Modeling and experimental evaluation of biphasic enantioselective liquid-liquid extraction of racemic equol

The enantiomeric separation of chiral drugs remains a challenge for the pharmaceutical industry as the pharmacological activities of different isomers may differ, which can cause incalculable secondary effects in the diseases treatment. The highlight of this study is to develop a biphasic recognition chiral extraction (BRCE) platform utilized tartaric acids (TAs) and chiral ionic liquids (CILs) as the synergistic hydrophilic and hydrophobic chiral additives to enhance the extraction performance. The BRCE systems such as organic solvents, type and concentration of chiral additives, initial concentration of equol, extraction temperature, aqueous pH has been systematically investigated. The superior enantioselectivity (α) value of 2.55 was achieved at the initial equol concentration of 2 mmol/L, the aqueous pH of 7.5, extraction temperature of 25 °C, and the ratio of 1:1 of [Bmim][L-Trp] to [D-di-isopropyl-tartrate], which is remarkably better than other previous extraction systems. In particular, the density functional theory (DFT) method was used to explain the extraction performance from the perspective of interaction energy. Overall, this work provides guidance on screening cooperative chiral additives for construction of an enhanced BRCE platform not only for separating equol enantiomers but also task-specific applications.