Molecular encapsulation of emodin with various β-cyclodextrin derivatives: A computational study

Abstract Emodin (ED), one prominent variant of naturally occurring anthraquinones traditionally used in Chinese medicine, exhibits a wide spectrum of pharmacological properties. However, the poor aqueous solubility of ED limits its significant usage in practical applications. β-cyclodextrin (βCD) and its derivatives have been extensively utilized to enhance the water solubility and stability of lipophilic guest molecules by acting as a molecular shield through host-guest encapsulation. In this work, the structural dynamics details of inclusion complexation of ED with βCD and its two derivatives: 2-hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD), were studied using all-atom molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM/GBSA)-based binding free energy (ΔGbind) calculations. The 500-ns MD simulations revealed that ED is able to form inclusion complexes with βCDs in two possible orientations: resorcinol ring insertion (R-form) and m-cresol ring insertion (C-form) mainly driven by van der Waals interaction. The ED/SBEβCD inclusion complex showed the highest number of atom contacts and the lowest solvent accessibility at the hydrophobic cavity, in line with the ΔGbind results ranked in the order of ED/SBEβCD (−6.18 ± 1.15 kcal/mol) > ED/HPβCD (−3.81 ± 0.65 kcal/mol) > ED/βCD (0.11 ± 0.51 kcal/mol). All findings suggested that βCD derivatives, especially SBEβCD, could be the appropriate host for ED in the potential development of ED into pharmaceutical applications.