Preparation method of magnetic carbon quantum dots with high relaxation rate

Abstract

The present invention relates to a preparation method of magnetic carbon quantum dots with high relaxation rate, comprising the following steps: (1) dissolving sp<supgt;3< / supgt> precursor and sp<supgt;2< / supgt> precursor in a solvent for solvothermal reaction to obtain a first mixed system; (2) redispersing the reaction product in water, performing suction filtration, and then adding gadolinium ions for hydrothermal reaction to obtain a second mixed system; (3) performing dialysis on the second mixed system to obtain magnetic carbon quantum dots with high relaxation rate. During the preparation process of the present invention, the reaction conditions are controllable and the product purification is simple. The obtained carbon quantum dots not only have the paramagnetism of gadolinium ions but also have the fluorescence characteristics of carbon quantum dots, and can be used as a probe for nuclear magnetic resonance relaxation-fluorescence dual-mode in vitro diagnostic technology to improve the accuracy of in vitro diagnostic technology.

Description

Technical Field

[0001] The present invention belongs to the field of new materials, and particularly relates to a preparation method of magnetic carbon quantum dots with high relaxation rate. Background Art

[0002] Carbon quantum dots are carbon nanomaterials with a size of about 2 - 10 nm. Their size is at the nanoscale, and they have characteristics such as good biocompatibility, easy modification and preparation, adjustable bandgap, and high quantum yield. They are widely used in research in fields such as fluorescence in vitro detection, magnetic contrast agents, LEDs, and electrochemistry. By modifying carbon quantum dots with magnetic groups, magnetic carbon quantum dots can be obtained, which can be applied to magnetic relaxation-fluorescence dual-mode in vitro detection. Carbon quantum dots combined with magnetic groups - paramagnetic iron oxides or rare earth elements can be used as magnetic resonance imaging contrast agents to improve tissue imaging contrast and shorten the imaging time, or can be used as magnetic relaxation sensing probes for in vitro diagnostic techniques.

[0003] The seven unpaired electrons of gadolinium atoms in the 4f electron orbit lead to its strong paramagnetism. The preparation of gadolinium-based magnetic carbon quantum dots is usually completed through two-step reactions. The first step is to prepare carbon quantum dots through a bottom-up or top-down reaction, and the second step is to form a coordination structure between gadolinium ion groups and functional groups (oxygen-containing functional groups - hydroxyl, carboxyl, carbonyl, etc. and nitrogen-containing functional groups - amino, etc.) on the surface of the quantum dots to obtain magnetic carbon quantum dots. However, the structural controllability of the gadolinium-based magnetic carbon quantum dots obtained by the above preparation method is low, and the binding ability of the obtained gadolinium ions is uncertain.

[0004] In the application field, due to the adjustable fluorescence properties and good biocompatibility, carbon quantum dots are often combined with biomolecules for tissue and cell fluorescence imaging and pathogen-specific detection. Because carbon quantum dots are easy to modify and have good dispersibility, this material can combine magnetic groups to improve the magnetic susceptibility of biological media in nuclear magnetic resonance imaging, providing a more accurate reference for clinical diagnosis. Thus, carbon quantum dots can achieve dual-mode detection of fluorescence signals and magnetic signals, improving the detection accuracy.

[0005] Therefore, how to design carbon quantum dots with controllable structure to achieve controllable binding of gadolinium ions in carbon quantum dots, so that carbon quantum dots have high relaxation rate and excellent fluorescence properties is a problem that needs to be solved by those skilled in the art. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a preparation method of magnetic carbon quantum dots with high relaxation rate. The carbon quantum dots prepared by this method have high relaxation rate and excellent fluorescence properties, and have good market application prospects.

[0007] The present invention provides a preparation method of magnetic carbon quantum dots with high relaxation rate, including the following steps:

[0008] (1) Dissolve the sp 2 precursor and the sp 3 precursor in a solvent to conduct a solvothermal reaction to obtain a first mixed liquid; wherein, the molar ratio of the precursor to the chain-like precursor is 1-2:1-2;

[0009] (2) Redisperse the reaction product in water, perform suction filtration, and then add gadolinium ions to conduct a hydrothermal reaction to obtain a second mixed system; (3) Dialyze the second mixed system to obtain high-relaxivity magnetic carbon quantum dots.

[0010] The sp 3 precursor in step (1) is one or more of 1-bromoadamantane, 2-bromoadamantane, 1,3,5,7-tetrabromoadamantane, 1,3-dibromoadamantane, 1-bromo-3,5-dimethyladamantane, 1-adamantylmethylamine.

[0011] The sp 2 precursor in step (1) is one or more of o-phenylenediamine, m-phenylenediamine, 2-chloro-1,4-phenylenediamine, p-phenylenediamine, 1,5-diaminonaphthalene, 4-chloro-o-phenylenediamine, 1,8-diaminonaphthalene, 4-chloro-1,3-phenylenediamine, 4,4'-diaminotriphenyl, 1-aminoanthracene, 2-aminoanthracene, ethylenediamine, 4,4'-diaminobiphenyl, 9-aminoanthracene, 2,6-diaminoanthracene. The solvent in step (1) is one or more of deionized water, ethanol, acetone, ethyl acetate, carbon tetrachloride, dichloromethane.

[0012] In the first mixed liquid in step (1), the concentrations of the sp 3 precursor and the sp 2 precursor are respectively 0.5-4 mg / mL.

[0013] The process parameters of the solvothermal reaction in step (1) are: the reaction temperature is 130°C - 150°C, and the reaction time is 24 h - 72 h.

[0014] The molar ratio of gadolinium ions to the precursor in step (2) is 0.1-0.5:1.

[0015] The process parameters of the hydrothermal reaction in step (2) are: the reaction temperature is 130°C - 150°C, and the time is 24 h - 72 h.

[0016] The filter membrane used for suction filtration in step (2) is of 200-250 nm grade.

[0017] The dialysis in step (3) is carried out using a dialysis bag with a cut-off molecular weight of 100-500 Da, the dialysis time is 3-10 days, and the deionized water outside the dialysis bag is changed every 3-12 hours.

[0018] The relaxation rate of the high-relaxation-rate magnetic carbon quantum dots obtained in step (3) is 80 - 130 L / (mmol·s), the fluorescence emission wavelength is 400 - 500 nm; the size is 3 - 10 nm, the carbon content is 30% - 60%, and the gadolinium content is 3% - 5%.

[0019] Beneficial effects

[0020] During the preparation process of the present invention, the reaction conditions are controllable, the product purification is simple, the precursor provides good structural rigidity for the carbon quantum dots, and the chain-like precursor provides a better pore structure for the carbon quantum dots, realizing the

[0021] effective binding of gadolinium ions; the high-relaxation-rate magnetic carbon quantum dots obtained by the present invention not only have the paramagnetism of gadolinium ions but also have the fluorescence characteristics of carbon quantum dots, and can be used as a probe for in vitro diagnostic technology with nuclear magnetic resonance relaxation-fluorescence dual modes, improving the accuracy of in vitro diagnostic technology. Description of the Drawings

[0022] Figure 1 It is a schematic process flow diagram of Example 1.

[0023] Figure 2 It is the X-ray photoelectron spectrum of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 1.

[0024] Figure 3 It is the atomic force microscope photograph of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 1.

[0025] Figure 4 It is the relaxation rate fitting curve of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 1 measured in a very low-field nuclear magnetic resonance system.

[0026] Figure 5 It is the fluorescence emission spectrum of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 1.

[0027] Figure 6 It is the X-ray photoelectron spectrum of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 2.

[0028] Figure 7 It is the atomic force microscope photograph of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 2.

[0029] Figure 8 It is the relaxation rate fitting curve of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 2 measured in a very low-field nuclear magnetic resonance system.

[0030] Figure 9 It is the fluorescence emission spectrum of the high-relaxation-rate magnetic carbon quantum dots prepared in Example 2. Detailed Embodiments

[0031] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0032] Example 1

[0033] Combined with Figure 1 certain steps of

[0034] (1) Weigh 19.525 mg of 4,4'-diaminotriphenyl and 33.886 mg of 1,3,5,7-tetrabromoadamantane;

[0035] (2) Carry out a solvothermal reaction of the above-mentioned 4,4'-diaminotriphenyl and 1,3,5,7-tetrabromoadamantane in 15 mL of anhydrous ethanol at a temperature of 140 °C for a reaction time of 24 h to obtain a first mixed system;

[0036] (3) Redisperse the reaction product in water, filter it by suction with a 220 nm-level filter membrane, add gadolinium ions, and carry out a hydrothermal reaction at a temperature of 140 °C for a solvothermal reaction time of 24 h to obtain a second mixed system;

[0037] (4) Dialyze the second mixed system using a dialysis bag with a cut-off molecular weight of 100 - 500 Da for a dialysis time of 5 days, and change the deionized water outside the dialysis bag every 6 hours during this period to obtain a dispersion of magnetic carbon quantum dots with high relaxation rate.

[0038] It can be seen from Figure 2 that the carbon content of the carbon quantum dots is 36.7%, and the gadolinium content is 5.2%. It can be seen from Figure 3 that the size of the carbon quantum dots is 5 nm. It can be seen from Figure 4 that the transverse relaxation rate of the carbon quantum dots is 81.78 L / (mmol·s). It can be seen from Figure 5 that the maximum emission wavelength of the carbon quantum dots is 430 nm when the excitation wavelength is 301 nm.

[0039] Example 2

[0040] Combined with Figure 1 certain steps of

[0041] (1) Weigh 8.1105 mg of o-phenylenediamine and 33.886 mg of 1,3,5,7-tetrabromoadamantane;

[0042] (2) Carry out a solvothermal reaction of the above o-phenylenediamine and 1,3,5,7-tetrabromoadamantane in 15 mL of absolute ethanol at a temperature of 140 °C for a reaction time of 24 h to obtain a first mixed system;

[0043] (3) Redisperse the reaction product in water, filter it by suction through a 220 nm-level filter membrane, add gadolinium ions, and carry out a hydrothermal reaction at a temperature of 140 °C for a solvothermal reaction time of 24 h to obtain a second mixed system;

[0044] (4) Dialyze the second mixed system using a dialysis membrane with a molecular weight cut-off of 100 - 500 Da for a dialysis time of 5 days, and change the deionized water outside the dialysis membrane every 6 hours to obtain a dispersion of magnetic carbon quantum dots with a high relaxation rate.

[0045] It can be seen from Figure 6 that the carbon content of the carbon quantum dots is 30.8%, and the gadolinium content is 4.2%. It can be seen from Figure 7 that the size of the carbon quantum dots is 6 nm. It can be seen from Figure 8 that the transverse relaxation rate of the carbon quantum dots is 111.83 L / (mmol·s). It can be seen from Figure 9 that the maximum emission wavelength of the carbon quantum dots is 421 nm when the excitation wavelength is 306 nm.

[0046] The above embodiments only exemplarily illustrate the principles and effects of the present invention, rather than limiting the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the invention. Therefore, all equivalent modifications or changes completed by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A preparation method of high-relaxivity magnetic carbon quantum dots, comprising the following steps: (1) Dissolve the sp 3 precursor and the sp 2 precursor in a solvent to carry out a solvothermal reaction to obtain a first mixed system; wherein, The sp 3 precursor and the sp 2 precursor have a molar ratio of 1-2:1-2; the sp 3 precursor is one or more of 1-bromoadamantane, 2-bromoadamantane, 1,3,5,7-tetrabromoadamantane, 1,3-dibromoadamantane, 1-bromo-3,5-dimethyladamantane, 1-adamantanemethylamine; the sp 2 precursor is one or more of o-phenylenediamine, m-phenylenediamine, 2-chloro-1,4-phenylenediamine, p-phenylenediamine, 1,5-diaminonaphthalene, 4-chloro-o-phenylenediamine, 1,8-diaminonaphthalene, 4-chloro-1,3-phenylenediamine, 4,4'-diaminotriphenyl, 1-aminoanthracene, 2-aminoanthracene, ethylenediamine, 4,4'-diaminobiphenyl, 9-aminoanthracene, 2,6-diaminoanthracene; (2) Redisperse the reaction product in water, perform suction filtration, and then add gadolinium ions for hydrothermal reaction to obtain a second mixed system; (3) Dialyze the second mixed system to obtain high-relaxivity magnetic carbon quantum dots.

2. The preparation method according to claim 1, characterized in that: The solvent in the step (1) is one or more of ethanol, acetone, ethyl acetate, carbon tetrachloride, and dichloromethane.

3. The preparation method according to claim 1, characterized in that: The concentrations of the sp 3 precursor and the sp 2 precursor in the first mixed system in the step (1) are 0.5 - 4 mg / mL respectively.

4. The preparation method according to claim 1, characterized in that: The process parameters of the solvothermal reaction in the step (1) are: the reaction temperature is 130°C - 150°C, and the reaction time is 24h - 72h.

5. The preparation method according to claim 1, characterized in that: The molar ratio of gadolinium ions to the precursor in the step (2) is 0.1 - 1:

1.

6. The preparation method according to claim 1, characterized in that: The process parameters of the hydrothermal reaction in the step (2) are: the reaction temperature is 130°C - 150°C, and the time is 24h - 72h.

7. The preparation method according to claim 1, characterized in that: The dialysis in the step (3) is carried out using a dialysis bag with a molecular weight cut-off of 100 - 500 Da, the dialysis time is 3 - 10 days, and the deionized water outside the dialysis bag is changed every 3 - 12 hours.

8. The preparation method according to claim 1, characterized in that: The relaxivity of the high-relaxivity magnetic carbon quantum dots obtained in the step (3) is 80 - 130 L / (mmol·s), and the fluorescence emission wavelength is 400 - 500 nm.

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