{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:08:23Z","timestamp":1783480103723,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["22064020"],"award-info":[{"award-number":["22064020"]}]},{"name":"National Natural Science Foundation of China","award":["21964021"],"award-info":[{"award-number":["21964021"]}]},{"name":"National Natural Science Foundation of China","award":["22174125"],"award-info":[{"award-number":["22174125"]}]},{"name":"National Natural Science Foundation of China","award":["202101AT070101"],"award-info":[{"award-number":["202101AT070101"]}]},{"name":"National Natural Science Foundation of China","award":["202201AT070029"],"award-info":[{"award-number":["202201AT070029"]}]},{"name":"Applied Basic Research Foundation of Yunnan Province","award":["22064020"],"award-info":[{"award-number":["22064020"]}]},{"name":"Applied Basic Research Foundation of Yunnan Province","award":["21964021"],"award-info":[{"award-number":["21964021"]}]},{"name":"Applied Basic Research Foundation of Yunnan Province","award":["22174125"],"award-info":[{"award-number":["22174125"]}]},{"name":"Applied Basic Research Foundation of Yunnan Province","award":["202101AT070101"],"award-info":[{"award-number":["202101AT070101"]}]},{"name":"Applied Basic Research Foundation of Yunnan Province","award":["202201AT070029"],"award-info":[{"award-number":["202201AT070029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Porous organic cages (POCs) are a new subclass of porous materials, which are constructed from discrete cage molecules with permanent cavities via weak intermolecular forces. In this study, a novel chiral stationary phase (CSP) has been prepared by chemically binding a [4 + 6]-type chiral POC (C120H96N12O4) with thiol-functionalized silica gel using a thiol-ene click reaction and applied to HPLC separations. The column packed with this CSP presented good separation capability for chiral compounds and positional isomers. Thirteen racemates have been enantioseparated on this column, including alcohols, diols, ketones, amines, epoxides, and organic acids. Upon comparison with a previously reported chiral POC NC1-R-based column, commercial Chiralpak AD-H, and Chiralcel OD-H columns, this column is complementary to these three columns in terms of its enantiomeric separation; and can also separate some racemic compounds that cannot be separated by the three columns. In addition, eight positional isomers (iodoaniline, bromoaniline, chloroaniline, dibromobenzene, dichlorobenzene, toluidine, nitrobromobenzene, and nitroaniline) have also been separated. The influences of the injection weight and column temperature on separation have been explored. After the column has undergone multiple injections, the relative standard deviations (RSDs) for the retention time and selectivity were below 1.0 and 1.5%, respectively, indicating the good reproducibility and stability of the column for separation. This work demonstrates that POCs are promising materials for HPLC separation.<\/jats:p>","DOI":"10.3390\/molecules28073235","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T01:39:26Z","timestamp":1680658766000},"page":"3235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Preparation of Chiral Porous Organic Cage Clicked Chiral Stationary Phase for HPLC Enantioseparation"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7624-5755","authenticated-orcid":false,"given":"Ya-Nan","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Yu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5401-4035","authenticated-orcid":false,"given":"Jun-Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Xue","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang-Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Ming","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yunnan Normal University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.trac.2012.02.012","article-title":"Recent advances in pharmaceutical separations with supercritical fluid chromatography using chiral stationary phases","volume":"37","author":"Wang","year":"2012","journal-title":"TrAC-Trends Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0021-9673(00)00532-X","article-title":"Separation of enantiomers: Needs, challenges, perspectives","volume":"906","author":"Maier","year":"2001","journal-title":"J. Chromatogr. A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1021\/acs.chemrev.5b00317","article-title":"Efficient separation of enantiomers using stereoregular chiral polymers","volume":"116","author":"Shen","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115709","DOI":"10.1016\/j.trac.2019.115709","article-title":"Recent trends in preparation, investigation and application of polysaccharide-based chiral stationary phases for separation of enantiomers in high-performance liquid chromatography","volume":"122","author":"Chankvetadze","year":"2020","journal-title":"TrAC-Trends Anal. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.chroma.2009.10.022","article-title":"Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases","volume":"1217","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.talanta.2018.03.048","article-title":"A high-performance chiral selector derived from chitosan (p-methylbenzylurea) for efficient enantiomer separation","volume":"185","author":"Tang","year":"2018","journal-title":"Talanta"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Teixeira, J., Tiritan, M.E., Pinto, M.M., and Fernandes, C. (2019). Chiral stationary phases for liquid chromatography: Recent developments. Molecules, 24.","DOI":"10.3390\/molecules24050865"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/(SICI)1521-3773(19980504)37:8<1020::AID-ANIE1020>3.0.CO;2-5","article-title":"Polysaccharide derivatives for chromatographic separation of enantiomers","volume":"37","author":"Okamoto","year":"1998","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0021-9673(96)00137-9","article-title":"Quinine and quinidine derivatives as chiral selectors I. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers","volume":"741","author":"Lindner","year":"1996","journal-title":"J. Chromatogr. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"461075","DOI":"10.1016\/j.chroma.2020.461075","article-title":"Fragment-based design of zwitterionic, strong cation-and weak anion-exchange type mixed-mode liquid chromatography ligands and their chromatographic exploration","volume":"1621","author":"Ferri","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.chroma.2016.07.049","article-title":"Liquid chromatographic enantioseparations on crown ether-based chiral stationary phases","volume":"1467","author":"Hyun","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1021\/acs.analchem.6b00897","article-title":"Engineering thiol\u2013ene click chemistry for the fabrication of novel structurally well-defined multifunctional cyclodextrin separation materials for enhanced enantioseparation","volume":"88","author":"Yao","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.aca.2011.12.063","article-title":"Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography","volume":"718","author":"Wang","year":"2012","journal-title":"Anal. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107606","DOI":"10.1016\/j.cclet.2022.06.029","article-title":"Chiral phenethylamine synergistic tricarboxylic acid modified \u03b2-cyclodextrin immobilized on porous silica for enantioseparation","volume":"34","author":"Li","year":"2022","journal-title":"Chin. Chem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/ac00081a019","article-title":"Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography","volume":"66","author":"Armstrong","year":"1994","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"338861","DOI":"10.1016\/j.aca.2021.338861","article-title":"Modelling approaches for chiral chromatography on polysaccharide-based and macrocyclic antibiotic chiral selectors: A review","volume":"1198","author":"Vanommeslaeghe","year":"2022","journal-title":"Anal. Chim. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1021\/jacs.0c11276","article-title":"Highly stable Zr(IV)-based metal\u2013organic frameworks for chiral separation in reversed-phase liquid chromatography","volume":"143","author":"Jiang","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1039\/D0AY02310H","article-title":"Regulating metal\u2013organic frameworks as stationary phases and absorbents for analytical separations","volume":"13","author":"Meng","year":"2021","journal-title":"Anal. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16903","DOI":"10.1021\/acsami.0c01023","article-title":"Chiral metal\u2013organic framework d-His-ZIF-8@SiO2 core\u2013shell microspheres used for HPLC enantioseparations","volume":"12","author":"Yu","year":"2020","journal-title":"ACS Appl. Mater. Inter."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12104","DOI":"10.1038\/ncomms12104","article-title":"Bottom-up synthesis of chiral covalent organic frameworks and their bound capillaries for chiral separation","volume":"7","author":"Qian","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1039\/D2CC05650J","article-title":"Non-porous silica support covalent organic frameworks as stationary phases for liquid chromatography","volume":"59","author":"Xie","year":"2022","journal-title":"Chem. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"462239","DOI":"10.1016\/j.chroma.2021.462239","article-title":"In situ room-temperature preparation of a covalent organic framework as stationary phase for high-efficiency capillary electrochromatographic separation","volume":"1649","author":"Fu","year":"2021","journal-title":"J. Chromatogr. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1021\/jacs.1c11051","article-title":"Are Highly stable covalent organic frameworks the key to universal chiral stationary phases for liquid and gas chromatographic separations?","volume":"144","author":"Yuan","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"116268","DOI":"10.1016\/j.trac.2021.116268","article-title":"Application of microporous organic networks in separation science","volume":"139","author":"Cui","year":"2021","journal-title":"TrAC-Trends Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s00604-022-05448-6","article-title":"A chiral porous organic polymer COP-1 used as stationary phase for HPLC enantioseparation under normal-phase and reversed-phase conditions","volume":"189","author":"Yang","year":"2022","journal-title":"Microchim. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nmat2545","article-title":"Porous organic cages","volume":"8","author":"Tozawa","year":"2009","journal-title":"Nat. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1002\/anie.201000443","article-title":"Shape-persistent organic cage compounds by dynamic covalent bond formation","volume":"49","author":"Mastalerz","year":"2010","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1021\/acs.accounts.8b00298","article-title":"Porous shape-persistent organic cage compounds of different size, geometry, and function","volume":"51","author":"Mastalerz","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11333","DOI":"10.1039\/D2CC03692D","article-title":"Recent advances in the applications of porous organic cages","volume":"58","author":"Hu","year":"2022","journal-title":"Chem. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1002\/anie.201001517","article-title":"A shape-persistent organic molecular cage with high selectivity for the adsorption of CO2 over N2","volume":"49","author":"Jin","year":"2010","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17556","DOI":"10.1002\/anie.202104555","article-title":"SO2 capture using porous organic cages","volume":"60","author":"He","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/s41929-018-0030-8","article-title":"Encapsulating highly catalytically active metal nanoclusters inside porous organic cages","volume":"1","author":"Yang","year":"2018","journal-title":"Nat. Catal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5544","DOI":"10.1021\/acscatal.1c00587","article-title":"Incorporation of metals and enzymes with porous imine molecule cages for highly efficient semiheterogeneous chemoenzymatic catalysis","volume":"11","author":"Gao","year":"2021","journal-title":"ACS Catal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1039\/C8CC10078K","article-title":"Visible-light triggered selective reduction of nitroarenes to azo compounds catalysed by Ag@organic molecular cages","volume":"55","author":"Chen","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/nmat4035","article-title":"Separation of rare gases and chiral molecules by selective binding in porous organic cages","volume":"13","author":"Chen","year":"2014","journal-title":"Nat. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1021\/jacs.2c00318","article-title":"Highly ion-permselective porous organic cage membranes with hierarchical channels","volume":"144","author":"Xu","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1038\/s41467-021-24042-7","article-title":"Efficient ethylene purification by a robust ethane-trapping porous organic cage","volume":"12","author":"Su","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339376","DOI":"10.1016\/j.aca.2021.339376","article-title":"Fluorescent porous organic cage with good water solubility for ratiometric sensing of gold(III) ion in aqueous solution","volume":"1192","author":"Dai","year":"2022","journal-title":"Anal. Chim. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.aca.2018.11.006","article-title":"Carbon dot-decorated porous organic cage as fluorescent sensor for rapid discrimination of nitrophenol isomers and chiral alcohols","volume":"1050","author":"Lu","year":"2019","journal-title":"Anal. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"125860","DOI":"10.1016\/j.jhazmat.2021.125860","article-title":"Facile room temperature synthesis of ultra-small sized porous organic cages for fluorescent sensing of copper ion in aqueous solution","volume":"416","author":"Dai","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1021\/acsnano.1c08605","article-title":"Enhanced biological imaging via aggregation-induced emission active porous organic cages","volume":"16","author":"Dong","year":"2022","journal-title":"ACS Nano"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130872","DOI":"10.1016\/j.cej.2021.130872","article-title":"Encapsulating metal nanoclusters inside porous organic cage towards enhanced radio-sensitivity and solubility","volume":"426","author":"Liu","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7817","DOI":"10.1021\/acs.analchem.5b01512","article-title":"Homochiral porous organic cage with high selectivity for the separation of racemates in gas chromatography","volume":"87","author":"Zhang","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00604-020-04252-4","article-title":"A hydroxyl-functionalized homochiral porous organic cage for gas chromatographic separations","volume":"187","author":"Li","year":"2020","journal-title":"Microchim. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xie, S.M., Zhang, J.H., Fu, N., Wang, B.J., Hu, C., and Yuan, L.M. (2016). Application of homochiral alkylated organic cages as chiral stationary phases for molecular separations by capillary gas chromatography. Molecules, 21.","DOI":"10.3390\/molecules21111466"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106650","DOI":"10.1016\/j.microc.2021.106650","article-title":"A [3 + 6] prismatic homochiral organic cage used as stationary phase for gas chromatography","volume":"170","author":"Wang","year":"2021","journal-title":"Microchem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/jssc.201900762","article-title":"Recent advances of application of porous molecular cages for enantioselective recognition and separation","volume":"43","author":"Zhang","year":"2020","journal-title":"J. Sep. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1021\/acs.analchem.1c03626","article-title":"Preparation of novel chiral stationary phases based on the chiral porous organic cage by thiol-ene click chemistry for enantioseparation in HPLC","volume":"94","author":"Wang","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5","article-title":"Click chemistry: Diverse chemical function from a few good reactions","volume":"40","author":"Kolb","year":"2001","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1039\/c0cs00066c","article-title":"Application of click chemistry on preparation of separation materials for liquid chromatography","volume":"40","author":"Chu","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7495","DOI":"10.1039\/C6OB01429A","article-title":"Chiral, triformylphenol-derived salen-type [4+6] organic cages","volume":"14","author":"Petryk","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0021-9673(95)00269-S","article-title":"Retention and selectivity of flavanones on homopolypeptide-bonded stationary phases in both normal-and reversed-phase liquid chromatography","volume":"704","author":"Siles","year":"1995","journal-title":"J. Chromatogr. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7144","DOI":"10.1021\/ac201517c","article-title":"Metal-organic framework MIL-101 (Cr) for high-performance liquid chromatographic separation of substituted aromatics","volume":"83","author":"Yang","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1080\/00397910008086933","article-title":"Convenient one-step synthesis of 2-hydroxy-1,3,5-benzenetricarbaldehyde","volume":"30","author":"Anderson","year":"2000","journal-title":"Synth. Commun."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/7\/3235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:10:13Z","timestamp":1760123413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/7\/3235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,4]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["molecules28073235"],"URL":"https:\/\/doi.org\/10.3390\/molecules28073235","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,4]]}}}