Nonconventional NMR Spin-Coupling Constants in Oligosaccharide Conformational Modeling: Structural Dependencies Determined from Density Functional Theory Calculations

[Image: see text] 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 ((1)J(C1′,H1′), (1)J(C1′,C2′), (2)J(C1′,H2′), and (2)J(C2′,H1′)) and eight ((1)J(C4,H4), (1)J(C3,C4), (1)J(C4,C5), (2)J(C3,H4), (2)J(C4,H3), (2)J(C5,H4), (2)J(C4,H5), and (2)J(C3,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 (4)J(H1′,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.