Nucleotide-assisted ion-permeable polymer resin, preparation method thereof and application of nucleotide-assisted ion-permeable polymer resin in film

Abstract

The invention discloses nucleotide-assisted ion-permeable polymer resin, and belongs to the technical field of high-molecular compound synthesis, a preparation method of a polymer comprises the following specific steps: (1) taking a hydrophobic monomer, a functional monomer and a hydrophilic monomer as raw materials, adding an initiator, and carrying out polymerization reaction to obtain a polymer intermediate I; (2) carrying out nucleophilic substitution reaction on the polymer intermediate I and 6-bromohexanoic acid to obtain a polymer intermediate II; and (3) introducing NADP into the polymer intermediate II through EDC condensation modification so as to obtain the nucleotide-assisted ion permeation polymer resin. According to the preparation method, a strategy of combining hydrophilic and hydrophobic chain segments with nucleotide is adopted, firstly, a vinyl polymer is prepared through a thermal initiation or redox initiation strategy, and the hydrophilicity and the ion transmittance of a polymer film are adjusted by adjusting and controlling the feeding amount of a hydrophilic monomer and 6-bromohexanoic acid and adjusting the modification rate of a side chain hydrophilic group and NADP (Nicotinamide Adenine Dinucleotide Phosphate).

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer compound synthesis, and particularly relates to a nucleotide-assisted ion-permeable polymer resin, a preparation method thereof, and an application thereof in a film. Background Art

[0002] The nucleotide-assisted ion-permeable polymer resin film is a novel functional polymer film that combines biomolecules with synthetic resin, aiming to enhance the ion transport efficiency through the characteristics of nucleotides. As an auxiliary component, nucleotides (such as ATP, GTP) may affect ion transport through electrostatic interaction or structural guidance by virtue of the negative charge of the phosphate group and the hydrogen bond ability of the base; the negative charge of nucleotides attracts cations (such as Na+, K+), promoting their diffusion. Nucleotides serve as templates to guide the polymer to form ordered pores or increase the porosity of the film, reducing the ion transport resistance. The hydrophilicity of nucleotides may form local hydrophilic regions in the hydrophobic polymer, facilitating ion dissolution and migration. The application scenarios mainly include the following aspects: Energy field: As an ion exchange membrane for fuel cells or lithium-ion batteries to improve conductivity; Environmental separation: For the selective adsorption and separation of heavy metal ions in water treatment; Biosensing: Using the specific recognition of nucleotides (such as ATP binding to metal ions) to design responsive sensors.

[0003] The challenges and aspects that need to be optimized for the nucleotide-assisted ion-permeable polymer resin film are as follows: (1) Stability: Nucleotides are prone to degradation at high temperatures or extreme pH values, and chemical modification or protective layers are required to enhance durability; (2) Uniformity: Ensure the uniform distribution of nucleotides in the film to avoid local aggregation affecting performance; (3) Selectivity: It is necessary to regulate the pore size or charge distribution to achieve the selective permeation of specific ions (such as distinguishing Na + and K + ). At present, the main research frontiers in this direction are: Biomimetic design: Simulating biological ion channels (such as K + channels), and using nucleotide self-assembly to form nanoscale pores; Dynamic response: Developing pH- or temperature-responsive intelligent films, and regulating permeability through nucleotide conformational changes; This kind of film provides new ideas for efficient ion transport through the synergistic effect of biomolecules and synthetic materials. In the future, further optimization in terms of stability and selectivity is required to expand its applications in the fields of energy, environmental protection, and biomedicine.

[0004] Therefore, it is an urgent problem for those skilled in the art to be able to provide a new nucleotide-assisted ion-permeable polymer resin and a preparation method thereof. Summary of the Invention

[0005] To solve the above problems, the present invention provides a nucleotide-assisted ion-permeable polymer resin, a preparation method thereof, and an application in a film. The present invention synthesizes a random copolymer with monomer units of hydrophobic styrene or lauryl methacrylate, functional 4-vinylpyridine, and hydrophilic methoxypolyethylene glycol methacrylate or 2-hydroxyethyl methacrylate in the main chain through a radical polymerization reaction. By adjusting the feeding ratio of monomers and initiators and the degree of polymerization of the polymerization reaction, the number-average molecular weight of the polymerization product is made to reach more than 50,000 to ensure the stability of the resin in the aqueous phase to meet the long-term use requirements. First, a carboxyl functional group (-COOH) is modified on the poly-4-vinylpyridine unit through a nucleophilic substitution reaction on the pyridine nitrogen atom, and then NADP is coupled to -COOH through a 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) condensation reaction. The introduction of NADP can improve the hydrophilicity of the resin, thereby improving the ion permeation ability. The presence of hydrophobic monomer units can ensure the stability of the resin in the aqueous phase, while hydrophilic monomer units help improve the biocompatibility of the resin and synergistically promote the ion permeability. In addition, by adjusting the percentage of NADP modification, an excellent ion permeation ability can be achieved for the resin film.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A preparation method of a nucleotide-assisted ion-permeable polymer resin, comprising the following specific steps:

[0008] (1) Using a hydrophobic monomer, a functional monomer, and a hydrophilic monomer as raw materials, adding an initiator and then carrying out a polymerization reaction to obtain a polymer intermediate I;

[0009] (2) After carrying out a nucleophilic substitution reaction on the polymer intermediate I and 6-bromohexanoic acid, obtaining a polymer intermediate II;

[0010] (3) Introducing NADP (β-nicotinamide adenine dinucleotide phosphate hydrate) into the polymer intermediate II through EDC condensation modification to obtain a nucleotide-assisted ion-permeable polymer resin.

[0011] Vinyl polymers resins obtained by traditional radical polymerization have poor biocompatibility in vivo and are difficult to biodegrade. The vinyl polymers modified by side-chain ionic groups in the present invention have the advantages of good hydrophilicity, good biocompatibility and high ion permeability. In the present invention, a random copolymer containing hydrophobic monomers, functional monomers and hydrophilic monomers is synthesized by a radical polymerization reaction. By adjusting the feeding ratio of monomers and initiators and the degree of polymerization of the polymerization reaction, the number-average molecular weight of the polymerization product is made to reach more than 50,000, improving the stability of the resin in the aqueous phase and meeting the use requirements; at the same time, the presence of hydrophobic monomer units can ensure the stability of the resin in the aqueous phase, while hydrophilic monomer units contribute to improving the ion permeability. At the same time, through the nucleophilic substitution reaction on the pyridine nitrogen atom, 6-bromohexanoic acid is easily attacked by the nucleophilicity of the pyridine nitrogen atom, thus undergoing a nucleophilic substitution reaction to introduce hydrophilic -COOH on the polymer main chain. Further, through EDC condensation modification, other functional groups are introduced; since the efficiency of the above two-step reaction is close to 100%, by controlling the feeding ratio of 6-bromohexanoic acid and the hydrophilic group, the modification rate of the side-chain hydrophilic group can be adjusted.

[0012] Preferably, in step (1), the mass ratio of the hydrophobic monomer, the functional monomer, the hydrophilic monomer and the initiator is 1-10:8-90:0.2-5:0.1-0.5;

[0013] The polymerization reaction is divided into thermal initiation polymerization or redox initiation polymerization. The conditions for the thermal initiation polymerization are: reacting at 60-70 °C for 6-24 h, and the conditions for the redox initiation polymerization are: reacting at room temperature for 6-24 h.

[0014] Preferably, in step (1), the hydrophobic monomer includes styrene or lauryl methacrylate;

[0015] The functional monomer includes 4-vinylpyridine;

[0016] The hydrophilic monomer includes methoxypolyethylene glycol methacrylate or 2-hydroxyethyl methacrylate;

[0017] The initiator is an azo thermal initiator or a redox initiator. Among them, the azo thermal initiator includes azobisisobutyronitrile (AIBN) or azodiisovaleronitrile (V65), and the redox initiator is a combination of potassium persulfate (KPS) and N,N,N',N'-tetramethylethylenediamine (TEMED). The mass ratio of KPS to TEMED is 0.10-1.35:0.06-0.86.

[0018] Preferably, the polymerization reaction in step (1) further includes a solvent, which is tetrahydrofuran or water. The mass ratio of the tetrahydrofuran to the hydrophobic monomer is 10 - 80:1 - 10, and the mass ratio of the water to the hydrophobic monomer is 200 - 1000:1 - 10;

[0019] After the polymerization reaction is completed, a precipitate is obtained, and after reprecipitation, washing, and drying, the polymer intermediate I is obtained.

[0020] Preferably, the mass ratio of the polymer intermediate I to the 6-bromohexanoic acid in step (2) is 10 - 30:0.2 - 2.4;

[0021] The reaction conditions are: reacting at 60 - 90 °C for 12 - 24 h.

[0022] Preferably, the nucleophilic substitution reaction in step (2) further includes a solvent, which is tetrahydrofuran. The mass ratio of the tetrahydrofuran to the polymer intermediate I is 10 - 32:10 - 30;

[0023] After the nucleophilic substitution reaction is completed, a precipitate is obtained, and after reprecipitation, washing, and drying, the polymer intermediate II is obtained.

[0024] Preferably, the specific steps of the EDC condensation modification in step (3) are:

[0025] Mix the polymer intermediate II, NADP hydrate, EDC, HOBt, and a solvent evenly and react at room temperature for 6 - 24 h;

[0026] Among them, the mass ratio of the polymer intermediate II, NADP hydrate, EDC, HOBt, and the solvent is 2 - 10:0.6 - 1.5:0.1 - 0.5:0.1 - 0.4:8 - 20.

[0027] A nucleotide-assisted ion-permeable polymer resin obtained by the preparation method as described above.

[0028] Use of a nucleotide-assisted ion-permeable polymer resin obtained by the preparation method as described above in the preparation of a film.

[0029] Preferably, the film includes a hemodialysis membrane or an insulin sensing membrane.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The present invention adopts a strategy of combining hydrophilic and hydrophobic segments with nucleotides. First, a vinyl-based polymer is prepared through a thermal initiation or redox initiation strategy. By regulating the feeding amounts of hydrophilic monomers and 6-bromohexanoic acid, the modification rates of hydrophilic groups on the side chain and NADP are adjusted, thereby regulating the hydrophilicity of the polymer membrane and the ion permeability. Description of the Drawings

[0032] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on the provided drawings without creative efforts.

[0033] Figure 1 Schematic diagram of the synthetic route of the polymer resin of the present invention;

[0034] Figure 2 1H NMR spectrum of the polymer intermediate I in Example 1 of the present invention;

[0035] Figure 3 1H NMR spectrum of the polymer intermediate II in Example 1 of the present invention;

[0036] Figure 4 1H NMR spectrum of the polymer resin in Example 1 of the present invention;

[0037] Figure 5 1H NMR spectrum of the polymer resin in Example 2 of the present invention;

[0038] Figure 6 1H NMR spectrum of the polymer resin in Example 3 of the present invention;

[0039] Figure 7 Ion permeability diagram of different NADP-modified polymer membranes with different ions in Example 1 of the present invention. Detailed Embodiments

[0040] The following will clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0041] Example 1

[0042] As Figure 1 , the present invention provides a method for preparing a nucleotide-assisted ion-permeable polymer resin, which includes the following specific steps:

[0043] (1) Styrene (St), 4-vinylpyridine (4VP), methoxypolyethylene glycol methacrylate (PEGMA), and tetrahydrofuran (THF) were mixed uniformly in a mass ratio of 9:90:1:67. Subsequently, AIBN with a mass ratio of 0.1:9 to styrene was added. The system was degassed with argon to remove residual air in the system, the reaction flask was sealed, and a polymerization reaction was initiated at 70 °C with a stirring speed of 500 rpm. As the reaction proceeded, the viscosity of the reaction system gradually increased until the stirring of the tetrahydrofuran solution stopped, and the reaction was terminated. The reaction product was dissolved and diluted with methanol with a mass ratio of 500:9 to styrene, and then precipitated in water to obtain a white solid product. The precipitated white solid product was cut into small pieces with scissors, soaked, washed in pure water, and vacuum dried to obtain the polymer intermediate IPSt-P4VP-PPEGMA (as Figure 2 1 1H NMR, 400 MHz, CD3OD);

[0044] (2) PSt-P4VP-PPEGMA, 6-bromohexanoic acid, and THF were mixed uniformly in a mass ratio of 10:1:12 and placed in a single-neck round-bottom flask. The reaction was carried out at 90 °C for 12 h. After the reaction was completed, precipitation was carried out with ethyl acetate, and the precipitant ethyl acetate was removed to obtain a white solid product. The product was redissolved in methanol and precipitated in pure water. The solid product was soaked overnight in pure water, washed three times, and then vacuum dried at 50 °C to remove residual solvent and moisture, obtaining the polymer intermediate II PSt-P4VP-PPEGMA@COOH (as Figure 3 1 1H NMR, 400 MHz, CD3OD);

[0045] (3) PSt-P4VP-PPEGMA@COOH, NADP hydrate, EDC, HOBt, and THF were mixed uniformly in a mass ratio of 10:0.6:0.1:0.1:10 and placed in a single-neck round-bottom flask. The reaction was carried out at room temperature for 24 h. The resulting reaction mixture was precipitated in water to remove impurities, obtaining the final product PSt-P4VP-PPEGMA@CO-NADP (as Figure 4 1 1H NMR, 400 MHz, CD3OD);

[0046] (4) PSt-P4VP-PPEGMA@CO-NADP and THF were mixed uniformly in a mass ratio of 0.01:9, and the polymer concentration was 1 mg / mL. It was poured into a polytetrafluoroethylene rectangular mold. After the solvent had completely evaporated, it was placed in a constant temperature and humidity box at 60 °C for heat treatment for 24 h to remove residual tetrahydrofuran. After cooling to room temperature, it was peeled off from the polytetrafluoroethylene plate to obtain an ion permeable membrane;

[0047] Test the ion permeability of the ion-permeable membrane to different ions (Na + , K + , Ca + , Mg + ) in aqueous solution, and compare it with the ion permeability of the polymer membrane without sulfonate modification. The results are shown in Figure 5 , where (a) is the bar chart of the passing rates of different ions, and (b) is the bar chart of the ratio of the passing rates of different ions. It can be seen from the figure that the ion-permeable membrane prepared by the present invention has good passing rates for different ions. Furthermore, the ion-permeable membrane modified with sulfonate prepared by the present invention has better passing rates for different ions than the ion permeability of the unmodified polymer membrane; and Figure 2-4 The nuclear magnetic resonance hydrogen spectrum of

[0048] Example 2

[0049] The present invention provides a method for preparing a nucleotide-assisted ion-permeable polymer resin, which includes the following specific steps:

[0050] (1) Mix lauryl methacrylate (LMA), 4-vinylpyridine (4VP), methoxypolyethylene glycol methacrylate (PEGMA) and tetrahydrofuran (THF) evenly according to the mass ratio of 9:90:1:67. Subsequently, add AIBN with a mass ratio of 0.5:9 to styrene, degas with argon to remove the residual air in the system, seal the reaction flask, and initiate the polymerization reaction at 70 °C with a stirring speed of 500 rpm. As the reaction proceeds, the viscosity of the reaction system gradually increases until the stirring of the tetrahydrofuran solution stops, and then stop the reaction; add the reaction product to methanol with a mass ratio of 1000:9 to styrene for dissolution and dilution, and then precipitate in water to obtain a white solid product. Cut the precipitated white solid product into small pieces with scissors, soak and wash it in pure water, and vacuum dry it to obtain the polymer intermediate IPLMA-P4VP-PPEGMA;

[0051] (2) Mix PLMA-P4VP-PPEGMA, 6-bromohexanoic acid and THF evenly according to the mass ratio of 10:1:12, and place them in a single-neck round-bottom flask. React at 90 °C for 12 h. After the reaction is completed, precipitate with ethyl acetate, and remove the precipitant ethyl acetate to obtain a white solid product. Dissolve it again in methanol and precipitate in pure water. The solid product is soaked in pure water overnight, washed three times, and then vacuum dried at 50 °C to remove the residual solvent and water to obtain the polymer intermediate II PSt-P4VP-PPEGMA@COOH;

[0052] (3) Mix PLMA-P4VP-PPEGMA@COOH, NADP hydrate, EDC, HOBt, and THF in a mass ratio of 10:0.6:0.1:0.1:10 evenly, place them in a single-neck round-bottom flask, react at room temperature for 24 h, precipitate the resulting reaction mixture in water, remove impurities, and obtain the final product PLMA-P4VP-PPEGMA@CO-NADP (as Figure 5 1 HNMR, 400 MHz, CD3OD).

[0053] Example 3

[0054] The present invention provides a method for preparing a nucleotide-assisted ion-permeable polymer resin, which includes the following specific steps:

[0055] (1) Mix styrene (St), 4-vinylpyridine (4VP), 2-hydroxyethyl methacrylate (HEMA), and water in a mass ratio of 10:90:1:500 evenly. Subsequently, add potassium persulfate, stir at a high speed (1000 rpm) to mix evenly to emulsify the monomers in water, degas with argon to remove the residual air in the system, immediately add N,N,N',N'-tetramethylethylenediamine and seal the reaction flask, and initiate a polymerization reaction at room temperature. The reaction product gradually precipitates until the amount of precipitate no longer increases, then stop the reaction; remove the aqueous solution from the above polymer product, wash the solid product with a large amount of deionized water, cut the white solid product into small pieces with scissors, soak, wash in pure water, and vacuum dry to obtain the polymer intermediate IPSt-P4VP-PHEMA;

[0056] (2) Mix PSt-P4VP-PHEMA, 6-bromohexanoic acid, and THF in a mass ratio of 10:1:10 evenly, place them in a single-neck round-bottom flask, react at 90 °C for 12 h. After the reaction is completed, precipitate with ethyl acetate, remove the precipitant ethyl acetate to obtain a white solid product, dissolve it again in methanol, precipitate in pure water, soak the solid product in pure water overnight, wash three times, and then vacuum dry at 50 °C to remove the residual solvent and moisture to obtain the polymer intermediate II PSt-P4VP-PHEMA@COOH;

[0057] (3) Mix PSt-P4VP-PHEMA@COOH, NADP hydrate, EDC, HOBt, and THF in a mass ratio of 10:0.6:0.1:0.1:10 evenly, place them in a single-neck round-bottom flask, react at room temperature for 24 h, precipitate the resulting reaction mixture in water, remove impurities, and obtain the final product PSt-P4VP-PHEMA@CO-NADP (as Figure 6 11H NMR, 400 MHz, d6-DMSO).

[0058] Each embodiment is described in a progressive manner. The key point of each embodiment is to illustrate the differences from other embodiments. For the same or similar parts among the embodiments, reference can be made to each other.

[0059] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a nucleotide-assisted ion-permeable polymer resin, characterized in that, It includes the following specific steps: (1) Using a hydrophobic monomer, a functional monomer, and a hydrophilic monomer as raw materials, after adding an initiator, a polymerization reaction is carried out to obtain polymer intermediate I; (2) After carrying out a nucleophilic substitution reaction between the polymer intermediate I and 6-bromohexanoic acid, polymer intermediate II is obtained; (3) By introducing NADP through EDC condensation modification to the polymer intermediate II, a nucleotide-assisted ion-permeable polymer resin can be obtained.

2. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, characterized in that, In step (1), the mass ratio of the hydrophobic monomer, the functional monomer, the hydrophilic monomer, and the initiator is 1-10:8-90:0.2-5:0.1-0.5; The polymerization reaction is divided into thermal-initiated polymerization or redox-initiated polymerization. Among them, the conditions for the thermal-initiated polymerization are: reacting at 60-70 °C for 6-24 h, and the conditions for the redox-initiated polymerization are: reacting at room temperature for 6-24 h.

3. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, wherein, The hydrophobic monomer in step (1) includes styrene or lauryl methacrylate; The functional monomer includes 4-vinylpyridine; The hydrophilic monomer includes methoxypolyethylene glycol methacrylate or 2-hydroxyethyl methacrylate; The initiator is an azo thermal initiator or a redox initiator. Among them, the azo thermal initiator includes azobisisobutyronitrile or azobisisopentanenitrile, and the redox initiator is a combination of potassium persulfate (KPS) and N,N,N',N'-tetramethylethylenediamine (TEMED). The mass ratio of KPS and TEMED is 0.10-1.35:0.06-0.

86.

4. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, characterized in that, The polymerization reaction in step (1) also includes a solvent, and the solvent is tetrahydrofuran or water. The mass ratio of tetrahydrofuran and the hydrophobic monomer is 10-80:1-10, and the mass ratio of water and the hydrophobic monomer is 200-1000:1-10; After the polymerization reaction is completed, a precipitate is obtained, and after reprecipitation, washing, and drying, the polymer intermediate I is obtained.

5. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, characterized in that, In step (2), the mass ratio of the polymer intermediate I and 6-bromohexanoic acid is 10-30:0.2-2.4; The conditions for the reaction are: reacting at 60-90 °C for 12-24 h.

6. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, characterized in that The nucleophilic substitution reaction in step (2) also includes a solvent, and the solvent is tetrahydrofuran. The mass ratio of tetrahydrofuran and the polymer intermediate I is 10-32:10-30; After the nucleophilic substitution reaction is completed, a precipitate is obtained, and after reprecipitation, washing, and drying, the polymer intermediate II is obtained.

7. The preparation method of a nucleotide-assisted ion-permeable polymer resin according to claim 1, characterized in that, The specific steps of the EDC condensation modification in step (3) are: Mixing the polymer intermediate II, NADP hydrate, EDC, HOBt, and a solvent evenly and reacting at room temperature for 6-24 h; Among them, the mass ratio of the polymer intermediate II, NADP hydrate, EDC, HOBt, and the solvent is 2-10:0.6-1.5:0.1-0.5:0.1-0.4:8-20.

8. A nucleotide-assisted ion-permeable polymer resin obtained by the preparation method according to any one of claims 1-8.

9. Use of a nucleotide-assisted ion-permeable polymer resin obtained by the preparation method according to any one of claims 1-8 in the preparation of a film.

10. The application according to claim 9, characterized in that, The film includes a hemodialysis membrane or an insulin sensing membrane.

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