Two-bond ¹³C-¹³C spin-coupling constants in saccharides: dependencies on exocyclic hydroxyl group conformation

Seven doubly ¹³C-labeled isotopomers of methyl β-D-glucopyranoside, methyl β-D-xylopyranoside, methyl β-D-galactopyranoside, methyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside and methyl β-D-galactopyranosyl-(1→4)-β-D-xylopyranoside were prepared, crystallized, and studied by single-crystal X-ray crystallography and solid-state ¹³C NMR spectroscopy to determine experimentally the dependence of ²J_C1,C3 values in aldopyranosyl rings on the C1-C2-O2-H torsion angle, θ₂, involving the C2 carbon of the C1-C2-C3 coupling pathway. Using X-ray crystal structures to determine θ₂ in crystalline samples and by selecting compounds that exhibit a relatively wide range of θ₂ values in the crystalline state, ²J_C1,C3 values measured in crystalline samples were plotted against θ₂ and the resulting plot compared to that obtained from density functional theory (DFT) calculations. For θ₂ values ranging from ∼90° to ∼240°, very good agreement was observed between the experimental and theoretical plots, providing strong validation of DFT-calculated spin-coupling dependencies on exocyclic C-O bond conformation involving the central carbon of geminal C-C-C coupling pathways. These findings provide new experimental evidence supporting the use of ²J_CCC values as non-conventional spin-coupling constraints in MA'AT conformational modeling of saccharides in solution, and the use of NMR spin-couplings not involving coupled hydroxyl hydrogens as indirect probes of C-O bond conformation. Solvomorphism was observed in crystalline βGal-(1→4)-βGlcOCH₃ wherein the previously-reported methanol solvate form was found to spontaneously convert to a monohydrate upon air-drying, leading to small but discernible conformational changes in, and a new crystalline form of, this disaccharide.