AB-INITIO MOLECULAR-ORBITAL CALCULATION OF CARBOHYDRATE MODEL COMPOUNDS .3. EFFECT OF THE ELECTRIC-FIELD ON CONFORMATIONS ABOUT THE GLYCOSIDIC LINKAGE

The effect of the electric field on the conformational behavior of mod el compounds for glycosidic linkages, 2-methoxytetrahydropyran (MTHP) with axially and equatorially oriented methoxy groups has been investi gated by the ab initio molecular orbital method. The geometry of rotam ers about the glycosidic C-O bond was determined by gradient optimizat ion at the 6-31G level. The potential of rotation about the glycosidi c C-O bond has been calculated using the 6-31+G basis set in an elect ric field. The 6-31G optimized geometries were used to calculate ener gy differences between the AGT, ATG, AGG, EGT, ETG, and EGG conformers with 6-31G, 6-31+G*, 6-31+G**, 6-311++G*, and MP2/6-31G* basis sets. The electric field has been applied in various directions and strengt hs. The calculations revealed that strong electric fields influence th e topology of the rotational; potential energy. At all levels of theor y, the electric field has shown to have a significant effect on the re lative energies of conformers. This effect is so pronounced that in fi elds of E(x) = 0.01, E(x) = -0.01, and E(z) = -0.01 au the axial-equat orial equilibrium is reversed. Whereas in gas-phase axial MTHP is pref erred by 1.08 kcal/mol, in the presence of these fields, contrary to t he anomeric effect, equatorial MTHP is favored by 1.63, 1.14, and 3.48 kcal/mol, respectively. Electric fields also influence the relative s tability of conformers in both MTHP anomers. In the field of E(y) = -0 .01 au, the TG conformers are found to be favored over GT in both anom ers, contrary to the exo-anomeric effect which prefers the GT conforme rs. All larger basis sets give relative energies which agree fairly we ll with the 6-31+G results. These results suggest that strong externa l fields present on membrane surfaces might considerably influence con formational equilibria around the glycosidic linkages of carbohydrate portions of membrane glycoconjugates and thus their overall shape. The y also imply that conformations not found in gas-phase or solution equ ilibria might be of importance in the biological activity of membrane bound molecules.