Nonconventional NMR 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 ( 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.