Evaluation of hexamethyldisiloxane/ethyl isobutyrate/ethanol/water solvent system for liquid-liquid chromatography

The most commonly used solvent systems in liquid-liquid chromatography (LLC), such as heptane/ethyl acetate/methanol/water (ARIZONA) or its variant hexane/ethyl acetate/methanol/water (HEMWat), contain toxic petroleum-based solvents that raise serious risks to human health and environment. Therefore, there is a great need to find alternative, greener, and safer solvent systems for LLC applications. This work comprehensively evaluated an alternative biphasic solvent system, hexamethyldisiloxane/ethyl isobutyrate/ethanol/water (HMDSO/EIB/ethanol/water), by considering its thermodynamic properties, physical properties, and suitability for LLC applications. Compared with the HEMWat system, the HMDSO/EIB/ethanol/water system had a similar phase density difference, higher phase viscosity, and longer settling times. The distribution constants (K_i) of 12 test compounds with different polarities and chemical structural features representative of various classes of natural products were assessed in 16 compositions of the HMDSO/EIB/ethanol/water and HEMWat systems. System compositions with similar K_i values were identified for the two solvent systems. Since COSMO-RS provided good predictions of the K_i of the test compounds, its use can significantly reduce the process of finding an HMDSO/EIB/ethanol/water system composition for separating other components, using only their molecular structures as input. The results of countercurrent chromatography and centrifugal partition chromatography experiments showed comparable separation behaviors of selected compounds in both solvent systems, demonstrating that the HMDSO/EIB/ethanol/water system could be a viable, safer replacement for HEMWat and ARIZONA solvent systems in LLC.