Chirality最新文献

{"title":"Resolution Characteristics of Optically Active (1S,2S)-(+)-1-(p-Nitrophenyl)-2-Amino-1,3-Propanediol for trans-1,2-Cyclohexanedicarboxylic Acid","authors":"Haibing Jin,&nbsp;Yangfeng Peng,&nbsp;Tianzhong Tong,&nbsp;Hongliang Zhao,&nbsp;Yani Dai,&nbsp;Quan He","doi":"10.1002/chir.70067","DOIUrl":"10.1002/chir.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>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, <i>trans</i>-1,2-cyclohexanedicarboxylic acid (CHDA) was enantiomerically separated using optically active (1<i>S</i>,2<i>S</i>)-(+)-1-(<i>p</i>-nitrophenyl)-2-amino-1,3-propanediol ((<i>SS</i>)-ANP) as a resolving agent in ethanol solvent. Remarkably, regardless of the initial molar ratio of (<i>SS</i>)-ANP to CHDA (ranging from 1:3 to 3:1), only a cocrystal, di-(<i>SS</i>)-ANP·CHDA·ethanol was obtained. When the molar ratio was adjusted to 1:2, a pair of diastereomeric salts was formed, and (<i>RR</i>)-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 (<i>RR</i>)-CHDA reached 96.5 e.e.%. To elucidate the resolution mechanism, single crystals of both the less soluble salt 2(<i>SS</i>)-ANP·(<i>RR</i>)-CHDA·ethanol and the more soluble salt 2(<i>RR</i>)-ANP·(<i>RR</i>)-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(<i>SS</i>)-ANP·(<i>RR</i>)-CHDA·ethanol.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantiomeric Resolution of Odevixibat via Immobilized Polysaccharide Columns: Impact of NP, RP, and PO Modes on LC–MS-Compatible Method Design","authors":"S. R. Krishna Murthy Kasa,&nbsp;Muvvala Venkatanarayana,&nbsp;Lakshmi Narayana Chennuru,&nbsp;M. V. N. Kumar Talluri","doi":"10.1002/chir.70065","DOIUrl":"10.1002/chir.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>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 <i>n</i>-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 (<i>r</i>² &gt; 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⁻¹), 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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of 13-Membered Ring L-Bitryptophanes and Their Enantioselective Indole Friedel–Crafts Reactions","authors":"Xinliang Guo,&nbsp;Huan Chang,&nbsp;Ruizhe Chang,&nbsp;Kehong Duan,&nbsp;Huajie Zhu","doi":"10.1002/chir.70064","DOIUrl":"10.1002/chir.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>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 <b>8B</b> with a 13-membered ring was found in the model reaction.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chiral Chromatography and Artificial Intelligence Integration in Enantiomers Separation","authors":"Imran Ali,&nbsp;Mouslim Messali,&nbsp;Ann Gogolashvili,&nbsp;Khaled Sekkoum","doi":"10.1002/chir.70066","DOIUrl":"https://doi.org/10.1002/chir.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Inflammatory Jatrophane Diterpenoids With Multiple Chiral Carbon Centers From Jatropha curcas","authors":"Yi-Lin He,&nbsp;Guo-Li Li,&nbsp;Hong-Ying Yang,&nbsp;Na Gao,&nbsp;Kun Gao","doi":"10.1002/chir.70061","DOIUrl":"10.1002/chir.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Two previously undescribed jatrophane-type diterpenoids (<b>1</b>, <b>2</b>) and 11 known compounds (<b>3</b>–<b>13</b>) were isolated from the whole plants of <i>Jatropha curcas</i> 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 <b>5</b>, <b>8</b>–<b>11,</b> and <b>13</b> showed potent activity with IC₅₀ values ranging from 16.86 to 32.49 μM, which were comparable with that of the positive control <span>l</span>-NMMA (IC₅₀: 21.90 μM). The structure–activity relationships of jatrophane-type diterpenoids revealed that compounds <b>5</b> and <b>11</b> showed the most potent anti-inflammatory effects.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing the Sanger Reagent for Optical Sensing of the Concentration and Enantiomeric Ratio of Chiral Amines, Amino Alcohols, and Amino Acids","authors":"F. Safia Kariapper,&nbsp;Austin U. Wolf,&nbsp;Christian Wolf","doi":"10.1002/chir.70062","DOIUrl":"https://doi.org/10.1002/chir.70062","url":null,"abstract":"<p>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 <i>er</i> analysis without any workup or tedious sample preparation.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/chir.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Stereoselective Pharmacokinetics and Neuroprotective Effects on HT22 Cells of Pinocembrin Enantiomers","authors":"Lirong Chen,&nbsp;Xiaofen Chen,&nbsp;Dongting Huang,&nbsp;Yongjing Liu,&nbsp;Yuqing Zhang,&nbsp;Hua Li","doi":"10.1002/chir.70063","DOIUrl":"10.1002/chir.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chiral Luminescent Sensor for Enantiomer Discrimination","authors":"Vivek Sharma,&nbsp;Akash Kumar Mishra,&nbsp;Neeraj Kumar Mishra,&nbsp; Vinod","doi":"10.1002/chir.70057","DOIUrl":"https://doi.org/10.1002/chir.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of β-Cyclodextrin–Calix[4]arene Polymer-Based Chiral Stationary Phase for Chromatographic Separation of Enantiomers","authors":"Shuling Dong,&nbsp;Jiayi Sun,&nbsp;Fan Ding,&nbsp;Ji Wu,&nbsp;Ronghua Fan,&nbsp;Li Zhou","doi":"10.1002/chir.70060","DOIUrl":"10.1002/chir.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereoisomeric Separation of Flavonoids by Two-Dimensional Supercritical Fluid Chromatography: Identification of Adequate Chiral Columns and Application to Honey Analysis","authors":"Laurine Réset,&nbsp;Bibi Ousseni,&nbsp;Mélodie Degrelle,&nbsp;Clément De Saint Jores,&nbsp;Caroline West","doi":"10.1002/chir.70058","DOIUrl":"10.1002/chir.70058","url":null,"abstract":"<p>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.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"37 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/chir.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}