A near-infrared organic room-temperature phosphorescent material based on benzothiadiazole and a preparation method and application thereof

Abstract

The application discloses a near-infrared organic room-temperature phosphorescent material based on benzothiadiazole and a preparation method and application thereof, and belongs to the technical field of organic luminescent materials. The near-infrared organic room-temperature phosphorescent material based on benzothiadiazole can effectively inhibit the quenching effect of water and oxygen on phosphorescence, has high-brightness long-life water-phase room-temperature phosphorescence, and can realize high-brightness organic room-temperature phosphorescence in water phase. The application further provides a preparation method of the near-infrared organic room-temperature phosphorescent material based on benzothiadiazole, and has the advantages of simple process and low cost. The near-infrared organic room-temperature phosphorescent material based on benzothiadiazole shows excellent tissue penetration ability in a living body, realizes high-signal-to-noise ratio phosphorescence imaging of various organs in practical application, and has a good application prospect in the field of biological imaging.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic luminescent materials, and particularly relates to a near-infrared organic room-temperature phosphorescent material based on benzothiadiazole and a preparation method and application thereof. BACKGROUND

[0002] Bioimaging plays a pivotal role in modern biomedical research, providing important detection means for complex biological structures and biochemical processes. Optical nanomaterials have become a powerful bioimaging tool due to their adjustable optical properties, high optical stability, good biocompatibility, high sensitivity and rapid response. Among them, organic phosphorescent imaging does not depend on real-time excitation and has almost no background interference, usually with a high signal-to-noise ratio. However, most room-temperature phosphorescent materials have green or yellow phosphorescent colors, with an emission wavelength shorter than 600 nm. The tissue penetration ability of this band of phosphorescence is poor, which limits the application of phosphorescent imaging in in vivo imaging. Therefore, it is particularly important and urgent to construct a high-efficiency near-infrared organic room-temperature phosphorescent material with small light scattering, deep penetration and little damage to biological samples.

[0003] At present, some effective strategies for realizing near-infrared phosphorescence / afterglow have been proposed, including introducing strong intramolecular charge transfer effect, regulating aggregation behavior, phosphorescent resonance energy transfer, etc. The non-radiative transition process of the triplet excited state is largely inhibited, so that the phosphorescent lifetime increases from 59 μs to 344 ms accordingly.

[0004] For example, the Chinese invention patent with the publication number CN104761578A discloses a rhodium tetraphenyl porphyrin-aza fluorine boron dipyrrin near-infrared absorption phosphorescent material, a preparation method and use thereof. A rhodium porphyrin-aza fluorine boron dipyrrin {Rh(ttp)-aza-BODIPY} compound is synthesized by a Rh-C bond axial connection method. Such a compound has the optical properties of both transition metal rhodium and aza-BODIPY. On the one hand, due to the central metal Rh Ш The unique d 6 electronic configuration makes the compound have a very effective intersystem crossing coefficient, producing long-lifetime phosphorescent emission and singlet oxygen. On the other hand, aza-BODIPY has very strong absorption in the near-infrared region, which can successfully red-shift the absorption wavelength of the compound to the near-infrared region, which is more conducive to wide application. However, once these near-infrared phosphorescent materials are applied to an aqueous phase, their lifetime will usually be sharply shortened to about the microsecond level, and the phosphorescent intensity will also decrease by orders of magnitude, which is mainly due to the strong quenching effect of water and oxygen.

[0005] In summary, how to realize bright and long-lasting near-infrared phosphorescence in aqueous phase, especially under physiological conditions, through aggregation state regulation is a great challenge. Providing a near-infrared organic room-temperature phosphorescent material solves the above technical problems, which is of great significance to the field of biological imaging SUMMARY

[0006] In view of the above defects of the prior art, in the first aspect of the present application, a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material with high brightness, long lifetime, aqueous room-temperature phosphorescent properties, and excellent biological tissue penetration ability is provided, which structure includes a conjugated group and a structural fragment (methyl 4-(5-(5,6-bis(dodecyloxy)-7-(4-(2-hexyldecyl)-5l3-thiophen-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)-3-(2-hexyldecyl)thiophen-2-yl)benzoate, BT) connected to the conjugated group; wherein the structure of the structural fragment is as follows, denoted as BT:

[0007] .

[0008] Based on the above technical solution, the concept of the present application is to use the structural fragment as the light-emitting unit, use the thiophene unit as the electron donor, and use the benzothiadiazole unit as the electron acceptor, so that the donor-acceptor structure formed can promote the red shift of the absorption and emission wavelength, and at the same time, can reduce the energy level difference (ΔE ST ) between the singlet state and the triplet state, promote the emission of near-infrared phosphorescence; at the same time, introducing multiple alkyl chains and alkoxy chains on the light-emitting unit can isolate the quenching effect of water and oxygen to a certain extent, and realize efficient phosphorescence in aqueous phase.

[0009] Preferably, the conjugated group includes one of tetraphenylmethane (TPM), 9,9'-spirobi[9H-fluorene] (SFlu), dibenzo[g,p]chrysene (DBC), and tetraphenylethylene (TPE).

[0010] Further preferably, 1-4 structural fragments are connected to 1 conjugated group to form a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material including the following molecular structure:

[0011] 、 、 、 、 、 .

[0012] The inventors adopt the conjugated groups with different geometrical shapes of the above type to effectively adjust the configuration of the phosphorescent molecules, affect the interaction forces and arrangement modes between the structural fragments, and further affect the aggregate behavior of the whole molecules. The number of branches of the molecules is from single branch to double branch to four branches, the molar absorption coefficient is continuously increased, and the interaction between the branches is enhanced, which is beneficial to promote and optimize the high-efficiency room-temperature phosphorescent performance.

[0013] In the second aspect of the present application, a preparation method of the near-infrared organic room-temperature phosphorescent material based on benzothiadiazole of the first aspect of the present application is provided, which is simple in process and low in cost, comprising the following steps:

[0014] (1) Under a solution environment, 3-(2-hexyldecyl) thiophene and n-butyllithium, and tri-tert-butyl tin chloride are reacted to obtain compound 1;

[0015] ;

[0016] (2) Under a solution environment, compound 1 and 4,7-dibromo-5,6-bis(dodecyloxy) benzothiadiazole compound 2 are reacted by Stille coupling reaction under the action of a catalyst to obtain compound 3;

[0017] , ;

[0018] (3) Under a solution environment, compound 3 and N-bromosuccinimide are reacted to obtain compound 4;

[0019] ;

[0020] (4) Under a solution environment, compound 4 and 4-methoxycarbonyl phenylboronic acid are reacted by Suzuki coupling reaction under the action of a catalyst to obtain compound 5;

[0021] ;

[0022] (5) Under a solution environment, compound 5 and N N-bromosuccinimide are reacted to obtain a bromo structural fragment BT-Br;

[0023] ;

[0024] (6) Under a solution environment, the bromo structural fragment BT-Br and a pinacol borate compound of a conjugated group are reacted under the action of a catalyst to obtain the near-infrared organic room-temperature phosphorescent material based on benzothiadiazole.

[0025] Preferably, the reaction conditions of step (1) are as follows: the solution environment is created by tetrahydrofuran; the molar ratio of n-butyllithium to 3-(2-hexyldecyl)thiophene is 1:1.0-1.5; the molar ratio of tributyltin chloride to compound 3 is 1-1.2:1; the reaction is first carried out at a temperature of -78 ℃ for 1-2 h, and then gradually warmed to room temperature for 10-15 h.

[0026] Preferably, the reaction conditions of step (2) are as follows: the solution environment is created by tetrahydrofuran; the catalyst is bis[di-tert-butyl-(4-dimethylamino phenyl) phosphine] palladium dichloride, and the molar ratio of the catalyst to compound 2 is 0.01-0.05:1; the molar ratio of compound 2 to compound 1 is 1:2.2-2.5; the Stille coupling reaction is carried out at a temperature of 80-85 ℃ under reflux for 8-12 h.

[0027] Preferably, the reaction conditions of step (3) are as follows: the solution environment is created by tetrahydrofuran; N - the molar ratio of bromosuccinimide to compound 3 is 1-1.1:1; the reaction is carried out under ice bath for 1-5 h.

[0028] Preferably, the reaction conditions of step (4) are as follows: the solution environment is created by a mixed solvent formed by tetrahydrofuran and water in a volume ratio of 5-20:1; the catalyst is bis[di-tert-butyl-(4-dimethylamino phenyl) phosphine] palladium dichloride, and the molar ratio of the catalyst to compound 4 is 0.01-0.05:1; the molar ratio of compound 4 to 4-methoxycarbonyl phenylboronic acid is 1:1.0-1.5, and the Suzuki coupling reaction is carried out at a temperature of 80-85 ℃ under reflux for 8-12 h.

[0029] Preferably, the reaction conditions of step (5) are as follows: the solution environment is created by a mixed solvent formed by chloroform and acetic acid in a volume ratio of 5-20:1; N - the molar ratio of bromosuccinimide to compound 5 is 1.1-1.2:1; the reaction is carried out at room temperature for 1-3 h.

[0030] Preferably, the reaction conditions of step (6) are as follows: the solution environment is created by a mixed solvent formed by tetrahydrofuran and water in a volume ratio of 5-20:1; the catalyst is bis[di-tert-butyl-(4-dimethylamino phenyl) phosphine] palladium dichloride, and the molar ratio of the catalyst to the bromo structural fragment is 0.01-0.05:1; the molar ratio of the bromo structural fragment to the pinacol borate compound of the conjugated group is 1:1-4; the reaction is carried out at a temperature of 80-85 ℃ under reflux for 12-24 h.

[0031] Preferably, in the step (6), the pinacol boronate compound of the conjugated group comprises one of tetraphenylmethane pinacol boronate compound (TPM-4Bpin), 9,9'-spirobi[fluorene] pinacol boronate compound (Sflu-4Bpin), dibenzo[g,p]chrysene pinacol boronate compound (DBC-4Bpin), tetraphenylstyrene pinacol boronate compound (TPE-Bpin, TPE-2Bpin, TPE-2Bpin-m, TPE-4Bpin), and the structure formula is as follows:

[0032] , , , , , , .

[0033] Those skilled in the art can select the commonly used synthesis equipment, environment and purification means in the field based on the above synthesis path. For example, in the process of synthesis, the above operation is suitable to be carried out under inert atmosphere, and after each stage reaction is ended, the product recovery means such as extraction, reduced pressure distillation, column chromatography and the like can be selected according to the actual conditions.

[0034] In the third aspect of the present application, the application provides the application of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material of the first aspect of the present application or the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material prepared by the preparation method of the second aspect of the present application, and specifically the application as an organic luminescent material in the field of biological imaging and the like.

[0035] Preferably, the application method comprises loading the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material with an amphiphilic high molecular material as a carrier to prepare a near-infrared organic room-temperature phosphorescent nanoparticle.

[0036] Compared with the prior art, the present application has the following advantages and beneficial effects:

[0037] The present application provides a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material, which can effectively inhibit the quenching effect of water and oxygen on phosphorescence, has high-brightness long-life water-phase room-temperature phosphorescence, and can realize high-brightness organic room-temperature phosphorescence in water phase.

[0038] The present application provides a preparation method of a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material, which has the advantages of simple process and low cost.

[0039] The application provides application of a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material, which exhibits excellent tissue penetration ability in vivo, realizes high signal-to-noise ratio phosphorescent imaging of various organs, and has a good application prospect in the field of biological imaging. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1 The phosphorescent spectrum of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material in a solid state is provided.

[0041] Figure 2 The lifetime decay graph of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material in a solid state at about 650 nm is provided.

[0042] Figure 3 The lifetime decay graph of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material in a solid state at about 740 nm is provided.

[0043] Figure 4 The phosphorescent spectrum of the near-infrared organic room-temperature phosphorescent nanoparticle in an aqueous phase is provided.

[0044] Figure 5 The lifetime decay graph of the near-infrared organic room-temperature phosphorescent nanoparticle in an aqueous phase at about 600 nm is provided.

[0045] Figure 6 The lifetime decay graph of the near-infrared organic room-temperature phosphorescent nanoparticle in an aqueous phase at about 660 nm is provided.

[0046] Figure 7 The afterglow imaging of the near-infrared organic room-temperature phosphorescent nanoparticle prepared by using TPE-4BT and applied to mouse liver is provided.

[0047] Figure 8 The afterglow imaging of the near-infrared organic room-temperature phosphorescent nanoparticle prepared by using TPE-4BT and applied to monitor mouse gastrointestinal tract is provided.

[0048] Figure 9 The afterglow imaging of the near-infrared organic room-temperature phosphorescent nanoparticle prepared by using TPE-4BT and applied to mouse tumor is provided.

[0049] Figure 10 The afterglow imaging of the near-infrared organic room-temperature phosphorescent nanoparticle prepared by using TPE-4BT and applied to rabbit in vivo at different penetration depths (subcutaneous: about 2 mm, muscle: about 10 mm) is provided.

[0050] Figure 11 The afterglow imaging of the near-infrared organic room-temperature phosphorescent nanoparticle prepared by using TPE-4BT and applied to rabbit in vivo lymph node is provided. DETAILED DESCRIPTION

[0051] The application will be further described in the following by way of examples without limiting the application to the examples described. The experimental methods in the following examples, for which no specific conditions are indicated, are carried out according to standard methods and conditions, or according to the instructions of the commercial suppliers.

[0052] In the following examples:

[0053] This study was in accordance with the ethical guidelines of the 2013 revised version of the Declaration of Helsinki; in animal experiments, the mouse experiment was approved by the Experimental Animal Welfare and Ethics Committee of the School of Life Sciences, Wuhan University, and the rabbit experiment was approved by the Experimental Animal Welfare and Ethics Committee of Wuhan Wanqianjiaxing Biotechnology Co., Ltd.

[0054] Example 1

[0055] The preparation method of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material is as follows:

[0056]

[0057] (1) Under an inert gas atmosphere, 3-(2-hexyldecyl) thiophene (9.26 g, 30.0 mmol) was dissolved in 60 mL of tetrahydrofuran solution and stirred at -78 °C; then n-butyllithium (12.0 mL, 2.5 mol L -1 , 30.0 mmol) was added dropwise, and the temperature was kept at -78 °C for 1 h; then tributyltin chloride (8.1 mL, 30.0 mmol) was added, the reaction mixture was raised to room temperature and stirred overnight; after the reaction was completed, the reaction liquid was poured into water, extracted with dichloromethane three times, the organic phase was collected and dried with anhydrous sodium sulfate; after the solvent was removed under reduced pressure, it was directly used in the next step without further purification;

[0058] (2) Under an inert gas atmosphere, compound 1 (17.93 g, 30.0 mmol), compound 2 (7.95 g, 12.0 mmol) and bis[di-tert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride (0.42 g, 0.6 mmol) were dissolved in 40 mL of tetrahydrofuran solution, stirred at 80 °C for 12 h; after the reaction was completed, it was cooled to room temperature, the reaction liquid was poured into water, extracted with dichloromethane three times, and the combined organic phase was dried with anhydrous sodium sulfate; after the solvent was removed under reduced pressure, column chromatography purification was carried out with petroleum ether as the eluent to obtain orange compound 3 (10.53 g, 69%);

[0059] (3) Compound 3 (8.94 g, 8.0 mmol) was dissolved in 100 mL of tetrahydrofuran and stirred in an ice bath; then N- bromosuccinimide (1.42 g, 8.0 mmol) at ice-bath for 3 h; after the reaction was completed, the reaction solution was poured into water, extracted with dichloromethane for three times, and the combined organic phase was dried over anhydrous sodium sulfate; after the solvent was removed under reduced pressure, column chromatography was performed with petroleum ether:dichloromethane = 10:1 (v / v) as the eluent to obtain orange compound 4 (4.88 g, 51%);

[0060] (4) Compound 4 (4.78 g, 4.0 mmol), 4-bromobenzoic acid methyl ester (0.86 g, 4.8 mmol), bis [di-tert-butyl-(4-dimethylamino phenyl) phosphine] palladium dichloride (0.14 g, 0.20 mmol) and potassium carbonate (2.76 g, 20.0 mmol) were dissolved in 40 mL of a mixed solvent of tetrahydrofuran:water = 10:1 (v / v) under an inert gas atmosphere, stirred at 80 °C for 12 h; after cooling to room temperature, the mixture was poured into water, extracted with dichloromethane for three times. After the reaction was completed, the reaction solution was cooled to room temperature, poured into water, extracted with dichloromethane for three times, and the combined organic phase was dried over anhydrous sodium sulfate; after the solvent was removed under reduced pressure, column chromatography was performed with petroleum ether:dichloromethane = 5:1 (v / v) as the eluent to obtain orange compound 5 (3.80 g, 76%);

[0061] (5) Compound 5 (3.76 g, 3.0 mmol) was dissolved in 44 mL of a mixed solvent of chloroform:acetic acid = 10:1 (v / v); then under dark conditions, 2,3-dibromopropanoic acid (0.58 g, 3.3 mmol) was added in batches; N - bromosuccinimide (1.42 g, 8.0 mmol) at ice-bath for 3 h; after the reaction was completed, the reaction solution was poured into water, extracted with dichloromethane for three times, and the combined organic phase was dried over anhydrous sodium sulfate; after the solvent was removed under reduced pressure, column chromatography was performed with petroleum ether:dichloromethane = 10:1 (v / v) as the eluent to obtain orange compound 4 (4.88 g, 51%);

[0062] (6) In an inert gas atmosphere, bromo structure fragment BT-Br (0.53 g, 0.4 mmol), compound TPE-4Bpin (0.08 g, 0.1 mmol), bis [di-tert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride (0.004 g, 0.005 mmol) and potassium carbonate (0.14 g, 1.0 mmol) were dissolved in 20 mL of a mixed solvent of tetrahydrofuran: water = 10:1 (v / v), and stirred at 80 ℃ for 24 h; after cooling to room temperature, the mixture was poured into water, extracted with dichloromethane three times; after the reaction was completed and cooled to room temperature, the reaction liquid was poured into water, extracted with dichloromethane three times, and the combined organic phase was dried over anhydrous sodium sulfate; after removing the solvent under reduced pressure, column chromatography purification was performed with petroleum ether:dichloromethane = 2:1 (v / v) as the eluent to obtain an orange near-infrared organic room-temperature phosphorescent material based on benzothiadiazole, i.e., TPE-4BT (0.23 g, 43%). 1 H NMR (400 MHz, CDCl3) δ (ppm): 8.43-8.37 (m, 8H, ArH), 8.13-8.09 (m, 8H, ArH), 7.65-7.61 (m, 8H, ArH), 7.41-7.37 (m, 8H, ArH), 7.26-7.22 (m, 8H, ArH), 4.21-4.13 (m, 16H, OCH2), 3.96 (s, 12H, CH3), 2.78-2.71 (m, 16H, CH2), 2.00-1.92 (m, 16H, CH2), 1.81-1.69 (m, 8H, CH), 1.53-1.46 (m, 16H, CH2), 1.40-1.15 (m, 320H, CH2), 0.89-0.80 (m, 72H, CH3). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.92, 152.11,151.71, 151.03, 150.92, 142.64, 140.82, 140.65, 139.85, 139.04, 138.72,137.82, 134.14, 133.44, 133.24, 131.98, 131.74, 129.80, 129.28, 128.81,128.69, 117.77, 116.94, 74.45, 74.29, 52.16, 39.18, 33.52, 33.41, 33.24,31.98, 31.96, 30.50, 30.14, 30.09, 29.79, 29.76, 29.73, 29.69, 29.46, 29.44,29.41, 26.56, 26.49, 26.44, 26.42, 26.18, 22.73, 22.70, 14.17, 14.15.

[0063] Example 2

[0064] In the preparation method of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material of the present example, the synthesis of the bromo structural fragment BT-Br is consistent with that of Example 1; the difference of the present example is only that the synthesis path of step (6) is different, and the specific process is as follows:

[0065]

[0066] Under an inert gas atmosphere, the bromo structural fragment BT-Br (0.53 g, 0.4 mmol), compound TPE-4Bpin (0.08 g, 0.1 mmol), bis[ditert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride (0.004 g, 0.005 mmol) and potassium carbonate (0.14 g, 1.0 mmol) were dissolved in 20 mL of a mixed solvent of tetrahydrofuran: water = 10:1 (v / v), and stirred at 80°C for 24 h; after cooling to room temperature, the mixture was poured into water and extracted with dichloromethane three times; after the reaction was completed and cooled to room temperature, the reaction solution was poured into water and extracted with dichloromethane three times, and the combined organic phase was dried over anhydrous sodium sulfate; after the solvent was removed under reduced pressure, column chromatography purification was performed with petroleum ether:dichloromethane = 2:1 (v / v) as the eluent to obtain the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material, i.e. TPE-4BT (0.24 g, 45%) in orange. 1H NMR (400 MHz, CDCl3)δ (ppm): 9.03–8.79 (m, 8H, ArH), 8.54 (s, 4H, ArH), 8.44 (s, 4H, ArH), 8.12–8.09 (m, 8H, ArH), 7.92–7.88 (m, 4H, ArH), 7.64–7.61 (m, 8H, ArH), 4.24–4.17(m, 16H, OCH2), 3.96 (s, 12H, CH3), 2.96–2.93 (m, 8H, CH2), 2.77–2.73 (m, 8H,CH2),2.05–1.92 (m, 16H, CH2), 1.87–1.70 (m, 8H, CH), 1.52–1.45 (m, 16H, CH2),1.39–1.05 (m, 320H, CH2), 0.89–0.69 (m, 72H, CH3). 13 C NMR (100 MHz, CDCl3) δ(ppm): 166.92, 152.10, 151.82, 151.02, 150.97, 140.70, 139.84, 139.11,138.74, 138.37, 134.20, 133.50, 133.22, 132.74, 131.00, 129.80, 129.28,128.71, 128.59, 127.71, 124.56, 117.69, 117.10, 74.48, 74.40, 52.16, 39.46,39.19, 33.61, 33.42, 33.26, 31.94, 31.91, 31.87, 30.50, 30.14, 30.08, 29.80,29.75, 29.72, 29.67, 29.39, 29.36, 26.67, 26.60, 26.44, 26.41, 26.18, 26.13,22.71, 22.69, 22.67, 22.63, 14.13, 14.09, 14.07.

[0067] Example 3

[0068] In the preparation method of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material of the present example, the synthesis of BT-Br, i.e. the step of bromo structure fragment, is consistent with that of Example 1; the difference of the present example is only that the synthesis path of step (6) is different, and the specific process is as follows:

[0069]

[0070] Bromide moiety BT-Br (0.13 g, 0.1 mmol), compound TPE-Bpin (0.05 g, 0.1 mmol), bis [di-tert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride (0.004 g, 0.005 mmol) and potassium carbonate (0.07 g, 0.5 mmol) were dissolved in 20 mL of tetrahydrofuran: water = 10:1 (v / v) mixed solvent under inert gas atmosphere, stirred at 80 °C for 24 h; after cooling to room temperature, the mixture was poured into water, extracted with dichloromethane three times; after the reaction was completed and cooled to room temperature, the reaction solution was poured into water, extracted with dichloromethane three times, and the combined organic phase was dried over anhydrous sodium sulfate; after removing the solvent under reduced pressure, column chromatography purification was carried out with petroleum ether:dichloromethane = 4:1 (v / v) as eluent to obtain orange benzothiadiazole-based near-infrared organic room-temperature phosphorescent material, i.e. TPE-BT (0.12 g, 78%). 1 H NMR (400 MHz, CDCl3)δ (ppm): 8.42 (s, 1H, ArH), 8.35 (d, J = 1.7 Hz, 1H, ArH), 8.13–8.09 (m, 2H,ArH), 7.66–7.59 (m, 2H, ArH), 7.31–7.26 (m, 2H, ArH), 7.18–7.03 (m, 17H,ArH), 4.19–4.13 (m, 4H, OCH2), 3.96 (s, 3H, OCH3), 2.76–2.65 (m, 4H, CH2),2.02–1.89 (m, 4H, CH2), 1.76–1.67 (m, 2H, CH), 1.54–1.43 (m, 4H, CH2), 1.39–1.14 (m, 80H, CH2), 0.93–0.82 (m, 18H, CH3). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.92, 152.08, 151.67, 151.02, 150.93, 143.74, 143.71, 143.60, 142.78, 141.32, 140.63, 140.60, 139.84, 139.04, 138.73, 137.78, 134.13, 133.23, 132.98, 131.81, 131.46, 131.43, 131.39, 129.80, 129.28, 128.69, 128.66, 127.73, 127.68, 126.55, 117.74, 116.95, 74.44, 74.36, 52.16, 39.18, 38.99, 33.44, 33.34, 33.24, 31.98, 31.95, 30.47, 30.16, 30.08, 29.82, 29.76, 29.72, 29.70, 29.46, 29.42, 29.40, 26.44, 26.15, 22.77, 22.73, 22.70, 14.19, 14.17, 14.15.

[0071] Example 4

[0072] This example is based on the preparation method of the near-infrared organic room-temperature phosphorescent material based on benzothiadiazole as in Example 1, and the bromo structure fragment BT-Br is synthesized, and is reacted with TPM-4Bpin, Sflu-4Bpin, TPE-2Bpin, TPE-2Bpin-m respectively using the above route to synthesize the target structure of TPM-4BT, SFlu-4BT, TPE-2BT, TPE-2BT-m.

[0073] Example 5

[0074] This example studies the organic room-temperature phosphorescent performance of the seven near-infrared organic room-temperature phosphorescent materials based on benzothiadiazole of TPM-4BT, SFlu-4BT, DBC-4BT, TPE-BT, TPE-2BT, TPE-2BT-m and TPE-4BT in application, and the phosphorescent spectrum and lifetime thereof are tested by a steady-state / transient fluorescence spectrometer (Edinburgh, model: FLS980). The phosphorescent spectrum of the above near-infrared organic room-temperature phosphorescent material in solid state is shown in Figure 1 ; wherein the lifetime decay graphs at about 650 nm and about 740 nm in solid state are shown in Figure 2 , Figure 3 . Figure 1It is shown that the seven compounds all exhibit phosphorescence emission in the red to near-infrared region in the solid state; Figure 2 It is shown that the phosphorescence emission peak near 650 nm exhibits a lifetime of 165.58-303.54 ms; Figure 3 It is shown that the phosphorescence emission peak near 740 nm exhibits a lifetime of 26.15-30.87 ms. The above results show that the benzothiadiazole-based near-infrared organic room-temperature phosphorescent materials exhibit excellent organic room-temperature phosphorescent performance.

[0075] In this embodiment, amphiphilic polymer distearoyl phosphoethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000) is used as a carrier, and TPM-4BT, SF1u-4BT, DBC-4BT, TPE-BT, TPE-2BT, TPE-2BT-m, and TPE-4BT are used as organic light-emitting materials to construct near-infrared organic room-temperature phosphorescent nanoparticles, and the phosphorescence spectra and lifetimes of the nanoparticles are tested by a steady-state / transient fluorescence spectrometer. The phosphorescence spectra of the obtained various types of near-infrared organic room-temperature phosphorescent nanoparticles in an aqueous phase are shown in FIG. 6, wherein the lifetime decay graphs of the nanoparticles in the aqueous phase at about 600 nm and about 660 nm are shown in FIGS. 7 and 8, respectively. Figure 4 Figure 5 Figure 6 Figure 4 It is shown that the phosphorescence spectra of the seven types of near-infrared organic room-temperature phosphorescent nanoparticles in the aqueous phase range from 550 nm to 750 nm; Figure 5 It is shown that the phosphorescence emission peak near 600 nm exhibits a lifetime of 75.84-133.31 ms; Figure 6 It is shown that the phosphorescence emission peak near 660 nm exhibits a lifetime of 30.03-38.34 ms. The above results show that the near-infrared organic room-temperature phosphorescent nanoparticles can maintain a millimeter-level lifetime.

[0076] The above results show that the benzothiadiazole-based near-infrared organic room-temperature phosphorescent materials can effectively isolate the quenching effect of water and oxygen, and achieve high-efficiency phosphorescence performance in the solid state or in an aqueous phase.

[0077] Example 6

[0078] In this embodiment, the near-infrared organic room-temperature phosphorescent nanoparticles prepared by using TPE-4BT in Example 5 (hereinafter referred to as TPE-4BT nanoparticles) are applied to liver afterglow imaging of mice. The TPE-4BT nanoparticles (100 μL of 0.5 mg / mL) are effectively delivered to the liver of a living mouse through tail vein injection. After 30 min of injection, the white light (power density: 100 mW / cm2) is used to excite the liver of the mouse, and the afterglow image of the liver of the mouse is captured by a cooled charge-coupled device (CCD) camera. The results are shown in FIG. 9.​​​2 Mice were irradiated for 5 seconds, and then phosphorescent images of the live mice were captured in bioluminescence mode (open filter; exposure time: 10 seconds) using an in vivo imaging system (IVIS Spectrum). The results are as follows: Figure 7 As shown, this invention enables phosphorescence imaging of the liver in mice, with a phosphorescence quantization intensity as high as 2.02 ± 0.67 × 10⁶ ps. -1 cm -2 sr -1 The signal-to-noise ratio is 16.

[0079] TPE-4BT nanoparticles were used for afterglow imaging of the gastrointestinal tract in mice. TPE-4BT nanoparticles (200 μL, 0.5 mg / mL) were effectively delivered into the gastrointestinal tract of live mice via gavage. Afterglow imaging was performed at different time points (1 min, 1 h, 3 h, 5 h, and 7 h) using white light (power density: 100 mW / cm²). 2 After irradiating mice for 5 seconds, phosphorescent images of live mice were captured using a live imaging system in bioluminescence mode (open filter; exposure time: 10 seconds). The results are as follows. Figure 8 As shown. Changes in in vivo phosphorescence signals were monitored at different time points, and corresponding afterglow in the in vitro digestive tract and feces was detected. Real-time in vivo phosphorescence imaging showed the pathway of TPE-4BT nanoparticles in the digestive tract, reflecting intestinal peristalsis from the stomach to the small intestine and then to the colon. In vivo imaging of the stomach was achieved in the first 1 minute. After 1 h and 3 h, TPE-4BT nanoparticles were mainly enriched in the small intestine and began to be excreted. At 5 h, the phosphorescence signal in the feces reached its peak, while the phosphorescence signal in the gastrointestinal tract decreased both in vivo and in vitro. Finally, at 7 h, most of the TPE-4BT nanoparticles were excreted from the mouse digestive system, so only a weak afterglow signal could be detected in the colon.

[0080] TPE-4BT nanoparticles were used for afterglow imaging of mouse tumors. Six-week-old female BALB / cJGpt mice were subcutaneously injected with 4T1 cells at a density of 1×10⁶ cells, resulting in tumor formation approximately 10 days later. Then, nanoparticles (100 μL, 1.0 mg / mL) were injected via the tail vein into the mice with subcutaneous 4T1 tumors. Five hours after injection, white light (power density: 100 mW / cm²) was used for afterglow imaging. 2 Immediately after 5 seconds of irradiation, phosphorescent images of live mice were captured in the bioluminescence mode (open filter; exposure time: 10 seconds) of the in vivo imaging system. The results are as follows: Figure 9 As shown. Therefore, this invention achieves afterglow imaging of tumors, with clear and complete tumor outlines and a signal-to-noise ratio as high as 75.

[0081] The experimental subjects were changed from mice to rabbits. TPE-4BT nanoparticles were applied to subcutaneous and muscle afterglow imaging in rabbits. TPE-4BT nanoparticles (100 μL 0.5 mg / mL) were injected subcutaneously / intramuscularly into the left hind limb of anesthetized live female New Zealand rabbits (average weight: 1.5–2.2 kg). White light (power density: 100 mW / cm²) was used. 2 After irradiating rabbits for 5 seconds, phosphorescent images of the live rabbits were captured in the bioluminescence mode (open filter; exposure time: 10 seconds) of the in vivo imaging system. The results are as follows. Figure 10 As shown, under approximately 2 mm thick rabbit skin, the quantitative afterglow intensity reaches 6.80 ± 1.07 × 10⁻⁶. 7 p s-1cm -2 sr -1 The signal-to-noise ratio was 5125. Then, nanoparticles were injected intramuscularly into the left hind limb of rabbits to a tissue depth of approximately 10 mm, resulting in an afterglow intensity of 1.61 ± 0.33 × 10⁶ ps. -1 cm -2 sr -1 The signal-to-noise ratio is 360.

[0082] TPE-4BT nanoparticles were used for afterglow imaging of rabbit axillary lymph nodes. The nanoparticles (800 μL 0.5 mg / mL) were injected into the forepaws of anesthetized live female New Zealand rabbits (average weight: 1.5–2.2 kg). Six hours after injection, afterglow imaging was performed under white light (power density: 100 mW / cm²). 2 Immediately after 5 seconds of irradiation, phosphorescent images of live rabbits were captured in the bioluminescence mode (open filter; exposure time: 10 seconds) of the in vivo imaging system. The results are as follows: Figure 11 As shown in the figure, the axillary lymph nodes are clearly outlined using phosphorescence imaging, with a quantitative afterglow intensity of 1.27 ± 0.62 × 10⁻⁶. 6 ps -1 cm -2 sr -1 Furthermore, the signal-to-noise ratio of rabbit lymph node imaging is as high as 305.

[0083] The above results show that the application provides a near-infrared organic room-temperature phosphorescent material based on benzothiadiazole, uses a structural fragment as a light-emitting unit, uses a thiophene unit as an electron donor, and uses a benzothiadiazole unit as an electron acceptor, so that the donor-acceptor structure formed can promote red shift of an absorption and emission wavelength, can reduce an energy level difference between a singlet state and a triplet state, and can promote near-infrared phosphorescence emission. Meanwhile, introduction of multiple alkyl chains and alkoxy chains on the light-emitting unit can isolate the quenching effect of water and oxygen to a certain extent, can effectively inhibit the quenching effect of water and oxygen on phosphorescence, has high-brightness long-lifetime aqueous room-temperature phosphorescence, and can realize high-brightness organic room-temperature phosphorescence in an aqueous phase. The near-infrared organic room-temperature phosphorescent material based on benzothiadiazole can be synthesized by a relatively simple and low-cost method. As an organic light-emitting material, the material can be combined with an amphiphilic polymer material carrier, can exhibit excellent tissue penetration ability in a living body, can realize high-signal-to-noise ratio phosphorescence imaging of various organs, and has a good application prospect in the field of biological imaging.

[0084] The preferred embodiments of the application are described in detail above. It should be understood that those skilled in the art can make many modifications and changes without creative labor based on the concept of the application. Therefore, any technical solution obtained by logical analysis, reasoning or limited experiments based on the prior art according to the concept of the application should be within the protection scope defined by the claims.

Claims

1. A near-infrared organic room-temperature phosphorescent material based on benzothiadiazole, characterized in that, The structure comprises a conjugated group and a structure fragment connected with the conjugated group; wherein the structure of the structure fragment is as follows, denoted as BT: The conjugated group is one of tetraphenylmethane, 9,9'-spirobi[fluorene], dibenzo[g,p]chrysene, tetraphenylstyrene; 1 conjugated group connects 1-4 structure fragments to form a near-infrared organic room-temperature phosphorescent material based on benzothiadiazole with the following molecular structure:

2. A method for preparing a benzothiadiazole-based near-infrared organic room-temperature phosphorescent material according to claim 1, characterized by, The method comprises the following steps: (1) under a solution environment, 3-(2-hexyldecyl) thiophene and n-butyllithium, and tri-n-butyltin chloride are reacted to obtain compound 1; (2) under a solution environment, compound 1 and 4,7-dibromo-5,6-bis(dodecyloxy) benzothiadiazole compound 2 are reacted under the action of a catalyst through a Stille coupling reaction to obtain compound 3; (3) under a solution environment, compound 3 and N-bromosuccinimide are reacted to obtain compound 4; (4) under a solution environment, compound 4 and 4-methoxycarbonyl phenylboronic acid are reacted under the action of a catalyst through a Suzuki coupling reaction to obtain compound 5; (5) Compound 5 and N - bromosuccinimide to obtain the bromo structure fragment BT-Br; (6) under a solution environment, a bromo structure fragment BT-Br and a pinacol boronic acid ester compound of a conjugated group are reacted under the action of a catalyst to obtain a near-infrared organic room-temperature phosphorescent material based on benzothiadiazole.

3. The method of producing a benzo-thiadiazole-based near-infrared organic room-temperature phosphorescent material according to claim 2, characterized by, The reaction condition of the step (1) is as follows: the solution environment is created by tetrahydrofuran; the molar ratio of n-butyllithium to 3-(2-hexyldecyl) thiophene is 1:1.0-1.5; the molar ratio of tri-n-butyltin chloride to compound 3 is 1-1.2:1; first, the reaction is carried out at a temperature of-78 ℃ for 1-2 h, and then the temperature is gradually increased to room temperature for 10-15 h.

4. The method of preparing a benzo-thiadiazole based near-infrared organic room temperature phosphorescent material according to claim 2, characterized in that, The reaction condition of the step (2) is as follows: the solution environment is created by tetrahydrofuran; the catalyst is bis[bis(tert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride, the molar ratio of the catalyst to compound 2 is 0.01-0.05:1; the molar ratio of compound 2 to compound 1 is 1:2.2-2.5; the Stille coupling reaction is carried out at a temperature of 80-85 ℃ under reflux for 8-12 h.

5. The method of preparing a benzo-thiadiazole based near-infrared organic room temperature phosphorescent material according to claim 2, characterized in that, The reaction conditions of step (3) are as follows: the solution environment is created by tetrahydrofuran; N - the molar ratio of bromosuccinimide to compound 3 is 1-1.1 : 1; the reaction is carried out under ice bath for 1-5 h.

6. The method of preparing a benzo-thiadiazole based near-infrared organic room temperature phosphorescent material according to claim 2, characterized in that, The reaction condition of the step (4) is as follows: the solution environment is created by a mixed solvent formed by tetrahydrofuran and water in a volume ratio of 5-20:1; the catalyst is bis[bis(tert-butyl-(4-dimethylaminophenyl) phosphine] palladium dichloride, the molar ratio of the catalyst to compound 4 is 0.01-0.05:1; the molar ratio of compound 4 to 4-methoxycarbonyl phenylboronic acid is 1:1.0-1.5, and the Suzuki coupling reaction is carried out at a temperature of 80-85 ℃ under reflux for 8-12 h.

7. The method of preparing a benzo-thiadiazole based near-IR organic room temperature phosphorescent material according to claim 2, characterized in that, The reaction condition of the step (5) is as follows: the solution environment is formed by the mixed solvent of chloroform and acetic acid with the volume ratio of 5-20:1; N The molar ratio of bromosuccinimide to compound 5 is 1.1-1.2:1, and the reaction is carried out at room temperature for 1-3 h.

8. The method of preparing a benzo-thiadiazole based near-IR organic room temperature phosphorescent material according to claim 2, characterized in that, The reaction conditions of the step (6) are as follows: the solution environment is formed by a mixed solvent of tetrahydrofuran and water in a volume ratio of 5-20:1; the catalyst is bis[di-tert-butyl-(4-dimethylamino phenyl) phosphine] palladium dichloride, the molar ratio of the catalyst to the bromo structural fragment is 0.01-0.05:1; the molar ratio of the bromo structural fragment to the pinacol boronic acid ester compound of the conjugated group is 1:1-4; the reaction is refluxed at a temperature of 80-85 DEG C for 12-24 h; the pinacol boronic acid ester compound of the conjugated group is one of tetraphenylmethane pinacol boronic acid ester compound, 9,9'-spirobis[fluorene] pinacol boronic acid ester compound, dibenzo[g,p] fused dinaphthalene pinacol boronic acid ester compound, tetraphenylstyrene pinacol boronic acid ester compound, and the structural formula is as follows:

9. Use of the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material according to claim 1 or the benzothiadiazole-based near-infrared organic room-temperature phosphorescent material produced by the production method according to any one of claims 2 to 8, characterized by: Application of the organic luminescent material in the field of biological imaging.

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