Conformational properties of the disaccharide building units of hyaluronan

The conformational space of the disaccharide building units of hyaluronan, beta-(1-->4) and beta-(1-->3)-linked N-acetyl-beta-d-glucosamine (GN) and beta-D-glucuronic acid (GA), has been investigated by density functional theory calculations at the B3LYP/6-31G(**) level. The study covered the anionic disaccharides, the neutral acids as well as the sodium salts in the isolated state and in aqueous solution using the PCM model approach. We elucidated the intramolecular hydrogen bonding interactions characterizing the most favoured conformers. The protonation and salt formation change these secondary interactions in the vicinity of the carboxyl group, resulting often in a considerable alteration of the conformational preferences. The Na(+) ion in the salt is involved in multiple bonding in the most stable structures: beyond the primary ionic bond with the carboxylate group it forms slightly weaker interactions with neighbouring oxygens. The main effect of protonation and salt formation on the electron density distribution is restricted to the surroundings of the broken/formed interactions near the carboxylate group.