Computational Insights into the Structure and Mechanism of Encapsulating Mangostin Derivatives in Crystalline Cucurbituril Architectures to Improve Solubility

Mangostin is a bioactive compound derived from mangosteen with significant therapeutic potential. However, mangostin has limitations in biomedical applications due to its low solubility in water. This study aims to increase the solubility of mangostin derivatives through encapsulation in cucurbituril crystalline architecture using in silico methods. The results showed that cucurbituril significantly enhanced the solubility of mangostin derivatives through supramolecular encapsulation, which stabilized the bioactive compound within the hydrophobic cavity of cucurbituril. This encapsulation not only improved the solubility but also maintained the bioactivity of mangostin derivatives, offering potential for the development of advanced delivery systems for hydrophobic bioactive compounds in the pharmaceutical and nutraceutical fields. This study utilized molecular dynamics simulations, docking studies, and computational chemistry techniques to reveal the host-guest interaction between cucurbituril and mangostin derivatives. Molecular dynamics simulations were performed using GROMACS software with CHARMM force field to evaluate the stability of the host-guest complex. Docking studies were performed with AutoDock Vina to predict the binding affinity and interaction position. In addition, computational chemistry calculations were performed using density function theory (DFT) with B3LYP calculation level and 6-31G(d,p) basis set to optimize the geometry and describe the electron distribution. This technique comprehensively describes the supramolecular interaction mechanism underlying the enhanced solubility of mangostin derivatives.