Enantioselective Separation Research Articles

Chiral Metal-Organic Frameworks.

In the past two decades, metal-organic frameworks (MOFs) or porous coordination polymers (PCPs) assembled from metal ions or clusters and organic linkers via metal-ligand coordination bonds have captivated significant scientific interest on account of their high crystallinity, exceptional porosity, and tunable pore size, high modularity, and diverse functionality. The opportunity to achieve functional porous materials by design with promising properties, unattainable for solid-state materials in general, distinguishes MOFs from other classes of materials, in particular, traditional porous materials such as activated carbon, silica, and zeolites, thereby leading to complementary properties. Scientists have conducted intense research in the production of chiral MOF (CMOF) materials for specific applications including but not limited to chiral recognition, separation, and catalysis since the discovery of the first functional CMOF (i.e., d- or l-POST-1). At present, CMOFs have become interdisciplinary between chirality chemistry, coordination chemistry, and material chemistry, which involve in many subjects including chemistry, physics, optics, medicine, pharmacology, biology, crystal engineering, environmental science, etc. In this review, we will systematically summarize the recent progress of CMOFs regarding design strategies, synthetic approaches, and cutting-edge applications. In particular, we will highlight the successful implementation of CMOFs in asymmetric catalysis, enantioselective separation, enantioselective recognition, and sensing. We envision that this review will provide readers a good understanding of CMOF chemistry and, more importantly, facilitate research endeavors for the rational design of multifunctional CMOFs and their industrial implementation.

Homochiral Metal-Organic Framework Based Mixed Matrix Membrane for Chiral Resolution.

Efficient separation of enantiomers is critical in the chemical, pharmaceutical, and food industries. However, conventional separation methods, such as chromatography, crystallization, and enzymatic kinetic resolution, require high energy costs and specific reaction conditions for the efficient purification of one enantiomer. In contrast, membrane-based processes are continuous processes performed with less energy than conventional separation processes. Enantioselective polymer membranes have been developed for the chiral resolution of pharmaceuticals; however, it is difficult to generate sufficient enantiomeric excess (ee) with polymer membranes. In this work, a homochiral filler of L-His-ZIF-8 was synthesized by the ligand substitution method and mixed with polyamide(imide) (i.e., Torlon®) to fabricate an enantioselective mixed-matrix membrane (MMM). The enantio-selective separation of R-1-phenylethanol over S-1-phenylethanol was demonstrated with a 25 wt% loaded L-His-ZIF-8/Torlon® MMM in an organic solvent nanofiltration (OSN) mode.

Chiral stationary phases and applications in gas chromatography.

Chiral compounds are ubiquitous in nature and play a pivotal role in biochemical processes, in chiroptical materials and applications, and as chiral drugs. The analysis and determination of the enantiomeric ratio (er) of chiral compounds is of enormous scientific, industrial, and economic importance. Chiral separation techniques and methods have become indispensable tools to separate chiral compounds into their enantiomers on an analytical as well on a preparative level to obtain enantiopure compounds. Chiral gas chromatography and high-performance liquid chromatography have paved the way and fostered several research areas, that is, asymmetric synthesis and catalysis in organic, medicinal, pharmaceutical, and supramolecular chemistry. The development of highly enantioselective chiral stationary phases was essential. In particular, the elucidation and understanding of the underlying enantioselective supramolecular separation mechanisms led to the design of new chiral stationary phases. This review article focuses on the development of chiral stationary phases for gas chromatography. The fundamental mechanisms of the recognition and separation of enantiomers and the selectors and chiral stationary phases used in chiral gas chromatography are presented. An overview over syntheses and applications of these chiral stationary phases is presented as a practical guidance for enantioselective separation of chiral compound classes and substances by gas chromatography.

Enantioselective Separation of Amino Acids Using Chiral Polystyrene Microspheres Synthesized by a Post-Polymer Modification Approach.

The enantioselective separation of a racemic mixture of amino acids was achieved by chiral amino acid-modified polystyrene (PS) that was developed by a post-polymer modification approach. Styrene was polymerized using the reversible addition-fragmentation chain-transfer (RAFT) polymerization technique and further post-polymer modification was applied by Friedel-Crafts acylation reaction with chiral N-phthaloyl-l-leucine acid chloride to obtain the protected PS-l-Leu. The chiral PS (protected PS-l-Leu) was assembled into microspheres using a surfactant and was used for carrying out the enantioselective separation of amino acid racemic mixtures by enantioselective adsorption followed by a simple filtration process. Compared to as-precipitated chiral PS (protected PS-l-Leu) powder, the protected PS-l-Leu microspheres exhibited a better enantioselective separation efficiency (ee %). Furthermore, the protected PS-l-Leu was deprotected to obtain the amine-functionalized deprotected PS-l-Leu chiral PS, which was also assembled into microspheres and used for carrying out enantioselective separation. Deprotected PS-l-Leu-functionalized chiral PS microspheres could achieve up to 81.6 ee % for the enantioselective separation of a racemic mixture of leucine. This is one of the first reports of the synthesis of amino acid-modified chiral PS microspheres and their application to the simple filtration-based enantioselective separation of native amino acids from their racemic mixtures.

Electrospinning of polymer nanofibers based on chiral polymeric nanoparticles

AbstractChiral polymeric nanoparticles (NPs) have emerged as a new and exciting field of research and in the last years due to their possible use for many applications in chiral chemistry however the efficiency of separating enantiomerically pure compounds has been always challenging. In this article, we focus on electrospun nanofibers formed by chiral functional NPs based on leucine or phenylalanine amino acids with polysulfone (PSF). Combining chiral functional NPs with PSF in electrospinning method provides us to get intertwined electrospun membranes with chiral property and used them for separation of racemic mixtures. We have also studied chiral functional conventional membranes formed by PSF and NPs. The NPs were prepared by miniemulsion polymerization and were characterized by DLS, SEM, MS, and NMR and display spherical structure with a narrow size distribution in the range of 200 to 250 nm. The characteristics of the membranes in terms of their morphology were analyzed. The permselective properties of the all membranes in the separation of racemic mixture were studied using aqueous solutions of leucine. Time‐resolved circular dichroism and chiral column high‐performance liquid chromatography (HPLC) were used to provide evidence for enantioselective separation. Our results show the membrane which is based on PSF and leucine NPs and formed by conventional method gives the best results for enantioselective separation by showing 18% enantiomeric excess (EE).

Enantioselective high-performance liquid chromatographic separation of fluorinated ß- phenylalanine derivatives utilizing Cinchona alkaloid-based ion-exchanger chiral stationary phases: Enantioselective separation of fluorinated ß-phenylalanine derivatives

The enantioselective separation of newly synthesized fluorine-substituted β-phenylalanines has been performed utilizing Cinchona alkaloid-based ion-exchanger chiral stationary phases. Experiments were designed to study the effect of eluent composition, counterion content, and temperature on the chromatographic properties in a systematic manner. Mobile phase systems containing methanol or mixtures of methanol and acetonitrile together with acid and base additives ensured highly efficient enantioseparations. Zwitterionic phases [Chiralpak ZWIX (+) and ZWIX(–)] were found to provide superior performance compared to that by the anion-exchangers (Chiralpak QN-AX and QD-AX). A detailed thermodynamic characterization was also performed by employing van't Hoff analysis. Using typical liquid chromatographic experimental conditions, no marked effect of the flow rate could be observed on the calculated thermodynamic parameters. In contrast, a clear tendency has been revealed about the effect of the eluent composition on the thermodynamics for the zwitterionic phases.

Sub/supercritical Fluid Chromatography for Chiral Compounds Analysis

Chirality is an essential feature of nature as it is common for many biologically active compounds. The different biological effects of individual enantiomers in a chiral environment are generally known. Therefore, there is a need for fast, efficient, and robust methods for their separation, quantification, and purification, too. The easiest way is to use chromatographic methods utilizing chiral stationary phases. Sub/supercritical fluid chromatography has become popular in the field of enantioselective separations in various scopes and, in some cases, has become a method of the first choice.
 Therefore, this review article covers actual trends and possibilities of sub/supercritical fluid chromatography in enantioseparations. Ways to influence enantioselectivity of the separation system by column coupling, screening approaches, and processes of methodical development for fast and efficient analyses are discussed.
 Sub/supercritical fluid chromatography under suitable experimental conditions provides fast and highly efficient separation of chiral compounds.

Inversion of Supramolecular Chirality by In Situ Hydrolyzation of Achiral Diethylene Glycol Motifs.

Chiral inversion of supramolecular assemblies is of great research interest due to its broad practical applications. However, chiral structure transition induced by in situ regulation of building molecules has remained a challenge. Herein, left-handed fibrous assemblies were constructed by C2-symmetic l-phenylalanine coupled with diethylene glycol (LPFEG) molecules. In situ hydrolyzing terminal diethylene glycol motifs in LPFEG successfully inverted the chirality of the nanofibers from left- to right-handedness. The transition of right-handed fibers into left-handed fibers could also be achieved via hydrolyzing DPFEG molecules. Circular dichroism (CD) spectroscopy, 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy revealed that the back-folded achiral diethylene glycol played a vital role in L/DPFEG molecular arrangements and removing terminal diethylene glycol could induce the opposite rotation of molecular assemblies. Thanks to this merit, the enantioselective separation of racemic phenylalanine was obtained and the enantiomeric excess (ee) values could achieve around ±20% after separation. This study not only provides a new strategy to regulate the chiral structure via dynamic modulation of terminal substituents but also presents a promising application in the field of enantioselective separation.

Production of Organizational Chiral Structures by Design.

Organizational chirality on surfaces has been of interest in chemistry and materials science due to its scientific importance as well as its potential applications. Current methods for producing organizational chiral structures on surfaces are primarily based upon the self-assembly of molecules. While powerful, the chiral structures are restricted to those dictated by surface reaction thermodynamics. This work introduces a method to create organizational chirality by design with nanometer precision. Using atomic force microscopy-based nanolithography, in conjunction with chosen surface chemistry, various chiral structures are produced with nanometer precision, from simple spirals and arrays of nanofeatures to complex and hierarchical chiral structures. The size, geometry, and organizational chirality is achieved in deterministic fashion, with high fidelity to the designs. The concept and methodology reported here provide researchers a new and generic means to carry out organizational chiral chemistry, with the intrinsic advantages of chiral structures by design. The results open new and promising applications including enantioselective catalysis, separation, and crystallization, as well as optical devices requiring specific polarized radiation and fabrication and recognition of chiral nanomaterials.

Hydrogen-Bonded, Hierarchically Structured Single-Component Chiral Poly(ionic liquid) Porous Membranes: Facile Fabrication and Application in Enantioselective Separation

Hydrogen-Bonded, Hierarchically Structured Single-Component Chiral Poly(ionic liquid) Porous Membranes: Facile Fabrication and Application in Enantioselective Separation

A biomimetic metal–organic framework with cuboid inner cavities for enantioselective separation

A biomimetic metal–organic framework with cuboid inner cavities and multiple recognition sites was constructed from a phenylalanine-derived ligand. It can enantioselectively separate various racemic alcohols, diols and epoxides with ee up to 99.5%.

Self-assembled monolayer protection of chiral-imprinted mesoporous platinum electrodes for highly enantioselective synthesis.

In modern chemistry, chiral (electro)catalysis is a powerful strategy to produce enantiomerically pure compounds (EPC). However, it still struggles with uncontrollable stereochemistry due to side reactions, eventually producing a racemic mixture. To overcome this important challenge, a well-controlled design of chiral catalyst materials is mandatory to produce enantiomers with acceptable purity. In this context, we propose the synergetic combination of two strategies, namely the elaboration of mesoporous Pt films, imprinted with chiral recognition sites, together with the spatially controlled formation of a self-assembled monolayer. Chiral imprinted metals have been previously suggested as electrode materials for enantioselective recognition, separation and synthesis. However, the outermost surface of such electrodes is lacking chiral information and thus leads to unspecific reactions. Functionalising selectively this part of the electrode with a monolayer of organosulfur ligands allows an almost total suppression of undesired side reactions and thus leads to a boost of enantiomeric excess to values of over 90% when using these surfaces in the frame of enantioselective electrosynthesis. In addition, this strategy also decreases the total reaction time by one order of magnitude. The study therefore opens up promising perspectives for the development of heterogeneous enantioselective electrocatalysis strategies.

Sieving nanometer enantiomers using bound states in the continuum from the metasurface.

Enantioseparation of chiral molecules is an important aspect of life sciences, chemical syntheses, and physics. Yet, the prevailing chemical techniques are not effective. Recently, a few types of plasmonic apertures have been theoretically proposed to distinguish between chiral molecules that vary based on their handedness under circularly polarized illumination. Both analytic calculations and numerical simulation demonstrated that enantioselective optical sieving could be obtained at the nanoscale using a large chiral optical force based on plasmonic resonance enhanced near-field chiral gradients in the aperture. Nevertheless, scaling this scheme to chiral entities of a few nanometer size (i.e., proteins and DNA) faces formidable challenges owing to the fabrication limit of a deeply sub-nanometer aperture and the intense power levels needed for nanoscale trapping. In contrast, by extending the Friedrich–Wintgen theory of the bound states in the continuum (BIC) to photonics, one may explore another mechanism to obtain enantioselective separation of chiral nanoparticles using all-dielectric nanostructures. Here, we present a metasurface composed of an array of silicon (Si) nanodisks embedded with off-set holes, which supports a sharp high-quality (Q) magnetic dipolar (MD) resonance originating from a distortion of symmetry-protected BIC, so called quasi-BIC. We, for the very first time, show that such a quasi-BIC MD resonance can markedly improve the chiral lateral force on the paired enantiomers with linearly polarized illumination. This quasi-BIC MD resonance can enhance the chirality density gradient with alternating sign at each octant around the Si nanodisk, while exhibiting a small gradient for the electromagnetic (EM) density. This offers a chiral lateral force that is 1 order larger in magnitude compared to the non-chiral lateral forces on sub-2 nm chiral objects with a chirality parameter of ±0.01. Moreover, the quasi-BIC MD resonance can excite four pairs of diverse optical potential wells (−13kBT) that are distributed uniformly along the outer edge of the resonator, enabling a simultaneous separation of four paired enantiomers. Our proposed dielectric metasurface may move forward the techniques of enantioseparation and enantiopurification, taking a novel perspective to advanced all-optical enantiopure synthesis.

Metal-Organic Framework-Based Enzyme Composites as Chiral Stationary Phase for High-Efficiency Capillary Electrochromatographic Enantioselective Separation

Metal-Organic Framework-Based Enzyme Composites as Chiral Stationary Phase for High-Efficiency Capillary Electrochromatographic Enantioselective Separation

Enzyme Metal-Organic Framework Composites as Chiral Stationary Phase for High-Efficiency Capillary Electrochromatographic Enantioselective Separation

Enzyme Metal-Organic Framework Composites as Chiral Stationary Phase for High-Efficiency Capillary Electrochromatographic Enantioselective Separation

A Polymer-based Monolithic Capillary Column with Polymyxin-B Chiral Selector for the Enantioselective Nano-High Performance Liquid Chromatographic Pharmaceutical Analysis

Herein, we report the first use of Polymyxin-B antibiotic as a enantio-selector in polymer monolithic capillary. The capillaries were functionalised, characterized and tested for the enantioselective nano-HPLC separation of 50 racemic pharmaceutical drugs. They have been easily prepared by immobilizing Polymyxin-B over the organic polymer for 48 h (P1) or encapsulating Polymyxin-B within the organic polymer (P2) and tested for the enantioselective resolution of racemic drugs. Acceptable resolution was achieved for 21 drugs using RP-HPLC conditions on both (P1) and (P2) capillary columns, while no separation was observed under NP-HPLC conditions. Polymyxin-B is commercially available, easily solubilized and stable in both acidic and neutral media. The developed Polymyxin-B-based polymer monolithic capillaries provide a promising expansion of platform in enantioselective HPLC separations.

Enantioselective separation, analysis and stereoselective dissipation of the chiral pesticide cloquintocet-mexyl using a modified QuEChERS method by high-performance liquid chromatography tandem mass spectrometry

An efficient and novel enantioseparation method was successfully developed and validated to quantify the enantiomers of cloquintocet-mexyl in soil, millet, enoki mushroom, oilseed rape, and watermelon using a modified QuEChERS technique combined with HPLC-MS/MS. This method showed reliable performances for determining both enantiomers of cloquintocet-mexyl in all five matrices. The limits of detection and limits of quantification were in the range of 0.06–0.15 μg kg−1 and 0.2–0.5 μg kg−1, respectively. Good linearities were obtained with correlation coefficients ≥0.9954. The mean recoveries were between 84.1% and 111.5%, with relative standard deviations ranging from 1.2% to 9.8% at three spiked levels. Additionally, the study of stereoselective dissipation of cloquintocet-mexyl in soil indicated that (R)-cloquintocet-mexyl was preferentially degraded. This work is the first to describe a chiral analytical method and enantioselective behavior of cloquintocet-mexyl and provide basic data for the risk evaluation of cloquintocet-mexyl in food and environmental safety.

Enantioselective Separations Based on High-performance Liquid Chromatography

Enantioselective Separations Based on High-performance Liquid Chromatography

Stimuli-Responsive Chiroptical Switching.

"Chirality" governs many fundamental properties in chemistry and biochemistry. While early investigations on stereochemistry are primarily dedicated to static chirality, there is an increasing interest in the field of dynamic chirality (chiral switches). These chiral switches are essential in controlling the directionality in molecular motors. Dynamic chiralities are equally crucial in switchable stereoselectivity, switchable asymmetric catalysis and enantioselective separation. Herein, we limit our discussion to recent advances on stimuli-induced chiroptical switching of axial, helical, and planar chirality in response to external stimuli. We also discuss a few examples of applications of the switchable chirality.

Design of MOFs with Absolute Structures: A Case Study

AbstractMetal‐organic frameworks (MOFs) with absolute structures are of particular interest as the asymmetry of their crystal structures enables wide applications from asymmetric catalysis to enantioselective separation. Previous reports on the synthetic strategies toward MOFs with absolute structures always required the use of chiral precursors or chiral templates, however, it is not always easy to obtain enantiopure starting materials. Here in, we report a new non‐centrosymmetric MOF, MOF‐829, synthesized from aluminium salt and achiral organic linker. Further comparisons are made between MOF‐829 and a reported Al‐based chiral MOF (MOF‐520) that is composed of the same metal ion and linker, and similarly synthesized without using chiral compounds. The configurations of the building units, the absolute structures of both MOFs, and their topologies were investigated in detail. We found that (i) topology is one of the determining factors in the formation of non‐centrosymmetric MOFs; (ii) the formation of chiral MOFs further requires the directionality of chiral linkers but more importantly chiral secondary building units (SBUs), which can be realized by fine tuning of the synthetic conditions. We envision that both synthetic exploration of chiral SBUs and the design of non‐centrosymmetric topologies will open a new direction in the design of MOFs with absolute structures.