The role of deep eutectic solvents in chiral capillary electrokinetic chromatography: A comparative study based on α-cyclodextrin chiral selector

• The first investigation of the effect of HBAs of DESs on chiral EKC. • The comparison of the performance of chiral and achiral DESs in chiral EKC. • The comparison of the performance of DESs and ILs as additives in chiral EKC. • The objective evaluation of the feasibility of DESs as additives in chiral EKC. Deep eutectic solvents (DESs) are emerging as potential candidates as additives/modifiers in chiral electrokinetic chromatography (EKC). However, the true role of DESs in the chiral separation process is far from being fully elucidated. Since most previous studies have been restricted to using choline chloride as the hydrogen-bond acceptor (HBA) in DESs, here we first evaluated the effect of five types of DESs (containing different HBAs) on the enantioseparation performance of an α-CD-based EKC system. The results demonstrate that these DESs are capable of moderately improving the enantioresolutions of several model drugs. A series of comparative experiments indicate that the improvement is mainly due to the contribution of the HBAs, rather than the selected hydrogen-bond donors (HBDs). Considering that most of these DESs are achiral, we further prepared five chiral DESs, aiming to investigate whether there is a synergistic effect between α-cyclodextrin and chiral DESs. However, these chiral DESs did not show obvious superiority compared with achiral DESs. This conclusion is different from the use of achiral or chiral ionic liquids (ILs) as additives in chiral EKC, in which chiral ILs usually exhibit significantly better enantioseparation performance than achiral ILs. Another important conclusion of this work is that there seems to be no significant difference between using DESs and their individual components, which is also different from the performance of most previously reported ILs. This conclusion indicates that the DESs may be virtually completely dissociated into their initial components (HBAs + HBDs) in the separation medium due to the destruction of their hydrogen-bond network. Therefore, a question which deserves particular attention of researchers in this field is raised here: whether it is absolutely necessary to use DESs in chiral EKC since adding HBAs and HBDs separately seems to have the same function?