Guest molecule diffusion in the chitosan-ZnCl₂ complex crystal: A molecular dynamics simulation study

We present combined molecular dynamics (MD) simulations using adaptive steered MD and umbrella sampling MD methods. The simulations can be used to evaluate the potential of mean force (PMF), i.e., the free energy change, for the diffusion of a ZnCl₂ molecule in the pathway introduced in the chitosan-ZnCl₂ complex crystal models. With some exceptions, most of the PMF plots showed a moderate increase in endothermic free energy of approximately 10 kcal/mol up to a ZnCl₂ moving distance of 1.5 times the fiber repeat distance, accompanied by exothermic peaks in free energy. During its movement, the ZnCl₂ molecule made more frequent contact with the O6 hydroxyl groups than with the N2 primary amino groups, whereas these contacts readily disappeared in the gap crystal models with the expanded pathway. These results suggest that ZnCl₂ molecules prefer to interact with O6 hydroxyl groups rather than N2 amino groups in the confined space inside the crystal. The O6 hydroxyl group, which is connected to a freely rotatable C5-C6 bond, can adopt oriented positions of wider range. This is consistent with the fact that the chitosan-ZnCl₂ complex crystal was obtained by in situ solid-state conversion of the original chitosan crystal.