Intermolecular Interaction and Molecular Dynamics Study of Carboxymethyl Chitosan..Vitamin C Molecular Complex for Understanding Encapsulation and Kinetics-Controlled Released Mechanism

Abstract

To Application of carboxymethyl chitosan (CMC) as a basic material for drug delivery is based on its solubility in water. Degree of Substitution (DS) of a carboxyl group which bound to the nucleophile -NH2, -OH, or both of chitosan (N-CMC; O-CMC; N,0-CMC) can affect the solubility of CMC in the water. Furthermore, DS of CMC is the potential factor in the complex system of CMC.. Vitamin C that affect the encapsulation and controlled release. However, the experiment was still difficult to explain the location of interaction between vitamin C and the substituted carboxyl group of CMC. In this study, the interaction between vitamin C and substituted carboxyl group of CMC on the -NH2, -OH, or both nucleophile have been modeled by in silico approach using molecular docking and dynamics. The results showed that the substituted carboxyl group on the nucleophile -NH2, -OH, or both can affect its binding energy value (AG) with vitamin C, and those data were able to explain the encapsulation process. The binding energy of carboxymethyl chitosan trimer (CMC-3).. Vitamin C complex, the substitution of the carboxyl group on the -NH2 nucleophile (N-CMC-3), was -3.36 kcal/mole. This AG was stronger (more stable) than O-CMC-3.. Vitamin C complex and N,O-CMC-3.. Vitamin C complex. Whereas the binding energy of carboxymethyl chitosan with 5 monomers (CMC-5), the substitution of the carboxyl group on the -OH nucleophile (O-CMC-5), was -3.15 kcal/mole, stronger than N-CMC-5.. Vitamin C complex and N,0-CMC-5.. Vitamin C complex. The molecular dynamics simulation explained that the stability of the C M C. Vitamin C complexes was affected by the binding energy, and this data was assumed able to explain the kinetics-controlled released Mechanism. So, it can be concluded that the substitution position of carboxyl groups in chitosan and DS of CMC was the important factor of the stability C M C. Vitamin C complexes.