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

Abstract

Density functional theory (DFT) and Hartree-Fock (HF) quantum mechanical calculations have been performed on the disaccharides, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Galp-OMe, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Glcp-OMe, and [small beta]-l-Fucp-(1[rightward 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.

Comparative 1H NMR and molecular modeling study of hydroxy protons of β-d-Galp-(1→4)-β-d-GlcpNAc-(1→2)-α-d-Manp-(1→O)(CH2)7CH3 analogues in aqueous solution

“…28 To summarize, the upfield shifts of the GlcNAc 3-OH group are probably caused by the nearby ring and glycosidic O atoms as described for structures with a similar structural arrangement. [11][12][13][14][15][16] The shielding of Gal 4-OH when reducing the 2-C atom in 3 and 4 can only be attributed to a significant change in the water network covering the carbohydrate, since no direct interaction between 2-OH and 4-OH is possible. In addition, the large downfield shift introduced to some OH groups when introducing a NH 3 þ group at Gal 6-C (11 and 12) is likely to be caused by the positive charge, since the effect is only observed on adjacent groups and decreases with the distance.…”

“…Positioning of the 3-OH proton in close proximity to the Gal ring and the glycosidic O has been found to provide a shielding effect. 15 In lactose and compounds with similar stereochemistry and conformation around the glycosidic linkage, such a close proximity renders possibly the formation of a hydrogen bond between Gal 5-O and Glc 3-OH. 22 The effects observed for GlcNAc 2-NH and GlcNAc 6-OH are weaker.…”

“…Only some signals in 3-4 (Gal!Gal 2d ) and 9-10 (Gal!Gal 6d ) generated exchange rate values (Tables 1-3 may originate either from the presence of hydrogen bonds 14,15 or from the proximity with some nearby bulky groups, 19 which limits the access to the solvent. However, since only very few K ex values could be calculated, no solid conclusions can be drawn from these data.…”

“…Taking into account the importance of hydrogen bond interactions in carbohydrates, 1,2 the use of the exchangeable hydroxy protons in H 2 O in conformational studies has given new insights into the 3D structure of carbohydrates in solution. Typical 1 H NMR examples comprise the conformational analysis of polysaccharides, [3][4][5][6][7][8] synthetic and isolated oligosaccharides, [9][10][11][12][13][14][15][16][17] and glycopeptides. [18][19][20] To obtain structural information in terms of stereochemistry, inter-proton distances, hydrogen bonding, and hydration, hydroxy protons are usually studied at low temperatures in a solvent mixture of 85% H 2 O and 15% deuterated acetone.…”

NMR study on the hydroxy protons of the Lewis X and Lewis Y oligosaccharides

“…The results suggested that in strongly hydrated systems, the interaction between bulk water and hydroxy protons is the key factor contributing to the values of chemical shifts. 8 Thus, when the hydration of a hydroxy group is reduced due to interaction with acetal oxygens or to steric factors, the hydroxy proton is shielded.…”