Titration Properties and pH-Dependent Aggregation of Chitosan

Chitosan is a polysaccharide consisting of N-acetyl-glucosamine and glucosamine units, prepared by the deacetylation of chitin. Glucosamine contains an ionizable primary amine, rendering chitosan water-soluble at low pH and insoluble at pH above ∼6.5. This pH dependent solubility can be exploited to make hydrogels used for coatings and sensors. We have used constant-pH molecular dynamics (CpHMD) to investigate the pH dependence of chitosan. Starting from a stable aggregate of neutral chitosan, we performed replica exchange simulations over a pH range 4.0-8.5. The aggregate remains stable at high pH and dissociates at low pH, as expected. Interestingly, the transition occurs cooperatively at around pH 6.5, in a remarkable agreement with experiment. The calculated bulk pKa was found to be similar to the transition pH, again in agreement with experiment. The role of electrostatic interactions and aggregation-induced desolvation in the protonation equilibria of the amine groups was also examined. This work provides atomic-level insight into the pH-dependent behavior of chitosan which may aid in the design and development of various chitosan-based materials.