A quantum chemical study of encapsulation and stabilization of gallic acid in β-cyclodextrin as a drug delivery system

Abstract

This research paper describes the study of the inclusion complex formation of a 1:1 stoichiometry ratio of host–guest inclusion complex (X-β-CD) between gallic acid (GA), which is reported to have anti-cancer effects, and β-cyclodextrin (β-CD). The use of β-CD for the encapsulation of bioactive compounds can protect the drugs against conjugation and metabolic inactivation and improve the aqueous solubility for increasing their capacity to functionalize the products. The objective of this study is to give insight on the mechanism of complexation and the capability of β-CD to encapsulate GA compound (X) in gas and solution phases. We examine and compare the performances of different quantum mechanical methods, namely HF/6-31G* and density functional theory (DFT; B97D3/6-31G* functional including dispersion correction), to study the importance of the contribution of the dispersion forces and the hydrogen bonding in the mechanism of interaction. The stability of the optimized geometries of the complex was evaluated with the supermolecule method. Two modes of complexation are taken into consideration. Moreover, the inclusion complex can be confirmed using the frontier molecular orbital (FMO) theory, the global indices of reactivity, the electronic populations condensed natural bond orbital (NBO) analysis, and the molecular docking, which examine the quality and the nature of the hydrophobic interactions during the complexation process.