Density functional theory (DFT) has been used to investigate the structural dependencies of NMR spin-couplingconstants (
J-couplings) involving the exchangeable hydroxyl protons of saccharides.
3JHCOH,
3JCCOH, and
2JCOHvalues were calculated at different positions in model aldopyranosyl rings as a function of one or more torsionangles, and results support the use of a generalized Karplus equation to treat
3JHCOH involving the
non-anomericOH groups. The presence of O5 appended to the H1-C1-O1-H coupling pathway introduces asymmetry in
3JH1,O1H Karplus curves due to internal electronegative substituent effects on the
gauche couplings, thus requiringseparate equations to treat this coupling.
3JCCOH values depend not only on the C-C-O-H torsion angle butalso on the orientation of terminal substituents on the coupled carbon, similar to
3JCOCC studied previously(Bose et al.,
J. Am. Chem. Soc.
1998,
120, 11158-11173). "In-plane" oxygen increased
3JCCOH by ~3-4 Hz,whereas "in-plane" carbon gave more modest enhancements (~1 Hz). Three Karplus equations were derivedfor non-anomeric
3JCCOH based on the nature and orientation of substituents on the coupled carbon. Like
3JH1,O1H,
3JC2,O1H is also subject to internal electronegative substituent effects on the
gauche couplings, thus necessitatingseparate equations to treat this coupling.
2JCOH values were found not to be useful probes of C-O torsions asa result of their nonsystematic dependence on these torsions. Experimental measurements of
3JHCOH and
3JCCOHin doubly
13C-labeled methyl -lactoside
20 and its constituent
13C-labeled methyl aldopyranosides in H
2O/acetone-
d6 at -20 C showed that some C-O torsion angles are influenced by molecular context and do notexperience complete rotational averaging in solution. A strong bias in the H3-C3-O3-H torsion angle in theGlc residue of
20 favoring a
gauche conformation suggests the presence of inter-residue H-bonding betweenO3H
Glc and O5
Gal. Quantitative analysis of
3JHCOH and
3JCCOH values in
20 indicates that ~85% of the formsin solution have geometries consistent with H-bonding. These results suggest that H-bonding between adjacentand/or remote residues may play a role in dictating preferred glycosidic bond conformation in simple andcomplex oligosaccharides in aqueous solution.
