Synthesis, structural characterization and properties of water-soluble N-(γ-propanoyl-amino acid)-chitosans

Water-soluble peptide-chitosans were obtained by reaction of low-molecular-weight chitosan, having a low degree of acetylation, with peptide substituents under mild conditions. These peptide substituents were prepared by standard peptide chemistry from 3-bromopropanoic acid and tert-butyl esters of the α-amino acids glycine and phenylalanine. The structure of the new peptide-chitosan polymers was confirmed by proton nuclear magnetic resonance and infrared spectroscopy. The thermotropic and morphological properties of both the new peptide-chitosans and two other analogues, derived from valine and aspartic acid [synthesis reported in Batista, M. K. S., Pinto, L. F., Gomes, C. A. R., & Gomes, P. (2006). Novel highly soluble peptide-chitosan polymers: Synthesis and spectral characterization. Carbohydrate Polymers, 64, 299–305], were evaluated by differential scanning calorimetry and scanning electron microscopy, respectively. As compared to the parent unmodified chitosan, the four peptide-chitosans had higher thermosensitivity, porosity and water-holding capacity, and such effects increased with the hydrophilicity of the peptide ligands. The acid-base properties of the four peptide-chitosans were also evaluated by potentiometric techniques and reflected the influence of the inserted ligands on the polymers’ acidity constants. It was also possible to confirm the polymers’ solubility over the 2–10 pH range. Overall, these polymers present physico-chemical properties that make them promising candidates for the design of novel drug delivery systems.