Impact of polyampholyte macromolecular structure on the conformation of chitosan derivatives

Chitosan is a biocompatible and bioresorbable polymer family whose primary amine groups allow easy chemical modification through re-acetylation or functionalization, producing derivatives with tailored properties. While many chitosan derivatives have been characterized, detailed studies of ampholytic chitosan derivatives remain limited. This study investigates how the macromolecular structure of modified chitosans influences their physicochemical properties. The work focuses on chitosan functionalized with chelating ligands: polycarboxylates (DOTAGA, DTPA, EDTA) and the octadentate ligand DFO. Using several analytical techniques, the study examines the relationship between these structural modifications and resulting physicochemical behavior. A key contribution is a charge-based classification derived from two parameters: the mean charge of the repeat unit (c̅) and the charge fluctuation between adjacent units (δc²). Based on charge fluctuation, chitosan derivatives are categorized into three groups: cationic derivatives (δc² < 0.5), weak polyampholytes (0.5 < δc² < 1.5), and strong polyampholytes (δc² > 1.5). This classification correlates strongly with measured properties such as isoelectric point, Newtonian viscosity, and polymer conformation in solution, including gyration and hydrodynamic radii at high ionic strength and polyelectrolyte peak behavior at low ionic strength. The results demonstrate that charge distribution is a key determinant of the solution behavior and physicochemical properties of chitosan derivatives.