Solvation mechanisms of bioactive curcuminoid drug candidates in natural deep eutectic solvents: A molecular-level study

Curcuminoid compounds (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) present in turmeric exhibit strong anti-inflammatory and antioxidant properties. Consequently, the efficient extraction of these valuable bioactive molecules from turmeric is of considerable importance. In response to the increasing demand for green and sustainable solvents in the pharmaceutical industry, this study systematically investigates the interactions between curcuminoid antioxidants and deep eutectic solvent (DES) systems based on terpenes and fatty acids. The COSMO-RS model was first employed to predict the solubility of the antioxidants at infinite dilution. Subsequently, molecular dynamics (MD) simulations were performed to elucidate the structural and dynamical behavior of the curcuminoid–DES systems. The MD results indicate that hydrophobic eutectic solvents composed of monoterpenes and caprylic acid form stable hydrogen-bonding networks and favorable van der Waals interactions with the curcuminoids, thereby enhancing solvation. Radial distribution function (RDF) analyses reveal strong intermolecular correlations between the hydroxyl and carbonyl groups of the curcuminoids and the carboxylic oxygen atoms of the DES components. In addition, diffusion coefficient and mean square displacement analyses confirm the mobility of the antioxidant species within the solvent matrix, supporting efficient molecular dispersion. Overall, these findings demonstrate that hydrophobic natural deep eutectic solvents exhibit favorable solvation dynamics and structural compatibility with curcuminoid antioxidants, highlighting their potential as efficient and sustainable media for turmeric extraction.