MM3 modeling of fructose ring shapes and hydrogen bonding

Abstract

MM3(92) was used to minimize energies in exhaustive searches of the ring shapes and orientations of exocyclic groups for four fructose tautomers (α-furanose, β-furanose, α-pyranose and α-pyranose). A dielectric constant of 4.0 was used to emulate a “general condensed phase” environment. Calculated energies of the three major tautomers were within a range of 0.86 kcal after the correction by −5.5 kcal as done by MM3 for heats of formation for five-membered rings. The energy of the minor α-pyranose form was 2.5 kcal above the minimum. Tautomeric ratios from crystal structures and from DMSO as well as aqueous solutions differ depending on the environment. However, no experiment has found quite as much α-furanose as we predict, unlike our results on other monosaccharides where the extents of β-anomers are slightly over-estimated. In all cases, however, the apparent error of the MM3 calculations has been less than 1.0 kcal/mol. Energy surfaces for ring puckering depict the degree of pseudorotation and rationalize the distribution of conformers of each tautomer. Numerous β-furanose rings in crystals fit well as do the β-pyranose rings, and our interpretation of literature NMR data requires a north-south equilibrium for α-furanose. Model bond lengths were compared with averaged data from precise X-ray studies of crystals containing β- d-fructopyranose. Bonds between heavy atoms based on r α (an optional computation corresponding to distances between thermally averaged centers) fit about 25% better than the normal MM3 values that correspond to r g (gas-phase electron diffraction results). The C2O2 (anomeric) bond length was over-estimated by 0.024 Å, but the mean absolute deviation of the other bonds was only 0.006 Å. Intramolecular hydrogen bonds were weak in most preferred fructose models, shown by a plot of energy vs. lengths and angles of hydrogen bonds. The stabilization of sugar models with peripheral intramolecular hydrogen bonds is augmented by the lack of destabilizing dipole-dipole forces. MM3(92) (with a dielectric constant of 4.0) accommodated hydrogen bond geometries found in crystals.