A small molecule monomer containing an azobenzene group and a ferrocene group, and a synthesis method and use thereof

Abstract

The application discloses a small-molecule monomer containing an azobenzene group and a ferrocene group and a synthesis method and application thereof, and comprises the following steps: step one, obtaining an alkyne functionalized azobenzene from 4,4'-dihydroxyazobenzene; step two, obtaining a ferrocene functionalized azobenzene by a CuAAC click reaction of ferrocene formate-3-azidopropyl ester and the alkyne functionalized azobenzene; and step three, obtaining the small-molecule monomer containing the azobenzene group and the ferrocene group by a substitution reaction of methacryloyl chloride and the ferrocene functionalized azobenzene. The monomer synthesized by the application can be conveniently copolymerized with other functional monomers, and then a water-soluble polymer with a clear structure and uniformity is obtained. The polymer can be used as a Fenton reagent, efficiently kills tumor cells through an oxidative stress mechanism, and is applied to the chemical kinetics treatment of tumors.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and in particular relates to a small molecule monomer containing an azophenyl group and a ferrocenyl group, and a synthesis method and application thereof. Background Art

[0002] Chemodynamic therapy is a highly specific and selective anti-tumor strategy. It mainly utilizes the high concentration of hydrogen peroxide in the tumor microenvironment, and under the action of iron-based nanomaterials, generates highly cytotoxic hydroxyl radicals through the Fenton reaction, thereby achieving the effect of tumor clearance. Compared with other reactive oxygen species-mediated cancer treatments, chemodynamic therapy does not rely on oxygen and laser equipment. These advantages enable it to avoid the problem of limited light tissue penetration and show a general therapeutic effect on hypoxic tumors. More importantly, chemodynamic therapy mainly utilizes the high level of hydrogen peroxide in the tumor microenvironment to trigger the Fenton reaction, which rarely occurs in normal tissues. Therefore, it is tumor-specific and selective, and thus exhibits the advantage of low systemic toxicity and side effects.

[0003] Most of the currently used Fenton reagents are iron-based materials. However, they require strictly acidic conditions (pH 2-4) to release free iron ions and thus undergo an effective Fenton reaction. Ferrocene, on the other hand, is a unique Fenton reagent. It is a structurally stable organometallic compound that is not restricted by the pH conditions of the tumor microenvironment in the Fenton reaction. Moreover, its lipophilicity makes its derivatives more easily penetrate cell membranes.

[0004] Although chemodynamic therapy can utilize Fenton reagents to generate hydroxyl radicals in tumor cells, the powerful redox balance regulation ability of tumor cells will neutralize the reactive oxygen species produced by chemodynamic therapy by increasing the concentration of glutathione, thus limiting the therapeutic effect of chemodynamic therapy. Therefore, while Fenton reagents increase intracellular reactive oxygen species, reducing or even depleting the concentration of intracellular glutathione is an effective strategy to improve the efficacy of chemodynamic therapy. In recent years, azobenzene, as a classic light-responsive molecular switch, has also been reported to be able to break down under the action of intracellular azoreductase and consume glutathione at the same time. Therefore, constructing a Fenton reagent containing both azobenzene and ferrocene is expected to effectively increase the level of intracellular reactive oxygen species and improve the efficacy of chemodynamic therapy.

[0005] Glossary:

[0006] CuAAC: copper(I)-catalyzed azide-alkynyl cycloaddition.

[0007] DCC: dicyclohexylcarbodiimide.

[0008] DMAP: 4-dimethylaminopyridine.

[0009] DMF: N,N-dimethylacetamide.

[0010] K2CO3: potassium carbonate.

[0011] CuBr: cuprous bromide.

[0012] PMDETA: pentamethyldiethylenetriamine.

[0013] OEGMA: oligoethylene glycol monomethyl ether methacrylate.

[0014] DMAEMA: N,N-dimethylaminoethyl methacrylate.

[0015] DMF: N,N'-dimethylformamide.

[0016] ATRP: atom transfer radical polymerization. Summary of the Invention

[0017] In order to solve the above problems, the present invention discloses a small molecule monomer containing an azophenyl group and a ferrocenyl group, a synthesis method and application thereof.

[0018] The present invention is achieved through the following technical solutions:

[0019] A small molecule monomer M-Azo-Fc containing an azophenyl group and a ferrocenyl group, wherein the chemical formula of the small molecule monomer is as follows:

[0020]

[0021] A method for synthesizing a small molecule monomer M-Azo-Fc comprises the following steps:

[0022] Step 1: 4,4'-dihydroxyazobenzene Azo is subjected to a substitution reaction to obtain alkynyl-functionalized azobenzene Alkynyl-Azo;

[0023] Step 2: A ferrocene azidate Fc-N3 reacts with Alkynyl-Azo via CuAAC click reaction to obtain ferrocene-functionalized azobenzene Azo-Fc;

[0024] Step 3: Azo-Fc reacts with methacryloyl chloride through substitution reaction to obtain a small molecule monomer M-Azo-Fc;

[0025] For further improvement, the specific steps of step 1 are as follows:

[0026] Dissolve Azo-benzene in anhydrous acetone, stir well, then add 3-bromopropynyl, stir at room temperature for 30 min under nitrogen protection, then add K2CO3, and reflux for 10 h. After purification, Alkynyl-Azo is obtained, wherein the molar ratio of Azo, 3-bromopropynyl and K2CO3 is 2:2.2:1.

[0027] Further improvement, the specific steps of step two are as follows:

[0028] Dissolve Alkynyl-Azo, Fc-N3 and bipyridine in DMF, then add CuBr under nitrogen protection, and react at 35°C in an oil bath for 12 h. After purification, Azo-Fc is obtained; wherein the molar ratio of Alkynyl-Azo, Fc-N3, bipyridine and CuBr is 1:1.1:2:4.

[0029] Further improvement, the specific steps of step three are as follows:

[0030] Dissolve Azo-Fc in dry tetrahydrofuran, then add triethylamine, and drop methyl acryloyl chloride solution into the reaction under nitrogen protection in an ice bath. After drop completion, continue to react at room temperature for 4 h, and then purify to obtain M-Azo-Fc; wherein the molar ratio of Azo-Fc, triethylamine and methyl acryloyl chloride is 1:2:1.6; the methyl acryloyl chloride solution is obtained by dissolving methyl acryloyl chloride in dry tetrahydrofuran, and the volume ratio of methyl acryloyl chloride to tetrahydrofuran in the methyl acryloyl chloride solution is 1:10.

[0031] An application of M-Azo-Fc in the synthesis of Fenton reagent, wherein the M-Azo-Fc is as described above, and is used as a raw material for the synthesis of Fenton reagent (P(OEGMA x -st-DMAEMA y -st-(M-Azo-Fc)) z ) has the following chemical formula:

[0032]

[0033] wherein x=7-30, y=17-22, and z=3-13.

[0034] Further improvement, the synthesis method of Fenton reagent comprises the following steps:

[0035] Step one, through substitution reaction, Alkynyl-Azo and 2-bromoisobutyryl bromide are reacted to obtain bromo-functionalized azobenzene Alkynyl-Azo-Br; the synthesis method of Alkynyl-Azo is as described above.

[0036] Step two, after mixing M-Azo-Fc, Alkynyl-Azo-Br, PMDETA, OEGMA and DMAEMA, Fenton reagent is obtained by ATRP technology under the action of catalyst CuBr, and the chemical formula of M-Azo-Fc is as shown in claim 1.

[0037] Further improvement, the specific steps of step one are as follows:

[0038] Alkynyl-Azo is added to tetrahydrofuran, triethylamine is added after sufficient dissolution, and then 2-bromoisobutyryl bromide is added in an ice bath, and 2-bromoisobutyryl bromide is slowly dropped into the reaction liquid under nitrogen protection, and after the dropping is completed, the reaction is continued at room temperature for 4h, and purification is obtained Alkynyl-Azo-Br; wherein the molar ratio of Alkynyl-Azo, triethylamine and 2-bromoisobutyryl bromide is 1:2:1.6.

[0039] Further improvement, the specific steps of step two are as follows:

[0040] Alkynyl-Azo-Br, PMDETA, OEGMA, DMAEMA and M-Azo-Fc are dissolved in DMF, then after 3 times of freeze-pumping-thaw cycle, CuBr is added under nitrogen protection, and after 3 times of freeze-pumping-thaw cycle operation, the reaction is carried out at 60°C oil bath for 5-10h, and after the polymerization reaction is stopped, the polymer is obtained by dialysis purification; wherein the molar feeding ratio of Alkynyl-Azo-Br, PMDETA, CuBr, OEGMA, DMAEMA and M-Azo-Fc is 1:1:1:15-60:30:5-20; with reference to the molar feeding ratio, OEGMA, DMAEMA and M-Azo-Fc are added in excess based on Alkynyl-Azo-Br, and PMDETA and CuBr are added in equimolar amount; PMDETA and CuBr are catalysts.

[0041] Use of a Fenton reagent, the Fenton reagent is as described above, and the Fenton reagent is used as a drug for killing tumor cells.

[0042] The present application has the following beneficial effects:

[0043] The monomer containing azobenzene and ferrocenyl synthesized by the present application can be conveniently copolymerized with other functional monomers to obtain a polymer. The polymer can be used as a Fenton reagent, and can efficiently kill tumor cells through oxidative stress mechanism in chemical dynamic therapy. The monomer, its synthesis method and use reported in the present application provide a reliable way to obtain a Fenton reagent. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 Alkynyl-Azo in DMSO-d6 1 H NMR spectrum;

[0045] Figure 2 Azo-Fc in DMSO-d6 1 H NMR spectrum;

[0046] Figure 3 M-Azo-Fc in DMSO-d6 1 HNMR spectrum;

[0047] Figure 4 Alkynyl-Azo-Br in DMSO-d6 1 H NMR spectrum;

[0048] Figure 5 The elution curves of size exclusion chromatography (SEC) of four Fenton reagents P1, P2, P3 and P4 are shown;

[0049] Figure 6 Representative Fenton reagent P3 in CDCl3 1 HNMR spectrum;

[0050] Figure 7 This is a fluorescent image of P3 generating ROS in 4T1 cells;

[0051] Figure 8 This is a diagram showing the killing effect of different concentrations of P3 on 4T1 cells. DETAILED DESCRIPTION

[0052] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0053] The reaction process of the present invention is shown in the following reaction formula:

[0054] (a)

[0055]

[0056] (b)

[0057]

[0058] (d)

[0059]

[0060] (e)

[0061]

[0062] (f)

[0063]

[0064] 1. Synthesis of Alkynyl-Azo from 4,4'-dihydroxyazobenzene (Azo):

[0065] Under nitrogen protection, 4,4'-dihydroxyazobenzene and 3-bromopropyne react with the catalysis of potassium carbonate to obtain alkynyl-functionalized azobenzene.

[0066] The procedure is as follows: 4,4'-dihydroxyazobenzene (1.0 g, 4.7 mmol) was dissolved in 15 mL of acetone and stirred thoroughly. 3-Bromopropyne (0.4 mL, 5.1 mmol) was added. Under nitrogen, the reaction was stirred at room temperature for 30 minutes. K2CO3 (0.3 g, 2.3 mmol) was then added, and the mixture was refluxed for 10 hours. The molar ratio of 4,4'-dihydroxyazobenzene, 3-Bromopropyne, and K2CO3 was 2:2.2:1.

[0067] Post-treatment: Use a rotary evaporator to remove the acetone from the reaction mixture, then add 50 mL of ethyl acetate and dissolve thoroughly. The solution is then transferred to a 250 mL separatory funnel, and the organic phase is washed three times with 50 mL of water. Anhydrous MgSO₄ is added to the organic phase and dried overnight. The MgSO₄ is then removed by suction filtration, and the resulting ethyl acetate solution is subjected to a rotary evaporation to remove most of the ethyl acetate, yielding the crude product. The crude product is purified by column chromatography, eluting with a developing solvent ratio of ethyl acetate to cyclohexane (1:4 by volume). After solvent removal, an orange-yellow solid product is obtained. 1 HNMR (500 MHz, DMSO-d3, Figure 1 )δ7.79(dd,J=32.6,8.7Hz,4H),7.15(d,J=8.8Hz,2H),6.92(d,J=8.7Hz,2H),4.91(d,J=1.9Hz,2H),3.66(s,1H).

[0068] 2. Synthesis of Ferrocene-Functionalized Azobenzene (Azo-Fc) via CuAAC Click Reaction

[0069] Ferrocene-functionalized azobenzene (Azo-Fc) was synthesized by CuAAC click reaction of the small molecule 3-azidopropyl ferrocenylcarboxylate and alkynyl-functionalized azobenzene (Alkynyl-Azo).

[0070] The specific method is as follows: Alkynyl-functionalized azobenzene (Alkynyl-Azo, 0.9 g, 3.6 mmol), 3-azidopropyl ferrocenylcarboxylate (1.0 g, 3.3 mmol), and bipyridine (2.1 mg, 13.2 mmol) were weighed and dissolved in 1 mL of DMF. Under nitrogen, CuBr (0.9 g, 6.6 mmol) was added, and the mixture was reacted in an oil bath at 35°C for 12 h. After completion of the reaction, DMF was removed by rotary evaporation to obtain a crude product. The crude product was first passed through a neutral alumina column to remove copper salts, and then further purified by column chromatography. The column chromatography was eluted with a developing solvent of ethyl acetate:n-hexane (volume ratio = 1:20). After complete solvent removal, a yellow solid product was obtained. The molar ratio of Alkynyl-Azo, 3-azidopropyl ferrocenylcarboxylate, bipyridine, and CuBr was 1.1:1:4:2.

[0071] 1 H NMR (500 MHz, DMSO-d3, Figure 2 )δ10.19(s,1H),8.36(s,1H),7.78(ddd,J=32.3,6.9,5.0Hz,4H),7.22(d,J=9.0Hz,2H),7.00-6.85(m,2H),5.27(s,2H) ,4.76(t,J=1.9Hz,2H),4.58(t,J=6.9Hz,2H),4.53-4.44(m,2H),4.25(s,5H),4.21-4.11(m,2H),2.27(p,J=6.5Hz,2H).

[0072] 3. Synthesis of Ferrocene and Azobenzene-Containing Monomer (M-Azo-Fc)

[0073] Ferrocene-functionalized azobenzene Azo-Fc (1.8 g, 3.2 mmol) was dissolved in 30 mL of dry tetrahydrofuran. Triethylamine (0.9 mL, 6.4 mmol) was then added. Under nitrogen, the reaction mixture was placed in an ice bath. Methacryloyl chloride (0.5 mL, 5.1 mmol) was added dropwise. After the addition was complete, the reaction was continued at room temperature for 4 hours. The molar ratio of Azo-Fc, triethylamine, and methacryloyl chloride was 1:2:1.6.

[0074] Post-processing: Remove the solvent using a rotary evaporator. Dissolve thoroughly in 50 mL of ethyl acetate, transfer to a 250 mL separatory funnel, and wash the organic phase three times with 50 mL of water. Add anhydrous MgSO₄ to the organic phase, dry overnight, and remove the MgSO₄ by filtration. Remove the solvent using a rotary evaporator to obtain the crude product. Purify the crude product by column chromatography using a developing solvent ratio of dichloromethane to methanol (volume ratio) of 1:80. After drying the solvent, obtain an orange solid.

[0075] 1 H NMR (500 MHz, DMSO-d3, Figure 3 )δ8.38(s,1H),8.01-7.86(m,4H),7.47-7.22(m,4H),6.33(s,1H),6.07-5.89(m,1H),5.30(s,2H),4.77(t,J=1.9Hz,2H),4 .58(t,J=6.9Hz,2H),4.55-4.45(m,2H),4.26(s,5H),4.17(t,J=6.1Hz,2H),2.27(p,J=6.5Hz,2H),2.02(d,J=21.1Hz,3H).

[0076] 4. Synthesis of ATRP initiator (Alkynyl-Azo-Br)

[0077] Add alkynyl-functionalized azobenzene (0.5 g, 2.0 mmol) to 15 mL of tetrahydrofuran. Once fully dissolved, add triethylamine (1.1 mL, 8.0 mmol). Place in an ice bath, then add 2-bromoisobutyryl bromide (0.8 mL, 6.0 mmol). Slowly drip 2-bromoisobutyryl bromide into the reaction mixture under a nitrogen balloon. After the addition is complete, continue the reaction at room temperature for 4 hours. The molar ratio of Alkynyl-Azo:triethylamine:2-bromoisobutyryl bromide is 1:4:3.

[0078] Post-processing: Remove the solvent using a rotary evaporator. Dissolve thoroughly in 50 mL of ethyl acetate, transfer to a 250 mL separatory funnel, and wash the organic phase three times with 50 mL of water. Collect the organic phase and dry over anhydrous MgSO₄. After overnight, remove the MgSO₄ by suction. The resulting solution is then subjected to a rotary evaporator to remove most of the solvent, yielding the crude product. The crude product is purified by column chromatography, eluting with a developing solvent ratio of ethyl acetate to n-hexane (1:15 by volume). The solvent is then evaporated to dryness, yielding the product as an orange-yellow solid.

[0079] 1 HNMR (500 MHz, DMSO-d3, Figure 4 )δ8.05-7.86(m,4H),7.48-7.34(m,2H),7.28-7.13(m,2H),4.95(d,J=2.3Hz,2H),3.67(t,J=2.2Hz,1H),2.07(s,6H).

[0080] 5. Polymer Synthesis

[0081] ATRP polymerization technology can be used to control the preparation of polymer P(OEGMA x -st-DMAEMAy -st-(M-Azo-Fc) z ), using PMDETA / CuBr as the catalytic system, the degree of polymerization of the monomers in the polymer was regulated by changing the monomer feed ratio and polymerization time. Table 1 shows the monomer feed ratio and polymerization time of four representative polymers. The SEC curves of these four polymers are shown in Figure 1. Figure 5 shown.

[0082] Table 1 Monomer feed molar ratio and polymerization time

[0083]

[0084] With chemical composition of P(OEGMA 10 -st-DMAEMA 20 -st-(M-Azo-Fc)4) polymer P3( Figure 6 ) as an example, specifically as follows:

[0085] Alkynyl-Azo-Br (25.3 mg, 63.2 μmol), PMDETA (11.0 mg, 63.2 μmol), OEGMA (284.4 mg, 948.0 μmol), M-Azo-Fc (200.0 mg, 316.0 μmol), and DMAEMA (297.7 mg, 1.9 mmol) were accurately weighed and dissolved in 750 μL of DMF. After thorough mixing, the mixture was transferred into a 10 mL polymerization tube. After three freeze-pump-thaw cycles, accurately weighed CuBr (9.0 mg, 63.2 μmol) was added under nitrogen. After three more freeze-pump-thaw cycles, the polymerization tube was sealed and placed in an oil bath preheated to 60°C. After 5 h of reaction, the tube was opened to expose the reaction mixture to air, and 1 mL of tetrahydrofuran was added to terminate the polymerization reaction. The reaction mixture was then placed in a dialysis bag with a molecular weight cut-off of 3.5 kDa and dialyzed in a large amount of deionized water for 48 h, with the water changed every 12 h to remove unreacted monomers and CuBr, and freeze-dried to obtain the product. The monomer polymerization degree and number average molecular weight (M n ) and molecular weight dispersion coefficient As listed in Table 2, all polymers All were effectively controlled and were less than 1.2.

[0086] Table 2. Molecular weight and molecular weight distribution coefficient results of polymers with different compositions

[0087]

[0088] a Determined by1 H NMR b Determined by SEC

[0089] 6. Detection of intracellular ROS generation using Fenton reagent

[0090] With chemical composition of P(OEGMA 10 -st-DMAEMA 20 -st-(M-Azo-Fc)4) polymer P3 was used as an example for the detection of intracellular ROS.

[0091] Mouse breast cancer 4T1 cells were cultured at 1×10 5 The cells were inoculated into 24-well plates at a density of 100 μg / mL and incubated at 37°C and 5% CO2 for 24 hours. A 70 μg / mL P3 solution was then prepared with complete culture medium and incubated with the cells for 4 hours. The wells without drug were used as blank controls. After removing the medium containing the drug from the well plate, the cells were washed twice with PBS and ROS detection reagent (Biyuntian Biotechnology Co., Ltd.) was added. After incubation for 20 minutes, the green fluorescence intensity induced by ROS production in the cells was observed using an inverted fluorescence microscope ( Figure 7 ).

[0092] 7. MTT assay to detect the toxicity of Fenton's reagent to breast cancer cells 4T1:

[0093] With chemical composition of P(OEGMA 10 -st-DMAEMA 20 -st-(M-Azo-Fc)4) polymer P3 was used as an example for cytotoxicity detection.

[0094] 4T1 cells were plated at 7 x 10 3 The cells were inoculated into 96-well plates at a density of 100 μg / mL and incubated at 37°C and 5% CO2 for 24 hours. A series of P3 solutions (0.1, 10, 20, 30, 40, 60, 80, 100 μg / mL) were then prepared with complete culture medium and incubated with the cells for 24 hours. After removing the medium containing the drug from the well plate, a blank medium containing MTT was added and incubated at 37°C for 4 hours. Then, the medium containing MTT in the well plate was removed, 150 μL of DMSO was added, and the well plate was shaken on a shaker for 15 minutes to fully dissolve the generated blue-purple crystalline formazan. The optical density of the well plate was then measured at a wavelength of 490 nm using a microplate reader. The relationship between different concentrations of P3 and cell survival rate is shown in the figure. Figure 8 As shown, the results showed that the half-maximal inhibitory concentration (IC 50 ) was 71 μg / mL, indicating that Fenton reagent P3 had significant killing effect on tumor cells 4T1.

[0095] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all details in detail, nor do they limit the invention to only the specific embodiments described.

Claims

1. A small molecule monomer M-Azo-Fc containing an azophenyl group and a ferrocenyl group, characterized in that: The chemical formula of the small molecule monomer is as follows:

2. A method for synthesizing the small molecule monomer M-Azo-Fc according to claim 1, characterized in that: The steps include: Step 1: 4,4'-dihydroxyazobenzene Azo is subjected to a substitution reaction to obtain alkynyl-functionalized azobenzene Alkynyl-Azo; Step 2: A ferrocene azidate Fc-N3 reacts with Alkynyl-Azo via CuAAC click reaction to obtain ferrocene-functionalized azobenzene Azo-Fc; Step 3: Azo-Fc reacts with methacryloyl chloride through substitution reaction to obtain a small molecule monomer M-Azo-Fc; 3. The method for synthesizing the small molecule monomer M-Azo-Fc according to claim 2, wherein: The specific steps of step one are as follows: Azobenzene was dissolved in anhydrous acetone and stirred evenly, and then propargyl bromide was added. Under nitrogen protection, the reaction was stirred at room temperature for 30 minutes, and K2CO3 was added. The mixture was refluxed for 10 hours and purified to obtain Alkynyl-Azo, wherein the molar ratio of Azo, propargyl bromide and K2CO3 was 1:1.1:0.

5.

4. The method for synthesizing the small molecule monomer M-Azo-Fc according to claim 2, wherein: The specific steps of step 2 are as follows: Alkynyl-Azo, Fc-N3, and bipyridine were weighed and mixed, then dissolved in DMF. CuBr was then added under nitrogen protection, and the mixture was reacted in an oil bath at 35°C for 12 hours to purify Azo-Fc. The molar ratio of Alkynyl-Azo, Fc-N3, bipyridine, and CuBr was 1:1.1:2:

4.

5. The method for synthesizing the small molecule monomer M-Azo-Fc according to claim 2, wherein: The specific steps of step three are as follows: Azo-Fc is dissolved in dry tetrahydrofuran, and triethylamine is then added. Under nitrogen protection, the reaction is placed in an ice bath, and a methacryloyl chloride solution is added dropwise. After the addition is complete, the reaction is continued at room temperature for 4 hours, and then purified to obtain M-Azo-Fc; wherein the molar ratio of Azo-Fc, triethylamine, and methacryloyl chloride is 1:2:1.6; the methacryloyl chloride solution is obtained by dissolving methacryloyl chloride in dry tetrahydrofuran and mixing, and the volume ratio of methacryloyl chloride to tetrahydrofuran in the methacryloyl chloride solution is 1:

10.

6. An application of M-Azo-Fc in the synthesis of Fenton reagent, characterized in that: The chemical formula of the M-Azo-Fc is as described in claim 1, and the M-Azo-Fc is used as a raw material for synthesizing the Fenton reagent, the Fenton reagent P(OEGMA x -st-DMAEMA y -st-(M-Azo-Fc)) z The chemical formula is as follows: Where x=7-30, y=17-22, z=3-13.

7. The use according to claim 6, characterized in that The synthesis method of the Fenton reagent comprises the following steps: Step 1: Alkynyl-Azo is reacted with 2-bromoisobutyryl bromide through a substitution reaction to obtain bromine-functionalized azobenzene Alkynyl-Azo-Br; the synthesis method of Alkynyl-Azo is as described in claim 3; Step 2: M-Azo-Fc is mixed with Alkynyl-Azo-Br, PMDETA, OEGMA, and DMAEMA, and then the Fenton reagent is obtained by ATRP technology under the action of CuBr catalyst. The chemical formula of M-Azo-Fc is as described in claim 1.

8. The use according to claim 7, characterized in that The specific steps of step one are as follows: Alkynyl-Azo was added to tetrahydrofuran, triethylamine was added after it was fully dissolved, and the mixture was placed in an ice bath. 2-bromoisobutyryl bromide was then added and slowly dripped into the reaction solution under nitrogen protection. After the addition was complete, the reaction was continued at room temperature for 4 hours and purified to obtain Alkynyl-Azo-Br; wherein the molar ratio of Alkynyl-Azo, triethylamine, and 2-bromoisobutyryl bromide was 1:2:1.

6.

9. The use according to claim 7, characterized in that The specific steps of step 2 are as follows: Alkynyl-Azo-Br, PMDETA, OEGMA, DMAEMA and M-Azo-Fc are dissolved in DMF, and then subjected to three freeze-pump-thaw cycles. CuBr is added under nitrogen protection, and then subjected to three freeze-pump-thaw cycles. The mixture is reacted in a 60°C oil bath for 5-10 hours. After stopping the polymerization reaction, the polymer is purified by dialysis to obtain a polymer. The molar feed ratio of Alkynyl-Azo-Br, PMDETA, CuBr, OEGMA, DMAEMA and M-Azo-Fc is 1:1:1:15-60:30:5-20. Referring to the molar feed ratio, OEGMA, DMAEMA and M-Azo-Fc are added in excess, and PMDETA and CuBr are added in equal molar amounts based on Alkynyl-Azo-Br. PMDETA and CuBr are used as catalysts.

10. A use of Fenton's reagent, characterized in that: The Fenton reagent is as described in claim 6, and is used for preparing a drug that kills tumor cells.

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