Method for modifying mesoporous SiO2 materials

Abstract

The application discloses a modification method of mesoporous SiO2 material. The specific steps are as follows: the terminal hydroxyl group of alkyl phenol polyoxyethylene ether is oxidized into a carboxyl group by KMnO4, and then the carboxyl group is chlorinated into an acyl chloride by SOCl2; the surface hydroxyl group of the mesoporous SiO2 material is hydrophobically modified by using gamma-aminopropyl triethoxysilane to obtain an amino structure at the gamma position; an amide bond is constructed, and oil-water amphiphilic modification is completed. The alkyl phenol polyoxyethylene ether is octyl phenol polyoxyethylene ether, nonyl phenol polyoxyethylene ether or dodecyl polyoxyethylene ether, and the polymerization degree of the polyoxyethylene chain is 8-20. The modification method is suitable for nano fumed silica, monodisperse mesoporous SiO2 microspheres, mesoporous SiO2 molecular sieves and the like. Compared with unmodified or conventionally hydrophobically modified mesoporous SiO2 materials, the mesoporous SiO2 material modified according to the above method has hydrophilicity and lipophilicity, and can be well dispersed in water and organic solvents; when used as a drug carrier material, the mesoporous SiO2 material can simultaneously realize the loading and effective release of water-soluble and fat-soluble drugs.

Description

Technical Field

[0001] This invention relates to a method for modifying mesoporous SiO2 materials, belonging to the fields of materials engineering and pharmaceutical formulation. The mesoporous SiO2 materials modified by this method have amphiphilic properties, being both hydrophilic and lipophilic, and can be practically applied to drug carriers, etc. Background Technology

[0002] Mesoporous SiO2 materials are promising drug carriers due to their fine particle size, uniform particle size distribution, high porosity, large specific surface area, strong surface adsorption, good dispersibility and flowability, high chemical purity, and non-toxicity, tastelessness, and odorlessness. However, mesoporous SiO2 materials contain numerous hydrophilic active hydroxyl groups, which give them extremely high surface energy. The strong hydrogen bonds and electrostatic forces between particles make them prone to adsorbing moisture from the environment and agglomerating, which is detrimental to their own stability and the stability of the loaded drug.

[0003] Hydrophobic modification of the surface hydroxyl groups is a conventional method to address the aforementioned shortcomings. Commonly used hydrophobic modifiers mainly include: organochlorosilanes, such as dimethyldichlorosilane and phenyldimethylchlorosilane; siloxanes, such as polydimethylsiloxane and hexamethyldisiloxane; silane coupling agents, such as hexamethyldisilazane, hexamethylcyclotrisilazane, n-octyltriethoxysilane, γ-aminopropyltriethoxysilane (KH550), and γ-epoxypropoxypropyltrimethoxysilane (KH560); and alcohols, such as n-heptanol, n-octanol, and n-dococaprol. However, conventional hydrophobic modification can simultaneously limit the loading of water-soluble drugs onto mesoporous silica materials and the dissolution of the loaded drugs in water.

[0004] Alkylphenol polyoxyethylene ethers (APEOs) possess both hydrophobic alkylphenyl groups and hydrophilic polyoxyethylene chains in their chemical structure. If APEOs can be used to modify the surface hydrophilic active hydroxyl groups of mesoporous SiO2 materials, the modified mesoporous SiO2 materials can exhibit amphiphilic properties, being both hydrophilic and lipophilic. Currently, APEOs are mainly used in polyoxyethylene-type nonionic surfactants, and there are no research reports on their application in modifying mesoporous SiO2 materials. Summary of the Invention

[0005] This invention aims to address the problems of mesoporous SiO2 materials being rich in hydrophilic active hydroxyl groups, having high surface energy, strong hydrogen bonds and electrostatic forces between particles, easily adsorbing environmental moisture, easily agglomerating, and being highly hydrophobic after conventional hydrophobic modification, which is not conducive to loading water-soluble drugs and restricts the dissolution of loaded drugs in water. The invention provides a method for modifying mesoporous SiO2 materials that simultaneously possesses hydrophilicity and oleophilicity.

[0006] The technical solution adopted in this invention, the reaction formula for the modification method of mesoporous SiO2 materials, is as follows:

[0007]

[0008] The steps for modifying mesoporous SiO2 materials are as follows:

[0009] (1) Oxidize the terminal hydroxyl groups of alkylphenol polyoxyethylene ether to carboxyl groups.

[0010] Dissolve 0.1 mol alkylphenol polyoxyethylene ether and 0.11–0.15 mol NaOH in 300–500 mL of deionized water, add 0.11–0.15 mol KMnO4, and continuously stir the oxidation reaction for 4–24 hours. Filter to remove unreacted KMnO4 and byproduct MnO2. Adjust the pH to 1.0–3.0 by adding hydrochloric acid dropwise at a rate of 1 drop / second. Freeze-dry under vacuum at -80–-30°C to remove water, with a vacuum degree of 0–200 Pa. Redissolve in 50 mL of toluene, filter, and remove toluene by rotary evaporation to obtain the purified terminal carboxyl group sample.

[0011] The alkylphenol polyoxyethylene ether is octylphenol polyoxyethylene ether, nonylphenol polyoxyethylene ether or dodecyl polyoxyethylene ether, and the degree of polymerization of the polyoxyethylene chain is 8 to 20.

[0012] (2) Prepare acyl chloride by terminating the carboxyl group.

[0013] Dissolve 0.1 mol of purified terminal carboxyl group sample in 100–300 mL of anhydrous CH2Cl2, add 0.11–0.15 mol of SOCl2 dropwise at a rate of 1 drop / second, and continue stirring until the reaction is complete; filter and rotary evaporate to remove solvent CH2Cl2, unreacted SOCl2, residual byproducts HCl and SO2, to obtain purified terminal acyl chloride sample;

[0014] (3) Mesoporous SiO2 material was hydrophobically modified with γ-aminopropyltriethoxysilane to obtain an amino structure at the γ-position.

[0015] Mesoporous SiO2 material was treated in an oven at 120–350 °C for 2–24 hours; the treated mesoporous SiO2 material was added to 50 mL of toluene to prepare a uniformly dispersed suspension; 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 130–150 °C for 2–8 hours; the reaction system was allowed to cool naturally to room temperature, and the hydrophobically modified mesoporous SiO2 material was filtered, washed with ethanol, and dried at 120–200 °C to constant weight;

[0016] (4) Construct amide bonds to complete the amphiphilic modification of mesoporous SiO2 materials.

[0017] The hydrophobically modified mesoporous SiO2 material with γ-aminopropyltriethoxysilane was dispersed in 50 mL of toluene solvent. Triethylamine was added and stirred until homogeneous, with an addition amount of 1–10 μL of triethylamine per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the mesoporous SiO2 material dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond, completing the amphiphilic modification. After the reaction, the amphiphilic modified mesoporous SiO2 material was filtered, washed with ethanol, and dried at 120–200 °C to constant weight. The modified mesoporous SiO2 material in this invention is nano-fumed silica, monodisperse mesoporous SiO2 microspheres, or mesoporous SiO2 molecular sieves.

[0018] The modified mesoporous SiO2 material of this invention has amphiphilic properties, being both hydrophilic and oleophilic.

[0019] Mesoporous SiO2 materials suitable for the above modification methods mainly include nano-fumed silica, monodisperse mesoporous SiO2 microspheres, SBA-15, KIT-6 and other mesoporous SiO2 molecular sieves.

[0020] The beneficial effects of the present invention are as follows: the mesoporous SiO2 material modified according to the above method has amphiphilic properties, being both hydrophilic and lipophilic; the modified mesoporous SiO2 material can be used as a drug carrier material, and can be well dispersed in both water and organic solvents, enabling the simultaneous loading and effective release of water-soluble and lipid-soluble drugs.

[0021] The above modification method is applicable to the amphiphilic modification of mesoporous Al2O3 materials, which also have surface hydrophilic active hydroxyl groups.

[0022] The mesoporous SiO2 and mesoporous Al2O3 materials modified according to the above method can also be applied to the modification of resin materials and rubber materials. Attached Figure Description

[0023] Figure 1 Microstructure of amphiphilic modified nano-fumed silica under transmission electron microscopy

[0024] Figure 2 Transmission electron microscopy morphology of amphiphilic modified monodisperse mesoporous SiO2 microspheres

[0025] Figure 3 Transmission electron microscopy morphology of amphiphilic modified SBA-15 mesoporous SiO2 molecular sieve

[0026] Figure 4 Transmission electron microscopy morphology of amphiphilic modified KIT-6 mesoporous SiO2 molecular sieve

[0027] Figure 5 Dissolution curve of fat-soluble vitamin D3 loaded into unmodified monodisperse mesoporous SiO2 microspheres in ethanol

[0028] In the graph: the horizontal axis represents dissolution time in hours (hr); the vertical axis represents dissolution rate in percent.

[0029] Figure 6 Dissolution curve of water-soluble vitamin C loaded into γ-aminopropyltriethoxysilane hydrophobically modified monodisperse mesoporous SiO2 microspheres in water

[0030] In the graph: the horizontal axis represents dissolution time in hours (hr); the vertical axis represents dissolution rate in percent.

[0031] Figure 7 Dissolution curve of fat-soluble vitamin D3 loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres in ethanol

[0032] In the graph: the horizontal axis represents dissolution time in hours (hr); the vertical axis represents dissolution rate in percent.

[0033] Figure 8 Dissolution curve of water-soluble vitamin C loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres in water

[0034] In the graph: the horizontal axis represents dissolution time in hours (hr); the vertical axis represents dissolution rate in percent. Detailed Implementation

[0035] The present invention will be further described below with reference to the embodiments and accompanying drawings.

[0036] Example 1

[0037] 0.1 mol nonylphenol polyoxyethylene ether (polyoxyethylene chain degree of polymerization of 20) and 0.15 mol NaOH were dissolved in 500 mL of deionized water, and 0.15 mol KMnO4 was added. The oxidation reaction was carried out under magnetic stirring for 24 hours. Unreacted KMnO4 and byproduct MnO2 were removed by filtration. The pH value was adjusted to 1.0 by adding hydrochloric acid dropwise at a rate of 1 drop / second. The sample was then freeze-dried under vacuum at -80℃ with a vacuum degree of 0 to 200 Pa to remove water. The sample was reconstituted with 50 mL of toluene, filtered, and rotary evaporated to remove toluene, thus obtaining the purified terminal carboxyl group sample.

[0038] 0.1 mol of purified terminal carboxyl group sample was dissolved in 300 mL of anhydrous CH2Cl2, and 0.15 mol of SOCl2 was added dropwise at a rate of 1 drop / second. The mixture was stirred continuously until the reaction was complete. The solvent CH2Cl2, unreacted SOCl2, and residual byproducts HCl and SO2 were removed by filtration and rotary evaporation to obtain purified terminal acyl chloride sample.

[0039] Nano-sized fumed silica was treated in an oven at 120°C for 24 hours, and then 50 mL of toluene was added to prepare a uniformly dispersed suspension. 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 130°C for 4 hours. The reaction system was allowed to cool naturally to room temperature. The hydrophobically modified nano-sized fumed silica was then filtered, washed with ethanol, and dried at 120°C to constant weight.

[0040] γ-aminopropyltriethoxysilane-modified nano-fumed silica was dispersed in 50 mL of toluene solvent, and triethylamine was added and stirred evenly. The amount of triethylamine added was 10 μL per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the nano-fumed silica dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond. After the reaction was completed, the amphiphilic modified nano-fumed silica was filtered, washed with ethanol, and dried at 120 °C to constant weight.

[0041] The microstructure of amphiphilic modified nano-fumed silica under transmission electron microscopy is as follows: Figure 1 As shown.

[0042] Example 2

[0043] 0.1 mol octylphenol polyoxyethylene ether (polyoxyethylene chain degree of polymerization of 10) and 0.11 mol NaOH were dissolved in 300 mL of deionized water, and 0.11 mol KMnO4 was added. The reaction was mechanically stirred for 4 hours. Unreacted KMnO4 and byproduct MnO2 were removed by filtration. The pH was adjusted to 3.0 by adding hydrochloric acid at a rate of 1 drop / second. The sample was then freeze-dried under vacuum at -30℃ with a vacuum degree of 0 to 200 Pa to remove water. The sample was reconstituted with 50 mL of toluene, filtered, and rotary evaporated to remove the toluene, yielding a purified terminal carboxyl group sample.

[0044] 0.1 mol of purified terminal carboxyl group sample was dissolved in 100 mL of anhydrous CH2Cl2, and 0.11 mol of SOCl2 was added dropwise at a rate of 1 drop / second. The mixture was stirred continuously until the reaction was complete. The solvent CH2Cl2, unreacted SOCl2, and residual byproducts HCl and SO2 were removed by filtration and rotary evaporation to obtain purified terminal acyl chloride sample.

[0045] Monodisperse mesoporous SiO2 microspheres were treated at 350℃ in an oven for 2 hours, and then 50 mL of toluene was added to prepare a uniformly dispersed suspension. 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 150℃ for 2 hours. The reaction system was allowed to cool naturally to room temperature. The hydrophobically modified monodisperse mesoporous SiO2 microspheres were filtered, washed with ethanol, and dried at 200℃ to constant weight.

[0046] γ-aminopropyltriethoxysilane-modified monodisperse mesoporous SiO2 microspheres were dispersed in 50 mL of toluene solvent, and triethylamine was added and stirred until homogeneous. The amount of triethylamine added was 1 μL per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the monodisperse mesoporous SiO2 microsphere dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond. After the reaction was completed, the amphiphilic modified monodisperse mesoporous SiO2 microspheres were filtered, washed with ethanol, and dried at 200 °C to constant weight.

[0047] The microstructure of amphiphilic modified monodisperse mesoporous SiO2 microspheres under transmission electron microscopy is as follows: Figure 2 As shown.

[0048] Example 3

[0049] 0.1 mol octylphenol polyoxyethylene ether (polyoxyethylene chain degree of polymerization of 8) and 0.13 mol NaOH were dissolved in 400 mL deionized water, and 0.13 mol KMnO4 was added. The oxidation reaction was carried out at room temperature with magnetic stirring for 10 hours. Unreacted KMnO4 and byproduct MnO2 were removed by filtration. The pH value was adjusted to 2.0 by adding hydrochloric acid dropwise at a rate of 1 drop / second. The sample was then freeze-dried under vacuum at -60℃ with a vacuum degree of 0 to 200 Pa to remove water. The sample was reconstituted with 50 mL toluene, filtered, and rotary evaporated to remove toluene, thus obtaining the purified terminal carboxyl group sample.

[0050] 0.1 mol of purified terminal carboxyl group sample was dissolved in 200 mL of anhydrous CH2Cl2, and 0.13 mol of SOCl2 was added dropwise at a rate of 1 drop / second. The mixture was stirred continuously until the reaction was complete. The solvent CH2Cl2, unreacted SOCl2, and residual byproducts HCl and SO2 were removed by filtration and rotary evaporation to obtain purified terminal acyl chloride sample.

[0051] Mesoporous SiO2 SBA-15 molecular sieve was treated in an oven at 280℃ for 8 hours, and then 50 mL of toluene was added to prepare a uniformly dispersed suspension. 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 140℃ for 8 hours. The reaction system was naturally cooled to room temperature, and the hydrophobically modified SBA-15 molecular sieve was filtered, washed with ethanol, and dried at 180℃ to constant weight.

[0052] The SBA-15 molecular sieve modified with γ-aminopropyltriethoxysilane was dispersed in 50 mL of toluene solvent, and triethylamine was added and stirred until homogeneous. The amount of triethylamine added was 6 μL per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the SBA-15 molecular sieve dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond. After the reaction was completed, the amphiphilic modified SBA-15 molecular sieve was filtered, washed with ethanol, and dried at 180 °C to constant weight.

[0053] Example 4

[0054] 0.1 mol dodecylphenol polyoxyethylene ether (polyoxyethylene chain degree of polymerization of 16) and 0.12 mol NaOH were dissolved in 450 mL of deionized water, and 0.12 mol KMnO4 was added. The oxidation reaction was carried out by stirring at room temperature for 16 hours. Unreacted KMnO4 and byproduct MnO2 were removed by filtration. The pH value was adjusted to 1.0 by adding hydrochloric acid dropwise at a rate of 1 drop / second. The sample was freeze-dried at -45℃ to remove water under a vacuum of 0-200 Pa. The sample was reconstituted with 50 mL of toluene, filtered, and rotary evaporated to remove toluene, thus obtaining the purified terminal carboxyl group sample.

[0055] 0.1 mol of purified terminal carboxyl group sample was dissolved in 250 mL of anhydrous CH2Cl2, and 0.12 mol of SOCl2 was added dropwise at a rate of 1 drop / second. The mixture was stirred continuously until the reaction was complete. The solvent CH2Cl2, unreacted SOCl2, and residual byproducts HCl and SO2 were removed by filtration and rotary evaporation to obtain purified terminal acyl chloride sample.

[0056] Mesoporous SiO2 KIT-6 molecular sieve was treated at 200℃ for 16 hours in a vacuum drying oven, and then toluene was added to prepare a uniformly dispersed suspension. 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 130℃ for 6 hours. The reaction system was allowed to cool naturally to room temperature. The hydrophobically modified KIT-6 molecular sieve was filtered, washed with ethanol, and dried at 150℃ to constant weight.

[0057] The KIT-6 molecular sieve modified with γ-aminopropyltriethoxysilane was dispersed in 50 mL of toluene solvent, and triethylamine was added and stirred evenly. The amount of triethylamine added was 4 μL per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the KIT-6 molecular sieve dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond. After the reaction was completed, the amphiphilic modified KIT-6 molecular sieve was filtered, washed with ethanol, and dried at 150 °C to constant weight.

[0058] The microstructure of the amphiphilic modified KIT-6 molecular sieve under transmission electron microscopy is as follows: Figure 4 As shown.

[0059] Example 5

[0060] Example 5 is a comparative example.

[0061] Fat-soluble vitamin D3 was loaded into unmodified monodisperse mesoporous SiO2 microspheres: Since unmodified monodisperse mesoporous SiO2 microspheres have a large number of hydrophilic surface-active hydroxyl groups, they cannot be fully wetted by organic solvents. Therefore, a saturated solution of vitamin D3 in a water-ethanol mixture (volume ratio 1:1) is required. The unmodified monodisperse mesoporous SiO2 microspheres were dispersed in the vitamin D3 solution and placed in a vacuum oven for pressure permeation to remove air from the mesopores, while ensuring that the drug is fully loaded into the pores and fully adsorbed onto the carrier. The pressure-permeated solution was filtered, washed, and dried to achieve drug loading.

[0062] Vitamin D3, loaded onto unmodified monodisperse mesoporous SiO2 microspheres, was dissolved in ethanol (dissolution curve shown in Figure 1). Figure 5 As shown): Because the unmodified monodisperse mesoporous SiO2 microspheres have a large number of hydrophilic surface-active hydroxyl groups, they cannot be fully wetted by ethanol. The drug needs to be gradually wetted by the dissolution medium to dissolve slowly. After 225 hours, the drug dissolution rate reaches about 90%.

[0063] Example 6

[0064] Example 6 is a comparative example.

[0065] Water-soluble vitamin C was loaded into monodisperse mesoporous SiO2 microspheres modified with hydrophobic γ-aminopropyltriethoxysilane. Since the hydrophobically modified monodisperse mesoporous SiO2 microspheres could not be fully wetted by water, a saturated solution of vitamin C in a water-ethanol mixture (volume ratio 1:1) was prepared. The monodisperse mesoporous SiO2 microspheres modified with hydrophobic γ-aminopropyltriethoxysilane were dispersed in the vitamin C solution and placed in a vacuum oven for pressure permeation to remove air from the mesopores, while ensuring that the drug was fully loaded into the pores and fully adsorbed onto the carrier. The pressure-permeated solution was filtered, washed, and dried to achieve drug loading.

[0066] Vitamin C loaded onto γ-aminopropyltriethoxysilane hydrophobically modified monodisperse mesoporous SiO2 microspheres was dissolved in water (dissolution curve shown in Figure 1). Figure 6 As shown): Since the monodisperse mesoporous SiO2 microspheres modified with hydrophobicity cannot be fully wetted by water, the drug needs to be gradually wetted by the dissolution medium to dissolve slowly. After 225 hours, the drug dissolution rate reaches about 70%.

[0067] Example 7

[0068] Fat-soluble vitamin D3 was loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres: the amphiphilic modified monodisperse mesoporous SiO2 microspheres can be fully wetted by organic solvents, and saturated ethanol solutions of vitamin D3 can be directly prepared; the amphiphilic modified monodisperse mesoporous SiO2 microspheres were dispersed in the vitamin D3 solution, and pressure permeation was performed in a vacuum oven to remove air from the mesopores, while ensuring that the drug was fully loaded into the pores and fully adsorbed onto the carrier; the pressure-permeated solution was filtered, washed, and dried to achieve drug loading.

[0069] Vitamin D3, loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres, was dissolved in ethanol (dissolution curve shown in Figure 1). Figure 7 As shown in the figure: Because the amphiphilic modified monodisperse mesoporous SiO2 microspheres can be fully wetted by ethanol, the drug has a good dissolution rate, and the drug dissolution rate exceeds 90% after 2 hours.

[0070] Example 8

[0071] Water-soluble vitamin C is loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres: the amphiphilic modified monodisperse mesoporous SiO2 microspheres can be fully wetted by water, and a water-saturated solution of vitamin C can be directly prepared; the amphiphilic modified monodisperse mesoporous SiO2 microspheres are dispersed in the vitamin C solution, and pressure permeation is performed in a vacuum oven to remove air from the mesopores, while ensuring that the drug is fully loaded into the pores and fully adsorbed onto the carrier; the pressure-permeated solution is filtered, washed, and dried to achieve drug loading.

[0072] Vitamin C, loaded into amphiphilic modified monodisperse mesoporous SiO2 microspheres, dissolves in water (dissolution curve shown in Figure 1). Figure 8 As shown in the figure: Because the amphiphilic modified monodisperse mesoporous SiO2 microspheres can be fully wetted by water, the drug has a good dissolution rate, and the drug dissolution rate exceeds 90% after 2 hours.

Claims

1. A method for modifying mesoporous SiO2 materials, characterized in that... The steps of this method are as follows: (1) Oxidize the terminal hydroxyl groups of alkylphenol polyoxyethylene ether to carboxyl groups. Dissolve 0.1 mol alkylphenol polyoxyethylene ether and 0.11–0.15 mol NaOH in 300–500 mL of deionized water, add 0.11–0.15 mol KMnO4, and continuously stir the oxidation reaction for 4–24 hours. Filter to remove unreacted KMnO4 and byproduct MnO2. Adjust the pH to 1.0–3.0 by adding hydrochloric acid dropwise at a rate of 1 drop / second. Freeze-dry under vacuum at -80–-30°C to remove water, with a vacuum degree of 0–200 Pa. Redissolve in 50 mL of toluene, filter, and remove toluene by rotary evaporation to obtain the purified terminal carboxyl group sample. The alkylphenol polyoxyethylene ether is octylphenol polyoxyethylene ether, nonylphenol polyoxyethylene ether or dodecyl polyoxyethylene ether, and the degree of polymerization of the polyoxyethylene chain is 8 to 20. (2) Prepare acyl chloride by terminating the carboxyl group. Dissolve 0.1 mol of purified terminal carboxyl group sample in 100–300 mL of anhydrous CH2Cl2, add 0.11–0.15 mol of SOCl2 dropwise, and stir continuously until the reaction is complete; filter and rotary evaporate to remove solvent CH2Cl2, unreacted SOCl2, residual byproducts HCl and SO2, to obtain purified terminal acyl chloride sample; (3) Mesoporous SiO2 material was hydrophobically modified with γ-aminopropyltriethoxysilane to obtain an amino structure at the γ-position. Mesoporous SiO2 material was treated in an oven at 120–350 °C for 2–24 hours; the treated mesoporous SiO2 material was added to 50 mL of toluene to prepare a uniformly dispersed suspension; 100 mL of γ-aminopropyltriethoxysilane was added dropwise at a rate of 1 drop / second, and the mixture was stirred and refluxed in an oil bath at 130–150 °C for 2–8 hours; the reaction system was allowed to cool naturally to room temperature, and the hydrophobically modified mesoporous SiO2 material was filtered, washed with ethanol, and dried at 120–200 °C to constant weight; (4) Construct amide bonds to complete the amphiphilic modification of mesoporous SiO2 materials. The hydrophobically modified mesoporous SiO2 material with γ-aminopropyltriethoxysilane was dispersed in 50 mL of toluene solvent. Triethylamine was added and stirred until homogeneous. The amount of triethylamine added was 1–10 μL per 1 mL of toluene. The purified terminal acyl chloride sample was redissolved in 50 mL of toluene and added dropwise to the mesoporous SiO2 material dispersion system at a rate of 1 drop / second. The terminal acyl chloride reacted with the γ-amino group to form an amide bond, completing the amphiphilic modification. After the reaction was completed, the amphiphilic modified mesoporous SiO2 material was filtered, washed with ethanol, and dried at 120–200 °C to constant weight. The modified mesoporous SiO2 material is nano-fumed silica, monodisperse mesoporous SiO2 microspheres, or mesoporous SiO2 molecular sieve.

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