Synthesis and NMR characterization of new hyaluronan-based NO donors.
Nitric oxide (NO) and hyaluronic acid (HA), two species widely different in terms of molecular complexity and biological competence, are both known to play an important role in the wound healing process. To combine the properties of HA and NO, we synthesized new NO-donors based on hyaluronic acid derivatives exhibiting a controlled NO-release under physiological conditions (in vitro tests). Since two molecules of NO can form a covalent bond with secondary amines to yield structures, named NONO-ates, able to release NO in solution, we used spermidine bound to HA as the NO-linker. The HA-spermidine derivative was obtained by controlled HA amidation in aqueous media, activating the biopolymer carboxylate groups with a water soluble carbodiimide. The resulting derivative, soluble in water, was fully characterized by high field 1H and 13C NMR spectroscopy. The amount of grafting of spermidine on HA was determined by integration of suitable 1H NMR signals. In addition, cross-linked derivatives of HA were synthesized by the Ugi's four-component reaction using formaldehyde, cyclohexylisocyanide, and spermidine. The HA-spermidine networks were characterized by 13C CP-MAS NMR spectroscopy. The degree of cross-linking of the networks was also determined. Finally, the release of NO from the swollen hydrogels freshly saturated with NO, in contact with aqueous media, was monitored by means of UV spectrophotometric measurements.
Di Meo
Chiara
C
Department of Chemistry, University of Rome La Sapienza, p.le Aldo Moro 5, 00185 Rome, Italy.
Capitani
Donatella
D
Mannina
Luisa
L
Brancaleoni
Enzo
E
Galesso
Devis
D
De Luca
Gilda
G
Crescenzi
Vittorio
V
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002247:Carbon Isotopes; D006820:Hyaluronic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017942:Nitric Acid / Q000737:chemistry*; D011522:Protons; D012680:Sensitivity and Specificity; D013095:Spermidine / Q000138:chemical synthesis* / Q000737:chemistry*
D002247:Carbon Isotopes; D011522:Protons; D017942:Nitric Acid; D006820:Hyaluronic Acid; D013095:Spermidine