Radiation-resistant selenium-containing melanin polymer material as well as preparation method and application thereof

Abstract

The invention relates to a selenium-containing melanin polymer as well as a preparation method and application thereof. The compound represented by the formula (I) is a selenium-containing melanin polymer PDOPSe, and has excellent anti-oxidation, anti-inflammatory and anti-radiation capabilities. The method can be used for preparing products with prevention or treatment anti-oxidation performance and radiation protection performance, including medicines, cosmetics, medical protection appliances, wearable devices and the like, and can also be used for preparing functional interfaces, biocompatible films, coatings and the like. # imgabs0 # R1 is selected from the group consisting of-COOH,-H,-OH,-CH3,-CH (CH3) 2,-C (CH3) 3,-OCH3,-NH2,-CONH2,-CN,-NO2,-CHO,-SO3H,-F,-Cl,-Br,-I,-CF3,-CCl3,-N (CH3) 2,-NHCOCH3,-OCOCH3,-C6H5,-COCH3,-COOCH3,-CH = CH2,-CH2NO, and the like.

Description

Technical Field

[0001] The present invention relates to a selenium-containing melanin polymer, a preparation method thereof, and an application thereof. Background Art

[0002] Polydopamine (PDA), as the most typical artificially synthesized melanin polymer, has functions such as biocompatibility, free radical scavenging, and antioxidant properties, and has attracted attention in the fields of hair dyeing, inflammation treatment, wound repair, and biomimetic materials. As a natural adhesive, PDA also has many important applications in the fields of coatings, interface repair, adhesives, etc. By forming stable interfaces through multiple interactions such as hydrogen bonding, Π-Π stacking, and metal coordination, universal adhesion can be achieved on the surfaces of various substrates such as metals, ceramics, polymers, and biological tissues. This includes antibacterial coatings, modification of the antioxidant interface layer of lithium battery electrodes, self-repair of microcracks in flexible electronic devices using the dynamic bonding ability of PDA, biomedical and extreme environment adhesion, etc. However, with the improvement of application requirements, melanin can no longer meet the increasing number of application scenarios. Therefore, the improvement of the key properties of melanin has attracted the attention of many people. Patent CN114028251A invented an artificial melanin shampoo, wash, and dye three-in-one lotion. By introducing 5,6-dihydroxyindole melanin, it not only has the functions of shampooing, washing, and dyeing, but also has excellent antistatic and sunscreen effects. Patent CN110279613A invented a light-colored melanin sunscreen. The sunscreen is a crosslinking product of polydopamine oligomer and a hydrophilic polymer with mercapto, amino, and boric acid groups, and has low visible light absorption, good biological stability, and free radical scavenging ability.

[0003] The structure of the artificial melanin polydopamine is also very complex, including a variety of covalent and non-covalent chemical reaction processes, and there is still no particularly clear research conclusion at present. Therefore, it is very necessary to explore the structure of melanin starting from the synthesis process. In addition, polydopamine also has the problem of single element.

[0004] Selenium is an important trace element and has various effects on human health. Although the reported selenium-containing melanin has been improved in terms of free radical scavenging, antioxidant, and radiation protection, etc., Patent CN118496222A invented a selenium-containing melanin, which has excellent antioxidant ability and radiation protection ability. Especially, the antioxidant ability and radiation protection ability of the compound SeMNPs-4 (a copolymerized selenium-containing melanin obtained by oxidative copolymerization of dopamine and selenocysteamine) are the best, but there are still disadvantages such as poor material homogeneity and low conjugation degree. Introducing selenium into polydopamine not only enriches the element composition but also has new discoveries in the polymer structure and preparation method.

[0005] Therefore, uniformly introducing the heteroatom selenium into the macromolecular structure of melanin is expected to make breakthroughs in both chemical structure and function. Summary of the Invention

[0006] In a first aspect, the present invention provides a compound of formula (I):

[0007]

[0008] wherein, R1 is selected from -COOH, -H, -OH, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -NH2, -CONH2, -CN, -NO2, -CHO, -SO3H, -F, -Cl, -Br, -I, -CF3, -CCl3, -N(CH3)2, -NHCOCH3, -OCOCH3, -C6H5, -COCH3, -COOCH3, -CH=CH2, -CH2NO, etc.

[0009] The compound of formula (I) is a polyheterocyclic compound capable of forming selenium-containing melanin-like substances.

[0010] Optionally, the heterocycle can be a four-membered, five-membered, six-membered, seven-membered ring, etc. containing a carbon-carbon double bond, or a four-membered, five-membered, six-membered, seven-membered ring, etc. without a carbon-carbon double bond.

[0011] Optionally, the number of phenolic hydroxyl groups on the benzene ring is 0, 1, or 2.

[0012] Optionally, the two phenolic hydroxyl groups on the benzene ring of the compound of formula (I) can be replaced by 0, 1, or 2 carbon-oxygen double bonds.

[0013] Optionally, R1 is H.

[0014] In a second aspect, the present invention provides a method for preparing the above-mentioned compound of formula (I), and the reaction route is as follows:

[0015] Route 1:

[0016]

[0017] Route 2:

[0018]

[0019] The compound of formula (I) is a polyheterocyclic compound capable of forming selenium-containing melanin-like substances.

[0020] Optionally, the heterocycle can be a four-membered, five-membered, six-membered, seven-membered ring, etc. containing a carbon-carbon double bond, or a four-membered, five-membered, six-membered, seven-membered ring, etc. without a carbon-carbon double bond.

[0021] Optionally, the number of phenolic hydroxyl groups on the benzene ring is 0, 1, or 2.

[0022] Optionally, the two phenolic hydroxyl groups on the benzene ring of the compound of formula (I) can be replaced by 0, 1, or 2 carbon-oxygen double bonds.

[0023] Among them, the definition of R1 is the same as above. Optionally, R1 is H.

[0024] R2 is selected from -OTs, -OMs, -OTf, -ONO2, -OAc, -N2 + , -SR2 + , -I, -Br, -Cl. Optionally, R2 is Br.

[0025] Specifically, the compound of formula (Ⅱ) generates the compound of formula (Ⅲ) in the presence of disodium diselenide.

[0026] Specifically, the compound of formula (Ⅲ) reacts with a reducing agent to generate the compound of formula (Ⅳ); optionally, the reducing agent is selected from sodium sulfite, ferrous sulfate, stannous chloride, oxalic acid, potassium borohydride, sodium borohydride, lithium aluminum hydride, TCEP·HCl, etc., and preferably TCEP·HCl.

[0027] Specifically, the compound of formula (Ⅳ) or the compound of formula (Ⅴ) polymerizes in the presence of an oxidizing agent to generate the compound of formula (Ⅰ); optionally, the oxidizing agent is selected from at least one of potassium permanganate, oxygen, sodium periodate, ammonium persulfate, sodium periodate, hydrogen peroxide, sodium hypochlorite, potassium peroxymonosulfate compound salt, ruthenium tetroxide, ammonium cerium nitrate, manganese dioxide, selenium dioxide, peroxybenzoic acid, m-chloroperoxybenzoic acid, peracetic acid, potassium dichromate, pyridinium dichromate, ruthenium tetroxide, cobalt tetrapyridine dichromate, dimethyl sulfoxide, dibenzoyl peroxide, Dess-Martin periodinane, 2,3-dichloro-5,6-dicyano-p-benzoquinone, methyl(trifluoromethyl)dioxirane, dimethyl dioxirane, and preferably ammonium persulfate.

[0028] Specifically, the compound of formula (Ⅳ) can polymerize to generate the compound of formula (Ⅰ) under both acidic and basic conditions (pH = 3 - 10). The polymer synthesized under the condition of pH = 3 - 7 is named PDOPSe-A, and the polymer synthesized under the condition of pH = 7 - 10 is named PDOPSe-B.

[0029] In some embodiments, in a mixed solvent system of absolute ethanol and water (such as ultrapure water), TCEP·HCl is used to reduce the compound of formula (Ⅲ) to generate the compound of formula (Ⅳ), and then the compound of formula (Ⅳ) reacts with the oxidizing agent ammonium persulfate to generate the compound of formula (Ⅰ), which is the compound PDOPSe-A.

[0030] In some embodiments, in a mixed solvent system of absolute ethanol and a basic buffer solution, TCEP·HCl is used to reduce the compound of formula (Ⅲ) to generate the compound of formula (Ⅳ), and then the compound of formula (Ⅳ) reacts with the oxidizing agent ammonium persulfate to generate the compound of formula (Ⅰ), which is the compound PDOPSe-B.

[0031] Specifically, the reaction time of the above-mentioned generative formula (IV) compound can be 5 - 30 minutes. After the reaction of the generative formula (IV) compound proceeds for 5 - 30 minutes, the reaction of the generative formula (I) compound is started, and the reaction is stirred for 6 - 48 hours. Finally, the product obtained after washing is collected by centrifugation.

[0032] In a third aspect, the compound of formula (IV) or the compound of formula (V) can be oxidatively copolymerized with other melanin precursors to prepare a copolymer;

[0033] Optionally, the melanin precursor is selected from dopamine, L - levodopa, catechol, 1,8 - dihydroxynaphthalene, tyrosine, homovanillic acid, phenylalanine, 5,6 - dihydroxyindole, 5,6 - dihydroxyindole - 2 - carboxylic acid, 5 - S - cysteinyldopa, 1,4,6,7,9,12 - hexahydroxyperylenequinone, tyramine, epinephrine, norepinephrine, etc.

[0034] The present invention provides a preparation method of the compound of formula (VI), and its reaction route is as follows:

[0035]

[0036] Specifically, the compound of formula (IV) and the compound of formula (VI) are polymerized in the presence of an oxidant to form the compound of formula (VII); optionally, the oxidant is selected from at least one of potassium permanganate, oxygen, sodium periodate, ammonium persulfate, sodium periodate, hydrogen peroxide, sodium hypochlorite, potassium peroxymonosulfate compound salt, ruthenium tetroxide, ammonium cerium nitrate, manganese dioxide, selenium dioxide, peroxybenzoic acid, m - chloroperoxybenzoic acid, peracetic acid, potassium dichromate, pyridinium dichromate, ruthenium tetroxide, cobalt tetrapyridine dichromate, dimethyl sulfoxide, dibenzoyl peroxide, Dess - Martin periodinane, 2,3 - dichloro - 5,6 - dicyano - p - benzoquinone, methyl(trifluoromethyl)dioxirane, dimethyl dioxirane, and is preferably ammonium persulfate.

[0037] Specifically, the compound of formula (IV) and the compound of formula (VI) can be oxidatively copolymerized to form the compound of formula (VII) under both acidic and alkaline conditions (pH = 3 - 10). The copolymer synthesized under the condition of pH = 3 - 7 is named P(DOPSe - DA) - A, and the copolymer synthesized under the condition of pH = 7 - 10 is named P(DOPSe - DA) - B.

[0038] In some embodiments, in a mixed solvent system of absolute ethanol and water (such as ultrapure water), the compound of formula (III) is reduced with a reducing agent to form the compound of formula (IV), where the reducing agent is selected from sodium sulfite, ferrous sulfate, stannous chloride, oxalic acid, potassium borohydride, sodium borohydride, lithium aluminum hydride, TCEP·HCl, etc., and is preferably TCEP·HCl. Then the compound of formula (IV) and the compound of formula (VI) react in the presence of the oxidant ammonium persulfate to form the compound of formula (VII), which is the compound P(DOPSe - DA) - A.

[0039] In some embodiments, in a mixed solvent system of absolute ethanol and an alkaline buffer solution, a reducing agent is used to reduce the compound of formula (III) to generate the compound of formula (IV), wherein the reducing agent is selected from sodium sulfite, ferrous sulfate, stannous chloride, oxalic acid, potassium borohydride, sodium borohydride, lithium aluminum hydride, TCEP·HCl, etc., and preferably TCEP·HCl. Then the compound of formula (IV) and the compound of formula (VI) react in the presence of an oxidizing agent ammonium persulfate to generate the compound of formula (VII), which is the compound P(DOPSe-DA)-B.

[0040] Specifically, the reaction time for generating the compound of formula (IV) can be 5 - 30 minutes. After the reaction for generating the compound of formula (IV) proceeds for 5 - 30 minutes, the reaction for generating the compound of formula (VII) starts, and the reaction is stirred for 6 - 48 h, and finally the product obtained by washing is collected by centrifugation.

[0041] Fourthly, the present invention also monitors the reaction process of PDOPSe-A to better understand the polymerization mechanism.

[0042] Fifthly, the present invention also provides the selenium-containing melanin prepared by the above method, that is, the compound of formula (I).

[0043] Specifically, the selenium-containing melanin is nanoparticles and thin films. The particle size of the nanoparticles is usually about 200 - 900 nm, such as 200 - 300 nm. The nanoparticles are usually uniformly spherical, which is more conducive to entering the interior of cells, so as to better exert the antioxidant performance.

[0044] Sixthly, the present invention also provides the application of the compound of formula (I) in the preparation of products with antioxidant properties for prevention or treatment. The products include drugs, cosmetics, medical protective appliances, wearable devices, etc., and can also be used for the preparation of functional interfaces, biocompatible thin films and coatings, etc.

[0045] Through the regulation of molecular design and synthesis methods, the present invention obtains a selenium-containing melanin polymer, introducing a heteroatom selenium, which exists in each heterocycle and has a clearer structure. As a radiation protection material with simple preparation, good safety, good biocompatibility and good antioxidant performance, the selenium-containing melanin polymer is expected to be widely used in fields such as oral drugs, external application materials, medical protective articles, nuclear power plant shielding, nuclear wastewater treatment, etc., showing great application prospects. Description of the Drawings

[0046] To more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0047] Figure 1 It is the preparation flow chart of the selenium-containing melanin polymer of the present invention.

[0048] Figure 2 It is the preparation flow chart of the DOPSe and DA copolymer of the present invention.

[0049] Figure 3 It is the characterization results of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Among them, A is the UV-Vis diagram, B is the DLS measurement of the hydrated particle size diagram, C is the zeta potential test result, D is the XPS test result, E is the ICP test result of the selenium content and the X-ray energy dispersive spectrometer distribution image, and F is the SEM test result.

[0050] Figure 4 It is the intermediate process monitoring data of PDOPSe-A prepared in Example 1 of the present invention. Among them, A is the monitoring process picture and the chemical process schematic diagram, B is the UV-Vis diagram, C is the signal change diagram at 244 nm, 269 nm, 282 nm, and 314 nm in the UV-Vis diagram over time, D is the signal change diagram at 365 nm and 498 nm in the UV-Vis diagram over time, and E is the signal change diagram at 700 nm in the UV-Vis diagram over time.

[0051] Figure 5 It is the intermediate process monitoring HPLC-MS data of PDOPSe-A prepared in Example 1 of the present invention. Among them, A is the HPLC diagram at 2 h of the reaction, B is the mass spectrometry diagram at 7.8 min of HPLC, C is the mass spectrometry diagram at 9.8 min of HPLC, D is the monomer mass spectrometry simulation diagram, E is the dimer mass spectrometry simulation diagram, and F is the mass spectrometry diagram of the intermediate captured by TEMPO.

[0052] Figure 6 It is the structural characterization data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Among them, A is the EPR result diagram with water as the solvent, B is the solid EPR diagram, C is the EPR test result diagram of DMPO capturing oxygen-centered free radicals (DMSO as the solvent), D is the EPR test result diagram of DMPO capturing carbon-centered free radicals (water as the solvent), E is the FTIR test result, and F is the Raman spectroscopy test result.

[0053] Figure 7They are the MALDI-TOF test data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention.

[0054] Figure 8 They are the MALDI-TOF test data of P(DOPSe-DA)-A prepared in Example 3 of the present invention. Wherein B is an enlarged view.

[0055] Figure 9 They are the X-ray attenuation ability data and antioxidant ability data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Wherein A is the X-ray attenuation ability data, and B-E are the antioxidant ability test data.

[0056] Figure 10 They are the test data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention respectively for scavenging excessive reactive oxygen species caused by radiation in cells. Among them, A is the intracellular toxicity data, B is the cell uptake data tested by ICP, C is the test result of flow cytometry, D is the statistical result of flow cytometry test, and E is the laser confocal image.

[0057] Figure 11 They are the clone experiment data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention respectively for cell radiation protection test. A is the picture of the clone experiment result, and B is the quantitative statistics of A using ImageJ software.

[0058] Figure 12 They are the body weight monitoring data and survival rate data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention respectively for mouse radiation protection test.

[0059] Chinese-English comparison table

[0060]

[0061] Detailed implementation manners

[0062] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below with reference to the accompanying drawings in the present invention. Obviously, the described embodiments are some but not all of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without making creative efforts shall fall within the protection scope of the present invention.

[0063] Unless otherwise specified, all kinds of raw materials used in the embodiments are commercially available conventional raw materials, and the technical means used are conventional means well known to those skilled in the art.

[0064] Among them, the specific preparation flowchart of selenium-containing melanin can be seen in Figure 1 .

[0065] Example 1

[0066] This example provides a selenium-containing melanin polymer - PDOPSe-A, and its preparation method includes the following steps:

[0067] Weigh 102.74 mg of NaBH4 and 214.43 mg of Se powder into a round-bottom flask, add 1.4 mL of deionized water to react in a nitrogen environment, then dissolve 560 mg of 4-bromoethylcatechol in tetrahydrofuran and add it to the flask, and heat and stir overnight in an oil bath at 40 - 70 °C. Extract with dichloromethane, dry, and separate and concentrate by column chromatography to obtain a yellow solid, which is DDOPSe.

[0068] Weigh 6.5 mg of DDOPSe and 4.3 mg of TCEP·HCl and mix them in an ethanol aqueous solution to react for 10 min, then add APS and react overnight. After completion, centrifuge to discard the supernatant, add ultrapure water and wash and purify ultrasonically three times, and freeze-dry and weigh.

[0069] Example 2

[0070] This example provides a selenium-containing melanin polymer - PDOPSe-B, and its preparation method includes the following steps:

[0071] Weigh 6.5 mg of DDOPSe and 4.3 mg of TCEP·HCl and mix them in an ethanol aqueous solution to react for 10 min, add APS dissolved in a sodium carbonate / sodium bicarbonate buffer solution, and react overnight. After completion, centrifuge to discard the supernatant, add ultrapure water and wash and purify ultrasonically three times, and freeze-dry and weigh.

[0072] The specific preparation flowchart of the copolymer of DDOPSe and DA can be seen in Figure 2 .

[0073] Example 3

[0074] This example provides a selenium-containing copolymer - P(DOPSe-DA)-A, and its preparation method includes the following steps:

[0075] Weigh 6.5 mg of DDOPSe and 4.3 mg of TCEP·HCl and mix them in an ethanol aqueous solution to react for 10 min, then add 4.6 mg of DA, oxidize with APS, and react overnight. After completion, centrifuge to discard the supernatant, add ultrapure water and wash and purify ultrasonically three times, and freeze-dry and weigh.

[0076] Example 4

[0077] This embodiment provides a selenium-containing copolymer, P(DOPSe-DA)-B, the preparation method of which comprises the following steps:

[0078] Weigh 6.5 mg of DDOPSe and 4.3 mg of TCEP·HCl in an ethanol-water solution and mix them for 10 min, add 4.6 mg of DA, and oxidize with APS dissolved in a sodium carbonate / sodium bicarbonate buffer solution, and react overnight. After the reaction, centrifuge and discard the supernatant, add ultrapure water and ultrasonically wash and purify three times, and freeze-dry and weigh.

[0079] Comparative Example 1

[0080] This comparative example provides a polydopamine nanoparticle (PDA) solution, and its preparation method comprises the following steps:

[0081] Mix 1 mL of anhydrous ethanol (99.5%) and 6 mL of ultrapure water in a round-bottom flask. Add 32 μL of 28-30% monohydrate ammonia (NH3·H2O) solution to the flask and stir vigorously for 10 min to mix thoroughly. Take 20 mg of dopamine hydrochloride (DA·HCl) (0.105 mmol) and slowly add it to 500 μL of ultrapure water, and stir vigorously overnight at room temperature. Collect the product, wash it three times with ultrapure water, and freeze-dry it and weigh it.

[0082] Figure 3 These are the characterization results of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Wherein A is the UV-Vis graph, it can be seen that PDOPSe-A and PDOPSe-B have absorption in the range of 200nm to 1000nm, which is similar to the wide wavelength range absorption of PDA. B is the DLS measurement of hydrated particle size, the hydrated particle size of PDOPSe-A and PDOPSe-B is 300nm to 600nm. C is the zeta potential test result, the potential of PDOPSe-A and PDOPSe-B is between -20mV and -30mV, and has good dispersibility. D is the XPS test result, PDOPSe-A and PDOPSe-B both produce C-Se-C bonds. E is the ICP test result of selenium content and the energy dispersive X-ray spectrometer distribution image. The selenium content of PDOPSe-A and PDOPSe-B is about 30%, which is close to the calculated result. The energy dispersive X-ray spectrometer distribution image shows that there is Se element on the nanoparticles. F is the SEM test result of PDOPSe-B, and the particle size is 200-300nm.

[0083] Figure 4These are the intermediate process monitoring data of PDOPSe-A prepared in Example 1 of the present invention. Among them, A are the monitoring process pictures and chemical process schematic diagrams. During the experiment, it was found that a red intermediate was generated in PDOPSe-A. B is the UV-Vis diagram, which monitors the change of the UV-Vis signal with time within 0 - 200 min of the reaction of PDOPSe-A. C is the diagram of the signal change with time at 244 nm, 269 nm, 282 nm, and 314 nm in the UV-Vis diagram. Among them, the signal at 282 nm decreases with the increase of time, and it is speculated that it is the reactant DOPSe. D is the diagram of the signal change with time at 365 nm and 498 nm in the UV-Vis diagram, both showing a signal change trend of first increasing and then decreasing, and it is speculated to be a semiquinone radical intermediate. E is the diagram of the signal change with time at 700 nm in the UV-Vis diagram, and the signal increases with the increase of time, and it is speculated to be the PDOPSe-A polymer signal.

[0084] Figure 5 These are the intermediate process monitoring HPLC-MS data of PDOPSe-A prepared in Example 1 of the present invention. Among them, A is the HPLC diagram at 2 h of the reaction, and signal peaks can be seen at 7.8 min and 9.8 min. B is the mass spectrometry diagram at 7.8 min of HPLC, and it can be observed that the characteristic peak of the monomer coincides with the simulation result. C is the mass spectrometry diagram at 9.8 min of HPLC, and it can be observed that the characteristic peak of the dimer coincides with the simulation result. F is the mass spectrometry diagram of the intermediate captured by TEMPO, indicating that TEMPO successfully captured the monomer radical.

[0085] Figure 6 These are the structure characterization data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Among them, A is the EPR result diagram with water as the solvent, and B is the solid EPR diagram. Persistent radical signals can be seen in both PDOPSe-A and PDOPSe-B. C is the result diagram of the DMPO-captured oxygen-centered radical in the EPR test (with DMSO as the solvent), indicating the generation of ·OOH radical signals. D is the result diagram of the DMPO-captured carbon-centered radical in the EPR test (with water as the solvent), indicating the generation of carbon radicals. E is the FTIR test result, and F is the Raman spectroscopy test result, and stretching vibration signals of C=C and C=O are found.

[0086] Figure 7 These are the MALDI-TOF test data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. The degree of polymerization above 10 can be detected for both, and the molecular weight of the repeating unit is 210 - 214.

[0087] Figure 8It is the MALDI-TOF test data of P(DOPSe-DA)-A prepared in Example 3 of the present invention, where B is an enlarged view, indicating successful copolymerization.

[0088] Figure 9 They are the X-ray attenuation ability data and antioxidant ability data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention. Among them, A is the X-ray attenuation ability data. At the same mass concentration, compared with PDA prepared in Comparative Example 1, the CT signals of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention are significantly stronger, which is due to the presence of selenium element with a high atomic number. B-D are the antioxidant ability test data of PDOPSe and PDA synthesized under different pH (3, 5, 7, 9) conditions at the same molar concentration. B is the hydrogen peroxide (H2O2) scavenging data, C is the DPPH scavenging data, and D is the ABTS scavenging data. The results show that PDOPSe has a better reactive oxygen species scavenging effect than PDA. And it was found during the synthesis that under the same conditions, PDOPSe nanoparticles can be synthesized while PDA nanoparticles cannot be synthesized in an acidic buffer solution with pH = 3.

[0089] Figure 10 They are the test data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention respectively for scavenging excessive reactive oxygen species caused by radiation in HaCat cells. Among them, A is the cytotoxicity data in cells, indicating that PDOPSe-A and PDOPSe-B are non-toxic at concentrations less than 50 μg / mL. B is the cell uptake data tested by ICP, indicating that both PDOPSe-A and PDOPSe-B can enter cells. C is the test result of flow cytometry, D is the statistical result of flow cytometry test, and E is the laser confocal image, indicating that both PDOPSe-A and PDOPSe-B can scavenge excessive reactive oxygen species caused by 10 Gy gamma-ray radiation and return to the normal cell level.

[0090] Figure 11 They are the clonogenic assay data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention respectively for cell radiation protection test. A is the picture of the clonogenic assay result, and B is the quantitative statistics of A using ImageJ software. The results show the comparison of the radiation protection effects of PDOPSe synthesized under different pH (3, 5, 7, 9) conditions against 6 Gy gamma-ray radiation. Under the alkaline synthesis condition with pH = 9, the radiation protection effect of PDOPSe is the best, and there is no significant difference compared with non-irradiation.

[0091] Figure 12 Figure 11Weight monitoring data and survival rate data of PDOPSe-A and PDOPSe-B prepared in Examples 1 and 2 of the present invention for mouse radiation protection tests. A is the weight monitoring data, and B is the survival rate data. The results show that under 6 Gy gamma-ray whole-body irradiation, PDOPSe-B has a better radiation protection effect on mice.

[0092] Although the present invention has been described in detail with general descriptions and specific embodiments above, based on the present invention, some modifications or improvements can be made, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of the present invention claimed.

Claims

1. The compound of formula (Ⅰ), Among them, R1 is selected from -COOH, -H, -OH, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -NH2, -CONH2, -CN, -NO2, -CHO, -SO3H, -F, -Cl, -Br, -I, -CF3, -CCl3, -N(CH3)2, -NHCOCH3, -OCOCH3, -C6H5, -COCH3, -COOCH3, -CH=CH2, -CH2NO, etc.

2. The compound of formula (I) according to claim 1, characterized in that, is a polyheterocyclic compound capable of forming selenium-containing melanin-like substances, Optionally, the heterocycle can be a four-membered ring, five-membered ring, six-membered ring, seven-membered ring, etc. containing a carbon-carbon double bond, or a four-membered ring, five-membered ring, six-membered ring, seven-membered ring, etc. without a carbon-carbon double bond; Optionally, the number of phenolic hydroxyl groups on the benzene ring is 0, 1, or 2; Optionally, two phenolic hydroxyl groups on the benzene ring can be replaced by 0, 1, or 2 carbon-oxygen double bonds; Optionally, R1 is H.

3. A process for preparing the compound of formula (I), characterized in that, The reaction route is as follows: Route 1: Route 2: wherein, R1 is selected from -COOH, -H, -OH, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -NH2, -CONH2, -CN, -NO2, -CHO, -SO3H, -F, -Cl, -Br, -I, -CF3, -CCl3, -N(CH3)2, -NHCOCH3, -OCOCH3, -C6H5, -COCH3, -COOCH3, -CH=CH2, -CH2NO, etc.; Optionally, R1 is H; wherein R2 is selected from -OTs, -OMs, -OTf, -ONO2, -OAc, -N2 + , -SR2 + , -I, -Br, -Cl; Optionally, R2 is Br; Optionally, the heterocycle can be a four-membered ring, five-membered ring, six-membered ring, seven-membered ring, etc. containing a carbon-carbon double bond, or a four-membered ring, five-membered ring, six-membered ring, seven-membered ring, etc. without a carbon-carbon double bond; Optionally, the number of phenolic hydroxyl groups on the benzene ring is 0, 1, or 2; Optionally, two phenolic hydroxyl groups on the benzene ring in the compound of formula (Ⅰ) can be replaced by 0, 1, or 2 carbon-oxygen double bonds.

4. The preparation method according to claim 3, characterized in that, The compound of formula (Ⅱ) generates the compound of formula (Ⅲ) in the presence of disodium diselenide, and the compound of formula (Ⅲ) reacts with a reducing agent to generate the compound of formula (Ⅳ); Optionally, the reducing agent is sodium sulfite, ferrous sulfate, stannous chloride, oxalic acid, potassium borohydride, sodium borohydride, lithium aluminum hydride, TCEP·HCl, etc., preferably TCEP·HCl; wherein R2 is selected from -OTs, -OMs, -OTf, -ONO2, -OAc, -N2 + , -SR2 + , -I, -Br, -Cl, etc., preferably -Br.

5. The preparation method according to claim 3, characterized in that, The compound of formula (Ⅳ) or the compound of formula (Ⅴ) polymerizes in the presence of an oxidizing agent to generate the compound of formula (Ⅰ); Optionally, the oxidizing agent is selected from at least one of potassium permanganate, oxygen, sodium periodate, ammonium persulfate, sodium periodate, hydrogen peroxide (hydrogen peroxide), sodium hypochlorite, potassium peroxymonosulfate compound salt, ruthenium tetroxide, ammonium cerium nitrate, manganese dioxide, selenium dioxide, peroxybenzoic acid, m-chloroperoxybenzoic acid, peracetic acid, potassium dichromate, pyridinium dichromate, ruthenium tetroxide, cobalt tetrapyridine dichromate, dimethyl sulfoxide, dibenzoyl peroxide, Dess-Martin periodinane, 2,3-dichloro-5,6-dicyano-p-benzoquinone, methyl(trifluoromethyl)dioxirane, dimethyl dioxirane, preferably ammonium persulfate.

6. The preparation method according to claim 3 or 5, characterized in that The compound of formula (IV) can polymerize to form the compound of formula (I) under both acidic and alkaline conditions (pH = 3 - 10).

7. Selenium-containing eumelanin, characterized in that, Prepared by the method described in claims 3 - 8, with the repeating unit molecular weight of 210 - 214; the selenium-containing melanin is nanoparticles and thin films; optionally, the particle size of the nanoparticles is 200 - 900 nm.

8. According to claims 3-4, characterized in that, The compound of formula (IV) or the compound of formula (V) can undergo oxidative copolymerization with other melanin precursors to prepare copolymers; Optionally, the melanin precursors are selected from dopamine, L-levodopa, catechol, 1,8-dihydroxynaphthalene, tyrosine, homovanillic acid, phenylalanine, 5,6-dihydroxyindole, 5,6-dihydroxyindole-2-carboxylic acid, 5-S-cysteinyl dopa, 1,4,6,7,9,12-hexahydroxyperylenequinone, tyramine, epinephrine, norepinephrine, etc.; When the melanin precursor is dopamine, the preparation method can prepare the copolymer (VII).

9. The preparation method according to claim 8, characterized in that, The compound of formula (IV) and the compound of formula (VI) can copolymerize to form the compound of formula (VII) under both acidic and alkaline conditions (pH = 3 - 10) in the presence of an oxidant; Optionally, the oxidant is selected from at least one of potassium permanganate, oxygen, sodium periodate, ammonium persulfate, sodium periodate, hydrogen peroxide (hydrogen peroxide), sodium hypochlorite, potassium peroxymonosulfate compound salt, ruthenium tetroxide, ammonium cerium nitrate, manganese dioxide, selenium dioxide, peroxybenzoic acid, m-chloroperoxybenzoic acid, peracetic acid, potassium dichromate, pyridinium dichromate, ruthenium tetroxide, cobalt tetrapyridine dichromate, dimethyl sulfoxide, dibenzoyl peroxide, Dess-Martin periodinane, 2,3-dichloro-5,6-dicyano-p-benzoquinone, methyl(trifluoromethyl)dioxirane, dimethyl ketone peroxide, and is preferably ammonium persulfate.

10. Use of the compound of formula (I) as claimed in claim 1 or 2 or the selenium-containing melanin as claimed in claim 7 in the preparation of a product having antioxidant and radiation protection properties for prevention or treatment; Optionally, the product includes drugs, cosmetics, medical protective equipment, wearable devices, etc., and can also be used in the preparation of functional interfaces, biocompatible thin films and coatings, etc.

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