MM3 MODELING OF FRUCTOSE RING SHAPES AND HYDROGEN-BONDING

MM3(92) was used to minimize energies in exhaustive searches of the ri ng shapes and orientations of exocyclic groups for four fructose tauto mers (alpha-furanose, beta-furanose, alpha-pyranose and alpha-pyranose ). A dielectric constant of 4.0 was used to emulate a ''general conden sed phase'' environment. Calculated energies of the three major tautom ers 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 en ergy of the minor alpha-pyranose form was 2.5 kcal above the minimum. Tautomeric ratios from crystal structures and from DMSO as well as aqu eous solutions differ depending on the environment. However, no experi ment has found quite as much alpha-furanose as we predict, unlike our results on other monosaccharides where the extents of beta-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 rationaliz e the distribution of conformers of each tautomer. Numerous beta-furan ose rings in crystals fit well as do the beta-pyranose rings, and our interpretation of literature NMR data requires a north-south equilibri um for alpha-furanose. Model bond lengths were compared with averaged data from precise X-ray studies of crystals containing beta-D-fructopy ranose. Bonds between heavy atoms based on r(alpha) (an optional compu tation corresponding to distances between thermally averaged centers) ft about 25% better than the normal MM3 values that correspond to r (g as-phase electron diffraction results). The C2-O2 (anomeric) bond leng th was over-estimated by 0.024 Angstrom, but the mean absolute deviati on of the other bonds was only 0.006 Angstrom. 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 augment ed by the lack of destabilizing dipole-dipole forces. MM3(92) (with a dielectric constant of 4.0) accommodated hydrogen bond geometries foun d in crystals. (C) 1997 Elsevier Science B.V.