CN111634951A - Preparation method of iron oxide/gadolinium oxide composite nanoparticles with uniformly distributed elements - Google Patents
Preparation method of iron oxide/gadolinium oxide composite nanoparticles with uniformly distributed elements Download PDFInfo
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- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 38
- 239000002131 composite material Substances 0.000 title claims abstract description 36
- 229910001938 gadolinium oxide Inorganic materials 0.000 title claims abstract description 36
- 229940075613 gadolinium oxide Drugs 0.000 title claims abstract description 36
- CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000010438 heat treatment Methods 0.000 claims abstract description 21
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052688 Gadolinium Inorganic materials 0.000 claims abstract description 18
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- HOIQWTMREPWSJY-GNOQXXQHSA-K iron(3+);(z)-octadec-9-enoate Chemical compound [Fe+3].CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O HOIQWTMREPWSJY-GNOQXXQHSA-K 0.000 claims abstract description 14
- 239000002243 precursor Substances 0.000 claims abstract description 14
- 238000010992 reflux Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 8
- DZAUWHJDUNRCTF-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(O)C(O)=C1 DZAUWHJDUNRCTF-UHFFFAOYSA-N 0.000 claims abstract description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 20
- 239000012498 ultrapure water Substances 0.000 claims description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- 238000005303 weighing Methods 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadec-1-ene Chemical compound CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 9
- 239000002086 nanomaterial Substances 0.000 claims description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- PNYPSKHTTCTAMD-UHFFFAOYSA-K trichlorogadolinium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Gd+3] PNYPSKHTTCTAMD-UHFFFAOYSA-K 0.000 claims description 5
- 238000009826 distribution Methods 0.000 claims description 4
- 239000002244 precipitate Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 3
- 238000012986 modification Methods 0.000 abstract description 3
- 230000004048 modification Effects 0.000 abstract description 3
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 abstract description 3
- 238000005979 thermal decomposition reaction Methods 0.000 abstract description 3
- 238000009835 boiling Methods 0.000 abstract 1
- 239000003960 organic solvent Substances 0.000 abstract 1
- 239000002872 contrast media Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000005540 biological transmission Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 3
- 230000002902 bimodal effect Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000724 energy-dispersive X-ray spectrum Methods 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 1
- 238000012307 MRI technique Methods 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- -1 gadolinium diamine Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000000593 microemulsion method Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C01G49/00—Compounds of iron
- C01G49/02—Oxides; Hydroxides
- C01G49/06—Ferric oxide [Fe2O3]
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Abstract
A preparation method of iron oxide/gadolinium oxide composite nano-particles with uniformly distributed elements comprises the following steps: (1) preparing an iron oleate/gadolinium precursor compound by using a reflux device; (2) preparing ferric oxide gadolinium oxide composite nano particles by using a high-temperature thermal decomposition method, placing a ferric oleate/gadolinium precursor compound in an organic solvent with a high boiling point, and heating at a high temperature to obtain a product; (3) and placing the prepared product and 3, 4-dihydroxyphenyl propionic acid in a three-neck flask, and controlling the reaction temperature and time to obtain the hydrophilic ferric oxide/gadolinium oxide composite nano-particles with uniformly distributed elements. The preparation method has the advantages of simple preparation process and low cost, and the obtained product has good dispersibility and safety. The invention has good application value in the aspects of preparation, modification and application of the magnetic resonance contrast agent material.
Description
Technical Field
The invention relates to a preparation method of hydrophilic ferric oxide/gadolinium oxide composite nano particles with uniformly distributed elements, belongs to the field of nano materials, and can be used for the preparation, modification, application and other aspects of magnetic resonance contrast agent materials.
Background
Magnetic resonance imaging techniques are important in clinical disease diagnosis due to the characteristics of non-invasiveness, high resolution, high penetrability and the like, however, with the increase of disease complexity, contrast agents are often required to assist disease diagnosis. The contrast agent does not generate a signal, and can react with the protons of the surrounding water after entering the human body to shorten the relaxation time so as to generate the signal, thereby achieving the contrast effect.
Contrast agents are classified according to imaging effect and can be generally classified into two categories: positive contrast agents and negative contrast agents. The gadolinium-based contrast agent is a contrast agent commonly used in clinic at present, such as gadolinium meglumine pentajetting, gadolinium diamine and the like, belongs to a positive contrast agent, and can shorten the longitudinal relaxation time (T)1) And the bright signal is presented, and the clinical diagnosis application is wider. However, gadolinium-based contrast agents induce renal systemic fibrosis and brain deposition that cannot be ignored. Therefore, the development of low-toxicity contrast agents has attracted attention. The iron oxide nanoparticles have good biocompatibility, belong to negative contrast agents, and can shorten the transverse relaxation time (T)2) A dark signal is present. However, such contrast agents are prone to artifact when applied, which affects the accuracy of disease diagnosis. Thus, T having two imaging effects is prepared1-T2The bimodal contrast agent not only can integrate the advantages of the two contrast agents, but also can reduce the influence caused by the defects, and the bimodal contrast agent and the contrast agent mutuallyThe method has the advantages of supplementing imaging information, improving the accuracy of disease diagnosis and having better application value in the aspect of clinical diagnosis.
The existing methods for preparing the iron oxide nano particles include various methods such as a coprecipitation method, a high-temperature thermal decomposition method, a microemulsion method, a hydrothermal method and the like.
Disclosure of Invention
The invention provides a preparation method of highly biocompatible and hydrophilic iron oxide/gadolinium oxide nanoparticles with uniformly distributed elements.
1. The preparation method of the iron oxide/gadolinium oxide nano-particles with uniformly distributed elements comprises the following steps:
(1) preparation of iron oleate/gadolinium precursor complex: 5.47g of sodium oleate (10 mmol), 60ml of ultrapure water and 20ml of absolute ethanol were placed in a 250ml three-necked flask and dissolved with stirring, and 0.81g of anhydrous ferric chloride (5.0 mmol) and 0.38g of gadolinium chloride hexahydrate (1.0 mmol) were placed in 20ml of ultrapure water and dissolved with stirring. And then dropwise adding the solution into the three-neck flask, heating to 75 ℃ for refluxing for 4h, stopping the reaction, cooling the solution with liquid, transferring the cooled solution into a separating funnel, adding 20ml of n-hexane, standing for layering, discarding the lower layer, washing for 2 times by using ultrapure water, and drying the product in an oven at 55 ℃ for 24h to obtain the waxy iron oleate/gadolinium precursor compound.
(2) Preparing iron oxide/gadolinium oxide composite nanoparticles: weighing 1.12g of iron oleate/gadolinium precursor compound in a beaker, adding 0.17ml of oleic acid and 15ml of 1-octadecene, ultrasonically stirring to dissolve the compound, transferring the mixture into a 250ml three-neck flask, and introducing N2Heating to 200 deg.C, reacting for 30min, heating to 320 deg.C at 4 deg.C/min, reacting for 30min, stopping reaction, transferring into a centrifuge tube, adding 80ml anhydrous ethanol for precipitation, centrifuging at 8000rpm for 5min, repeatedly cleaning with anhydrous ethanol for 3 times (if the solid is tightly attached to the centrifuge tube wall, small amount of n-hexane can be added for suspension), collecting precipitate, adding 3ml n-hexane, and storing at 4 deg.C.
(3) Preparing hydrophilic ferric oxide/gadolinium oxide composite nanoparticles: weighing 200mg of 3, 4-dihydroxyphenyl propionic acid and 60ml of tetrahydrofuran, introducing nitrogen, heating to 50 ℃, weighing 100mg of ferric oxide/gadolinium oxide composite nano particles, dissolving in 20ml of tetrahydrofuran, dropwise adding into the three-neck flask, refluxing for 4h at 50 ℃, stopping reaction, adding 5ml of 0.5mol/L sodium hydroxide, centrifuging at 10000rpm for 10min, discarding supernatant, and adding 3ml of ultrapure water for re-suspension to obtain the hydrophilic ferric oxide/gadolinium oxide composite nano material.
The hydrophilic ferric oxide/gadolinium oxide composite nano-particles with uniformly distributed elements are regular in appearance, cubic, good in dispersity and uniform in particle size, and the particle size is 4-8 nm.
The invention utilizes a high-temperature thermal decomposition method to prepare the ferric oxide/gadolinium oxide composite nano-particles with uniformly distributed elements, obtains cubic nano-particles with regular appearance, uniform particle size distribution and good dispersibility, and utilizes non-toxic 3, 4-dihydroxyphenyl propionic acid to modify the cubic nano-particles, so that the nano-particles not only obtain hydrophilicity, but also improve the biocompatibility, and the application of the nano-particles in organisms has practical value.
The preparation method has the advantages of simple preparation process and low cost, and the obtained product has good dispersibility and safety. Has good application value in the aspects of preparation, modification and application of magnetic resonance contrast agent materials.
Hydrophilic iron oxide/gadolinium oxide nanoparticles were diluted to different concentrations with cell culture medium (Fe content: 15. mu.g/ml, 30. mu.g/ml, 45. mu.g/ml, 60. mu.g/ml). L929 cells were treated with 1 × 104The density of each hole is planted in a 96-hole plate, the plate is placed in a cell culture box for 24 hours, the culture medium is removed and replaced by the cell culture medium containing the nano-particles, and after the plate is cultured for 12 hours, 24 hours and 48 hours, the cell activity of the plate is measured by using a CCK-8 kit. The result shows that the obtained hydrophilic ferric oxide/gadolinium oxide nano-particles have good biocompatibility.
Drawings
FIG. 1 is a transmission electron microscope image of a composite nanoparticle of iron oxide/gadolinium oxide;
FIG. 2 is a transmission electron microscope image of hydrophilic ferric oxide/gadolinium oxide composite nano-particles;
FIG. 3 is an EDS spectrum (Fe element area distribution diagram) of hydrophilic iron oxide/gadolinium oxide composite nanoparticles;
fig. 4 is an EDS spectrum (Gd element area distribution diagram) of the hydrophilic iron oxide/gadolinium oxide composite nanoparticle.
Detailed Description
The foregoing and other objects, features, and advantages of the invention will be apparent from the following more particular description of the embodiments of the invention, as illustrated in the accompanying drawings. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples. Various substitutions and alterations according to the general knowledge and conventional practice in the art are intended to be included within the scope of the present invention without departing from the technical spirit of the present invention as described above.
Example 1
5.47g of sodium oleate, 60ml of ultrapure water and 20ml of absolute ethanol were placed in a 250ml three-necked flask and dissolved with stirring, and 0.81g of anhydrous ferric chloride and 0.38g of gadolinium chloride hexahydrate were placed in 20ml of ultrapure water and dissolved with stirring. And then dropwise adding the solution into the three-neck flask, heating to 75 ℃ for refluxing for 4h, stopping the reaction, cooling the solution with liquid, transferring the cooled solution into a separating funnel, adding 20ml of n-hexane, standing for layering, removing the lower layer, leaving the product, washing the product for 2 times by using ultrapure water, and drying the product in an oven at 55 ℃ for 24h to obtain a waxy iron oleate/gadolinium precursor compound.
Weighing 1.12g of iron oleate/gadolinium composite precursor in a beaker, adding 0.17ml of oleic acid and 15ml of 1-octadecene, ultrasonically stirring to dissolve the mixture, transferring the mixture into a 250ml three-neck flask, and introducing N2Heating to 200 ℃, reacting for 30min, heating to 320 ℃ at the speed of 4 ℃/min, reacting for 30min, stopping the reaction, transferring to a centrifuge tube, adding 80ml of absolute ethyl alcohol to precipitate, centrifuging at 8000rpm for 5min, repeatedly washing with absolute ethyl alcohol for 3 times, and finally obtaining the iron oxide/gadolinium oxide composite nanoparticles (the picture of the nanoparticle transmission electron microscope is shown in figure 1).
Weighing 200mg of 3, 4-dihydroxyphenyl propionic acid and 60ml of tetrahydrofuran, introducing nitrogen, heating to 50 ℃, weighing 100mg of ferric oxide/gadolinium oxide composite nanoparticles, dissolving in 20ml of tetrahydrofuran, dropwise adding into the three-neck flask, refluxing for 4h at 50 ℃, stopping the reaction, adding 5ml of 0.5mol/L sodium hydroxide, centrifuging at 10000rpm for 10min, discarding the supernatant, and adding 3ml of ultrapure water for resuspension to obtain the hydrophilic ferric oxide/gadolinium oxide composite nanomaterial (the picture of the hydrophilic nanoparticle transmission electron microscope is shown in figure 2, and the EDS map is shown in figure 3).
Example 2
5.47g of sodium oleate, 60ml of ultrapure water and 20ml of absolute ethanol were placed in a 250ml three-necked flask and dissolved with stirring, and 0.81g of anhydrous ferric chloride and 0.38g of gadolinium chloride hexahydrate were placed in 20ml of ultrapure water and dissolved with stirring. And then dropwise adding the solution into the three-neck flask, heating to 80 ℃ for refluxing for 4h, stopping the reaction, cooling the solution with liquid, transferring the cooled solution into a separating funnel, adding 20ml of n-hexane, standing for layering, removing the lower layer, leaving the product, washing the product for 2 times by using ultrapure water, and drying the product in a vacuum drying oven at 55 ℃ for 24h to obtain a waxy iron oleate/gadolinium composite precursor.
Weighing 1.12g of iron oleate/gadolinium composite precursor in a beaker, adding 0.17ml of oleic acid and 15ml of 1-octadecene, ultrasonically stirring to dissolve the mixture, transferring the mixture into a 250ml three-neck flask, and introducing N2Heating to 200 ℃, reacting for 30min, heating to 320 ℃ at the speed of 3 ℃/min, reacting for 30min, stopping the reaction, transferring to a centrifuge tube, adding 80ml of absolute ethyl alcohol to precipitate, centrifuging at 8000rpm for 5min, repeatedly washing for 3 times by using the absolute ethyl alcohol, and finally obtaining the iron oxide/gadolinium oxide composite nano-particles.
Weighing 200mg of 3, 4-dihydroxyphenyl propionic acid and 60ml of tetrahydrofuran, introducing nitrogen, heating to 50 ℃, weighing 100mg of ferric oxide/gadolinium oxide composite nano particles, dissolving in 20ml of tetrahydrofuran, dropwise adding into the three-neck flask, refluxing for 4h at 50 ℃, stopping reaction, adding 5ml of 0.5mol/L sodium hydroxide, centrifuging at 10000rpm for 10min, discarding supernatant, and adding 3ml of ultrapure water for re-suspension to obtain the hydrophilic ferric oxide/gadolinium oxide composite nano material.
Example 3
6.02g of sodium oleate, 60ml of ultrapure water and 20ml of absolute ethanol were placed in a 250ml three-necked flask and dissolved with stirring, and 0.89g of anhydrous ferric chloride and 0.42g of gadolinium chloride hexahydrate were placed in 20ml of ultrapure water and dissolved with stirring. And then dropwise adding the solution into the three-neck flask, heating to 80 ℃ for refluxing for 4h, stopping the reaction, cooling the solution with liquid, transferring the cooled solution into a separating funnel, adding 20ml of n-hexane, standing for layering, discarding the lower layer, washing the Liu product for 2 times by using ultrapure water, and drying the product in an oven at 55 ℃ for 24h to obtain the waxy iron oleate/gadolinium precursor compound.
Weighing 1.12g of iron oleate/gadolinium composite precursor in a beaker, adding 0.17ml of oleic acid and 15ml of 1-octadecene, ultrasonically stirring to dissolve the mixture, transferring the mixture into a 250ml three-neck flask, and introducing N2Heating to 200 ℃, reacting for 30min, heating to 310 ℃ at the speed of 4 ℃/min, reacting for 30min, stopping the reaction, transferring to a centrifuge tube, adding 80ml of absolute ethyl alcohol to precipitate, centrifuging at 8000rpm for 5min, repeatedly washing with absolute ethyl alcohol for 3 times, and finally obtaining the iron oxide/gadolinium oxide composite nanoparticles.
Weighing 300mg of 3, 4-dihydroxyphenyl propionic acid and 60ml of tetrahydrofuran in a three-neck flask, introducing nitrogen, heating to 50 ℃, weighing 150mg of ferric oxide/gadolinium oxide composite nanoparticles, dissolving in 20ml of tetrahydrofuran, dropwise adding into the three-neck flask, refluxing for 4.5h at 50 ℃, stopping reaction, adding 5ml of 0.5mol/L sodium hydroxide, centrifuging at 10000rpm for 10min, discarding the supernatant, and adding 3ml of ultrapure water for re-suspension to obtain the hydrophilic ferric oxide/gadolinium oxide composite nanomaterial.
Claims (2)
1. The preparation method of the iron oxide/gadolinium oxide composite nano-particles with uniformly distributed elements is characterized by comprising the following specific steps of:
(1) preparation of iron oleate/gadolinium precursor complex: placing 10mmol of 5.47g of sodium oleate, 60ml of ultrapure water and 20ml of absolute ethyl alcohol into a 250ml three-neck flask and stirring for dissolving; placing 5.0mmol of 0.81g of anhydrous ferric chloride and 1.0mmol of 0.38g of gadolinium chloride hexahydrate in 20ml of ultrapure water, stirring for dissolving, dropwise adding into the three-neck flask, heating to 75 ℃, refluxing for 4 hours, and stopping the reaction; after cooling, transferring the liquid into a separating funnel, adding 20ml of n-hexane, standing for layering, discarding the lower layer, washing for 2 times by using ultrapure water, and placing the product in an oven for drying at 55 ℃ for 24 hours to obtain a waxy iron oleate/gadolinium precursor compound;
(2) preparing iron oxide/gadolinium oxide composite nanoparticles: weigh 1.12g of iron oleate/gadolinium precursor complex into a beaker, add 0.17ml of oleic acid and15ml of 1-octadecene is dissolved by ultrasonic stirring, then transferred into a 250ml three-neck flask, and N is introduced2Heating to 200 ℃, reacting for 30min, heating to 320 ℃ at the speed of 4 ℃/min, reacting for 30min, stopping the reaction, transferring to a centrifuge tube, adding 80ml of absolute ethyl alcohol to precipitate the product, centrifuging at 8000rpm for 5min, repeatedly washing with absolute ethyl alcohol for 3 times to finally obtain precipitate, namely iron oxide/gadolinium oxide composite nanoparticles, adding 3ml of n-hexane, and storing in an environment at 4 ℃;
(3) preparing hydrophilic ferric oxide/gadolinium oxide composite nanoparticles: weighing 200mg of 3, 4-dihydroxyphenyl propionic acid and 60ml of tetrahydrofuran, introducing nitrogen, heating to 50 ℃, weighing 100mg of ferric oxide/gadolinium oxide composite nano particles, dissolving in 20ml of tetrahydrofuran, dropwise adding into the three-neck flask, refluxing for 4h at 50 ℃, stopping reaction, adding 5ml of 0.5mol/L sodium hydroxide, centrifuging at 10000rpm for 10min, discarding supernatant, and adding 3ml of ultrapure water for re-suspension to obtain the hydrophilic ferric oxide/gadolinium oxide composite nano material.
2. The method as claimed in claim 1, wherein the hydrophilic iron oxide/gadolinium oxide composite nanoparticles have regular shape, cubic shape, good dispersibility, uniform particle size distribution, and particle size of 4-8 nm.
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