A red light emitting organic molecule and its preparation method and application

Abstract

This application discloses a deep red / near-infrared red-emitting organic molecule, its preparation method, and applications. The preparation method, conducted under relatively mild conditions, is simple, rapid, energy-efficient, and efficient. Raw materials and reagents are readily available and inexpensive, facilitating large-scale applications. This red-emitting organic molecule can emit fluorescence in the deep red / near-infrared region and be used for bioluminescent imaging. Furthermore, it can generate cytotoxic reactive oxygen species under light irradiation, promoting cell apoptosis and achieving sterilization and anti-cancer effects.

Description

Technical Field

[0001] The present application relates to a red light emitting organic molecule and a preparation method and application thereof, belonging to the technical field of synthesis of fluorescent compounds. Background Art

[0002] The study of deep red / near-infrared fluorescent molecules that emit solid-state light is a challenging task. Among the organic fluorescent materials reported so far, fluorescent molecules that emit light in the deep red / near-infrared region (λ=650-900nm) play a vital role in the field of bioimaging. This is because hemoglobin in organisms causes visible light to be absorbed, and it absorbs most of the blue-green light band in visible light. However, in the red light band of visible light greater than 600nm, the absorption effect of hemoglobin is very small. Therefore, in the reddish light region, a large amount of light can pass through tissues and skin and be detected, and the longer excitation wavelength is less harmful to tissues and organs than ultraviolet (UV) light. The design and development of red-emitting materials with multifunctional intelligent responsiveness and good stability are of great significance. They have broad application prospects in biomedical applications such as fluorescence bioimaging. Summary of the Invention

[0003] According to one aspect of the present application, a red-light-emitting organic molecule is provided. The present application uses a benzothiadiazole AIE photosensitizer to provide ideas for the design of photosensitizers and provides a method for the key problem of fluorescence aggregation quenching in traditional PDT. The reactions involved in the benzothiadiazole AIE photosensitizer used are all classic reactions, the raw materials are easily available, and the product purity is high. The benzothiadiazole-based AIE photosensitizer provided in the present application has an effective ROS-generating ability, also has good biocompatibility and can perform biological imaging, providing ideas for the design and synthesis of fluorescent molecules that can be used for integrated diagnosis and treatment.

[0004] This application adopts the following technical solutions:

[0005] A red light emitting organic molecule, wherein the chemical structure of the red light emitting organic molecule is:

[0006]

[0007] Wherein, the X atom is an S atom or a Se atom;

[0008] R1 and R3 are independently selected from hydrogen atom H, hydroxyl group -OH, alkoxy group -OR3, alkyl group -(CH2) n An electron-donating group in CH3;

[0009] R2 is selected from hydrogen atom H, alkyl -(CH2) n CH3, 0≤n<10.

[0010] Optionally, the red light emission is deep red and / or near infrared red light emission.

[0011] According to a second aspect of the present application, another method for preparing the above-mentioned red light-emitting organic molecule is provided, comprising the following steps:

[0012] S1, heating a mixture containing raw material I, diphenylamine or a diphenylamine derivative, catalyst I, ligand, base I, and organic solvent under an inert atmosphere to react I to obtain an intermediate;

[0013] The raw material I is selected from one of 4,7-dibromobenzo[c]-1,2,5-thiadiazole and 4,7-dibromobenzo[c]-1,2,5-selenodiazole;

[0014] S2, heating the material containing raw material II, the intermediate, base II, catalyst II, and solvent to react II to obtain the red light emitting organic molecule;

[0015] The raw material II is selected from the compounds of the following structural formula:

[0016] Wherein, R2 is selected from H, -(CH2) n CH3, 0≤n<10.

[0017] Optionally, the reaction I is a coupling reaction.

[0018] Optionally, the diphenylamine derivative is selected from the compounds of the following structural formula:

[0019] Wherein R1 and R3 are independently selected from -OH, -OR3, -(CH2) n One of CH3, 0≤n<10.

[0020] Optionally, the diphenylamine derivative is at least one selected from 4,4'-dimethoxydiphenylamine, p-hydroxydiphenylamine, p-methoxydiphenylamine, and carbazole.

[0021] Optionally, the raw material II is selected from 3,5-bis(methoxycarbonyl)phenylboronic acid.

[0022] Optionally, the catalyst I and catalyst II are independently selected from at least one of palladium acetate, cuprous iodide, and tetrakis(triphenylphosphine)palladium.

[0023] Optionally, the ligand is selected from at least one of tri-tert-butylphosphine and trans-1,4-diaminocyclohexane.

[0024] Optionally, the base I and base II are independently selected from at least one of sodium tert-butoxide, potassium phosphate, and sodium carbonate.

[0025] Optionally, the organic solvent is selected from at least one of toluene, methanol and ethanol.

[0026] Optionally, the solvent is water and / or an organic solvent.

[0027] Optionally, in step S1, the conditions of the heating reaction I include: reaction temperature of 90 to 120° C., and reaction time of 10 to 14 h.

[0028] Optionally, the conditions of the heating reaction II include: a reaction temperature of 60 to 110° C. and a reaction time of 10 to 14 hours.

[0029] Optionally, in step S1, the weight ratio of 4,7-dibromobenzo[c]-1,2,5-thiadiazole to diphenylamine or a diphenylamine derivative, catalyst I, ligand, and base I is 1:(0.5-1.5):(0.015-0.15):(0.1-0.5):(0.3-1.3).

[0030] Optionally, the solid-liquid ratio of 4,7-dibromobenzo[c]-1,2,5-thiadiazole to the organic solvent is 1 g:5 to 50 mL.

[0031] Optionally, in step S2, the weight ratio of 3,5-bis(methoxycarbonyl)phenylboronic acid to the intermediate, base II, and catalyst II is 1:(1-1.5):(1-1.5):(0.3-0.6).

[0032] Optionally, the solid-liquid ratio of 3,5-bis(methoxycarbonyl)phenylboronic acid to the solvent is 1 g:80-140 mL.

[0033] Optionally, in step S2, after heating reaction II, the following steps are further included:

[0034] The product after heating reaction II is dissolved in an organic solvent, and then a strong base solution is added to perform reaction III, and the pH is adjusted to 2-3 with an acid.

[0035] Optionally, the conditions of reaction III include: reaction temperature of 70-90° C., and reaction time of 10-30 h.

[0036] According to a third aspect of the present application, another application of the above-mentioned red light-emitting organic molecule or the red light-emitting organic molecule prepared according to the above-mentioned preparation method in cell imaging is provided.

[0037] According to the fourth aspect of the present application, another application of the above-mentioned red light-emitting organic molecule or the red light-emitting organic molecule prepared according to the above-mentioned preparation method in a soluble fluorescent probe material is provided, characterized in that the application includes the application of the red light-emitting organic molecule as a fluorescent probe in in vivo imaging.

[0038] According to the fifth aspect of the present application, there is provided another use of the above-mentioned red light-emitting organic molecule or the red light-emitting organic molecule prepared according to the above-mentioned preparation method in the preparation of anticancer drugs or sterilization materials that can sensitize chemotherapy, photodynamic therapy, and immunotherapy, characterized in that the red light-emitting organic molecule produces reactive oxygen under light.

[0039] According to the sixth aspect of the present application, another red light-emitting organic molecule mentioned above or a red light-emitting organic molecule prepared according to the above preparation method is provided as a mechanical force sensitive material for use in mechanical sensing, data storage, anti-counterfeiting materials, rewritable optoelectronic application materials, active switching materials, and biosensors.

[0040] The beneficial effects of this application include:

[0041] The red-light-emitting organic molecules prepared in the present application have good biocompatibility and a relatively stable structure. They are not easily degraded in the body and are self-fluorescent. They do not require modification with other fluorescent groups or loading with other fluorescent molecules. The components are relatively simple, which can effectively reduce the impact of adding components on the organic molecular structure.

[0042] Compared with other organic molecules, the present invention can be prepared by a relatively simple method that is suitable for practical applications, and the raw materials are cheap and easily available. The synthesis and purification steps are highly operational. By optimizing the process and appropriately expanding the synthesis scale, the commercialization and application of the drug can be achieved.

[0043] The red-light-emitting organic molecules provided in this application have bright red fluorescence properties in vivo when used in the field of cell imaging. When used as a tool for cell imaging, obvious luminescence can be observed at a relatively low concentration. The excitation wavelength is relatively long, which is less harmful to the organism. When used in anti-tumor drugs, they have the effect of sensitizing chemotherapy, photodynamic therapy, and immunotherapy. When used as a mechanically sensitive material, they can be used as an intelligent material to respond to external stimuli. The sensitivity of the material to mechanical force makes it have huge potential application value in the fields of optical materials such as mechanical sensing, data storage, anti-counterfeiting materials, rewritable optoelectronic application materials, active switch materials, and biosensors. When used as a solvatochromic fluorescent probe, its fluorescence behavior has a strong dependence on organic liquids, especially for some common organic solvents with similar structures and properties. It has significant distinguishing ability. The fluorescence emission wavelength almost covers the entire visible light region, and can be used as a very ideal solvatochromic fluorescent probe material. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 This is a bar graph of cell viability detected by CCK8 of the compound prepared in Example 1 of the present application.

[0045] Figure 2 This is a graph of cellular uptake of the compound prepared in Example 1 over 12 hours.

[0046] Figure 3 This is an ultraviolet spectrum of the compound prepared in Example 1 that generates singlet oxygen over time of illumination.

[0047] Figure 4 This is the aggregation-induced emission property spectrum of the molecule in test example 3.

[0048] Figure 5 This is the fluorescence emission spectrum of Test Example 6.

[0049] Figure 6 This is the fluorescence emission spectrum of Example 4 in different types of organic solvents. DETAILED DESCRIPTION

[0050] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0051] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0052] Unless otherwise specified, conventional methods were used for testing, and instrument settings were those recommended by the manufacturer.

[0053] The UV spectrum of singlet oxygen was measured using a Perkin-Elmer Lambda 365 UV / Vis spectrophotometer at room temperature.

[0054] The fluorescence emission spectra of the aggregation-induced emission effect were measured using an Edinburgh Instruments FLS1000 fluorescence spectrometer at room temperature.

[0055] CCK8 assay was used to detect cell viability using the following method: CCK-8 assay was used to detect cell viability. Cells were cultured in 95% air, 5% carbon dioxide using double-antibody α-MEM medium containing 5% fetal bovine serum and 100 U / mL at a constant temperature of 37°C. The culture medium was changed every 2 days, and cells were passaged every 3-5 days. RAW 264.7 macrophages were then seeded in 96-well plates. 2B at different concentrations (0, 2.5, 5, 10, 20, 40, 80 μg / mL) was added to each well 24, 48, and 72 hours after treatment. 10 μL of CCK-8 reagent was added to each well for CCK-8 assay. The cells were then incubated in the dark at 37°C for 2 hours and then detected on a microplate reader. The absorbance values ​​measured were converted to the 0 group (control group) as the benchmark (100% survival rate) to calculate the cell survival rate of each group. The calculation formula is as follows:

[0056] Cell viability (%) = (average OD value of experimental group / average OD value of control group) * 100%. Live and dead cell staining was used to assess cell viability. RAW264.7 cells were seeded in 24-well plates at a density of 5 × 104 cells / well. 24 hours after seeding, different concentrations of 2B (0, 2.5, 5, 10, 20, 40, and 80 μg / mL) were added to each well and incubated for 24 hours. After aspirating the culture medium, approximately 250 μL of Calcein AM / PI working solution was added between each well and incubated at 37°C in the dark for 30 minutes. The cells were then observed under a fluorescence microscope for staining.

[0057] Cell uptake image. RAW264.7 cells were seeded at the same seeding density onto confocal microplates. 24 hours after seeding, 10 μg / mL of 2B was added to each well and incubated at 37°C for 24 hours. Hoechst 33258 nuclear stain and mitotracker mitochondrial stain were then added at a concentration of 50 nM and incubated for 1 hour (the probe-containing culture medium must be preheated at 37°C). The cells were then washed twice and observed under a confocal microscope.

[0058] Example 1

[0059] Preparation of compound 1A:

[0060]

[0061] 4,7-Dibromobenzo[c]-1,2,5-thiadiazole (3.14 g, 10.68 mmol), diphenylamine (1.80 g, 10.68 mmol), palladium acetate (0.06 g, 0.26 mmol), tri-tert-butylphosphine (1.10 g, 5.34 mmol), and sodium tert-butoxide (1.30 g, 17.36 mmol) were mixed with toluene (20 mL) and heated at 110°C under a nitrogen atmosphere for 12 hours. The mixture was then extracted with dichloromethane (DCM), and the organic phase was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with DCM:petroleum ether (PE) = 1:5, v:v, to obtain the intermediate as an orange-yellow solid (1.52 g, 60% yield).

[0062] A toluene (120 ml) solution of the intermediate (1.52 g, 3.98 mol) and an ethanol (24 ml) solution of 3,5-bis(methoxycarbonyl)phenylboronic acid (1.20 g, 5.04 mmol) were added to a water (8 ml) solution of sodium carbonate (1.48 g, 14 mmol). After the mixture was stirred for 10 minutes, tetrakis(triphenylphosphine)palladium (0.46 g, 0.4 mmol) was added. The temperature was raised to 80°C and the reaction was refluxed for 12 hours. The reaction solution was cooled to room temperature, most of the solvent was evaporated at low pressure, and the reaction solution was extracted three times with DCM. The extracts were combined and dried over anhydrous sodium sulfate, filtered, and dried. The pure product was obtained by column chromatography (chromatographic solution PE: DCM = 1:1R f =0.5) was an orange solid (1.52 g, yield 90%). The results of the nuclear magnetic resonance test are as follows: 1 H NMR(600MHz,Chloroform-d)δ8.81(d,J=1.5Hz,2H),8.73-8.71(m,1H),7.68(dd,J=7.7,0.7Hz,1H),7.32-7.28(m,4 H),7.24(dd,J=7.7,0.9Hz,1H),7.12(td,J=3.2,2.8,0.9Hz,4H),7.10(td,J=2.0,1.2Hz,2H),3.99(d,J=0.8Hz,6H). 13 C NMR(151MHz,Chloroform-d)δ166.36,154.68,151.27,147.64,140.28,138.40,1 34.23,131.09,129.88,129.41,129.24,126.77,124.53,123.87,122.73,52.60.

[0063] Example 2

[0064] Preparation of compound 1B:

[0065]

[0066] A solution of 1A (1.52 g) prepared in Example 1 in methanol (100 ml) and a 4% NaOH solution in water (100 ml) were added to a 500 ml flask and refluxed at 80°C for 24 h until the solid dissolved. The reaction solution was cooled to room temperature and filtered. Concentrated hydrochloric acid was added to the mother liquor to adjust the pH to 2-3, and an orange solid precipitated. After filtration, the solid was dried in a vacuum drying oven (1.43 g, 100% yield). The results of the NMR test are as follows: 1H NMR (400MHz, DMSO-d6) δ13.40(s,2H),8.71(t,J=1.2Hz,2H),8.48(q,J=1.4Hz,1H),7.92(d,J=7.8H z,1H),7.28(t,J=7.7Hz,4H),7.23(d,J=7.8Hz,1H),7.09-7.03(m,2H),7.01(dt,J=8.5,1.1Hz,4H). 13 C NMR(101MHz,DMSO-d6)δ167.08,154.62,151.41,147.69,139.92,138.30, 133.94,132.22,130.29,129.96,129.61,126.70,124.41,124.08,123.99.

[0067] Example 3

[0068] Preparation of compound 2A:

[0069]

[0070] 4,7-Dibromobenzo[c]-1,2,5-thiadiazole (3.14 g, 10.68 mmol), 4,4'-dimethoxydiphenylamine (2.44 g, 10.68 mmol), palladium acetate (0.06 g, 0.26 mmol), tri-tert-butylphosphine (1.10 g, 5.34 mmol), and sodium tert-butoxide (1.30 g, 17.36 mmol) were mixed with toluene (20 mL) and heated to 110°C under a nitrogen atmosphere for 12 hours. The mixture was then extracted with DCM, and the organic phase was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (DCM:PE = 1:3, v:v) to obtain a red solid intermediate (60% yield).

[0071] A toluene (200ml) solution of the intermediate (3g, 6.80mmol) and an ethanol (28ml) solution of 3,5-bis(methoxycarbonyl)phenylboronic acid (1.93g, 8.11mmol) were added to a water (15ml) solution of sodium carbonate (2.43g, 22.90mmol). After the mixture was stirred for 10min, tetrakis(triphenylphosphine)palladium (0.76g, 0.66mmol) was added. The temperature was raised to 80°C and the reaction was refluxed for 12 minutes. The reaction solution was cooled to room temperature, most of the solvent was evaporated at low pressure, and the reaction solution was extracted three times with DCM. The extracts were combined and dried over anhydrous sodium sulfate, filtered, and dried. The pure product was obtained by column chromatography (chromatographic liquid PE:DCM=1:1R f =0.5) was a red solid (3.40 g, yield 90%). The results of the nuclear magnetic resonance test are as follows:1 H NMR(400MHz,Chloroform-d)δ8.79(d,J=1.6Hz,2H),8.69(t,J=1.6Hz,1H),7.62(d,J=7 .8Hz,1H),7.06-7.02(m,4H),7.02(s,1H),6.88-6.82(m,4H),3.98(s,6H),3.82(s,6H). 13 C NMR(101MHz,DMSO-d6)δ165.94,156.42,154.63,150.42,141.28,141.16,138.92 ,133.84,131.12,130.65,128.79,126.57,123.90,119.87,115.22,55.76,53.19.

[0072] Example 4

[0073] Preparation of compound 2B:

[0074]

[0075] A solution of 2A (3.40 g) in methanol (100 ml) and a 4% NaOH solution in water (100 ml) were added to a 500 ml flask and refluxed at 80°C for 24 h until the solid dissolved. The reaction solution was cooled to room temperature and filtered. Concentrated hydrochloric acid was added to the mother liquor to adjust the pH to 2-3, and an orange solid precipitated. After filtration, the solid was dried in a vacuum drying oven (3.22 g, 100% yield). The NMR test results are as follows: 1 HNMR(600MHz,DMSO-d6)δ13.40(s,2H),8.72(d,J=1.6Hz,2H),8.48(t,J=1.6Hz ,1H),7.88(d,J=7.9Hz,1H),7.01-6.97(m,5H),6.91-6.87(m,4H),3.75(s,6H). 13 C NMR(151MHz,DMSO-d6)δ167.14,156.37,154.67,150.48,141.20,141.10, 138.52,133.73,132.15,130.45,129.28,126.53,120.04,115.21,55.71.

[0076] Example 5

[0077] Preparation of compound 3A:

[0078]

[0079] 4,7-Dibromobenzo[c]-1,2,5-thiadiazole (4.18 g, 14.20 mmol), p-hydroxydiphenylamine (2.63 g, 14.20 mmol), palladium acetate (0.078 g, 0.35 mmol), tri-tert-butylphosphine (1.44 g, 7.10 mmol), and sodium tert-butoxide (2.20 g, 17.36 mmol) were mixed with 30 mL of toluene and heated to 110°C under a nitrogen atmosphere for 12 hours. The mixture was then extracted with dichloromethane (DCM), and the organic phase was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography with pure DCM to obtain the intermediate as a red solid (60% yield).

[0080] A solution of the intermediate (2.00 g, 5.04 mmol) in toluene (100 ml) and a solution of 3,5-bis(methoxycarbonyl)phenylboronic acid (1.43 g, 6.01 mmol) in ethanol (20 ml) were added to a solution of sodium carbonate (2.00 g, 18.90 mol) in water (10 ml). The mixture was stirred for 10 minutes, and then tetrakis(triphenylphosphine)palladium (0.58 g, 0.66 mmol) was added. The temperature was raised to 80°C and the reaction was refluxed for 12 hours. The reaction solution was cooled to room temperature, most of the solvent was evaporated at low pressure, and the reaction solution was extracted three times with DCM. The extracts were combined and dried over anhydrous sodium sulfate, filtered, and dried. The pure product was obtained by column chromatography. The chromatographic solution was DCM: ethyl acetate (EA) = 1:1R f =0.5, a red solid (2.30 g, yield 90%). The results of the nuclear magnetic resonance test are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.80(d,J=1.6Hz,2H),8.71(t,J=1.6Hz,1H),7.65(d,J=7.8Hz,1H),7.28(d,J= 1.8Hz,1H),7.24(d,J=1.6Hz,1H),7.15(d,J=7.8Hz,1H),7.07-6.99(m,5H),6.84-6.79(m,2H),3.98(s,6H). 13 C NMR(151MHz,DMSO-d6)δ165.95,155.37,154.52,150.84,148.28,140.71,138.97,138.72,133 .92,131.05,130.48,129.69,129.01,128.02,124.86,123.07,121.87,120.68,116.81,53.14.

[0081] Example 6

[0082] Preparation of compound 3B:

[0083]

[0084] A solution of 3A (2.30 g) in methanol (100 ml) and a 4% NaOH solution in water (100 ml) were added to a 500 ml flask and refluxed at 80°C for 24 h until the solid dissolved. The reaction solution was cooled to room temperature and filtered. Concentrated hydrochloric acid was added to the mother liquor to adjust the pH to 2-3, and a red solid precipitated. After filtration, the solid was dried in a vacuum drying oven (2.19 g, 100% yield). The NMR test results are as follows: 1 HNMR (600MHz, DMSO-d6) δ13.41(s,2H),9.47(s,1H),8.73(d,J=1.6Hz,2H),8.49(t,J=1.6Hz,1H),7.92(d,J=7 .8Hz,1H),7.27-7.20(m,2H),7.13(d,J=7.8Hz,1H),7.02-6.96(m,3H),6.93-6.87(m,2H),6.80-6.74(m,2H). 13 C NMR (151MHz, DMSO-d6) δ167.10,155.42,154.61,150.97,148.36,140.56,138.95,138. 43,133.82,132.20,130.39,129.58,129.43,127.95,125.47,122.86,122.12,116.86.

[0085] Example 7

[0086] Preparation of compound 4A:

[0087]

[0088] 4,7-Dibromobenzo[c]-1,2,5-thiadiazole (4.18 g, 14.20 mmol), p-methoxydiphenylamine (2.74 g, 14.20 mmol), palladium acetate (0.078 g, 0.35 mmol), tri-tert-butylphosphine (1.44 g, 7.10 mmol), and sodium tert-butoxide (2.20 g, 17.36 mmol) were mixed with 30 mL of toluene and heated to 110°C under a nitrogen atmosphere for 12 hours. The mixture was then extracted with dichloromethane (DCM), and the organic phase was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography and purified with pure DCM to obtain a red solid intermediate in a 60% yield.

[0089] A solution of the intermediate (2.10 g, 5.04 mmol) in toluene (100 ml) and a solution of 3,5-bis(methoxycarbonyl)phenylboronic acid (1.43 g, 6.01 mmol) in ethanol (20 ml) were added to a solution of sodium carbonate (2.00 g, 18.90 mmol) in water (10 ml). The mixture was stirred for 10 minutes, and then tetrakis(triphenylphosphine)palladium (0.58 g, 0.66 mmol) was added. The temperature was raised to 80°C and the reaction was refluxed for 12 hours. The reaction solution was cooled to room temperature, most of the solvent was evaporated under reduced pressure, and the reaction solution was extracted three times with DCM. The extracts were combined and dried over anhydrous sodium sulfate, filtered, and dried. The pure product was obtained by column chromatography, with the chromatographic solution being DCM: ethyl acetate (EA) = 1:1R f =0.5, a red solid (2.30 g, yield 90%). The results of the nuclear magnetic resonance test are as follows: 1 H NMR (400MHz, DMSO-d6) δ8.76(d,J=1.6Hz,2H),8.50(t,J=1.8Hz,1H),7.93(d,J=7.8Hz,1H),7.26(dd,J=9.1,6.4Hz,2H),7.1 5(d,J=7.8Hz,1H),7.07(dd,J=8.8,6.5Hz,2H),7.02(d,J=7.4Hz,1H),6.94(dd,J=8.6,3.8Hz,4H),3.93(s,6H),3.76(s,3H). 13 C NMR 101MHz, DMSO-d6)δ166.02,159.48,156.59,146.92,145.68,141.34,137.44,137.04,132.21,13 1.29,130.74,130.47,128.98,125.77,125.64,125.41,123.27,122.92,114.82,55.32,52.45.

[0090] Example 8

[0091] Preparation of compound 4B:

[0092]

[0093] A solution of 4A (2.30 g) in methanol (100 ml) and a 4% NaOH solution in water (100 ml) were added to a 500 ml flask and refluxed at 80°C for 24 h until the solid dissolved. The reaction solution was cooled to room temperature and filtered. Concentrated hydrochloric acid was added to the mother liquor to adjust the pH to 2-3, and a red solid precipitated. After filtration, the solid was dried in a vacuum drying oven (2.19 g, 100% yield). The NMR test results are as follows: 1HNMR(400MHz,DMSO-d6)δ13.43(s,2H),8.73(d,J=1.6Hz,2H),8.50(t,J=1.6Hz,1H),7.92(dd,J=7.9,1.2Hz,1H),7.29-7 .22(m,2H),7.16(dd,J=7.8,0.9Hz,1H),7.11-7.05(m,2H),7.02(td,J=7.3,1.0Hz,1H),6.96-6.90(m,4H),3.76(s,3H). 13 C NMR(101MHz,DMSO-d6)δ167.12,156.85,154.63,151.04,148.19,140.56,140.36,138.38, 133.85,132.22,130.33,129.70,129.50,127.49,125.81,123.23,122.45,115.43,55.78.

[0094] Example 9

[0095] Preparation of compound 5A:

[0096]

[0097] Combine 4,7-dibromobenzo[c]-1,2,5-thiadiazole (2.00 g, 6.80 mmol), carbazole (2.74 g, 6.80 mmol), trans-1,4-diaminocyclohexane (0.20 ml), cuprous iodide (0.21 g, 1.10 mmol), and potassium phosphate (2.20 g, 15.50 mmol) with 60 mL of toluene. Heat to 110°C under a nitrogen atmosphere and reflux for 24 hours. The mixture is then diluted with EA, filtered through Celite, and the organic phase is dried over anhydrous sodium sulfate. The solvent is concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography using PE:DCM = 5:1 to obtain a red solid intermediate (60% yield).

[0098] A toluene (100 ml) solution of the intermediate (1.70 g, 4.20 mmol) and an ethanol (20 ml) solution of 3,5-bis(methoxycarbonyl)phenylboronic acid (1.43 g, 6.01 mmol) were added to a water (10 ml) solution of sodium carbonate (2.00 g, 18.90 mmol). After the mixture was stirred for 10 minutes, tetrakis(triphenylphosphine)palladium (0.58 g, 0.66 mmol) was added. The temperature was raised to 80°C and the reaction was refluxed for 12 hours. The reaction solution was cooled to room temperature, most of the solvent was evaporated at low pressure, and the reaction solution was extracted three times with DCM. The extracts were combined and dried over anhydrous sodium sulfate, filtered, and dried. The pure product was obtained by column chromatography, with the chromatographic solution PE:DCM=3:1R f =0.5, a red solid (2.30 g, yield 90%). The results of the nuclear magnetic resonance test are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.93(dt,J=4.1,1.5Hz,1H),8.83(d,J=1.8Hz,1H),8 .06-7.95(m,1H),7.45-7.30(m,2H),7.23(d,J=8.1Hz,1H),4.03(d,J=1.2Hz,2H). 13 C NMR (151MHz, DMSO-d6) δ165.81,154.36,151.93,141.10,134.53,131.28,129.82,129.47,129.03,126.66,123.59,120.94,111.27,53.27.

[0099] Example 10

[0100] Preparation of compound 5B:

[0101]

[0102] A solution of 5A (2.30 g) in methanol (100 ml) and a 4% NaOH solution in water (100 ml) were added to a 500 ml flask and refluxed at 80°C for 24 h until the solid dissolved. The reaction solution was cooled to room temperature and filtered. Concentrated hydrochloric acid was added to the mother liquor to adjust the pH to 2-3, and a red solid precipitated. After filtration, the solid was dried in a vacuum oven (2.19 g, 100% yield). The NMR test results are as follows: 1HNMR(600MHz,DMSO-d6)δ8.87(d,J=1.6Hz,1H),8.61(s,0H),8.32-8.28(m,1H),8.25(d,J=7.4Hz,1H),8.14(d,J=7.5Hz, 1H),7.39(ddd,J=8.2,7.1,1.3Hz,1H),7.32(ddd,J=7.9,7.1,1.0Hz,1H),7.29(dt,J=8.2,0.8Hz,1H),2.52-2.48(m,2H). 13 C NMR(101MHz,DMSO-d6)δ167.65,167.03,154.43,151.98,141.14,137.98,134.43, 132.41,131.67,130.98,130.11,129.90,129.66,126.68,123.59,120.94,111.28.

[0103] Test Example 1

[0104] The cell viability was detected by CCK8 using compound 2B prepared in Example 4, and the cell uptake graph of compound 1A prepared in Example 1 was obtained. The results are shown in FIG. Figure 1 As shown in Figure 2, the molecule shows good uptake, low cytotoxicity and co-localization with mitochondria. It can be seen that the red light-emitting organic molecules prepared in this application can be used as fluorescent probes for cell imaging.

[0105] Test Example 2

[0106] The ability of Example 1 to generate singlet oxygen was investigated. 1,3-Diphenylisobenzofuran (DPBF) is one of the most active singlet oxygen scavengers known. DPBF can react with 1 O2 reacts to form endoperoxides, which are unstable and convert to 1,2-dibenzoylbenzene. The consumption of DPBF can be reflected by observing the decrease in the absorption of DPBF at its maximum absorption wavelength of 418nm, that is, 1 The amount of O2 present. Compound 1A prepared in Example 1 was mixed with DPBF, and the UV spectra at different times were detected. The results were as follows: Figure 3 As shown, with the change of irradiation time (0 min, 1 min, 2 min, 3 min, 5 min, 7 min, 10 min, 15 min, 20 min from top to bottom in the figure), the absorption intensity of DPBF also changes, indicating that the molecule can effectively generate singlet oxygen and can be used for photodynamic therapy.

[0107] Test Example 3

[0108] The aggregation-induced emission effect of the organic molecule compound 1B prepared in Example 2 was investigated in dimethyl sulfoxide (DMSO) solution. The concentration of 1B was 1×10 -4 M, detect its fluorescence emission intensity, the fluorescence emission excitation wavelength is 467nm, the results are as follows Figure 4 It was investigated whether Examples 1-10 all had the aggregation-induced emission effect, and the test results of Examples 1-10 were similar to those of Test Example 3.

[0109] Test Example 4

[0110] The mechanochromic effect of compound 1B prepared in Example 2 was investigated. Stimuli-responsiveness, as an application branch of fluorescent materials, refers to the material's significant changes in luminescence behavior under external stimuli such as heat, pressure, light, solvent, and pH, including changes in emission intensity and blue / red shifts in emission wavelength.

[0111] The fluorescence emission spectra of compound 1B prepared in Example 2 before and after grinding were detected. The grinding conditions were manual grinding using an agate mortar. The results were as follows: Figure 5 As shown, the emission wavelength of the molecule is red-shifted after grinding.

[0112] Test Example 5

[0113] The ability of compound 2B prepared in Example 4 to generate singlet oxygen was investigated. The assay method and conditions were identical to those in Test Example 2, except that compound 2B was used as the test substance. The results showed that the DPBF absorption intensity varied with irradiation time, demonstrating that the molecule can effectively generate singlet oxygen and can be used for photodynamic therapy.

[0114] Test Example 6

[0115] The ability of compound 3A prepared in Example 5 to generate singlet oxygen was investigated. The assay method and conditions were the same as those in Test Example 2, except that compound 3A was used as the test substance. The results showed that the DPBF absorption intensity varied with irradiation time, indicating that the molecule can effectively generate singlet oxygen and can be used for photodynamic therapy.

[0116] Test Example 7

[0117] The ability of compound 3B prepared in Example 6 to generate singlet oxygen was investigated. The assay method and conditions were identical to those in Test Example 2, except that compound 3B was used as the test substance. The results showed that the DPBF absorption intensity varied with irradiation time, demonstrating that the molecule can effectively generate singlet oxygen and can be used for photodynamic therapy.

[0118] Test Example 8

[0119] The solvent color change effect of compound 2B prepared in Example 4 was investigated. Compound 2B was mixed with different solvents to prepare mixed solutions, and the fluorescence emission spectra were detected. The results were as follows: Figure 6 As shown in the figure, from left to right, the emission spectra of diethyl ether, tetrahydrofuran, chloroform, acetone, acetonitrile, N,N-dimethylacetamide, and methanol are shown. The emission peaks of the molecules in solvents of different polarities cover the entire visible light region. The fluorescence behavior of this type of compound is highly dependent on the organic liquid, and its emission peak covers almost the entire visible light region, making it an ideal solvatochromic fluorescent probe material.

[0120] The above descriptions are merely a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application discloses the preferred embodiments as above, they are not intended to limit the present application. Any technical personnel familiar with the present profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A red light emitting organic molecule, characterized in that The chemical structural formula of the red light emitting organic molecule is: Wherein, the X atom is an S atom or a Se atom; R1 and R3 are independently selected from H, -OH, alkoxy, -(CH2) n One of CH3; R2 is selected from H, -(CH2) n CH3, 0≤n<10.

2. The method for preparing the red light emitting organic molecule according to claim 1, characterized in that: The steps include: S1, heating a mixture containing raw material I, diphenylamine or a diphenylamine derivative, catalyst I, ligand, base I, and organic solvent under an inert atmosphere to react I to obtain an intermediate; The raw material I is selected from one of 4,7-dibromobenzo[c]-1,2,5-thiadiazole and 4,7-dibromobenzo[c]-1,2,5-selenodiazole; S2, heating the material containing raw material II, the intermediate, base II, catalyst II, and solvent to react II to obtain the red light emitting organic molecule; The raw material II is selected from the compounds of the following structural formula: Wherein, R2 is selected from H, -(CH2) n CH3, 0≤n<10.

3. The preparation method according to claim 2, characterized in that The diphenylamine derivative is selected from the compounds of the following structural formula: Wherein R1 and R3 are independently selected from -OH, alkoxy, -(CH2) n One of CH3, 0≤n<10.

4. The preparation method according to claim 2, characterized in that The diphenylamine derivative is at least one selected from 4,4'-dimethoxydiphenylamine, p-hydroxydiphenylamine, and p-methoxydiphenylamine.

5. The preparation method according to claim 2, characterized in that The raw material II is selected from 3,5-bis(methoxycarbonyl)phenylboronic acid.

6. The preparation method according to claim 2, characterized in that The catalyst I and catalyst II are independently selected from at least one of palladium acetate, cuprous iodide, and tetrakis(triphenylphosphine)palladium.

7. The preparation method according to claim 2, characterized in that The ligand is selected from at least one of tri-tert-butylphosphine and trans-1,4-diaminocyclohexane.

8. The preparation method according to claim 2, characterized in that The base I and the base II are independently selected from at least one of sodium tert-butoxide, potassium phosphate and sodium carbonate.

9. The preparation method according to claim 2, characterized in that The organic solvent is selected from at least one of toluene, methanol and ethanol.

10. The preparation method according to claim 2, characterized in that The solvent is water and / or an organic solvent.

11. The preparation method according to claim 2, characterized in that In step S1, the conditions of the heating reaction I include: reaction temperature of 90 to 120° C., and reaction time of 10 to 14 hours.

12. The preparation method according to claim 2, characterized in that The conditions of the heating reaction II include: a reaction temperature of 60 to 110° C. and a reaction time of 10 to 14 hours.

13. The preparation method according to claim 2, characterized in that In step S1, the weight ratio of 4,7-dibromobenzo[c]-1,2,5-thiadiazole to diphenylamine or a diphenylamine derivative, catalyst I, ligand, and base I is 1:(0.5-1.5):(0.015-0.15):(0.1-0.5):(0.3-1.3).

14. The preparation method according to claim 2, characterized in that The solid-liquid ratio of 4,7-dibromobenzo[c]-1,2,5-thiadiazole to the organic solvent is 1 g: 5 to 50 mL.

15. The preparation method according to claim 2, characterized in that In step S2, the weight ratio of 3,5-bis(methoxycarbonyl)phenylboronic acid to the intermediate, base II, and catalyst II is 1:(1-1.5):(1-1.5):(0.3-0.6).

16. The preparation method according to claim 2, characterized in that The solid-liquid ratio of 3,5-bis(methoxycarbonyl)phenylboronic acid to the solvent is 1 g:80-140 mL.

17. The preparation method according to claim 2, characterized in that In step S2, after heating reaction II, the following steps are further included: The product after heating reaction II is dissolved in an organic solvent, and then a strong base solution is added to perform reaction III, and the pH is adjusted to 2-3 with an acid.

18. The preparation method according to claim 17, characterized in that: The conditions of the reaction III include: a reaction temperature of 70 to 90° C. and a reaction time of 10 to 30 hours.

19. Use of the red light emitting organic molecule according to claim 1 or the red light emitting organic molecule prepared according to the preparation method according to any one of claims 2 to 18 in cell imaging.

20. Use of the red light emitting organic molecule according to claim 1 or the red light emitting organic molecule prepared according to the preparation method according to any one of claims 2 to 18 in a solvatochromic fluorescent probe material, characterized in that: The applications include the use of red-emitting organic molecules as fluorescent probes in in vivo imaging.

21. Use of the red light emitting organic molecule according to claim 1 or the red light emitting organic molecule prepared by the preparation method according to any one of claims 2 to 18 in the preparation of anticancer drugs or sterilization materials that can enhance chemotherapy, photodynamic therapy, and immunotherapy, characterized in that: The red light emitting organic molecules generate active oxygen species upon illumination.

22. Use of the red light-emitting organic molecule according to claim 1 or the red light-emitting organic molecule prepared according to the preparation method according to any one of claims 2 to 18 as a mechanical force sensitive material in mechanical sensing, data storage, anti-counterfeiting material, active switch material, and biosensor.

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