Metal-gallic acid amphiphilic ultra-small nanoparticle and preparation method thereof

Abstract

The application discloses a kind of metal-gallic acid amphiphilic ultra-small nanoparticles and preparation method thereof, belong to the technical field of amphiphilic nanomaterials.The application is under the green preparation condition of whole water system, using the water or tris buffer solution system of low molecular weight (M.W.=6000~10000) polyvinylpyrrolidone (PVP), rely on weak coordination interaction between N atom in PVP and metal ion, slow down the combination speed between metal ion and gallic acid, inhibit the growth of metal-gallic acid amphiphilic ultra-small nanoparticles, and metal-gallic acid acid amphiphilic ultra-small nanoparticles are prepared.The application has the advantages of mild reaction condition, simple operation, green environmental protection, good product dispersibility, convenient mass production, good applicability for the preparation of various metal-gallic acid amphiphilic ultra-small nanoparticles, and the prepared product has excellent water dispersibility and good emulsifying capacity, and the HLB value is between 12~14.

Description

Technical Field

[0001] This invention belongs to the field of amphiphilic nanomaterials technology, specifically relating to a metal-gallic acid amphiphilic ultrasmall nanoparticle and its preparation method. Background Technology

[0002] Solid nanoparticles of a certain size and with desired wettability have proven to be alternatives to traditional emulsifiers. For example, hydroxyapatite, nano-silica, molecular sieves, carbon materials, and clays have all been modified and used in the preparation of Pickering emulsions. Pickering emulsions, using solid particles instead of traditional polymeric surfactants, result in more stable emulsions with many useful properties. Furthermore, solid particles exhibit enhanced biocompatibility when relatively safe in vivo. Selective modification of nanoparticle surfaces allows for directional modification of materials to meet the requirements of target application environments, enabling wide-ranging applications in biopharmaceuticals, food, fine chemical synthesis, and cosmetics.

[0003] Gallic acid is a polyphenolic compound with natural antioxidant activity. Because its molecule contains five oxygen atoms on both sides and the distance between the phenolic oxygen atoms is large, gallic acid can form stable complexes with transition metal ions, thus exhibiting strong reducing and coordinating properties. Gallic acid derivatives have wide applications in medicine, food, and cosmetics. Soluble salts of iron, cobalt, nickel, and copper ions are inexpensive and readily available, and can serve as coordination center ions to form stable amphiphilic (both hydrophilic and lipophilic) nanoparticles with gallic acid.

[0004] In the emulsification application of amphiphilic nanoparticles, smaller nanoparticles often more easily form dense emulsion systems with small droplets, maintaining the stability advantages of Pickering emulsions. However, due to the influence of specific surface energy, the redispersion of ultrasmall nanoparticles after drying the prepared system to obtain a solid is usually plagued by agglomeration. The lack of large-scale preparation methods for amphiphilic ultrasmall nanoparticles limits their development and application. Metal ions and gallic acid can rapidly coordinate and stably form ultrasmall nanoparticles under certain conditions, and some studies have already applied them in the biomedical field. However, research on the amphiphilic properties (hydrophilic and lipophilic) of "metal-gallic acid" ultrasmall nanoparticles has not received much attention. Therefore, it is very important to study a preparation method for amphiphilic ultrasmall nanoparticles based on "metal-gallic acid" complexes. Summary of the Invention

[0005] The purpose of this invention is to provide a metal-gallic acid amphiphilic ultrasmall nanoparticle and its preparation method, wherein the metal element is Fe, Co, Ni or Cu.

[0006] This invention utilizes an aqueous solution of low molecular weight polyvinylpyrrolidone (PVP) in a green, all-aqueous preparation system. By relying on the weak coordination interaction between the nitrogen atoms in PVP and metal ions, the binding rate between metal ions and gallic acid is slowed, thus inhibiting the growth of metal-gallic acid amphiphilic ultrafine nanoparticles. For cobalt and nickel ions, which have poor nucleation ability with gallic acid, the pH value is controlled using a Tris buffer solution to promote the growth rate of the nanoparticles in a controllable manner.

[0007] The method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles provided by this invention features mild reaction conditions, simple operation, and is environmentally friendly (no organic solvents are used). The product exhibits good dispersibility and is suitable for large-scale production. It is applicable to the preparation of various metal-gallic acid amphiphilic ultrasmall nanoparticles, and the prepared product demonstrates excellent water dispersibility. When used for emulsification of toluene / water and n-octane / water two-phase systems, it exhibits excellent emulsifying performance, showing good emulsifying ability under a wide pH range. Furthermore, the prepared metal-gallic acid amphiphilic ultrasmall nanoparticles, as a semi-hydrophilic solid emulsifier material, have an HLB value between 12 and 14.

[0008] The preparation method of metal-gallic acid amphiphilic ultrasmall nanoparticles according to the present invention comprises the following steps:

[0009] (1) Dissolve ferric chloride hexahydrate, cobalt chloride, nickel chloride hexahydrate or copper chloride dihydrate in water to prepare an aqueous solution of metal ions;

[0010] (2) Add the metal ion aqueous solution obtained in step (1) to the Tris buffer solution system of low molecular weight polyvinylpyrrolidone or the aqueous solution system of polyvinylpyrrolidone, and stir to disperse to promote the weak coordination between polyvinylpyrrolidone and metal ions.

[0011] (3) Slowly add gallic acid aqueous solution to the solution obtained in step (2) and stir continuously at a certain temperature for a period of time;

[0012] (4) Transfer the reaction system obtained in step (3) into a dialysis bag (20000Da), change the water every 10 to 15 hours, and perform dialysis continuously for 2 to 3 days;

[0013] (5) The contents of the bag after dialysis in step (4) are heated and dried at 90-110°C to obtain the metal-gallic acid amphiphilic ultra-small nanoparticles.

[0014] The metal-gallic acid amphiphilic ultra-small nanoparticles (Fe-GA, Co-GA, Ni-GA, Cu-GA) obtained in step (5) were dispersed in water to prepare a nanoparticle dispersion with a concentration of 2-10 mg / mL. The surface tension was measured using a surface tension meter.

[0015] The metal-gallic acid amphiphilic ultra-small nanoparticles (Fe-GA, Co-GA, Ni-GA, Cu-GA) obtained in step (5) were dispersed in water to prepare a nanoparticle dispersion with a concentration of 1-3 mg / mL. The dispersion was then mixed with toluene, cyclohexane, and n-octane (volume ratio 1:1) and ultrasonically emulsified at a certain power (180W-360W) for a certain time (1-3 min). After standing for 24 h, the emulsification rate was measured, and the microstructure of the emulsion bubbles was studied using an optical microscope.

[0016] The metal-gallic acid amphiphilic ultra-small nanoparticles (Fe-GA, Co-GA, Ni-GA, Cu-GA) obtained in step (5) were dispersed in an aqueous system with pH adjusted by HCl or NaOH (pH = 1-13) to prepare metal-gallic acid aqueous dispersions and polyvinylpyrrolidone aqueous dispersions with concentrations of 1-3 mg / mL at different pH values. The product dispersions and polyvinylpyrrolidone aqueous dispersions at different pH values ​​were mixed with n-octane at a volume ratio of 1:1, and sonicated for a certain time (1-3 min) at a certain power (180W-360W) using a probe-type ultrasonic instrument. After standing for 24 h, the emulsification rate was measured, and the microstructure of the emulsion bubbles was examined using a microscope.

[0017] Preferably, in the aqueous solution of metal ions in step (1), the concentration of metal ions is 0.3–0.5 mol / L;

[0018] Preferably, in step (2), the low molecular weight polyvinylpyrrolidone Tris buffer solution system is prepared by adding low molecular weight polyvinylpyrrolidone to a Tris buffer solution with pH = 7.3 to 7.5; the low molecular weight polyvinylpyrrolidone aqueous solution system is prepared by adding low molecular weight polyvinylpyrrolidone to deionized water; the concentration of polyvinylpyrrolidone is 6000 to 9000 ppm, and the molecular weight of polyvinylpyrrolidone is MW = 6000 to 10000;

[0019] Preferably, in step (2), after the metal ion aqueous solution is added to the Tris buffer solution system of low molecular weight polyvinylpyrrolidone or the aqueous solution system of low molecular weight polyvinylpyrrolidone, the concentration of metal ions is 6.67 to 11.1 mmol / L.

[0020] Preferably, the reaction temperature in step (3) is 20-30°C, the reaction time is 2-12 h, and the molar ratio of gallic acid to metal ions is 0.6-0.9:1.

[0021] According to one embodiment of the present invention, compared with conventional emulsifiers, it is applicable to a wider pH range, and the toluene / water and n-octane / water emulsion systems prepared with these ultrasmall metal-gallic acid amphiphilic nanoparticles exhibit superior stability. Furthermore, surface tension measurements show that the prepared metal-gallic acid product demonstrates excellent surface activity, significantly reducing the surface tension of aqueous systems. Attached Figure Description

[0022] Figure 1 Transmission electron microscopy (TEM) image of the Fe-GA amphiphilic ultrasmall nanoparticles prepared in Example 1;

[0023] Figure 2 The dynamic light scattering particle size distribution of the ultrasmall nanoparticles prepared for the example is shown in the figure; wherein, Figure 2 a) Dynamic light scattering particle size distribution of Fe-GA ultrasmall nanoparticles prepared in Example 1; Figure 2 b) is a dynamic light scattering particle size distribution diagram of the Co-GA ultrasmall nanoparticles prepared in Example 2; Figure 2 c) is the dynamic light scattering particle size distribution of the Ni-GA ultrasmall nanoparticles prepared in Example 3; Figure 2 d) is the dynamic light scattering particle size distribution of the Cu-GA ultrasmall nanoparticles prepared in Example 4;

[0024] Figure 3 The images show the microstructure of the Fe-GA, Co-GA, Ni-GA, and Cu-GA amphiphilic ultrafine nanoparticles prepared in Examples 1-4 on the emulsion droplets of toluene / water, cyclohexane / water, and n-octane / water two-phase emulsion systems.

[0025] Figure 4 The images show the emulsification rate and average emulsion particle size distribution of the Fe-GA, Co-GA, Ni-GA, and Cu-GA amphiphilic ultrafine nanoparticles prepared in Examples 1-4 for toluene / water, cyclohexane / water, and n-octane / water two-phase emulsion systems.

[0026] Figure 5 Photographs of the appearance of Fe-GA, Co-GA, Ni-GA, Cu-GA amphiphilic ultrasmall nanoparticles and polyvinylpyrrolidone n-octane / water two-phase emulsion systems prepared in Examples 1-4 at different pH values.

[0027] Figure 6The emulsification rate and statistical distribution of the average droplet size of the Fe-GA, Co-GA, Ni-GA, Cu-GA amphiphilic ultra-small nanoparticles and polyvinylpyrrolidone prepared in Examples 1-4 at different pH values ​​are shown in the figure.

[0028] Figure 7 The graph shows the average particle size variation of Fe-GA, Co-GA, Ni-GA, and Cu-GA amphiphilic ultrasmall nanoparticles prepared in Examples 1-4 in an oil-water system with gradient HLB values. Detailed Implementation

[0029] To provide a more detailed explanation of the technical aspects and application scenarios of this invention, and to facilitate those skilled in the art in manufacturing and using the technical content of this invention, a more detailed and complete description will be provided below in conjunction with the accompanying drawings and specific embodiments. It should be noted that the embodiments described below are not all embodiments, but only embodiments of the preferred inventive conditions of this patent. The necessary pharmaceuticals and instruments involved in this invention can all be purchased through normal commercial channels.

[0030] Example 1

[0031] 330 mg of polyvinylpyrrolidone (MW8000) was added to 44 mL of deionized water and dissolved by stirring at room temperature to obtain a 7500 ppm polyvinylpyrrolidone aqueous solution. 1 mL of 0.37 mol / L ferric chloride hexahydrate solution was added and stirred for 30 min to ensure that polyvinylpyrrolidone could regulate nanoparticle growth during the subsequent nanoparticle formation process. 5 mL of 10 mg / mL gallic acid aqueous solution was slowly added dropwise to the system, which quickly turned black. After stirring and reacting for 10 h at room temperature, the system was transferred to a dialysis bag (20000 Da) for dialysis, with water changed every 12 h for two consecutive days to remove free chloride ions, polyvinylpyrrolidone, and other impurities. The microstructure was imaged using a transmission electron microscope, and the results are shown below. Figure 1 As shown, the Fe-GA amphiphilic ultrasmall nanoparticles exhibit a relatively uniform spherical shape. The particle size distribution of the Fe-GA ultrasmall nanoparticles was measured using dynamic light scattering (DLS). Figure 2 As shown in a, its average diameter is 5.46 nm. Finally, the dialysis bag liquid was dried at 100 °C to obtain 224 mg of black Fe-GA ultra-small nanoparticle product. The iron content in Fe-GA is 1.59 wt%. The surface tension of the 2 mg / mL aqueous dispersion prepared using this product decreased by 8.07% compared with pure water.

[0032] Example 2

[0033] 330 mg of polyvinylpyrrolidone (MW8000) was added to 44 mL of Tris buffer solution (pH 7.4) and dissolved by stirring at room temperature to obtain a 7500 ppm polyvinylpyrrolidone Tris buffer solution. 1 mL of cobalt chloride (0.37 mol / L) solution was added and the solution was stirred for 30 min to ensure that polyvinylpyrrolidone could regulate nanoparticle growth during subsequent nanoparticle formation. 5 mL of 10 mg / mL gallic acid aqueous solution was slowly added dropwise to the system, which quickly turned brownish-yellow. After stirring and reacting for 10 h at room temperature, the system was transferred to a dialysis bag (20000 Da) for dialysis, with water changed every 12 h for two consecutive days to remove free chloride ions, polyvinylpyrrolidone, and other impurities. The particle size distribution of the Co-GA ultrafine nanoparticles was measured using dynamic light scattering (DLS). Figure 2 As shown in b, its average diameter is 10.20 nm. Finally, the dialysis bag liquid was dried at 100 °C to obtain 265 mg of brownish-black Co-GA ultra-small nanoparticle product. The cobalt content in Co-GA is 1.21 wt%. The surface tension of the 2 mg / mL aqueous dispersion prepared using this product decreased by 8.38% compared with pure water.

[0034] Example 3

[0035] 330 mg of polyvinylpyrrolidone (MW8000) was added to 44 mL of Tris buffer solution (pH 7.4) and dissolved by stirring at room temperature to obtain a 7500 ppm polyvinylpyrrolidone Tris buffer solution. 1 mL of nickel chloride hexahydrate (0.37 mol / L) solution was added and stirred for 30 min to ensure that polyvinylpyrrolidone could regulate nanoparticle growth during subsequent nanoparticle formation. 5 mL of 10 mg / mL gallic acid aqueous solution was slowly added dropwise to the system, which quickly turned brownish-yellow. After stirring and reacting for 10 h at room temperature, the system was transferred to a dialysis bag (20000 Da) for dialysis, with water changed every 12 h for two consecutive days to remove free chloride ions, polyvinylpyrrolidone, and other impurities. The particle size distribution of the Ni-GA ultrafine nanoparticles was measured using dynamic light scattering (DLS). Figure 2 As shown in c, its average diameter is 9.18 nm. Finally, the dialysis bag liquid was dried at 100 °C to obtain 263 mg of brownish-black Ni-GA ultra-small nanoparticle product. The nickel content in Ni-GA is 0.86 wt%. The surface tension of the 2 mg / mL aqueous dispersion prepared using this product decreased by 7.37% compared with pure water.

[0036] Example 4

[0037] 330 mg of polyvinylpyrrolidone (MW8000) was added to 44 mL of deionized water and dissolved by stirring at room temperature to obtain a 7500 ppm polyvinylpyrrolidone aqueous solution. 1 mL of copper chloride dihydrate (0.37 mol / L) solution was added and stirred for 30 min to ensure that polyvinylpyrrolidone controlled nanoparticle growth during subsequent nanoparticle formation. 5 mL of 10 mg / mL gallic acid aqueous solution was slowly added dropwise to the system, which quickly turned brownish-yellow. After stirring and reacting at room temperature for 10 h, the system was transferred to a dialysis bag (20000 Da) for dialysis, with water changed every 12 h for two consecutive days to remove free chloride ions, polyvinylpyrrolidone, and other impurities. The particle size distribution of Cu-GA ultrafine nanoparticles was measured using dynamic light scattering (DLS). Figure 2 As shown in d, its average diameter is 7.23 nm. Finally, the dialysis bag liquid was dried at 100 °C to obtain 230 mg of brownish-black Cu-GA ultrafine nanoparticle product. The copper content in Cu-GA is 0.68 wt%. The surface tension of the 2 mg / mL aqueous dispersion prepared using this product decreased by 6.68% compared with pure water.

[0038] Table 1 shows the surface tension of the aqueous dispersions of metal-gallic acid amphiphilic ultrafine nanoparticles (Fe, Co, Ni, Cu) prepared in Examples 1-4 at 25°C.

[0039]

[0040]

[0041] Example 5

[0042] Using the metal-gallic acid amphiphilic ultrafine nanoparticles prepared in Examples 1, 2, 3, and 4 as raw materials, 2 mg / mL aqueous dispersions were prepared respectively. Then, at a water-to-oil volume ratio of 1:1, the dispersions were mixed with toluene, cyclohexane, and n-octane respectively, and ultrasonically emulsified for 3 min (instrument: SCIENTZ-1500F ultrasonic disperser from Ningbo Xinzhi Biotechnology Co., Ltd.; parameters: 3 min, 30%, 2.0 Sed, ultrasonic power 270 W). After standing for 24 h, the emulsification rate was measured, and the microstructure of the emulsion bubbles was studied using an optical microscope. The state of the emulsion droplets under the microscope is shown in the figure below. Figure 3 As shown, the emulsion droplets are dense and the droplet size distribution is relatively uniform. Figure 4This study demonstrates the emulsification rate and average droplet size of emulsions prepared by using metal-gallic acids (Fe, Co, Ni, Cu, and PVP) as surfactants to emulsify three organic solvents. The results indicate that metal-gallic acid ultrafine nanoparticles exhibit superior emulsification performance compared to polyvinylpyrrolidone (8000 M.W.). Specifically, in the toluene / water system, although both PVP (8000 M.W.) and metal-gallic acids (Fe, Co, Ni, Cu) achieved emulsification rates of around 75%, the droplet size of the latter was only 50%–60% of that of the former. In cyclohexane / water and n-octane / water systems, after standing for one day, the PVP (8000 M.W.) emulsion system completely demulsified, while the metal-gallic acid emulsion still maintained an emulsification rate of 70%–75% and a dense emulsion state with an average droplet size of 20 μm. This indicates that the metal-gallic acid amphiphilic ultra-small nanoparticle emulsifier has better emulsification performance, and the stability of the prepared emulsion is significantly better than that of (PVP, 8000 M.W.).

[0043] Example 6

[0044] The ultra-small metal-gallic acid amphiphilic nanoparticles and polyvinylpyrrolidone (8000 M.W.) prepared in Examples 1, 2, 3, and 4 were dispersed in water systems with pH values ​​adjusted by NaOH or HCl (pH = 1, 3, 5, 7, 9, 11, and 13), respectively, to prepare metal-gallic acid aqueous dispersions and polyvinylpyrrolidone aqueous dispersions with a concentration of 2 mg / mL at different pH values. Then, the metal-gallic acid aqueous dispersions and polyvinylpyrrolidone aqueous dispersions were mixed with n-octane at an oil-water volume ratio of 1:1. The mixture was ultrasonicated for 3 min at 270 W using a probe-type ultrasonic instrument. After standing for 24 h, the emulsification rate was measured, and the average particle size of the emulsion droplets was observed and counted under a microscope. Figure 5 The emulsification of ultrasmall metal-gallic acid amphiphilic ultrasmall nanoparticles (Fe, Co, Ni, Cu) and polyvinylpyrrolidone (PVP, 8000 M.W.) under different pH conditions is presented. Figure 6 The emulsification rates and average droplet sizes of ultrasmall metal-gallic acid amphiphilic nanoparticles and polyvinylpyrrolidone (PVP, 8000 M.W.) at different pH values ​​are presented. Figure 5 and Figure 6Our results show that metal-gallic acid amphiphilic ultrafine nanoparticles have a wider applicable pH range as solid emulsifiers. Fe-GA, Co-GA, and Ni-GA exhibit excellent surface activity in aqueous solutions with pH values ​​ranging from 1 to 13, while Cu-GA maintains excellent surface activity in aqueous solutions with pH values ​​ranging from 5 to 11. They also demonstrate good emulsifying properties in oil-water two-phase systems. Compared to traditional polyvinylpyrrolidone nonionic surfactants, they exhibit a wider range of applicability.

[0045] Example 7

[0046] Table 2 shows the proportions of cottonseed oil and turpentine oil blends with HLB values.

[0047]

[0048] The metal-gallic acid ultrasmall amphiphilic nanoparticles prepared in Examples 1, 2, 3, and 4 were dispersed in water to prepare an aqueous dispersion of 1 mg / mL. Following the conventional emulsification method, cottonseed oil and turpentine oil were used to prepare a mixed oil phase with gradient HLB values ​​according to the proportions in Table 2. 4 mL of the 1 mg / mL nanoparticle dispersion was added to the prepared gradient oil phases with HLB values ​​of 11, 12, 13, 14, and 15. The mixture was sonicated at 270 W for 2 min, allowed to stand for 1 week, and the average particle size of the emulsion bubbles was measured and statistically analyzed. Figure 7 The particle size distribution of emulsion droplets in an oil-water system with gradient HLB values ​​is shown. We can consider the prepared metal-gallic acid amphiphilic ultra-small nanoparticles as a surfactant with an HLB value in the range of 12 to 14, which is hydrophilic.

Claims

1. A method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles, comprising the following steps: (1) Prepare an aqueous solution of metal ions by dissolving ferric chloride hexahydrate, cobalt chloride, nickel chloride hexahydrate or copper chloride dihydrate in water; (2) Add the aqueous solution of metal ions obtained in step (1) to a Tris buffer solution system of low molecular weight polyvinylpyrrolidone or an aqueous solution system of low molecular weight polyvinylpyrrolidone, and stir to disperse and promote the weak coordination between polyvinylpyrrolidone and metal ions; wherein, The molecular weight of low molecular weight polyvinylpyrrolidone is MW=6000~10000; (3) Slowly add the gallic acid aqueous solution to the solution obtained in step (2) and stir continuously at a certain temperature for a period of time; (4) Transfer the reaction system obtained in step (3) into a dialysis bag with a capacity of 20,000 Da, change the water every 10 to 15 hours, and dialyze continuously for 2 to 3 days; (5) The contents of the bag after dialysis in step (4) are heated and dried at 90~110℃ to obtain the metal-gallic acid amphiphilic ultra-small nanoparticles.

2. The method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles as described in claim 1, characterized in that: In step (1), the concentration of metal ions in the aqueous solution of metal ions is 0.3~0.5 mol / L.

3. The method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles as described in claim 1, characterized in that: In step (2), the low molecular weight polyvinylpyrrolidone Tris buffer solution system is prepared by adding low molecular weight polyvinylpyrrolidone to a Tris buffer solution with pH=7.3~7.5; the low molecular weight polyvinylpyrrolidone aqueous solution system is prepared by adding low molecular weight polyvinylpyrrolidone to deionized water; the concentration of polyvinylpyrrolidone is 6000~9000ppm.

4. The method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles as described in claim 1, characterized in that: In step (2), after the metal ion aqueous solution is added to the tris buffer solution system of low molecular weight polyvinylpyrrolidone or the aqueous solution system of low molecular weight polyvinylpyrrolidone, the concentration of metal ions is 6.67~11.1 mmol / L.

5. The method for preparing metal-gallic acid amphiphilic ultrasmall nanoparticles as described in claim 1, characterized in that: In step (3), the reaction temperature is 20~30℃, the reaction time is 2h~12h, and the molar ratio of gallic acid to metal ions is 0.6~0.9:

1.

6. A metal-gallic acid amphiphilic ultrasmall nanoparticle, characterized in that: It is prepared by the method described in any one of claims 1 to 5.

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