Ab initio and NMR studies on the effect of hydration on the chemical shift of hydroxy protons in carbohydrates using disaccharides and water/methanol/ethers as model systems

Density functional theory (DFT) and Hartree-Fock (HF) quantum mechanical calculations have been performed on the disaccharides, small beta]-l-Fucp-(1rightward arrow]4)-small alpha]-d-Galp-OMe, small beta]-l-Fucp-(1rightward arrow]4)-small alpha]-d-Glcp-OMe, and small beta]-l-Fucp-(1rightward arrow]3)-small alpha]-d-Glcp-OMe. The capital Delta]small delta]-values (difference between the chemical shift in the disaccharide and the corresponding monosaccharide methyl glycoside) for the exchangeable hydroxy protons have been calculated and compared to experimental values previously measured by NMR spectroscopy for samples in aqueous solutions. The calculations performed on molecules in vacuum showed that hydroxy protons hydrogen bonded to the neighboring ring oxygens have large positive capital Delta]small delta]-values, indicating that they are deshielded relative to those in the corresponding methyl glycoside. The NMR experiments showed instead that these hydroxy protons close to the neighboring ring oxygens were shielded. This discrepancy between calculated and experimental data was attributed to solvent effects, and this hypothesis has been confirmed in this work by monitoring the chemical shift of the hydroxy proton of methanol in water, ethers and water/ether solutions. Shielding of the hydroxy proton of methanol is observed for increased ether concentrations, whereas deshielding is observed for increased concentration of water. The shielding observed for hydroxy protons in disaccharides is a consequence of reduced hydration due to intermolecular hydrogen bonding or steric effects. In strongly hydrated systems such as carbohydrates, the hydration state of a hydroxy proton is the key factor determining the value of the chemical shift of its NMR signal, and the capital Delta]small delta] will be a direct measure of the change in hydration state.