Investigation of the enantioselectivity of tetramethylammonium‐lactobionate chiral ionic liquid based dual selector systems toward basic drugs in capillary electrophoresis

Abstract

Recently, chiral ionic liquids (CILs) have received increasing interest in chiral separation by CE. Nevertheless, the lack of deep perception of the specific mechanism about CILs in CE for enantioseparation still perplexes a legion of researchers, despite the strenuous efforts. In this paper, a lactobionic acid based ionic liquid, tetramethylammonium‐lactobionate (TMA‐LA) was applied for the first time in CE to establish dual selector system with clindamycin phosphate (CP) for enantiomeric separation. Compared to single CP system or single TMA‐LA system significantly improved separations of seven tested rameric drugs (propranolol, nefopam, citalopram, chlorphenamine, metoprolol, bisoprolol, and esmolol) were observed in the dual selector systems. Several crucial parameters such as type and proportion of organic modifier, buffer composition and pH, and concentration of TMA‐LA/CP were systematically investigated to achieve satisfied enantioseparation. Meanwhile, molecular modeling was applied to demonstrate the chiral recognition mechanism of the TMA‐LA/CP dual‐selector separation system using the molecular docking software Autodock, which well supported the experimental results. The existence of TMA‐LA/CP complex may give rise to a higher discriminatory ability against the enantiomers, indicating the reason of improved separation in TMA‐LA/CP system. All the influence factors evaluated by means of Statistical Product and Service Solutions (SPSS) to research the influences on the chiral separation system.

From capillaries to microchips, green electrophoretic features for enantiomeric separations: A decade review (2013–2022)

“…CILs have attracted much attention for several applications, such as chiral solvents, asymmetric synthesis, a, recently, chiral CE for the separation of enantiomers. CILs are commonly used as chiral selectors, chiral ligands, and in the BGE, as listed in Table 2 [114–154]. ACILs such as the ones based on alkylpyridinium, alkyl imidazolium, and tetraalkylammonium are also used in CE separation with combinations of β‐CD derivatives and furnish a favored interaction with enantiomers.…”

“…The most typical ILs and CILs cations used for enantiomeric separations in CE are commonly used in combination with CDs and are based on tetrabutylammonium, tetramethylammonium, methylimidazolium, and their derivatives (Figure 3B) [117, 120, 124, 128–130, 132, 138, 139, 142, 143, 146, 149, 151, 153]. These nitrogen‐based cations deeply influence the greenness of ILs, and most of them display toxic behavior due to their hydrophobicity.…”

Advances of capillary electrophoresis enantioseparations in pharmaceutical analysis (2017–2020)

“…The chiral recognition mechanisms by CILs have been reviewed [89]. Lactobionic acid-based CILs were evaluated as novel selectors in CE for the enantioseparation of basic drugs [90][91][92]. The enantiomer migration order could be correlated to the formation of hydrogen bonds established between the analyte enantiomers and the CILs in molecular modeling studies.…”

Chiral Separations by Capillary Electrophoresis and related Techniques with Different Chiral Selectors: A Review

“…The obvious superiority of chiral ILs to equal ILs is due to their ability to gain an extra enantiomeric recognition, so separating ability, while maintaining a "system modification" capability [227]. Based on their potential, which is related to ability for recognitions on chiral separations, scientific interest in CILs has warmly increased [228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243][244][245][246]. In chiral separations studies, it is observed that the performance of the systems created by modifying ionic liquids with SPs enhances the enantiorecognition ability compared to conventional type stationary phases alone [247].…”