Self-crosslinking stabilized polymerization-induced self-assembly nanoparticles and preparation method thereof

Abstract

The invention relates to a preparation method of self-crosslinking stabilized polymerization-induced self-assembly nanoparticles, which is characterized in that hydroxymethyl acrylamide with self-reaction activity is used as a self-crosslinking monomer, and crosslinking stabilized nano-micelles with various morphologies are efficiently prepared through polymerization-induced self-assembly. In the polymerization process, hydroxymethyl in hydroxymethyl acrylamide reacts to remove water and formaldehyde to form a methylene bisacrylamide structure for gradual cross-linking, the cross-linking reaction rate is moderate, the transformation of the micelle morphology in the dynamic process is not influenced, and the cross-linking density is further improved in the later stage of polymerization, so that the effective stabilization of the micelle morphology is realized. Compared with the prior art, the preparation method has the advantages that the common potential crosslinking monomer with self-reaction tendency is adopted, and the efficient crosslinking stability of the micelle structure is realized while the morphology diversity is ensured.

Description

Technical Field

[0001] This invention relates to the field of polymer nanomaterials technology, and in particular to a self-crosslinking stabilized polymerization-induced self-assembly nanoparticle and its preparation method. Background Technology

[0002] Polymerization-induced self-assembly (PIS) is a highly efficient method combining polymerization and self-assembly. It typically uses a solubilizing macromolecular initiator or chain transfer agent as a stabilizing block to initiate the polymerization of nucleating monomers in a selective solvent. As the nucleating chain segment gradually grows, its solubility changes from solubilizing to hydrophobic, thereby driving in-situ self-assembly during polymerization and forming nanoparticles with various morphologies. Over the past two decades, PIS has developed rapidly and has become an important tool for preparing polymer nanoparticles.

[0003] However, nanoparticles prepared by polymerization-induced self-assembly technology are mostly thermodynamically stable dynamic structures, which face the problem of insufficient stability in practical applications. When the external environment (such as concentration, temperature, dispersion medium, etc.) changes, nanoparticles are prone to dissociation. Therefore, self-crosslinking stabilization is a necessary treatment method in many practical application scenarios.

[0004] There are currently two main methods of cross-linking: The first method involves introducing crosslinking monomers during chain extension polymerization, such as adding diacrylate or triacrylate monomers in free radical polymerization. However, this crosslinking method tends to result in excessively high crosslinking density, which limits the fusion and morphological evolution of micelles during the kinetic process. Typically, only spherical micelles can be obtained, making it difficult to form more complex structures.

[0005] The second method involves pre-introducing reactive functional groups such as hydroxyl and aldehyde groups into the polymer chain, followed by a post-crosslinking reaction after the nanoparticles are formed. Although this method allows for control over morphology, the steps are more complex, involving the design of functional group monomers, additional crosslinking reactions, and purification processes.

[0006] In comparison, the first method is simpler to operate and more likely to produce a system with more uniformly dispersed crosslinking points. Currently, some scholars have proposed using asymmetric double-bond active divinyl monomers as comonomers, which can control the crosslinking density to a certain extent. That is, maintaining a low degree of crosslinking during the micelle morphology evolution stage and increasing the degree of crosslinking after the micelle morphology is formed to further stabilize it (ACS Macro Letters, 2016, 5, 3, 316).

[0007] Overall, the options for crosslinking stabilization of polymerization-induced self-assembled nanoparticles are still relatively limited, and further exploration is needed to enrich the "toolbox" of synthetic methods. Summary of the Invention

[0008] Based on this, the present invention provides a method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles. This method produces nanoparticles with diverse morphologies and stable crosslinking, which maintain their morphology in a good solvent and also avoid gelation.

[0009] First aspect: A method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles includes the following steps: The stable chain monomer, trithioester, and azobisisobutyronitrile were added to ethanol to obtain a first ethanol solution. The first ethanol solution was placed under an inert atmosphere and reacted at 70°C for 4-24 hours. Subsequently, the precipitate was formed and dried under vacuum to obtain a solvent-friendly macromolecular chain transfer agent. The macromolecular chain transfer agent, self-crosslinking monomer, nucleating monomer and azobisisobutyronitrile were added to ethanol to obtain a second ethanol solution. The second ethanol solution was placed under an inert atmosphere and reacted at 70~80℃ for 24h to obtain the self-crosslinking stabilized polymerization-induced self-assembly nanoparticles. The stabilizing monomer is at least one of acrylamide, dimethacrylamide, polyethylene glycol monomethyl ether methacrylate, and N-(2-dimethylaminoethyl)acrylamide; The self-crosslinking monomer is hydroxymethylacrylamide; The nucleating monomer is at least one of styrene, methyl methacrylate, benzyl methacrylate, ethyl methacrylate, and butyl methacrylate.

[0010] This invention utilizes self-reactive hydroxymethylacrylamide as a self-crosslinking monomer to efficiently prepare crosslinked and stabilized nanomicelles with various morphologies through polymerization-induced self-assembly. During polymerization, the hydroxymethyl group in hydroxymethylacrylamide reacts to dehydrate and remove formaldehyde, forming a methylenebisacrylamide structure that gradually crosslinks. This crosslinking reaction has a moderate rate, does not affect the transformation of micelle morphology during the kinetic process, and further increases the crosslinking density in the later stages of polymerization, thereby achieving effective stabilization of the micelle morphology. Compared with existing technologies, this invention uses a common, potentially crosslinking monomer with self-reactive properties, achieving efficient crosslinking stabilization of the micelle structure while ensuring morphological diversity.

[0011] As a preferred embodiment, the trisulfide is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid and / or 4-cyano-4-(propyltrithiocarbonate)valerate.

[0012] As a preferred embodiment, the molar ratio of the stabilizing monomer, trithioester, and azobisisobutyronitrile is 40~80:1:0.1~0.3.

[0013] As a preferred embodiment, the solid content in the first ethanol solution is 20~40wt%.

[0014] As a preferred embodiment, the molar ratio of the nucleating monomer, the macromolecular chain transfer reagent, and the azobisisobutyronitrile is 60~300:1:0.1~0.3.

[0015] As a preferred embodiment, the molar amount of the self-crosslinking monomer is 10-15% of the nucleating monomer, measured by molar mass.

[0016] As a preferred embodiment, the solid content in the second ethanol solution is 15-30 wt%.

[0017] As a preferred embodiment, the method further includes the following steps: after the first ethanol solution is reacted in an inert atmosphere, it is cooled and then precipitated in diethyl ether; The second ethanol solution was reacted in an inert atmosphere, cooled, and then precipitated in diethyl ether.

[0018] The second aspect: A self-crosslinking stabilized polymerization-induced self-assembly nanoparticle prepared by the preparation method described in the first aspect has the following structural formula: .

[0019] As a preferred embodiment, the microstructure of the self-crosslinking stabilized polymerization-induced self-assembly nanoparticles is at least one of spherical, worm-like, rod-like, or vesicular shapes. Attached Figure Description

[0020] Figure 1 The image shows the GPC spectrum of the polydimethylacrylamide macromolecular chain transfer agent prepared in Example 1.

[0021] Figure 2 The image shows the SEM image of the nanomicelles prepared in Example 1 when dispersed in ethanol.

[0022] Figure 3 The image shows the SEM image of the nanomicelles prepared in Example 1 when dispersed in tetrahydrofuran.

[0023] Figure 4 The image shows the SEM image of the nanomicelles prepared in Example 2 when dispersed in ethanol.

[0024] Figure 5 The image shows the SEM image of the nanomicelles prepared in Example 3 when dispersed in ethanol.

[0025] Figure 6 This is a SEM image of the nanomicelles prepared in Example 4 when dispersed in ethanol.

[0026] Figure 7 The images show the DLS results of the nanomicelles prepared in Examples 1-4 when dispersed in ethanol and tetrahydrofuran. Detailed Implementation

[0027] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0028] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0029] A method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles includes the following steps: The stable chain monomer, trithioester, and azobisisobutyronitrile were added to ethanol to obtain a first ethanol solution. The first ethanol solution was placed under an inert atmosphere and reacted at 70°C for 4-24 hours. Subsequently, the precipitate was placed in diethyl ether and dried under vacuum to obtain a solvent-friendly macromolecular chain transfer agent.

[0030] A macromolecular chain transfer agent, a self-crosslinking monomer, a nucleating monomer, and azobisisobutyronitrile were added to ethanol to obtain a second ethanol solution. The second ethanol solution was placed under an inert atmosphere and reacted at 70-80℃ for 24 h. Subsequently, the solution was precipitated in diethyl ether and dried under vacuum to obtain self-crosslinking stabilized polymerization-induced self-assembly nanoparticles.

[0031] The stabilizing monomer is at least one of acrylamide, dimethacrylamide, polyethylene glycol monomethyl ether methacrylate, and N-(2-dimethylaminoethyl)acrylamide.

[0032] The molar ratio of the stabilizing monomer, trithioester, and azobisisobutyronitrile is 40~80:1:0.1~0.3. The solid content in the first ethanol solution is 20~40wt%.

[0033] The self-crosslinking monomer is hydroxymethylacrylamide; the nucleating monomer is at least one of styrene, methyl methacrylate, benzyl methacrylate, ethyl methacrylate, and butyl methacrylate.

[0034] The molar ratio of nucleating monomer, macromolecular chain transfer reagent, and azobisisobutyronitrile is 60~300:1:0.1~0.3. The molar amount of the self-crosslinking monomer is 10~15% of the nucleating monomer by molar weight. The solid content in the second ethanol solution is 15~30 wt%.

[0035] A self-crosslinking stabilized polymerization-induced self-assembly nanoparticle has a microstructure of at least one of spherical, worm-like, rod-like, or vesicular shapes. Its structural formula is: .

[0036] Example 1 1. Synthesis of polydimethylacrylamide macromolecular chain transfer agent 10.0 g of dimethacrylamide, 466.3 mg of 4-cyano-4-(propyltrithiocarbonate)valerate, and 27.3 mg of azobisisobutyronitrile were dissolved in 40 g of ethanol. After cooling with liquid nitrogen, the mixture was evacuated and then purged with nitrogen. This process was repeated three times. The mixture was then reacted at 70 °C for 8 h. After cooling, the precipitate was collected in diethyl ether and dried under vacuum to obtain a polydimethacrylamide macromolecular chain transfer agent. Figure 1 The GPC image of the polydimethylacrylamide macromolecular chain transfer agent confirms the synthesis of the polymer. NMR calculations show a DP of 54 and a molecular weight of 5623.

[0037] 2. Synthesis of cross-linked stabilized nanomicelles 100.0 mg of polydimethylacrylamide macromolecular chain transfer agent, 10.8 mg of hydroxymethylacrylamide, 187.8 mg of benzyl methacrylate, 0.6 mg of azobisisobutyronitrile, and 1120 mg of ethanol were added to an ampere tube and dissolved evenly to a solid content of 15 wt%. After cooling with liquid nitrogen, a vacuum was drawn, and nitrogen gas was introduced. This process was repeated three times. The tube was then sealed, and the reaction was carried out at 70 °C for 24 h. After cooling, the precipitate was placed in diethyl ether and dried under vacuum to obtain cross-linked stabilized nanomicelles. Figure 2 The image shows a SEM image of nanomicelles in ethanol, which are spherical micelles. Figure 3 The image shows a SEM image of the nanomicelles in the good solvent tetrahydrofuran (THF). It can be seen that their morphology is still maintained, proving that the core has been cross-linked and stabilized.

[0038] Example 2 The method is basically the same as in Example 1, except that in step 2, the amount of hydroxymethylacrylamide is 14.9 mg, the amount of benzyl methacrylate is 259.8 mg, and the amount of ethanol is 2127 mg. Figure 4 The image shows a SEM image of the nanomicelles, which reveals that their morphology is worm-like / rod-like.

[0039] Example 3 The method is basically the same as in Example 1, except that in step 2, the amount of hydroxymethylacrylamide is 24.1 mg, the amount of benzyl methacrylate is 419.4 mg, and the amount of ethanol is 3083 mg. Figure 5 The image shows a SEM image of the nanomicelles, which reveals that their morphology is vesicular (hollow and collapsed into a bowl shape in the dry state).

[0040] Example 4 It is basically the same as Example 1, except that in step 2, the reaction temperature is 80°C. Figure 6 The image shows a SEM image of the nanomicelles, which reveals that they are spherical micelles.

[0041] Figure 7The insets A, B, C, and D are DLS particle size distribution diagrams of micelles in Examples 1, 2, 3, and 4 after dispersion in ethanol and the good solvent tetrahydrofuran, respectively. It can be seen that even in the good solvent THF, the particle size is almost unchanged, and the slight increase in particle size in THF may be due to swelling.

[0042] Example 5 1. Synthesis of polyethylene glycol monomethyl ether methacrylate (PMPEGMA) macromolecular chain transfer agent 5.0 g of MPEGMA (Mn~475), 58.3 mg of 4-cyano-4-(propyltrithiocarbonate)valeric acid, 10.2 mg of azobisisobutyronitrile, and 8.0 g of ethanol were dissolved in an ampere tube. After cooling with liquid nitrogen, the mixture was evacuated and then purged with nitrogen. This process was repeated three times. The mixture was reacted at 70 °C for 8 h. After cooling, the precipitate was placed in diethyl ether and dried under vacuum to obtain PMPEGMA macromolecular chain transfer agent. The DP was calculated to be 34 and the molecular weight was 16427 by NMR.

[0043] 2. Synthesis of cross-linked stabilized nanomicelles 105.0 mg of PMPEGMA, 17.1 mg of hydroxymethylacrylamide, 169.8 mg of methyl methacrylate, and 0.3 mg of azobisisobutyronitrile were dissolved in 877 mg of ethanol, with a solid content of 25 wt%. After cooling with liquid nitrogen, the mixture was evacuated and then purged with nitrogen. This process was repeated three times. The mixture was reacted at 70 °C for 24 h. After cooling, the precipitate was placed in diethyl ether and dried under vacuum to obtain cross-linked stabilized nanomicelles.

[0044] Comparative Example 1 The procedure was essentially the same as in Example 1, except that the amount of hydroxymethylacrylamide added in step 2 was 8.5 mg. The resulting nanoparticles were dissolved in tetrahydrofuran.

[0045] Comparative Example 2 The process is basically the same as in Example 1, except that in step 2, the amount of hydroxymethylacrylamide added is 22.0 mg, and the system gels.

[0046] Comparative Example 3 The process is basically the same as in Example 1, except that the reaction time in step 2 is 12 hours, and the resulting nanoparticles are dissolved in tetrahydrofuran.

[0047] Comparative Example 4 The reaction was basically the same as in Example 1, except that the reaction time in step 2 was 60°C and the resulting nanoparticles were dissolved in tetrahydrofuran.

[0048] Comparative Example 5 It is basically the same as Example 1, except that in step 2 the reaction time is 95°C and the system gels.

[0049] As can be seen from Comparative Examples 1-5, when the amount of crosslinking monomer added is insufficient (Comparative Example 1), the reaction time is short (Comparative Example 3), or the reaction temperature is low (Comparative Example 4), the crosslinking strength is low and insufficient to maintain the stability of the micelle morphology; however, when the amount of crosslinking monomer added is too high (Comparative Example 2) or the reaction temperature is too high (Comparative Example 5), the crosslinking of the system will be too high, and the common gel phenomenon will occur during the reaction.

[0050] The above embodiments are merely illustrative of several implementations of the present invention, and their descriptions are relatively specific and detailed. However, they should not be construed as limiting the scope of the invention patent. For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles, characterized in that, Includes the following steps: The stable chain monomer, trithioester, and azobisisobutyronitrile were added to ethanol to obtain a first ethanol solution. The first ethanol solution was placed under an inert atmosphere and reacted at 70°C for 4-24 hours. Subsequently, the precipitate was formed and dried under vacuum to obtain a solvent-friendly macromolecular chain transfer agent. The macromolecular chain transfer agent, self-crosslinking monomer, nucleating monomer and azobisisobutyronitrile were added to ethanol to obtain a second ethanol solution. The second ethanol solution was placed under an inert atmosphere and reacted at 70~80℃ for 24h to obtain the self-crosslinking stabilized polymerization-induced self-assembly nanoparticles. The stabilizing monomer is at least one of acrylamide, dimethacrylamide, polyethylene glycol monomethyl ether methacrylate, and N-(2-dimethylaminoethyl)acrylamide; The self-crosslinking monomer is hydroxymethylacrylamide; The nucleating monomer is at least one of styrene, methyl methacrylate, benzyl methacrylate, ethyl methacrylate, and butyl methacrylate.

2. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 1, characterized in that, The trisulfide is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid and / or 4-cyano-4-(propyltrithiocarbonate)valerate.

3. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 2, characterized in that, The molar ratio of the stabilizer monomer, trithioester and azobisisobutyronitrile is 40~80:1:0.1~0.

3.

4. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 3, characterized in that, The first ethanol solution has a solid content of 20-40 wt%.

5. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 1, characterized in that, The molar ratio of the nucleating monomer, the macromolecular chain transfer reagent, and the azobisisobutyronitrile is 60~300:1:0.1~0.

3.

6. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 5, characterized in that, According to the molar amount of the self-crosslinking monomer, the molar amount of the nucleating monomer is 10 to 15% of the molar amount of the self-crosslinking monomer.

7. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 6, characterized in that, The second ethanol solution has a solid content of 15-30 wt%.

8. The method for preparing self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 1, characterized in that, The process also includes the following steps: after the first ethanol solution is reacted in an inert atmosphere, it is cooled and then precipitated in diethyl ether; The second ethanol solution was reacted in an inert atmosphere, cooled, and then precipitated in diethyl ether.

9. A self-crosslinking stabilized polymerization-induced self-assembly nanoparticle prepared by the preparation method according to any one of claims 1 to 8, having the following structural formula: 。 10. The self-crosslinking stabilized polymerization-induced self-assembly nanoparticles according to claim 9, characterized in that, The microscopic morphology is at least one of spherical, worm-like, rod-shaped, or vesicular.

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