A chiral Se / Fe2O3 nanomaterial, its preparation method and applications

Abstract

The present invention relates to a chiral Se / Fe2O3 nanomaterial, its preparation method and application, belonging to the technical field of inorganic chemistry. In the present invention, a variety of chiral amino acids are used as chiral inducers to synthesize the Se / Fe2O3 nanomaterial in one step under hydrothermal reaction conditions, and interact with chiral ligands to form chiral units. By regulating the temperature, time, type and content of reducing agent, and type of chiral ligand, etc., chiral Se / Fe2O3 nanomaterials are obtained. The different chiral Se / Fe2O3 synthesized in the present invention all have good chiral optical activity in the visible light region, have high biocompatibility, can be applied to the treatment of Alzheimer's disease, and have broad application prospects in the field of neurodegenerative therapy.

Description

Technical Field

[0001] The present invention relates to the technical field of nanomaterial synthesis, and particularly to a chiral Se / Fe2O3 nanomaterial, a preparation method thereof, and an application thereof. Background Art

[0002] Chirality is ubiquitous in nature and is an important hallmark of life on Earth. Chiral molecules refer to molecules with a certain configuration or conformation that are not identical to their mirror images and cannot be superimposed on each other. Chirality is a basic substance that constitutes living organisms. Proteins and RNA in living organisms are both chiral, resulting in a special chiral environment in living organisms. This makes chiral nanomaterials have great application prospects in the fields of life health and bioengineering.

[0003] Iron exists in the human body as a trace element and plays various roles. From the oxygen transport of the body to immune metabolism, the assistance of iron element is indispensable. Iron element also plays an important role in the treatment of major diseases such as cardiovascular and cerebrovascular diseases and cancer. Selenium is an essential trace element for the human body and is a component of various enzymes in the human body. It plays many biological functions in life, such as resisting diseases, delaying aging, enhancing immune function, anti-cancer, protecting the cardiovascular system, regulating hormone secretion, and scavenging excess free radicals. Bimetallic composite materials can achieve the effect of 1+1>2 in the treatment of diseases, making them play a synergistic effect, and can effectively improve the important role of nanomaterials in the fields of bioengineering and disease treatment.

[0004] Chiral materials have good biocompatibility and differential affinity effects, and Aβ contains an α-helix in the 13-23 fragment. Since the α / β inconsistency plays a key role in the formation of Aβ fibrils, targeting the α-helix form in this region of the Aβ peptide may be a new method for designing and screening Aβ aggregation inhibitors. Due to the α-helix structure and the chirality of the l-amino acids that make up the peptide, Aβ is sensitive to the chiral environment, and the interaction between Aβ and the chiral inhibitor also shows a specific orientation. It has good scavenging ability for β-amyloid fibrils in cells and in vivo, and thus plays an important role in the treatment of neurodegenerative diseases.

[0005] However, the use of chiral ligands to induce the generation of Se / Fe2O3 nanomaterials with circular dichroism absorption signals in the visible and near-infrared light regions for the treatment of neurodegenerative diseases has not been reported. Summary of the Invention

[0006] Therefore, the technical problem to be solved by the present invention is to overcome the problems in the prior art, such as poor biocompatibility, inability to precisely control the morphology and size of nanomaterials, and poor binding effect between chiral ligands and nanomaterials.

[0007] To solve the above technical problems, the present invention provides a method for preparing a chiral Se / Fe₂O₃ nanomaterial. Ferric salts and selenide salts are respectively used as the iron source and the selenium source, and chiral amino acid ligands are used as chiral inducers to interact with Se / Fe₂O₃ nanoparticles to form chiral units; by regulating the temperature, time, type and content of the reducing agent, and type of chiral ligand, etc., the chiral ligand is induced to obtain chiral Se / Fe₂O₃ nanoparticles through intermolecular interactions, which have excellent circular dichroism absorption signals in the visible light and near-infrared light regions.

[0008] The first object of the present invention is to provide a method for preparing a chiral Se / Fe₂O₃ nanomaterial, comprising the following steps:

[0009] Add the iron source, selenium source and chiral ligand into a solvent and mix evenly, add a reducing agent and mix to obtain a mixture, and perform a hydrothermal reaction on the obtained mixture to obtain a reaction solution of the chiral Se / Fe₂O₃ nanomaterial.

[0010] In any embodiment of the present invention, the iron source is one or more of ferrous sulfate, ferrous nitrate, ferrous chloride, ferric nitrate and ferric chloride.

[0011] In any embodiment of the present invention, the chiral ligand is one or more of cysteine, penicillamine, glutathione, tartaric acid and proline.

[0012] In any embodiment of the present invention, the cysteine, penicillamine, glutathione, tartaric acid and proline all include L-type and / or D-type.

[0013] In any embodiment of the present invention, the selenium source is selected from one or more of sodium selenite, selenium powder and selenium dioxide.

[0014] In any embodiment of the present invention, the solvent is one or more of water, methanol, ethanol, ethylene glycol and isopropanol; the conditions of the hydrothermal reaction: the reaction temperature is 90 - 150 °C, and the reaction time is 2 h - 12 h.

[0015] In any embodiment of the present invention, the reducing agent is one or more of sodium borohydride, hydrazine hydrate, ethylenediamine, ascorbic acid and ammonia water, and the molar ratio of the reducing agent to the selenium source is 1:0.5 - 4.

[0016] In any embodiment of the present invention, the molar ratio of the iron source to the selenium source is 1:0.5 - 3;

[0017] The molar ratio of the chiral ligand to the iron in the iron source is 1:0.5 - 2.

[0018] In any embodiment of the present invention, after the hydrothermal reaction, it further includes solid-liquid separation of the reaction solution after the hydrothermal reaction. The method used for the solid-liquid separation is a conventional method in the art, and centrifugal separation can be used. The conditions for the centrifugal separation method are: rotation speed 4000 rpm - 10000 rpm, time 5 min - 10 min, and number of times 1 - 3 times.

[0019] The second object of the present invention is to provide a chiral Se / Fe2O3 nanomaterial obtained by the preparation method; the chiral Se / Fe2O3 nanomaterial has a nanoscale sea cucumber-like structure; the characteristic peak of the circular dichroism spectrum signal of the chiral Se / Fe2O3 nanomaterial is 300 - 400 nm and 500 - 700 nm.

[0020] The third object of the present invention is to provide the application of the chiral Se / Fe2O3 nanomaterial in the preparation of drugs for neurodegenerative diseases.

[0021] The above technical solutions of the present invention have the following advantages compared with the prior art:

[0022] (1) The chiral Se / Fe2O3 nanomaterial described in the present invention has excellent optical activity, has strong CD activity in the visible light region, and can accurately regulate its structure and chiral signal.

[0023] (2) The chiral Se / Fe2O3 nanomaterial described in the invention has excellent biocompatibility. Iron elements play an important role in the treatment of major diseases such as cardiovascular and cerebrovascular diseases and cancer. Selenium plays many biological functions in life, such as resisting diseases, delaying aging, and scavenging excess free radicals. The iron and selenium bimetallic composite material can achieve an effect of 1 + 1 > 2 in the treatment of diseases, making it play a synergistic effect, and can greatly improve the ability to treat neurodegenerative diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to make the content of the present invention easier to be clearly understood, the following further describes the present invention in detail according to the specific embodiments of the present invention and in combination with the drawings, where

[0025] Figure 1 is the present invention Figure 1 is the CD diagram of the chiral Se / Fe2O3 nanomaterial obtained by the present invention.

[0026] Figure 2 is the UV spectrum diagram of the chiral Se / Fe2O3 nanomaterial obtained by the present invention.

[0027] Figure 3 is the SEM diagram of the chiral Se / Fe2O3 nanomaterial obtained by the present invention.

[0028] Figure 4 TEM image of the chiral Se / Fe2O3 nanomaterial obtained in the present invention.

[0029] Figure 5 TEM-Mapping image of the chiral Se / Fe2O3 nanomaterial obtained in the present invention.

[0030] Figure 6 XRD pattern of the chiral Se / Fe2O3 nanomaterial obtained in the present invention.

[0031] Figure 7 Improvement effect of the chiral Se / Fe2O3 nanomaterial obtained in the present invention on the behavior of AD mice in the water maze.

[0032] Figure 8 Statistical analysis of the behavioral data of the chiral Se / Fe2O3 nanomaterial obtained in the present invention for AD mice in the water maze. Specific Embodiments

[0033] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the embodiments given are not intended to limit the present invention.

[0034] Example 1

[0035] Add 1 mL of FeCl2·4H2O (0.3 M) to 7 mL of high-purity water and stir continuously at 600 rpm. Then add 1 mL of L- / D-Pen (0.75 M), stir evenly, then add 1 mL of Na2SeO3 (0.3 M), stir evenly, and finally add 3 mL of ethylenediamine, stir evenly, and then heat in a autoclave at 120 °C for 6 h, wash three times with 6000 rpm / 10 min to obtain L- / D-chiral Se / Fe2O3 nanoparticles.

[0036] Example 2

[0037] Add 1 mL of FeCl2·4H2O (0.3 M) to 7 mL of high-purity water and stir continuously at 600 rpm. Then add 1 mL of L- / D-Cys (0.75 M), stir evenly, then add 1 mL of Na2SeO3 (0.3 M), stir evenly, and finally add 3 mL of ethylenediamine, stir evenly, and then heat in a autoclave at 120 °C for 6 h, wash three times with 6000 rpm / 10 min to obtain L- / D-chiral Se / Fe2O3 nanoparticles.

[0038] Example 3

[0039] Add 1 mL of FeCl2·4H2O (0.3 M) to 7 mL of high-purity water and stir continuously at 600 rpm. Then add 1 mL of L- / D-Tar (0.75 M), stir evenly, then add 1 mL of Na2SeO3 (0.3 M), stir evenly, and finally add 3 mL of ethylenediamine, stir evenly. Then heat in an autoclave at 120 °C for 6 h, wash three times with 6000 rpm / 10 min of water to obtain L- / D-chiral Se / Fe2O3 nanoparticles.

[0040] Example 4

[0041] Add 1 mL of Fe(NO3)2 (0.3 M) to 7 mL of high-purity water and stir continuously at 600 rpm. Then add 1 mL of L- / D-Pen (0.75 M), stir evenly, then add 1 mL of Na2SeO3 (0.3 M), stir evenly, and finally add 3 mL of ethylenediamine, stir evenly. Then heat in an autoclave at 120 °C for 6 h, wash three times with 6000 rpm / 10 min of water to obtain L- / D-chiral Se / Fe2O3 nanoparticles.

[0042] Example 5

[0043] Add 1 mL of FeCl2·4H2O (0.3 M) to 7 mL of high-purity water and stir continuously at 600 rpm. Then add 1 mL of L- / D-Pen (0.75 M), stir evenly, then add 1 mL of SeO2 (0.3 M), stir evenly, and finally add 3 mL of ethylenediamine, stir evenly. Then heat in an autoclave at 120 °C for 6 h, wash three times with 6000 rpm / 10 min of water to obtain L- / D-chiral Se / Fe2O3 nanoparticles.

[0044] The characterization methods and results involved in the above examples are as follows:

[0045] (1) Circular dichroism spectrum: The chiral Se / Fe2O3 nanoparticles prepared in Example 1 were tested using a circular dichroism instrument. First, take 1 mL of the stock solution, centrifuge at 6000 rpm for 10 min, remove the supernatant, disperse it in 1 mL of high-purity water, repeat 2 times, and then perform the test. The range is 300 - 1700 nm, temperature: 25 °C; scanning speed, 200 nm / min; data interval: 0.5 nm; bandwidth: 5 nm (visible light region bandwidth: 10 nm); digital integration time: 2 s. The results correspond to Figure 1 and Figure 2 . It can be seen from the data in the figure that the characteristic peaks of the CD signal mainly appear at 300 - 400 nm and 500 - 700 nm, and its highest intensity can reach 56 millidegrees, which is beneficial to the utilization rate of circularly polarized light.

[0046] (2) Scanning transmission microscope: The chiral Se / Fe2O3 nanoparticles prepared in Example 1 were characterized and analyzed. First, 0.1 mL of the stock solution was taken, centrifuged at 6000 rpm for 10 min, the supernatant was removed, and it was dispersed in 1 mL of high-purity water and repeated twice. A cut silicon wafer was taken, cleaned and dried with nitrogen. Then, 5 μL of the centrifuged sample was dropped on the silicon wafer and air-dried at room temperature. The scanning electron microscope (SEM) images were taken using Hitachi SU9000 with an acceleration voltage of 100 kV. The results are as Figure 3 shown. The chiral Se / Fe2O3 nanomaterial is a conical material with a length of 1 μm.

[0047] (3) Transmission electron microscope: The chiral Se / Fe2O3 nanoparticles prepared in Example 1 were characterized and analyzed. First, 0.1 mL of the stock solution was taken, centrifuged at 6000 rpm for 10 min, the supernatant was removed, and it was dispersed in 1 mL of high-purity water and repeated twice. A cut copper grid was taken, cleaned and dried with nitrogen. Then, 5 μL of the centrifuged sample was dropped on the copper grid and air-dried at room temperature. It was photographed using a transmission electron microscope (TEM), and then Mapping was carried out to collect elemental signals. The results are as Figures 4 - 5 shown. It can be concluded that the four elements Fe, Se, C, O, and S are evenly dispersed, indicating that the material is synthesized evenly.

[0048] (4) X-ray diffraction: The chiral Se / Fe2O3 nanoparticles prepared in Example 1 were tested by XRD. 30 mL of parallel samples were collected, centrifuged at 6000 rpm for 10 min, the supernatant was removed, and it was dispersed in 1 mL of ethanol and repeated twice. Then, it was dried overnight in an oven at 60 °C, ground in a mortar, and then subjected to XRD testing. X-ray diffraction (XRD) was carried out on a Bruker D8, irradiated with CuKα, and the scanning rate was 10 min -1 , the range was 5 - 90°, the target voltage was 40 kV, and the current was 40 mA. The results are as Figure 6 shown. It can be seen from the figure that the material has a good crystal structure.

[0049] (5) Characterization of the therapeutic effect on Alzheimer's disease: Behavioral characterization was carried out through the water maze test. After three months of treatment of the mice in the Se / Fe2O3 treatment group, the water maze test was carried out on the mice in different groups. The specific test steps of the water maze are as follows:

[0050] ① For the first three days, it was water maze adaptation training. The escape platform was 2 cm above the water surface, and the mice were allowed to swim freely to find the platform.

[0051] ② For days 4 - 8, it was the positioning cruise experiment, 4 times a day. During this period, the escape platform was 1 cm below the water surface, and the time to find the platform and the swimming trajectory were recorded.

[0052] ③ When the behavior of the mice in the Se / Fe2O3 treatment group improved, it was mainly manifested as significant differences in behavior compared with the AD mouse control group, and no significant differences compared with the wild mouse control group. Specifically, it was manifested as the change in the time to find the platform in the water maze test.

[0053] The statistical chart of the behavior of AD mice in different groups is as Figure 7 shown, and the statistical data chart is as Figure 8 shown. It can be seen from Figure 7 that the mice in the AD group still did not find the escape platform at 2 minutes, and the timing was manually stopped. After preliminary training, the wild group mice could quickly find the platform. After the AD mice were treated with Se / Fe2O3 nanoparticles, they could quickly find the escape platform in the water maze test, and their memory ability improved.

[0054] The chiral Se / Fe2O3 nanomaterial described in the present invention has a strong CD signal in the near-infrared region, and has good stability and biocompatibility, and can be used for the recognition and detection of polarized light. At the same time, this chiral nanomaterial has a differential affinity effect, which is of great significance for the treatment of Alzheimer's disease.

[0055] Obviously, the above embodiments are only examples for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A preparation method of chiral Se / Fe2O3 nanomaterials, characterized in that, The chiral Se / Fe2O3 nanomaterial is a nanoscale sea cucumber-like structure, and the preparation method comprises the following steps: Adding an iron source, a selenium source and a chiral ligand into a solvent, mixing evenly, adding a reducing agent and mixing to obtain a mixture, and subjecting the obtained mixture to a hydrothermal reaction to obtain a reaction solution of the chiral Se / Fe2O3 nanomaterial; the characteristic peak of the circular dichroism spectrum signal of the chiral Se / Fe2O3 nanomaterial is 300-400 nm and 500-700 nm; The chiral ligand is one or more of cysteine, penicillamine, glutathione, tartaric acid and proline; The reducing agent is one or more of sodium borohydride, hydrazine hydrate, ethylenediamine, ascorbic acid and ammonia water; the molar ratio of the reducing agent to the selenium source is 1:0.5-4; The molar ratio of the iron source to the selenium source is 1:0.5-3; the molar ratio of the chiral ligand to iron in the iron source is 1:0.5-2.

2. The preparation method according to claim 1, wherein The cysteine, penicillamine, glutathione, tartaric acid and proline all include L-type and / or D-type.

3. The preparation method according to claim 1, characterized in that, The solvent is one or more of water, methanol, ethanol, ethylene glycol and isopropanol.

4. A chiral Se / Fe2O3 nanomaterial, characterized in that, Obtained by the preparation method according to any one of claims 1-3; the chiral Se / Fe2O3 nanomaterial is a nanoscale sea cucumber-like structure.

5. Use of the chiral Se / Fe2O3 nanomaterial according to claim 4 in the preparation of drugs for neurodegenerative diseases.

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