Hyaluronic acid and sulfated hyaluronic acid in aqueous solution: effect of the sulfation on the protonation and complex formation with Cu2+ and Zn2+ ions

Abstract

The behaviour of hyaluronic acid (Hyal) and sulfated hyaluronic acid (HyalS) in aqueous solution was investigated in terms of protonation and complex formation by thermodynamic and spectroscopic techniques. The presence of the scarcely protonable sulfate groups in the polymer chain provided the HyalS molecule with a more rigid structure in aqueous solution, allowing this polysaccharide to remain in the stretched conformation even after neutralisation of the carboxylate moieties. The presence of the sulfate groups also increases the basic character of the COO- group. Both Hyal and HyalS were able to form complexes with Cu 2+ and Zn 2+ ions in aqueous solution. The metal ion has a preferential binding site on these polysaccharides, providing a precise stoichiometry for the metal ion complex. The sulfate groups were not directly involved in the coordination of the metal ion, and the stoichiometry of the complex species is not affected by the presence of these groups. However, by increasing the negative charge on the polymer chain, the sulfate groups are responsible for the electrostatic attraction of the metal ion.