Enantioseparation Performance Research Articles

Synergistic enantioseparation system based on anovel nanomaterial synthesized by chiral metal-organic framework and chiral molecularly imprinted polymer in capillary electrochromatography.

Acapillary electrochromatography (CEC) synergistic enantioseparation system based on a novel nanomaterial synthesized by chiral molecularly imprinted polymers (CMIPs) and chiral metal organic frameworks (CMOFs) was developed. Compared with CMIPs and CMOFs alone, the enantioseparation performance of ofloxacin (OFL)of the CEC with the novel nanomaterial as stationary phases was greatly improved. CMOFs with chiral recognition ability have synergize with CMIPs to greatly improve the chiral selectivity of the novel stationary phases in CEC.As a proof-of-concept demonstration, a coated capillary column was prepared by a sol-gel method using S-OFL (template), iron-based cyclodextrin MOF (Fe-CD-MOF, a CMOF), 3-aminopropyltriethoxysilane (functional monomer), and tetraethyl orthosilicate (cross-linking agent). Then, the newly constructed CEC system has excellent enantioseparation performance of OFL with a resolution of 3.92. Finally, computerized molecular docking revealed that the difference in the binding ability of Fe-CD-MOF to ofloxacin enantiomers was an important mechanism for CEC chiral separation. This innovative development of synergistic chiral stationary phases based on CMOFs and CMIPs creates a highly efficient potential direction for enantiomer separation.

Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78. To further explore the effect of DNFs on enantioseparation, different types of chiral columns including DNA strand containing the complementary sequence of the template (DCT)-modified CSMs, DNF2-modified CSMs, and DNF3-modified CSMs were prepared as well. It was observed that DNF-modified CSMs displayed better chiral separation ability compared with DCT-based columns. The intra-day and inter-day repeatability of model analytes' retention time and resolution kept desirable relative standard deviation values of less than 8.28%. DNF2/DNF3-modified CSMs were able to achieve baseline separation of atenolol, propranolol, 2'-deoxyadenosine, and nefopam enantiomers. Molecular docking simulations were performed to investigate enantioselectivity mechanisms of DNA sequences for enantiomers. To indicate the successful construction of DNFs and DNF-modified CSMs, various charaterization approaches including scanning electron microscopy, agarose gel electrophoresis, dynamic light scattering analysis, electroosmotic flow, and Fourier-transform infrared spectroscopy were utilized. Moreover, the enantioseparation performance of DNF-modified CSMs was characterized in terms of sample volume, applied voltage, and buffer concentration. This work paves the way to applying DNF-based capillary electrochromatography microsystems for chiral separation.

Maltodextrin-modified graphene oxide composite membrane applied to the enantioseparation of amino acids

The separation of enantiomers using chiral membranes has garnered much research interest. In this study, the enantioseparation of amino acids using chiral membranes, namely graphene oxide-ethylenediamine-maltodextrin (GO-EDA-MD) and GO-EDA-hydroxypropyl-MD (GO-EDA-HP-MD), was evaluated. HP-MD and MD were investigated as chiral selectors due to their inherent chirality. Various characterization techniques, including atomic force microscopy, Fourier transform infrared spectrometry, field emission scanning electron microscopy, water contact angle analysis, tensile properties, and thermal gravimetric analysis were employed to analyze the membrane structures. The evaluation of enantioseparation performance was conducted by employing tryptophan, phenylalanine, and tyrosine enantiomers. Optimal conditions for enantiomer separation were achived using a GO-EDA-HP-MD chiral composite (1.75 wt%), a feed concentration of 10 mg/L for each enantiomer, a separation time of 15 min, and a membrane effective surface area of 1.0 cm2. Also, the bovine serum albumin rejection was 90.0 %, and the water flux reached 37.1 L m−2 h−1. The highest enantiomeric excess (ee.%) values were 46.33 %, 76.97 %, and 73.04 % for tryptophan, phenylalanine, and tyrosine, respectively. The impact of voltage on ee.% and substance flux was also explored. This membrane was able to separate enantiomers successfully.

Enantiomeric analysis of chiral phenyl aromatic compounds by coated capillary electrochromatography based on aMOF-on-MOF stationary phase.

Chiral phenyl aromatic compounds (CPACs) are widely used in drug development, food/cosmetic production, and other organic synthesis processes, and their different enantiomers have distinct physiological activities and application differences. A double-layer metal-organic framework composite (MOF-on-MOF) was obtained by in situ synthesis of chiral metal-organic framework (CMOM-3S) on the surface of an iron-based metal-organic framework (NH2-MIL-101(Fe)). According to ourinvestigation, MOF-on-MOF composite was for the first time applied tothe stationary phase of capillary electrochromatography (CEC), and enantioseparations of eight CPACs were accomplished. Compared with single CMOM-3S, the enantioseparation performance of the coated capillary columns based on NH2-MIL-101(Fe)@CMOM-3S was improved by 34.07 ~ 720.0%. The R-/S-mandelic acid in actual sample (apricot leaves) was detected by the newly CEC system to be 0.0118mgmL-1 and 0.0523mgmL-1, respectively. The spike recoveries were 96.60 ~ 104.7%, indicating its good stability and accuracy. In addition, the selective adsorption capacity of MOF-on-MOF composites was verified by adsorption experiments.

Chiral metal-organic frameworks grown in situ for monolithic capillary electrochromatographic enantioseparation.

Chiral metal-organic frameworks (CMOFs) with chiral selectivity are one of the high-quality stationary phases for capillary electrochromatography (CEC). However, there is a problem of unsatisfactory enantioseparation performance of capillary columns due to insufficient loading. In this work, a lamellar CMOF (Cu-TC) was grown in situ on the surface of the monolith in a capillary monolithic column to obtain a Cu-TC@monolithic column. The CEC system constructed based on the Cu-TC@monolithic column shows a satisfactory chiral separation performance. Compared with the Cu-TC-based coated column (Cu-TC@coated column), the enantioseparation performance of the CEC system based on the Cu-TC@monolithic column was greatly improved, and the resolutions (Rs) of the model analytes were increased by 80-500%. In addition, the effects of experimental conditions such as the number of cycles of Cu-TC in situ growth, buffer concentration, buffer pH, organic solvent addition and applied voltage on the performance of CEC were also investigated. Finally, the chiral selection mechanism of the stationary phase was explored by selective adsorption experiments. The present work provides a new idea for the development of capillary stationary phases, which has great potential considering the diversity of CMOFs.

A free carboxyl-decorated metal-organic framework with 3D helical chirality for highly enantioselective recognition

With the judicious selection of a designed polycarboxylate derived from L-phenylalanine, (S)-5-(((1-carboxy-2-phenylethyl)amino)methyl)isophthalic acid (H3L), a novel homochiral metal-organic framework decorated with a free carboxyl, {[Cu2(HL)2(bipy)]∙2H2O}n (Cu-MOF), has been designed and synthesized in a solvothermal process. The result of single crystal X-ray diffraction analysis showed that Cu-MOF had the character of a three-dimensional structure with helical chirality. As we expected, in Cu-MOF, one accessible free carboxylic acid group on H3L pointed toward the spiral channels, and the other two –COOH groups were utilized in bonding. The enantioseparation performance of Cu-MOF was thoroughly investigated and the results showed that Cu-MOF can specifically recognize S-1-(1-naphthyl) ethanol (S-NE) with enantiomeric excess (ee) value of 99.35 %, which was much higher than the other three racemates. The appropriate size together with suitable interaction sites played an important role in enantioseparations. Inspired by the excellent chiral recognition effects towards S-NE, the chiral recognition mechanism was experimentally clarified. A fully agreement observed in 13C CP MAS NMR analysis as well as the X-ray photoelectron spectroscopy (XPS) determination revealed that a strong hydrogen bonding interaction forces existed between the hydroxyl of the optical S-NE and the decorated –COOH in the chiral framework. The control experiment further identified the decisive role of the uncoordinated carboxyl group in Cu-MOF. In addition, the strong intermolecular off-set π-π interactions between the phenyl ring involved with the coordinated COO− groups in Cu-MOF and the naphthyl ring of S-NE, was the another important factor for the specifical enantioseparation of S-enantiomer. On the basis of strong intermolecular hydrogen bonding, NE racemates were enantioselective discriminated and enantiomeric purity can be determined by means of Raman scattering spectroscopy.

Separation of chiral drugs through dual chiral ionic liquid functionalized composite membrane and study on chiral recognition mechanism

With the increase of demand for single enantiomer drugs, chiral separation methods have been rapidly developed. Benefiting from the characteristics of simple preparation, low equipment requirement, continuous operation and easy scale-up, membrane separation method has great potential in realizing large-scale separation of chiral drugs. In this study, by means of ion exchange, three different amino acids were combined with mono-6-deoxy-6-(3-benzylimidazolium)-β-cyclodextrin ([β-CD-BIM]) to synthesize three dual chiral ionic liquids: [β-CD-BIM][L-Cys], [β-CD-BIM][L-Asp] and [β-CD-BIM][L-Lys]. Then, they were introduced into cellulose acetate membrane by interfacial polymerization to fabricate chiral composite membrane for enantioseparation. In order to improve the separation effect of the composite membrane for chiral molecule, the filtration conditions were investigated and optimized. Under the optimal conditions, for the chiral composite membrane applying [β-CD-BIM][TsO], [β-CD-BIM][L-Cys], [β-CD-BIM][L-Asp] and [β-CD-BIM][L-Lys], the e.e.% of racemic mandelic acid was 33.9%, 47.9%, 31.3% and 60.4% respectively, and the e.e.% obtained for racemic naproxen was 5.5%, 10.3%, 5.7% and 8.7%, individually. Finally, the separation mechanism of different dissociation form for chiral molecule and the recognition mechanism of different chiral ionic liquids were studied by molecular simulation. These findings reveal the excellent enantioseparation performance of prepared chiral membrane, providing a new perspective on the design of chiral membranes.

A novel pillar[3]trianglimine macrocycle with a deep cavity used as a chiral selector to prepare a chiral stationary phase by thiol-ene click reaction for enantioseparation in high-performance liquid chromatography.

A chiral pillar[3]trianglimine (C60 H72 N6 O6 ) with a deep cavity has been developed as a chiral selector and bonded to thiolated silica by thiol-ene click reaction to fabricate a novel chiral stationary phase for enantioseparation in high-performance liquid chromatography. The enantioseparation performance of the fabricated chiral stationary phase has been evaluated by separating various racemic compounds, including alcohols, esters, amines, ketones, amino acids, and epoxides, in both normal-phase and reversed-phase elution modes. In total, 14 and 17 racemates have been effectively separated in these two separation modes, respectively. In comparison with two widely used chiral columns (Chiralcel OD-H and Chiralpak AD-H), our novel chiral stationary phase offered good chiral separation complementarity, separating some of the tested racemates that could not be separated or were only partially separated on these two commercial columns. The influences of analyte mass, mobile phase composition, and column temperature on chiral separation have been investigated. Good repeatability, stability, and column-to-column reproducibility of the chiral stationary phase for enantioseparation have been observed. After the fabricated column had been eluted up to 400 times, the relative standard deviations (n=5) of resolution (Rs) and retention time of the separated analytes were<0.39% and<0.20%, respectively. The relative standard deviations (n=3) of Rs and retention time for column-to-column reproducibility were<4.6% and<5.2%, respectively. This study demonstrated that the new chiral stationary phase has great prospects for chiral separation in high-performance liquid chromatography.

Optimization of the regioselective synthesis of mixed cellulose 3,5-dimethylphenyl and α-phenylethyl carbamate selectors as separation phases for chiral HPLC

Regioselective tritylation and carbonate aminolysis were employed in this work to synthesize cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate)-type chiral selectors. We evaluated and optimized the critical aspects of regioselective tritylation and detritylation at C6 of the glucopyranose units of the polysaccharide backbone. The advantage of using cellulose II in comparison to cellulose I for tritylation was analyzed and the detritylation time was determined by a fast and simple thin-layer chromatography method. Optimization of both tritylation and detritylation was accompanied by a combination of analytical techniques. Oxycarbonylation with phenyl chloroformate was used to introduce a reactive phenyl carbonate moiety at C6 of the intermediate cellulose 2,3-bis(3,5-dimethylphenyl carbamate), which was subsequently converted to the respective cellulose 6-(α-phenylethyl carbamate) derivative by aminolysis with enantiopure (R)- or (S)-α-phenylethylamine. The starting material, intermediates, and target cellulose derivatives were comprehensively analytically characterized by ATR-FTIR, solid- and liquid-state 13C NMR, GPC, and elemental analysis. With the optimized protocol, it became possible to obtain cellulose carbamate-type chiral selectors through carbonate aminolysis with simple and commercially available primary amines instead of reaction with isocyanate reagents. The enantioseparation performance of the obtained chiral selectors was evaluated against cellulose tris(3,5-dimethylphenyl carbamate) as a reference selector with a selection of chiral analytes.Graphical abstract

Use of chiral ionic liquid as additive for synergistic enantioseparation of basic drugs in capillary electrophoresis

This work presents a synergistic system for enantioseparation in capillary electrophoresis (CE) with a chiral ionic liquid (CIL) based on D-10-camphorsulfonic acid as additive and carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral selector. The proposed method showed excellent enantioseparation performance towards sixteen chiral drugs. In contrast to the single CM-β-CD system, the notably improved resolution (Rs) and selectivity factor (α) of model drugs were observed in synergistic system. Several key parameters such as CIL concentration, CM-β-CD concentration, buffer pH and separation voltage were investigated, after which Statistical Product and Service Solutions (SPSS) was used to prove the potential synergistic effect. The nuclear magnetic resonance (NMR) results further demonstrated the function of the CIL and the superiority of synergistic system. Finally, chiral impurity determination of chlorpheniramine maleate sample was successfully carried out using the established method.

Immobilization of a cellulose carbamate-type chiral selector onto silica gel by alkyne-azide click chemistry for the preparation of chiral stationary chromatography phases

A new synthesis strategy for the preparation of cellulose derivative-based chiral selectors and the subsequent mild immobilization onto pre-functionalized silica gel are introduced, utilizing Cu(I)-catalyzed alkyne-azide Huisgen cycloaddition (“click”) chemistry. A cellulose 3,5-dimethylphenyl carbamate derivative carrying propynyl carbamate groups was prepared by a combination of carbonate aminolysis and isocyanate chemistry. For immobilization, 3-azidopropyl-functionalized silica gel as an inert carrier was used, synthesized via a 3-chloropropyl intermediate. The chiral selector, as well as the inorganic/organic hybrid materials (silica gel/chiral selector), were comprehensively characterized by ATR-FTIR, solid-state 13C and 29Si NMR, liquid-state NMR, GPC, TGA, and elemental analysis. The enantioseparation performance of the immobilized-type chiral stationary phase was evaluated by HPLC with a set of representative chiral test analytes and different eluents and compared to a respective coated-type (=non-covalently bound) chiral stationary phase carrying the same selector quality and quantity on the same silica gel matrix. The immobilization did not adversely affect the chiral separation performance; on the contrary, in some chromatographic separations the immobilized-type chiral stationary phase surprisingly even surpassed the coated reference material.Graphical abstract

Synthesis by carbonate aminolysis and chiral recognition ability of cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) selectors

Novel chiral selectors based on cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) were regioselectively synthesized by carbonate aminolysis and isocyanate chemistry. By oxycarbonylation with phenyl chloroformate, carbamoylation with 3,5-dimethylphenyl isocyanate, and subsequent aminolysis of the previously introduced reactive carbonate moiety at C6 with enantiopure (R)-or (S)-α-phenylethylamine, chiral selectors have been obtained, which regioselectively carry two different phenyl carbamate substituents. The cellulose derivatives were comprehensively characterized by ATR-FTIR, solid-state NMR, GPC, and elemental analysis. In parallel, 3-aminopropyl-functionalized silica gel as an inert carrier material for the chiral selectors was prepared and the obtained coated-type chiral stationary phases were characterized by both solid-state 29Si NMR, 13C NMR, and elemental analysis. The enantioseparation performance of the chiral selectors was studied and compared to cellulose tris(3,5-dimethylphenyl carbamate) as a reference. With this protocol in hand, certain shortcomings of conventional approaches towards the regioselective synthesis of polysaccharide-based chiral selectors were overcome, such as the limitation to standard isocyanate reagents, being able to apply now the whole wealth of commercially available (chiral) primary and also secondary alkylamines instead.Graphical abstract

β-Cyclodextrin-ionic liquid functionalized chiral composite membrane for enantioseparation of drugs and molecular simulation

With the development of pharmaceutical field, the demand for single enantiomer drugs is gradually increasing. Recently, chiral membrane separation technology has great potential in the field of enantioseparation due to its simple preparation, continuous operation and easy scale-up. In this study, a novel β-cyclodextrin-ionic liquid thin film composite membrane (β-CD-IL TFCM) was fabricated by interfacial polymerization method to achieve the enantioseparation of chiral drugs. Various fabrication conditions of the membrane were optimized with tryptophan as a model molecule to improve its enantioselectivity. Under optimal fabrication conditions, the percent enantiomeric excess (e.e.%) of tryptophan was 100.0% and the solute flux (JS) was 8.0 nmol cm−2 h−1. Enantioseparation of various chiral drugs was achieved using β-CD-IL TFCM, including propranolol (e.e.% = 73.4%), warfarin (e.e.% = 11.4%), metoprolol (e.e.% = 3.4%), ibuprofen (e.e.% = 17.8%) and terbutaline (e.e.% = 3.3%). In addition, molecular docking simulation was applied to investigate the separation mechanism of chiral drugs, demonstrating that multiple interactions promote the separation of drug enantiomers. These results reveal the excellent enantioseparation performance of β-CD-IL TFCM, which has a wide prospect in realizing industrial application of chiral membranes.

Investigation on improvement of enantioseparation in capillary electrophoresis based on maltodextrin by chiral ionic liquids.

Taking advantage of chiral ionic liquids, this study deals with the improvement of the enantioseparation performance of a traditional chiral selector (maltodextrin) in capillary electrophoresis. Herein, two polyhydroxy compound-based chiral ionic liquids, namely tetramethylammonium-D-gluconic acid and tetramethylammonium-shikimic acid were designed and utilized as additives for chiral separation for the first time. The synergistic systems provided much better enantioseparations of twelve model drugs compared to the single maltodextrin system. These model analytes contained analgesics, antidepressants, antiallergic drugs, antifungal drugs, antihypertensive drugs, and antiparkinsonian drugs. After optimizing the separation conditions, the chiral recognition mechanism was probed by means of ultraviolet spectroscopy, nuclear magnetic resonance, and molecular modeling. The results of spectroscopic and computational analyses were in good consistency with enantioseparation outcomes. Finally, the proposed method was successfully used for the determination of the enantiomeric purity of duloxetine hydrochloride.

Zeolitic imidazolate framework-67-modified open-tubular column with cyclodextrin for enantioseparation in capillary electrochromatography.

The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co2+ under ambient temperature. His-ZIF-67 was bonded via a glycidyl methacrylate copolymer to the internal surface of capillary and then functionalized with the NH2 -β-cyclodextrin (NH2 -β-CD). The materials were characterized by field emission scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherm, X-ray diffraction, and X-ray photoelectron spectroscopy. In comparison with the NH2 -β-CD@capillary, the NH2 -β-CD@His-ZIF-67@capillary-coated column shows significantly enhanced resolution for chiral molecules. The NH2 -β-CD@His-ZIF-67@capillary column achieved the baseline separation of amlodipine and metoprolol (the resolution of amlodipine: 1.70; metoprolol: 1.50) and the partial separation of atenolol and propranolol (the resolution of atenolol: 1.03; propranolol: 0.60). These were attributed to the histidine modification and the features of ZIF-67, including an excellent surface area and the abundant porosity. The pH and proportion of organic modifier in the buffer were crucial for enantioseparation performance and were evaluated in detail. The fabricated NH2 -β-CD@His-ZIF-67@capillary-coated column showed good stability and repeatability (relative standard deviation <6.3%). The molecular modeling with AutoDock and grand canonical ensemble was carried out to evaluate the interactions between chiral stationary phase and racemic drugs.

The role of deep eutectic solvents in chiral capillary electrokinetic chromatography: A comparative study based on α-cyclodextrin chiral selector

Deep eutectic solvents (DESs) are emerging as potential candidates as additives/modifiers in chiral electrokinetic chromatography (EKC). However, the true role of DESs in the chiral separation process is far from being fully elucidated. Since most previous studies have been restricted to using choline chloride as the hydrogen-bond acceptor (HBA) in DESs, here we first evaluated the effect of five types of DESs (containing different HBAs) on the enantioseparation performance of an α-CD-based EKC system. The results demonstrate that these DESs are capable of moderately improving the enantioresolutions of several model drugs. A series of comparative experiments indicate that the improvement is mainly due to the contribution of the HBAs, rather than the selected hydrogen-bond donors (HBDs). Considering that most of these DESs are achiral, we further prepared five chiral DESs, aiming to investigate whether there is a synergistic effect between α-cyclodextrin and chiral DESs. However, these chiral DESs did not show obvious superiority compared with achiral DESs. This conclusion is different from the use of achiral or chiral ionic liquids (ILs) as additives in chiral EKC, in which chiral ILs usually exhibit significantly better enantioseparation performance than achiral ILs. Another important conclusion of this work is that there seems to be no significant difference between using DESs and their individual components, which is also different from the performance of most previously reported ILs. This conclusion indicates that the DESs may be virtually completely dissociated into their initial components (HBAs + HBDs) in the separation medium due to the destruction of their hydrogen-bond network. Therefore, a question which deserves particular attention of researchers in this field is raised here: whether it is absolutely necessary to use DESs in chiral EKC since adding HBAs and HBDs separately seems to have the same function?

Ethylenediamine-β-cyclodextrin modified graphene oxide nanocomposite membranes for highly efficient chiral separation of tryptophan and propranolol enantiomers

The separation of racemic drugs remains significance and challenge for pharmaceutical production. Recently, chiral drugs permeation separation based on membrane is a promising technology with advantages of energy efficient, continuous operation and cost-effectiveness. Herein, ethylenediamine-β-cyclodextrin (EDA-β-CD) mixed matrix membranes (EDA-β-CD MMMs) and EDA-β-CD modified graphene oxide thin-film nanocomposite membranes (GO/EDA-β-CD TFNMs) were fabricated via precipitation phase inversion and interfacial polymerization process, respectively. The corresponding membrane structure and GO nanosheets were characterized by SEM, TEM, ATR FT-IR, EA. Subsequently, the water flux, BSA rejection and stability of the membranes were studied. Moreover, enantioseparation performances of GO/EDA-β-CD TFNMs and EDA-β-CD MMMs toward (DL)-tryptophan (Trp) and (RS)-propranolol (Prop) were examined. Results showed that the GO/EDA-β-CD TFNMs exhibited extraordinary enantioselectivity, which remained high percent enantiomeric excess (ee.%) of Trp (100.00%) and Prop (75.34%). GO nanosheets with a multilayer structure and an interlayer spacing not only provided bonding site of EDA-β-CD but also improved permeation flux of the membrane. Finally, molecular docking technology was used to study the separation mechanism of the membranes. These findings demonstrate that GO/EDA-β-CD TFNMs might possess possibilities of high permeability and high enantioselectivity for chiral drugs separation.

Fabrication of PVDF-blended ultrafiltration membranes incorporated by chiral mesoporous silica for enantioseparation

Novel poly(vinylidene fluoride) (PVDF) ultrafiltration membranes blending with chiral mesoporous SiO2 materials were constructed to improve the anti-fouling and separation performance of PVDF-blended membranes. The formation of asymmetric mesoporous structure of chiral mesoporous SiO2 caused their large hydrophilic surface and significant chiral features, which enhanced the hydrophilicity and polarity of the resulting PVDF membranes blended with chiral mesoporous SiO2. So, the PVDF-blended membranes containing chiral mesoporous SiO2 had a high permeation performance and anti-fouling property. After blending with chiral mesoporous SiO2, the maximum flux of membranes exceeded 500 L·m−2·h−1 and was 6.5-fold higher than that of neat PVDF. Due to the stereo-specific interaction between enantiomers and chiral recognition sites introduced by chiral mesoporous SiO2 in the membranes, all PVDF-blended membranes had evident enantioseparation performance for DL-racemic tryptophan. The C-SiO2-20/PVDF-blended membranes had the highest enantioseparation performance under the same addition content and the maximum enantiomeric excess (e.e.%) was more than 20 %. Given the strong stereo-specific interaction and hydrogen bonding between d-tryptophan and β-cyclodextrin (β-CD), the addition of more β-CD would introduce more chiral recognition sites into the membranes, thereby enhancing the enantioseparation performance of the membranes for d-tryptophan. The maximum e.e.% of C-SiO2-20/β-CD/PVDF-blended membranes for the tryptophan enantiomer reached 55%.

Enhanced enantioseparation of drugs by capillary electrochromatography with a L-cysteine functionalized gold nanoparticle based stationary phase.

Nanoparticles, which have unique properties, have attracted growing attention in enantiomeric separation nowadays. In this paper, an L-cysteine functionalized gold nanoparticle (L-Cys-GNP) based capillary column was prepared and applied in separating drug enantiomers in capillary electrochromatography (CEC) with lactobionic acid (LA) as a chiral selector. Compared with bare fused-silica capillary columns, the capillary columns modified with L-Cys-GNPs showed excellent chiral separation performance. A series of parameters affecting the enantiomeric separation were systematically investigated.

β-Cyclodextrin covalent organic framework modified-cellulose acetate membranes for enantioseparation of chiral drugs

Membrane-based chiral separation has attracted widespread research attention. However, traditional chiral membranes remain an unbridgeable trade-off between permeability and selectivity. Chiral covalent organic frameworks (CCOFs) with inherently high porosity and intrinsic chirality are highly promising solutions. Herein we report novel CCOF membranes for enantioseparation of chiral drugs. A β-cyclodextrin covalent organic framework (β-CD COF) was used as the chiral selector to fabricate two types of β-CD COF membranes by physically and chemically modifying cellulose acetate substrates, including a β-CD COF mixed matrix membrane (β-CD COF MMM) and a β-CD COF thin film nanocomposite membrane (β-CD COF TFN). In particular, the β-CD COF TFN was the first reported interfacial polymerized COF membrane for enantioseparation and performed more preferentially than β-CD COF MMM. The optimal enantioselectivities of d, l-tryptophan (e.e% = 100%), (RS)-mandelic acid (e.e% = 58.1%), d, l-phenylalanine (e.e% = 36.3%), and (RS)-propranolol (e.e% = 18.0%) and comparable solute flux (Flux = 1.9–5.4 nmol·cm−2·h−1) were achieved using β-CD COF TFN. Benefiting from the remarkable chemical stability of β-CD COF, such membranes also had excellent thermal stability, acid resistance, and long-term storage stability. Moreover, the chiral recognition mechanism was investigated using molecular docking simulations. Fabricated membranes with high enantioseparation performance and stability provide a new perspective on establishing chiral membranes and show potential for industrial application.