Separation Of Enantiomers Research Articles

Continuous chiral separation process for high-speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation.

An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as a chiral selector in high-speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two-phase solvent system consisting of n-hexane/ethyl acetate/100mmol/L phosphate buffer solution (pH=3.0, containing 50mmol/L SBE-β-CD) (1.5:0.5:2, v/v/v). A fast and predictable scale-up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11-fold. Preparative HSCCC successfully separated 506mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high-performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale-up process and attaining continuous separation of chiral drugs.

Influence of theoretical and semi-empirical peak models on the efficiency calculation in chiral chromatography

Height equivalent to theoretical plate (H) equations, such as the van Deemter or Knox-Saleem equations, and other efficiency vs. linear velocity equations (u), provide kinetic insights into chromatographic separations phenomena and column performance. In enantioselective separations, the peak shape of the two enantiomers can differ significantly and are often asymmetric. The peak efficiency calculations heavily impact these efficiency-flow profiles, leading to erroneous estimations of eddy diffusion, longitudinal diffusion, and mass transfer terms. In this work, new asymmetric peak functions are employed for modeling enantiomer peaks based on the Haarhoff-Van der Linde function, its generalized variant (GHVL), once Generalized Asymmetric Gaussian (AGN), and Twice Generalized Gaussian (TGN). The new models (AGN, TGN, and GHVL) incorporate higher statistical moments besides the zeroth, first, and second moments to account for two-sided asymmetry (fronting or tailing). The fit results are compared with the traditional efficiency calculation methods endorsed by official pharmacopeia and numerical estimation of moments from the raw data. Enantiomeric separations of ibuprofen and dl-homophenylalanine were chosen as probe molecules. The results demonstrate that non-linear least squares fitted functions provide better estimations of peak efficiency data even in the presence of high noise. In particular, the generalized models consistently offered the best quality fits for various peak shapes in chiral separations. Conversely, the half-height Gaussian method greatly overpredicted skewed peak efficiencies. This investigation reveals that the commonly held assumptions of peak shape and numerical integration of raw data are highly insufficient for chiral chromatography. The impact of asymmetry on plate height should not be overlooked when accurate data from efficiency-flow rate curves is derived. We advocate for the broader adoption of these new generalized peak (AGN, TGN, GHVL) models because they provide robustness at various SNRs that account for right or left asymmetry while accurately representing peak geometry.

Synthesis Strategies, Preparation Methods, and Applications of Chiral Metal-Organic Frameworks.

Chiral Metal-Organic Frameworks (CMOFs) is a kind of material with great application value in recent years. Formed by the coordination of metal ions or metal clusters with organic ligands. It has ordered and adjustable pores, multi-dimensional network structure, large specific surface area and excellent adsorption properties. This material structure combines the properties of metal-organic frameworks (MOFs) with the chiral properties of chiral molecules. It has great advantages in catalysis, adsorption, separation and other fields. Therefore, it has a wide range of applications in chemistry, biology, medicine and materials science. In this paper, various synthesis strategies and preparation methods of chiral metal-organic frameworks are reviewed from different perspectives, and the advantages of each method are analyzed. In addition, the applications of chiral metal-organic framework materials in enantiomer recognition and separation, circular polarization luminescence and asymmetric catalysis are systematically summarized, and the corresponding mechanisms are discussed. Finally, the challenges and prospects of the development of chiral metal-organic frame materials are analyzed in detail.

BINOL‐based Chiral Macrocycles and Cages

Chirality, a fundamental principle in chemistry, biology, and medicine, is prevalent in nature and in organisms. Chiral molecules, such as DNA, RNA, and proteins, are crucial in biomolecular synthesis, as well as in the development of functional materials. Among these, 1,1´‐binaphthyl‐2,2´‐diol (BINOL) stands out for its stable chiral configuration, versatile functionality, and commercial availability. BINOL is widely employed in asymmetric catalysis and chiral materials. This review mainly focuses on recent research over the past five years concerning the use of BINOL derivatives for constructing chiral macrocycles and cages. Their contributions to chiral luminescence, enantiomeric separation, transmembrane transport, and asymmetric catalysis were examined.

Development of a scalable recombinant system for cyclic beta-1,2-glucans production

BackgroundCyclic β-1,2-glucans (CβG) are bacterial cyclic homopolysaccharides with interesting biotechnological applications. These ring-shaped molecules have a hydrophilic surface that confers high solubility and a hydrophobic cavity able to include poorly soluble molecules. Several studies demonstrate that CβG and many derivatives can be applied in drug solubilization and stabilization, enantiomer separation, catalysis, synthesis of nanomaterials and even as immunomodulators, suggesting these molecules have great potential for their industrial and commercial exploitation. Nowadays, there is no method to produce CβG by chemical synthesis and bacteria that synthesize them are slow-growing or even pathogenic, which makes the scaling up of the process difficult and expensive. Therefore, scalable production and purification methods are needed to afford the demand and expand the repertoire of applications of CβG.ResultsWe present the production of CβG in specially designed E. coli strains by means of the deletion of intrinsic polysaccharide biosynthetic genes and the heterologous expression of enzymes involved in CβG synthesis, transport and succinilation. These strains produce different types of CβG: unsubstituted CβG, anionic CβG and CβG of high size. Unsubstituted CβG with a degree of polymerization of 17 to 24 glucoses were produced and secreted to the culture medium by one of the strains. Through high cell density culture (HCDC) of that strain we were able to produce 4,5 g of pure unsubstituted CβG /L in culture medium within 48 h culture.ConclusionsWe have developed a new recombinant bacterial system for the synthesis of cyclic β-1,2-glucans, expanding the use of bacteria as a platform for the production of new polysaccharides with biotechnological applications. This new approach allowed us to produce CβG in E. coli with high yields and the highest volumetric productivity reported to date. We expect this new highly scalable system facilitates CβG availability for further research and the widespread use of these promising molecules across many application fields.

Sorting of enantiomers using optical chirality in uniform light field

Enantiomer sorting greatly promotes the advancement of chemistry, bioscience, and medicine while also facing significant challenges. Recently, all-optical solutions have attracted considerable interest due to their non-invasiveness. While, it should be noted that the achiral optical force is always much larger than the chiral gradient force that plays a key role in all-optical enantiomer sorting, hindering the separation of enantiomers. Previously proposed methods to boost the chiral gradient forces by plasmonic and photonic nanostructures are often accompanied by the enhancement of achiral optical forces. The sorted chiral particles are also difficult to be transferred from the complex nanostructures. Here, we propose an approach for separating enantiomers using uniform light field formed by two waves, which is capable of sorting deep sub-wavelength chiral particles. In our method, the chiral particles can be sorted within a simple planar structure while the achiral gradient force is equal to zero. Our research reveals a promising perspective on large-scale sorting for enantiomers.

Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood.

Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.

Novel Separation Processes and Their Applications

Separation processes are an integral part of any process flow sheet. Various techniques can beused to separatethe mixture depending on the raw mix. Sometimes, two or more methods must be used to get the desiredproduct. Differences in chemical and physical properties also help decide the separation technique that mustbe used. An external agent, any form of energyor matter, can act as the driving force for the separation. Someof these techniques are conventional processes like distillation, filtration, adsorption, and absorption, whichhave already been well-studied and extensively used. These days newer separation processes called novelseparation processes, such as membrane separation, gas separation, supercritical fluid extraction, use ofultrasonics, chromatographic separation, magnetic projection, and liquid- liquid extraction, among manyothers, are gaining importance in the area of research and implementation. Novel processes were firstimplemented as analytical tools in laboratories. However, they developed rapidly to become significant commercially and technically. The development in gas separation techniques has led to using Liquified Natural Gas in Air Separation Units to produce high-purity nitrogen and oxygen4. Novel separation methods also include ultrasound to enhance separation processes like extraction, demulsification, and crystallisation. Pressure-driven processes are a subset of membrane separation techniques where pressure is utilised as a driving force for separation, with asemipermeable membrane acting as a barrier. This method has various applications ranging from wastewater treatment to dairy processing. Chiral chromatography is used for enantiomeric separations by the use ofHPLC. A new magnetic separation process proposes the separation of plastics by submerging them in a paramagnetic medium and attaching a magnet. This results in moving the particles inside the medium with different trajectories, thereby separating them. This article will scrutinise and briefly describe the essential aspects and developments of novelseparation processes and their applications.

Chiral analysis of ostarine in commercially available products and doping control urine samples

Various substances classified as prohibited in sport by the World Anti-Doping Agency (WADA) comprise one or more chiral centers. One such substance is enobosarm ((2S)-3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethyl)phenyl]-2‑hydroxy-2-methylpropanamide, S-ostarine, S-22, MK-2866, GTx-024, VERU-024). Although ostarine is not an approved drug, it has been readily available via Internet-based suppliers, and to date it is unknown to what extent R-ostarine, S-ostarine, or a mixture of both is used in these products. Likewise, such information is not available with regards to urine samples that returned an adverse analytical finding in the context of sports drug testing programs and, hence, this pilot-study aimed at establishing a test method to provide first insights into the presence of R- and S-ostarine in commercially available products and in authentic doping control urine samples.Here, a chiral liquid chromatographic - mass spectrometric method, employing a teicoplanin-containing (chiral) stationary phase that allows the differentiation of R- and S-enantiomers of ostarine, is presented. Ostarine products were extracted and diluted prior to analysis, while urine samples were prepared for analysis by enzymatic hydrolysis followed by liquid-liquid extraction.Seven products declaring to contain ostarine were investigated, five of which were ordered via the Internet and two were confiscated and made available by a customs authority. Only 2 of the 5 purchased products contained ostarine. In these two products and the confiscated products, only the ostarine S-enantiomer was found. Further, five authentic doping control urine samples containing the target analyte were subjected to chiral analysis, also confirming the sole presence of the S-ostarine enantiomer.The developed approach proved suitable for the separation of ostarine enantiomers, which adds further information e.g. in the context of illicit drug production, trafficking, and doping controls, especially when additional details are desirable that might assist in determining the origin of a drug or drug residue.

Enantiomeric separation of tryptophan via novel chiral polyamide composite membrane.

The separation of chiral drugs continues to pose a significant challenge. However, in recent years, the emergence of membrane-based chiral separation has shown promising effectiveness due to its environmentally friendly, energy-efficient, and cost-effective characteristics. In this study, we prepared chiral composite membrane via interfacial polymerization (IP), utilizing β-cyclodextrin (β-CD) and piperazine (PIP) as mixed monomers in the aqueous phase. The chiral separation process was facilitated by β-CD, serving as a chiral selective agent. The resulting membrane were characterized using SEM, FT-IR, and XPS. Subsequently, the chiral separation performance of the membrane for DL-tryptophan (Trp) was investigated. Lastly, the water flux, dye rejection, and stability of the membrane were also examined. The results showed that the optimized chiral PIP0.5β-CD0.5 membrane achieved an enantiomeric excess percentage (ee%) of 43.0% for D-Trp, with a solute flux of 66.18 nmol·cm-2·h-1, and maintained a good chiral separation stability. Additionally, the membrane demonstrated positive performance in the selective separation of mixed dyes, allowing for steady operation over a long period of time. This study offers fresh insights into membrane-based chiral separations.

Optical dipolar chiral sorting forces and their manifestation in evanescent waves and nanofibers

Optical fields can exert forces of chiral nature on molecules and nanoparticles, which would prove extremely valuable in the separation of enantiomers with pharmaceutical applications, yet it is inherently complex, and the varied frameworks used in the literature further complicate the theoretical understanding. This paper unifies existing approaches used to describe dipolar optical forces and introduces a symmetry-based “force basis” consisting of twelve vector fields, each weighted by particle-specific coefficients, for a streamlined description of force patterns. The approach is rigorously applied to evanescent waves and dielectric nanofibers, yielding concise analytical expressions for optical forces. Through this, we identify optimal strategies for enantiomer separation, offering invaluable guidance for future experiments. Published by the American Physical Society 2024

Ion-pair chromatographic attribute in the retention of ammonium ion on a crown ether-based and a polysaccharide-based chiral stationary phases. Some mobile phase additives compatible with liquid chromatography-electrospray ionization-mass spectrometry

The design of the mobile phase additive useful in HPLC analysis on two types of chiral stationary phases, one based on chiral crown ether, and another based on polysaccharide derivative, was developed. CROWNPAK® CR-I, the chiral stationary phase bearing (R)- or (S)-(3,30-diphenyl-1,10-binaphtyl)-20-crown-6 (1) moiety is a useful CSP to separate primary amine enantiomers. While perchloric acid had been recommended as the mobile phase additive to attain a better separation, we have reexamined the effect of mobile phase additives and revealed that the retention of an ammonium ion is enhanced by a chaotropic or a hydrophobic anion in a water-based mobile phase like well-known ion pair chromatography in an RPLC. However, the retention was enhanced in reverse by a rather cosmotropic or a hydrophilic anion in an acetonitrile (ACN)-based mobile phase. These results looking contradictory to each other may be rationalized both in the basis of ion pair chromatography. A similar but smaller effect of pairing anion species was also observed on a polysaccharide-based CSP. Based on these findings, some types of mobile phase have been proposed and some of them were demonstrated to be compatible with liquid chromatography-electrospray ionization-mass spectrometry (ESI LC/MS).

Chiral liquid chromatography-tandem mass spectrometry for enantiomeric profiling of ten alkaloids in tobacco: Assessing interconversion in precursor materials and aerosol

Multiple chiral enantiomer separation poses challenges in analyzing complex matrices like natural plant materials. Currently, there is no straightforward method for simultaneous separation and analysis of ten alkaloids and enantiomers, mainly due to most of their low levels. Here, we present an improved chiral liquid chromatography-tandem mass spectrometry method for accurate quantification of ten alkaloids and enantiomers. This method exhibits recoveries of 92.3 to 118.1 %, intra-day precisions of 0.6 to 4.7 %, and inter-day precisions of 1.2 to 4.5 %, with detection limits ranging from 0.03 to 3.0 ng/mL. Successfully applied to the ten alkaloids and enantiomers quantification in precursor tobacco materials and aerosols from traditional cigarettes and heated tobacco products, our results show higher concentrations of ten alkaloids in traditional cigarette aerosol compared to heated tobacco products aerosol. During aerosol formation, (R)-cotinine, N-methylanabasine, and β-nornicotyrine were produced. Notably, high temperatures during aerosol formation favored the (R)-enantiomer of several chiral alkaloids, and lead to the formation of new secondary alkaloids. This proposed mechanism represents the first attempt to elucidate the interconversion of alkaloids during aerosol formation.

Two-dimensional chiral metal-organic framework nanosheets L-hyp-Ni/Fe@SiO2 composite for HPLC separation

In this study, we have synthesised a chiral l-hyp-Ni/Fe@SiO2 composite as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) for the first time. This was achieved by coating two-dimensional (2D) chiral metal-organic framework nanosheets (MONs) l-hyp-Ni/Fe onto the surface of activated SiO2 microspheres using the “wrapped in net” method. The separation efficiency of the l-hyp-Ni/Fe chromatographic column was systematically evaluated in normal-phase HPLC (NP-HPLC) and reversed-phase HPLC (RP-HPLC) configurations, employing various racemates as analytes. The findings revealed that 16 chiral compounds were separated using NP-HPLC, and five were separated using RP-HPLC, encompassing alcohols, amines, ketones, esters, alkanes, ethers, amino acids and sulfoxides. Notably, the resolution (Rs) of nine chiral compounds exceeded 1.5, indicating baseline separation. Furthermore, the resolution performance of the l-hyp-Ni/Fe@SiO2-packed column was compared with that of Chiralpak AD-H. It was observed that certain enantiomers, which either could not be resolved or were inadequately separated on the Chiralpak AD-H column, attained separation on the 2D chiral MONs column. These findings suggest a complementary relationship between the two columns in racemate separation, with their combined application facilitating the resolution of a broader spectrum of chiral compounds. In addition, baseline separation was achieved for five positional isomers on the l-hyp-Ni/Fe@SiO2-packed column. The effects of the analyte mass and column temperature on the resolution were also examined. Moreover, during HPLC analysis, the l-hyp-Ni/Fe columns demonstrated commendable repeatability, stability and reproducibility in enantiomer separation. This research not only advances the utilisation of 2D chiral MONs as CSPs but also expands their applications in the separation sciences.

Quantitative determination of R/S-methadone in human serum using ultra-high performance supercritical fluid chromatography-tandem mass spectrometry: A method for routine use.

Methadone has two enantiomers, which exhibit differences in pharmacological effects, with R-methadone being the active and S-methadone the inactive enantiomer. A robust, simple and rapid method for chiral separation of the two enantiomers in serum samples using ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MSMS) has been developed and validated. Enantiomeric separation was achieved using a Chiralpak IH-3 column with a mobile phase consisting of CO2 and 30mM ammonium acetate in methanol/water (98/2, v/v). Runtime was 4minutes. Sample preparation was semi-automated using a Hamilton ML Star robot with protein precipitation, and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. The calibration range was 50.0-1,500 nM for each enantiomer. The between-assay relative standard deviations were in the range of 1.2-3.6%. Matrix effects ranged from 99% to 115% corrected with internal standard. The method has been implemented in our laboratory and has proven to be a robust and reliable method for determining the ratio of R/S-methadone in authentic patient samples.

Organocatalytic desymmetrization provides access to planar chiral [2.2]paracyclophanes

Planar chiral [2.2]paracyclophanes consist of two functionalized benzene rings connected by two ethylene bridges. These organic compounds have a wide range of applications in asymmetric synthesis, as both ligands and catalysts, and in materials science, as polymers, energy materials and dyes. However, these molecules can only be accessed by enantiomer separation via (a) time-consuming chiral separations and (b) kinetic resolution approaches, often with a limited substrate scope, yielding both enantiomers. Here, we report a simple, efficient, metal-free protocol for organocatalytic desymmetrization of prochiral diformyl[2.2]paracyclophanes. Our detailed experimental mechanistic study highlights differences in the origin of enantiocontrol of pseudo-para and pseudo-gem diformyl derivatives in NHC catalyzed desymmetrizations based on whether a key Breslow intermediate is irreversibly or reversibly formed in this process. This gram-scale reaction enables a wide range of follow-up derivatizations of carbonyl groups, producing various enantiomerically pure planar chiral [2.2]paracyclophane derivatives, thereby underscoring the potential of this method.

Novel ethylenediamine-β-cyclodextrin grafted membranes for the chiral separation of mandelic acid and its derivatives.

In the present study, flat cellulose acetate ultrafiltration membranes were prepared first by nonsolvent induced phase separation method. Then chiral membranes for separating the enantiomers were prepared by grafting the ultrafiltration membranes using ethylenediamine-β-cyclodextrin as the chiral selector and epichlorohydrin as the spacer arm. The pure water permeability of the ultrafiltration membrane was around 115 L·m-2·h-1·bar-1. The properties of the chiral membranes were characterized using infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The chiral membrane performance in enantiomer separation was evaluated with racemates, such as mandelic acid (MA), 2-chloromandelic acid (2-ClMA), 4-chloromandelic acid (4-ClMA), and methyl mandelate (MM). The influence of feed concentration on the separation efficiency was also investigated. The results indicated that the enantiomeric excess percentages (e.e%) of the racemic mixtures for these four chiral compounds were up to 31.8%, 25.4%, 17.8%, and 32.6%, respectively. The binding free energy of the chiral selector with the (S)-enantiomer calculated by molecular dynamics simulations was stronger than that with the (R)-enantiomer, which was consistent with the experimental results (higher concentration of (R)-enantiomer in the permeate). This supports the affinity absorption-separation mechanism.

Separation of enantiomers of chiral fullerene derivatives through enantioselective encapsulation within an adaptable helical cavity of syndiotactic poly(methyl methacrylate) with helicity memory.

Optically active left (M)- and right (P)-handed helical syndiotactic poly(methyl methacrylate)s (M- and P-st-PMMAs) with a helicity memory enantioselectively encapsulated the racemic C60 derivatives, such as 3,4-fulleroproline tert-butyl ester (rac-1) and tetraallylated C60 (rac-2), as well as the C60-bound racemic 310-helical peptides (rac-3) within their helical cavities to form peapod-like inclusion complexes and a unique "helix-in-helix" superstructure, respectively. The enantiomeric excess (ee) and separation factor (enantioselectivity) (α) of the analyte 1 (ee = 23%-25% and α = 2.35-2.50) encapsulated within the helical cavities of the M- and P-st-PMMAs were higher than those of the analytes 2 and 3 (ee = 4.3%-6.0% and α = 1.28-1.50). The optically pure (S)- and (R)-1 were found to more efficiently induce an excess one-handed helical conformation in the st-PMMA backbone than the optically pure (S)- and (R)-1-phenylethylamine, resulting in intense mirror-image vibrational circular dichroism (VCD) spectra in the PMMA IR regions. The excess one-handed helices induced in the st-PMMAs complexed with (S)- and (R)-1 were memorized after replacement with the achiral C60, and the complexes exhibited induced electric CDs in the achiral C60 chromophore regions.

Enantiomeric separation of four pairs of alkaloids by using a C18 column tandem polysaccharide-based chiral column

Abstract Alkaloid enantiomers have different physiological and pharmacological effects, and different chiral compositions have a large impact on cigarette sensory and use safety. Studying the effects of different configurations of alkaloid enantiomers on cigarette sensory is important for the development of tobacco products, but the chiral separation of alkaloid enantiomers has become the core problem. Here, the application of a C18 column coupled with a polysaccharide-based chiral column to separate and detect four pairs of alkaloid enantiomers in tobacco and cigarette smoke of different brands was investigated. Results showed that the tandem technology of the two columns enabled the baseline separation of four pairs of alkaloid enantiomers. The resolution of enantiomers of alkaloids in different tobacco samples differed in content and ratio, showing different chiral distribution characteristics. According to the different distribution characteristics of alkaloid enantiomers, tobacco samples of different brands can be distinguished and real cigarettes can be identified.

Enantioseparation via Chiral Supramolecular Gels Comprising Ambidextrous Gelators Based on β-Peptide-type Primary Amines.

While β-peptides have been paid attention due to their diverse secondary structures, their application to the design of low-molecular-weight gelators (LMWGs) is less explored. In this work, chiral cyclic β-amino acid-based β-peptides were developed as ambidextrous LMWGs, wherein multiple hydrogen bonds between the amide moieties led to high gelation ability. Their molecular assembly was elucidated using spectroscopies, microscopy, and X-ray analysis. Further, the supramolecular gel was used as a platform for the enantioselective extraction of (S)-naproxen from its racemate under optimized conditions. These findings have expanded the utility of β-peptides and shown the potential of supramolecular gels as a distinct dynamic medium for enantiomer separation.