Chiral separation composite membrane as well as preparation method and application thereof

Abstract

The invention discloses a chiral separation composite membrane as well as a preparation method and application thereof, and belongs to the technical field of membrane separation. In order to solve the technical problems of low enantioselectivity and poor stability of the existing chiral membrane, the invention provides a composite membrane prepared by a surfactant-assisted interfacial polymerization technology. The membrane comprises a porous supporting substrate and a chiral polyamide separation layer arranged on the porous supporting substrate. The key point of the preparation method is that an aqueous phase solution containing a short-chain chiral amine monomer and a surfactant and an organic phase solution containing multifunctional acyl halide are subjected to interfacial polymerization. The introduction of the surfactant reduces the interfacial tension and regulates and controls the diffusion kinetics of the chiral monomer, thereby forming a sub-nano separation channel with more uniform structure, higher chiral site density and highly matched pore size with the target molecule size. The prepared composite membrane shows up to 99% of enantioselectivity to chiral enantiomers such as D / L-tryptophan, and has high flux and excellent cycle stability.

Description

Technical Field

[0001] This invention relates to a chiral separation composite membrane, its preparation method, and its application, belonging to the field of membrane separation technology. Background Technology

[0002] Currently, chiral drugs account for over 60% of the top 200 best-selling drugs globally. Enantiomers of chiral drugs often exhibit significant differences in pharmacological activity, metabolic processes, and toxicity, leading to a continuous expansion of the market share of single-isomer drugs. Therefore, chiral separation has become a crucial step in the modern pharmaceutical industry. However, traditional chiral separation techniques such as preparative chromatography and crystallization suffer from drawbacks such as low processing capacity, high energy consumption, and high solvent consumption, severely restricting the industrial production of chiral drugs. Membrane separation technology, with its significant advantages of continuous operation, low energy consumption, and scalability, has become a highly promising candidate for chiral separation, providing a promising solution for chiral drug separation.

[0003] Although membrane technology has been widely applied in many fields, traditional membrane separation techniques based on size exclusion and the Donan effect are not suitable for chiral separation because they require the construction of a chiral environment to provide selective affinity. Nojavan et al. developed a novel maltodextrin-starch chiral membrane for separating chiral amino acids and drugs, achieving an enantiomeric purity of 98.2%. Peng et al. prepared a chiral membrane for amino acid separation by embedding β-cyclodextrin into a piperazine polyamide membrane, increasing the ee value from nearly 0 to 25.6%. Furthermore, the size of nanochannel membranes significantly affects chiral selectivity. Matching the membrane pore size to the size of the chiral drug can greatly improve membrane separation performance. Due to the difficulty in controlling membrane structure, traditional chiral membranes often face challenges of low flux and uncompetitive enantioselectivity. In recent years, various nanochannel membranes for chiral drug separation have been reported by growing chiral porous materials, such as metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and graphene oxide (GO), on the membrane surface. However, its poor film-forming ability and nanoscale pore size often lead to low separation accuracy of chiral small molecules, making it difficult to achieve both high selectivity and high throughput, thus hindering its widespread application.

[0004] Chiral polymer membranes offer advantages such as low cost and high processability. They achieve enantioselectivity through chiral selectors on the membrane and have been applied to enantioselective recognition. Interfacial polymerization (IP) is one of the most promising methods for membrane preparation, introducing chiral selectors by reacting amine monomers with acyl chlorides at the water-oil interface to form polyamide (PA) nanofilms. Functionalized cyclodextrins and a series of amino acids have been applied to membrane preparation and chiral separation. However, the limited number of chiral recognition sites in the PA network can only bind a few enantiomers, thus limiting the separation accuracy and lifespan of the membrane. Furthermore, polyamide nanofilms typically exhibit a wide pore size distribution due to the uncontrollable polymerization reaction, leading to non-selective channels and reduced separation accuracy. Therefore, constructing uniform membrane nanochannels and increasing the density of chiral sites within the channels are key factors in improving enantioselectivity. Summary of the Invention

[0005] The technical problem this patent aims to solve is that existing chiral separation membranes prepared by interfacial polymerization suffer from limited chiral recognition site density, uneven pore structure, and non-selective porosity in their separation layers, making it difficult to simultaneously achieve high enantioselectivity, high throughput, and long-term operational stability when separating enantiomeric substances. This invention proposes a novel surfactant-assisted interfacial polymerization (SAIP) technology, which simultaneously enhances the chiral site density and highly matched nanochannels through the simultaneous addition of (2s)-1,2-(s-PD) and acyl chloride, thereby improving enantioselectivity. The polymer chains obtained through the polymerization of short-chain chiral amine monomers are tightly packed, significantly increasing the chiral site density. The surfactant reduces the interfacial tension between the two phases and regulates the monomer diffusion process. By adjusting the monomer diffusion and reaction processes, uniform nanochannels highly matched to chiral drug molecules are constructed. This synthesized membrane achieves an ee% value of up to 99% for D / L-tryptophan while maintaining high throughput.

[0006] A chiral separation composite membrane, comprising:

[0007] A porous support substrate; and a chiral polyamide separation layer disposed on the porous support substrate; wherein the chiral polyamide separation layer is formed by interfacial polymerization of an aqueous solution containing a chiral amine monomer and a surfactant with an organic solution containing a polyfunctional acyl halide on the surface of the porous support substrate.

[0008] The chiral amine monomer is a C2-C6 chiral diamine; preferably, the chiral amine monomer is (2s)-1,2-propanediamine.

[0009] The surfactant is at least one of a cationic surfactant, anionic surfactant, or nonionic surfactant.

[0010] The surfactant is a cationic surfactant; preferably, the cationic surfactant is a quaternary ammonium salt surfactant, more preferably hexadecyltrimethylammonium bromide.

[0011] The polyfunctional acyl halide is an aromatic or aliphatic acyl halide having at least two acyl halide groups; preferably, the polyfunctional acyl halide is 1,3,5-benzenetricarboxyl chloride.

[0012] The thickness of the chiral polyamide separation layer is 40-150 nm; the average effective pore radius of the composite membrane is 0.3-0.8 nm.

[0013] The thickness of the chiral polyamide separation layer is 50-100 nm; the average effective pore radius of the composite membrane is 0.3-0.5 nm.

[0014] The porous support substrate is made of at least one of polyimide, polysulfone, polyethersulfone, polyvinylidene fluoride, or polyacrylonitrile.

[0015] A method for preparing the chiral separation composite membrane according to claim 1 includes the following steps:

[0016] (a) Provide an aqueous solution comprising a chiral amine monomer and a surfactant;

[0017] (b) Provide an organic phase solution containing a polyfunctional acyl halide;

[0018] (c) Contact the porous support substrate with the aqueous solution;

[0019] (d) The porous support substrate, after being in contact with the aqueous solution, is then contacted with the organic solution to form a chiral polyamide separation layer through interfacial polymerization.

[0020] In the aqueous solution, the concentration of the chiral amine monomer is 0.5-5.0 wt%, and the concentration of the surfactant is 0.05-5.0 wt%; in the organic solution, the concentration of the polyfunctional acyl halide is 0.01-1.0 wt%.

[0021] In the aqueous solution, the concentration of the chiral amine monomer is 1.0-3.0 wt%, and the concentration of the surfactant is 0.5-3.0 wt%; in the organic solution, the concentration of the polyfunctional acyl halide is 0.05-0.2 wt%.

[0022] In step (a), the pH value of the aqueous solution is 7-10, preferably 8.

[0023] The contact time described in step (c) is 0.5-5 minutes; and / or, the contact time described in step (d) is 1-10 minutes.

[0024] In step (b), the organic phase solution is prepared using a water-insoluble organic solvent, preferably an aliphatic hydrocarbon solvent, more preferably n-hexane.

[0025] The application of the chiral separation composite membrane in the separation of enantiomers.

[0026] The enantiomers are chiral amino acids, preferably D / L-tryptophan or D / L-histidine.

[0027] The beneficial effects of this invention are: Attached Figure Description

[0028] Figure 1 Schematic diagram of a precise chiral separation membrane prepared based on SAIP technology.

[0029] Figure 2 Figure 1 shows the characterization results of the membrane materials. (a) Fourier transform infrared spectra of polyimide substrate membrane, CIP membrane and SAIP1 membrane; (b) XPS spectra of different membrane materials; (c) Oxygen 1s element XPS spectra of CIP membrane, (d) SAIP1 membrane and (e) SAIP3 membrane.

[0030] Figure 3 Figure 1 shows the effect of CTAB on the IP process. (a) Interfacial tension between the two phases at different CTAB concentrations; (b) s-PD absorbance with / without CTAB at different diffusion times; (c) s-PD absorbance at different CTAB concentrations; (d) Pore size distribution of CIP, SAIP1 and SAIP3 films.

[0031] Figure 4 : Result of the contact water angle of the prepared membrane.

[0032] Figure 5 : Morphological characterization of the membrane. (a) CIP, (b) SAIP1 and (c) SAIP3 surface, cross-section and AFM images. (d) Schematic diagram of CIP and (e) SAIP process.

[0033] Figure 6 : Schematic diagram of membrane performance optimization process. (a) Schematic diagram of chiral separation process; (b) Tryptophan molecular size (molecular size was calculated using Chem3D software combined with MM2 force field parameters); (c) ee% value and flux of membrane at different concentrations of CTAB and (d) s-PD; (e) Flux of membrane to enantiomers at different IP times.

[0034] Figure 7 SEM and AFM images of PI substrates and PA films prepared with different s-PD concentrations and 1% CTAB.

[0035] Figure 8 : Pore size distribution of membranes at different s-PD concentrations.

[0036] Figure 9 SEM images of the membrane after 1 min and 4 min of interfacial polymerization reaction.

[0037] Figure 10 : Results of chiral separation performance. (a) Enantiomeric purity percentage (ee%) and flux of the membrane at different feed concentrations; (b) Comparison of chiral separation performance between this membrane and advanced chiral membranes.

[0038] Figure 11 High-performance liquid chromatograms of two enantiomers in the feed solution and permeate at a concentration of 0.1 mmol / L.

[0039] Figure 12 Figure 1 shows the results of the long-term stability test of the membrane. The relationship between the membrane flux and the operating time and the yield percentage (ee%) are shown when the feed concentrations are (a) 0.1 mmol / L, (b) 0.3 mmol / L and (c) 0.5 mmol / L.

[0040] Figure 13 Figure: Results of membrane separation performance for histidine, arginine and phenylalanine. Detailed Implementation

[0041] To improve the enantioselectivity and operational stability of small molecule chiral drugs, this invention employs (2s)-1,2-propanediamine (s-PD) as a chiral selector and prepares novel chiral films via surfactant-assisted interfacial polymerization (SAIP). Figure 1 This strategy offers several advantages: First, the smaller molecular volume of s-PD significantly reduces steric hindrance during polymerization, resulting in more precise cavity dimensions of polyacrylamide (PA) and a higher degree of size matching with the chiral drug. Furthermore, the reaction of the small-molecule chiral selector with the acyl chloride effectively increases the network density of chiral groups, which is beneficial for enhancing chiral sites in the membrane pores and improving enantioselectivity. More importantly, surfactant-assisted ionic polymerization significantly modulates the diffusion rate of s-PD, thereby forming more uniform nanochannels and avoiding the formation of non-selective pores. Based on these advantages, the designed composite membrane exhibits excellent separation selectivity due to its uniform nanostructure, highly matched nanochannels, and enhanced chiral sites. At a feed concentration of 0.1 mM, the ee% of D / L-tryptophan reaches as high as 99%, while maintaining a high throughput.

[0042] The main raw materials used in this patent are: polyimide PI (P84®), polyethylene glycol (PEG, molecular weight = 400 Da, (2s)-1,2-propanediamine dihydrochloride (s-PD), hexadecyltrimethylammonium bromide (CTAB), and 1,3,5-benzenetricarboxyl chloride (TMC).

[0043] Example 1: Preparation of polyimide film substrate

[0044] Polyimide substrates were prepared using a solvent-inducible phase inversion method. The specific steps are as follows: First, polyimide powder was dried in a vacuum oven at 60°C for 10 hours to remove moisture. Then, 20% (mass fraction) of polyimide particles were dissolved in a mixed solvent of polyethylene glycol 400 and N-methylpyrrolidone (NMP) (ratio 16%:64%) to prepare a casting solution. The casting solution was stirred for 8 hours until homogeneous and allowed to stand for 10 hours to remove air bubbles. The solution was then uniformly cast onto a nonwoven fabric substrate using a 100 μm thick doctor blade. The prepared substrate was washed with deionized water to remove residual solvent and stored in deionized water before use.

[0045] Example 2 Preparation of composite membrane

[0046] The composite membrane was prepared via interfacial polymerization. First, 2 wt% s-PD and different concentrations of CTAB were dissolved in deionized water, and the pH of the aqueous solution was adjusted to 8 with 1 mol / L NaOH. Then, 0.1 wt% TMC was dissolved in n-hexane and stirred until completely dissolved. The aqueous solution was poured onto a freshly prepared PI membrane substrate and allowed to stand for 2 minutes. After wiping away any residual solution from the membrane surface, a 0.1% (wt%) TMC solution was poured on for another 4 minutes. The prepared membrane was labeled SAIPx membrane, where x represents the CTAB concentration (wt%). The prepared membrane was stored in deionized water until use. For comparison, a CTAB-free PA membrane was also prepared and labeled CIP membrane.

[0047] The diffusion rate of amines was determined using a UV spectrophotometer. The specific procedure was as follows: 10 mL of an aqueous solution of para-diphenylamine (s-PD) and s-PD / CTAB was first added to a quartz cuvette, followed by the slow addition of 10 mL of n-hexane to the surface of the aqueous solution. The concentration change of the amine monomer in the n-hexane was monitored every 20 seconds.

[0048] Chiral separation performance was determined using a high-performance liquid chromatograph (HPLC, Shimadzu DGU-20A) equipped with a Crownpak CR(+) / CR(-) column (5 μm, 150 mm × 4 mm). The mobile phase was a perchloric acid solution containing 15% pure methanol (pH 1.5). The flow rate was 0.4 mL / min, the column temperature was 20 °C, and the UV detector wavelength was 220 nm.

[0049] Membrane performance evaluation methods

[0050] The enantioselectivity of the membrane was evaluated using a diffusion cell. The prepared membrane was placed between two chambers with an effective area of ​​2.27 cm². 100 mL of racemic or single enantiomer solutions of different concentrations were added to the feed side, and an equal volume of deionized water was added to the dialysis side. Both chambers were stirred simultaneously. To evaluate separation performance, 2 mL of permeate was taken from the permeate side after a set time for HPLC analysis, and the enantiomeric excess (ee%) and flux J (mmol·m⁻²·s⁻¹) were calculated. Simultaneously, an equal volume of solution was taken from the feed side to ensure a constant solution volume in both chambers.

[0051] The enantiomeric excess percentage (ee%) is calculated using the following formula:

[0052]

[0053] c D and c L These are the concentrations of D-tryptophan and L-tryptophan, respectively.

[0054] The fluxes of D-tryptophan and L-tryptophan are calculated using the following formula:

[0055]

[0056] Q represents the molar mass of the permeate, A represents the effective membrane area, and t is the experimental time.

[0057] The pore size distribution of the membrane was analyzed using neutral solutes diethylene glycol, glucose, sucrose, and raffinose. The relationship between the molecular weight (MW) of the solute and the Stokes radius (rs) can be obtained through the following equation:

[0058]

[0059] The membrane pore size distribution is calculated by the following formula:

[0060]

[0061] Where rp is the effective pore radius of the membrane, i.e., the geometric mean radius of the solute when R=50%; the geometric standard deviation σp is the ratio of the value of rs when RT=84.13% to the value when RT=50%; and μp is the average effective pore radius.

[0062] Membrane characterization

[0063] Chiral membranes were prepared using interfacial polymerization assisted by the chemically stable cationic surfactant CTAB. The successful preparation of the composite membrane was verified by studying functional group changes using ATR-FTIR technology. Figure 2As shown in Figure a, both the CIP and SAIP films exhibit characteristic peaks of amide bonds. Specifically: the peak at 1300 cm⁻¹ corresponds to the CH stretching vibration; the peak at 1490 cm⁻¹ corresponds to the C=C stretching vibration of the benzene ring; and the peak at 1630 cm⁻¹ corresponds to the C=O stretching vibration of the amide bond. Compared to the polyimide substrate, the composite film shows a new peak at 1540 cm⁻¹, which can be attributed to the CN stretching vibration of the polyamide, confirming the formation of the polyamide layer through ionic polymerization. Furthermore, the peak intensities of the SAIP film at 1540 and 1630 cm⁻¹ are higher than those of the CIP film, indicating the formation of more amide bonds. This preliminarily confirms that the introduction of CTAB can effectively promote the polymerization process and increase the crosslinking density of the polyamide film. The elemental composition of the films was further analyzed by XPS. Figure 2 As shown in b, the contents of O1s and N1s in the post-IP membrane are both higher than those in the PI substrate, further confirming the successful preparation of the PA layer. To further analyze the oxygen-containing functional groups within the PA layer, the O1s spectrum was decomposed into two peaks: the 531.5 eV peak corresponds to polyamide, and the 533 eV peak originates from the OC=O functional group generated by the hydrolysis of unreacted acyl chloride. With increasing s-PD concentration, the NC=O ratio increased from 50.71% to 54.67%, which is attributed to the increased number of amino groups participating in the IP reaction, thereby enhancing the crosslinking degree of the PA layer. Furthermore, the NC=O ratio of the CTAB-based membrane is 62.5%, higher than that of the conventional membrane (50.71%), and this ratio increases with increasing CTAB concentration. Figure 2 (ce). In addition, N1s elemental analysis was performed. When the CTAB concentration was 0%, 1%, and 3%, the proportion of primary amines decreased from 9.31% to 8.18%, while the proportion of -NC=O groups increased accordingly. The increase in the proportion of NC=O groups indicates that more primary amine groups participated in the ionic polymerization reaction. The results show that the surfactant-assisted IP process can effectively inhibit the hydrolysis reaction of acyl chlorides and improve the degree of IP reaction, thereby preparing a PA layer with higher crosslinking degree and denser structure. Since the primary amine groups in the enantiomeric polybutene are chiral sites, the polyacrylate network prepared by the SAIP strategy has more chiral sites available for enantiomer binding, which is more conducive to the precise separation of enantiomers.

[0064] Structure and property regulation of membrane preparation

[0065] During ionic polymerization, CTAB tends to self-assemble at the water-organic interface, with its hydrophobic alkyl groups facing the organic phase and its quaternary ammonium groups facing the aqueous phase. Therefore, the interfacial tension between the two phases is effectively reduced. In the following experiments, the IP time was controlled at 4 minutes. Figure 3 As shown in Figure a, with increasing CTAB concentration, the interfacial tension decreases from 13.74 mN / m -1 Significantly reduced to 2.23 mN / m -1This can be attributed to the formation of a dense monolayer of CTAB at the interface between the two phases. The reduced interfacial tension decreases the energy barrier for transinterfacial diffusion, promoting the diffusion of amine monomers into the organic phase, thus making the ionic polymerization process more regular. To further investigate the effect of CTAB on the diffusion process of amine monomers, UV-Vis spectroscopy was used to monitor the diffusion behavior of terephthalamide (s-PD). Figure 3 As shown in figures b and c, the amount of s-PD diffusing into the organic phase significantly increases in the presence of CTAB, and more s-PD signals are detected with increasing CTAB concentration. This is attributed to the decrease in interfacial tension, indicating that more monomers participate in the internal phase reaction, which is conducive to the formation of a denser polystyrene network structure. Furthermore, both CTAB and s-PD monomers are positively charged in aqueous solution, and there is a strong electrostatic repulsion between them. This enhanced electrostatic repulsion will promote the diffusion of s-PD into the organic phase. This was verified by measuring the absorbance changes of s-PD under different diffusion times with and without CTAB. Figure 3 As shown in b, when only s-PD is present, the absorbance does not increase significantly between 20 and 80 seconds, indicating that s-PD has essentially reached its maximum diffusion level within 20 seconds. However, after introducing CTAB, the absorbance of s-PD continuously increases between 20 and 40 seconds, and then tends to stabilize. In summary, the addition of CTAB not only increases the number of chiral monomers diffusing but also alters their diffusion rate. This process can simultaneously achieve precise control over the microstructure and properties of chiral polystyrene networks.

[0066] like Figure 3 As shown in Figure d, the pore size distribution of the membranes differed significantly when the CTAB concentrations were 0%, 1%, and 3%. Without CTAB, the CIP membrane had a pore size of 0.48 nm and a relatively wide pore size distribution. This inhomogeneous pore structure leads to uneven distribution of chiral sites, resulting in an imbalance in the interaction between enantiomers and the membrane, thus reducing the accuracy of chiral separation. Conversely, the membranes prepared with CTAB exhibited a narrow pore size distribution, with pore sizes of 0.37 and 0.35 nm at CTAB concentrations of 1% and 3%, respectively. The reduction in membrane pore size is attributed to the increased diffusion of s-PD into the hexane phase, which enhances the activity of the polymerization reaction and promotes the formation of a denser PA structure. Furthermore, the water contact angle of the membranes was investigated. Figure 4 As shown, the hydrophilicity of the membrane is enhanced after ion polymerization treatment, and the hydrophilicity is further improved with increasing CTAB concentration. This is attributed to the formation of hydrophilic amide bonds. Simultaneously, increasing CTAB concentration can increase the polyacrylic acid network density, thereby promoting enhanced hydrophilicity.

[0067] The introduction of CTAB also significantly affected the surface and cross-sectional morphology of the membrane. For example... Figure 5As shown, when the CTAB concentration is 0%, irregular annular protrusions cover the entire membrane surface. As the CTAB concentration increases to 1%, the annular particles gradually evolve into a nodular structure. With continued increases in CTAB concentration, the protrusions on the membrane surface disappear, becoming relatively smooth. Simultaneously, the average roughness of the membrane decreases from 7.66 nm at 0% CTAB concentration to 1.73 nm at 1% concentration, and further to 1.54 nm at 3% concentration. Figure 5 The evolution of membrane surface morphology stems from the regulation of monomer diffusion and reaction kinetics by CTAB: (1) CTAB significantly reduces the surface tension of the water-organic interface, making the contact between the two phases more uniform. This will reduce local concentration fluctuations of reactive monomers at the interface and inhibit excessive growth of nanoprotrusions caused by uneven diffusion. (2) For example Figure 3 As shown in b, without the addition of CTAB, the concentration of terephthalamide diffused into n-hexane no longer increased after 20 seconds; while with the addition of CTAB, the absorbance continued to rise between 20 and 40 seconds. This indicates that the surfactant may form a dynamic interfacial layer at the interface, slowing down the diffusion rate of terephthalamide into the organic phase. This controlled diffusion avoids local explosive reactions, making the interfacial reaction rate tend to be slower, thus forming a smoother PA layer. (3) The electrostatic interaction between CTAB and polyamide can further inhibit PA aggregation and promote surface smoothness. The reduction in membrane roughness can effectively slow down the adsorption of pollutants on the membrane surface and enhance its washability. It is worth noting that the CTAB-assisted IP strategy increases the PA layer thickness from 31.7 nm to 93.3 nm. The reduction in interfacial tension will increase the thickness of the reaction zone. In addition, during the IP process, s-PD needs to pass through the CTAB molecular layer to react with TMC, and the diffusion path becomes longer, making the IP reaction more likely to occur in the extended interfacial region. While increased membrane thickness may enhance permeation resistance and reduce separation efficiency, a thicker active layer provides a longer mass transfer path, which will enhance the interaction between enantiomers and chiral sites and help to significantly improve the enantioselectivity of chiral membranes.

[0068] The chiral separation performance test results are as follows: using D / L tryptophan (D / L-Trp) as a model solution, the chiral separation performance of the membrane was evaluated using a two-chamber permeation device. Figure 6 (a and b, feed concentration 0.1 mM). Interfacial polymerization parameters have a significant impact on the nanostructure of chiral films; therefore, it is necessary to study the effects of monomer concentration and reaction time on film performance. Under conditions of a chiral amine concentration of 2% and a reaction time of 4 min, such as... Figure 5As shown in Figure c, when the CTAB concentration is fixed at 1%, the enantiomeric excess (ee%) of D / L-Trp reaches 98%, significantly higher than that of the membrane without CTAB (92%). With continuous increase in CTAB concentration, the enantioselectivity shows only slight fluctuations. The increase in ee% can be attributed to the increased thickness of the membrane selective layer after the introduction of CTAB. The extended transport path effectively prolongs the contact time between chiral sites and tryptophan within the membrane channels, thereby enhancing the strength of the chiral interaction between them. On the other hand, the reduction in pore size and the sharpening of the pore size distribution also contribute to improved separation accuracy. Simultaneously, the racemic tryptophan flux increases with increasing CTAB addition. Figure 5 As shown in Figure c, when the CTAB concentration increases from 0% to 3%, the flux increases from 26.4 to 30.26 × 10⁻⁻⁻⁶. 4 The concentration of CTAB was mmol·m⁻²·s⁻¹. This can be attributed to the effective improvement of membrane hydrophilicity by the addition of CTAB. Considering that the membrane exhibited optimal enantioselectivity at this concentration, the CTAB concentration was ultimately fixed at 1%. The effect of s-PD concentration on performance was then further investigated. The results showed that, under the conditions of 1% CTAB and a reaction time of 4 min, the enantioselectivity (ee%) increased from 84% to 97% as the concentration increased from 1% to 3%. The ee% value tended to stabilize as the concentration continued to increase. With further increases in concentration, the flux decreased from 32.4 to 22.2 × 10⁻¹. 4 mmol·m⁻²·s⁻¹ Figure 6 (d). It can be seen that as the s-PD concentration increases, the nodular structure on the membrane surface increases. When the s-PD concentration reaches 3%, the nodular structure transforms into a network structure, and the membrane surface roughness continues to increase. This indicates that increasing the s-PD concentration can significantly enhance the PA layer density and effectively reduce the pore size (d). Figure 7 At low s-PD concentrations, the membrane pore size (0.86 nm) is much larger than the tryptophan molecule size (0.65 nm). D / L-Trp passes through the membrane channel more easily, resulting in poor enantioselectivity. As the concentration of chiral polyxylene increases, the membrane pore size shrinks to 0.5 nm, effectively reducing the transmembrane transport rate of D / L-tryptophan. Figure 8 When the concentration of chiral amine is 2%, the membrane exhibits optimal performance (pore size 0.7 nm, see...). Figure 3 (d), therefore this condition was selected for further research.

[0069] Extending the IP time leads to the formation of a dense polyacrylic acid network, which has a certain impact on the enantioselectivity and permeation flux of the membrane. For example... Figure 5 As shown in Figure e, when IP is performed for only 1 minute, the ee% value is only about 70%. As the IP time increases, the ee% value rises to 98%. However, when the IP time is extended to 4 minutes, the ee% value no longer increases. This phenomenon can also be explained by the membrane pore structure: as... Figure 9 As shown, significant defects were observed on the membrane surface when the polymerization time was 1 minute, indicating a loose polyamide structure that made high-precision separation difficult. When the time was extended to 4 minutes, the surface exhibited a complete nodular structure, forming a dense separation layer, thus effectively improving the ee% value. In summary, a membrane prepared with 2% amine concentration, 1% CTAB, and a reaction time of 4 minutes was ultimately used for subsequent studies.

[0070] Chiral separation performance and mechanism study: Changes in feed concentration also have a significant impact on the separation process. For example... Figure 10 As shown in Figure a, when the feed solution concentration changed from 0.1 mmol / L to 0.7 mmol / L, the membrane flux increased from 17.69 to 36.41 × 10⁻⁻⁻⁶. 4 mmol·m⁻²·s⁻¹. This is because the concentration gradient is the main driving force of the separation process. Therefore, increasing the feed concentration can enhance the membrane flux. However, as the feed concentration increases, the enantioselectivity percentage (ee%) of the membrane gradually decreases. When the feed concentration is 0.1, 0.3, and 0.5 mmol / L, the ee% values ​​are 99% ( Figure 11 The enantioselectivity (ee%) values ​​were 98.6% and 97%, respectively. When the feed concentration increased to 0.7 mmol / L, the ee% value significantly decreased to 74%. At low feed concentrations, the sufficient chiral sites within the membrane efficiently distinguish enantiomers. However, as the feed concentration increases, the limited chiral sites within the membrane are competitively occupied by excess molecules, leading to a decrease in enantioselectivity. Furthermore, the enhanced separation driving force induced by high feed concentrations (where non-selective Fick diffusion dominates) weakens the chiral sieving effect of the membrane. The feed concentration and separation accuracy of the prepared membrane are comparable to those of the most advanced membrane materials currently available. Compared to the enantioselectivity performance of membrane materials reported in recent literature, the prepared membrane exhibits a leading ee% value and high feed concentration ( Figure 10 (b).

[0071] To ensure the large-scale application of chiral membranes in practical engineering production, it is necessary to study membrane stability. First, the effect of feed concentration on membrane separation stability was investigated. For example... Figure 12 As shown in the AC data, when the feed concentration was 0.1 mmol / L, the membrane ee% value was consistently above 95%, and the L-Trp flux was significantly higher than that of D-Trp. However, with prolonged operation, the L-Trp flux gradually decreased, while the D-Trp flux increased slightly, indicating a decline in separation precision. When the operation time was extended to 30 hours, the membrane ee% value dropped to 72%, and the membrane lost its selectivity. Similarly, with increasing feed concentration, the membrane exhibited a higher ee% value in the initial stage. Worse still, compared to the feed concentration of 0.1 mmol / L, the membrane ee% value fell below 90% after only 20 hours of operation.

[0072] To verify the membrane's versatility, three other amino acids were selected for chiral separation, with the feed concentration controlled at 0.1 mM. For example... Figure 13 As shown, the membrane exhibits good selectivity for histidine, with an ee% value as high as 90%. However, it does not show chiral selectivity for phenylalanine and arginine. During chiral separation, a three-point interaction occurs between the recognition site on the chiral membrane and the enantiomer. The difference in the strength of the interaction between the chiral recognition site and the enantiomer leads to different retention times of the isomers on the membrane, thus causing differences in diffusion rates. For tryptophan, the indole ring on its main chain undergoes strong π-π stacking with the benzene ring of the membrane, while the -NH- group on the indole ring acts as a hydrogen bond donor, forming hydrogen bonds with the membrane acceptor. In addition, the amino and carboxyl groups on the tryptophan side chain can provide additional ionic or hydrogen bonding interactions. Similarly, the -NH- and tertiary amine groups in the imidazole ring of histidine act as hydrogen bond donors and acceptors, specifically binding to the membrane through hydrogen bonds. Weak π-π stacking or dipole-dipole interactions also exist between its aromatic ring and the membrane. The difference lies in the fact that the positively charged guanidinium group on the arginine side chain has a strong hydrogen bond with the membrane, firmly anchoring it to the membrane surface, resulting in a lack of selectivity in the membrane. In contrast to the amino acids mentioned above, phenylalanine's interaction with the membrane is too simple to form a three-point interaction, thus failing to achieve highly selective separation.

Claims

1. A chiral separation composite membrane, characterized in that, include: Porous support substrate; And a chiral polyamide separation layer disposed on the porous support substrate; wherein the chiral polyamide separation layer is formed by interfacial polymerization reaction of an aqueous solution containing a chiral amine monomer and a surfactant with an organic solution containing a polyfunctional acyl halide on the surface of the porous support substrate.

2. The chiral separation composite membrane according to claim 1, characterized in that, The chiral amine monomer is a C2-C6 chiral diamine, and the polyfunctional acyl halide is an aromatic or aliphatic acyl halide having at least two acyl halide groups.

3. The chiral separation composite membrane according to claim 1 or 2, characterized in that, The surfactant is at least one of a cationic surfactant, anionic surfactant, or nonionic surfactant.

4. The chiral separation composite membrane according to claim 3, characterized in that, The surfactant is a cationic surfactant; the cationic surfactant is a quaternary ammonium salt surfactant.

5. The chiral separation composite membrane according to any one of claims 1-4, characterized in that, The thickness of the chiral polyamide separation layer is 40-150 nm; the average effective pore radius of the composite membrane is 0.3-0.8 nm; the thickness of the chiral polyamide separation layer is 50-100 nm; and the average effective pore radius of the composite membrane is 0.3-0.5 nm.

6. A method for preparing the chiral separation composite membrane according to claim 1, characterized in that, Includes the following steps: (a) Provide an aqueous solution comprising a chiral amine monomer and a surfactant; (b) Provide an organic phase solution containing a polyfunctional acyl halide; (c) Contact the porous support substrate with the aqueous solution; (d) The porous support substrate, after being in contact with the aqueous solution, is then contacted with the organic solution to form a chiral polyamide separation layer through interfacial polymerization.

7. The preparation method according to claim 6, characterized in that: In the aqueous phase solution, the concentration of the chiral amine monomer is 0.5-5.0 wt%, and the concentration of the surfactant is 0.05-5.0 wt%; in the organic phase solution, the concentration of the polyfunctional acyl halide is 0.01-1.0 wt%; in the aqueous phase solution, the concentration of the chiral amine monomer is 1.0-3.0 wt%, and the concentration of the surfactant is 0.5-3.0 wt%; in the organic phase solution, the concentration of the polyfunctional acyl halide is 0.05-0.2 wt%.

8. The preparation method according to claim 6, characterized in that, In step (a), the pH value of the aqueous phase solution is 7-10; in step (c), the contact time is 0.5-5 minutes; and / or, in step (d), the contact time is 1-10 minutes; in step (b), the organic phase solution is prepared using a water-insoluble organic solvent, preferably an aliphatic hydrocarbon solvent, more preferably n-hexane.

9. The application of the chiral separation composite membrane according to any one of claims 1-4 in the separation of enantiomers.

10. The application according to claim 9, characterized in that, The enantiomers are chiral amino acids.

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