Gas chromatographic separation of enantiomers on novel chiral stationary phases

https://doi.org/10.1016/j.trac.2020.115808Get rights and content

Highlights

  • Advances on various novel CSPs for GC enantioseparation were reviewed during 2010–2019.

  • The synthesis strategies to construct chiral porous materials were covered.

  • The resolution of different types of enantiomers on the novel CSPs was discussed.

  • The chiral recognition mechanisms between novel CSPs and chiral analytes were explained.

  • We summarize the advantages and disadvantages of novel CSPs used in GC.

Abstract

Chiral capillary gas chromatography has been widely applied to separate volatile and thermally stable enantiomers due to its advantages of simplicity, high efficiency, fast analysis, good sensitivity, and absence of liquid mobile phases. In the first part of this article, recent research progress (from 2010 to the present) concerning newly developed chiral stationary phases based on cyclofructan derivatives and chiral porous materials, including metal-organic frameworks, covalent organic frameworks, inorganic mesoporous silicas, and molecular cages for use in gas chromatography, and the synthetic strategies for obtaining chiral porous materials, was reviewed. Finally, we discussed in detail the separation performances and chiral recognition mechanisms of novel chiral recognition materials coated on capillary columns towards various types of enantiomers, namely (1) amino acid derivatives; (2) alcohols, amines, and amino alcohols; (3) organic acids; (4) aldehydes and ketones; (5) ethers and epoxides, and (6) esters and other enantiomers.

Introduction

Chirality remains an important topic in many fields, such as life sciences, the pharmaceutical industry, the chemical industry, agriculture, food additives, and clinical analysis, to name but a few [1]. The enantiomers of chiral compounds display the same physical and chemical properties in an achiral environment. However, in a chiral environment, as in living systems, the two enantiomers of a chiral molecule, especially chiral drugs, may exhibit very different biological, pharmacological, toxicological, and/or pharmacokinetic profiles. Generally, only one of the enantiomers (eutomer) can produce the desired therapeutic activity, while the other (distomer) may be inactive, elicit an antagonistic response, or even show toxic effects [2]. For instance, the d-isomer of chloramphenicol has a bactericidal effect, while the l-isomer is inactive. Barbiturate is commonly used as a hypnotic analgesic drug. Its S-isomer has the effect of inhibiting nerve activity, while its R-isomer has excitation action. For this reason, the drug regulatory agencies in various countries (e.g., the U.S. Food and Drug Administration, the China Food and Drug Administration) have issued certain guidelines for the marketing of racemic compounds. In the pharmaceutical industry, regulations clearly define that a comprehensive pharmacokinetic and toxicological study must be performed for each enantiomer of a newly developed chiral drug.

In light of the importance of chirality, several methods are available for obtaining enantiomerically pure compounds, including the resolution of racemates, isolation from natural sources, fermentation, and asymmetric catalysis, with resolution and asymmetric catalysis still being the most widely used [3]. In recent years, chromatographic techniques, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC), thin-layer chromatography (TLC), high-speed counter-current chromatography (HSCCC), and capillary electrochromatography (CEC) based on chiral stationary phases (CSPs), have become some of the most attractive ways for the separation of racemic compounds [1,4]. The choice of separation technique is often governed by the properties of the chiral molecule. Among them, chiral GC is well recognized as a powerful, simple, convenient, fast, and efficient method for the separation or precise determination of enantiomeric compositions of volatile and thermally stable optically active components, and has been applied for many different analytes, such as essential oils, flavours, fragrances, intermediates, auxiliaries, metabolites, precursors, pharmaceuticals, pesticides, fungicides, herbicides, pheromones and so on [5,6]. In addition, established ancillary techniques, including multidimensional GC (e.g., GC × GC), solid-phase microextraction, and interfacing and coupling methods (GC-MS), have made chiral GC an alluring technique for the analysis of enantiomers in complex samples [6].

The first GC resolution of enantiomers on a capillary column, employing derivatives of amino acids as the CSP, was performed in 1966 by Gil-Av and co-workers [7]. To date, various classical types of CSPs have been used for GC enantioseparations, which can be mainly classified into three categories: chiral amino acid derivatives, metal coordination complexes, and cyclodextrin derivatives. Besides, some other chiral GC stationary phases, such as chiral ionic liquids, polysaccharides, and cyclopeptides, have also been applied for the separation of enantiomers. However, the commercially available CSPs based on cyclodextrin derivatives are by far the most widely used for chiral separation in GC. Moreover, the resolution ability of a single cyclodextrin derivative-based capillary column is limited, and commercial capillary columns are relatively expensive [2]. Therefore, it is essential to develop novel CSPs with higher enantioselectivities and broader resolving ability for GC enantioseparations. In the past decade, researchers have directed a great deal of effort towards exploiting new chiral recognition materials, such as cyclofructan derivatives and chiral porous materials (e.g., metal-organic frameworks, covalent organic frameworks, porous organic frameworks, porous organic cages, metal-organic cages, and inorganic mesoporous materials) as GC CSPs for resolving chiral compounds.

Recently, some review articles covering newly developed CSPs used in GC were published [2,4,8]. In the past few years, reports have steadily appeared concerning new chiral functional materials, such as chiral porous materials with potential as novel CSPs with distinctive resolution efficiency for GC enantioseparations. This review deals mainly with recent advances in novel GC CSPs based on cyclofructan derivatives and chiral porous materials (2010–2019), and is focused on the following aspects: (a) introducing the design and construction strategies for some chiral functional materials; (b) comprehensively summarizing the resolution efficiencies of these novel GC CSPs according to their categories based on the building blocks or pore sizes; (c) discussing in detail the advantages and disadvantages of cyclofructan derivatives and chiral porous materials as CSPs in GC; (d) summarizing the separation performances and chiral recognition mechanisms of these novel CSPs in resolving a broad range of enantiomers, namely (1) amino acid derivatives; (2) alcohols, amines, and amino alcohols; (3) organic acids; (4) aldehydes and ketones; (5) ethers and epoxides; (6) esters and (7) other enantiomers.

Section snippets

Cyclofructan derivatives

Cyclofructans (CFs), a new class of macrocyclic oligosaccharides obtained by enzymatic conversion of inulin, were first reported by Kawamura and Uchiyama in 1989 [9]. The structure and behavior of CFs are quite different from those of well-known macrocyclic oligosaccharides such as cyclodextrins (CDs). They are composed of six to eight β-(2 → 1)-linked d-fructofuranose units, and their names are usually abbreviated as CF6, CF7, and CF8. Each fructofuranose unit contains four stereogenic centers

Amino acid derivatives

Analysis of the enantiomeric forms of amino acids and their derivatives, especially proteinogenic amino acids, is very important in food chemistry, the pharmaceutical industry, and geochronology. The first direct separation of derivatized amino acids on an N-trifluoroacetyl-l-isoleucine lauryl ester CSP by GC was described in 1966 by Gil-Av et al. [7].

Enantiomeric separations of chiral amino acid derivatives on newly developed chiral capillary GC columns are listed in Table 2. It can be seen

Conclusions

Cyclofructans and chiral porous materials are of particular interest because of the increasing demand for functional materials for chiral separations by chromatographic techniques. In this review, we have focused on recent noteworthy strategies for the construction of chiral porous materials, including metal-organic frameworks, covalent organic frameworks, inorganic mesoporous silicas, and molecular cages, newly developed CSPs based on cyclofructans and chiral porous materials, and their

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 21765025, 21964021, 21675141, 21705142 and 21365024) and the Applied Basic Research Foundation of Yunnan Province (Grant No. 2017FB013).

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