CN115975252A - Preparation method of magnetic polymer microsphere with double-layer shell structure - Google Patents
Preparation method of magnetic polymer microsphere with double-layer shell structure Download PDFInfo
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- CN115975252A CN115975252A CN202310128133.6A CN202310128133A CN115975252A CN 115975252 A CN115975252 A CN 115975252A CN 202310128133 A CN202310128133 A CN 202310128133A CN 115975252 A CN115975252 A CN 115975252A
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- 125000000524 functional group Chemical group 0.000 claims description 11
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 8
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 4
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- SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 claims description 3
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- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
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- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
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- 239000012298 atmosphere Substances 0.000 claims description 2
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- OIWOHHBRDFKZNC-UHFFFAOYSA-N cyclohexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC1CCCCC1 OIWOHHBRDFKZNC-UHFFFAOYSA-N 0.000 claims description 2
- 239000011790 ferrous sulphate Substances 0.000 claims description 2
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- 239000004312 hexamethylene tetramine Substances 0.000 claims description 2
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- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 2
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- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 12
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- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
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- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
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- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 1
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Abstract
The invention discloses a preparation method of magnetic polymer microspheres with a double-layer shell structure, which comprises the following steps: the polystyrene seed microspheres are subjected to first-step swelling under the action of a swelling agent and a surfactant, and are subjected to second-step swelling under the action of a functional monomer, an initiator and the surfactant to prepare functionalized porous polymer microspheres; preparing a magnetic polymer microsphere precursor by using a functionalized porous polymer microsphere as a template through a hydrothermal precipitation method; performing first polymerization encapsulation on a magnetic polymer microsphere precursor, and coating a hydrophobic coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic coating is a first shell of the magnetic polymer microsphere; performing second polymerization packaging on the magnetic polymer microspheres with the first shell, and coating a hydrophilic coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic coating is a second shell of the magnetic polymer microspheres; thereby obtaining the magnetic polymer microsphere with a double-layer shell structure.
Description
Technical Field
The invention relates to a preparation method of magnetic polymer microspheres with a double-layer shell structure.
Background
The magnetic polymer microsphere not only has the characteristics of non-toxicity and superparamagnetism of the magnetic inorganic nanoparticles, but also has the characteristics of polarity, biocompatibility, easy surface functionalization and the like of the polymer, and has wide application in many fields, particularly in biological detection and in-vitro diagnostic reagents. The magnetic microspheres for diagnostic reagents are required to have uniform particle size, fast magnetic response, good suspension property and low non-specific adsorption to biological macromolecules such as protein, nucleic acid and the like.
Among the disclosed preparation methods of magnetic polymer microspheres, the template method has become the mainstream preparation method of commercialized magnetic polymer microspheres due to the advantages of high process stability, uniform product particle size, strong magnetic responsiveness, surface multifunctionalization and the like. Patent document US8038987B2 discloses a method for preparing coated magnetic polymer particles, which utilizes nitrified porous polystyrene microspheres as a template, and then iron salt and manganese salt are coprecipitated into the porous microspheres to prepare the magnetic polymer microspheres. Similarly, patent document US20170218095 discloses a three-step process for producing superparamagnetic polymeric microspheres, which comprises synthesizing seeds of low molecular weight polystyrene microspheres by emulsion polymerization, swelling and crosslinking the seeds to obtain porous crosslinked polystyrene microspheres, finally nitrating benzene rings in the microspheres with a mixture of sulfuric acid and nitric acid, and using the nitrated microspheres together with ammonia (25%) and ferrous sulfate heptahydrate in the subsequent magnetization step. In the above-described magnetization process, the adsorption, deposition and centrifugation operations must be repeated in a laborious and time-consuming manner in order to deposit as many iron nanoparticles as possible in the nitrated microspheres. Also, each pair of 5g of dried polystyrene microspheres was nitrated, consuming 125mL of a mixture of concentrated nitric acid and concentrated sulfuric acid, which caused serious environmental problems. Most importantly, free iron nanoparticles and iron ions generated by the free iron nanoparticles exist in a reaction system all the time, so that the practical application effect of the product microspheres is limited.
In order to further solve the above problems, researchers have further explored the surface encapsulation process of magnetic polymer microspheres. Patent document CN108467461a discloses a method for preparing surface carboxyl core-shell superparamagnetic microspheres, which comprises preparing polyglycidyl methacrylate microspheres by emulsion polymerization, preparing large-size monodisperse porous polyglycidyl methacrylate microspheres by one-step seed swelling polymerization, preparing monodisperse superparamagnetic microspheres in situ by using an iron salt deposition-alkaline coprecipitation method, and performing surface carboxyl modification on the magnetic microspheres by distillation precipitation polymerization. The method carries out polymer encapsulation on the surface of the magnetic microsphere and simultaneously finishes functional modification. However, in the packaging process, the used monomer is hydrophilic monomer such as methacrylic acid or acrylic acid, and the single-layer hydrophilic copolymer coating obtained by distillation, precipitation and polymerization in acetonitrile has very limited improvement on the stability of the product microsphere. Patent document US5814687a discloses a method for testing leakage of ferric ions in magnetic polymer microspheres, which comprises: almost no superparamagnetic substance exists near the surface of the magnetic polymer microspheres, and when 1g of the magnetic polymer microspheres are soaked in 10mL of water at 70 ℃ for 2 hours, the amount of metal dissolved in the solvent must be 10mg/L or less. Experiments prove that after the magnetic polymer microspheres prepared by the method disclosed in the patent document CN108467461A are treated by the steps, the amount of iron ions dissolved in the solvent is far greater than 10mg/L, namely the problem of iron ion leakage still exists.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a preparation method of magnetic polymer microspheres without free iron nanoparticles and iron ion leakage.
The technical scheme is as follows: the preparation method of the magnetic polymer microsphere with the double-layer shell structure comprises the following steps:
(1) The polystyrene seed microsphere is subjected to first-step swelling under the action of a swelling agent and a surfactant, and is subjected to second-step swelling under the action of a functional monomer, an initiator and the surfactant to prepare a functionalized porous polymer microsphere; the first swelling can enable polymer molecular chains to become softer, so that functional monomers are better dissolved into the molecular chains during the second swelling, and the functional monomers are used for carrying out chelation reaction with iron ions in the second step;
(2) Preparing a magnetic polymer microsphere precursor by using a hydrothermal precipitation method by taking the functionalized porous polymer microsphere as a template; by limiting the mass ratio of ferrous ions to the microspheres and simultaneously carrying out the reaction in an ethylene glycol system, the ferrous ions in the reaction system are all captured and chelated by functional groups on the surface of the sphere, so that the generated ferroferric oxide can be completely adsorbed in the interior and pores of the microspheres, and free iron ions do not exist in the system;
(3) Performing first polymerization encapsulation on the magnetic polymer microsphere precursor, and coating a hydrophobic polymer coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic polymer coating is a first shell of the magnetic polymer microsphere; by controlling the mass ratio of the hydrophobic monomer to the microspheres, the thickness of the obtained hydrophobic polymer coating is 10-60 nm, the low-activity property of the hydrophobic layer plays a role in protecting the microspheres, and the leakage of iron ions in the microspheres can be effectively prevented;
(4) Performing second polymerization packaging on the magnetic polymer microspheres with the first shell, and coating a hydrophilic polymer coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic polymer coating is a second shell of the magnetic polymer microspheres; the thickness of the hydrophilic polymer coating is 15-25 nm, and if the hydrophilic thickness is too high, the microspheres can be adhered to each other; obtaining the magnetic polymer microsphere with a double-layer shell structure.
Based on different application scenes, the magnetic polymer microsphere with the second shell is placed in one or more of sulfuric acid, sodium hydroxide, ethylenediamine, ammonia water or acid anhydride, and reacts for 1-24 h at 30-120 ℃ to obtain the magnetic polymer microsphere with different functional groups on the surface. Different practical application scenes have different requirements on the types of the functional groups on the surface of the magnetic polymer microsphere, and the magnetic polymer microsphere can be grafted with different bioactive molecules such as protein, nucleic acid and the like through the different functional groups on the surface of the magnetic polymer microsphere.
In the step (1), the functional monomer is a monomer with one or more functional groups of amino, carboxyl, epoxy or hydroxyl; the functional groups on the surface of the functionalized porous polymer microsphere are at least two of amino, carboxyl, epoxy or hydroxyl.
Wherein, in the step (2), the hydrothermal precipitation method specifically comprises the following steps: dispersing functionalized porous polymer microspheres, ferrous compounds, hexamethylenetetramine and nitrate in a mixed solution of water and ethylene glycol, and reacting for 0.5-6 h at 50-150 ℃ in an inert atmosphere; the ferrous compound is ferrous chloride and/or ferrous sulfate; the mass ratio of the functionalized porous polymer microspheres to the ferrous compound is 1:3-3:1.
Wherein, in the step (3), the first polymerization encapsulation by the reflux precipitation method specifically comprises: dispersing the magnetic polymer microsphere precursor, the hydrophobic monomer, the cross-linking agent and the initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
Wherein the hydrophobic monomer is one or more of styrene, methyl methacrylate, isobutyl methacrylate or cyclohexyl methacrylate; the crosslinking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate or N, N' -methylene bisacrylamide, and the addition amount of the crosslinking agent is 1-25% of the mass of the hydrophobic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, potassium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophobic monomer; the mass ratio of the hydrophobic monomer to the magnetic polymer microsphere precursor is 1:3 to 10:1.
wherein, in the step (4), the second polymerization and encapsulation by the reflux precipitation method specifically comprises the following steps: dispersing the magnetic polymer microsphere with the first shell, the hydrophilic monomer, the cross-linking agent and the initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
Wherein the hydrophilic monomer is one or more of glycidyl methacrylate, hydroxyethyl methacrylate, methacrylic acid, tert-butyl methacrylate or methacrylamide; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate, butanediol dimethacrylate, bisphenol A dimethacrylate or N, N' -methylene bisacrylamide, and the addition amount of the cross-linking agent is 1 to 25 percent of the mass of the hydrophilic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, tert-amyl hydroperoxide, potassium persulfate, sodium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophilic monomer; the mass ratio of the hydrophilic monomer to the magnetic polymer microsphere with the first shell is 1:3 to 10:1.
the magnetic polymer microsphere prepared by the method has uniform and controllable particle size and high magnetic content (not less than 18 wt%), and can lead ferrous ions in a reaction system to be completely captured and chelated by functional groups on the surface of the sphere by the cooperation of polyfunctional groups while having high magnetic content, thereby avoiding the generation of free iron nano particles; meanwhile, the problem that iron ions are easy to leak in the practical application process of the magnetic polymer microsphere is solved through a hydrophobic-hydrophilic double-layer shell structure, wherein the hydrophobic polymer coating on the inner layer plays an effective role in fixing and protecting the iron nanoparticles; the hydrophilic polymer coating on the outer layer has the functionalization characteristic, and the specific adsorption of the magnetic polymer microspheres to protein, nucleic acid and other biological macromolecules is realized.
Has the advantages that: compared with the prior art, the invention has the following remarkable advantages: in the magnetization process of the porous polymer microspheres, the generation of free iron nanoparticles is avoided by the synergistic effect of a hydrothermal precipitation method and polyfunctional groups on the surfaces of the microspheres; the encapsulation of the hydrophobic-hydrophilic double-layer shell structure solves the problem of iron ion leakage in the practical application process of the magnetic polymer microsphere; according to the practical application scene, the controllable and diversified functional groups on the surface of the magnetic polymer microsphere can be realized by regulating the types of the functional monomers in the polymerization process of the second shell, and the grafting of bioactive molecules such as protein, nucleic acid and the like is facilitated.
Drawings
In fig. 1, a and B are respectively a scanning electron microscope image and a transmission electron microscope image of the functionalized porous polymer microsphere prepared in example 1;
in FIG. 2, A and B are scanning electron micrographs of the magnetic polymer microsphere precursor prepared in example 1 at different magnifications, respectively;
in fig. 3, a and B are scanning electron micrographs of the magnetic polymer microsphere with the second shell prepared in example 1 at different magnifications.
Detailed Description
The technical scheme of the invention is further explained by combining the attached drawings.
Example 1
The preparation method of the magnetic polymer microsphere with the double-layer shell structure comprises the following steps:
(1) Synthesis of functionalized porous polymeric microspheres: firstly, uniformly mixing 3:2, then adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azobisisobutyronitrile, heating to 75 ℃ under the protection of nitrogen, and reacting for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 micron; adding 0.6mL of toluene and 1.8mL of dibutyl phthalate into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, carrying out ultrasonic emulsification, adding 0.1g of polystyrene seed microspheres into the aqueous solution, and swelling the mixture for 12h at room temperature; then 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate for ultrasonic emulsification; adding the emulsion into the reaction solution after swelling for 12h, and continuing swelling for 6h; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% aqueous solution of sodium hydroxide at 60 ℃ for 8h, washing the porous polymer microspheres with distilled water to be neutral after the hydrolysis is finished, and condensing and refluxing the porous polymer microspheres with 50mL of 0.2mol/L aqueous solution of sulfuric acid at 80 ℃ for 4h to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: respectively weighing 40mL of water, 10mL of ethylene glycol and 0.16g of functionalized porous polymer microspheres, adding the weighed materials into a 100mL three-neck flask with mechanical stirring, and uniformly dispersing the materials at the mechanical stirring speed of 200 rpm; then, 0.08g of ferrous chloride tetrahydrate, 0.5g of hexamethylenediamine and 0.1g of potassium nitrate are rapidly added into the three-neck flask in sequence, the mixture is fully stirred for 15min under the protection of nitrogen, the temperature of the water bath is increased to 80 ℃, the stirring speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product with distilled water in a magnetic field for several times, and drying in vacuum to obtain a magnetic polymer microsphere precursor;
(3) Polymerization encapsulation of the first shell: weighing 1g of the magnetic polymer microsphere precursor, ultrasonically dispersing the precursor in 150mL of acetonitrile, and adding the mixture into a 250mL four-neck flask with a reflux device; then weighing 2g of methyl methacrylate, 0.2g of divinylbenzene and 0.05g of azodiisobutyronitrile, sequentially adding the methyl methacrylate, the divinylbenzene and the azodiisobutyronitrile into a four-neck flask, transferring the four-neck flask with a reflux device into a water bath, setting the temperature of the water bath to be 110 ℃, and reacting for 4 hours; washing the product with distilled water in a magnetic field for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 60nm;
(4) Polymerization encapsulation of the second shell: weighing 1g of the magnetic polymer microspheres with the first shell, ultrasonically dispersing the magnetic polymer microspheres in 150mL of acetonitrile, and adding the mixture into a 250mL four-neck flask with a reflux device; weighing 4g of methacrylic acid, 1g of glycidyl methacrylate, 1g of N, N' -methylene bisacrylamide and 0.25g of azobisisobutyronitrile, dissolving the materials by ultrasonic dispersion, and adding the dissolved materials into a four-neck flask; transferring the four-neck flask with the reflux device into a water bath, setting the temperature of the water bath to 93 ℃, and reacting for 4 hours; washing the product with distilled water in a magnetic field for several times to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 23nm;
hydrolysis of magnetic polymer microspheres: weighing 1g of the magnetic polymer microsphere with the second shell, ultrasonically dispersing the magnetic polymer microsphere in 100mL of 10wt% sulfuric acid aqueous solution, carrying out hydrolysis reaction for 3h at 80 ℃, and washing a hydrolyzed product in a magnetic field for several times by using distilled water to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiment of iron ion leakage: 1g of the hydrolyzed magnetic polymer microspheres are weighed, dispersed in 30mL of water and continuously stirred for 2h in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in a 70 ℃ water bath, cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting with water to 100 mL) and 2mL of a phenanthroline solution, developing for 15min after stirring uniformly, adjusting to zero with a blank by using a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison.
Example 2
The preparation method of the magnetic polymer microsphere with the double-layer shell structure comprises the following steps:
(1) Synthesis of functionalized porous polymeric microspheres: firstly, uniformly mixing 3:2, adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azobisisobutyronitrile into the mixture, heating the mixture to 75 ℃ under the protection of nitrogen, and reacting for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 micron; adding 0.6mL of toluene and 1.8mL of dibutyl phthalate into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, carrying out ultrasonic emulsification, adding 0.1g of polystyrene seed microspheres into the aqueous solution, and swelling the mixture for 12h at room temperature; then 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate for ultrasonic emulsification; adding the emulsion into the reaction solution after swelling for 12 hours, and continuing swelling for 6 hours; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% sodium hydroxide aqueous solution at 60 ℃ for 8h, washing the hydrolyzed porous polymer microspheres with distilled water to be neutral, and condensing and refluxing the hydrolyzed porous polymer microspheres with 50mL of 0.2mol/L sulfuric acid aqueous solution at 80 ℃ for 4h to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: respectively weighing 40mL of water, 10mL of ethylene glycol and 0.1g of functionalized porous polymer microspheres, adding the weighed materials into a 100mL three-neck flask with mechanical stirring, and uniformly dispersing the materials at the mechanical stirring speed of 200 rpm; then, 0.08g of ferrous chloride tetrahydrate, 0.5g of hexamethylenediamine and 0.1g of potassium nitrate are rapidly added into a three-neck flask in sequence, the mixture is fully stirred for 15min under the protection of nitrogen, the temperature of a water bath is increased to 80 ℃, the stirring speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product with distilled water in a magnetic field for several times, and drying in vacuum to obtain a magnetic polymer microsphere precursor;
(3) Polymerization encapsulation of the first shell: weighing 1g of the magnetic polymer microsphere precursor, ultrasonically dispersing the precursor in 150mL of acetonitrile, and adding the mixture into a 250mL four-neck flask with a reflux device; then weighing 1g of methyl methacrylate, 1g of styrene, 0.2g of divinylbenzene and 0.05g of azobisisobutyronitrile, sequentially adding the methyl methacrylate, the styrene, the divinylbenzene and the azobisisobutyronitrile into a four-neck flask, transferring the four-neck flask with a reflux device into a water bath, setting the temperature of the water bath to be 110 ℃, and continuously reacting for 4 hours; washing the product with distilled water in a magnetic field for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 10nm;
(4) Polymerization encapsulation of the second shell: weighing 1g of the magnetic polymer microspheres with the first shell, ultrasonically dispersing the magnetic polymer microspheres in 150mL of acetonitrile, and adding the mixture into a 250mL four-neck flask with a reflux device; weighing 4g of hydroxyethyl methacrylate, 1g of tert-butyl methacrylate, 1g of N, N' -methylene bisacrylamide and 0.25g of azobisisobutyronitrile, dissolving the materials by ultrasonic dispersion, and adding the dissolved materials into a four-neck flask; transferring the four-neck flask with the reflux device into a water bath, setting the temperature of the water bath to be 93 ℃, and continuing the reaction for 4 hours; washing the product in a magnetic field for several times by using distilled water to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 21nm;
hydrolysis of magnetic polymer microspheres: weighing 1g of the magnetic polymer microsphere with the second shell, ultrasonically dispersing the magnetic polymer microsphere in 100mL of 10wt% sulfuric acid aqueous solution, carrying out hydrolysis reaction for 3h at 80 ℃, and washing a hydrolyzed product in a magnetic field for several times by using distilled water to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiment of iron ion leakage: 1g of the hydrolyzed magnetic polymer microspheres are weighed, dispersed in 30mL of water and continuously stirred for 2h in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in 70 ℃ water bath, then cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting to 100mL with water) and 2mL of an o-phenanthroline solution, stirring uniformly, developing for 15min, adjusting zero by blank with a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison.
Example 3
The preparation method of the magnetic polymer microsphere with the double-layer shell structure comprises the following steps:
(1) Synthesis of functionalized porous polymeric microspheres: firstly, uniformly mixing 3:2, then adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azobisisobutyronitrile, heating to 75 ℃ under the protection of nitrogen, and reacting for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 micron; adding 0.6mL of toluene and 1.8mL of dibutyl phthalate into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, performing ultrasonic emulsification, adding 0.1g of polystyrene seed microspheres into the aqueous solution, and swelling the mixture for 12 hours at room temperature; then 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate for ultrasonic emulsification; adding the emulsion into the reaction solution after swelling for 12 hours, and continuing swelling for 6 hours; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% aqueous solution of sodium hydroxide at 60 ℃ for 8h, washing the porous polymer microspheres with distilled water to be neutral after the hydrolysis is finished, and condensing and refluxing the porous polymer microspheres with 50mL of 0.2mol/L aqueous solution of sulfuric acid at 80 ℃ for 4h to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: respectively weighing 40mL of water, 10mL of ethylene glycol and 0.16g of functionalized porous polymer microspheres, adding the weighed materials into a 100mL three-neck flask with mechanical stirring, and uniformly dispersing the materials at the mechanical stirring speed of 200 rpm; then, 0.08g of ferrous chloride tetrahydrate, 0.5g of hexamethylenediamine and 0.1g of potassium nitrate are rapidly added into the three-neck flask in sequence, the mixture is fully stirred for 15min under the protection of nitrogen, the temperature of the water bath is increased to 80 ℃, the stirring speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product with distilled water in a magnetic field for several times, and drying in vacuum to obtain a magnetic polymer microsphere precursor;
(3) Polymerization encapsulation of the first shell: weighing 1g of the magnetic polymer microsphere precursor, dispersing the precursor in 150mL of acetonitrile by ultrasonic, and adding the mixture into a 250mL four-neck flask with a reflux device; then weighing 2g of methyl methacrylate, 0.2g of divinylbenzene and 0.05g of azodiisobutyronitrile, sequentially adding the methyl methacrylate, the divinylbenzene and the azodiisobutyronitrile into a four-neck flask, transferring the four-neck flask with a reflux device into a water bath, setting the temperature of the water bath to be 110 ℃, and continuously reacting for 4 hours; washing the product with distilled water in a magnetic field for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 20nm;
(4) Polymerization encapsulation of the second shell: weighing 1g of the magnetic polymer microspheres with the first shell, ultrasonically dispersing the magnetic polymer microspheres in 150mL of acetonitrile, and adding the mixture into a 250mL four-neck flask with a reflux device; weighing 8g of methacrylic acid, 2g of glycidyl methacrylate, 2g of N, N' -methylene-bis-acrylamide and 0.5g of azodiisobutyronitrile, dissolving the materials through ultrasonic dispersion, and adding the dissolved materials into a four-neck flask; transferring the four-neck flask with the reflux device into a water bath, setting the temperature of the water bath to be 93 ℃, and continuing the reaction for 4 hours; washing the product with distilled water in a magnetic field for several times to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 15nm;
hydrolysis of magnetic polymer microspheres: weighing 1g of the magnetic polymer microsphere with the second shell, ultrasonically dispersing the magnetic polymer microsphere in 100mL of 10wt% sulfuric acid aqueous solution, carrying out hydrolysis reaction for 3h at 80 ℃, and washing a hydrolyzed product in a magnetic field for several times by using distilled water to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiment of iron ion leakage: 1g of the hydrolyzed magnetic polymer microspheres are weighed, dispersed in 30mL of water and continuously stirred for 2h in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in a 70 ℃ water bath, cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting with water to 100 mL) and 2mL of a phenanthroline solution, developing for 15min after stirring uniformly, adjusting to zero with a blank by using a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison.
Comparative example 1 is the surface carboxyl core-shell superparamagnetic microsphere prepared by the method disclosed in CN108467461A
Quantitative experiment of iron ion leakage: 1g of surface carboxyl core-shell superparamagnetic microspheres are weighed, dispersed in 30mL of water and continuously stirred for 2h in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in a 70 ℃ water bath, cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting with water to 100 mL) and 2mL of a phenanthroline solution, developing for 15min after stirring uniformly, adjusting to zero with a blank by using a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison.
Comparative example 2
Comparative example 2 the preparation method of the magnetic polymer microsphere is substantially the same as that of example 3, the only difference is that comparative example 2 adopts a coprecipitation method to prepare the magnetic polymer microsphere precursor in step (2), and the specific process of preparing the magnetic polymer microsphere precursor by adopting the coprecipitation method is as follows: respectively weighing 0.9g of ferrous chloride tetrahydrate, 1.4g of ferric chloride hexahydrate, 0.16g of functionalized porous polymer microsphere and 50mL of water, adding the materials into a 100mL three-neck flask with mechanical stirring, stirring at the rotating speed of 1000rpm to quickly and uniformly disperse the materials, then raising the temperature to 70 ℃, continuously stirring for 1h, quickly adding 8mL of ammonia water into the system, reacting for 0.5h, washing the obtained black product with distilled water in a magnetic field for several times, and drying in vacuum to obtain the precursor of the magnetic polymer microsphere.
Quantitative experiment of iron ion leakage: 1g of the magnetic polymer microspheres prepared in comparative example 2 was weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in a 70 ℃ water bath, cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting with water to 100 mL) and 2mL of a phenanthroline solution, developing for 15min after stirring uniformly, adjusting to zero with a blank by using a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison. Comparative example 3
Comparative example 3 the preparation method of the magnetic polymeric microspheres was substantially identical to the method of example 3, with the only difference that comparative example 3 did not perform the first polymerization encapsulation of the magnetic polymeric microsphere precursor, but performed the encapsulation of the hydrophilic polymeric coating directly on the magnetic polymeric microsphere precursor.
Quantitative experiment of iron ion leakage: 1g of the magnetic polymer microspheres prepared in comparative example 3 was weighed, dispersed in 30mL of water, and stirred continuously for 2h in a water bath at 70 ℃. After stirring, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of a 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring for 1-2 h in a 70 ℃ water bath, cooling to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of a buffer solution (the buffer solution is formed by mixing 40g of acetic acid and 50mL of glacial acid and then diluting with water to 100 mL) and 2mL of a phenanthroline solution, developing for 15min after stirring uniformly, adjusting to zero with a blank by using a 10mm cuvette, measuring absorbance at 510nm, and determining the content of free iron ions in the system through standard curve comparison.
TABLE 1 quantitative test results for iron ion leakage of magnetic polymer microspheres
| Numbering | Leakage amount of iron ion (mg/L) | Magnetic content (mg/mg) |
| Example 1 | 8 | 18.9 |
| Example 2 | 5 | 25.6 |
| Example 3 | 2 | 28.4 |
| Comparative example 1 | 65 | 14.1 |
| Comparative example 2 | 230 | 33.2 |
| Comparative example 3 | 77 | 19.7 |
As can be seen from Table 1, the magnetic polymer microsphere prepared by the method has good monodispersity and high magnetic content, the leakage amount of iron ions in the system is less than 10mg/L, the packaging coating with the hydrophobic-hydrophilic double-layer shell structure has a reliable stabilizing effect on the magnetic polymer microsphere, and the problem of iron ion leakage in the practical application process of the magnetic polymer microsphere is solved. The experimental results of comparative examples 1 and 3 show that the packaging effect of the monolayer hydrophilic copolymer coating on the magnetic polymer microspheres is far lower than that of a combined coating mode of a double-layer shell structure or even a multilayer shell structure.
Claims (10)
1. A preparation method of magnetic polymer microspheres with a double-layer shell structure is characterized by comprising the following steps:
(1) The polystyrene seed microspheres are subjected to first-step swelling under the action of a swelling agent and a surfactant, and are subjected to second-step swelling under the action of a functional monomer, an initiator and the surfactant to prepare functionalized porous polymer microspheres;
(2) Preparing a magnetic polymer microsphere precursor by using a hydrothermal precipitation method by taking the functionalized porous polymer microsphere as a template;
(3) Performing first polymerization encapsulation on the magnetic polymer microsphere precursor, and coating a hydrophobic polymer coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic polymer coating is a first shell of the magnetic polymer microsphere;
(4) Performing second polymerization packaging on the magnetic polymer microspheres with the first shell, and coating a hydrophilic polymer coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic polymer coating is a second shell of the magnetic polymer microspheres; obtaining the magnetic polymer microsphere with the double-layer shell structure.
2. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 1, wherein the method comprises the following steps: based on different application scenes, the magnetic polymer microsphere with the second shell is placed in one or more solutions of sulfuric acid, sodium hydroxide, ethylenediamine, ammonia water or acid anhydride, and reacts for 1-24 h at 30-120 ℃ to obtain the magnetic polymer microsphere with different functional groups on the surface.
3. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (1), the functional monomer is a monomer with one or more functional groups of amino, carboxyl, epoxy or hydroxyl; the functional group on the surface of the functionalized porous polymer microsphere is one or more of amino, carboxyl, epoxy or hydroxyl.
4. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (2), the hydrothermal precipitation method specifically comprises the following steps: dispersing functionalized porous polymer microspheres, ferrous compounds, hexamethylenetetramine and nitrate in a mixed solution of water and glycol, and reacting for 0.5-6 h at 50-150 ℃ in an inert atmosphere; the ferrous compound is ferrous chloride and/or ferrous sulfate; the mass ratio of the functionalized porous polymer microspheres to the ferrous compound is 1:3-3:1.
5. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (3), the first polymerization and encapsulation by a reflux precipitation method specifically comprises the following steps: dispersing a magnetic polymer microsphere precursor, a hydrophobic monomer, a cross-linking agent and an initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
6. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 5, wherein the method comprises the following steps: the thickness of the hydrophobic polymer coating is 10-60 nm.
7. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 5, wherein the method comprises the following steps: the hydrophobic monomer is one or more of styrene, methyl methacrylate, isobutyl methacrylate or cyclohexyl methacrylate; the crosslinking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate or N, N' -methylene bisacrylamide, and the addition amount of the crosslinking agent is 1-25% of the mass of the hydrophobic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, potassium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophobic monomer; the mass ratio of the hydrophobic monomer to the magnetic polymer microsphere precursor is 1:3 to 10:1.
8. the method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (4), the second polymerization and encapsulation by the reflux precipitation method specifically comprises the following steps: dispersing the magnetic polymer microsphere with the first shell, the hydrophilic monomer, the cross-linking agent and the initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
9. The method for preparing magnetic polymer microspheres with a double-layer shell structure according to claim 8, wherein the method comprises the following steps: the thickness of the hydrophilic polymer coating is 15-25 nm.
10. The method for preparing magnetic polymer microsphere with double-layer shell structure according to claim 8, wherein the method comprises the following steps: the hydrophilic monomer is one or more of glycidyl methacrylate, hydroxyethyl methacrylate, methacrylic acid, tert-butyl methacrylate or methacrylamide; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate, butanediol dimethacrylate, bisphenol A dimethacrylate or N, N' -methylene bisacrylamide, and the addition amount of the cross-linking agent is 1 to 25 percent of the mass of the hydrophilic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, tert-amyl hydroperoxide, potassium persulfate, sodium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophilic monomer; the mass ratio of the hydrophilic monomer to the magnetic polymer microsphere with the first shell is 1:3 to 10:1.
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| CN1468898A (en) * | 2003-07-02 | 2004-01-21 | 北京倍爱康生物技术股份有限公司 | Prepn of super-paramagnetic polymer microsphere |
| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114192079A (en) * | 2021-12-13 | 2022-03-18 | 广州光驭超材料有限公司 | Magnetic hollow polymer microsphere and preparation method and application thereof |
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| CN1468898A (en) * | 2003-07-02 | 2004-01-21 | 北京倍爱康生物技术股份有限公司 | Prepn of super-paramagnetic polymer microsphere |
| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114192079A (en) * | 2021-12-13 | 2022-03-18 | 广州光驭超材料有限公司 | Magnetic hollow polymer microsphere and preparation method and application thereof |
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| HONG MAN: "Fabrication of Fe3O4@poly(methyl methacrylateco- glycidyl methacrylate) microspheres via miniemulsion polymerization using porous microspheres as templates for removal of cationic dyes", 《ROYAL SOCIETY OF CHEMISTRY》, vol. 46, pages 13442 - 13453 * |
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