DFT and NMR studies of 2JCOH 3JHCOH, and 3JCCOH spin-couplings in saccharides:: C-O torsional bias and H-bonding in aqueous solution

Density functional theory (DFT) has been used to investigate the structural dependencies of NMR spin-coupling constants (J-couplings) involving the exchangeable hydroxyl protons of saccharides. (3)J(HCOH), (3)J(CCOH), and (2)J(COH) values were calculated at different positions in model aldopyranosyl rings as a function of one or more torsion angles, and results support the use of a generalized Karplus equation to treat (3)J(HCOH) involving the non-anomeric OH groups. The presence of 05 appended to the H1-Cl-O1-H coupling pathway introduces asymmetry in (3)J(H1.O1H) H Karplus curves due to internal electronegative substituent effects on the gauche couplings, thus requiring separate equations to treat this coupling. (3)J(CCOH) values depend not only on the C-C-O-H torsion angle but also on the orientation of terminal substituents on the coupled carbon, similar to 3J(COCC) studied previously (Bose et al., J. Am. Chem. Soc. 1998, 120, 11158-11173). "In-plane" oxygen increased (3)J(CCOH) by similar to 3-4 Hz, whereas "in-plane" carbon gave more modest enhancements (similar to 1 Hz). Three Karplus equations were derived for non-anomeric (3)J(CCOH) based on the nature and orientation of substituents on the coupled carbon. Like (3)J(H1.O1H), (3)J(C2,O1H) is also subject to internal electronegative substituent effects on the gauche couplings, thus necessitating separate equations to treat this coupling. (2)J(COH) values were found not to be useful probes of C-O torsions as a result of their nonsystematic dependence on these torsions. Experimental measurements Of (3)J(HCOH) and (3)J(CCOH) in doubly 13 C-labeled methyl P-lactoside 20 and its constituent 13 C-labeled methyl aldopyranosides in H2O/ acetone-d(6) at -20 degrees C showed that some C-O torsion angles are influenced by molecular context and do not experience complete rotational averaging in solution. A strong bias in the H3-C3-O3-H torsion angle in the Glc residue of 20 favoring a gauche conformation suggests the presence of inter-residue H-bonding between O3H(Glc) and 05(Gal). Quantitative analysis of (3)J(HCOH) and (3)J(CCOH) values in 20 indicates that similar to 85% of the forms in solution have geometries consistent with H-bonding. These results suggest that H-bonding between adjacent and/or remote residues may play a role in dictating preferred glycosidic bond conformation in simple and complex oligosaccharides in aqueous solution.