MODIFICATION OF HYALURONIC-ACID BY INSERTION OF SULFATE GROUPS TO OBTAIN A HEPARIN-LIKE MOLECULE .1. CHARACTERIZATION AND BEHAVIOR IN AQUEOUS-SOLUTION TOWARDS H+ AND CU2+ IONS

Hyaluronic acid (Hyal) was modified by insertion of sulphate groups to obtain a heparin-like molecule. The sulphation reaction is reported, and the behaviour of the modified polysaccharide (HyalSO(3)) toward H and Cu2+ ions in aqueous solution is evaluated and compared to that o f the native hyaluronic acid and heparin. The potentiometric, viscosim etric and infrared protonation studies revealed that the insertion of sulphate groups in the Hyal polysaccharide chains is reflected in a po lyelectrolyte behaviour, very close to that of heparin. With regard to the Cu(II)-complex formation, both carboxyl and amide moieties of Hya lSO(3) have been demonstrated to be directly involved in the coordinat ion process, as happened in the case of heparin. The sulphate groups, even if not directly involved in the coordination site, appear to play an important cooperative role in the metal-ligand interaction and sta bility of the complex, without affecting its stoicheiometry.