Molecular Insights into β-Cyclodextrin-Based Supramolecular Deep Eutectic Solvent Formation and Its Interactions with Curcumin

This study investigates the molecular organization and interaction behavior of curcumin in a choline chloride (ChCl):glycerol (Gly):β-cyclodextrin (βCD) supramolecular deep eutectic solvent (supraDES) using classical all-atom molecular dynamics (MD) simulations. The formation of the βCD-containing supraDES and its interactions with curcumin were analyzed mainly using molecular snapshots, radial distribution functions (RDFs), hydrogen bond analysis, interaction energies, density profiles, and root-mean-square deviation (RMSD). Regarding supraDES formation, molecular structure, RDF, hydrogen bond, and interaction energy analyses revealed that the incorporation of βCD modifies the local coordination environment of the DES components. Upon curcumin addition, a correlation between curcumin and βCD was observed, indicating a preferential association between curcumin and the supramolecular host, as revealed by the analysis of classical all-atom MD simulation outputs. Future studies should combine MD simulations with experimental investigations and enhanced free-energy calculations to further elucidate the host–guest binding mechanisms and assess the potential of βCD-based supraDESs for curcumin solubilization and delivery.