Carboxyl-functionalized hydrophilic polyglycidyl methacrylate-based microspheres as well as preparation method and application thereof

Abstract

The invention relates to a carboxyl-functionalized hydrophilic polyglycidyl methacrylate-based microsphere and a preparation method and application thereof, the microsphere is of a core-shell structure, carboxyl-containing poly (methyl) acrylate or poly (methyl) acrylic acid is used as a shell layer, and a cross-linked polyglycidyl methacrylate-based polymer is used as a core layer. The preparation method comprises the following steps: firstly, preparing a poly (methyl) acrylate macroinitiator by adopting atom transfer radical polymerization, then initiating homopolymerization of a glycidyl methacrylate monomer or copolymerization of a glycidyl methacrylate and (methyl) acrylate monomer mixture by the initiator, and carrying out atom transfer radical polymerization-mediated polymerization-induced self-assembly reaction to obtain the polymer. And after the polymerization is finished, adding a crosslinking agent to crosslink the glycidyl methacrylate unit to obtain the stable polymer microspheres. And finally, hydrolyzing the poly (methyl) acrylate chain segment of the shell layer to prepare the hydrophilic microspheres. The preparation method disclosed by the invention has the advantages of simplicity and convenience in operation and high solid content of a product, and the hydrophilicity, the particle size and the like of the microspheres can be accurately regulated and controlled by changing monomer types and polymerization modes.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer materials, and in particular to carboxyl-functionalized hydrophilic poly(glycidyl methacrylate)-based microspheres, and a preparation method and application thereof. Background Art

[0002] The hydrophilicity and functional design of polymer microspheres play a decisive role in their application in many key fields. In the field of biomedicine, hydrophilic microspheres, as drug carriers, can improve the solubility and bioavailability of drugs and achieve precise drug delivery; hydrophilic microspheres can encapsulate anticancer drugs and reach tumor cells more efficiently (Journal of Drug Delivery Science and Technology, 2023, 87: 104754.). In terms of environmental governance, hydrophilic microspheres can be used to treat heavy metal ions and organic pollutants in sewage due to their excellent pollutant adsorption performance (RSCA Advances, 2020, 10 (67): 41187-41196.). As an important functional polymer, poly (glycidyl methacrylate) contains epoxy functional groups that are easy to open in its molecular structure and has high reactivity. It has attracted much attention in the field of polymer self-assembly preparation. Previous studies have used traditional solution self-assembly methods to prepare a variety of poly(glycidyl methacrylate)-based microspheres. For example, Ma et al. synthesized poly(n-butyl methacrylate)-b-poly(glycidyl methacrylate) spherical self-assemblies via atom transfer radical polymerization (Electrophoresis, 2012, 33(13):2019-2027). However, traditional solution self-assembly can usually only be performed under dilute solution conditions (<1 wt%), which greatly limits its industrial application (Macromolecules, 2017, 50(9):3439-3463).

[0003] Although the polymerization-induced self-assembly technique has advantages such as ease of operation and the ability to prepare polymer self-assemblies at high solid contents (up to 50 wt%) (Macromolecules, 2016, 49(6): 1985-2001), it still has many shortcomings in the preparation and functional modification of poly(methacrylate)-based microspheres. On the one hand, there is a large gap in the exploration of poly(methacrylate)-based microspheres in emerging self-assembly systems such as polymerization-induced self-assembly; on the other hand, the functional modification and application expansion of poly(methacrylate)-based microspheres prepared based on polymerization-induced self-assembly also need to be further explored. At the same time, hydrophilic polymer microspheres prepared using polymerization-induced self-assembly technology have initially shown broad application prospects. However, most existing studies focus on using amino groups as functional groups to achieve hydrophilicity of microspheres, and relatively few studies have been conducted on carboxyl-containing poly(meth)acrylate microspheres. For example, Chen et al. used 2-(N-methyl-N-(4-pyridyl)amino)ethyl acrylate monomer in a reversible addition-fragmentation chain transfer polymerization system in water to prepare block / random copolymer self-assemblies (Molecular Catalysis, 2022, 518: 112073.). This is mainly because carboxyl-containing monomers, such as acrylic acid and methacrylic acid, are difficult to achieve controlled / "living" polymerization, which greatly limits their application in polymerization-induced self-assembly systems. Poly(meth)acrylate tert-butyl ester can be hydrolyzed to poly(meth)acrylic acid under acidic conditions. Its molecular chain contains a large number of carboxyl groups, has high hydrophilicity and thermal stability, and is an ideal choice for constructing hydrophilic block copolymer microspheres (Macromolecular Chemistry and Physics, 2018, 219(17): 1800192.). In general, the current research on the preparation of hydrophilic microspheres based on poly(tert-butyl methacrylate) and poly(glycidyl methacrylate) systems and their functional modification and application expansion is not in-depth enough, and there is still a lot of room for exploration. Summary of the Invention

[0004] The purpose of the present invention is to provide a carboxyl functionalized hydrophilic poly(glycidyl methacrylate) based microspheres and a preparation method and application thereof, which are simple to operate, have a high solid content of the product, and can control the hydrophilicity of the microspheres.

[0005] The purpose of the present invention can be achieved by the following technical solution: a carboxyl functionalized hydrophilic poly(methacrylate) glycidyl ester-based microsphere, wherein the microsphere has a core-shell structure, wherein the carboxyl-containing poly(meth)acrylate or poly(meth)acrylic acid is the shell layer, and the cross-linked poly(methacrylate) glycidyl ester-based polymer is the core layer.

[0006] The core-shell hydrophilic polymer microspheres proposed in this invention use a poly(glycidyl methacrylate)-based polymer as the core and a carboxyl-containing poly(meth)acrylate or poly(meth)acrylic acid) as the shell. The carboxyl groups on the microspheres' surface impart excellent hydrophilicity, potentially leading to their potential applications in biomedicine, environmental remediation, and other fields.

[0007] Preferably, the microspheres (self-assembly) are spherical in shape, and have a particle size ranging from 30 nm to 5000 nm.

[0008] A method for preparing the above-mentioned carboxyl-functionalized hydrophilic poly(glycidyl methacrylate) microspheres comprises the following steps:

[0009] S1: Using ethyl 2-bromoisobutyrate as a small molecule initiator, a poly(meth)acrylate macroinitiator was prepared by atom transfer radical polymerization of (meth)acrylate monomers;

[0010] S2: Using poly(meth)acrylate as a macroinitiator, a polymerization-induced self-assembly reaction mediated by atom transfer radical polymerization is initiated to homopolymerize glycidyl methacrylate monomers or copolymerize a blend of glycidyl methacrylate and (meth)acrylate monomers to prepare microspheres with a poly(meth)acrylate shell and a poly(meth)acrylate-based polymer core;

[0011] S3: using a cross-linking agent to cross-link the glycidyl methacrylate units in the core to obtain cross-linked and stable polymer microspheres;

[0012] S4: using a hydrolysis agent to selectively hydrolyze the shell poly (meth)acrylate to obtain carboxyl functionalized hydrophilic poly (glycidyl methacrylate) based microspheres.

[0013] Preferably, the (meth)acrylate monomer in steps S1 and S2 is one or more combinations of tert-butyl acrylate, tert-butyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, polyethylene glycol monomethyl ether methacrylate, polyethylene glycol monomethyl ether acrylate, methoxypolyethylene glycol methacrylate, methoxypolyethylene glycol acrylate, 2-(dimethylamino)ethyl methacrylate, 2-morpholinoethyl methacrylate, methyl methacrylate, and methyl acrylate.

[0014] Wherein, at least one of S1 is a monomer of tert-butyl acrylate or tert-butyl methacrylate, and the molar content of tert-butyl acrylate or tert-butyl methacrylate is 25 to 100%;

[0015] Wherein, when the blend of glycidyl methacrylate and (meth)acrylate monomer in S2 is copolymerized, the molar content of glycidyl methacrylate is 25 to 100%.

[0016] More preferably,

[0017] Wherein, at least one of S1 is a monomer of tert-butyl acrylate or tert-butyl methacrylate, and the molar content of tert-butyl acrylate or tert-butyl methacrylate is 50 to 100%;

[0018] Wherein, when the blend of glycidyl methacrylate and (meth)acrylate monomer in S2 is copolymerized, the molar content of glycidyl methacrylate is 50 to 100%.

[0019] Preferably, the solvent used in step S1 is one or more combinations of toluene, xylene, anisole, dimethylformamide, and dimethyl sulfoxide.

[0020] Preferably, the polymerization temperature in step S1 is 25° C. to 100° C., and the polymerization time is 6 h to 48 h.

[0021] Preferably, the poly(meth)acrylate prepared in step S1 has a random structure or a block structure.

[0022] Preferably, the degree of polymerization of the poly(meth)acrylate prepared in step S1 is in the range of 5 to 500.

[0023] Further preferably, the degree of polymerization of the poly(meth)acrylate prepared in step S1 is in the range of 10 to 300.

[0024] Preferably, the atom transfer radical polymerization in step S2 includes any one of forward atom transfer radical polymerization, electron transfer activation and catalyst regeneration atom transfer radical polymerization, and initiator continuous catalyst regeneration atom transfer radical polymerization.

[0025] Further preferably, when forward atom transfer radical polymerization is adopted, the catalyst is a combination of cuprous bromide and one or more of tris(2-dimethylaminoethyl)amine, N,N,N′,N′,N″-pentamethyldiethylenetriamine, and tris(2-pyridylmethyl)amine complex.

[0026] Further preferably, when electron transfer activation and regeneration catalyst atom transfer radical polymerization is used, the catalyst is one or more combinations of copper bromide and complexes such as tris(2-dimethylaminoethyl)amine, N,N,N′,N′,N″-pentamethyldiethylenetriamine, and tris(2-pyridylmethyl)amine, and the reducing agent is stannous octoate.

[0027] Further preferably, when the initiator is continuously regenerated into the catalyst for atom transfer radical polymerization, the catalyst is one or more combinations of copper bromide and tris(2-dimethylaminoethyl)amine, N,N,N′,N′,N″-pentamethyldiethylenetriamine, and tris(2-pyridylmethyl)amine complex, and the free radical initiator is azobisisobutyronitrile.

[0028] Preferably, the solid content of the reaction system in step S2 is 1 to 30 wt %, and the monomer is glycidyl methacrylate monomer or a blend of glycidyl methacrylate and (meth)acrylate monomer.

[0029] Further preferably, the solid content of the reaction system in step S2 is 10-30 wt %, and the monomer is glycidyl methacrylate.

[0030] Preferably, the solvent used in step S2 is one or more combinations of n-hexane, cyclohexane, n-heptane, ethanol, methanol, dimethylformamide, and dimethyl sulfoxide.

[0031] Preferably, the polymerization temperature in step S2 is 25° C. to 100° C., and the polymerization time is 6 h to 48 h.

[0032] Preferably, the degree of polymerization of the poly(glycidyl methacrylate)-based polymer prepared in step S2 is in the range of 50 to 5000.

[0033] Further preferably, the degree of polymerization of the polyglycidyl methacrylate-based polymer prepared in step S2 is in the range of 100 to 1000.

[0034] Preferably, the cross-linking agent in step S3 is one or more combinations of ethanedithiol, 1,4-butanedithiol, 1,6-hexanedithiol, ethylenediamine, and piperazine.

[0035] Preferably, the solvent used in step S3 is one or more combinations of n-hexane, cyclohexane, n-heptane, ethanol, and methanol.

[0036] Preferably, the cross-linking temperature in step S3 is 25° C. to 100° C., and the cross-linking time is 6 h to 48 h.

[0037] Preferably, the hydrolysis reagent in step S4 is one or more combinations of trifluoroacetic acid, hydrochloric acid, p-toluenesulfonic acid, and trifluoromethanesulfonic acid.

[0038] Further preferably, the hydrolysis reagent in step S4 is trifluoroacetic acid.

[0039] Preferably, the solvent used in step S4 is one or more combinations of dichloromethane, toluene, chloroform, ethanol, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and dioxane.

[0040] Preferably, the hydrolysis temperature in step S4 is 25° C. to 100° C., and the time is 6 h to 48 h.

[0041] An application of the carboxyl functionalized poly(glycidyl methacrylate) microspheres is to use the microspheres as drug carriers, biological detection, and pollutant adsorption.

[0042] The hydrophilic microspheres of the present invention have potential applications in aqueous media fields such as drug delivery, biological detection, and pollutant adsorption.

[0043] In the present invention, the microspheres can be used as drug carriers to achieve targeted delivery and controlled release of drugs; can be used in the field of biological detection to achieve high-sensitivity detection of specific biological molecules; can be used in the field of pollutant adsorption to separate heavy metal ions or organic pollutants in water.

[0044] In the present invention, the core layer and the shell layer are connected by blocks, which are formed by microphase separation of different blocks or components of the same copolymer in a selective solvent and are connected by covalent bonds.

[0045] In the present invention, when the microspheres of the present invention are used to adsorb pollutants, the electrostatic attraction between the carboxyl radicals formed by the ionization of the carboxyl groups on the shell and the positive charges of the metal ions, as well as the complexation between the carboxyl oxygen and the metal ions can be relied upon.

[0046] The working principle of the present invention is:

[0047] In the present invention, first, a poly(meth)acrylate macroinitiator is prepared by atom transfer radical polymerization, and the macroinitiator is used to initiate polymerization-induced self-assembly mediated by atom transfer radical polymerization of glycidyl methacrylate monomer or a mixture of glycidyl methacrylate and (meth)acrylate monomer in a selective solvent; since the selective solvent is a good solvent for the poly(meth)acrylate macroinitiator and the glycidyl methacrylate monomer, and is also a poor solvent for the poly(meth)acrylate-based polymer, self-assembly occurs simultaneously during the polymerization process to form poly(meth)acrylate-based microspheres. Then, a cross-linking agent is used to cross-link and stabilize the glycidyl methacrylate units in the core. Finally, a hydrolysis reaction is performed to convert the (meth)acrylate units into (meth)acrylic acid, and a carboxyl group is introduced. By changing the polymerization formula and the structure of the polymer, poly(meth)acrylate-based microspheres of different sizes and hydrophilic properties can be prepared to meet the needs of different application scenarios.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] 1. The carboxyl-functionalized hydrophilic poly(glycidyl methacrylate)-based microspheres prepared by the present invention can achieve adjustable microsphere particle size and carboxyl content through atom transfer radical polymerization-mediated polymerization-induced self-assembly technology and post-polymerization modification, thereby achieving good dispersion and stability in water, broadening the application range of poly(glycidyl methacrylate)-based microspheres in the field of aqueous media.

[0050] 2. The method for preparing hydrophilic polymer microspheres proposed in the present invention adopts atom transfer radical polymerization-mediated polymerization-induced self-assembly technology to achieve polymerization and assembly simultaneously, is simple to operate, saves raw materials, and can obtain a high solid content product.

[0051] 3. The present invention provides a method for efficiently preparing carboxyl-functionalized hydrophilic polymer microspheres and develops its application research.

[0052] 4. The hydrophilic polymer microspheres prepared by the present invention can have potential application value in the fields of drug delivery, biological detection, pollutant adsorption, etc. by adjusting the copolymer structure and functional modification.

[0053] 5. The self-assembly method of the present invention is not limited to dilute solution conditions and is suitable for industrial applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 This is a transmission electron micrograph of the poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate)-based microspheres prepared in Example 1. The average size of the microspheres is 723±44 nm.

[0055] Figure 2 This is a transmission electron micrograph of the polymethacrylic acid-b-poly(methacrylic acid-co-glycidyl methacrylate) hydrophilic polymer microspheres prepared in Example 8. The average size of the microspheres is 401±16 nm.

[0056] Figure 3 This is a transmission electron micrograph of poly(tert-butyl methacrylate)-b-poly(methoxypolyethylene glycol methacrylate-co-glycidyl methacrylate) microspheres prepared in Example 9. The average size of the microspheres is 242±53 nm.

[0057] Figure 4 This is a transmission electron micrograph of the poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-poly(glycidyl methacrylate)-based microspheres prepared in Example 10. The average size of the microspheres is 235±107 nm. DETAILED DESCRIPTION

[0058] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0059] The present invention provides carboxyl functionalized hydrophilic poly(glycidyl methacrylate)-based microspheres and a preparation method and application thereof. The microspheres have a core-shell structure, wherein carboxyl-containing poly(meth)acrylate or poly(meth)acrylic acid is a shell layer and a cross-linked poly(glycidyl methacrylate)-based polymer is a core layer.

[0060] The preparation method involves first preparing a poly(meth)acrylate macroinitiator via atom transfer radical polymerization (ATRP). This initiator then initiates homopolymerization of glycidyl methacrylate monomers or copolymerization of a mixture of glycidyl methacrylate and (meth)acrylate monomers, followed by a polymerization-induced self-assembly reaction mediated by ATRP. After polymerization, a crosslinking agent is added to crosslink the polymer microspheres, yielding stable polymer microspheres. Finally, hydrophilic microspheres are prepared by hydrolyzing the poly(meth)acrylate segments in the shell.

[0061] The preparation method of the present invention has the advantages of simple operation and high solid content of the product, and can accurately control the hydrophilicity and particle size of the microspheres by changing the monomer type and polymerization method.

[0062] The following describes it in detail with reference to specific embodiments.

[0063] Unless otherwise specified, the reagents, methods, instruments and equipment used in the present invention are conventional reagents, methods, instruments and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0064] Example 1

[0065] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0066] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0067] Poly(tert-butyl methacrylate) macroinitiator was prepared by forward atom transfer radical polymerization. First, ethyl 2-bromoisobutyrate (0.4095 g, 2.099 mmol), tert-butyl methacrylate (35.0454 g, 246.5 mmol), N,N,N′,N′,N″-pentamethyldiethylenetriamine (1.4277 g, 8.244 mmol) and toluene (10.3 mL) were added to 500 mL of In the Schlenk flask, the dissolved oxygen was removed by three freeze-pump-thaw cycles. Dry cuprous bromide solid (0.5974 g, 4.164 mmol) was added in the third frozen state, and the freeze-pump-thaw operation was performed again. After the system returned to room temperature, nitrogen was introduced and the flask was placed in a 60°C oil bath and heated with stirring. The polymerization time was controlled so that the monomer conversion rate reached about 30%. The heating was stopped and the flask was allowed to cool naturally to room temperature before being opened to terminate the reaction. The polymer solution was then subjected to a neutral oxidizing The aluminum column was eluted with tetrahydrofuran (400 mL) to remove residual copper salts. The eluate was concentrated using a rotary evaporator and then dripped dropwise into a methanol / water mixture (50% v / v) to precipitate the polymer. The solid-liquid mixture was filtered under reduced pressure, and the filter cake was washed three times with a methanol / water mixture (50% v / v). Finally, the purified product was transferred to a Petri dish and dried in a vacuum oven at 45°C to constant weight to obtain a white powdery solid, which was the poly(tert-butyl methacrylate)-bromine macroinitiator.

[0068] (2) Preparation of poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0069] Poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres were prepared using initiator-continuously regenerated catalyst atom transfer radical polymerization. First, poly(tert-butyl methacrylate)-bromo-macroinitiator (1.5121 g, 0.1937 mmol), glycidyl methacrylate (2.7653 g, 19.43 mmol), copper bromide (0.0044 g, 0.0197 mmol), tris(2-dimethylaminoethyl)amine (0.0092 g, 0.0399 mmol), azobisisobutyronitrile (0.0645 g, 0.3927 mmol), and ethanol (48.8 mL) were added sequentially to a 200 mL round-bottom flask to control the solid content of the system to 10 wt%. The air in the flask was replaced with nitrogen by bubbling for 30 minutes, and the flask was placed in a 60°C oil bath to initiate the polymerization reaction. The reaction was continued at 60°C for 24 hours to complete the polymerization-induced self-assembly process mediated by atom transfer radical polymerization (ATRP) with continuous initiator regeneration and catalyst regeneration. Subsequently, the poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) reaction solution (20.1332 g, approximately 9.150 mmol of glycidyl methacrylate units) was placed in a 50 mL round-bottom flask. Ethanedithiol (345 μL, 4.213 mmol) was added as a crosslinker, and the flask was placed in a 50°C oil bath for 24 hours to crosslink the poly(glycidyl methacrylate) segments within the core. Finally, the reaction solution was concentrated and added dropwise to methanol to precipitate the polymer, which was then washed repeatedly with methanol three times. The purified precipitate was collected and dried in a 45°C vacuum oven to constant weight, yielding a white powdery solid, the poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0070] (3) Preparation of polymethacrylic acid-b-polyglycidyl methacrylate polymer microspheres

[0071] First, poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres (1.0324 g, 2.580 mmol of tert-butyl methacrylate units) were weighed and placed in a 30 mL sample vial. Dichloromethane (7.40 mL) was then added dropwise to disperse the microspheres. Trifluoroacetic acid (1.50 mL, 19.60 mmol) was then added dropwise to the vial, and the mixture was stirred at room temperature for 24 hours. After the reaction, the dichloromethane was removed using a rotary evaporator, and the remaining product was redispersed with ethanol (3.80 mL). The ethanol dispersion was then dripped dropwise into deionized water for precipitation, followed by centrifugation. This dissolution-precipitation cycle was repeated three times. Finally, the purified precipitate was dried in a 45°C vacuum oven to constant weight, yielding a white powdery solid, the hydrolyzed poly(methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0072] Example 2

[0073] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0074] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0075] The preparation of poly(tert-butyl methacrylate) macroinitiator was carried out by atom transfer radical polymerization with continuous initiator regeneration catalyst. First, ethyl 2-bromoisobutyrate (0.0587 g, 0.3009 mmol), tert-butyl methacrylate (4.3981 g, 30.93 mmol), copper bromide (0.0077 g, 0.0344 mmol), tris(2-dimethylaminoethyl)amine (0.0155 g, 0.0683 mmol), azobisisobutyronitrile (0.0537 g, 0.3270 mmol) and toluene (10.3 mL) were added to a 50 mL round-bottom flask in sequence. Then, the air in the flask was replaced with nitrogen by bubbling for 30 minutes, and then the flask was placed in an oil bath at 60°C to start the polymerization reaction. Finally, the polymerization time was controlled so that the monomer conversion rate reached about 30%, the heating was stopped, and the flask was allowed to cool naturally to room temperature before being opened to terminate the reaction. The subsequent purification operation was the same as in Example 1 (1).

[0076] (2) Preparation of poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0077] The amount of ethanol solvent added in Example 1 (2) was reduced by half to control the solid content of the system to 5 wt %. The remaining steps were the same as those in Example 1 (2) to obtain poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0078] (3) Preparation of polymethacrylic acid-b-polyglycidyl methacrylate polymer microspheres

[0079] The dichloromethane solvent in Example 1 (3) was replaced with toluene, and the solid content of the system was controlled to be 10 wt %. The remaining steps were the same as those in Example 1 (3), and polymethacrylic acid-b-polymethacrylate glycidyl ester polymer microspheres were obtained.

[0080] Example 3

[0081] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0082] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0083] The steps are the same as those in Example 1 (1) to prepare poly(tert-butyl methacrylate) macroinitiator.

[0084] (2) Preparation of poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0085] The azobisisobutyronitrile in Example 1 (2) was replaced with stannous octoate, and the electron transfer activation regeneration catalyst atom transfer radical polymerization was used to prepare poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres. First, poly(tert-butyl methacrylate) (1.0066 g, 0.1289 mmol), glycidyl methacrylate (1.8373 g, 12.94 mmol), copper bromide (0.0029 g, 0.0130 mmol), tris(2-dimethylaminoethyl)amine (0.0061 g, 0.0265 mmol), ethanol (29.1 mL) and dimethylformamide (0.30 mL) were added to a 100 mL round-bottom flask in sequence. After stirring evenly, the mixed solution (1.00 mL) was collected and retained. Then, the air in the flask was replaced with nitrogen by bubbling for 30 minutes, and the flask was placed in an oil bath at 60°C. After the temperature stabilized, a degassed ethanol solution (1.00 mL) containing stannous octoate (0.1035 g, 0.2567 mmol) was injected into the flask to initiate the polymerization reaction. The reaction was carried out at 60°C for 24 h to complete the polymerization-induced self-assembly process mediated by electron transfer activation and regeneration of the catalyst through atom transfer radical polymerization. The subsequent crosslinking and purification steps were the same as in Example 1 (2), and poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres were obtained.

[0086] (3) Preparation of polymethacrylic acid-b-polyglycidyl methacrylate polymer microspheres

[0087] The dichloromethane solvent in Example 1 (3) was replaced with toluene, and the solid content of the system was controlled to be 10 wt %. The remaining steps were the same as those in Example 1 (3), and polymethacrylic acid-b-polymethacrylate glycidyl ester polymer microspheres were obtained.

[0088] Example 4

[0089] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0090] The ligand in Example 1 (2) was replaced with tris(2-pyridylmethyl)amine, the solvent was replaced with cyclohexane, and the crosslinker was replaced with ethylenediamine. The hydrolysis solvent in Example 1 (3) was replaced with toluene, and the temperature was raised to 60°C. The remaining steps were the same as in Example 1 to produce polymethacrylic acid-b-polyglycidyl methacrylate polymer microspheres.

[0091] Example 5

[0092] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic poly(methacrylic acid-co-hydroxyethyl methacrylate)-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0093] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0094] The monomer tert-butyl methacrylate in Example 1(1) was replaced with a mixture of tert-butyl methacrylate and hydroxyethyl methacrylate (molar ratio 1:1), the solid content was increased to 20 wt%, and the remaining steps were the same as in Example 1(1), thereby preparing a poly(tert-butyl methacrylate-co-hydroxyethyl methacrylate) macroinitiator.

[0095] (2) Preparation of Poly(tert-butyl methacrylate-co-hydroxyethyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0096] The amount of ethanol solvent added in Example 1 (2) was reduced by half, and the solid content of the system was controlled to be 5 wt %. The remaining steps were the same as those in Example 1 (2), and poly(tert-butyl methacrylate-co-hydroxyethyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres were obtained.

[0097] (3) Preparation of poly(methacrylic acid-co-hydroxyethyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0098] The dichloromethane solvent in Example 1 (3) was replaced with toluene, the hydrolysis reagent was replaced with p-toluenesulfonic acid, the solid content of the system was controlled to be 10 wt %, and the remaining steps were the same as in Example 1 (3) to obtain poly(methacrylic acid-co-hydroxyethyl methacrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0099] Example 6

[0100] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic poly(methacrylic acid-co-(2-(dimethylamino)ethyl methacrylate))-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0101] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0102] The monomer tert-butyl methacrylate in Example 1(1) is replaced with a mixture of tert-butyl methacrylate and 2-(dimethylamino)ethyl methacrylate (molar ratio 1:1), and the remaining steps are the same as in Example 1(1) to prepare the poly(tert-butyl methacrylate-co-(2-(dimethylamino)ethyl methacrylate)) macroinitiator.

[0103] (2) Preparation of Poly(tert-butyl methacrylate-co-(2-(dimethylamino)ethyl methacrylate))-b-Poly(glycidyl methacrylate) Polymer Microspheres

[0104] The ethanol in Example 1(2) was replaced with methanol, the solid content of the system was controlled to be 10 wt %, and the remaining steps were the same as those in Example 1(2), thereby obtaining poly(tert-butyl methacrylate-co-(2-(dimethylamino)ethyl methacrylate))-b-poly(glycidyl methacrylate) polymer microspheres.

[0105] (3) Preparation of Poly(Methacrylic Acid-co-(2-(Dimethylamino)ethyl Methacrylate))-b-Poly(Glycidyl Methacrylate) Polymer Microspheres

[0106] The dichloromethane solvent in Example 1 (3) was replaced with methanol, and the solid content of the system was controlled to be 10 wt %. The remaining steps were the same as those in Example 1 (3), and poly(methacrylic acid-co-(2-(dimethylamino)ethyl methacrylate))-b-poly(glycidyl methacrylate) polymer microspheres were obtained.

[0107] Example 7

[0108] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic poly(acrylic acid-co-hydroxyethyl acrylate)-b-polyglycidyl methacrylate polymer microspheres, and the specific steps are as follows:

[0109] (1) Preparation of poly(tert-butyl acrylate) macroinitiator

[0110] The monomer tert-butyl methacrylate in Example 1(1) is replaced with a mixture of tert-butyl acrylate and hydroxyethyl acrylate (molar ratio 1:1), and the remaining steps are the same as Example 1(1) to prepare the poly(tert-butyl acrylate-co-hydroxyethyl acrylate) macroinitiator.

[0111] (2) Preparation of Poly(tert-butyl acrylate-co-hydroxyethyl acrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0112] The ethanol in Example 1(2) was replaced by a mixed solvent of methanol and ethanol (volume ratio of 1:1), the solid content of the system was controlled to 10 wt%, and the remaining steps were the same as those in Example 1(2), thereby obtaining poly(tert-butyl acrylate-co-hydroxyethyl acrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0113] (3) Preparation of poly(acrylic acid-co-hydroxyethyl acrylate)-b-poly(glycidyl methacrylate) polymer microspheres

[0114] The dichloromethane solvent in Example 1 (3) was replaced with toluene, the hydrolysis reagent was replaced with p-toluenesulfonic acid, the solid content of the system was controlled to be 10 wt %, and the remaining steps were the same as in Example 1 (3) to obtain poly(acrylic acid-co-hydroxyethyl acrylate)-b-poly(glycidyl methacrylate) polymer microspheres.

[0115] Example 8

[0116] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylic acid-b-poly(methacrylic acid-co-glycidyl methacrylate) microspheres, and the specific steps are as follows:

[0117] The monomer glycidyl methacrylate in Example 1(2) is replaced by a mixture of glycidyl methacrylate and tert-butyl methacrylate (molar ratio 3:1), the remaining raw materials and amounts are the same as in Example 1(2), and the remaining operating steps are the same as in Example 1, to obtain polymethacrylic acid-b-poly(methacrylic acid-co-glycidyl methacrylate) hydrophilic polymer microspheres.

[0118] Example 9

[0119] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-poly(methoxypolyethylene glycol methacrylate-co-glycidyl methacrylate) hydrophilic microspheres, and the specific steps are as follows:

[0120] The monomer glycidyl methacrylate in Example 1(2) is replaced with a mixture of methoxy polyethylene glycol methacrylate and tert-butyl methacrylate (molar ratio 1:2), and the remaining raw materials and amounts are the same as in Example 1(2). The remaining operating steps are the same as in Example 1, and polymethacrylic acid-b-poly(methoxy polyethylene glycol methacrylate-co-glycidyl methacrylate) hydrophilic polymer microspheres can be prepared.

[0121] Example 10

[0122] This embodiment provides a method for preparing carboxyl-functionalized hydrophilic polymethacrylate-b-polymethoxypolyethylene glycol methacrylate-b-polyglycidyl methacrylate hydrophilic polymer microspheres, and the specific steps are as follows:

[0123] (1) Preparation of poly(tert-butyl methacrylate) macroinitiator

[0124] The steps are the same as those in Example 1 (1) to prepare poly(tert-butyl methacrylate) macroinitiator.

[0125] (2) Preparation of hydrophilic polymer microspheres of poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-poly(glycidyl methacrylate)

[0126] Hydrophilic polymer microspheres of poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-polyglycidyl methacrylate were prepared by initiator-continuously regenerated catalyst atom transfer radical polymerization. First, poly(tert-butyl methacrylate) (1.0223 g, 0.1312 mmol), methoxypolyethylene glycol methacrylate (5.9201 g, 19.73 mmol), copper bromide (0.0058 g, 0.0260 mmol), tris(2-dimethylaminoethyl)amine (0.0121 g, 0.0525 mmol), azobisisobutyronitrile (0.0663 g, 0.4037 mmol), ethanol (87 mL), and N,N-dimethylformamide (0.80 mL) were added sequentially to a 250 mL round-bottom flask and stirred until uniform. The mixed solution (1.00 mL) was then retained. The air in the flask was then replaced with nitrogen using a bubbling method for 30 minutes. The flask was then placed in a 60°C oil bath to initiate the polymerization reaction, with samples taken every 2 hours to monitor the monomer conversion. Simultaneously, glycidyl methacrylate (0.9714 g, 6.834 mmol) was weighed into a 30 mL sample vial and dissolved in ethanol (11.5 mL). Azobisisobutyronitrile (0.0221 g, 0.1345 mmol) was then added to the solution and degassed using a bubbling method for 30 minutes. When the methoxypolyethylene glycol methacrylate monomer conversion reached approximately 90%, the degassed glycidyl methacrylate / azobisisobutyronitrile mixture was injected into the flask using a syringe. Polymerization was continued in a 60°C oil bath for 24 hours, completing the polymerization-induced self-assembly process mediated by atom transfer radical polymerization (ATRP) with continuous initiator regeneration and catalyst regeneration. Next, a poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-polyglycidyl methacrylate reaction solution (40.1524 g, approximately 3.466 mmol of glycidyl methacrylate units) was weighed and placed in a 50 mL round-bottom flask. Ethylene dithiol (125 μL, 1.492 mmol) was added as a cross-linker, and the flask was placed in a 50°C oil bath for 24 hours to crosslink the poly(glycidyl methacrylate) segments within the core. Finally, the reaction solution was concentrated and added dropwise to methanol to precipitate the polymer, which was then washed three times with methanol. The precipitate was collected and dried in a vacuum oven at 45°C to constant weight, yielding a white powdery solid, the poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-polyglycidyl methacrylate-based microspheres.

[0127] (3) Preparation of polymethacrylate-b-polymethoxypolyethylene glycol methacrylate-b-polymethacrylate glycidyl microspheres

[0128] The hydrolysis time in Example 1 (3) is extended to 48 h, and the remaining steps are the same as in Example 1 (3), and polymethacrylic acid-b-polymethoxy polyethylene glycol methacrylate-b-polymethacrylate glycidyl hydrophilic polymer microspheres can be prepared.

[0129] Example 11

[0130] This example provides a method for characterizing the particle size and morphology of the carboxyl-functionalized hydrophilic microspheres prepared in each of the above examples, as follows:

[0131] The polymerization reaction solution was diluted with deuterated chloroform and tested by nuclear magnetic resonance hydrogen spectrum to characterize the polymerization reaction conversion rate; the prepared microspheres were purified and dispersed in solvents such as ethanol, tetrahydrofuran, and water, with a solid content controlled at about 0.1 to 5 wt%, and the microsphere particle size was measured using a dynamic light scattering particle size analyzer; the dispersed microsphere solution was dropped onto a copper mesh coated with a carbon support film, and the size and morphology of the microspheres were characterized using a high-contrast transmission electron microscope ( Figures 1-4 ).

[0132] from Figure 1 It can be seen that the average size of the poly(tert-butyl methacrylate)-b-poly(glycidyl methacrylate)-based microspheres prepared in Example 1 is 723±44 nm.

[0133] from Figure 2 It can be seen that the average size of the polymethacrylic acid-b-poly(methacrylic acid-co-glycidyl methacrylate) hydrophilic polymer microspheres prepared in Example 8 is 401±16 nm.

[0134] from Figure 3 It can be seen that the average size of the poly(tert-butyl methacrylate)-b-poly(methoxypolyethylene glycol methacrylate-co-glycidyl methacrylate) microspheres prepared in Example 9 is 242±53 nm.

[0135] from Figure 4 It can be seen that the average size of the poly(tert-butyl methacrylate)-b-polymethoxypolyethylene glycol methacrylate)-b-poly(glycidyl methacrylate)-based microspheres prepared in Example 10 is 235±107 nm.

[0136] Comparative Example 1

[0137] This comparative example provides a preparation method of polybutyl methacrylate-b-polyglycidyl methacrylate polymer microspheres and a test of their hydrophilic properties. The specific steps are as follows:

[0138] The tert-butyl methacrylate in Example 1(1) was replaced by butyl methacrylate, and the other steps were the same as in Example 1.

[0139] result:

[0140] After treatment of polybutyl methacrylate-b-polyglycidyl methacrylate polymer microspheres with trifluoroacetic acid, the polybutyl methacrylate segments failed to hydrolyze, and the microsphere periphery remained hydrophobic polybutyl methacrylate. Consequently, the microspheres precipitated directly in water and lacked hydrophilicity. These results suggest that the presence of tert-butyl acrylate and tert-butyl methacrylate monomers in the shell polymer is essential. These monomers can be hydrolyzed to introduce hydrophilic acrylic or methacrylic acid monomers, and that the hydrophilicity of the microspheres can be controlled by adjusting the ratio of these monomers.

[0141] Comparative Example 2

[0142] This comparative example provides a preparation method of poly(glycidyl methacrylate)-g-mercaptopropionic acid) microspheres and a test of their hydrophilic properties. The specific steps are as follows:

[0143] Poly(glycidyl methacrylate) microspheres were prepared by traditional dispersion polymerization using polyvinyl alcohol as dispersant, glycidyl methacrylate and ethylene glycol dimethacrylate as monomers. Then, the epoxy groups on the periphery of the microspheres were modified with mercaptopropionic acid to introduce carboxyl groups.

[0144] result:

[0145] The microspheres are approximately 2 μm in size. When dispersed in water, they exhibit low turbidity and a noticeable precipitate at the bottom of the bottle. This is due to the relatively small number of carboxyl groups introduced into the microspheres' periphery, making it difficult to effectively stabilize the poly(glycidyl methacrylate)-based polymer in the core in water. Furthermore, using traditional dispersion polymerization, the microspheres produced are often large and have poor size controllability.

[0146] The one-pot polymerization-induced self-assembly and post-modification approach adopted in the present invention can significantly improve the dispersion stability, uniformity and synthesis efficiency of the microspheres.

[0147] The present invention first adopts atom transfer radical polymerization to prepare poly (meth) acrylate macroinitiator, and then uses the initiator to initiate homopolymerization of glycidyl methacrylate monomer or copolymerization of glycidyl methacrylate and (meth) acrylate monomer mixture, and undergoes polymerization-induced self-assembly reaction mediated by atom transfer radical polymerization. After the polymerization is completed, a cross-linking agent is added for cross-linking to obtain stable polymer microspheres. Finally, hydrophilic microspheres are prepared by hydrolyzing the poly (meth) acrylate segments of the shell. The preparation method of the present invention has the advantages of simple operation and high solid content of the product, and can accurately control the hydrophilicity and particle size of the microspheres by changing the type of monomer and the polymerization method. The prepared microspheres show good application potential in the fields of drug delivery, biological detection, pollutant adsorption, etc., and are expected to provide excellent performance material selection for related fields.

[0148] Specifically, the present invention can adjust the hydrophilicity of the microspheres by regulating the monomer type and copolymerization method. For example, when methoxy polyethylene glycol (meth)acrylate is used, the hydrophilicity is the strongest, and when tert-butyl (meth)acrylate is used, the hydrophilicity is weak; block copolymerization has a better hydrophilic effect than random copolymerization.

[0149] The present invention can adjust the particle size by regulating the polymerization degree ratio. For example, increasing the polymerization degree of the core layer block (polyglycidyl methacrylate) can increase the particle size; increasing the polymerization degree of the shell layer segment (polymethacrylic acid, polymethoxy polyethylene glycol methacrylate, etc.) can reduce the particle size.

[0150] The above description of the embodiments is intended to facilitate understanding and use of the invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the above-described embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention, without departing from the scope of the present invention, should be within the scope of protection of the present invention.

Claims

1. A carboxyl functionalized hydrophilic poly(glycidyl methacrylate) based microsphere, characterized in that: The microspheres are of a core-shell structure, wherein the carboxyl-containing poly(meth)acrylate or poly(meth)acrylic acid is the shell layer and the cross-linked poly(methacrylate glycidyl) polymer is the core layer.

2. The carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 1, characterized in that: The microspheres are spherical in shape and have a particle size range of 30 nm to 5000 nm.

3. A method for preparing carboxyl-functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to any one of claims 1 to 2, characterized in that: The following steps are involved: S1: Preparation of poly(meth)acrylate by atom transfer radical polymerization of (meth)acrylate monomers using ethyl 2-bromoisobutyrate as a small molecule initiator; S2: Using poly(meth)acrylate as a macromolecular initiator, a polymerization-induced self-assembly reaction mediated by atom transfer radical polymerization is initiated to initiate homopolymerization of glycidyl methacrylate monomer or copolymerization of a mixture of glycidyl methacrylate and (meth)acrylate monomers to prepare microspheres with a shell of poly(meth)acrylate and a core of poly(meth)acrylate-based polymer; S3: using a cross-linking agent to cross-link the glycidyl methacrylate units in the core to obtain cross-linked and stable polymer microspheres; S4: using a hydrolysis agent to selectively hydrolyze the shell poly (meth)acrylate to obtain carboxyl functionalized hydrophilic poly (glycidyl methacrylate) based microspheres.

4. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The (meth)acrylate monomers in steps S1 and S2 are one or more combinations of tert-butyl acrylate, tert-butyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, methoxypolyethylene glycol methacrylate, methoxypolyethylene glycol acrylate, 2-(dimethylamino)ethyl methacrylate, 2-morpholinoethyl methacrylate, methyl methacrylate, and methyl acrylate; Wherein, at least one of S1 is a monomer of tert-butyl acrylate or tert-butyl methacrylate, and the molar content of tert-butyl acrylate or tert-butyl methacrylate is 25 to 100%; Wherein, when the glycidyl methacrylate and (meth)acrylate monomer mixture in S2 are copolymerized, the molar content of glycidyl methacrylate is 25 to 100%.

5. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The poly(meth)acrylate in step S1 has a random structure or a block structure.

6. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The degree of polymerization of the poly(meth)acrylate in step S1 is in the range of 5 to 500.

7. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The degree of polymerization of the poly(glycidyl methacrylate)-based polymer in step S2 is in the range of 50 to 5000.

8. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The cross-linking agent in step S3 is one or more combinations of ethanedithiol, 1,4-butanedithiol, 1,6-hexanedithiol, ethylenediamine, and piperazine.

9. The method for preparing carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to claim 3, wherein: The hydrolysis reagent in step S4 is one or more combinations of trifluoroacetic acid, hydrochloric acid, p-toluenesulfonic acid, and trifluoromethanesulfonic acid.

10. Use of the carboxyl functionalized hydrophilic poly(glycidyl methacrylate) microspheres according to any one of claims 1 to 2, characterized in that: The microspheres are used for drug carriers, biological detection, and pollutant adsorption.

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