Near-infrared two-region material with high fluorescence quantum yield as well as preparation method and application of near-infrared two-region material

Abstract

The invention belongs to the field of organic photoelectric functional materials, and particularly relates to a near-infrared two-region material with high fluorescence quantum yield as well as a preparation method and application of the near-infrared two-region material. The near-infrared two-region material with high fluorescence quantum yield prepared by the invention has good solubility, has relatively strong light absorption capability and strong near-infrared fluorescence emission capability in infrared and near-infrared regions, and has potential of being applied to the field of biomedicine.

Description

Technical Field

[0001] This invention belongs to the field of organic optoelectronic functional materials, specifically relating to a near-infrared II material with high fluorescence quantum yield, its preparation method, and its application. Background Technology

[0002] Cancer, a major disease threatening human health, faces numerous limitations with traditional treatments (surgical resection, radiotherapy, chemotherapy), including systemic toxicity, drug resistance, and the separation of diagnosis and treatment. Fluorescence imaging, with its superior spatiotemporal resolution, ultra-high sensitivity, and real-time dynamic imaging capabilities, has become an indispensable key technology in modern biomedical diagnosis and image-guided surgery. In particular, fluorescence imaging operating in the near-infrared window, benefiting from the deep penetration of the near-infrared band and its ability to significantly reduce autofluorescence in biological tissues, as well as tissue absorption and scattering, has attracted widespread attention from scholars worldwide for achieving a superior signal-to-noise ratio (SBR) in in vivo deep tissue imaging. Among various near-infrared materials, organic near-infrared fluorescent molecules exhibit greater clinical translational potential than inorganic materials due to their tunable band gap, ease of chemical modification, well-defined structure, and good biocompatibility.

[0003] In recent years, the development of aromatic fused-ring Y-series non-fullerene acceptor materials, especially their strong absorption in the infrared and near-infrared bands, has attracted widespread attention from researchers. Y-series non-fullerene acceptor materials are near-infrared luminescent materials constructed from ADA units (acceptor-donor-acceptor). However, due to their planar structure, they often experience fluorescence quenching in the aggregated state due to strong π-π interactions, i.e., aggregation-induced quenching (ACQ), resulting in low PLQY in the aggregated state, which limits their application in fluorescence imaging. The concept of aggregation-induced emission (AIE) provides an important approach to overcoming the ACQ problem. Based on this, researchers have designed a series of near-infrared AIE luminescent organisms (AIEgens) by introducing twisted, rotatable AIE units into the strong DA framework. Their non-planar structure effectively suppresses intermolecular π-π interactions, thus maintaining high fluorescence in the aggregated state. However, the absorption capacity of most near-infrared AIEgens is not ideal. Therefore, how to utilize the strong light absorption capabilities of Y-series non-fuller materials in the infrared and near-infrared bands to enable their aggregated states to maintain high fluorescence in the near-infrared region remains a technical challenge. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention proposes a high-fluorescence quantum yield near-infrared II material, its preparation method, and its applications. By introducing units with aggregation-induced emission (AIE) properties onto the thiophene side chain of a Y-series non-fullerene acceptor, and utilizing mechanisms such as enhanced molecular steric hindrance and improved stacking, a high-fluorescence quantum yield near-infrared II luminescent material is prepared. Furthermore, after being encapsulated into nanoparticles by the amphiphilic polymers DSPE-PEG2000-FA and DSPE-PEG2000-L-arginine, it successfully enables vascular imaging in mice and treatment of breast cancer in mice.

[0005] On the one hand, the present invention provides a near-infrared II material with high fluorescence quantum yield, which is a compound as shown in formula (I), or a stereoisomer, geometric isomer or pharmaceutically acceptable salt of the compound shown in formula (I); (I); Where: Ring A is , , , or ; Each ring B is independently selected from the following groups: , , or ; Each Ar group is independently selected from the following groups: , , , , , , or ; R1, R2, R3, and R4 are each independently selected from C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 Alkylsilyl, the C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I.

[0006] R5~ R 33 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, benzene, thiophene, and C. 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C1-30 Alkylsilyl, the C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I.

[0007] In some implementation schemes, R1, R2, R3, and R4 are each independently C 4-10 Alkyl, C 4-10 Alkoxy, C 4-10 Alkylthio, C 4-10 Alkylsilyl, the C 4-10 Alkyl, C 4-10 Alkoxy, C 4-10 alkylthio and C 4-10 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I.

[0008] In some embodiments, R1, R2, R3, and R4 are independently C4 straight-chain alkyl, C5 straight-chain alkyl, C6 straight-chain alkyl, C7 straight-chain alkyl, C8 straight-chain alkyl, C9 straight-chain alkyl, and C6 straight-chain alkyl, respectively. 10 Straight-chain alkyl groups.

[0009] In some implementations, R1 and R3 are both straight-chain C4H9; R2 and R4 are both straight-chain C6H9. 13 .

[0010] In some implementation schemes, R5~R 33 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, benzene, thiophene, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -CH2CF2CHF2, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, -OCHF2, -OCF3, -OCHFCH2F, -OCF2CHF2, -OCH2CF3, or -OCH2CF2CHF2.

[0011] In some embodiments, it is a compound having one of the following structures or a stereoisomer, geometric isomer, or pharmaceutically acceptable salt of a compound having one of the following structures: .

[0012] On the other hand, the present invention provides a method for preparing the above-mentioned high fluorescence quantum yield near-infrared II material, comprising the following steps: Step 1: Compound 1 is coupled to give compound 2 via a Suzuki coupling reaction; Step 2: Compound 2 is reacted with the Stille reaction to yield compound 3; Step 3: Compound 3 is coupled with Stille reaction to give compound 4; Step 4: Compound 4 was converted to compound 5 by condensation ring closure and nucleophilic substitution reaction; Step 5: Compound 5 is reacted with Vilsmeier-Haack to give compound 6; Step 6: Compound 6 is reacted with Knoevenagel to give the compound shown in formula (I); The reaction route is as follows: .

[0013] On the other hand, the present invention provides phototherapy nanoparticles comprising the above-mentioned high fluorescence quantum yield near-infrared II material, and a matrix for encapsulating the above-mentioned material.

[0014] In some embodiments, the matrix is ​​one or both of DSPE-PEG2000-L arginine or DSPE-PEG2000-FA.

[0015] On the other hand, this invention protects the application of the above-mentioned high fluorescence quantum yield infrared II materials and phototherapy nanoparticles in the preparation of near-infrared II fluorescence imaging reagents, tumor photothermal therapy reagents, or integrated tumor phototherapy reagents.

[0016] In some implementations, the tumor includes solid tumors such as breast cancer, lung cancer, liver cancer, and colon cancer.

[0017] The present invention has achieved the following beneficial effects: 1) The high fluorescence quantum yield near-infrared II material prepared by this invention has good solubility, strong light absorption and emission of strong near-infrared fluorescence in the infrared and near-infrared regions, and has the potential for application in the biomedical field. Moreover, the synthesis conditions are mild and the price is moderate, making it potential for large-scale production.

[0018] 2) The high fluorescence quantum yield near-infrared II material prepared by this invention maintains high near-infrared fluorescence emission capability, while exhibiting good reactive oxygen species (ROS) generation capability and photothermal conversion capability under 808nm laser irradiation, and has excellent tumor therapeutic capability under the combined action of nitric oxide (NO) carrier L-arginine.

[0019] Unless otherwise stated, the following definitions will apply in this invention. For the purposes of this invention, chemical elements are defined according to the periodic table, CAS version, and the Chemical Handbook, 75th Ed, 1994. Furthermore, general principles of organic chemistry are found in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007; therefore, all content incorporates these references.

[0020] The term "alkyl" as used in this invention includes a monovalent hydrocarbon group with 1-20 carbon atoms, or 1-10 carbon atoms, or 1-6 carbon atoms, or 1-4 carbon atoms, or 1-3 carbon atoms, or 1-2 carbon atoms, consisting of a saturated straight-chain or branched chain, wherein the alkyl group may be independently and optionally substituted by one or more substituents described in this invention. Further examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t... -Bu, -C(CH3)3), n-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl -1-Butyl (-CH2CH(CH3)CH2CH3), n-Hexyl (-CH2CH2CH2CH2CH2CH3), 2-Hexyl (-CH(CH3)CH2CH2CH2CH3), 3-Hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-Methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-Methyl-2-pentyl (-CH(CH3)CH(CH3)CH2C) H3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), n-heptyl, and n-octyl, etc. The term "alkyl" and its prefix "alkane" are used here, both encompassing straight-chain and branched saturated carbon chains.

[0021] The term "alkoxy" or "alkyloxy" as used in this invention refers to an alkyl group, as defined herein, that is attached to other parts of a compound molecule via an oxygen atom. In some embodiments, the alkoxy group is C10. 1-4 Alkoxy groups; examples of which include, but are not limited to, methoxy, ethoxy, propoxy, and butoxy groups. Furthermore, the alkoxy group may be independently unsubstituted or substituted by one or more substituents described in this invention.

[0022] A ring system formed by a substituent connected to a ring by a bond means that the substituent can be substituted at any substituted position on the ring. For example, formula (a) means that the substituent R can be monosubstituted or polysubstituted at any possible substituted position on the pyridine ring.

[0023] Unless otherwise explicitly stated, the descriptive phrases “each and each is independently”, “each and each is independently”, and “each and each is independently” used throughout this document are interchangeable and should be interpreted broadly. They can mean either that the specific options expressed by the same symbols in different groups do not affect each other, or that the specific options expressed by the same symbols in the same group do not affect each other.

[0024] Unless otherwise indicated, the structural formulas described in this invention include all isomers (e.g., enantiomers, diastereomers, geometric isomers, or conformational isomers): for example, R and S configurations containing an asymmetric center, (Z) and (E) isomers of double bonds, and (Z) and (E) conformational isomers. Therefore, any single stereochemical isomer of the compounds of this invention, or a mixture of its enantiomers, diastereomers, geometric isomers, or conformational isomers, is within the scope of this invention.

[0025] The term "pharmaceutically acceptable salt" as used in this invention refers to the organic and inorganic salts of the compounds of this invention. Pharmaceutically acceptable salts are well-known in the field, as described in the literature: SMBerge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66:1-19, 1977. Salts formed from pharmaceutically acceptable non-toxic acids include, but are not limited to: inorganic acid salts formed by reaction with amino groups, such as hydrochlorides, hydrobromic acids, phosphates, sulfates, and perchlorates; organic acid salts, such as acetates, oxalates, maleates, tartrates, citrates, succinates, and malonates; or salts obtained by other methods described in the literature, such as ion exchange. Other pharmaceutically acceptable salts include adipate, malate, 2-hydroxypropionate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, cyclopentylpropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, transbutenedioic acid, gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, palmitate, pyrate, pectinate, persulfate, 3-phenylpropionate, picrate, pentanoate, propionate, stearate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0026] Unless otherwise stated herein or the context clearly indicates otherwise, the terms “an,” “a,” “the,” and similar terms used herein, as well as in the context of the invention (especially in the context of the claims), may be interpreted as including both the singular and the plural. Attached Figure Description

[0027] Figure 1 Dynamic light scattering and TEM images of BPTI-sTPE NPs.

[0028] Figure 2 The absorption curves of compound BPTI-sTPE in tetrahydrofuran and BPTI-sTPE NPs in water are shown.

[0029] Figure 3 The emission spectra of compound BPTI-sTPE in tetrahydrofuran and BPTI-sTPE NPs in water are shown.

[0030] Figure 4 The graph shows the photothermal conversion efficiency (PCE) of BPTI-sTPE NPs.

[0031] Figure 5 This is a graph showing the ROS generation capacity of the compound BPTI-sTPE.

[0032] Figure 6 Image of the tumor 15 days after treatment with BPTI-sTPE NPs.

[0033] Figure 7 This is a near-infrared image of the blood vessels throughout the mouse body. Detailed Implementation

[0034] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] The endpoints and any values ​​of the ranges described in this invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein. The raw materials and reagents used in the following examples are commercially available.

[0036] Example 1: Preparation of compound BPTI-sTPE Step 1: Preparation of compound C

[0037]

[0038] Under argon atmosphere, 3-bromothiophene[3,2-b]thiophene (1 g, 4.8 mmol), 1-(4-phenylboronic acid pinacol ester)-1,2,2-tristyrene (2 g, 4.4 mmol), Pb(PPh3)4 (510 mg, 0.44 mmol), and K2CO3 (4.4 g, 32 mmol) were charged into a 250 mL round-bottom flask, followed by the addition of anhydrous THF (10 mL) and water (4 mL). The reaction mixture was heated to 80°C and stirred continuously for 12 hours. After cooling to room temperature, the crude product was quenched in water and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by silica gel column chromatography using dichloromethane / petroleum ether (1 / 3, v / v) as eluent. The final product was obtained by recrystallization from a mixture of dichloromethane and methanol to give 1.74 g of white solid, in 84% yield.

[0039] 1 H NMR (500 MHz, Chloroform-d) δ 7.56 (d, J = 8.0 Hz, 2H), 7.51 (d, J= 1.4 Hz, 1H), 7.46 (d, J = 5.2 Hz, 1H), 7.33 (d, J = 5.2 Hz, 1H), 7.17 –7.14 (m, 11H), 7.12 (dd, J = 7.5, 2.3 Hz, 4H), 7.08 (dd, J = 7.0, 2.7 Hz, 2H). 13 C NMR (126 MHz, Chloroform-d) δ 143.73, 143.64, 143.12, 141.33,140.42, 139.54, 137.69, 134.08, 132.55, 131.96, 131.47, 131.38, 127.84,127.76, 127.68, 127.26, 126.60, 126.56, 126.50, 125.47, 122.37, 119.76. Step 2: Preparation of compound D

[0040]

[0041] Under argon atmosphere, compound C (1.3 g, 2.77 mmol) was added to a two-necked flask and dissolved in 10 mL of dry tetrahydrofuran. The mixture was then placed at -78 °C and 1.4 mL of n-butyllithium solution (2.4 M) was added dropwise. After stirring at -78 °C for one hour, 1 mL of tributyltin chloride was added dropwise. The mixture was slowly brought to room temperature and stirred for another 6 hours. The reaction was quenched with potassium fluoride solution, and the mixture was extracted three times with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product, compound D.

[0042] Step 3: Preparation of compound E

[0043] Under argon atmosphere, 4,7-dibromo-5,6-dinitrobenzo[c][1,2,5]thiadiazole (300 mg, 0.78 mmol), compound D (1.3 g, 1.71 mmol), toluene (10 mL), and 5% Pd(PPh3)4 (117 mg, 0.10 mmol) were added to a 250 mL two-necked flask. The mixture was heated to 110 °C and reacted in the dark for 10 h. After cooling to room temperature, the crude product was quenched in potassium fluoride solution and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The extracts were then purified by silica gel column chromatography using dichloromethane / petroleum ether (1 / 3, v / v) as the eluent. The final product, compound E, was obtained by recrystallization from a mixed solvent of dichloromethane and methanol, yielding 0.59 g of a purple solid (64.9%).

[0044] 1 H NMR (500 MHz, Chloroform-d) δ 7.73 (s, 2H), 7.63 (s, 2H), 7.53 –7.50 (m, 4H), 7.16 – 7.12 (m, 16H), 7.11 – 7.07 (m, 14H), 7.05 – 7.03 (m,4H). 13 C NMR (126 MHz, Chloroform-d) δ 152.20, 143.67, 143.59, 141.98,141.57, 140.27, 139.81, 134.47, 132.15, 131.84, 131.49, 131.42, 131.39,127.91, 127.82, 127.72, 126.71, 126.64, 125.62, 125.48, 123.74, 121.45.

[0045] Step 4: Preparation of compound F

[0046] Under argon protection, compound E (350 mg, 0.3 mmol), triphenylphosphine (790 mg, 10 mmol), and o-dichlorobenzene (8 mL) were added to a 250 mL round-bottom flask. The mixture was reacted at 180 °C for 12 hours. After cooling to room temperature, the solvent was removed by vacuum distillation to obtain a crude product, a reddish-brown solid (320 mg). The reddish-brown crude product, potassium carbonate (404 mg, 2.9 mmol), 5-(bromomethyl)undecane (1.07 g, 3.5 mmol), and N,N-dimethylformamide (12 mL) were mixed and reacted at 80 °C for 10 hours. After cooling to room temperature, the mixture was extracted with dichloromethane, the solvent was evaporated, and the mixture was purified by silica gel column chromatography to obtain a red solid (136 mg, 31.5%), which was compound F.

[0047] 1 H NMR (500 MHz, Chloroform-d) δ 7.66 (d, J = 7.9 Hz, 4H), 7.48 (s,2H), 7.22 – 7.12 (m, 30H), 7.10 (dd, J = 6.7, 2.4 Hz, 4H), 4.65 (q, J = 5.6,3.9 Hz, 4H), 2.10 (p, J = 6.7 Hz, 2H), 0.96 (dtdd, J = 43.1, 29.7, 14.1, 7.1Hz, 30H), 0.64 (dq, J = 14.4, 7.2 Hz, 14H). 13 C NMR (126 MHz, Chloroform-d) δ 147.59, 143.70, 143.60, 143.58,141.45, 140.36, 139.93, 136.02, 132.19, 132.05, 131.92, 131.46, 131.39,127.87, 127.79, 127.69, 126.73, 126.60, 126.52, 125.93, 119.70, 111.50,55.10, 38.75, 31.57, 30.39, 30.26, 30.11, 29.37, 29.34, 28.03, 27.84, 25.32, 25.12, 22.78, 22.75, 22.49, 22.47, 13.99, 13.97, 13.81, 13.77. Step 5: Preparation of compound G

[0048]

[0049] In a three-necked flask, compound F (100 mg, 0.07 mmol), dichloroethane (5 mL), and anhydrous N,N-formamide (1 mL) were added. The temperature was lowered to 0 °C, and phosphorus oxychloride (0.2 mL) was added. The mixture was stirred for 1 hour. The temperature was then raised to 85 °C and stirred overnight. After cooling to room temperature, the mixture was extracted with dichloromethane, the solvent was evaporated, and the mixture was purified by silica gel column chromatography to obtain a bright yellow solid (90 mg, 86.6%), which was compound G.

[0050] 1 H NMR (500 MHz, Methylene Chloride-d2) δ 9.91 (s, 2H), 7.57 (d, J =8.0 Hz, 4H), 7.31 (d, J = 7.9 Hz, 4H), 7.24 – 7.13 (m, 30H), 4.73 (td, J =8.2, 7.4, 3.2 Hz, 4H), 2.11 (dd, J = 12.5, 6.3 Hz, 2H), 1.17 – 0.85 (m, 28H), 0.75 – 0.59 (m, 16H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 132.10, 131.32, 131.28,131.19, 128.97, 127.85, 127.84, 127.71, 53.90, 53.68, 53.47, 53.25, 53.03,31.54.

[0051] Step 6: Preparation of compound BPTI-sTPE (compound H)

[0052] Under argon protection, in a 250 mL round-bottom flask, compound G (90 mg, 0.06 mmol) and 3-(dicyanomethylene)indophenone (30 mg, 0.15 mmol) were dissolved in 5 mL chloroform, and 1 mL pyridine was added. The mixture was refluxed for 12 hours, cooled to room temperature, and poured into 100 mL anhydrous methanol. The crude product was obtained by filtration and purified by silica gel column chromatography to give a dark blue solid (87 mg, 78.2%), which was compound BPTI-sTPE.

[0053] 1H NMR (500 MHz, Chloroform-d) δ 8.89 (s, 2H), 8.71 (d, J = 7.3 Hz, 2H), 8.00 – 7.96 (m, 2H), 7.82 – 7.76 (m, 4H), 7.46 (d, J = 7.8 Hz, 4H), 7.34(d, J = 7.9 Hz, 4H), 7.19 (tdd, J = 22.6, 15.5, 5.4 Hz, 30H), 4.80 (hept, J =8.4, 7.9 Hz, 4H), 2.18 (p, J = 6.6 Hz, 2H), 1.26 – 0.85 (m, 30H), 0.68 (ddt,J = 29.0, 14.7, 7.3 Hz, 14H). 13 C NMR (126 MHz, Chloroform-d) δ 188.12, 150.72, 147.55, 146.25,144.40, 143.69, 143.41, 143.34, 142.32, 140.11, 139.99, 138.35, 137.59,136.92, 135.06, 134.31, 134.22, 133.85, 133.28, 132.75, 131.76, 131.69,131.44, 130.54, 129.76, 128.03, 127.85, 127.73, 126.90, 126.75, 126.67, 125.10, 123.63, 122.27, 115.07, 114.05, 113.33, 69.04, 55.65, 39.19, 31.61, 30.52, 30.42, 29.48, 22.90, 22.84, 22.53, 22.51, 14.06, 14.04, 13.84, 13.80. Example 2: Preparation of BPTI-sTPE nanoparticles (BPTI-sTPE NPs) 1 mg of the near-infrared II material (compound BPTI-sTPE) prepared in Example 1, 2.5 mg of DSPE-PEG2000-L arginine, and 2.5 mg of DSPE-PEG2000-FA were dissolved in 1 mL of tetrahydrofuran to obtain a photosensitizer solution. This photosensitizer solution was then added dropwise to 10 mL of ultrapure water, and the mixture was sonicated for 5 min using a cell disruptor (220 Hz). The mixture was then ultrafiltered and washed three times to obtain BPTI-sTPE nanoparticles based on the near-infrared II region.

[0054] Dynamic light scattering and TEM images of BPTI-sTPE nanoparticles are shown below. Figure 1 . To investigate the optical properties of the molecules, the absorption and emission spectra of compounds BPTI-sTPE and BPTI-sTPE NPs were measured. The results are shown below. Figure 2 and Figure 3 .

[0055] Depend on Figure 2 and Figure 3 It is known that in the THF solvent system, the absorption peak of compound BPTI-sTPE is around 696 nm, and the emission peak is around 780 nm. When prepared as nanoparticles, the absorption peak of BPTI-sTPE NPs in aqueous solvent is around 748 nm, and the emission peak is around 960 nm, with emission reaching up to 1400 nm. Therefore, the near-infrared II material prepared in this invention has strong light absorption and strong near-infrared fluorescence in the infrared and near-infrared regions.

[0056] Figure 4 The graph shows the photothermal conversion efficiency (PCE) of BPTI-sTPE NPs. After irradiation with an 808 nm laser (0.5 W·cm⁻²) for 5 minutes, the temperature of the BPTI-sTPE NPs aqueous solution can rise to above 63 °C, while the temperature rise of pure water is negligible, indicating that BPTI-sTPE NPs have a significant photothermal effect. After five laser switching cycles, the temperature rise curves of BPTI-sTPE NPs basically overlap, demonstrating excellent photothermal stability; the calculated photothermal conversion efficiency (PCE) of BPTI-sTPE NPs is 68%.

[0057] Dichlorofluorescein (DCFH) was used as a total reactive oxygen species (ROS) indicator to evaluate the ROS generation capacity of compound BPTI sTPE. Results are shown below. Figure 5Within 5 minutes of 808 nm laser irradiation, the fluorescence intensity of DCFH increased approximately 120-fold in the presence of compound BPTI sTPE, ​​indicating its effective generation of reactive oxygen species. To further distinguish reactive oxygen species, we used hydroxyfluorescein (HPF, for detecting ·OH) and dihydrorhodamine 123 (DHR123, for detecting O2), respectively. - ·) and 9,10 anthracene dimalonic acid (ABDA, detection) 1 Specific detection was performed using O2. The results showed that compound BPTI sTPE mainly generates hydroxyl radicals (·OH) and superoxide anions (O2) via a type I photodynamic pathway. - ·), while singlet oxygen ( 1 The generation of O2 is negligible.

[0058] BPTI-sTPE NPs were injected into breast cancer mice via tail vein at a concentration of 500 ug / mL. 24 h after injection, the mice were treated with an 808 nm laser (0.8 W / cm²). 2 The tumor site was exposed to light, and the tumor temperature was recorded. This was repeated every 3 days for a total of 2 treatments. Mice were euthanized after 14 days, and tumor tissue was collected for immunofluorescence sectioning to evaluate the treatment effect. Results are shown below. Figure 6 The results showed that BPTI-sTPE NPs have excellent tumor therapeutic capabilities at 808nm.

[0059] Images of the whole body and leg blood vessels of healthy mice were obtained by intravenous injection of BPTI-sTPE nanoparticles (0.5 mg / mL, 0.2 mL) under 808 nm laser irradiation in a live imaging system. Results are shown below. Figure 7 The results showed that blood vessels throughout the mouse's body and legs were clearly visible.

[0060] The above embodiments are merely illustrative examples and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A near-infrared II material with high fluorescence quantum yield, which is a compound as shown in formula (I), or a stereoisomer, geometric isomer or pharmaceutically acceptable salt of the compound shown in formula (I); （I）； Ring A is , , , or ; Each ring B is independently selected from the following groups: , , or ; Each Ar group is independently selected from the following groups: , , , , , , or ; R1, R2, R3, and R4 are each independently selected from C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 Alkylsilyl, the C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I; R5~ R 33 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, benzene, thiophene, and C. 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 Alkylsilyl, the C 1-30 Alkyl, C 1-30 Alkoxy, C 1-30 alkylthio and C 1-30 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I.

2. The high fluorescence quantum yield near-infrared II material according to claim 1, characterized in that, R1, R2, R3, and R4 are each independently C 4-10 Alkyl, C 4-10 Alkoxy, C 4-10 Alkylthio, C 4-10 Alkylsilyl, the C 4-10 Alkyl, C 4-10 Alkoxy, C 4-10 alkylthio and C 4-10 The alkylsilyl group can be independently and optionally replaced by substituents selected from F, Cl, Br and I.

3. The high fluorescence quantum yield near-infrared II material according to claim 2, characterized in that, R1, R2, R3, and R4 are independently C4 straight-chain alkyl, C5 straight-chain alkyl, C6 straight-chain alkyl, C7 straight-chain alkyl, C8 straight-chain alkyl, C9 straight-chain alkyl, and C4 straight-chain alkyl, respectively. 10 Straight-chain alkyl groups.

4. The high fluorescence quantum yield near-infrared II material according to claim 3, characterized in that, R1 and R3 are both straight-chain C4H9; R2 and R4 are both straight-chain C6H9. 13 .

5. The high fluorescence quantum yield near-infrared II material according to claim 1, characterized in that, R5~ R 33 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, benzene, thiophene, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -CH2CF2CHF2, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, -OCHF2, -OCF3, -OCHFCH2F, -OCF2CHF2, -OCH2CF3, or -OCH2CF2CHF2.

6. The high fluorescence quantum yield near-infrared II material according to claim 1, wherein it is a compound having one of the following structures or a stereoisomer, geometric isomer, or pharmaceutically acceptable salt of a compound having one of the following structures: 。 7. A method for preparing the high fluorescence quantum yield near-infrared II material according to any one of claims 1 to 6, comprising the following steps: Step 1: Compound 1 is coupled to give compound 2 via a Suzuki coupling reaction; Step 2: Compound 2 is reacted with the Stille reaction to yield compound 3; Step 3: Compound 3 is coupled with Stille reaction to give compound 4; Step 4: Compound 4 was converted to compound 5 by condensation ring closure and nucleophilic substitution reaction; Step 5: Compound 5 is reacted with Vilsmeier-Haack to give compound 6; Step 6: Compound 6 is reacted with Knoevenagel to give the compound shown in formula (I); The reaction route is as follows: 。 8. A phototherapy nanoparticle comprising the high fluorescence quantum yield near-infrared II material as described in any one of claims 1-7, and a matrix for encapsulating the aforementioned material.

9. The phototherapy nanoparticles according to claim 8, characterized in that the matrix is ​​one or both of DSPE-PEG2000-L arginine or DSPE-PEG2000-FA.

10. The use of the high fluorescence quantum yield infrared II material according to any one of claims 1-7, and the phototherapy nanoparticles according to claim 8 or 9 in the preparation of near-infrared II fluorescence imaging reagents, tumor photothermal therapy reagents, or integrated tumor phototherapy reagents.

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