Multifunctional bio-based super-crosslinked polymer as well as preparation method and application thereof

Abstract

The invention provides a multifunctional bio-based super-crosslinked polymer as well as a preparation method and application thereof. The multifunctional bio-based super-crosslinked polymer provided by the invention has a large number of hydrophilic functional groups, a relatively large specific surface area and multistage pore size distribution, and is prepared by taking a natural flavonoid compound as a functional monomer and carrying out Friedel-Crafts alkylation reaction at room temperature or under a heating condition under the catalytic action of Lewis acid. The method has the advantages of mild synthesis conditions, cheap and easily available reaction monomers, good physical and chemical stability, easy batch production and environmental friendliness, and the obtained multifunctional bio-based super-crosslinked polymer has the advantages of large adsorption capacity, high extraction efficiency and multiple reuse times, can be used as an adsorbent in the extraction and enrichment of trace hazard factors in complex samples, and has wide application prospects. The method can be widely applied to the fields of medicine separation and purification, environment monitoring, food and medicine safety, early disease diagnosis and the like.

Description

Technical Field

[0001] The present invention relates to the field of bio-based adsorbent preparation and sample pretreatment, and in particular to a multifunctional bio-based super-cross-linked polymer and a preparation method and application thereof. Background Art

[0002] The main purpose of sample pretreatment is to eliminate matrix interference, enrich and concentrate the target and convert it into a form more suitable for instrument detection. It is the core step of sample analysis and is usually considered the bottleneck of the entire analysis process. Since the emergence of solid phase extraction technology in the late 1970s, it has become one of the most commonly used sample pretreatment technologies after continuous development. Its core lies in the selection and preparation of adsorbents. At present, the commonly used commercial adsorbents are C 18 , HLB, silica gel, resin, carbon materials, etc. However, these adsorbents have disadvantages such as low adsorption capacity, slow mass transfer rate and small specific surface area, which limit their application in sample pretreatment. Therefore, the development of high-performance green adsorbents is of great significance for improving the extraction and enrichment of trace components in complex samples.

[0003] Hypercrosslinked polymers (HCPs), as an emerging class of microporous organic polymers, have developed rapidly in recent years. They mainly form a large number of rigid crosslinks between polymer chains or aromatic monomers through the Friedel-Crafts reaction, thereby producing a highly crosslinked polymer network. The Friedel-Crafts reaction is a type of electrophilic substitution reaction. Its reaction conditions use Lewis acids (FeCl3, AlCl3) as catalysts. At a certain temperature, the catalytic active groups (chloromethyl, vinyl, acyl halide, etc.) generate carbon cations to attack the electron-rich benzene ring to produce crosslinks, thereby achieving crosslinking of polymer chains. At present, there are three main methods for the synthesis of HCPs: (1) post-crosslinking of precursor polymers; (2) direct one-step condensation of multifunctional group monomers (or their mixtures); (3) weaving of rigid aromatic skeleton monomers using external crosslinkers. HCPs have excellent stability, high specific surface area, adjustable pore structure and functional groups, and low density. They are widely used in gas storage, micropollutant removal (small molecules and heavy metals), chromatographic separation, catalysis, drug delivery, sensing and other fields.

[0004] However, the monomers currently used to prepare HCPs are mostly hydrophobic aromatic compounds, which are more suitable for the extraction and separation of hydrophobic components. Their application in polar systems is limited. Furthermore, the raw materials used are non-renewable, and the reaction conditions are harsh, making them unsuitable for mass production. Therefore, the development of bio-based hypercross-linked polymers with mild synthesis conditions, good physicochemical stability, and ease of mass production is a hot topic in this field that needs to be addressed. Summary of the Invention

[0005] The purpose of the present invention is to provide a multifunctional bio-based hyper-crosslinked polymer and its preparation method and application, so as to solve the problems that most of the current hyper-crosslinked polymers are suitable for the extraction and separation of hydrophobic components, the reaction conditions are harsh, and they are not conducive to mass production.

[0006] The object of the present invention is achieved like this:

[0007] The multifunctional bio-based super-crosslinked polymer provided by the present invention is prepared by using a natural flavonoid compound rich in hydroxyl as a functional monomer and a crosslinking agent through a Friedel-Crafts alkylation reaction under Lewis acid catalysis at room temperature or heating conditions.

[0008] The preparation method of the multifunctional bio-based hyper-crosslinked polymer provided by the present invention specifically comprises the following steps:

[0009] (1) Using flavonoids as functional monomers, dissolving the functional monomers and a cross-linking agent, and then adding Lewis acid to react at room temperature or under heating conditions;

[0010] (2) The reactants are centrifuged, purified, and dried to obtain multifunctional bio-based hyper-cross-linked polymers.

[0011] Preferably, the flavonoids in step (1) include any one or more of quercetin, tannic acid, phloretin, rutin, resveratrol, apigenin, baicalein, thymol, gallic acid, kaempferol, naringin, cohen and diosgenin.

[0012] Preferably, in step (1), the Lewis acid is one or more of FeCl3, ZnCl2, AlCl3 and SnCl4.

[0013] Preferably, the cross-linking agent in step (1) is any one or more of 1,4-dichlorobenzyl, biphenyldichlorobenzyl, o-dichlorobenzyl, 3,4-dichlorobenzyl, and 2,6-dichlorobenzyl.

[0014] Preferably, in step (1), after adding the Lewis acid, the reaction is carried out under heating conditions at 25° C. or 80° C. for 24 hours.

[0015] Preferably, in step (1), after adding Lewis acid, the reaction is carried out at 25° C. for 24 hours; the functional monomer used is quercetin, baicalein, naringin, apigenin, gallic acid, tannic acid, diosgenin or cohen.

[0016] Preferably, in step (1), the molar ratio of the functional monomer to the cross-linking agent is 1:3 to 1:1.

[0017] Preferably, in step (1), the molar ratio of the cross-linking agent to the Lewis acid is 1:3 to 1:1.

[0018] Preferably, step (2) specifically comprises: centrifuging the reactants, washing them with ethanol and water, purifying them with methanol as an extraction solvent, and then drying them. After drying, washing them with water and drying them again to obtain a multifunctional bio-based hyper-cross-linked polymer.

[0019] The multifunctional bio-based hyper-crosslinked polymers prepared using the method of the present invention exhibit various structures, including spherical, blocky, and fibrous forms. They possess numerous hydrophilic functional groups, a large specific surface area, and a multi-level pore size distribution. They can be used as adsorbents for the extraction, separation, and enrichment of tumor markers, drugs and their metabolites, genotoxic impurities, organic pollutants, and active ingredients of traditional Chinese medicines from biological samples. Specifically, the multifunctional bio-based hyper-crosslinked polymers can be used as adsorbents for the extraction, separation, and enrichment of 3-chloro-4-(3-fluorobenzyloxy)aniline and 2,6-dichloroaniline from environmental and biological samples.

[0020] The method of the present invention has mild synthesis conditions, good physical and chemical stability, and is easy to mass produce. The bio-based hyper-cross-linked polymer prepared according to the method of the present invention has various structures such as spheres, blocks and fibers, has a large number of hydrophilic functional groups, a large specific surface area and a multi-level pore size distribution, and is widely used in the fields of drug separation and purification, environmental monitoring, food and drug safety, early disease diagnosis, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 These are the SEM, nitrogen adsorption and desorption, and BJH pore size distribution diagrams of the QR-HCPs prepared in Example 1; wherein, (a) is the SEM image of the QR-HCPs, and (b) is the nitrogen adsorption and desorption and BJH pore size distribution diagram of the QR-HCPs.

[0022] Figure 2 This is a diagram of the reuse of QR-HCPs prepared in Example 1.

[0023] Figure 3 3 is the water contact angle diagram of QR-HCPs prepared in Example 1.

[0024] Figure 4 3 is a comparison chart of the adsorption effect of the QR-HCPs prepared in Example 1 compared with commercial adsorbents; wherein a is the recovery rate chart and b is the loss rate chart.

[0025] Figure 5 This is a comparison chart of the adsorption performance of the materials QR-HCPs prepared in Example 1 and Example 2.

[0026] Figure 6These are the SEM, nitrogen adsorption-desorption and BJH pore size distribution diagrams of BC-HCPs prepared in Example 3; wherein, (a) is the SEM image of BC-HCPs, and (b) is the nitrogen adsorption-desorption and BJH pore size distribution diagram of BC-HCPs.

[0027] Figure 7 These are the SEM, nitrogen adsorption and desorption, and BJH pore size distribution diagrams of the material prepared in Example 5; wherein, (a) is the SEM diagram of the material, and (b) is the nitrogen adsorption and desorption, and BJH pore size distribution diagram of the material.

[0028] Figure 8 These are the SEM, nitrogen adsorption-desorption and BJH pore size distribution diagrams of the material prepared in Example 6; wherein, (a) is the SEM diagram of the material, and (b) is the nitrogen adsorption-desorption and BJH pore size distribution diagram of the material.

[0029] Figure 9 This is a water contact angle diagram of the material prepared in Example 6.

[0030] Figure 10 3 is a comparison chart of the adsorption performance of the materials prepared in Example 9 and Example 10. DETAILED DESCRIPTION

[0031] The present invention will be further described below with reference to the following examples. The following examples are for illustration only and are not intended to limit the scope of the present invention in any way. The processes and methods not described in detail in the following examples are conventional methods well known in the art. The reagents used in the examples are all analytically pure or chemically pure and can be purchased commercially or prepared by methods well known to those skilled in the art.

[0032] Example 1

[0033] 0.189 g (0.625 mmol) of quercetin and 0.328 g (1.875 mmol) of 1,4-dichlorobenzyl chloride were placed in a single-necked flask and dissolved in 40 mL of 1,2-dichloroethane by ultrasonication. 0.304 g (1.875 mmol) of anhydrous FeCl₃ was then added, and the mixture was heated and stirred at 25°C for 24 hours to complete polymerization. The solid product was then collected by centrifugation at room temperature, washed with 95% ethanol and then ultrapure water. The solid was further purified by Soxhlet extraction using methanol as the extraction solvent and dried under vacuum at 45°C for 3 hours. After drying, it was washed three times with purified water and finally dried under vacuum at 45°C for 3 hours to obtain QR-HCPs.

[0034] The morphology of the prepared QR-HCPs was characterized by SEM. Figure 1As shown in (a), QR-HCPs exhibit spherical shapes of uneven size and are easily agglomerated. The specific surface area of ​​the synthesized QR-HCPs was characterized by nitrogen adsorption-desorption isotherms and BJH pore size. Figure 1 As shown in (b), the BET surface area of ​​QR-HCPs is as high as 172.4 m 2 / g, with an average pore size of 9.5nm, which can achieve efficient loading.

[0035] Weigh 1.0 mg of QR-HCPs and fill it into the homemade tube tip according to the three-layer structure of cotton-QR-HCPs-cotton. The operation process is divided into four steps: (1) Activation: Use 1.0 mL of methanol and 1.0 mL of pure water to activate the material in sequence; (2) Sample loading: Add 1.5 mL of spiked sample (3-chloro-4-(3-fluorobenzyloxy)aniline (3-CFA) and 2,6-dichloroaniline (DCA)) respectively; (3) Rinse: Add 0.8 mL of water to remove matrix interferences; (4) Elution: Use 0.8 mL of acetonitrile-water (9:1, v / v) mixed solution to desorb the target. The reusability of QR-HCPs was investigated by multiple loading, rinsing and elution of the spiked sample. The results are shown in the figure. Figure 2 shown.

[0036] Depend on Figure 2 It can be seen that the QR-HCPs prepared in this example still has a recovery rate of more than 95% after being reused 30 times, which shows that the material QR-HCPs has excellent reproducibility.

[0037] The water contact angle of the QR-HCPs prepared in this example was tested to evaluate the hydrophilic and hydrophobic properties of the material. Figure 3 As shown, the system's built-in continuous shooting function captured the process of a water droplet dripping into the material. The water droplet completely wetted the QR-HCPs within 0.12 seconds, and the final contact angle of water was 0°. This shows that the QR-HCPs prepared in this example have good hydrophilic properties.

[0038] The adsorption performance of the QR-HCPs material prepared in this example was compared with six commercial solid phase extraction adsorbents (HLB, C18, WAX, MAX, WCX, and MCX) for 3-CFA and DCA. Under the same conditions, 2 mg of filler was weighed and filled into a homemade tube tip in a three-layer structure of cotton-filler-cotton. The comparison results are shown in Figure 2. Figure 4 As shown by Figure 4 It can be seen that the recovery rate of 3-CFA by the material QR-HCPs is over 98%, which is significantly higher than that of commercial adsorbents.

[0039] Example 2

[0040] 0.189 g (0.625 mmol) of quercetin and 0.328 g (1.875 mmol) of 1,4-dichlorobenzyl chloride were placed in a single-necked flask and dissolved in 40 mL of 1,2-dichloroethane by ultrasonication. 0.304 g (1.875 mmol) of anhydrous FeCl₃ was then added, and the mixture was heated and stirred at 80°C for 24 hours to complete polymerization. The reaction system was then cooled to room temperature. The solid product was collected by centrifugation, washed with 95% ethanol and then with ultrapure water. The solid was further purified by Soxhlet extraction using methanol as the extraction solvent and dried under vacuum at 45°C for 3 hours. After drying, it was washed three times with purified water and finally dried under vacuum at 45°C for 3 hours to obtain QR-HCPs.

[0041] Compared with Example 1, the material in this example was synthesized at 80°C, while the material in Example 1 was synthesized at 25°C. The QR-HCPs prepared in this example and the QR-HCPs prepared in Example 1 were used as adsorbents to compare the adsorption of two genotoxic impurities, 3-chloro-4-(3-fluorobenzyloxy)aniline (3-CFA) and 2,6-dichloroaniline (DCA). The results are as follows: Figure 5 It can be seen that the QR-HCPs materials synthesized at different temperatures have good adsorption properties.

[0042] Example 3

[0043] Compared with Example 1, this example uses 0.169 g (0.625 mmol) of baicalein to replace 0.189 g (0.625 mmol) of quercetin in Example 1, and the rest is the same as Example 1. The material prepared in this example is recorded as BC-HCPs.

[0044] The morphology of the prepared BC-HCPs was characterized by SEM. Figure 6 As shown in (a), BC-HCPs exhibit spherical shapes of uneven size and are prone to agglomeration. The specific surface area of ​​the synthesized BC-HCPs was characterized by nitrogen adsorption-desorption isotherms and BJH pore size. Figure 6 As shown in (b), the BET specific surface area of ​​BC-HCPs is as high as 62.0 m 2 / g, with an average pore size of 10.7nm, which can achieve efficient loading.

[0045] The water contact angle of the BC-HCPs synthesized in this example was tested, and it was found that they were hydrophilic materials.

[0046] Example 4

[0047] Compared to Example 3, the synthesis temperature in this example was changed to 80°C, and the resulting material was designated BC-HCPs. The materials in this example and those in Example 3 were used as adsorbents, respectively, to compare the adsorption properties of two genotoxic impurities, 3-chloro-4-(3-fluorobenzyloxy)aniline (3-CFA) and 2,6-dichloroaniline (DCA). The results showed that the QR-HCPs synthesized at different temperatures exhibited good adsorption performance.

[0048] Example 5

[0049] Compared with Example 3, 0.471 g (1.875 mmol) of biphenylbenzyl dichloride was used in this example to replace 0.328 g (1.875 mmol) of 1,4-dichlorobenzyl in Example 3, and the rest were the same as in Example 3.

[0050] The material prepared in this example was characterized by SEM. Figure 7 As shown in (a), the surface of the material shows agglomerated blocks. The specific surface area of ​​the synthesized material was characterized by nitrogen adsorption-desorption isotherms and BJH pore size. Figure 7 As shown in (b), the BET specific surface area of ​​the material is as high as 735.6 m 2 / g, with an average pore diameter of 3.4nm, which can achieve efficient loading.

[0051] Example 6

[0052] Compared with Example 1, this example uses 0.363 g (0.625 mmol) of naringin to replace 0.189 g (0.625 mmol) of quercetin in Example 1, and the rest is the same as Example 1. The material prepared in this example is recorded as NG-HCPs.

[0053] The morphology of the prepared NG-HCPs was characterized by SEM. Figure 8 As shown in (a), the surface of NG-HCPs presents a single bayberry-like structure. The specific surface area of ​​the synthesized NG-HCPs was characterized by nitrogen adsorption-desorption isotherms and BJH pore size. Figure 8 As shown in (b), the BET specific surface area of ​​NG-HCPs is as high as 577.8 m 2 / g, with an average pore diameter of 4.3nm, which can achieve efficient loading.

[0054] The water contact angle of the NG-HCPs synthesized in this example was tested to evaluate the hydrophilic and hydrophobic properties of the material. Figure 9 As shown in FIG, the final contact angle of water is 144°, indicating that the NG-HCPs material is a hydrophobic material.

[0055] Example 7

[0056] Compared with Example 5, 0.171 g (0.625 mmol) of phloretin was used in this example to replace 0.169 g (0.625 mmol) of baicalein in Example 5, and the rest was the same as Example 5. The obtained material was recorded as Ph-HCPs.

[0057] The water contact angle of the Ph-HCPs synthesized in this example was tested, and the final water contact angle was found to be 134.9°, indicating that the Ph-HCPs material is hydrophobic.

[0058] Example 8

[0059] Compared with Example 7, the synthesis temperature in this example is changed to 80° C., and the other conditions are the same as those in Example 6.

[0060] The materials in this example and the materials in Example 7 were used as adsorbents, respectively, to compare the adsorption properties of two genotoxic impurities, 3-chloro-4-(3-fluorobenzyloxy)aniline (3-CFA) and 2,6-dichloroaniline (DCA). The results showed that the adsorption performance of the material prepared at 25°C was lower than that of the material prepared at 80°C.

[0061] Example 9

[0062] Compared with Example 1, this example uses 0.179 g (0.625 mmol) of kaempferol to replace 0.189 g (0.625 mmol) of quercetin in Example 1, and the rest are the same as Example 1.

[0063] The water contact angle of the material synthesized in this example was tested and it was found to be a hydrophilic material.

[0064] Example 10

[0065] Compared with Example 9, the synthesis temperature of this example is changed to 80° C., and the other conditions are the same as those of Example 9.

[0066] The materials in this example and the materials in Example 9 were used as adsorbents to compare the adsorption of two genotoxic impurities, 3-chloro-4-(3-fluorobenzyloxy)aniline (3-CFA) and 2,6-dichloroaniline (DCA). The results are as follows: Figure 10 It can be seen that the adsorption performance of the material prepared at 25°C is lower than that of the material prepared at 80°C.

[0067] The present invention also uses different monomers, such as apigenin, gallic acid, tannic acid, diosgenin, caesalpin, rutin, resveratrol, and thymol, to replace the quercetin in Example 1. The results show that the adsorbent synthesized at 25°C using the monomers apigenin, gallic acid, tannic acid, diosgenin, and caesalpin has good adsorption performance for 3-CFA and DCA, while the adsorbent synthesized at 25°C using rutin, resveratrol, and thymol has poor adsorption performance for 3-CFA and DCA. The adsorbent synthesized at 80°C using these monomers has good adsorption performance for both 3-CFA and DCA.

Claims

1. A method for preparing a multifunctional bio-based hyper-crosslinked polymer, characterized in that: The steps include: (1) Using flavonoids as functional monomers, dissolving the functional monomers and a cross-linking agent, and then adding Lewis acid to react at room temperature or under heating conditions; (2) The reactants are centrifuged, purified, and dried to obtain multifunctional bio-based hyper-cross-linked polymers.

2. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: The flavonoids in step (1) include any one or more of quercetin, tannic acid, phloretin, rutin, resveratrol, apigenin, baicalein, thymol, gallic acid, kaempferol, naringin, cohen and diosgenin.

3. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: In step (1), the Lewis acid is one or more of FeCl3, ZnCl2, AlCl3 and SnCl4.

4. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: In step (1), the cross-linking agent is any one or more of 1,4-dichlorobenzyl, biphenyldichlorobenzyl, o-dichlorobenzyl, 3,4-dichlorobenzyl, and 2,6-dichlorobenzyl.

5. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: In step (1), after adding Lewis acid, the reaction is carried out under heating conditions of 25° C. or 80° C. for 24 hours.

6. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: In step (1), the molar ratio of the functional monomer to the cross-linking agent is 1:3 to 1:

1.

7. The method for preparing a multifunctional bio-based hyper-crosslinked polymer according to claim 1, wherein: step( 2) Specifically, the reactants are centrifuged, washed with ethanol and water, purified with methanol as an extraction solvent, and then dried. After drying, the reactants are washed with water and dried again to obtain a multifunctional bio-based hyper-cross-linked polymer.

8. A multifunctional bio-based hyper-cross-linked polymer prepared by the method according to any one of claims 1 to 7.

9. The multifunctional bio-based hyper-cross-linked polymer according to claim 8 is used as an adsorbent for the extraction, separation and enrichment of tumor markers, drugs and their metabolites, genotoxic impurities, organic pollutants and active ingredients of traditional Chinese medicine in biological samples.

10. The use according to claim 9, characterized in that: The multifunctional bio-based hyper-cross-linked polymer is used as an adsorbent for the extraction, separation and enrichment of 3-chloro-4-(3-fluorobenzyloxy)aniline and 2,6-dichloroaniline in environmental samples and biological samples.

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