Abstract:

Chiral analysis has been an important research field in modern separation science because the enantiomers of a racemic compound often show different or even opposite bioactivities. A variety of analytical techniques have been adopted for chiral analysis over the past few decades. In comparison with conventional chromatographic methods (e. g., high-performance liquid chromatography (HPLC), gas chromatography (GC)), capillary electrophoresis (CE) has multiple advantages such as high separation efficiency, low cost, and diverse separation modes, which have made it one of the most promising analytical techniques for enantioseparation in recent years. The simplest process for CE chiral separation is the addition of a chiral selector (e. g., cyclodextrins and their derivatives, polysaccharides, antibiotics, proteins, crown ethers, chiral exchangers, chiral ionic liquids) in a running buffer to create a chiral separation environment. However, with the ever-increasing number of chiral products in the modern industrial society, satisfactory enantioseparation cannot always be achieved with conventional CE methods. Hence, scientists are endeavoring to improve CE chiral methods. The availability of various fundamental operational modes such as capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC), ligand-exchange capillary electrophoresis (LECE), non-aqueous capillary electrophoresis (NACE), and capillary electrochromatography (CEC) has enabled researchers to realize flexible design of high-performance CE chiral separation systems by altering the CE operations, especially by the modification of various advanced materials. For example, ionic liquids (ILs) are a group of organic salts whose melting points are below 100℃, or more often, close to room temperature. ILs have been demonstrated to be effective modifiers in chiral CE because of their unique physical and chemical properties such as high conductivity, exceptional chemical and thermal stabilities, as well as excellent solubility in both organic and inorganic solvents. Besides, it is feasible to design and synthesize various task-specific ILs by altering their anion-cation combinations. ILs have been employed for CE enantioseparation through various modes such as achiral IL-modified conventional enantioseparation systems, chiral IL synergistic separation systems, chiral IL LECE systems, and IL-based MEKC, or by the development of novel IL chiral selectors. Nanoparticles are another class of materials that have received considerable interest for use in chiral CE. Nanoparticles have many advantages such as unique size effect, good chemical stability, significant mechanical strength, as well as ease of modification. Several studies have demonstrated that the combination of chiral selectors with nanomaterials such as gold nanoparticles, Fe₃O₄ magnetic nanoparticles, carbon nanotubes, and mesoporous silica nanomaterials is a promising approach to establish an EKC system or a CEC system. In this review, we summarize the current state-of-the-art of novel CE chiral separation systems, including enantioseparation systems based on achiral or chiral ILs, nanomaterials, metal-organic frameworks (MOFs), and deep eutectic solvents, as well as chiral plug-plug partial filling CE. Another important topic of research in chiral CE is the exploration of enantiorecognition mechanisms. Modern mechanistic studies focus on the applications of advanced analytical techniques such as nuclear magnetic resonance (NMR) or molecular simulations with computer technology, instead of the conventional chromatography- or CE-based thermodynamic methods. For example, nuclear Overhauser effect spectroscopy (NOESY) and rotating-frame Overhauser enhancement spectroscopy (ROESY) have attracted attention because they provide critical information about the spatial proximity of the functional groups of chiral selectors and enantiomers. Molecular simulations have also become popular because of their powerful ability to evaluate the selector-selectand interactions, in addition to enabling visualization of the complex structures. The main objective of this paper is to provide a comprehensive review of state-of-the art of CE techniques in the field of chiral analysis, especially during the period 2015-2019. Existing problems with these techniques and future perspectives are also presented.

Key words: capillary electrophoresis (CE), chiral separation, ionic liquid, nano material, metal organic framework (MOF), deep eutectic solvent, mechanism, review