Nonconventional spin-coupling constants in oligosaccharide conformational modeling: structural dependencies determined from density functional theory calculations

Nonconventional NMR spin-coupling constants were investigated to determine their potential as conformational constraints in MA'AT modeling of the O-glycosidic linkages of oligosaccharides. Four (1JC1',H1', 1JC1',C2', 2JC1',H2', and 2JC2',H1') and eight (1JC4,H4, 1JC3,C4, 1JC4,C5, 2JC3,H4, 2JC4,H3, 2JC5,H4, 2JC4,H5, and 2JC3,C5) spin-couplings in methyl β-d-galactopyranosyl-(1→4)-β-d-glucopyranoside (methyl β-lactoside) were calculated using density functional theory (DFT) to determine their dependencies on O-glycosidic linkage C-O torsion angles, ϕ and ψ, respectively. Long-range 4JH1',H4 was also examined as a potential conformational constraint of either ϕ or ψ. Secondary effects of exocyclic (hydroxyl) C-O bond rotation within or proximal to these coupling pathways were investigated. Based on the findings of methyl β-lactoside, analogous J-couplings were studied in five additional two-bond O-glycosidic linkages [βGlcNAc-(1→4)-βMan, 2-deoxy-βGlc-(1→4)-βGlc, αMan-(1→3)-βMan, αMan-(1→2)-αMan, and βGlcNAc(1→2)-αMan] to determine whether the coupling behaviors observed in methyl β-lactoside were more broadly observed. Of the 13 nonconventional J-couplings studied, 7 exhibit properties that may be useful in future MA'AT modeling of O-glycosidic linkages, none of which involve coupling pathways that include the linkage C-O bonds. The findings also provide new insights into the general effects of exocyclic C-O bond conformation on the magnitude of experimental spin-couplings in saccharides and other hydroxyl-containing molecules.