The past 10 years of molecular ferroelectrics: structures, design, and properties.

Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc., the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.

Revealing the Polarizations of Molecular Ferroelectrics via SHG Polarimetry at the Nanoscale.

Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.

Rational Design of Molecular Ferroelectrics with Negatively Charged Domain Walls.

Ferroelectric domains and domain walls are unique characteristics of ferroelectric materials. Among them, charged domain walls (CDWs) are a special kind of peculiar microstructure that highly improve conductivity, piezoelectricity, and photovoltaic efficiency. Thus, CDWs are believed to be the key to ferroelectrics' future application in fields of energy, sensing, information storage, and so forth. Studies on CDWs are one of the most attractive directions in conventional inorganic ferroelectric ceramics. However, in newly emerged molecular ferroelectrics, which have advantages such as lightweight, easy preparation, simple film fabrication, mechanical flexibility, and biocompatibility, CDWs are rarely observed due to the lack of free charges. In inorganic ferroelectrics, doping is a traditional method to induce free charges, but for molecular ferroelectrics fabricated by solution processes, doping usually causes phase separation or phase transition, which destabilizes or removes ferroelectricity. To realize stable CDWs in molecular systems, we designed and synthesized an n-type molecular ferroelectric, 1-adamantanammonium hydroiodate. In this compound, negative charges are induced by defects in the I- vacancy, and CDWs can be achieved. Nanometer-scale CDWs that are stable at temperatures as high as 373 K can be "written" precisely by an electrically biased metal tip. More importantly, this is the first time that the charge diffusion of CDWs at variable temperatures has been investigated in molecular ferroelectrics. This work provides a new design strategy for n-type molecular ferroelectrics and may shed light on their future applications in flexible electronics, microsensors, and so forth.

Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia.

Chimeric antigen receptor (CAR) T cells have radically improved the treatment of B cell-derived malignancies by targeting CD19. The success has not yet expanded to treat acute myeloid leukemia (AML). We developed a Sequentially Tumor-Selected Antibody and Antigen Retrieval (STAR) system to rapidly isolate multiple nanobodies (Nbs) that preferentially bind AML cells and empower CAR T cells with anti-AML efficacy. STAR-isolated Nb157 specifically bound CD13, which is highly expressed in AML cells, and CD13 CAR T cells potently eliminated AML in vitro and in vivo. CAR T cells bispecific for CD13 and TIM3, which are upregulated in AML leukemia stem cells, eradicated patient-derived AML, with much reduced toxicity to human bone marrow stem cells and peripheral myeloid cells in mouse models, highlighting a promising approach for developing effective AML CAR T cell therapy.

Carboxymethyl-ß-cyclodextrin and histidine-zeolitic imidazolate framework-8 used for enantioseparation of three basic drugs in open-tubular capillary electrochromatography.

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine-zeolitic imidazolate framework-8 (His-ZIF-8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl-ß-cyclodextrin (CM-ß-CD) as the chiral selector was chemically bonded to the His-ZIF-8@capillary column. The prepared CM-ß-CD@His-ZIF-8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM-ß-CD@capillary column without His-ZIF-8, the CM-ß-CD@His-ZIF-8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs : 0 → 2.29), propranolol (Rs : 0 → 1.69), and atenolol (Rs : 0 → 0.79). His-ZIF-8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day-to-day, and column-to-column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.

In-situ grown metal organic framework synergistic system for the enantioseparation of three drugs in open tubular capillary electrochromatography.

Metal organic frameworks have received great attention as the chiral stationary phase for racemic drug separation because of their fascinating structures and properties. However, the most homochiral metal organic frameworks were constructed by rare and precious chiral organic ligands. In this work, an achiral metal organic framework, together with a natural chiral selector carboxymethyl ß-cyclodextrin built a synergistic separation system in the open tubular capillary electrochromatography. The novel coated columns were developed by inducing metal organic framework nanoparticles to grow on the imidazolyl functional capillary inner wall. The baseline separations of hydroxychloroquine, ofloxacin, and atenolol were achieved in the synergistic separation system. The effects of the concentration of chiral selector, pH, voltage, and the concentration of organic additives were studied. Compared with chiral selector auxiliary bare capillary, the resolutions of three drugs were remarkably improved. The relative standard deviations for the retention time of intraday (n = 6), interday (n = 6), and column-to-column were less than 2.1, 2.6, and 5.2%, respectively. These results demonstrate that affordable synergistic separation systems are prospective for racemic drug enantioseparation in capillary electrochromatography.

USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation.

OBJECTIVE: We aimed to elucidate the mutual regulation mechanism of ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor-1α (HIF1α), and the mechanism they promote the stemness of hepatocellular carcinoma (HCC) cells under hypoxic conditions. DESIGN: Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were established to detect the stemness of HCC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were used to elucidate the mutual regulation mechanism of USP22 and HIF1α. HCC patient samples and The Cancer Genome Atlas data were used to demonstrate the clinical significance. In vivo USP22-targeting experiment was performed in mice bearing HCC. RESULTS: USP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1α. As direct target genes of HIF1α, USP22 and TP53 can be transcriptionally upregulated by HIF1α under hypoxic conditions. In TP53 wild-type HCC cells, HIF1α induced TP53-mediated inhibition of HIF1α-induced USP22 upregulation. In TP53-mutant HCC cells, USP22 and HIF1α formed a positive feedback loop and promote the stemness of HCC. HCC patients with a loss-of-function mutation at TP53 and high USP22 and/or HIF1α expression tend to have a worse prognosis. The USP22-targeting lipopolyplexes caused high tumour inhibition and high sorafenib sensitivity in mice bearing HCC. CONCLUSION: USP22 promotes hypoxia-induced HCC stemness by a HIF1α/USP22 positive feedback loop on TP53 inactivation. USP22 is a promising target for the HCC therapy.

Investigation of the synergistic effect with chiral D-penicillamine functionalized gold nanoparticle as an additive for enantiomeric separation in capillary electrophoresis.

The authors describe a synergistic system for nanoparticle based chiral separation. It is based on the use of a conventional chiral selector hydroxyproyl-ß-cyclodextrin and a kind of gold nanoparticle functionalized with D-penicillamine as an additive. This nanomaterial displays a synergistic effect on the efficiency of the enantioseparation of the chiral drugs amlodipine, tropicamide, and ofloxacin. A comparative study on the enantioseparation capability of three separation systems, viz. (a) single hydroxyproyl-ß-cyclodextrin system, (b) achiral citrate capped gold nanoparticle/ hydroxyproyl-ß-cyclodextrin system, and (c) chiral D-penicillamine functionalized gold nanoparticle/ hydroxyproyl-ß-cyclodextrin system was performed. The results show that the D-penicillamine functionalized gold nanoparticle/hydroxyproyl-ß-cyclodextrin synergistic system has remarkable superiority. The effects of concentrations of D-penicillamine functionalized gold nanoparticle and hydroxyproyl-ß-cyclodextrin, of buffer pH value and concentration, and of applied voltage on the performance of enantioseparation were investigated.

Synthesis, application and molecular modeling study of ionic liquid functionalized lactobionic acid, 3-methyl-1-(3-sulfopropyl)-1H-imidazol-3-ium lactobionate, as a chiral selector in capillary electrophoresis.

Recently, ionic liquids have been widely used for chiral separation. However, several papers have reported the use of ionic liquids as the sole chiral selector. In this work, a novel capillary electrophoresis method using the ionic liquid 3-methyl-1-(3-sulfopropyl)-1H-imidazol-3-ium lactobionate (MSI-LA) as a chiral selector was developed for the enantioseparation of propranolol, metoprolol, bisoprolol, esmolol, atenolol, sotalol, terbutaline and clenbuterol. Method optimization was conducted and the optimized method (40 mM borax buffer, v/v 30% methanol, pH 8.5, 160 mM MSI-LA; +10 kV voltage; capillary temperature, 15 °C; 50 mbar/5 s injection; detection wavelength, 230 nm) was successful for the baseline separation of the eight basic drugs. The LA (lactobionic acid) system was compared. The possible mechanisms of enantioseparation were investigated using molecular modeling. Both the cation and anion of MSI-LA provided interactions between the chiral selector and analytes, and finally enhanced chiral recognition capability compared with LA.

A rapid enantioseparation system of capillary electrochromatography modified by electrostatic adsorption with transfersomes.

Transfersomes were a special kind of nanomaterials with higher deformability and flexibility. A rapid method for coated-column preparation using anionic transfersomes as a coating material by electrostatic adsorption was developed. With carboxymethyl-ß-cyclodextrin added in running buffer as the chiral selector, the capillary electrochromatography enantioseparation system based on the transfersomes-coated column modified by electrostatic adsorption was established for the first time. Propranolol and metoprolol acted as model drugs to evaluate the enantioseparation performance, these two basic drugs achieved baseline separation with satisfactory resolution and selection factor in this transfersomes-electrochromatography system but only partial separation in bare column system. In order to get the optimal separation condition, concentration of chiral selector, buffer pH, and applied voltage were systematically investigated. A rapid and efficient enantioseparation electrochromatography system was established and showed that transfersomes as the stationary phase could efficiently improve chiral separation effect.

Gold nanoparticles-functionalized monolithic column for enantioseparation of eight basic chiral drugs by capillary electrochromatography.

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were prepared, and used as a support to attach gold nanoparticles (AuNP) via Au-S bond. Pepsin, acting as a chiral selector, was linked to the surface of the carboxyl-modified AuNP through a hydrochloride/N-hydroxysuccinimide coupling reaction. The material was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and N2 adsorption-desorption isotherm. The pepsin@AuNP@poly(GMA-co-EDMA) monolith showed preferable enantioselectivity for hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), labetalol (LAB), nefopam (NEF), clenbuterol (CLE), amlodipine (AML) and chlorpheniramine (CHL) in capillary electrochromatography (CEC). These racemic drugs were monitored at the maximum absorption wavelength (220 nm for HXQ, CHQ, HXY, LAB, NEF; 240 nm for AML; 215 nm for CLE, CHL). In comparison with the pepsin@poly(GMA-co-EDMA) monolith loaded with 5 nm AuNP, the pepsin@poly(GMA-co-EDMA) monolith loaded with 13 nm AuNP shows significantly enhanced enantiomeric resolution (HCQ: 0.62 → 3.45; CHQ: 0.60 → 2.11; HXY: 0.49 → 2.30; LAB: 1.03 → 2.45, 1.45 → 3.46, 0 → 0.67; NEF: 0.53 → 1.29; CLE: 0.42 → 0.56; AML: 0 → 0.83; CHL: 0.24 → 0.55). Pepsin concentration, buffer pH value, buffer concentration and applied voltage were investigated in detail with (±) HCQ and (±) HXY as model analytes. The reproducibility of intra-day, inter-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic presentation of the preparation of gold nanoparticles (AuNP) modified.

Gold nanoparticles coated with a tetramethylammonium lactobionate ionic liquid for enhanced chiral differentiation in open tubular capillary electrochromatography: application to enantioseparation of ß-blockers.

A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic ß-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments. Graphical abstractSchematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic ß-blockers.

Enantioseparation of amino alcohol drugs by nonaqueous capillary electrophoresis with a maltobionic acid-based ionic liquid as the chiral selector.

This study deals with the nonaqueous capillary electrophoretic enantioseparation of twenty-two amino alcohol drugs with a maltobionic acid (MA)-based ionic liquid (tetramethylammonium maltobionic acid, TMA-MA) as the novel chiral selector. In consideration of the poor solubility of MA in organic solvents, we managed to transform MA into ionic liquids (ILs) for the first time. Interestingly, this chiral selector exhibited powerful enantioselectivity towards the model analytes in company with boric acid. Systematical experiments were carried out to investigate the influence of concentration of TMA-MA, boric acid and tris (hydroxymethyl) aminomethane (Tris) as well as applied voltage on the enantioseparation. A great majority of enantiomers (except labetalol) were baseline separated under the optimized conditions and the effect of the molecular structure of amino alcohol drugs on the chiral separation was discussed. In addition, electrophoretic experiments, nuclear magnetic resonance (NMR), mass spectrometry (MS) and molecular modeling with the Gaussian program were employed to demonstrate the mechanism of chiral recognition. Based on the formation of an ionic liquid-boric acid-analyte complex, hydrogen binding was mainly responsible for enantioseparation.

Imidazolium-based ionic liquid surfactants as pseudostationary in combination with a chiral selector in micellar electrokinetic chromatography.

In recent years, ionic liquid-based surfactants have drawn more and more attention. As a new promising brand of surfactants, ionic liquid-based surfactants have their unique properties and superior aggregation behavior, which can be introduced as micellar pseudostationary in MEKC mode. In this paper, a novel ionic liquid-based surfactant, 1-butyl-3-methylimidazolum dodecyl sulfate [C4MIm][C12SO4], was synthesized through ion exchange reaction and applied for the first time to form micellar as pseudostationary phase for chiral separation with clindamycin phosphate as chiral selector. As observed, compared with conventional non-ionic liquid anionic surfactant, improved separation of tested drug enantiomers was obtained in the established MEKC system with ionic liquid-based surfactant. Parameters such as concentration of ionic liquid-based surfactants, type and proportion of organic modifier, concentration of chiral selector, and pH of buffer solution were systematically investigated to optimize the ionic liquid-based surfactant MEKC system. Graphical abstract.

Evaluation of an ionic liquid chiral selector based on clindamycin phosphate in capillary electrophoresis.

Recently, increasing attention has been given to the research on chiral ionic liquids (CILs) in chiral separation field; however, only a few literatures focus on the exploration of CILs as the sole chiral selector. In this study, an ionic liquid chiral selector based on antibiotic, namely tetramethylammonium clindamycin phosphate (TMA-CP), was originally synthesized and subsequently utilized for enantioseparation in capillary electrophoresis (CE). Remarkably improved separations of eight racemic analytes were achieved in TMA-CP system in contrast to the clindamycin phosphate (CP) system. The optimal separation conditions were determinated by systematic experiments on several crucial parameters including the type and proportion of organic modifier, CIL concentration, buffer pH, and applied voltage. Additionally, molecular modeling with AutoDock was applied to probe into the chiral recognition mechanism of the ionic liquid chiral selectors, which well corresponded with the experimental results. It is the first time that antibiotic-based ionic liquid was exploited as favorable sole chiral selector in CE, and this strategy has paved a new way for development of novel ionic liquids chiral selectors based on antibiotics. Graphical abstract.

A novel coating method for CE capillary using carboxymethyl-ß-cyclodextrin-modified magnetic microparticles as stationary for electrochromatography enantioseparation.

Magnetic microparticles (MMPs) have been extensively studied and aroused considerable interest in separation science owing to their superior characteristics. In this paper, a novel coated capillary with carboxymethyl-ß-cyclodextrin-functionalized magnetic microparticles (CD-MMPs) as stationary phase was constructed and then applied to establish an open-tubular capillary electrochromatography enantioseparation system. The preparation of the CD-MMP-coated open-tubular column was very convenient because the coating of the magnetic microparticles onto the capillary column could be easily manipulated by an external magnetic field. The preparation conditions of the coated capillary such as magnetic field intensity and coating time are discussed in detail. The new constructed CD-MMP capillary system was applied to separate enantiomers of several racemic drugs. Compared to the uncoated capillary system, obviously preferable separations of tested enantiomers were obtained. Several important parameters affecting the enantioseparation, such as CM-ß-CD concentration, running buffer pH, organic solvent, and applied voltage, were systematically optimized. Furthermore, satisfactory repeatability and chemical stability of this new CD-MMP capillary system were achieved in the experiment. Graphical abstract ᅟ.

Enantioseparation of propranolol, amlodipine and metoprolol by electrochromatography using an open tubular capillary modified with ß-cyclodextrin and poly(glycidyl methacrylate) nanoparticles.

The inner wall of a capillary was coated with glycidyl methacrylate (GMA) to form tentacle-type coating, and poly(glycidyl methacrylate) nanoparticles (PGMA NPs) were then immobilized on the film. Ethanediamine-ß-cyclodextrin as chiral selector was covalently bonded into the PGMA NPs through the ring-open reaction. The materials were characterized by SEM, TEM and FT-IR. The modified column was applied to the enantioseparation of the racemates of propranolol, amlodipine and metoprolol. Compared to a capillary with a single layer of CD-PGMA (without GMA coating) and to a CD-GMA system (without PGMA nanoparticles), the performance of the capillary is strongly improved. The effects of buffer pH value and applied voltage were optimized. Best resolutions (propranolol: 1.27, metoprolol: 1.01 and amlodipine: 2.93) were obtained when using the PGMA-coated capillary system. The run-to-run, day-to-day and column-to-column reproducibility were tested and found to be highly attractive. The new stationary phase is likely to have a large potential and scope in that it may also be applied to chiral separations of other enantiomers, such as amino acids and biogenic amines. Graphical abstract Schematic presentation of the preparation of a capillary column with glycidyl methacrylate (GMA) coating which was then immobilized with poly(glycidyl methacrylate) nanoparticles and ethanediamine-ß-cyclodextrin. This novel open tubular column was applied to construct capillary electrochromatography system for separation of basic racemic drugs.

Open-tubular capillary electrochromatography with ß-cyclodextrin-functionalized magnetic nanoparticles as stationary phase for enantioseparation of dansylated amino acids.

Magnetic nanoparticles (MNPs) modified with ß-cyclodextrin and mono-6-deoxy-6-(1-methylimidazolium)-ß-cyclodextrin tosylate (an ionic liquid), which called MNP-ß-CD and MNP-ß-CD-IL, were coated into the capillary inner wall. Compared to an uncoated capillary, the new systems show good reproducibility and durability. The systems based on the use of MNP-ß-CD or MNP-ß-CD-IL as stationary phases were established for enantioseparation of Dns-modified amino acids. Improved resolutions were obtained for both CEC systems. Primary parameters such as running buffer pH value and applied voltage were systematically optimized in order to obtain optimal enantioseparations. Under the optimized conditions, the capillaries exhibited excellent chiral recognition ability for six Dns-amino acids (the DL-forms of alanine, leucine, lsoleucine, valine, methionine, glutamic acid) and provided a promising way for the preparation of chiral column. Graphical Abstract Schematic presentation of the open-tubular capillary electrochromatography systems with MNP-ß-CD and MNP-ß-CD-IL as stationary phases for enantioseparation of dansylated amino acids.

A monolithic capillary modified with a copoplymer prepared from the ionic liquid 1-vinyl-3-octylimidazolium bromide and styrene for electrochromatography of alkylbenzenes, polycyclic aromatic hydrocarbons, proteins and amino acids.

A monolithic capillary column was prepared by single-step copolymerization of the ionic liquid 1-vinyl-3-octylimidazolium bromide (VOI) and styrene. The VOI and styrene monomers were introduced to provide multiple interaction sites and increase hydrophobicity and aromaticity of the monolithic column, respectively. The effect of porogen ratio, monomer ratio and reaction temperature on permeability was investigated. The resulting column was characterized by scanning electron microscopy, and the results suggest that the column possesses high porosity and good homogeneity. A relatively strong anodic electroosmotic flow was generated over a wide range of pH values (pH 2.0-10.0), and this facilitates the rapid separation of analytes within 12 min. Alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), proteins and amino acids were used to evaluate the performance of the monolithic column under capillary electrochromatography mode by UV detection. Mixed-mode retention mechanisms including hydrophobic interaction, π-stacking, ion-exclusion interaction were observed. The monolithic column exhibits high column efficiency (8.72 × 104 plates∙m-1) and satisfying separation capability (the resolution of four alkylbenzenes: 2.54, 2.86 and 4.62, four PAHs: 2.79, 4.83 and 4.77, three proteins: 4.35 and 2.86, two amino acids: 3.34). Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with ionic liquid and styrene based organic polymer monolithic column for separation of alkylbenzenes, polycyclic aromatic hydrocarbons, proteins and amino acids.

A metal organic framework-functionalized monolithic column for enantioseparation of six basic chiral drugs by capillary electrochromatography.

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.