BODIPY compounds, preparation methods and uses thereof as photosensitizers

Abstract

The present invention belongs to the field of photodynamic therapy technology, and more particularly to a BODIPY compound, a preparation method and its use as a photosensitizer. The present invention provides a series of novel small molecule compound photosensitizers with BODIPY dimer as basic skeleton and pure type I photodynamic. By the combined action of heavy atoms, 2,4,6-trimethylphenyl groups and limited structure R groups introduced at specific positions, the reactive oxygen species yield is increased, and the regulation of pure type I photosensitizer is carried out by regulating energy levels. Compared with common photosensitizer molecule indocyanine green (ICG), the reactive oxygen species yield is about 50 times that of ICG, has higher photothermal stability, can significantly increase the applicability of photodynamic agents, and the preparation method is simple, the reaction efficiency is high, the yield is high, and there is good industrial application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of photodynamic therapy, and particularly relates to a BODIPY compound, a preparation method and use thereof as a photosensitizer. Background Art

[0002] Photodynamic therapy (PDT) offers advantages such as minimal invasiveness, high controllability, low toxicity, and high spatiotemporal precision. It is a safe, effective, and low-cost cancer treatment technology that has been extensively studied for the treatment of solid tumors, such as melanoma, skin cancer, esophageal cancer, and lung cancer. The mechanism of PDT is that photosensitizers (PSs) react with oxygen and other substances under light-induced conditions to produce reactive oxygen species (ROS). These highly reactive ROS can induce cell apoptosis or necrosis, microvascular closure, and immune responses, thereby curing cancer and other diseases. PDT utilizes light of appropriate wavelength to activate photosensitizers, causing them to produce cytotoxic ROS through either type I or type II photosensitization mechanisms, thereby achieving anti-tumor effects. Compared with traditional treatments such as surgical resection, chemotherapy, and radiotherapy, PDT offers unique advantages such as minimal trauma, reduced toxicity, and a wide range of indications.

[0003] BODIPY molecules possess excellent photophysical and chemical properties, making them promising candidates for photosensitizers. However, existing photosensitizer molecules based on a BODIPY dimer backbone exhibit suboptimal ROS generation capabilities. Modifying their structure to enhance ROS generation remains a pressing technical challenge. Summary of the Invention

[0004] In light of the shortcomings of the prior art, the present invention provides a BODIPY-based compound, a preparation method, and its use as a photosensitizer. Through rational molecular design, the present invention achieves precise control of excited-state energy levels, constructing near-infrared pure type-I photosensitizer molecules with high reactive oxygen species yields. This can increase the photosensitizer's ISC rate, prolong the triplet state lifetime, and enhance the tumor treatment efficacy of photodynamic therapy.

[0005] In a first aspect, the present invention provides a BODIPY compound, the structural formula of which is shown in formula (I):

[0006]

[0007] Wherein: R is a C6-C10 aromatic hydrocarbon group, or a C6-C10 aromatic hydrocarbon group substituted by a C1-C6 alkoxy group; X is a halogen atom.

[0008] In some embodiments, R is phenyl or C1-C6 alkoxyphenyl.

[0009] In some embodiments, R is phenyl, methoxyphenyl, ethoxyphenyl, or propoxyphenyl.

[0010] In some embodiments, X is an iodine atom or a bromine atom.

[0011] In some embodiments, the structural formula of the compound is selected from any one of the following:

[0012]

[0013] In a second aspect, the present invention provides a method for preparing the aforementioned BODIPY compounds, as follows:

[0014]

[0015] Wherein: the definitions of R and X are the same as above and will not be repeated here.

[0016] Step 1: In the presence of a solvent, the compound represented by formula (a) reacts with a halogenating agent at 70-90° C. for 1-3 hours to obtain a compound represented by formula (b);

[0017] Step 2: reacting the compound represented by formula (b) in the presence of an inert gas, a catalyst, and a solvent at 100-120° C. for 1-2 hours to obtain a compound represented by formula (c);

[0018] Step 3: In the presence of a solvent, the compound represented by formula (c) reacts with a halogenating agent at room temperature for 1-3 hours to obtain a compound represented by formula (d);

[0019] Step 4: In the presence of a catalyst, a solvent, and a base, the compound represented by formula (d) reacts with the compound represented by formula (e) at 100-120° C. for 1-3 hours to obtain a compound represented by formula (f);

[0020] Step 5: The compound represented by formula (f) is reacted in the presence of a halogenating agent and a solvent at 0°C for 2-5 hours to obtain the compound represented by formula (I).

[0021] In some embodiments, in step 1, the molar ratio of the compound represented by formula (a) to the halogenating agent is 1:8-12. The halogenating agent is preferably a copper halide, more preferably copper chloride, and most preferably copper chloride dihydrate. The solvent is preferably acetonitrile. An oxidizing agent is also included, preferably potassium persulfate.

[0022] In some embodiments, in step 2, the inert gas includes but is not limited to nitrogen, argon, preferably argon. The catalyst includes a palladium catalyst, an organic phosphine and an organic tin catalyst. The palladium catalyst includes but is not limited to tetrakis(triphenylphosphine)palladium, palladium acetate, bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, preferably tris(dibenzylideneacetone)dipalladium; the organic phosphine includes but is not limited to tri(o-methylphenyl)phosphine, tributylphosphine, or triphenylphosphine, preferably tri(o-methylphenyl)phosphine; the organic tin catalyst includes but is not limited to hexa-n-butyltin, methyltin trichloride, triethyltin bromide, dibutyltin dichloride, dimethyltin dichloride, phenyltin trichloride, tin tetrachloride, trimethyltin chloride, stannous octoate, diphenyltin dichloride, tri-n-butyltin azide, preferably hexa-n-butyltin. The solvent is preferably a mixed solvent of toluene and water.

[0023] In some embodiments, in step 3, the molar ratio of the compound represented by formula (c) to the halogenating agent is 1:8-12. The halogenating agent is preferably a copper halide, more preferably copper chloride, and most preferably copper chloride dihydrate. The solvent is preferably a CH3CN / DCM mixed solvent.

[0024] In some embodiments, in step 4, the molar ratio of the compound represented by formula (d) to the compound represented by formula (e) is 1:2-4. The catalyst includes a palladium catalyst, which includes but is not limited to tetrakis(triphenylphosphine)palladium, palladium acetate, bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium, or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, preferably tetrakis(triphenylphosphine)palladium. The solvent is preferably a mixed solvent of toluene and water. The base includes but is not limited to sodium carbonate, potassium carbonate, cesium carbonate, piperidine, trimethylamine, triethylamine, pyridine, preferably sodium carbonate.

[0025] In some embodiments, in step 5, the molar ratio of the compound represented by formula (f) to the halogenating agent is 1:0.5-2. The halogenating agent is N-halosuccinimide, preferably N-bromosuccinimide or N-iodosuccinimide. The solvent is preferably a DCM / DMF mixed solvent.

[0026] In a third aspect, the present invention provides use of the aforementioned BODIPY compounds as photosensitizers for photodynamic therapy.

[0027] The beneficial effects of the present invention are:

[0028] This invention provides a series of novel small-molecule photosensitizers based on a BODIPY dimer as a basic framework, demonstrating pure Type I photodynamic activity. Specifically, through the combined effects of heavy atoms, 2,4,6-trimethylphenyl groups, and structurally defined R groups introduced at specific locations, the reactive oxygen species (ROS) yield is enhanced, allowing the pure Type I photosensitizer to be regulated by controlling energy levels. Compared to the common photosensitizer molecule indocyanine green (ICG), the ROS yield is approximately 50 times higher, and the photosensitizer exhibits higher photothermal stability, significantly increasing the applicability of photodynamic agents. Furthermore, the preparation method is simple, the reaction efficiency is high, and the yield is high, suggesting promising industrial applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the technical solution of the present invention, the following is a brief introduction to the drawings required for use in the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0030] Figure 1 is the hydrogen spectrum of compound B-2;

[0031] Figure 2 is the hydrogen spectrum of compound B-3;

[0032] Figure 3A is the normalized UV absorption spectrum of compound B-2 in different solutions;

[0033] Figure 3B is the normalized fluorescence emission spectrum of compound B-2 in different solutions under excitation at 750 nm;

[0034] Figure 4A DPBF blank indicator in methanol (10mWcm -2 ) degradation curve;

[0035] Figure 4B DPBF blank indicator in dimethyl sulfoxide (10 mW cm -2 ) degradation curve;

[0036] Figure 4C DPBF blank indicator in toluene (10mWcm -2 ) degradation curve;

[0037] Figure 5A is the DPBF of ICG in methanol (10 mWcm -2 ) degradation curve;

[0038] Figure 5B DPBF (10 mW cm -2) degradation curve;

[0039] Figure 5C is the DPBF of ICG in toluene (10 mW cm -2 ) degradation curve;

[0040] Figure 6A DPBF (5 mW cm) of compound B-2 in dichloromethane -2 ) degradation curve;

[0041] Figure 6B DPBF (5 mW cm) of compound B-2 in dichloromethane -2 )’s linear relationship with the degradation curve;

[0042] Figure 6C DPBF (5 mW cm) of compound ICG in dichloromethane -2 ) degradation curve;

[0043] Figure 6D DPBF (5 mW cm) of compound ICG in dichloromethane -2 )’s linear relationship with the degradation curve;

[0044] Figure 6E DPBF (5 mW cm) of compound B-2 in chloroform -2 ) degradation curve;

[0045] Figure 6F DPBF (5 mW cm) of compound B-2 in chloroform -2 )’s linear relationship with the degradation curve;

[0046] Figure 6G DPBF (5 mW cm) of compound ICG in chloroform -2 ) degradation curve;

[0047] Figure 6H DPBF (5 mW cm) of compound ICG in chloroform -2 )’s linear relationship with the degradation curve;

[0048] Figure 6I Comparison of slopes between compound B-2 and ICG in different solvents;

[0049] Figure 7A ABDA blank indicator in tetrahydrofuran (70 mWcm -2 ) degradation curve;

[0050] Figure 7B ABDA (70 mW cm) in tetrahydrofuran for ICG -2 ) degradation curve;

[0051] Figure 7C is ABDA (70 mW cm) of compound B-2 in tetrahydrofuran -2 ) degradation curve;

[0052] Figure 8 DHE (300 mW cm -2 ) curve changes;

[0053] Figure 9A The concentration is 50 μg mL -1 Temperature change curve of compound B-2 under laser irradiation at different power densities;

[0054] Figure 9B The different concentrations of compound B-2 at 1Wcm -2 Temperature change curve under laser irradiation;

[0055] Figure 9C For compound B-2 with a concentration of 20 μg / mL, 1 W cm -2 Temperature rise and fall curves after power irradiation;

[0056] Figure 9D For compound B-2 with a concentration of 20 μg / mL, 1 W cm -2 Temperature rise and fall curve after power irradiation. DETAILED DESCRIPTION

[0057] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention are clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0058] Definition of terms

[0059] Unless otherwise indicated, technical terms used in the present invention have the meanings commonly understood by those skilled in the art. The laboratory procedures involved are conventional procedures widely used by those skilled in the art. In order to better understand the present invention, definitions and explanations of relevant terms are provided below.

[0060] The term "C6-C10 aromatic hydrocarbon group" used herein refers to a hydrocarbon group containing a benzene ring and having 6 to 10 carbon atoms, such as phenyl, benzyl, phenethyl, and the like.

[0061] The term "C6-C10 aromatic hydrocarbon group substituted with a C1-C6 alkoxy group" as used herein refers to a C6-C10 aromatic hydrocarbon group in which 1 to 3 hydrogen atoms on the benzene ring are substituted with a C1-C6 alkoxy group.

[0062] The term "C1-C6 alkoxy" as used herein refers to an O-alkyl group having 1 to 6 carbon atoms, such as -OCH3, -OC2H5, -OC3H7, -OC4H9, -OC5H 11 、-OC6H 13 .

[0063] The term "halogen atom" as used herein refers to a fluorine, chlorine, bromine or iodine atom.

[0064] Example 1 Synthesis of Compound B-2

[0065] (1) Synthesis of Compound A-1

[0066]

[0067] In a round-bottom flask, compound A (310 mg, 1 mmol, 1.0 eq), potassium persulfate (1080 mg, 4 mmol, 4.0 eq), cupric chloride dihydrate (1700 mg, 10 mmol, 10.0 eq), and acetonitrile (20.0 mL) were added and reacted at 80°C for 2 h. After cooling to room temperature, the reaction solution was poured into dichloromethane (30 mL) and rinsed with water (3 × 50 mL). After drying over anhydrous sodium sulfate, the organic solvent was removed by distillation under reduced pressure. The product was purified by silica gel column chromatography to obtain 150 mg of a red solid, compound A-1.

[0068] (2) Synthesis of Compound B

[0069]

[0070] To a Shrek tube, add compound A-1 (577.9 mg, 1.68 mmol, 2.1 eq), tris(dibenzylideneacetone)dipalladium (40.48 mg), tri(o-methylphenyl)phosphine (52.80 mg), hexabutyltin (404 μL, 0.8 mmol, 1 eq), and 20 mL of toluene. Incubate at 110°C for 1.5 h. After cooling to room temperature, the reaction solution is purified by silica gel column chromatography to yield 60 mg of a blue solid, Compound B.

[0071] (3) Synthesis of compound B-Cl

[0072]

[0073] To a round-bottom flask, compound B (618 mg, 1 mmol, 1.0 eq), copper chloride dihydrate (1700 mg, 10 mmol, 10.0 eq), and a CH3CN / DCM mixture (V / V = 1:1, 200.0 mL) were added and allowed to react at room temperature for 2 h. The reaction solution was poured into water (250 mL) and rinsed with water (3 × 100 mL). After drying over anhydrous sodium sulfate, the organic solvent was removed by vacuum distillation. Silica gel column chromatography afforded 300 mg of a blue solid, compound B-Cl.

[0074] (4) Synthesis of Compound B-1

[0075]

[0076] To a Shrek tube, add compound B-Cl (131 mg, 0.2 mmol, 1.0 eq), p-methoxyphenylphenylboronic acid (106.8 mg, 0.6 mmol, 3.0 eq), and tetrakis(triphenylphosphine)palladium (12 mg, 0.01 mmol, 1.0 eq). After excluding air, add toluene (5.0 mL), water (1 mL), and sodium carbonate (32 mg, 0.3 mmol, 3.0 eq). React at 110°C for 2 h. Pour the reaction solution into dichloromethane (50 mL) and rinse with water (3 x 50 mL). After drying over anhydrous sodium sulfate, the organic solvent was removed by distillation under reduced pressure. The product was purified by silica gel column chromatography to obtain 25 mg of a bluish-black solid, compound B-1.

[0077] (5) Synthesis of Compound B-2

[0078]

[0079] In a round-bottom flask, compound B-1 (15 mg, 0.02 mmol, 1.0 eq) and NBS (3.56 mg, 0.02 mmol, 3.0 eq) were added, DCM 5 mL and DMF 5 mL were added, and the reaction was started at 0 ° C. After completion, the reaction mixture was poured into dichloromethane (20 mL), washed three times with water (20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by column chromatography to obtain 2.1 mg of a black-green solid product, which is compound B-2. The hydrogen spectrum is shown in FIG. Figure 1 shown.

[0080] Example 2 Synthesis of Compound B-3

[0081] Preparation steps (1) (2) (3) of compound B-3 are prepared according to Example 1

[0082] (4) Synthesis of Compound B-3-1

[0083]

[0084] To a Shrek tube, add compound B-Cl (131 mg, 0.2 mmol, 1.0 eq), styrene boronic acid (264.6.8 mg, 0.6 mmol, 3.0 eq), and tetrakis(triphenylphosphine)palladium (12 mg, 0.01 mmol, 1.0 eq). After excluding air, add toluene (5.0 mL), water (1 mL), and sodium carbonate (32 mg, 0.3 mmol, 3.0 eq). React at 110°C for 2 h. Pour the reaction solution into dichloromethane (50 mL) and rinse with water (3 × 50 mL). After drying over anhydrous sodium sulfate, the organic solvent was removed by distillation under reduced pressure. The product was purified by silica gel column chromatography to obtain 25 mg of a bluish-black solid, compound B-3-1.

[0085] (5) Synthesis of Compound B-3

[0086]

[0087] In a round-bottom flask, compound B-3-1 (14.4 mg, 0.02 mmol, 1.0 eq) and NIS (13.5 mg, 0.02 mmol, 3.0 eq) were added, DCM 5 mL and DMF 5 mL were added, and the reaction was started at 0 ° C. After completion, the reaction mixture was poured into dichloromethane (20 mL), washed three times with water (20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by column chromatography to obtain 3.8 mg of a black-green solid product, which is compound B-3. The hydrogen spectrum is shown in FIG. Figure 2 shown.

[0088] Example 3 Synthesis of Compound B-4

[0089] Preparation steps (1) (2) (3) (4) of compound B-4 are prepared according to Example 1

[0090] (5) Synthesis of Compound B-4

[0091]

[0092] In a round-bottom flask, compound B-1 (15 mg, 0.02 mmol, 1.0 eq) and NIS (13.5 mg, 0.02 mmol, 3.0 eq) were added, along with 5 mL of DCM and 5 mL of DMF. The reaction was started at 0°C. After completion, the reaction mixture was poured into dichloromethane (20 mL), washed three times with water (20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by column chromatography to give 2.3 mg of a carbon green solid product, compound B-4.

[0093] Example 4 Synthesis of Compound B-5

[0094] Preparation steps (1) (2) (3) (4) of compound B-5 are prepared according to Example 2

[0095] (5) Synthesis of Compound B-5

[0096]

[0097] In a round-bottom flask, compound B-3-1 (14.4 mg, 0.02 mmol, 1.0 eq) and NBS (3.56 mg, 0.02 mmol, 3.0 eq) were added, DCM 5 mL and DMF 5 mL were added, and the reaction was started at 0 ° C. After completion, the reaction mixture was poured into dichloromethane (20 mL), washed three times with water (20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by column chromatography to obtain 4.3 mg of a dark green solid product, which is compound B-5.

[0098] Experimental Example 1 Basic Spectra of the Compounds of the Invention

[0099] This test example tests the absorption spectrum and fluorescence spectrum of compound B-2 of the present invention in various solvents. Figure 3A Normalized UV absorption spectra of compound B-2 in different solutions. Figure 3B Normalized fluorescence emission spectra of compound B-2 in different solutions under excitation at 750 nm.

[0100] Test Example 2: Active oxygen generation ability test of the compounds of the present invention

[0101] 1. Test principle: DPBF (1,3-Diphenylisobenzofuran) is mainly used for the detection of reactive oxygen species (ROS). Reactive oxygen species (ROS) broadly refers to free radicals and non-free radicals derived from oxygen, including superoxide anions (O2 ·— ), hydrogen peroxide (H2O2), hydroxyl radical (·OH) and singlet oxygen ( 1 O2), which has a high chemical reactivity due to its unpaired electrons. When DPBF combines with reactive oxygen species, it is irreversibly oxidized, and the absorption intensity at UV-visible light (414nm) decreases rapidly, making it suitable for detecting the generation of reactive oxygen species.

[0102] ABDA (9,10-anthracenediyl-bis(methylene)dicarboxylic acid) is a singlet oxygen-indicating fluorescent probe. This water-soluble anthracene derivative reacts with singlet oxygen and photobleaches to generate the corresponding endoperoxide. This reaction is monitored by spectrophotometry by recording the decrease in optical density at 400 nm, and can be used to detect the generation of singlet oxygen.

[0103] Dihydroethidium (DHE) is a commonly used fluorescent probe for superoxide anions, often used to monitor intracellular reactive oxygen species (ROS) levels. Upon entry into cells, DHE undergoes dehydrogenation under the action of intracellular superoxide anions, forming ethidium. This is then incorporated into the cell's RNA or DNA, generating red fluorescence. The intensity of the fluorescence signal is positively correlated with the intracellular superoxide anion concentration, making it a useful tool for detecting superoxide anion production.

[0104] 2. Test method: Compound B-2 or indocyanine green was dissolved in different solvents, and then DPBF was added to each solution. Laser irradiation (10 mW cm -2 ) After different time, the relative attenuation of the absorbance intensity at 414 nm was measured. Compound B-2 or indocyanine green was dissolved in different solvents, and then ABDA was added to each solution. Laser irradiation (10 mW cm -2 ) After different time periods, the relative attenuation diagram of the absorbance intensity of the characteristic peak was measured.

[0105] 3. Test results:

[0106] Figure 4A DPBF blank indicator in methanol (10mWcm -2 ) degradation curve; Figure 4B DPBF blank indicator in dimethyl sulfoxide (10 mW cm -2 ) degradation curve; Figure 4C DPBF blank indicator in toluene (10mWcm -2 ). It can be seen that with the increase of irradiation time, the absorption at 414nm basically does not change, indicating that the DPBF blank indicator will not degrade in different solvents and is stable.

[0107] Figure 5A is the DPBF of ICG in methanol (10 mWcm -2 ) degradation curve, Figure 5B DPBF (10 mW cm -2 ) degradation curve, Figure 5C is the DPBF of ICG in toluene (10 mW cm -2 It can be seen that with the increase of irradiation time, the absorption degradation at 414 nm is less, indicating that the ICG active oxygen production rate is low.

[0108] Figure 6A DPBF (5 mW cm) of compound B-2 in dichloromethane -2 ) degradation curve, Figure 6BDPBF (5 mW cm) of compound B-2 in dichloromethane -2 ). It can be seen that with the increase of irradiation time, the absorption degradation at 414nm is obvious, indicating that the active oxygen production rate of the compound is high.

[0109] Figure 6C DPBF (5 mW cm) of compound ICG in dichloromethane -2 ) degradation curve, Figure 6D DPBF (5 mW cm) of compound ICG in dichloromethane -2 It can be seen that with the increase of irradiation time, the absorption degradation at 414nm is less, indicating that the active oxygen production rate of the compound is low.

[0110] Figure 6E DPBF (5 mW cm) of compound B-2 in chloroform -2 ) degradation curve, Figure 6F DPBF (5 mW cm) of compound B-2 in chloroform -2 ) shows a linear relationship with the degradation curve of the compound. It can be seen that with the increase of irradiation time, the absorption degradation at 414 nm is obvious, indicating that the active oxygen production rate of the compound is high.

[0111] Figure 6G DPBF (5 mW cm) of compound ICG in chloroform -2 ) degradation curve, Figure 6H DPBF (5 mW cm) of compound ICG in chloroform -2 ) shows a linear relationship between the degradation curves of the two compounds. It can be seen that with the increase of irradiation time, the absorption degradation at 414 nm is less, indicating that the active oxygen production rate of the compound is low.

[0112] Figure 6I The slope comparison of compound B-2 and ICG in different solvents is shown in Table 1.

[0113] Table 1

[0114]

[0115] Active oxygen production rate calculation formula: Φ Δx =Φ Δs (S x / S s )(F s / F x); where the subscript X represents the sample involved in the test, S represents the reference compound ICG; Φ represents the reactive oxygen species production, S is the slope of the linear fit with the irradiation time as the x-axis and the absorbance of DPBF at 414 nm after the corresponding irradiation time as the y-axis, and F represents the absorption correction factor, calculated as F = 1-10 -OD ,OD represents the ultraviolet absorption value of the compound at the corresponding wavelength of the irradiated laser (unified as 755nm in this test).

[0116] It can be seen that the active oxygen production rate of compound B-2 in DCM is 51.95 times that of ICG, and the active oxygen production rate of compound B-2 in TCM is 52.29 times that of ICG.

[0117] Figure 7A ABDA blank indicator in tetrahydrofuran (70 mWcm -2 ) degradation curve, Figure 7B ABDA (70 mW cm) in tetrahydrofuran for ICG -2 ) degradation curve, Figure 7C is ABDA (70 mW cm) of compound B-2 in tetrahydrofuran -2 ). The above test data show that at the same power, ABDA itself does not degrade at all, but the compound ICG degrades, indicating that ICG produces singlet oxygen and is not a pure Type I photosensitizer. B-2 shows little degradation, indicating that B-2 produces almost no singlet oxygen and that the types of reactive oxygen species produced are superoxide radicals and hydroxyl radicals, indicating that it is a pure Type I photosensitizer.

[0118] Figure 8 DHE (300 mW cm -2 ), it can be seen from the curve changes that the fluorescence of DHE at 610 nm is significantly enhanced, indicating that compound B-2 can effectively generate superoxide free radicals.

[0119] Test Example 3 Photothermal performance test of the compound of the present invention

[0120] This test example tests the photothermal performance of compound B-2 in Example 1. Different concentrations of the compound are used and different optical powers are used for laser irradiation. The temperature is measured and recorded. -2 The laser power was recorded every 10 seconds, and the photothermal heating curve and the negative natural logarithm of the cooling time and the temperature in the cooling stage were plotted. The test results are shown in Figure 9A 、 9B , 9C, 9D.

[0121] Figure 9AThe temperature curve of compound B-2 at a concentration of 50 μg / mL under laser irradiation at different power densities is shown. The results show that at the same concentration, the temperature of the compound rises more with increasing laser power.

[0122] Figure 9B The different concentrations of compound B-2 at 1Wcm -2 Temperature change curve under laser irradiation. The results show that under the same power conditions, the temperature rises higher with the increase of compound concentration.

[0123] Figure 9C For compound B-2 with a concentration of 20 μg / mL, 1 W cm -2 Temperature rise and fall curves after power irradiation.

[0124] Figure 9D For compound B-2 with a concentration of 20 μg / mL, 1 W cm -2 The temperature rise and fall curves after power irradiation. The results show that after four repetitions, the maximum temperature of compound B-2 remains basically unchanged, indicating good photothermal stability.

[0125] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

Claims

1. A BODIPY compound, characterized in that: The structural formula of the compound is shown in formula (I): (Ⅰ) in: R is a C6-C10 aromatic hydrocarbon group, or a C6-C10 aromatic hydrocarbon group substituted by a C1-C6 alkoxy group; X is a halogen atom.

2. The BODIPY compound according to claim 1, characterized in that The R is a phenyl group or a C1-C6 alkoxyphenyl group.

3. The BODIPY compound according to claim 2, characterized in that The R is phenyl, methoxyphenyl, ethoxyphenyl or propoxyphenyl.

4. The BODIPY compound according to claim 1, characterized in that The X is an iodine atom or a bromine atom.

5. The BODIPY compound according to claim 3, characterized in that The structural formula of the compound is selected from any one of the following:

6. A method for preparing the BODIPY compound according to any one of claims 1 to 5, characterized in that: The preparation method comprises: performing a first reaction on a compound represented by formula (d) and a compound represented by formula (e), and performing a second reaction on the first reaction product and a halogenating agent; ； in: R is a C6-C10 aromatic hydrocarbon group, or a C6-C10 aromatic hydrocarbon group substituted by a C1-C6 alkoxy group; X is a halogen atom.

7. The preparation method according to claim 6, characterized in that The conditions of the first reaction include: reacting at 100-120° C. for 1-3 hours in the presence of an inert gas, a palladium catalyst, a solvent, and a base.

8. The preparation method according to claim 6, characterized in that The conditions of the second reaction include: reacting at 0° C. for 2 to 5 hours in the presence of a solvent.

9. The preparation method according to claim 6, characterized in that The halogenating agent is N-halosuccinimide.

10. Use of the BODIPY compound according to any one of claims 1 to 5 for preparing a photosensitizer for photodynamic therapy.

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