Chiral recognition is a foundation in pharmaceutical and health sciences, particularly for the selective detection of enantiomers in chiral drugs. Over the past 5 years, significant progress has been made in developing chiral fluorescent sensors with improved sensitivity, selectivity, and biocompatibility. This review highlights the structural design, functionalization strategies, and sensing mechanisms of representative systems, including carbon-based quantum dots (CQDs, chiral carbon dots [CCDs], and graphene quantum dots [GQDs]), metal-organic frameworks (MOFs), and composite nanomaterials. Notable advances include graphene quantum dots functionalized with D-cysteine for morphine enantiomer discrimination, CdSe/ZnS QDs modified with L-pyroglutamic acid derivatives for stereoselective amino acid detection, Zn-MOC@CQDs composites enabling enantioselective lactic acid sensing, and Eu-BTB@D-carnitine MOFs for enhanced fluorescence-based recognition. More recent developments, such as BINOL-derived probes and carbazole-based sensors, demonstrate high enantioselectivity and ultralow detection limits in amino acid sensing. Compared with earlier reviews, this article emphasizes the integration of hybrid nanostructures and multifunctional composites as next-generation sensing platforms, bridging fluorescence, electrochemiluminescence, and coordination chemistry approaches. The progress discussed herein underscores how the rational design of chiral nanomaterials is shaping precise enantiomer discrimination technologies, with potential for real-world applications in drug analysis, biosensing, and food quality monitoring.

A novel kind of framework containing axial 5-OH L-bitryptophane was synthesized under the mild reaction conditions. This synthetic strategy provides an efficient method to construct axial catalysts based on the new framework, which can be easily and economically separated from each other using silica gel column chromatography because the coupling products were atropisomers. For its promising application of the framework, eight catalysts were prepared and the relationship of the different catalytic centers on the enantioselectivity was tested using known and widely used model reactions and good enantiomeric ratios were recorded. Quantum methods were applied for the absolute configurations assignment of the new framework, the transition states (TSs) calculations for reaction mechanism study. The theoretical results agree well with the experiments. One best catalyst 8B with a 13-membered ring was found in the model reaction.

The well-known, readily available Sanger reagent is used for quantitative chiroptical sensing of the amount and enantiomeric composition of amines, amino alcohols, and amino acids. A practical assay that is fast, adaptable to a variety of solvents, and only requires mixing of the sample and probe in the presence of triethylamine prior to the CD and UV measurements is introduced. The analyte tagging generates characteristic CD and UV signals at 405 and 345 nm, respectively, which allow accurate concentration and er analysis without any workup or tedious sample preparation.

Pinocembrin, as a natural dihydroflavone compound, is currently in the clinical phase II research stage as a candidate new drug due to its significant therapeutic effect on stroke. However, there is no report on the systematic study of the pharmacokinetic and pharmacological activity differences of the enantiomers of pinocembrin. This study comprehensively investigated the stereoselective properties of pinocembrin enantiomers through integrated pharmacokinetic, network pharmacological and neuroprotective evaluations on HT22 cells. The results demonstrated distinct stereoselective characteristics in rat plasma between the enantiomers of pinocembrin following intravenous administration, with the plasma concentration of (+)-pinocembrin consistently being higher than that of (-)-pinocembrin. Pharmacokinetic studies of individual enantiomers administered intravenously demonstrated no evidence of stereochemical inversion between the two enantiomers of pinocembrin in either plasma or brain tissue of rats. Network pharmacology analysis revealed multiple potential therapeutic targets related to ischemic stroke pathophysiology, particularly involving apoptosis regulation and inflammatory responses. Both (+)-pinocembrin and (-)-pinocembrin exhibited protective effects against OGD/R-induced injury in HT22 cells at concentrations of 6.25-50 μM and 12.5-50 μM, respectively; however, no statistically significant difference was observed between the two enantiomers. Western blot analysis further revealed that (+)-pinocembrin significantly upregulated the Bax/Bcl-2 ratio and the p-Akt/Akt ratio, suggesting that its neuroprotective effects are mediated through modulation of apoptosis and activation of the Akt signaling pathway. These findings provide a foundation for understanding the stereoselective pharmacological properties of pinocembrin and suggest potential therapeutic applications leveraging the unique characteristics of each enantiomer for neuroprotective interventions.

Two previously undescribed jatrophane-type diterpenoids (1, 2) and 11 known compounds (3-13) were isolated from the whole plants of Jatropha curcas L. Their structures were elucidated using IR, HR-ESI-MS, 1D-, and 2D-NMR spectra, and the absolute configurations were established by ECD. The anti-inflammatory activity of these compounds was evaluated by inhibiting NO production in LPS-stimulated RAW264.7 macrophages, and compounds 5, 8-11, and 13 showed potent activity with IC values ranging from 16.86 to 32.49 μM, which were comparable with that of the positive control l-NMMA (IC: 21.90 μM). The structure-activity relationships of jatrophane-type diterpenoids revealed that compounds 5 and 11 showed the most potent anti-inflammatory effects.

Chiral chromatography is the most sensitive technique in separation science due to the similar properties of the enantiomers, which require highly expert hands. This sort of chromatography has various limitations and issues, especially in efficient separation, detection, and reproducibility. These issues can be tackled by integrating chiral chromatography with artificial intelligence and machine learning approaches. This review article describes the present development in chiral chromatography integration with artificial intelligence and machine learning and future requirements. The most important aspects discussed in this article are the analysis of various software and models needed for integration, method development and optimization of chiral chromatography, and applications of artificial intelligence and machine learning integrated chiral chromatography in real-life samples. Besides, the challenges, recommendations, and future perspectives of artificial intelligence and machine learning integrated chiral chromatography are discussed. This article will be highly useful for applying artificial intelligence and machine learning integration in chiral chromatography in research and industrial applications.

Odevixibat, a selective and reversible inhibitor of the ileal bile acid transporter (IBAT), received approval from the US Food and Drug Administration (FDA) in 2021 as the first therapeutic option for pruritus associated with progressive familial intrahepatic cholestasis (PFIC). In this study, a comprehensive chiral high-performance liquid chromatography (HPLC) method was developed for the enantiomeric and diastereomeric separation of Odevixibat and its stereoisomeric impurities (RS, RR, SS, and SR) using immobilized polysaccharide-based chiral stationary phases. The various chromatographic modes-including normal-phase (NP), reversed-phase (RP), and polar organic (PO)-were systematically investigated. Optimal resolution was achieved using a CHIRALPAK IA column (4.6 × 250 mm, 3 μm) with a mobile phase of n-hexane/isopropanol/methanol/trifluoroacetic acid (50:35:15:0.1, v/v/v/v) at 40°C and a flow rate of 1.0 mL/min. The method was validated according to ICH Q2(R1) guidelines. Additionally, the CHIRALPAK IM in NP mode effectively resolved closely eluting isomeric impurities, enabling preparative isolation and characterization. The optimized RP-mode method was compatible with LC-MS detection, facilitating trace-level impurity profiling on CHIRALPAK ID-3 and structural characterization of stereoisomers and process-related impurities. Thermodynamic analysis revealed entropy-driven enantioseparations, with the NP-HPLC method on CHIRALPAK IA showing more favorable interactions (ΔG° = 0.06) than the RP-HPLC system (ΔG° = 1.34). The method demonstrated excellent linearity (r > 0.999) over the concentration range of 0.028-0.211 μg/mL, with recoveries between 87.1%-101.2% and precision within 0.8% RSD. High sensitivity was achieved, with LODs of 0.009-0.025 μg/mL and LOQs of 0.028-0.075 μg/mL. The method proved robust under deliberate variations in column temperature (±1°C), mobile phase composition (±2%), and flow rate (1.0 ± 0.1 mL min), showing no significant change in enantioresolution. These complementary approaches are suitable for routine quality control (CHIRALPAK IA), purification (CHIRALPAK IM) process monitoring and LC-MS impurity profiling (CHIRALPAK ID-3), and regulatory submissions, supporting current good manufacturing practices (cGMP) in the development of Odevixibat.

The resolution behavior of chiral compounds containing two carboxyl groups remains an interesting subject due to their potential for forming complex stereospecific interactions. In this study, a representative for this group of compounds, trans-1,2-cyclohexanedicarboxylic acid (CHDA) was enantiomerically separated using optically active (1S,2S)-(+)-1-(p-nitrophenyl)-2-amino-1,3-propanediol ((SS)-ANP) as a resolving agent in ethanol solvent. Remarkably, regardless of the initial molar ratio of (SS)-ANP to CHDA (ranging from 1:3 to 3:1), only a cocrystal, di-(SS)-ANP·CHDA·ethanol was obtained. When the molar ratio was adjusted to 1:2, a pair of diastereomeric salts was formed, and (RR)-CHDA freed from the less soluble diastereomeric salt exhibited an enantiomeric excess (e.e.) exceeding 85%. Upon two cycles of recrystallization of the less soluble salts, the optical purity of the freed (RR)-CHDA reached 96.5 e.e.%. To elucidate the resolution mechanism, single crystals of both the less soluble salt 2(SS)-ANP·(RR)-CHDA·ethanol and the more soluble salt 2(RR)-ANP·(RR)-CHDA·ethanol were grown and structurally analyzed. The crystallographic data revealed that the hydrogen bonding in the less soluble salt was stronger than that in the more soluble salt, enhancing the stability of the less soluble salt, 2(SS)-ANP·(RR)-CHDA·ethanol.

As one of the most widely used fungicides in global agriculture, chiral triazole fungicides play a crucial role in crop protection due to their broad-spectrum efficacy. However, the environmental problems caused by their widespread use are becoming increasingly prominent. These problems not only cause ecological pollution but also pose potential risks to human health and the safety of ecosystems. In response to these problems, developing optically pure monomer pesticides that are highly efficient yet low in toxicity has become a key strategy. This reduces both the dosage required and the impact on nontarget organisms. In recent years, the research focus on chiral triazole fungicides has expanded from evaluating a single biological activity to assessing stereoselective toxicity, environmental behavior, and metabolic fate in a multidimensional way. Despite growing academic interest in the stereoselective toxicological effects and metabolic differences of nontarget organisms (particularly mammals), most available reviews have focused on biological activity and environmental fate. Furthermore, there is a lack of reviews that systematically evaluate the stereoselective behavior of these pesticides in mammals, which restricts our overall understanding of the safety of this class of pesticides. Based on this, this paper not only lists the stereoselective bioactivities and toxicological differences of chiral triazole fungicides but also, for the first time, focuses on the mammalian system, providing a comprehensive elucidation of their stereoselective behaviors from the perspectives of metabolism in rat liver microsomes, toxicokinetic characteristics, metabolomics, and gut microbiota. The aim of this review is to address the shortcomings of existing reviews and to serve as a reference for the development of optically pure, environmentally friendly, low-toxicity, and efficient monomer pesticides.

Chiral flavonoids are frequently encountered in natural products consumed as food or therapeutic products. However, the taste and other bioactivities of stereoisomers are known to differ. Hence, stereoseparation methods are necessary to resolve these isomers, whether to measure stereoisomeric ratios or to purify individual stereoisomers for activity testing. In this study, we looked for the best conditions to resolve different families of chiral flavonoids, including auronols, flavanonols, aglycon, and glycosylated flavanones. Furthermore, we aimed to include this stereoseparation as the second-dimension method in a two-dimensional supercritical fluid chromatography system (SFC-SFC), to achieve the resolution of chiral flavonoids in complex samples. First, a set of 10 standards of chiral flavonoids was examined on 5 immobilized polysaccharide chiral stationary phases. With the help of Derringer desirability functions, the columns offering the best options for rapid resolution were identified. Then, a sample of honey was analyzed in an SFC-SFC system in heart-cutting mode. The first-dimension achiral separation resolved the complex mixture of honey and isolated the fraction of pinocembrin enantiomers, which were re-analyzed in the second-dimension chiral separation to measure the enantiomeric excess, and resolve co-eluting isobaric species. This experiment demonstrates the relevance of this strategy in the resolution of flavonoid enantiomers from complex samples.

In this work, a new strategy was proposed for the preparation of a chiral stationary phase based on β-cyclodextrin and calix[4]arene polymer. The chiral stationary phase was characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The introduction of calix[4]arene polymer increased chirality recognition by increasing recognition sites and interactions, including hydrogen bonding, π-π interaction and synergistic inclusion effect. Compared with the home-made β-cyclodextrin-based chiral column, the prepared β-cyclodextrin-calix[4]arene polymer-based chiral column showed superior enantioseparation performance toward 1-phenylethanol, prothioconazole, promethazine, propranolol, and bisoprolol. These chiral compounds can be separated within 10 min under reversed-phase mode with resolutions ranging from 1.62 to 1.80. These findings will provide an important reference for developing novel supramolecule-based chiral stationary phases.

(S)-Bepotastine is a highly selective histamine H1-receptor antagonist in the treatment of allergic rhinitis and other allergic diseases. We achieved a facile and convenient synthesis of (S)-bepotastine by resolving an early stage synthetic precursor. We devised a new class of resolving agent, BINOL-3,3'-dicarboxylic acid which could be considered as an axial version of tartaric acid. As the first example, we successfully resolved racemic piperidinyl ether by (S)-BINOL-3,3'-dicarboxylic acid with high optical purity. The final installation is quite straightforward and readily accomplished without any chiral loss.

In this work, a CDs-TpBD/UiO-66 hybrid material was firstly synthesized via Schiff base reaction using isocyanate-β-cyclodextrin (CDs) as a chiral modifier, TpBD COF and UiO-66-NH MOF as the frameworks, and was characterized by Fourier-transform infrared spectra, scanning/transmission electron microscopy, X-ray diffraction spectra, X-ray photoelectron spectroscopy, nitrogen adsorption-desorption, and thermogravimetric analysis. The results showed that the hybrid material exhibited a close-packed structure of TpBD and UiO-66-NH crystal, well-defined micropores, and good stability. It was used as the stationary phase in open-tubular (OT) capillary electrochromatography, and 7 amino acids (basic: D/L-arginine, D/L-histidine, D/L-lysine; neutral: D/L-methionine, D/L-valine; acidic: D/L-aspartate, D/L-glutamic acid) and D/L-carnitine (D/L-Car) were baseline separated under the optimal chromatographic conditions within 6 min by capillary electrochromatography. The resolution (Rs) ranged from 1.50 to 5.41, and the selectivity factor (α) ranged from 1.08 to 2.52, respectively. Enantioseparation was attributed to the synergistic effect of CDs, TpBD, and UiO-66-NH in the stationary phase as well as the difference of adsorption and selectivity between the enantiomers and the stationary phase through the adsorption experiments. The detection method of D/L-Car was established by CDs-TpBD/UiO-66 OT column. Good linearity (R ≥ 0.999) was obtained in the concentration ranges of 8.5-200 μg/mL for D-Car and 7.0-200 μg/mL for L-Car with detection limits of 2.5 and 2.1 μg/mL, respectively. The developed method was simple, rapid, high efficiency as well as broad application, and could be applied for the simultaneous separation and detection of D/L-Car in actual samples.

This study represents a special, time-dependent resolution strategy of an atropisomeric, bifunctional 1-phenylpyrrole derivative, using the nonactive enantiomer of the key amine intermediate Apremilast as an efficient resolving agent. Among the solvents investigated, ethyl acetate was identified as the optimal solvent, allowing rapid crystallization and high enantiomeric purity (> 99% ee). A detailed study of kinetic behavior revealed that early-stage crystallization and timely separation of diastereomeric salt are critical to achieving high enantiopurity and avoiding recrystallization to lead to a racemic product. Time-dependent studies suggest that solvate formation of enantiomers and ethyl acetate plays a crucial role in the resolution mechanism. This resolution process enables the direct separation of racemic 2-(2-carbamoyl-1H-pyrrol-1-yl)-3-(trifluoromethyl) benzoic acid suitable for further applications, such as resolving agents for amine-type compounds. Significantly, this approach recycles an amine-type drug intermediate that is typically discarded during the large-scale production of Apremilast, thus being in line with green chemistry principles by minimizing waste and enabling resource recovery.

Molecular homochirality - the uniformity of chirality in biological molecules - is a fundamental feature of life, yet its origins remain unresolved. The correspondence between the chirality of biological monomers on Earth and that observed in ancient meteorites implies a systematic selection of chirality sign in prebiotic chemistry, rather than a stochastic process. While classical theories attribute symmetry breaking to chiral autocatalysis, such self-amplifying processes are rare and have not been empirically demonstrated in the synthesis of amino acids and carbohydrates. In contrast, chiral cross-catalysis between amino acids and carbohydrates - a mechanism consistent with known chemical behavior - could similarly amplify chiral purity. However, cross-catalysis alone cannot determine the chirality sign due to its inherent symmetry, leaving the origin of the initial bias unexplained. Although weak interactions have been proposed as a potential source of this bias, their effects are theoretically negligible, raising questions about their sufficiency. Our kinetic analysis of cross-catalytic systems reveals that even an infinitesimal preference for left-handed amino acids and right-handed carbohydrates could be sufficient to establish the homochirality observed in life. This mechanism provides a plausible link between prebiotic chemistry and the homochirality of the biosphere, offering a potential resolution to this longstanding enigma.

The enantiomeric purity of Finerenone (FIN), a novel therapeutic for chronic kidney disease (CKD), is a critical quality attribute for ensuring patient safety. This study reports the first chiral HPLC method for the simultaneous determination of FIN and its enantiomer, developed and validated using a rigorous analytical quality by design (AQbD) framework. The method employs a CHIRALPAK AD-H column with an isocratic mobile phase of n-hexane: ethanol (62:38, v/v). Optimized conditions provide excellent baseline resolution (Rₛ = 3.5) in under 10 min. The method was validated using accuracy profiles, demonstrating high performance with limits of quantification established at 340 μg mL for FIN and 0.40 μg mL for its 4R enantiomer. The AQbD approach successfully defined a robust method operable design region (MODR) to ensure consistent performance. Furthermore, a multimetric sustainability evaluation confirmed the method's favorable eco-profile, achieving a Grade Index (BAGI) score of 77.5 and Red-Green-Blue 12 (RGB12) score of 80.8. This work provides a reliable, robust, and eco-conscious analytical tool essential for the quality control of FIN formulations.

A recent publication by Kopec et al., "The effect of enantiomers of thalidomide on colon cells-Raman spectroscopy studies", reported to "demonstrate that Raman spectroscopy reveals distinct spectral differences between the enantiomers of thalidomide" and provided both experimental and computational evidence. However, the theory of Raman spectroscopy inherently establishes that two enantiomers must exhibit identical Raman frequencies and intensities. While the slightly different experimental Raman spectra for the two enantiomers of thalidomide can be traced back to samples with different chemical and/or optical purities, the significant discrepancies observed in the computed Raman spectra arise from a computational artifact related to methodological shortcomings.

As enantiomers can have different pharmacological and toxicological impacts even though they have the analogous chemical composition, efficient chiral separation is crucial. Chromatography is one of the primary methods for separating enantiomers, and the key to chromatographic separation lies in the chiral stationary phase (CSP). Chiral porous materials have emerged as innovative chiral stationary phases and garnered extensive attention. Zr based MOF materials, have been regarded as one of the most stable metal-organic framework (MOF) materials. In this paper, after grafting with L-proline, UiO-66 was used for the first time for chiral gas chromatography separation. The newly developed CSP provided high resolution for xylenes within only 2-3 min. For substances like linalool, α-pinene, and xylenes, the UiO-66-NH-L-Pro-coated capillary column acquired bas3ic resolution and showed outstanding enantiomeric and positional isomer isolation. Comprehensive characterizations, including SEM, XRD, FT-IR, TGA, N adsorption-desorption isotherms, CD spectra, and XPS, were conducted to analyze the material stucture and chiral recognition mechanism. The chiral separation relies on transient diastereomeric complexes formed between L-proline and enantiomers, stabilized by hydrogen bonding, intermolecular forces, and steric constraints within UiO-66's micropores. These interactions enforce enantioselective discrimination via the pore's stereochemical filtering, enabling chiral resolution. This study is expected to provide significant value for both chromatographic chiral separation and large-scale chiral substance separation.

In this work, the silica gel bonded amylose[(S)-α-methylbenzyl carbamate] (CHIRALPAK IH) was chosen as the chiral stationary phase (CSP) for the separation of five quinolone enantiomers by high-performance liquid chromatography (HPLC), namely, ofloxacin, flumequine, nadifloxacin, lomefloxacin, and clinafloxacin. The mobile phase composition, organic modifier, and acid-base additive were systematically investigated for the baseline separation of these five interested quinolones. The optimized mobile phases were n-hexane-ethanol-acetic acid-diethylamine (60:40:0.2:0.2, v/v/v/v) for ofloxacin and nadifloxacin, n-hexane-ethanol-acetic acid-diethylamine (60:40:0.2:0.2, v/v/v/v) for flumequine, n-hexane-isopropanol-acetic acid-diethylamine (60:40:0.3:0.3, v/v/v/v) for lomefloxacin, and n-hexane-ethanol-acetic acid-diethylamine (70:30:0.3:0.3, v/v/v/v) for clinafloxacin. The interaction forces between the amylose CSP and target quinolones were simulated by computerized molecular docking to study their enantiorecognition mechanisms. The results indicated that hydrogen bonding, π-π stacking, and hydrophobic interactions collectively contributed to the stereoselective binding. The differences in these interaction forces between the quinolone enantiomers, particularly the greater contribution of hydrogen bonding in one enantiomer compared to the other, led to a significant difference in binding energy. This differential binding energy ultimately governed the elution order and enabled chiral recognition of the five quinolone enantiomers.

Specific rotations [α] of L-arginine in water and aqueous solutions of glycine, HCl, LiCl, KCl, NaOH, and NaSO were measured at 405 nm. The [α] value is 34.7 ± 0.5 deg·mL·dm·g in water and increases with the increasing acidity in accordance with the Clough-Lutz-Jirgensons (CLJ) rule. [α] changes little in glycine solutions, implying that the CLJ effect is the result of a proton-amino acid interaction. In the salt solutions, [α] gradually decreases with the increasing concentration, suggesting that binding between a metal ion and L-arginine produces a different structure from that of the protonated amino acid, producing the anti-CLJ effect.

Ketoprofen, also known as (RS)-2-(3-benzoylphenyl)-propionic acid, has the molecular formula CHO and is classified as a non-steroidal anti-inflammatory medication. R-ketoprofen has stronger analgesic effects than S-K, and as a result, there is a growing interest in enantio-recognition research, which may be accomplished through supramolecular interactions, particularly host-guest reactions. A 1:1 molar ratio was used to produce the combination of separate RK and SK and a 0.01 M stock solution of HP-β-CD to get the final concentration of 6 × 10 M. Ethanol was used to make stock solutions of ketoprofen enantiomers (1 mM). Researchers combined a specific volume of ketoprofen with 2-hydroxypropyl-beta-cyclodextrin (HPβ-CD) and then used spectroscopic methods to study how the S-ketoprofen (SK) and R-ketoprofen (RK) enantiomers interact with HPβ-CD to form inclusion complexes in an aqueous solution. The Benesi-Hildebrand plot was used to determine the inclusion complexes' stoichiometry ratio and binding constant; both enantiomers displayed a 1:1 stoichiometry ratio inclusion complex with HP-β-CD. Compared with SK (799 M), RK has a higher binding constant (1038 M). These results showed that HP-β-CD preferred to form inclusion complexes with RK over SK. At neutral pH, there are significant differences between RK and SK when HP-β-CD is present.