Aqueous-Phase Polyelectrolyte Behavior of HydroxypropylChitosan

Abstract Hydroxypropyl chitosan (HPCS) is a water-soluble, cationic derivative of chitosan whose combination of hydrophilic substituents and residual charged and hydrophobic groups creates a unique landscape of interactions in aqueous media. Despite growing interest in chitosan-based materials, the fundamental solution behavior of HPCS, and the way its weak polyelectrolyte character couples with hydrophilic substitution, has remained largely underexplored. Here, we present a comprehensive, multiscale characterization of HPCS structure and dynamics across ionic strengths ranging from salt-free to excess-salt conditions, integrating synchrotron small-angle X-ray scattering (SAXS) with dynamic light scattering (DLS) and complementary model-based analyses to resolve structural transitions across length scales. In salt-free semidilute conditions, HPCS behaves as a semirigid, hydrophilic polyelectrolyte, exhibiting a pronounced polyelectrolyte peak and rodlike chain conformations in SAXS. The scaling of the correlation length with polymer concentration confirms that long-range electrostatic interactions contribute toward chain organization despite the weakened charge density imposed by high degrees of hydroxypropyl group substitution. With the addition of monovalent salt, the correlated mesh dissolves, and DLS reveals fast hydrodynamic modes associated with screened chains, along with slow modes corresponding to large supramolecular aggregates. At higher salt concentrations (cs ≳ 0.25 M), salting-out is not observed, and the structural response becomes nonmonotonic, revealing underscreening-like behavior and salt-driven aggregation mechanisms captured through a phenomenological Random Phase Approximation (RPA) analysis. Together, these results establish how ionic environment dictates distinct HPCS structural regimes, from electrostatically repulsed networks to screened coils and salt-modulated supramolecular assemblies, providing foundational insight for tailoring hierarchical organization and self-assembly in HPCS-based solutions.