Polyrotaxanes with controllable cyclodextrin coverage and methods of making and using the same

Abstract

This invention discloses a polyrotaxane with controllable cyclodextrin coverage, its preparation method, and its applications, belonging to the field of polyrotaxane material technology. This invention involves dissolving α-cyclodextrin, 3-hydroxyadamantane-1-carboxylic acid, and polyethylene glycol diamine in deionized water and assembling them under cold conditions to form a quasi-polyrotaxane, which is then end-capped to obtain the polyrotaxane. The polyethylene glycol diamine is prepared from polyethylene glycol and N,N'-carbonyldiimidazole. The cyclodextrin coverage of the polyrotaxane is directionally controlled by adjusting the mass ratio of α-cyclodextrin to 3-hydroxyadamantane-1-carboxylic acid, the order of addition of 3-hydroxyadamantane-1-carboxylic acid, and the cold assembly time. Based on the mechanism of competition between 3-hydroxyadamantane-1-carboxylic acid and polyethylene glycol within the cyclodextrin cavity, this invention synthesizes polyrotaxanes with a cyclodextrin coverage of 0.5–2.5%, resulting in polymers with better extensibility and mechanical properties.

Description

Technical Field

[0001] This invention belongs to the field of polyrotaxane material technology, and more specifically, relates to a polyrotaxane with controllable cyclodextrin coverage, its preparation method, and its application. Background Technology

[0002] Polyrotaxanes (PRs) are classic supramolecular compounds with mechanically interlocked structures, possessing both dynamic topological structures and stable polymeric backbones. They have wide applications in gels, elastomers, battery adhesives, solid electrolytes, and biomedicine. Cyclodextrins, as macrocyclic molecules, are widely used in the synthesis of PRs. In terms of guest molecule selection, α-cyclodextrin and polyethylene glycol are size-matched, and PRs based on these two host-guest molecules have seen significant development and application.

[0003] To define the number of α-cyclodextrins on the polyethylene glycol (PEG) chain, Harada et al. proposed the concept of cyclodextrin coverage ratio (CD ratio) (Harada A, Li J, Kamachi M. Preparation and properties of inclusion complexes of polyethylene glycol with alpha-cyclodextrin[J]. Macromolecules, 1993, 26(21): 5698-5703). When the cyclodextrin coverage ratio is low, there is a longer sliding distance on the PEG chain, which releases more network stress and has lower hysteresis. When the cyclodextrin coverage ratio is low, cross-linked polyrotaxanes form a molecular pulley structure, and the cyclodextrins have a longer sliding distance on the PEG backbone, which releases more network stress, resulting in better ductility of the prepared material. When the cyclodextrin coverage ratio is 2%, a large amount of the PEG backbone is exposed, generating strain-induced crystals during stretching, further enhancing the mechanical properties of the material.

[0004] However, early methods for controlling the coverage of cyclodextrin involved adjusting the reaction temperature and using mixed solvents during end-capping, which were time-consuming and potentially dangerous. Therefore, developing a green, pollution-free, safe, rapid, and controllable method for synthesizing low-coverage polyrotaxanes is of great significance. Summary of the Invention

[0005] To address the aforementioned problems in existing technologies, the technical problem this invention aims to solve is to provide a method for preparing polyrotaxanes with controllable cyclodextrin coverage. Based on the mechanism of competition between 3-hydroxyadamantane-1-carboxylic acid and polyethylene glycol within the cyclodextrin cavity, a polyrotaxane with low CD coverage is synthesized. Another technical problem this invention aims to solve is to provide a polyrotaxane prepared by the above method that exhibits better mechanical properties. Furthermore, this invention also aims to provide applications of the above-mentioned polyrotaxane in gel materials, elastomer materials, battery adhesives, solid electrolytes, and biomedical materials.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0007] A method for preparing polyrotaxane with controllable cyclodextrin coverage involves dissolving α-cyclodextrin, 3-hydroxyadamantane-1-carboxylic acid, and polyethylene glycol diamine in deionized water and assembling them under cold conditions to form a quasi-polyrotaxane, followed by end-capping to obtain the polyrotaxane. The polyethylene glycol diamine is prepared from polyethylene glycol and N,N'-carbonyldiimidazole. The cyclodextrin coverage of the polyrotaxane is directionally controlled by adjusting the mass ratio of α-cyclodextrin to 3-hydroxyadamantane-1-carboxylic acid, the order of addition of 3-hydroxyadamantane-1-carboxylic acid, and the cold assembly time. The obtained polyrotaxane has a cyclodextrin coverage of 0.5% to 2.5%.

[0008] Preferably, the preparation process of the polyethylene glycol diamine is as follows: under the protection of an inert gas, polyethylene glycol is dissolved in anhydrous tetrahydrofuran, N,N'-carbonyldiimidazole and ethylenediamine are added, and after the reaction is completed, the mixture is dried to obtain polyethylene glycol diamine.

[0009] Preferably, the average molecular weight of the polyethylene glycol is 10,000.

[0010] Preferably, the ratio of polyethylene glycol, N,N'-carbonyldiimidazole, and ethylenediamine is 10:0.85:1 (g / g / mL). The reaction temperature is 50°C.

[0011] Preferably, the mass ratio of α-cyclodextrin, 3-hydroxyadamantane-1-carboxylic acid, and polyethylene glycol diamine is 100:14.4 to 1:20.

[0012] Preferably, the refrigeration assembly temperature is 4°C, and the refrigeration assembly time is 24h or 48h.

[0013] Preferably, the order of addition of the 3-hydroxyadamantane-1-carboxylic acid is as follows: first, 3-hydroxyadamantane-1-carboxylic acid and α-cyclodextrin are added for pre-assembly, then polyethylene glycol diamine is added for cold assembly to obtain a quasi-polyalkane, and then 3-hydroxyadamantane-1-carboxylic acid is added for end-capping reaction.

[0014] Preferably, the mass ratio of the 3-hydroxyadamantane-1-carboxylic acid added during pre-assembly to the 3-hydroxyadamantane-1-carboxylic acid added during the end-capping reaction is 1 to 14.4:12.

[0015] The method for preparing polyrotaxane with controllable cyclodextrin coverage specifically includes the following steps:

[0016] 1) Under inert gas protection, polyethylene glycol was dissolved in anhydrous tetrahydrofuran, N,N'-carbonyldiimidazole was added first to react, and after the reaction was completed, ethylenediamine was added dropwise to react and obtain a reaction solution; the obtained reaction solution was added dropwise to diethyl ether, filtered, the precipitate was dissolved in dichloromethane, and then added dropwise to diethyl ether again, the precipitate was filtered, dried, and polyethylene glycol diamine was obtained;

[0017] 2) Dissolve α-cyclodextrin in deionized water. After complete dissolution, add 3-hydroxyadamantane-1-carboxylic acid and stir until completely dissolved. Add the polyethylene glycol diamine obtained in step 1) and stir until the transparency of the system decreases. Then, refrigerate and assemble to obtain quasi-polyrotaxane.

[0018] 3) Dissolve 3-hydroxyadamantane-1-carboxylic acid and 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride in deionized water, add the quasi-polyrotaxane obtained in step 2), stir mechanically at room temperature for 24 h, then add 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride, continue the reaction for 12 h, remove the water in the system by rotary evaporation, add dimethyl sulfoxide, and obtain a transparent liquid;

[0019] 4) Dialyze the transparent liquid obtained in step 3) in deionized water for two days using a dialysis bag, changing the water 5-6 times, and freeze-dry to obtain cyclodextrin-coated polyrotaxane.

[0020] Preferably, in step 3), the mass ratio of the first addition of 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride to the second addition of 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride is 2:1.

[0021] The method for preparing polyrotaxane with controllable cyclodextrin coverage yields polyrotaxane.

[0022] The polyrotaxane described herein has the following structural formula:

[0023]

[0024] Where n is the number of repeating units on polyethylene glycol, and the molecular weight of this PEG is Mn = 10000, so n = 113.

[0025] The application of the polyrotaxane in gel materials, elastomer materials, battery adhesives, solid electrolytes, and biomedical materials.

[0026] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0027] 1) Based on the mechanism of competition between 3-hydroxyadamantane-1-carboxylic acid and polyethylene glycol in the cyclodextrin cavity, this invention synthesizes polyrotaxane with a cyclodextrin coverage of 0.5-2.5%; by changing the molecular molar ratio of adamantane derivative and cyclodextrin, PR with different cyclodextrin coverage is synthesized, and the cyclodextrin coverage is controllable within a certain range.

[0028] 2) In this invention, after α-cyclodextrin is dissolved in water and before PEG is added for assembly, a certain amount of OH-Ada-COOH is added to assemble with α-cyclodextrin first. After PEG is dissolved, because some α-cyclodextrin forms host-guest complexes with OH-Ada-COOH, the number of α-cyclodextrin that can be assembled with PEG decreases, thereby achieving the purpose of reducing the coverage of cyclodextrin.

[0029] 3) This invention proposes a safe, rapid, and controllable method for synthesizing high-yield, low-coverage polyrotaxanes. All reactions are carried out at room temperature in an aqueous phase, and the reaction conditions are mild, green, and pollution-free. Attached Figure Description

[0030] Figure 1 Synthetic routes for polyethylene glycol diamine (PEG-BA) and polyrotaxane (PR);

[0031] Figure 2 The 1H NMR spectrum of the polyrotaxane prepared in Example 1;

[0032] Figure 3 The 1H NMR spectrum of the polyrotaxane prepared in Example 2;

[0033] Figure 4 The 1H NMR spectrum of the polyrotaxane prepared in Example 3;

[0034] Figure 5 The 1H NMR spectrum of the polyrotaxane prepared in Example 4;

[0035] Figure 6 The 1H NMR spectrum of the polyrotaxane prepared in Example 5;

[0036] Figure 7 The 1H NMR spectrum of the polyrotaxane prepared in Example 6;

[0037] Figure 8 The 1H NMR spectrum of the polyrotaxane prepared in Example 7;

[0038] Figure 9 The graph shows the relationship between the number of CDs on a single PEG chain and the CD / OH-Ada-COOH concentration ratio in Examples 1-7. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of this invention clearer, the invention is further described below with reference to specific embodiments. Unless otherwise specified, the technical means used in the following embodiments are all conventional means well known to those skilled in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0040] In the following examples, α-CD is α-cyclodextrin, PEG is polyethylene glycol, CDI is N,N'-carbonyldiimidazole, EDA is ethylenediamine, OH-Ada-COOH is 3-hydroxyadamantane-1-carboxylic acid, PEG-BA is polyethylene glycol diamine, and DMT-MM is 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride.

[0041] Figure 1 The synthetic route diagram for polyethylene glycol diamine PEG-BA and polyrotaxane PR is as follows:

[0042] 1) Place a certain amount of PEG monomer in a three-necked flask and dry overnight to remove moisture from the system; under inert gas protection, add an organic solvent to dissolve the PEG monomer, then add the formulated amount of CDI, react for a period of time, add a small amount of EDA, after the reaction is complete, add diethyl ether to precipitate, filter and dry to obtain PEG-BA;

[0043] 2) Dissolve α-CD in a solvent. After it is completely dissolved, add a small amount of OH-Ada-COOH and stir to dissolve. Then add the formulated amount of PEG-BA and continue stirring until the transparency of the system decreases. After refrigeration, quasi-polyrotaxane is obtained.

[0044] 3) Dissolve the prescribed amounts of OH-Ada-COOH and DMT-MM in a solvent and add them to the quasi-polyrotaxane. After reacting for a period of time, add a small amount of DMT-MM. After removing the water by rotary evaporation, add a certain amount of DMSO to make the white solid transparent. Transfer the system to a dialysis belt for dialyzing, and then freeze-dry to obtain polyrotaxane with controllable cyclodextrin coverage.

[0045] Example 1

[0046] A method for preparing polyrotaxane with controllable cyclodextrin coverage specifically includes the following steps:

[0047] 1) Weigh 10g PEG (1mmol, Mn=10000) into a 250mL three-necked flask, dry it overnight in an oven at 85℃ to remove water from the system, add 25mL anhydrous THF under an argon atmosphere, and stir at 50℃ until the PEG is dissolved.

[0048] 2) Add 0.85 g CDI to the system obtained in step 1) through a solid funnel, react at 50 °C for 24 h, add 1 mL EDA dropwise after the reaction is complete, and continue to react at 50 °C for 24 h to obtain a reaction solution; add the obtained reaction solution dropwise to a large amount of diethyl ether, filter to obtain a white precipitate, dissolve the precipitate with a small amount of dichloromethane, add it dropwise to a large amount of diethyl ether again, precipitate and filter to obtain a white powdery solid, dry in an oven at 85 °C overnight to obtain PEG-BA;

[0049] 3) Weigh 5.0g of α-CD and dissolve it in 35mL of deionized water. After it is completely dissolved, add 0.05g of OH-Ada-COOH and stir until it is completely dissolved. The solution is clear and transparent. Add 1.0g of PEG-BA and stir until it is dissolved. A white precipitate begins to form. As the stirring time increases, the transparency of the system decreases. After the transparency of the system decreases, refrigerate at 4℃ for 24h to obtain quasi-polyrotaxane.

[0050] 4) Dissolve 0.6g OH-Ada-COOH and 1.2g DMT-MM in 12mL of deionized water, add the quasi-polyrotaxane obtained in step 3), stir mechanically at room temperature for 24h, add 0.6g DMTMM, continue the reaction for 12h, remove water from the system by rotary evaporation, add 20mL DMSO, and turn the white solid into a transparent liquid, proving that the disassembly is complete;

[0051] 5) Dialyze the transparent liquid obtained in step 4) in 4000 mL of deionized water for two days using a pretreated dialysis bag (MWCO:12000) to remove unreacted small molecules. Change the water 5-6 times, and then freeze-dry to obtain cyclodextrin-coated polyrotaxane with a yield of 15-22%.

[0052] Example 2

[0053] In preparing polyrotaxanes with controllable cyclodextrin coverage, the mass of OH-Ada-COOH added in step 3) was 0.1 g, and the remaining preparation methods and parameters were the same as in Example 1, resulting in a cyclodextrin-covered polyrotaxane yield of 20-23%.

[0054] Example 3

[0055] In preparing polyrotaxane with controllable cyclodextrin coverage, the mass of OH-Ada-COOH added in step 3) was 0.3 g, and the remaining preparation methods and parameters were the same as in Example 1. The yield of the obtained polyrotaxane was 14-20%.

[0056] Example 4

[0057] In preparing polyrotaxane with controllable cyclodextrin coverage, the mass of OH-Ada-COOH added in step 3) was 0.72 g, and the remaining preparation methods and parameters were the same as in Example 1. The yield of the obtained polyrotaxane was 17-26%.

[0058] Example 5

[0059] In preparing polyrotaxane with controllable cyclodextrin coverage, the cold assembly time in step 3) was 48 h, and the remaining preparation methods and parameters were the same as in Example 1. The yield of the obtained polyrotaxane was 19-25%.

[0060] Example 6

[0061] In preparing polyrotaxane with controllable cyclodextrin coverage, the cold assembly time in step 3) was 48 h, and the remaining preparation methods and parameters were the same as in Example 2. The yield of the obtained polyrotaxane was 16-21%.

[0062] Example 7

[0063] In preparing polyrotaxane with controllable cyclodextrin coverage, the cold assembly time in step 3) was 48 h, and the remaining preparation methods and parameters were the same as in Example 3. The yield of the obtained polyrotaxane was 18-24%.

[0064] Comparative Example 1

[0065] 1) Synthesis of PEG-BA:

[0066] 10 g of PEG (1 mmol, Mn = 10000) was weighed into a 250 mL three-necked flask and dried overnight in an oven at 85 °C to remove water from the system. 25 mL of anhydrous THF was added under an argon atmosphere, and the mixture was stirred at 50 °C until the PEG dissolved. 0.85 g of CDI was added to the resulting system through a solid funnel, and the reaction was carried out at 50 °C for 24 h. After the reaction was completed, 1 mL of EDA was added dropwise, and the reaction was continued at 50 °C for another 24 h to obtain a reaction solution. The reaction solution was added dropwise to a large amount of diethyl ether, filtered, and a white precipitate was obtained. The precipitate was dissolved in a small amount of dichloromethane and then added dropwise to a large amount of diethyl ether again. The precipitate was filtered to obtain a white powdery solid, which was dried overnight in an oven at 85 °C to obtain PEG-BA.

[0067] 2) PEG-BA and hydroxypropylated α-cyclodextrin assemble to form quasi-polyrotaxane:

[0068] Weigh 0.7680g HPCD and dissolve it in 5mL of deionized water. After it is completely dissolved, add 0.2214g PEG-BA and stir until it is completely dissolved. The solution remains clear and transparent. Place it in a refrigerator at 4℃ for 48 hours. After taking it out, it is still a clear and transparent solution.

[0069] 3) End-capping reaction of quasi-polyrotaxane:

[0070] Weigh 0.15 g of OH-Ada-COOH and 0.33 g of DMT-MM and add them to the above system. Stir magnetically at room temperature for 24 hours. After adding OH-Ada-COOH, the system changed from clear and transparent to pale yellow and turbid. Transfer the reaction solution to a pretreated dialysis bag (MWCO: 12000) and dialyze against deionized water for two days, changing the water 5-6 times. The liquid in the dialysis bag returned to clear and transparent. Freeze-dry to obtain a white powder product with a yield of 20-27%.

[0071] Example 8

[0072] The cyclodextrin-coated polyrotaxanes of Examples 1-7 and Comparative Example 1 were characterized by NMR. The number of α-CDs generating PRs was calculated by the integral area of ​​H on α-CDs and the integral ratio of H on the methylene groups of the PEG backbone. The results are shown in Table 1 below, where N CD / per PEG indicates the number of α-cyclodextrin molecules per PEG chain; CD coverage / % indicates the cyclodextrin coverage percentage. The 1H NMR spectra of the polyrotaxanes prepared in Examples 1-7 are shown below. Figure 2-8 As shown.

[0073] Table 1. Cyclodextrin coverage results of the polyrotaxanes prepared in Examples 1-7 and Comparative Example 1.

[0074] <![CDATA[N CD / per PEG]]> CD coverage / % Example 1 1.5 1.3 Example 2 0.8 0.7 Example 3 0.7 0.6 Example 4 0.5 0.5 Example 5 13 1.5 Example 6 3.2 2.5 Example 7 1.7 1.5 Comparative Example 1 1.6 1.4

[0075] From Table 1 and Figure 9 It is evident that shortening the assembly time and increasing the OH-Ada-COOH concentration both reduce the α-CD coverage on the PEG chain. When the α-CD to OH-Ada-COOH concentration ratio is constant, the number of α-CDs on a single PEG chain increases as the refrigerated assembly time increases from 24 hours to 48 hours. When the refrigerated assembly time is 24 hours, the number of α-CDs does not significantly increase with the increase in the α-CD to OH-Ada-COOH concentration ratio. When the refrigerated assembly time is 48 hours, the α-CD coverage increases with the increase in the concentration ratio. At 24 hours of refrigeration, the presence of OH-Ada-COOH within the α-CD cavity makes it difficult for PEG-BA to assemble with α-CDs to form polyrotaxane. However, when the refrigeration time is extended to 48 hours, as the OH-Ada-COOH ratio decreases, PEG-BA can assemble with more α-CDs, thus increasing the α-CD coverage of the resulting polyrotaxane. When the α-CD coverage is low, the synthesized polyrotaxane is water-soluble. When the number of α-CDs is 13, the synthesized polyrotaxane will form a white precipitate in water.

[0076] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing polyrotaxane with controllable cyclodextrin coverage, characterized in that, Specifically, the following steps are included: 1) Under inert gas protection, polyethylene glycol was dissolved in anhydrous tetrahydrofuran, N,N'-carbonyldiimidazole was added first to react, and after the reaction was completed, ethylenediamine was added dropwise to react and obtain a reaction solution; the obtained reaction solution was added dropwise to diethyl ether, filtered, the precipitate was dissolved in dichloromethane, and then added dropwise to diethyl ether again, the precipitate was filtered, dried, and polyethylene glycol diamine was obtained; 2) First, dissolve α-cyclodextrin in deionized water. After complete dissolution, add 3-hydroxyadamantane-1-carboxylic acid and stir until completely dissolved. Then, add the polyethylene glycol diamine obtained in step 1) and stir until the transparency of the system decreases. After cold assembly, quasi-polyrotaxane is obtained. The mass ratio of α-cyclodextrin, 3-hydroxyadamantane-1-carboxylic acid and polyethylene glycol diamine is 100:14.4~1:

20. The cold assembly temperature is 4℃ and the cold assembly time is 24h or 48h. 3) Dissolve 3-hydroxyadamantane-1-carboxylic acid and 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride in deionized water, add the quasi-polyrotaxane obtained in step 2), stir mechanically at room temperature for 24 h, then add 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride, continue the reaction for 12 h, remove water from the system by rotary evaporation, add dimethyl sulfoxide, and obtain a transparent liquid; the mass ratio of 3-hydroxyadamantane-1-carboxylic acid added in the pre-assembly to that added in the end-capping reaction is 1~14.4:12; 4) Dialyze the transparent liquid obtained in step 3) in deionized water for two days using a dialysis bag, changing the water 5-6 times, and freeze-dry to obtain cyclodextrin-coated polyrotaxane.

2. The polyrotaxane prepared by the method for preparing polyrotaxane with controllable cyclodextrin coverage as described in claim 1.

3. The polyrotaxane according to claim 2, characterized in that, The structural formula is as follows: ； Where n = 113.

4. The application of the polyrotaxane according to claim 2 or 3 in the preparation of gel materials, elastomer materials, battery adhesives, solid electrolytes, and biomedical materials.

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