A near-infrared second near-infrared region cyanine compound, its synthesis method and application

Abstract

The present invention relates to the field of organic synthesis, belonging to the technical field of organic light-emitting materials, and specifically relates to the synthesis and anti-tumor application of near-infrared II region heptamethine cyanine compounds. The compound provided by the present invention has stable fluorescence, exhibits aggregation-induced emission effect (AIE), and has advantages such as high photothermal conversion efficiency and photothermal stability compared with indocyanine green (ICG). Utilizing the characteristics such as the penetrability of the near-infrared II region, photothermal therapy and near-infrared II region fluorescence imaging of deep tumors can be achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of fluorescence bio-diagnosis and treatment; specifically, it relates to a near-infrared region II AIE cyanine compound with high photothermal conversion efficiency, and the present invention also relates to a synthesis method of this compound and its application in the diagnosis and treatment of deep tumors. Background Art

[0002] In recent years, cyanine dyes have attracted wide attention due to their excellent light absorption in the near-infrared region (NIR, 700 - 900 nm), deeper tissue penetration, easy synthesis, and low biological toxicity. Among them, the clinically approved cyanine dye indocyanine green (ICG) by the FDA has become the most representative cyanine photosensitizer due to its fluorescence imaging and photothermal properties. However, the near-infrared absorption of ICG is achieved by a long conjugated chain, but it also has the defects brought by this parent nucleus structure, such as poor stability, aggregation-caused fluorescence quenching, easy formation of π-π stacking, and low photothermal conversion efficiency. Therefore, improving the photothermal conversion efficiency and stability of cyanine photosensitizers is the primary key point and difficulty in the field of photodiagnosis and treatment research.

[0003] Most tumors are located deep in the body, such as glioblastoma, lung cancer, and liver cancer. Most existing tumor studies use NIR photosensitizers or chemotherapy drugs for diagnosis and treatment, which have problems such as low signal-to-noise ratio in fluorescence imaging, shallow laser penetration during phototherapy, and large side effects. Therefore, it is of great significance to seek more effective and safe diagnosis and treatment methods.

[0004] Based on this, since 2001 when Academician Tang Benzhong proposed the aggregation-induced emission effect (AIE), this theory has well solved the balance problem between imaging and treatment in molecular design. At the same time, compared with visible light (400 - 700 nm) and near-infrared region I (700 - 900 nm), the advantage of near-infrared region II (NIR-II, 1000 - 1700 nm) lies in its deeper penetration ability, better spatial resolution, and reduced light damage to biological tissues. As a new field of tumor photothermal therapy (PPT), NIR-II fluorescent materials can combine imaging to achieve safe, precise, and efficient diagnosis and treatment integration for deep tumors. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defects and deficiencies of existing cyanine dyes, such as low photothermal conversion efficiency, aggregation-caused fluorescence quenching, poor photothermal stability, and low absorption band, and to provide a near-infrared region II cyanine compound with AIE effect and excellent photothermal properties, and to use it in the diagnosis and treatment of deep tumors.

[0006] The second object of the present invention is to provide a preparation method of a near-infrared region II cyanine compound.

[0007] The third object of the present invention is to provide the application of near-infrared second-zone cyanine compounds.

[0008] The above-mentioned object of the present invention is achieved by the following technical solutions:

[0009] A near-infrared zone II AIE cyanine compound, the structure of which is shown in formula (I):

[0010]

[0011] Wherein, R is a hydrogen atom, a methyl group, a methoxy group, a sec-butyl group, a tert-butyl group, or a hydroxyl group; X is Cl - Br - ,I - PF6 - 、BF4 - ;

[0012] The present invention couples a diphenylamine structure with molecular rotor characteristics on a cyanine mother core unit to give the compound a stereostructure, high photothermal conversion efficiency and AIE effect. At the same time, the conjugated system of the compound is enlarged, causing the absorption spectrum and emission spectrum to red-shift. When the compound is in a specific aggregation state, the activity of the benzene ring on the diphenylamine is restricted, showing the performance of AIE response.

[0013] The present invention also provides a method for preparing near-infrared zone II cyanine compounds, comprising the following steps:

[0014] S1. 6-bromobenz[cd]indol-2(1H)-one and iodoethane are thoroughly mixed and heated to complete the reaction, and then post-treated to obtain a compound represented by formula (II);

[0015] S2. dissolving the compound represented by formula (II) and formula (III) in an organic solvent, heating in the presence of a catalyst to complete the reaction, and post-treating to obtain a compound represented by formula (IV);

[0016] S3. The compound represented by formula (IV) and methyl magnesium chloride are dissolved in an organic solvent, heated to complete the reaction, and the corresponding salt of X is added during post-treatment to obtain formula (V);

[0017] S4. The compound represented by formula (V) and 2-chloro-1-formyl-3-hydroxymethylenecyclohexene are dissolved in an organic solvent and heated to complete the reaction, followed by post-treatment to obtain;

[0018] The structural formulas of the compounds of formula (II), formula (III), formula (IV) and formula (V) are as follows:

[0019]

[0020] Wherein, R is a hydrogen atom, a methyl group, a methoxy group, a butyl group, a sec-butyl group, a tert-butyl group, or a hydroxyl group; X is Cl- , Br - , I - , PF6 - , BF4 - .

[0021] The specific synthesis route is as follows:

[0022]

[0023] Preferably, in step S1, the temperature of the heating reaction is 20 - 80 °C; in step S2, the temperature of the heating reaction is 20 - 110 °C; in step S3, the temperature of the heating reaction is 20 - 100 °C; in step S4, the temperature of the heating reaction is 20 - 110 °C.

[0024] Preferably, in step S1, the reaction time is 4 - 24 hours; in step S2, the reaction time is 12 - 48 hours; in step S3, the reaction time is 0.5 - 12 hours; in step S4, the reaction time is 0.5 - 12 hours.

[0025] Preferably, in step S1, the molar ratio of 6 - bromobenzo[cd]indol - 2(1H) - one to ethyl iodide is 1:1 - 1:5; in step S2, the molar ratio of the compound of formula (II) to that of formula (III) is 1:1 - 1:5; in step S3, the molar ratio of the compound of formula (IV) to methylmagnesium chloride is 1:1 - 1:5; in step S4, the molar ratio of the compound of formula (V) to 2 - chloro - 1 - formyl - 3 - hydroxymethylene cyclohexene is 2:1 - 4:1.

[0026] Preferably, the organic solvent is one or more of anhydrous acetonitrile, anhydrous toluene, anhydrous dimethylformamide, anhydrous tetrahydrofuran, anhydrous ethanol, acetic acid, or acetic anhydride.

[0027] More preferably, in step S1, the organic solvent is one of anhydrous acetonitrile, anhydrous toluene, anhydrous dimethylformamide, or anhydrous ethanol; in step S2, the organic solvent is one of anhydrous acetonitrile, anhydrous toluene, or anhydrous dimethylformamide; in step S3, the organic solvent is one of anhydrous tetrahydrofuran, anhydrous ethanol, or anhydrous acetonitrile; in step S4, the organic solvent is one or more of anhydrous tetrahydrofuran, anhydrous ethanol, anhydrous acetonitrile, acetic acid, or acetic anhydride.

[0028] Preferably, the catalyst is one of bis(tri - tert - butylphosphine), tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium(0) chloroform adduct, palladium acetate, or tris(dibenzylideneacetone)dipalladium.

[0029] The present invention also protects near-infrared II cyanine compounds and their applications in organic light-emitting materials.

[0030] Preferably, the applications in organic light-emitting materials include applications in fluorescent probes, bioimaging, and diagnosis and treatment of deep tumors (such as glioblastoma, liver cancer, lung cancer, etc.).

[0031] More preferably, the applications in bioimaging include applications in fluorescence imaging, photoacoustic imaging, and photothermal imaging.

[0032] More preferably, the diagnosis and treatment of deep tumors (such as glioblastoma, liver cancer, lung cancer, etc.) include applications in imaging diagnosis and photothermal treatment of deep tumors (such as glioblastoma, liver cancer, lung cancer, etc.).

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] The compound provided by the present invention has stable fluorescence and has the AIE effect. It not only has high photothermal conversion efficiency and photothermal stability in solution, but also can achieve near-infrared II photothermal treatment, photothermal imaging, and near-infrared II fluorescence and photoacoustic imaging in mice, showing obvious advantages compared with the near-infrared I dye ICG approved by the FDA. Description of the Drawings

[0035] Figure 1 HNMR spectrum of the compound (IRLy-DPA) in Example 1 of the present invention 1 HNMR spectrum.

[0036] Figure 2 HNMR spectrum of the compound (IRLy-MeO) in Example 2 of the present invention 1 HNMR spectrum.

[0037] Figure 3 HNMR spectrum of the compound (IV-tBu) in Example 3 of the present invention 1 HNMR spectrum.

[0038] Figure 4 Fluorescence spectra of the compound (IRLy-MeO) in Example 2 of the present invention in a water-tetrahydrofuran system with different water contents

[0039] Figure 5 Photothermal conversion efficiency of the compound (IRLy-MeO) in Example 2 of the present invention

[0040] Figure 6 Photothermal stability of the compound (IRLy-MeO) and ICG in Example 2 of the present invention

[0041] Figure 7The toxicity and photothermal toxicity of rat glioma cells (GL261) incubated with IRLy-MeO in Example 2 of the present invention were characterized by the MTT method.

[0042] Figure 8 IRLy-MeO of the compound in Example 2 of the present invention was intravenously administered to GL261 tumor-bearing nude mice (8 h) and then irradiated with a 1064 nm laser (0.8 W / cm 2 ) Thermal imaging of temperature changes under irradiation. DETAILED DESCRIPTION

[0043] The present invention is further described below in conjunction with the accompanying drawings and specific examples. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0044] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0045] Example 1 Preparation of IRLy-DPA Compound

[0046] S1. Weigh 3 mmol of 6-bromobenz[cd]indol-2(1H)-one, dissolve in 8 mL of anhydrous acetonitrile, and add 15 mmol of NaH at low temperature. After completion, continue to stir in an ice bath for 10 min, add 3.6 mmol of iodoethane, and stir at 20°C for 24 h. After the reaction, add 16 mL of deionized water and extract with 10 mL of ethyl acetate. The crude product is purified by silica gel chromatography, eluted with petroleum ether / ethyl acetate (v / v=10:1), and dried in a vacuum at 30°C and 10 Pa to obtain product II;

[0047]

[0048] S2. Weigh 2mmol of compound II, 10.0mmol of diphenylamine, and 3mmol of sodium tert-butoxide, add 20mL of anhydrous toluene to dissolve, then add 0.12mmol of tri-tert-butylphosphine and 0.08mmol of palladium catalyst under nitrogen atmosphere, and react at 20°C for 48h. After the reaction, add 15mL of acetone to dilute, filter, and purify the crude product by silica gel chromatography, using petroleum ether / ethyl acetate = (v / v = 5:1) for elution, and vacuum dry at 30°C 10Pa to obtain compound IV-DPA;

[0049]

[0050] S3. Dissolve 1 mmol of compound IV-DPA in 10 mL of anhydrous tetrahydrofuran, add 1 mmol of methylmagnesium chloride solution dropwise, and react at 20°C for 12 hours. After the reaction is completed, pour the reaction mixture into 30 mL of 5% dilute hydrochloric acid and add 2.5 mmol of KI to the aqueous mixture. Use 10 mL of dichloromethane for extraction, and purify the crude product by silica gel chromatography, using dichloromethane / methanol = (v / v = 10:1) for elution, and vacuum drying at 30°C 10Pa to obtain compound V-DPA;

[0051]

[0052] S4. Weigh 0.5 mmmol compound V-DPA and 0.25 mmol 2-chloro-1-formyl-3-hydroxymethylenecyclohexene, add 0.25 mL acetic anhydride, 0.25 mL triethylamine and 0.25 mL acetic acid respectively, react at 20°C for 22 h, cool to room temperature, add 5 mL deionized water, extract with 10 mL dichloromethane, and purify the crude product by silica gel chromatography, eluting with dichloromethane / methanol = (v / v = 10:1), and dry in vacuo at 30°C 10 Pa to obtain compound IRLy-DPA.

[0053]

[0054] Example 2 Preparation of IRLy Compound

[0055] S1. Weigh 3 mmol of 6-bromobenz[cd]indol-2(1H)-one, dissolve in 8 mL of anhydrous DMF, and add 15 mmol of NaH at low temperature. After completion, continue to stir in an ice bath for 10 min, add 5 mmol of iodoethane, and stir at 50°C for 4 h. After the reaction, add 16 mL of deionized water and extract with 10 mL of ethyl acetate. The crude product is purified by silica gel chromatography, eluted with petroleum ether / ethyl acetate (v / v=10:1), and dried in a vacuum at 30°C and 10 Pa to obtain product II;

[0056]

[0057] S2. Weigh 2mmol of compound II, 5mmol of 4,4'-dimethoxydiphenylamine, and 3mmol of sodium tert-butoxide, add 20mL of anhydrous acetonitrile to dissolve, then add 0.12mmol of tri-tert-butylphosphine and 0.08mmol of palladium catalyst under nitrogen atmosphere, and react at 80°C for 24h. After the reaction, add 15mL of acetone to dilute, filter, and purify the crude product by silica gel chromatography, using petroleum ether / ethyl acetate = (v / v = 5:1) for elution, and vacuum dry at 30°C 10Pa to obtain compound IV-MeO;

[0058]

[0059] S3. 1 mmol of compound IV-MeO was dissolved in 10 mL of tetrahydrofuran, 3 mmol of methylmagnesium chloride solution was added dropwise, and the mixture was reacted at 60°C for 2 hours. After the reaction, the reaction mixture was poured into 30 mL of 5% dilute hydrochloric acid and 2.5 mmol of KI was added to the aqueous mixture. The mixture was extracted with dichloromethane, and the crude product was purified by silica gel chromatography, eluted with dichloromethane / methanol = (v / v = 10:1), and dried under vacuum at 30°C and 10 Pa to obtain compound V-MeO;

[0060]

[0061] S4. Weigh 0.5 mmmol compound V-MeO and 0.125 mmol 2-chloro-1-formyl-3-hydroxymethylenecyclohexene, add 0.25 mL acetic anhydride, 0.25 mL triethylamine and 0.25 mL acetic acid respectively, react at 60°C for 0.5 h, cool to room temperature, add 5 mL deionized water, extract with 10 mL dichloromethane, and purify the crude product by silica gel chromatography, eluting with dichloromethane / methanol = (v / v = 10:1), and dry in vacuo at 30°C 10 Pa to obtain compound IRLy-MeO.

[0062]

[0063] Example 3 Preparation of IRLy-tBu Compound

[0064] S1. Weigh 3 mmol of 6-bromobenz[cd]indol-2(1H)-one, dissolve it in 8 mL of anhydrous toluene, and add 15 mmol of NaH at low temperature. After completion, continue to stir in an ice bath for 10 min, add 15.0 mmol of iodoethane, and stir at 80°C for 12 h. After the reaction, add 16 mL of deionized water and extract with 10 mL of ethyl acetate. The crude product is purified by silica gel chromatography, eluted with petroleum ether / ethyl acetate (v / v=10:1), and dried in a vacuum at 30°C and 10 Pa to obtain product II;

[0065]

[0066] S2. Weigh 2mmol of compound II, 2.0mmol of 4,4'-di-tert-butyldiphenylamine, and 3mmol of sodium tert-butoxide, add them to 20mL of anhydrous DMF to dissolve, then add 0.12mmol of tri-tert-butylphosphine and 0.08mmol of palladium catalyst under nitrogen atmosphere, and react at 110°C for 12h. After the reaction, add 15mL of acetone to dilute, filter, and purify the crude product by silica gel chromatography, using petroleum ether / ethyl acetate = (v / v = 5:1) for elution, and vacuum dry at 30°C 10Pa to obtain compound IV-tBu;

[0067]

[0068] S3. Dissolve 1 mmol of compound IV-tBu in 10 mL of tetrahydrofuran, dropwise add 5 mmol of methylmagnesium chloride solution, and react at 100 °C for 0.5 h. After the reaction is completed, pour the reaction mixture into 30 mL of 5% dilute hydrochloric acid, and at the same time add 2.5 mmol of KI to the aqueous mixture. Extract with dichloromethane, purify the crude product by silica gel chromatography, elute with dichloromethane / methanol = (v / v = 10:1), and dry under vacuum at 30 °C and 10 Pa to obtain compound V-tBu;

[0069]

[0070] S4. Weigh 0.5 mmol of compound V-tBu and 0.1 mmol of 2-chloro-1-formyl-3-hydroxymethylenecyclohexene, add 0.25 mL of acetic anhydride, 0.25 mL of triethylamine and 0.25 mL of acetic acid respectively, react at 100 °C for 3 h, cool to room temperature, add 5 mL of deionized water, extract with 10 mL of dichloromethane, purify the crude product by silica gel chromatography, elute with dichloromethane / methanol = (v / v = 10:1), and dry under vacuum at 30 °C and 10 Pa to obtain compound IRLy-tBu.

[0071]

[0072] Experimental Example:

[0073] Prepare a 10 mM stock solution of the compound (IRLy-MeO) obtained in Example 2 with DMSO and store it in a 4 °C refrigerator protected from light. Before use, dilute it to the target concentration with the corresponding diluent.

[0074] Experimental Example 1

[0075] Using tetrahydrofuran and water as the system, prepare 10 μM IRLy-MeO solutions with 0 - 90% water percentages of the compound (IRLy-MeO) obtained in Example 2. Take 1 mL and add it to a microcuvette, and use a fluorescence spectrophotometer (slit width = 29.4 nm, excitation wavelength = 980 nm) to sequentially record the fluorescence intensities at 1050 - 1550 nm.

[0076] The results are as Figure 4 shown. As the water percentage increases, the fluorescence emission peak of the compound (IRLy-MeO) redshifts and intensifies (F / F0 = 5.2 times), demonstrating that the compound (IRLy-MeO) has AIE properties.

[0077] Experimental Example 2

[0078] The compound (IRLy-MeO) obtained in Example 2 was diluted with deionized water to 20 μM. 200 μL was taken and placed in a 1.5 mL centrifuge tube. The position and angle of the centrifuge tube were adjusted so that the laser beam with a wavelength of 1064 nm passed through the liquid surface and the laser focus was at the center of the liquid. The changes in temperature over time within 10 min under the irradiation of a 0.8 W / cm 2 laser power and within 10 min after the irradiation was stopped were recorded separately by a thermal imager. The photothermal conversion efficiency was calculated from the cooling curve.

[0079] As Figure 5 shown, under the irradiation of a 1064 nm laser (0.8 W / cm 2 ), the photothermal conversion efficiency of the prepared IRLy-MeO was 59.33%.

[0080] Experimental Example 3

[0081] The compound (IRLy-MeO) obtained in Example 2 was diluted with deionized water to 20 μM. At the same time, a 15 μM ICG solution was prepared. 200 μL was taken from each and placed in a 1.5 mL centrifuge tube. The position and angle of the centrifuge tube were adjusted so that the laser beams with wavelengths of 1064 nm and 808 nm passed through the liquid surfaces respectively and the laser foci were at the centers of the liquids. The changes in temperature over time during 10 radiation-cooling cycles were recorded separately by a thermal imager under a 0.8 W / cm 2 laser power.

[0082] As Figure 6 shown, compared with ICG, the compound (IRLy-MeO) proved to have good photothermal stability.

[0083] Experimental Example 4

[0084] Select mouse glioma cells GL261 in the logarithmic growth phase. After digestion with trypsin, collect them into the medium containing serum. Centrifuge the cell suspension, resuspend the cells with the medium, count the cells and dilute them to 50,000 cells / mL, and inoculate them in a 96-well plate. After culturing in a CO2 incubator at 37 °C, 5% CO2 and 95% relative humidity for 24 hours, add IRLy-MeO at different concentrations (30 μM, 25 μM, 20 μM, 15 μM, 10 μM, 5 μM, 0 μM) and culture for 24 hours. Carefully aspirate the supernatant (cell culture medium), then add 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, 100 μL per well) solution at 0.5 mg / mL, and culture in the dark for 4 hours. After aspirating the supernatant (cell culture medium), add DMSO (150 μL) to dissolve it. After gently shaking on a shaker, measure the absorbance at a wavelength of 490 nm using a multi-functional microplate reader, and calculate the cell survival rate by the MTT method. At the same time, another photothermal toxicity experiment is carried out. After the GL261 cells are seeded and adhered, administer the drug (IRLy). After co-culturing for 4 h, irradiate with a 1064 nm laser (0.8 W / cm 2 ) for 6 min and then continue to culture for 12 h. Use the MTT method to measure the OD values of the cells in the experimental group and the control group. The data obtained above are used to calculate the cell growth viability by the following formula: Viability (%) = (average absorbance value of the experimental group / average absorbance value of the control group) * 100%.

[0085] As Figure 7 shown, in the dark environment, IRLy-MeO is non-toxic to cancer cells, and shows strong photothermal toxicity after laser irradiation, indicating that the present invention has good biosafety and photothermal toxicity.

[0086] Experimental Example 5

[0087] In vivo photothermal: Use GL261 to establish a subcutaneous xenograft tumor model in mice. When the tumor volume reaches about 100 mm 3 , after encapsulating IRLy-MeO, intravenously administer it to the tumor-bearing mice. 8 hours later, irradiate with a 1064 nm laser (0.8 W / cm 2 , for 10 minutes) and record the change of the tumor area temperature with time through an infrared thermal imager. The results are as Figure 8 .

[0088] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A near-infrared second near-infrared region AIE cyanine compound, characterized in that, The structure is shown in formula (I): Among them, R is a hydrogen atom, methyl group, methoxy group, sec-butyl group, tert-butyl group, hydroxyl group; X is Cl - , Br - , I - , PF6 - , BF4 - .

2. The preparation method of the near-infrared II AIE cyanine compound according to claim 1, characterized in that, The steps include: S1. 6-bromobenz[cd]indol-2(1H)-one and iodoethane are thoroughly mixed and heated to 20-80°C for reaction for 4-24 hours, followed by post-treatment to obtain a compound represented by formula (II); The molar ratio of 6-bromobenz[cd]indol-2(1H)-one to ethyl iodide is 1:1 to 1:

5. S2. dissolving the compound represented by formula (II) and formula (III) in an organic solvent, heating to 20-110° C. in the presence of a catalyst, reacting for 12-48 hours, and post-treating to obtain a compound represented by formula (IV); The molar ratio of the compound represented by formula (II) to the compound represented by formula (III) is 1:1 to 1:5 S3. The compound represented by formula (IV) and methyl magnesium chloride are dissolved in an organic solvent, heated to 20-100°C for reaction for 0.5 to 12 hours, and the corresponding salt of X is added during post-treatment to obtain formula (V); The molar ratio of the compound represented by formula (IV) to methyl magnesium chloride is 1:1 to 1:5 S4. The compound represented by formula (V) and 2-chloro-1-formyl-3-hydroxymethylenecyclohexene are dissolved in an organic solvent, heated at 20-110° C. for reaction for 0.5 to 12 hours, and then post-treated to obtain; The molar ratio of the compound represented by formula (V) to 2-chloro-1-formyl-3-hydroxymethylenecyclohexene is 2:1 to 4:1 The structural formulas of the compounds of formula (II), formula (III), formula (IV) and formula (V) are as follows: Among them, R is a hydrogen atom, methyl, methoxy, n-butyl, sec-butyl, tert-butyl, hydroxyl; X is Cl - , Br - , I - , PF6 - , BF4 - .

3. The preparation method of the near-infrared region II AIE cyanine compound according to claim 2, characterized in that In step S1, the organic solvent is one of anhydrous acetonitrile, anhydrous toluene, anhydrous dimethylformamide, and anhydrous ethanol.

4. The preparation method of the near-infrared II AIE cyanine compound according to claim 2, wherein In step S2, the organic solvent is one of anhydrous acetonitrile, anhydrous toluene or anhydrous dimethylformamide.

5. The preparation method of the near-infrared II AIE cyanine compound according to claim 2, wherein, In step S3, the organic solvent is one of anhydrous tetrahydrofuran, anhydrous ethanol or anhydrous acetonitrile.

6. The preparation method of the near-infrared region II AIE cyanine compound according to claim 2, wherein In step S4, the organic solvent is one or more of anhydrous tetrahydrofuran, anhydrous ethanol, anhydrous acetonitrile, acetic acid or acetic anhydride.

7. According to the preparation method described in claim 2, characterized in that, The catalyst in step S2 is one of bis(tri-tert-butylphosphine), tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium(0)chloroform adduct, palladium acetate or tris(dibenzylideneacetone)dipalladium.

8. Use of the near-infrared zone II AIE cyanine compound according to claim 1 in the preparation of anti-deep tumor drugs.

9. Use of the near-infrared second-zone AIE cyanine compound according to claim 1 in the preparation of organic light-emitting materials.

10. Use of the infrared region II AIE cyanine compound according to claim 9 in the preparation of an organic light-emitting material, characterized in that, The organic luminescent material is a fluorescent probe, a biological imaging material, and a deep tumor diagnosis and treatment material.

Images