How Solvent Influences the Anomeric Effect: Roles of Hyperconjugative versus Steric Interactions on the Conformational Preference

Abstract

The block-localized wave function (BLW) method, which can derive optimal electron-localized state with intramolecular electron delocalization completely deactivated, has been combined with the polarizable continuum model (PCM) to probe the variation of the anomeric effect in solution. Currently both the hyperconjugation and electrostatic models have been called to interpret the anomeric effect in carbohydrate molecules. Here we employed the BLW-PCM scheme to analyze the energy differences between α and β anomers of substituted tetrahydropyran C5OH9Y (Y = F, Cl, OH, NH2, and CH3) and tetrahydrothiopyran C5SH9Y (Y = F, Cl, OH, and CH3) in solvents including chloroform, acetone, and water. In accord with literature, our computations show that for anomeric systems the conformational preference is reduced in solution and the magnitude of reduction increases as the solvent polarity increases. Significantly, on one hand the solute-solvent interaction diminishes the intramolecular electron delocalization in β anomers more than in α anomers, thus destabilizing β anomers relatively. But on the other hand, it reduces the steric effect in β anomers much more than α anomers and thus stabilizes β anomers relatively more, leading to the overall reduction of the anomeric effect in anomeric systems in solutions.