The conformational properties of the sugar-phosphate linkage (the phosphate functional group is linked to the anomeric carbon in hexopyranosides) have been studied with ab initio methods using the 2-O-methylphosphono-tetrahydropyran anion (1) and sodium 2-O-methylphosphono-tetrahydropyran (2) as models. The ab initio energy and geometry of the conformers around the C1-O1 and O-P bonds have been determined at various levels of theory and solvent effects evaluated. At all levels of ab initio theory, 1 prefers the trans to the gauche conformer around the C1-O1 bond. The repulsive electrostatic interactions between the ring oxygen and the PO2- group are assumed to be responsible for this phenomenon, which has been termed the reverse exo-anomeric effect. For the PO2- group, we estimate a 2.3 kcal/mol magnitude for the reverse exoanomeric effect in a vacuum. The presence of the sodium counterion completely reverses the relative energy of the conformers, such that in the ion-pair complex 2, the gauche conformer about the C1-O1 bond is favored in agreement with crystallographic data. Ab initio results were compared with results obtained by several quantum semiempirical and molecular mechanics methods. On the basis of structural differences between 1 and 2, we suggest that the metal cofactor plays three roles in the catalytic mechanism of transferases. It stabilizes a suitable conformation for the sugar donor, activates the C1-O1 glycosidic linkage, and enables the protonation of the glycosidic oxygen to begin the scission of the glycosidic bond.