overestimated by ∼5% using current DFT methods.