Similar articles

Abstract: The presence of chirality, a fundamental attribute found in nature, is of great significance in the field of pharmaceutical science. chiral drugs are unique in that their molecular structure is non-superimposable on its mirror image. This stereoisomerism significantly impacts the functionality, metabolic pathway, effectiveness, and safety of chiral medications. The enantiomers of chiral drugs can exhibit diverse pharmacological effects in the human body. As a result, it is essential to separate and purify chiral drugs effectively. Despite the abundance of reports on chiral drug separation membranes, there is a dearth of comprehensive reviews. This paper aims to fill this gap by providing a thorough review from a materials perspective, with a focus on the design and construction of chiral drug separation membranes. Furthermore, it systematically analyzes the separation mechanisms employed by these membranes. The paper also delves into the challenges and prospects related to chiral drug separation membranes, with the intention of imparting valuable insights for further research and development in this field.

手性药物分离膜近期研究进展：设计、机制、挑战及展望

作者：王建宇^1,2,4，褚琴丹^1,4，方传杰^1,4，朱宝库^1,3,4，朱利平^1,3,4
机构：¹浙江大学绍兴研究院，大健康材料分中心，中国绍兴，312000；²凯里学院，理学院，中国凯里，556011；³浙江大学，高分子合成与功能构造教育部重点实验室，中国杭州，310058；⁴浙江大学，教育部膜与水处理技术工程研究中心，中国杭州，310058
概要：手性是自然界普遍存在的一种基本性质，在医药科学领域具有重要意义。手性药物的独特之处在于它们的分子结构互为镜像、不可重合，这种立体异构特性对药物的功能、代谢途径、有效性和安全性产生显著影响。手性药物的对映体可在人体内表现出不同的药理作用，通常一种分子具有良好药效，而其对映体没有药效甚至具有毒性。因此，有效分离和纯化手性药物对映体至关重要。虽然近年来关于手性药物分离膜的研究报道日益丰富，但综述类论文较少。本文从材料角度出发，对手性药物分离膜的近期研究进展进行系统梳理，重点介绍膜材料的种类及其制备方法，总结其分离机制，探讨其面临的挑战和未来发展前景，旨在为该领域的进一步研究和新型膜材料开发提供有益参考和借鉴。

关键词：手性药物；手性分离；分离机制；膜分离

[1]AliI, SuhailM, AlothmanZA, et al., 2018. Stereoselective interactions of profen stereomers with human plasma proteins using nano solid phase micro membrane tip extraction and chiral liquid chromatography. Separation and Purification Technology, 197:336-344.

[2]BewleyCA, SulikowskiGA, YangZJ, et al., 2023. Properties of configurationally stable atropoenantiomers in macrocyclic natural products and the chrysophaentin family. Accounts of Chemical Research, 56(4):414-424.

[3]ChanJY, ZhangHC, NolvachaiY, et al., 2018. Incorporation of homochirality into a zeolitic imidazolate framework membrane for efficient chiral separation. Angewandte Chemie International Edition, 57(52):17130-17134.

[4]ChangCL, QiXY, ZhangJW, et al., 2015. Facile synthesis of magnetic homochiral metal‍–‍organic frameworks for“enantioselective fishing”. Chemical Communications, 51(17):3566-3569.

[5]ChenWB, LiuHX, ChenYT, et al., 2023. Preparation and application of a chiral Am7CD-modified COF composite membrane by interfacial polymerization. Separation and Purification Technology, 323:124406.

[6]ChenXH, LiangR, QinC, et al., 2022. Regulating Co-MOF array films to construct Co₃O₄ in-situ sensors for ultrasensitive and highly selective triethylamine detection. Sensors and Actuators B: Chemical, 368:132147.

[7]ChenXX, SunWW, YangCY, et al., 2020. Preparation of poly L-glutamic acid ester membrane for enantioselective resolution of p-hydroxyphenylglycine. Membrane Science and Technology, 40(1):78-83 (in Chinese).

[8]ChenYL, XiaL, LuZC, et al., 2021. In situ fabrication of chiral covalent triazine frameworks membranes for enantiomer separation. Journal of Chromatography A, 1654:462475.

[9]ConleyKM, GodboutL, WhiteheadMA, et al., 2017. Reversing the structural chirality of cellulosic nanomaterials. Cellulose, 24(12):5455-5462.

[10]CuiYY, YangCX, YanXP, 2020. Thiol-yne click post-modification for the synthesis of chiral microporous organic networks for chiral gas chromatography. ACS Applied Materials & Interfaces, 12(4):4954-4961.

[11]DasS, XuSX, BenT, et al., 2018. Chiral recognition and separation by chirality-enriched metal-organic frameworks. Angewandte Chemie International Edition, 57(28):8629-8633.

[12]DuerinckT, DenayerJFM, 2015. Metal-organic frameworks as stationary phases for chiral chromatographic and membrane separations. Chemical Engineering Science, 124:179-187.

[13]DżygielP, WieczorekPP, 2010. Chapter 3‍–‍Supported liquid membranes and their modifications: definition, classification, theory, stability, application and perspectives. In: Kislik VS (Ed.), Liquid Membranes. Elsevier, Amsterdam, the Netherland, p.73-140.

[14]GaálováJ, YalcinkayaF, CuřínováP, et al., 2020. Separation of racemic compound by nanofibrous composite membranes with chiral selector. Journal of Membrane Science, 596:117728.

[15]GogoiM, GoswamiR, IngolePG, et al., 2020. Selective permeation of L-tyrosine through functionalized single-walled carbon nanotube thin film nanocomposite membrane. Separation and Purification Technology, 233:116061.

[16]GongHX, ZhangSZ, LiuN, et al., 2022. Retarded transport properties of graphene oxide based chiral separation membranes modified with dipeptide. Separation and Purification Technology, 288:120642.

[17]GössiA, RiedlW, SchuurB, 2018. Enantioseparation with liquid membranes. Journal of Chemical Technology & Biotechnology, 93(3):629-644.

[18]GuLN, ChenQB, LiXX, et al., 2020. Enantioseparation processes and mechanisms in functionalized graphene membranes: facilitated or retarded transport? Chirality, 32(6):842-853.

[19]GuoHK, XuXY, LiJQ, et al., 2022. Chemically tailored microporous nanocomposite membranes with multi-channels for intensified solvent permeation. Journal of Membrane Science, 660:120877.

[20]GuoX, WangY, QinYM, et al., 2020. Structures, properties and application of alginic acid: a review. International Journal of Biological Macromolecules, 162:618-628.

[21]HalmschlagB, SteurerX, PutriSP, et al., 2019. Tailor-made poly-‍γ‍-glutamic acid production. Metabolic Engineering, 55:239-248.

[22]HanHD, LiuW, XiaoY, et al., 2021. Advances of enantioselective solid membranes. New Journal of Chemistry, 45(15):6586-6599.

[23]HanZS, ShiW, ChengP, 2018. Synthetic strategies for chiral metal-organic frameworks. Chinese Chemical Letters, 29(6):819-822.

[24]HemasaAL, NaumovskiN, MaherWA, et al., 2017. Application of carbon nanotubes in chiral and achiral separations of pharmaceuticals, biologics and chemicals. Nanomaterials, 7(7):186.

[25]HuangB, LiK, MaQY, et al., 2023. Homochiral metallacycle used as a stationary phase for capillary gas chromatographic separation of chiral and achiral compounds. Analytical Chemistry, 95(35):13289-13296.

[26]HuangCH, GuoZH, ZhengX, et al., 2020. Deformable metal–organic framework nanosheets for heterogeneous catalytic reactions. Journal of the American Chemical Society, 142(20):9408-9414.

[27]HuangYN, ZengH, XieL, et al., 2022. Super-assembled chiral mesostructured heteromembranes for smart and sensitive couple-accelerated enantioseparation. Journal of the American Chemical Society, 144(30):13794-13805.

[28]IijimaSJN, 1991. Helical microtubules of graphitic carbon. Nature, 354(6348):56-58.

[29]JiangYD, ZhangJH, XieSM, et al., 2012. Chiral separation of D,L-tyrosine through nitrocellulose membrane. Journal of Applied Polymer Science, 124(6):5187-5193.

[30]KangZX, XueM, FanLL, et al., 2013. “Single nickel source” in situ fabrication of a stable homochiral MOF membrane with chiral resolution properties. Chemical Communications, 49(90):10569-10571.

[31]KeJ, YangK, BaiXP, et al., 2021. A novel chiral polyester composite membrane: preparation, enantioseparation of chiral drugs and molecular modeling evaluation. Separation and Purification Technology, 255:117717.

[32]KimJH, KimJH, JegalJ, et al., 2003. Optical resolution of α-amino acids through enantioselective polymeric membranes based on polysaccharides. Journal of Membrane Science, 213(1-2):273-283.

[33]KöhlerJEH, HohlaM, RichtersM, et al., 1992. Cyclodextrinderivate als chirale selektoren-untersuchung der wechselwirkung mit (R,S)‍-methyl-2-chlorpropionat durch enantio-selektive gaschromatographie, NMR-spektroskopie und moleküldynamiksimulation. Angewandte Chemie, 104(3):362-364 (in German).

[34]LeekH, ThunbergL, JonsonAC, et al., 2017. Strategy for large-scale isolation of enantiomers in drug discovery. Drug Discovery Today, 22(1):133-139.

[35]LiH, WangLP, YuG, 2021. Covalent organic frameworks: design, synthesis, and performance for photocatalytic applications. Nano Today, 40:101247.

[36]LiHC, HuangQ, LiD, et al., 2018. Generation of a molecular imprinted membrane by coating cellulose acetate onto a ZrO₂-modified alumina membrane for the chiral separation of mandelic acid enantiomers. Organic Process Research & Development, 22(3):278-285.

[37]LiHY, ZhangJL, JiangLL, et al., 2023. Chiral plasmonic Au–Ag core shell nanobipyramid for SERS enantiomeric discrimination of biologically relevant small molecules. Analytica Chimica Acta, 1239:340740.

[38]LiXX, ChenQB, TongXF, et al., 2021. Chiral separation of β‍-cyclodextrin modified graphene oxide membranes with a complete enantioseparation performance. Journal of Membrane Science, 634:119350.

[39]LiuGF, ShengJH, ZhaoYL, 2017. Chiral covalent organic frameworks for asymmetric catalysis and chiral separation. Science China Chemistry, 60(8):1015-1022.

[40]LiuJL, YuanWB, LiCF, et al., 2021. L-cysteine-modified graphene oxide-based membrane for chiral selective separation. ACS Applied Materials & Interfaces, 13(41):49215-49223.

[41]LiuJL, ChuTF, ChengMM, et al., 2023a. Bovine serum albumin functional graphene oxide membrane for effective chiral separation. Journal of Membrane Science, 668:121198.

[42]LiuJL, ZouGZ, HouSF, 2023b. Chiral gold nanoparticles/graphene oxide membranes with ultrahigh and stable permeance for sieving and enantioseparation. Chemical Engineering Journal, 467:143366.

[43]LiuTQ, LiZ, WangJJ, et al., 2021. Solid membranes for chiral separation: a review. Chemical Engineering Journal, 410:128247.

[44]LiuYH, LiuLM, ChenX, et al., 2021. Single-crystalline ultrathin 2D porous nanosheets of chiral metal‍–‍organic frameworks. Journal of the American Chemical Society, 143(9):3509-3518.

[45]LuYZH, ZhangHC, ChanJY, et al., 2019. Homochiral MOF–polymer mixed matrix membranes for efficient separation of chiral molecules. Angewandte Chemie International Edition, 58(47):16928-16935.

[46]LuYZH, ChanJY, ZhangHC, et al., 2021a. Cyclodextrin metal-organic framework-polymer composite membranes towards ultimate and stable enantioselectivity. Journal of Membrane Science, 620:118956.

[47]LuYZH, ZhangHC, ZhuYL, et al., 2021b. Emerging homochiral porous materials for enantiomer separation. Advanced Functional Materials, 31(25):2101335.

[48]LuYZH, ZhangHC, LiuSS, et al., 2022. Precise sieving of chiral molecules by a crosslinked cyclodextrin-cellulose nanofiber composite membrane. Journal of Membrane Science, 663:121016.

[49]LuoH, BaiXP, LiuHX, et al., 2022. β-Cyclodextrin covalent organic framework modified-cellulose acetate membranes for enantioseparation of chiral drugs. Separation and Purification Technology, 285:120336.

[50]LvS, MaCB, CongHL, et al., 2022. Synthesis of 3,5-dichlorobenzene isocyanate-derived β‍-cyclodextrin and 3,‍5-dimethyl phenyl isocyanate-derivedβ‍-cyclodextrin chiral stationary phases and their applications in the separation of chiral compounds. Separation and Purification Technology, 294:121147.

[51]MaMC, LuXF, GuoY, et al., 2022. Combination of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs): recent advances in synthesis and analytical applications of MOF/COF composites. TrAC Trends in Analytical Chemistry, 157:116741.

[52]MaruyamaA, AdachiN, TakatsukiT, et al., 1990. Enantioselective permeation of α-amino acid isomers through poly(amino acid)‍-derived membranes. Macromolecules, 23(10):2748-2752.

[53]MatencioA, Navarro-OrcajadaS, García-CarmonaF, et al., 2020. Applications of cyclodextrins in food science. A review. Trends in Food Science & Technology, 104:132-143.

[54]MiaoL, YangY, TuYY, et al., 2017. Chiral resolution by polysulfone-based membranes prepared via mussel-inspired chemistry. Reactive and Functional Polymers, 115:87-94.

[55]Navarro-SánchezJ, Argente-GarcíaAI, Moliner-MartínezY, et al., 2017. Peptide metal‍–‍organic frameworks for enantioselective separation of chiral drugs. Journal of the American Chemical Society, 139(12):4294-4297.

[56]NobleRD, 1992. Generalized microscopic mechanism of facilitated transport in fixed site carrier membranes. Journal of Membrane Science, 75(1-2):121-129.

[57]NovoselovKS, GeimAK, MorozovSV, et al., 2004. Electric field effect in atomically thin carbon films. Science, 306(5696):666-669.

[58]PanXR, JiJH, ZhangNN, et al., 2020. Research progress of graphene-based nanomaterials for the environmental remediation. Chinese Chemical Letters, 31(6):1462-1473.

[59]PetrusováZ, SloukaZ, VobeckáL, et al., 2023. Microreaction and membrane technologies for continuous single-enantiomer production: a review. Catalysis Reviews, 65(3):773-821.

[60]PintoMMM, FernandesC, TiritanME, 2020. Chiral separations in preparative scale: a medicinal chemistry point of view. Molecules, 25(8):1931.

[61]QiuX, KeJ, ChenWB, et al., 2022. β‍-cyclodextrin-ionic liquid functionalized chiral composite membrane for enantioseparation of drugs and molecular simulation. Journal of Membrane Science, 660:120870.

[62]QiuX, ChenWB, ChenYT, et al., 2023. Separation of chiral drugs through dual chiral ionic liquid functionalized composite membrane and study on chiral recognition mechanism. Journal of Membrane Science, 687:122087.

[63]ReaR, de AngelisMG, BaschettiMG, 2019. Models for facilitated transport membranes: a review. Membranes, 9(2):26.

[64]RenYF, YuF, LiXG, et al., 2021. Recent progress on adsorption and membrane separation for organic contaminants on multi-dimensional graphene. Materials Today Chemistry, 22:100603.

[65]SanganyadoE, LuZJ, FuQG, et al., 2017. Chiral pharmaceuticals: a review on their environmental occurrence and fate processes. Water Research, 124:527-542.

[66]ShiDC, YuX, FanWD, et al., 2021. Polycrystalline zeolite and metal-organic framework membranes for molecular separations. Coordination Chemistry Reviews, 437:213794.

[67]SoleymaniE, AlinezhadH, DarvishGM, et al., 2017. Enantioseparation performance of CNTs as chiral selectors for the separation of ibuprofen isomers: a dispersion corrected DFT study. Journal of Materials Chemistry B, 5(33):6920-6929.

[68]SonSH, JegalJ, 2007. Chiral separation of D,L-serine racemate using a molecularly imprinted polymer composite membrane. Journal of Applied Polymer Science, 104(3):1866-1872.

[69]SongLJ, PanM, ZhaoR, et al., 2020. Recent advances, challenges and perspectives in enantioselective release. Journal of Controlled Release, 324:156-171.

[70]SuttipatD, ButchaS, AssavapanumatS, et al., 2020. Chiral macroporous MOF surfaces for electroassisted enantioselective adsorption and separation. ACS Applied Materials & Interfaces, 12(32):36548-36557.

[71]TanHX, LiuTQ, ZhangX, et al., 2020. Preparation of vortex porous graphene chiral membrane for enantioselective separation. Analytical Chemistry, 92(20):13630-13633.

[72]TangB, WangW, HouHP, et al., 2022. A β-cyclodextrin covalent organic framework used as a chiral stationary phase for chiral separation in gas chromatography. Chinese Chemical Letters, 33(2):898-902.

[73]TangS, MeiXM, ChenW, et al., 2018. A high-performance chiral selector derived from chitosan (p-methylbenzylurea) for efficient enantiomer separation. Talanta, 185:42-52.

[74]UlbrichtM, 2004. Membrane separations using molecularly imprinted polymers. Journal of Chromatography B, 804(1):113-125.

[75]van der EntA, van’t RietA, KeurentjesJTF, et al., 2001. Design criteria for dense permeation-selective membranes for enantiomer separations. Journal of Membrane Science, 185(2):207-221.

[76]VedovelloP, Marcio ParanhosC, FernandesC, et al., 2022a. Chiral polymeric membranes: recent applications and trends. Separation and Purification Technology, 280:119800.

[77]VedovelloP, CostaJAS, FernandesC, et al., 2022b. Evaluation of chiral separation by Pirkle-type chiral selector based mixed matrix membranes. Separation and Purification Technology, 289:120722.

[78]WangBM, WangL, ZhaZ, et al., 2022. Hydrogen-bonded, hierarchically structured single-component chiral poly(ionic liquid) porous membranes: facile fabrication and application in enantioselective separation. CCS Chemistry, 4(9):2930-2937.

[79]WangFMJ, HeKQ, WangRX, et al., 2024. A homochiral porous organic cage-polymer membrane for enantioselective resolution. Advanced Materials, 36(29):2400709.

[80]WangJF, JinXX, LiCH, et al., 2019. Graphene and graphene derivatives toughening polymers: toward high toughness and strength. Chemical Engineering Journal, 370:831-854.

[81]WangY, ZhangYM, YuC, et al., 2024. Chiral covalent organic frameworks as promising materials for racemate resolution. ACS Applied Polymer Materials, 6(15):8706-8720.

[82]WangZH, ChenZ, ZhengZD, et al., 2023. Nanocellulose-based membranes for highly efficient molecular separation. Chemical Engineering Journal, 451:138711.

[83]WengXL, BaezJE, KhitererM, et al., 2015. Chiral polymers of intrinsic microporosity: selective membrane permeation of enantiomers. Angewandte Chemie International Edition, 54(38):11214-11218.

[84]XieR, ChuLY, DengJG, 2008. Membranes and membrane processes for chiral resolution. Chemical Society Reviews, 37(6):1243-1263.

[85]XuJ, XueYF, JianXX, et al., 2022. Understanding of chiral site-dependent enantioselective identification on a plasmon-free semiconductor based SERS substrate. Chemical Science, 13(22):6550-6557.

[86]XuJ, WangM, LiMM, et al., 2023. Paper-based chiral biosensors using enzyme encapsulation in hydrogel network for point-of-care detection of lactate enantiomers. Analytica Chimica Acta, 1279:341834.

[87]YangLL, SunJW, 2022. Ammonia to chiral α‍-‍amino acid. Nature Catalysis, 5(6):471-472.

[88]YeQ, LiJ, HuangYY, et al., 2023. Preparation of a cyclodextrin metal-organic framework (CD-MOF) membrane for chiral separation. Journal of Environmental Chemical Engineering, 11(2):109250.

[89]YooS, ParkQH, 2019. Metamaterials and chiral sensing: a review of fundamentals and applications. Nanophotonics, 8(2):249-261.

[90]YuC, YinBH, WangY, et al., 2023. Advances in membrane-based chiral separation. Coordination Chemistry Reviews, 495:215392.

[91]YuXX, WangYH, YangQW, et al., 2020. De novo synthesis of microspheical cellulose 3,‍5-dichlorophenylcarbamates: an organic-inorganic hybrid chiral stationary phase for enantiospearation. Separation and Purification Technology, 238:116480.

[92]YuYY, XuNY, ZhangJH, et al., 2020. Chiral metal–organic framework D-His-ZIF-8@SiO₂ core‍–‍shell microspheres used for HPLC enantioseparations. ACS Applied Materials & Interfaces, 12(14):16903-16911.

[93]YuanC, WuXW, GaoR, et al., 2019. Nanochannels of covalent organic frameworks for chiral selective transmembrane transport of amino acids. Journal of the American Chemical Society, 141(51):20187-20197.

[94]ZengLL, YiQ, LiuQ, et al., 2021. Development of a new method and device for chiral drug enrichment and enantioseparation: multiple-phase extraction and in situ coupling of crystallization. Separation and Purification Technology, 257:117884.

[95]ZengLL, PengXH, PengL, et al., 2022. Green and efficient enantioseparation of amlodipine using a novel pairwise crystallization-circulating extraction coupling method aimed at in situ reuse of mother liquor. Separation and Purification Technology, 299:121774.

[96]ZhangGH, FuKQ, XiJB, et al., 2019. Structure screening and performance restoration of chiral separation materials based on chitosan derivatives. Carbohydrate Polymers, 214:259-268.

[97]ZhangJH, XieSM, ChenL, et al., 2015. Homochiral porous organic cage with high selectivity for the separation of racemates in gas chromatography. Analytical Chemistry, 87(15):7817-7824.

[98]ZhangQ, RenSR, LiA, et al., 2021. Tartaric acid-based ionic liquid-type chiral selectors: effect of cation species on their enantioseparation performance in capillary electrophoresis. Separation and Purification Technology, 275:119228.

[99]ZhangQ, ZhaoXB, ChengY, et al., 2023. Multilayer-functionalized molecularly imprinted nanocomposite membranes for efficient acteoside separation. Microporous and Mesoporous Materials, 348:112345.

[100]ZhangSY, ChenX, SunLD, et al., 2020. β‍-‍Cyclodextrin-self-assembled nanochannel membrane for the separation of chiral drugs. ACS Applied Nano Materials, 3(5):4351-4356.

[101]ZhangSY, ZhouJ, LiHB, 2022. Chiral covalent organic framework packed nanochannel membrane for enantioseparation. Angewandte Chemie International Edition, 61(27):e202204012.

[102]ZhangXM, TuZH, LiH, et al., 2017. Supported protic-ionic-liquid membranes with facilitated transport mechanism for the selective separation of CO₂. Journal of Membrane Science, 527:60-67.

[103]ZhangYF, XuZH, ZhangTT, et al., 2020. Self-assembly of robust graphene oxide membranes with chirality for highly stable and selective molecular separation. Journal of Materials Chemistry A, 8(33):16985-16993.

[104]ZhangYQ, TanX, LiuX, et al., 2019. Fabrication of multilayered molecularly imprinted membrane for selective recognition and separation of artemisinin. ACS Sustainable Chemistry & Engineering, 7(3):3127-3137.

[105]ZhaoH, WangLR, LiuGH, et al., 2023. Hollow Rh-COF@COF S-scheme heterojunction for photocatalytic nicotinamide cofactor regeneration. ACS Catalysis, 13(10):6619-6629.

[106]ZhaoHW, CuiXF, YuanLM, 2024. Chiral separation of d,l-phenylglycine by cellulose triacetate membranes. Journal of Applied Polymer Science, 141(26):e55571.

[107]ZhaoX, WongM, MaoCY, et al., 2014. Size-selective crystallization of homochiral camphorate metal‍–‍organic frameworks for lanthanide separation. Journal of the American Chemical Society, 136(36):12572-12575.

[108]ZhouZZ, LiD, WuQG, et al., 2020. The investigation of the reversed enantio-selectivity by an alpha-cyclodextrin doped thin film composite membrane. Chemical Engineering Research and Design, 160:437-446.

[109]ZhuQJ, CaiZW, ZhouPL, et al., 2023. Recent progress of membrane technology for chiral separation: a comprehensive review. Separation and Purification Technology, 309:123077.