Effect of molecular structure and ionization state on aggregation of carboxymethyl chitosan: A molecular dynamics study

The aggregation behavior of carboxymethyl chitosan (CMCS) plays an important role in its extensive applications. Here, we perform molecular dynamics simulations to investigate aggregation behaviors of CMCS in water and the effects of degrees of deacetylation (DD) and substitution (DS) and ionization states (equivalently different pH conditions). CMCS prefers to aggregate in neutral condition, self-assembling into multimeric forms with interlaced stacking of molecular chains, while forming dimer or trimer through twisted stacking and parallel stacking in acidic and alkaline conditions, respectively. With the increase of DD and DS, the aggregation becomes weaker when in neutral and alkaline conditions, while gets stronger in acidic environment. The presence of intramolecular hydrogen bonds and exo-anomeric effect causes twisted, coplanar and extended conformations of individual chain in acidic, alkaline and neutral conditions, respectively, contributing to their distinct inter-chain stacking structures. Subsequently, the specific intermolecular hydrogen bonding, hydrophobic and electrostatic interactions stabilize the aggregation structures.