Uncovering the curcumin solubilization ability of selected natural deep eutectic solvents based on quaternary ammonium compounds

Abstract

The solubility of curcumin in ethanolic solutions can be increased twentyfold through the addition of natural deep eutectic solvents (NADES). Instead of only screening nine different NADES based on choline chloride, betaine, and carnitine mixed with lactic, levulinic, and pyruvic acid in terms of their solving ability, they were investigated regarding the mechanism of solvation as well. The curcumin solubility enhancement was assessed via UV/Vis measurements, while the investigation of the intermolecular effects was performed theoretically by COSMO-RS predictions of the chemical potential and experimentally via 1H and NOESY NMR measurements. The addition of the quaternary ammonium compounds to ethanol resulted in a solubility increase regardless of additional functionalities, which was not the case for the acids, where functionalities showed a significant influence. A solubility synergy in the levulinic acid NADES was reached, which could be explained through the combination of COSMO-RS and NMR experiments, yielding indications that an interplay of non-specific and directed intermolecular interactions was the responsible driving force for an efficient solubility enhancement of curcumin. Thus, the NADES based on levulinic acid achieved the best results.