Molecular insights into drug–deep eutectic solvent systems for flavone extraction using MD and COSMO-RS

• Deep eutectic solvents (DESs) composed of decanoic acid and l -menthol were examined. • Flavone exhibited remarkable solubility in these DES systems. • Hydrogen bonding and van der Waals interactions governed the solvation behavior. • Application of external fields modulated flavone – DES interactions. • COSMO-RS and molecular simulations elucidated the solvation mechanisms. • The studied DESs show strong potential for sustainable flavonoid extraction and formulation. The pharmaceutical industry's growing interest in antioxidant compounds leads to a growing demand for innovative and efficient separation techniques. Recently, deep eutectic solvents have been at the forefront of developing novel extraction methods. In this study, fatty acid-based deep eutectic solvents were explored for their adjustable physical-chemical properties and eco-friendly nature in extraction processes. Molecular dynamics (MD) simulations were employed to investigate the interactions between antioxidant-rich dried roots of Scutellaria and DESs. Intermolecular interactions were investigated through spatial distribution functions (SDFs), combined distribution functions (CDFs) derived from radial distribution functions (RDFs) and angular distribution functions (ADFs), non-bonded interaction energy analyses, and characterization of the hydrogen-bonding network between the antioxidant molecule and the eutectic solvent components. Furthermore, the influence of an external electric field (EEF) on these interactions was examined. The results reveal that the EEF markedly alters the nature and strength of intermolecular interactions, thereby modulating the extraction efficiency.