Preparation method of selenium-containing polymer material capable of fixing metal ions

Abstract

The invention belongs to the field of novel functional polymer materials, and discloses a preparation method of a selenium-containing polymer material capable of fixing metal ions, and the preparation method comprises the following steps: S1, adding PTMEG into a round-bottom reaction flask filled with inert gas, and placing the round-bottom reaction flask in an oil bath pan for melting; s2, MDI, dimethylglyoxime, DSe and anhydrous N, N-dimethylacetamide are sequentially added and fully mixed; s3, stannous octoate and CuCl2 are added at the same time; s4, keeping the temperature of the oil bath pan and continuously reacting; s5, after the reaction is finished, a polymer is precipitated out, and secondary cleaning is conducted through methyl alcohol. The preparation method has the advantages that oximido is introduced into a polyurethane molecular structure to fix metal ions, meanwhile, selenium is introduced in a covalent fixation mode, and through double-site introduction of the metal ions and the selenium, the molecular structure of the polyurethane is greatly improved; the NO catalytic release rate of the material can be regulated and controlled, so that the biocompatibility and applicability of the polymer material in a blood environment are improved, and the application scene is further widened.

Description

Technical Field

[0001] This invention relates to the field of novel functional polymer materials, specifically to a method for preparing a selenium-containing polymer material capable of immobilizing metal ions. Background Technology

[0002] Polyurethane materials, with their tunable structure, have become one of the research hotspots in functional polymers and are widely used in medical fields such as interventional catheters and artificial organs.

[0003] In the existing technology, there is a great deal of research on polyurethane materials, such as:

[0004] A prepolymer was obtained using polycaprolactone diol and 1,6-hexanediisocyanate as raw materials. Then, a diol containing selenium was added to the reaction solution of the prepolymer for further polymerization, and finally a polyurethane material containing selenium was obtained.

[0005] A polyurethane material capable of immobilizing copper ions was prepared using polytetrahydrofuran ether diol (PTMEG), dimethyl ethyl oxime, glycerol, and isophorone diisocyanate as raw materials.

[0006] However, the materials obtained by the above methods are all polymers with single functional sites. If the polymer contains only selenium or copper ions, there will be problems such as no significant difference in the efficacy of the samples or insufficient efficacy, and the differentiation of nitric oxide catalytic release rate cannot be achieved. Summary of the Invention

[0007] To address the above problems, this invention provides a method for preparing a selenium-containing polymer material capable of immobilizing metal ions. This invention is achieved through the following technical solution.

[0008] A method for preparing a selenium-containing polymer material capable of immobilizing metal ions includes the following steps:

[0009] S1, PTMEG is added to a round-bottom reaction flask filled with inert gas, and the round-bottom reaction flask is placed in an oil bath to melt it. PTMEG is polytetrahydrofuran ether diol.

[0010] S2, add MDI, butanedione oxime, DSe and anhydrous N,N-dimethylacetamide sequentially to a round-bottom reaction flask and mix thoroughly. MDI is diphenylmethane diisocyanate and DSe is selenium-containing diol.

[0011] S3, simultaneously add stannous octoate and CuCl2 to the round-bottom reaction flask;

[0012] S4, maintain the temperature of the oil bath and continue the reaction;

[0013] S5. After the reaction is complete, the solution in the round-bottom reaction flask is added dropwise to the methanol solution to precipitate the polymer. The precipitated polymer is then washed a second time with methanol to obtain the final product.

[0014] As a further embodiment of the present invention, in step S1, the number average molecular weight of PTMEG is 1000 or 2000, the amount of PTMEG added is 0.01 mol, and the temperature of the oil bath is 45℃~55℃.

[0015] As a further embodiment of the present invention, in step S2, the amount of MDI added is 0.02 mol, the amount of dimethylglyoxime added is 0.0025 mol to 0.0075 mol, the amount of DSe added is 0.0025 mol to 0.0075 mol, and the amount of anhydrous N,N-dimethylacetamide added is 80 mL to 110 mL.

[0016] As a further aspect of the present invention, in step S2, the preparation step of DSe is as follows:

[0017] T1, under inert gas protection and ice bath conditions, selenium powder in equimolar amounts with sodium borohydride is added to an aqueous solution of sodium borohydride;

[0018] T2, after the reaction has proceeded for 30 minutes, 2-bromoethanol, dissolved in tetrahydrofuran in an equal molar amount with sodium borohydride, is added to the reaction system, and the temperature of the reaction system is raised to 50°C and reacted for 6 hours.

[0019] T3. After the reaction was completed, the product was extracted with organic matter and purified by silica gel column chromatography to obtain DSe.

[0020] As a further embodiment of the present invention, in step T1, the concentration of the sodium borohydride aqueous solution is 1 mmol / mL, and in step T3, a mixture of dichloromethane and ethyl acetate is used as the mobile phase during the silica gel column purification process.

[0021] As a further embodiment of the present invention, in step S3, the ratio of the added weight of stannous octoate to the weight of the substances in the round-bottom reaction flask is 0.2wt% to 0.3wt%, and the added amount of CuCl2 is 0.00125mol to 0.0025mol.

[0022] As a further aspect of the present invention, in step S4, the reaction time is 5-7 hours.

[0023] The beneficial effects of this invention are that, while introducing oxime groups into the polyurethane molecular structure to fix metal ions, selenium is introduced in a covalently fixed manner. Through the dual-site introduction of metal ions and selenium, the NO catalytic release rate of this type of material can be controlled, thereby improving the biocompatibility and applicability of this type of polymer material in the blood environment and further expanding its application scenarios. Attached Figure Description

[0024] To more clearly illustrate the technical solution of the present invention, the accompanying drawings used in the description of the specific embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 : Molecular structure diagram of DSe;

[0026] Figure 2 : The proton NMR spectrum of DSe;

[0027] Figure 3 Digital photograph of 1000Cu25Se75;

[0028] Figure 4 Digital photograph of 1000Cu25Se75 without fixed copper ions;

[0029] Figure 5 Molecular structure diagram of 1000Cu25Se75;

[0030] Figure 6 : The 1H NMR spectrum of 1000Cu25Se75;

[0031] Figure 7 : The proton NMR spectrum of 1000Cu25Se75 without copper ions;

[0032] Figure 8 Schematic diagram of the average catalytic release rates of 1000Cu25Se75, 1000Cu50Se50, and 1000Cu75Se25. Detailed Implementation

[0033] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] First, DSe is prepared. The specific preparation steps are as follows:

[0035] T1, under inert gas protection and ice bath conditions, selenium powder in equimolar amounts with sodium borohydride was added to an aqueous solution of sodium borohydride, the concentration of which was 1 mmol / mL.

[0036] T2, after the reaction has proceeded for 30 minutes, 2-bromoethanol, dissolved in tetrahydrofuran in an equal molar amount with sodium borohydride, is added to the reaction system, and the temperature of the reaction system is raised to 50°C and reacted for 6 hours.

[0037] T3. After the reaction was completed, the product was extracted with organic matter and purified by silica gel column chromatography to obtain DSe. During the silica gel column chromatography purification, a mixture of dichloromethane and ethyl acetate was used as the mobile phase.

[0038] like Figures 1-2 As shown, the structure of the prepared DSe was identified using proton nuclear magnetic resonance spectroscopy. The detection was performed using deuterated methanol as a solvent. The chemical shifts at 3.06-3.13 ppm and 3.81-3.88 ppm correspond to the protons of the methylene group in the selenium-containing diol molecule, while the chemical shifts at 4.87 ppm and 3.34 ppm correspond to the deuterated methanol.

[0039] Then, based on the prepared DSe, selenium-containing polymer materials capable of immobilizing metal ions were prepared, with the following five specific embodiments.

[0040] Example 1

[0041] S1: Take 0.01 mol of polytetrahydrofuran ether diol (PTMEG, number average molecular weight 1000) and add it to a round-bottom reaction flask filled with an inert gas (such as nitrogen), and place it in an oil bath at 45°C.

[0042] S2: After PTMEG has completely melted, add 0.02 mol of diphenylmethane diisocyanate (MDI), 0.0025 mol of butanedione oxime, 0.0075 mol of selenium-containing diol and 80 mL of anhydrous N,N-dimethylacetamide;

[0043] S3: After the reactants in step S2 are mixed evenly, add 0.2 wt% stannous octoate and 0.00125 mol CuCl2 to the reaction system.

[0044] S4: Maintain the system reaction temperature at 45℃ and require inert gas protection; the reaction time is 5 hours.

[0045] S5: After the reaction is complete, the reaction solution is added dropwise to the methanol solution to precipitate the polymerization product in the reaction system. The precipitate is then washed twice with methanol to obtain the final product (1000Cu25Se75).

[0046] Example 2

[0047] S1: Take 0.01 mol of polytetrahydrofuran ether diol (PTMEG, number average molecular weight 1000) and add it to a round-bottom reaction flask filled with an inert gas (such as nitrogen), and place it in an oil bath at 50°C.

[0048] S2: After PTMEG has completely melted, add 0.02 mol of diphenylmethane diisocyanate (MDI), 0.005 mol of butanedione oxime, 0.005 mol of selenium-containing diol and 90 mL of anhydrous N,N-dimethylacetamide;

[0049] S3: After the reactants in step S2 are mixed evenly, add 0.2 wt% stannous octoate and 0.0025 mol CuCl2 to the reaction system.

[0050] S4: Maintain the system reaction temperature at 50℃ and require inert gas protection; the reaction time is 6 hours.

[0051] S5: After the reaction is complete, the reaction solution is added dropwise to the methanol solution to precipitate the polymerization product in the reaction system. The precipitate is then washed twice with methanol to obtain the final product (1000Cu50Se50).

[0052] Example 3

[0053] S1: Take 0.01 mol of polytetrahydrofuran ether diol (PTMEG, number average molecular weight 1000) and add it to a round-bottom reaction flask filled with an inert gas (such as nitrogen), and place it in an oil bath at 55°C.

[0054] S2: After PTMEG has completely melted, add 0.02 mol of diphenylmethane diisocyanate (MDI), 0.0075 mol of butanedione oxime, 0.0025 mol of selenium-containing diol and 100 mL of anhydrous N,N-dimethylacetamide;

[0055] S3: After the reactants in step S2 are mixed evenly, add 0.2 wt% stannous octoate and 0.0025 mol CuCl2 to the reaction system.

[0056] S4: Maintain the system reaction temperature at 55℃ and require inert gas protection; the reaction time is 7 hours.

[0057] S5: After the reaction is complete, the reaction solution is added dropwise to the methanol solution to precipitate the polymerization product in the reaction system. The precipitate is then washed twice with methanol to obtain the final product (1000Cu75Se25).

[0058] Example 4

[0059] S1: Take 0.01 mol of polytetrahydrofuran ether diol (PTMEG, number average molecular weight 2000) and add it to a round-bottom reaction flask filled with an inert gas (such as nitrogen), and place it in an oil bath at 50°C.

[0060] S2: After PTMEG has completely melted, add 0.02 mol of diphenylmethane diisocyanate (MDI), 0.0025 mol of butanedione oxime, 0.0075 mol of selenium-containing diol and 100 mL of anhydrous N,N-dimethylacetamide;

[0061] S3: After the reactants in step S2 are mixed evenly, add 0.3wt% stannous octoate and 0.00125mol of CuCl2 to the reaction system.

[0062] S4: Maintain the system reaction temperature at 50℃ and require inert gas protection; the reaction time is 6 hours.

[0063] S5: After the reaction is complete, the reaction solution is added dropwise to the methanol solution to precipitate the polymerization product in the reaction system. The precipitate is then washed twice with methanol to obtain the final product (2000Cu25Se75).

[0064] Example 5

[0065] S1: Take 0.01 mol of polytetrahydrofuran ether diol (PTMEG, number average molecular weight 2000) and add it to a round-bottom reaction flask filled with an inert gas (such as nitrogen), and place it in an oil bath at 50°C.

[0066] S2: After PTMEG has completely melted, add 0.02 mol of diphenylmethane diisocyanate (MDI), 0.005 mol of butanedione oxime, 0.005 mol of selenium-containing diol and 110 mL of anhydrous N,N-dimethylacetamide;

[0067] S3: After the reactants in step S2 are mixed evenly, add 0.3wt% stannous octoate and 0.0025mol of CuCl2 to the reaction system.

[0068] S4: Maintain the system reaction temperature at 55℃ and require inert gas protection; the reaction time is 7 hours.

[0069] S5: After the reaction is complete, the reaction solution is added dropwise to the methanol solution to precipitate the polymerization product in the reaction system. The precipitate is then washed twice with methanol to obtain the final product (2000Cu50Se50).

[0070] Example Analysis

[0071] 1. Digital photos of the product

[0072] The 1000Cu25Se75 prepared in Example 1 was dried and then digitally photographed, as shown below. Figure 3 As shown, a polymer without fixed copper ions was prepared as a control sample (the preparation method of the control sample differs from that in Example 1 in that, in step S3, only stannous octoate was added, and CuCl2 was not added). The control sample is shown below. Figure 4 As shown.

[0073] from Figure 3 and Figure 4 It can be seen that before copper ions were fixed, the polymer was yellow overall due to the introduction of selenium-containing diols, while the overall color of the polymer changed significantly after copper ions were fixed. These results preliminarily demonstrate the successful preparation of the 1000Cu25Se75 polymer.

[0074] 2. Proton NMR spectrum

[0075] The polymer material 1000Cu25Se75 obtained in Example 1 was dissolved in deuterated dimethyl sulfoxide, and its structure was detected using proton nuclear magnetic resonance spectroscopy. The specific structure is as follows: Figure 5 As shown.

[0076] The proton NMR spectra of polymer material 1000Cu25Se75 and its control sample are shown below. Figure 6 and Figure 7 As shown in the figure, the peaks at 7.08 ppm and 7.33 ppm correspond to the active hydrogen of the benzene ring in MDI, 3.77 ppm corresponds to the methylene structure in the MDI structure, 1.49 ppm corresponds to the inner methylene in the repeating unit of PTMEG, 3.34-3.37 ppm corresponds to the outer methylene in the repeating unit of PTMEG, 2.02 ppm corresponds to the methyl structure in dimethylglyoxime, and 4.33 ppm and 3.25 ppm correspond to the methylene structure in the selenium-containing diol. This result indicates the successful preparation of the 1000Cu25Se75 polymer. Furthermore, the changes in the 1H NMR spectrum of the polymer before and after copper ion fixation are small, with only some peak positions or shapes changing. For example, the peak shape of the methylene in the selenium-containing diol at 3.25 ppm changed significantly due to the introduction of copper ions, which is caused by the influence of copper ion introduction on the overall molecular configuration, further illustrating the successful preparation of the 1000Cu25Se75 polymer.

[0077] 3. NO catalytic release experiment

[0078] Step 1: The polymer materials (1000Cu25Se75, 1000Cu50Se50, 1000Cu75Se25) obtained in Examples 1-3 were respectively prepared into 20wt% polymer solutions using tetrahydrofuran. The resulting solutions were then poured into flat and clean polytetrafluoroethylene petri dishes, and plastic sheets with a thickness of about 0.1 mm were prepared by solvent evaporation.

[0079] Step 2: The NO catalytic release rate of the three samples obtained in Step 1 was detected using the Griess reagent method. First, uniformly sized plastic sheets were immersed in 5 mL of phosphate buffer solution (containing 200 μM GSNO, 200 μM GSH, and 500 μM EDTA) at pH 7.4 and reacted at 37°C. Then, every 25 minutes, 100 μL of the reaction solution was added to a 96-well plate, along with 100 μL of Griess reagent in each well. After standing for 15 minutes, the absorbance was measured at 540 nm using a microplate reader.

[0080] Step 3: Prepare nitrite solutions of varying concentrations using sodium nitrite solution standard, and add 100 μL of each solution to a 96-well plate. Simultaneously add 100 μL of Griess reagent to the same well. After allowing the reaction to stand for 15 minutes, measure the absorbance at 540 nm using an ELISA reader to obtain the standard curve.

[0081] Step 4: Convert the absorbance obtained in Step 2 using a standard curve to obtain the final average NO release rate of the sample.

[0082] In this experiment, GSNO is nitrosoglutathione, GSH is reduced glutathione, and EDTA is ethylenediaminetetraacetic acid.

[0083] NO has various biological functions in the blood environment, such as anti-inflammatory, antibacterial, and anticoagulant effects. The series of polymer materials of this invention can be used to regulate the NO catalytic release rate by controlling the content of metal ions and selenium-containing elements, and thus are expected to be used in different pathological environments.

[0084] like Figure 8 As shown, 1000Cu25Se75 has a strength of 3.32 × 10⁻⁶. -10 mol·cm -2 ·min -1 The value of 1000Cu50Se50 is 4.79 × 10⁻⁶. -10 mol·cm -2 ·min -1 The value of 1000Cu75Se25 is 5.84 × 10⁻⁶.-10 mol·cm -2 ·min -1 As can be seen, all three groups of samples exhibited high average NO catalytic release rates, and the rate values ​​showed significant differences. Because copper ions and selenium-containing structures have different catalytic catalytic decomposition efficiencies for endogenous NO donors, samples with different amounts of catalytic sites showed differences in the final results, fully demonstrating that the dual-site regulation strategy of this invention can effectively regulate the NO catalytic release rate.

[0085] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to any specific implementation. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention.

Claims

1. A method for preparing a selenium-containing polymer material capable of immobilizing metal ions, characterized in that, Includes the following steps: S1, PTMEG is added to a round-bottom reaction flask filled with inert gas, and the round-bottom reaction flask is placed in an oil bath to melt it. PTMEG is polytetrahydrofuran ether diol. S2, add MDI, butanedione oxime, DSe and anhydrous N,N-dimethylacetamide sequentially to a round-bottom reaction flask and mix thoroughly. MDI is diphenylmethane diisocyanate and DSe is selenium-containing diol. S3, simultaneously add stannous octoate and CuCl2 to the round-bottom reaction flask; S4, maintain the temperature of the oil bath and continue the reaction; S5. After the reaction is complete, the solution in the round-bottom reaction flask is added dropwise to the methanol solution to precipitate the polymer. The precipitated polymer is then washed a second time with methanol to obtain the final product.

2. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 1, characterized in that, In step S1, the number average molecular weight of PTMEG is 1000 or 2000, the amount of PTMEG added is 0.01 mol, and the temperature of the oil bath is 45℃~55℃.

3. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 1, characterized in that, In step S2, the amount of MDI added is 0.02 mol, the amount of dimethylglyoxime added is 0.0025 mol to 0.0075 mol, the amount of DSe added is 0.0025 mol to 0.0075 mol, and the amount of anhydrous N,N-dimethylacetamide added is 80 mL to 110 mL.

4. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 1, characterized in that, In step S2, the preparation steps of DSe are as follows: T1, under inert gas protection and ice bath conditions, selenium powder in equimolar amounts with sodium borohydride is added to an aqueous solution of sodium borohydride; T2, after the reaction has proceeded for 30 minutes, 2-bromoethanol, dissolved in tetrahydrofuran in an equal molar amount with sodium borohydride, is added to the reaction system, and the temperature of the reaction system is raised to 50°C and reacted for 6 hours. T3. After the reaction was completed, the product was extracted with organic matter and purified using a silica gel column to obtain DSe.

5. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 4, characterized in that, In step T1, the concentration of the sodium borohydride aqueous solution is 1 mmol / mL. In step T3, a mixture of dichloromethane and ethyl acetate is used as the mobile phase during the silica gel column purification process.

6. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 1, characterized in that, In step S3, the weight ratio of added stannous octoate to the weight of the substances in the round-bottom reaction flask is 0.2wt% to 0.3wt%, and the amount of CuCl2 added is 0.00125mol to 0.0025mol.

7. The method for preparing a selenium-containing polymer material capable of immobilizing metal ions according to claim 1, characterized in that, In step S4, the reaction continues for 5-7 hours.

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