Comparative (1)H NMR and molecular modeling study of hydroxy protons of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH(2))(7)CH(3) analogues in aqueous solution

The (1)H chemical shifts, coupling constants, temperature coefficients, exchange rates, and inter-residual ROEs have been measured, in aqueous solution, for the hydroxy and amine/amide proton resonances of a set of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH(2))(7)CH(3) analogues. From the structural data, a few significant structural features could be ascertained, such as a preferential anti-conformation for the amide protons of the N-acetyl and N-propionyl groups. The introduction of systematic modifications at Gal 2-C and Gal 6-C resulted in alterations of the Gal 4-OH, Gal 3-OH, and GlcNAc 3-OH areas, since variations in chemical shifts and temperature coefficient were observed. In order to verify the possibility of hydrogen bonds, molecular dynamics simulations in the gas phase and explicit solvent were performed and correlated with the experimental data. A network of hydrogen bonds to solvent molecules was observed, but no strong intramolecular hydrogen bonding was observed.