A tetramethyl-julolidine substituted azafluoroiondopyrromethene phototherapeutic agent and a method of preparation thereof

Abstract

This invention relates to a phototherapy agent for cancer treatment and its preparation method, particularly to a tetramethyljulonidine-substituted azafluoroboron dipyrrole phototherapy agent and its preparation method. This invention innovatively constructs a donor-acceptor structure locally at the molecular level by introducing the strongly electron-donating group tetramethyljulonidine into the aza-BODIPY backbone, resulting in a significant redshift in the absorption of the aza-BODIPY dye molecule, reaching the near-infrared II region, and simultaneously possessing the potential for combined photothermal and photodynamic therapy. The process involved is simple and efficient, and the raw materials are readily available, providing a new approach for developing synergistic aza-BODIPY phototherapy agents. The results of this invention further enrich the structural categories of azafluoroboron dipyrrole biomolecules, broadening design ideas for their application in fluorescence imaging, biomedicine, and functional dyes.

Description

Technical Field

[0001] This invention relates to a phototherapy agent for treating cancer and its preparation method, and particularly to a tetramethyljulonidine-substituted azirmonoborosiazole phototherapy agent and its preparation method. Background Technology

[0002] Aza-BODIPY fluorescent dyes are a class of organic heterocyclic compounds that have attracted considerable research interest due to their high molar extinction coefficient, high fluorescence quantum yield, and excellent photostability. Modification of the aza-BODIPY backbone can redshift its absorption and emission spectra to the near-infrared region, meeting diverse application requirements and offering broad potential for use in the biomedical field.

[0003] The Aza-BODIPY core is inherently electron-deficient, therefore electron-donating groups can be introduced at the 1,7- and 3,5- positions, effectively amplifying the molecular conjugation effect and thus altering the molecular absorption spectrum and excited state. Tetrahedron , 2021,83, 131983). Julonidine is a rigid planar tricyclic system derived from N,N-dialkylaniline, possessing strong electron-donating ability and structural rigidity ( J. PHOTOCH PHOTOBIO. A , 2023, 437, 114422).

[0004] Numerous studies have revealed that julonidine-substituted aza-BODIPY derivatives exhibit excellent photophysical properties and hold promise as imaging agents in the near-infrared II (NIR-II) region. Chin. Chem. Lett , 2024, 35, 109735).

[0005] However, the novel structure of tetramethyljulonidine in the aza-BODIPY system has not been reported to date. Based on this background, a novel near-infrared II phototherapy agent with synergistic phototherapy potential is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a tetramethyljulonidine-substituted azafluoroboron dipyrrole phototherapy agent and its preparation method. This invention involves introducing 1,1,7,7-tetramethyljulonidine as a donor group at the modification site to locally construct a donor-acceptor structure in an aza-BODIPY dye. Based on research on traditional julonidine in aza-BODIPY derivatives, tetramethyljulonidine was selected as a novel substituent to construct a new molecular platform for the application of aza-BODIPY derivatives in the field of phototherapy. The novel aza-BODIPY dye, under the influence of the four methyl groups, exhibits a highly distorted spatial configuration. While inheriting near-infrared II fluorescence emission levels and good photothermal stability, it also possesses reactive oxygen species generation capabilities, enabling combined photothermal and photodynamic therapy, thus broadening the application of aza-BODIPY in cancer phototherapy.

[0007] The objective of this invention is achieved through the following technical solution: Tetramethyljulodinidine-substituted aza-BODIPY phototherapy agent, with the general formula shown as BDP-Me:

[0008] In the formula BDP-Me, Ar is selected from Ar1-Ar8 aryl groups:

[0009] Examples of representative molecular structures are as follows:

[0010] A method for preparing aza-BODIPY phototherapy agent substituted with tetramethyljulodin, the method comprising the following steps: (1) Synthesis of compound M2: Compound M1 was dissolved in 1,2-dichloroethane under nitrogen protection. Meanwhile, N,N-dimethylformamide was mixed with POCl3 at low temperature. After the system solidified into a white solid, it was cooled to room temperature to dissolve. The two systems were then mixed and reacted at 75 °C for 30–45 min. After the reaction, the system was cooled to room temperature, and a saturated potassium carbonate solution was slowly injected. The mixture was then heated to 80 °C and refluxed for 30–45 min. After the reaction was complete, the mixture was extracted with dichloromethane, and the organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:15, v / v) to obtain a pale yellow solid, M2.

[0011]

[0012] (2) Synthesis of compound M4: Compound M2 and acetylbenzene M3 were dissolved in methanol, and solid potassium hydroxide was added and stirred until completely dissolved. The mixture was heated under reflux for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:50, v / v) to obtain a bright yellow solid M4.

[0013]

[0014] In M3 and M4, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0015] (3) Synthesis of compound M5: Compound M4 was dissolved in methanol and placed in a 250 mL round-bottom flask. Sodium methoxide and nitromethane were added sequentially. The mixture was heated and stirred for 3–6 h. After the reaction was complete, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (dichloromethane) to obtain a reddish-brown oily substance, M5.

[0016]

[0017] In M5, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0018] (4) Synthesis of compound M6: Compound M5 and ammonium acetate were dissolved in methanol and placed in a 250 mL round-bottom flask. The mixture was heated and stirred for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, washed in a saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain a dark blue solid, M6.

[0019]

[0020] In M6, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0021] (5) Synthesis of dye BDP-Me: Under nitrogen protection, compound M6 and triethylamine were dissolved in 1,2-dichloroethane and stirred for 10 min. Then, BF3·Et2O was slowly added dropwise. The mixture was heated for 2–4 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (n-hexane / dichloromethane = 1:1, v / v) to obtain a deep blue solid, BDP-Me.

[0022]

[0023] In BDP-Me, Ar is selected from the Ar1-Ar8 groups (e.g., BDP-MeSJ: Ar = Ar1).

[0024] The advantages and effects of this invention are: 1. The novel aza-BODIPY phototherapy agent studied in this invention exhibits near-infrared II fluorescence and demonstrates good photothermal conversion efficiency and singlet oxygen production. Through synergistic photothermal and photodynamic therapy, it can effectively inhibit tumor cell activity and induce apoptosis.

[0025] 2. The tetramethyljulodinium-substituted aza-BODIPY derivatives involved in this invention, as a novel near-infrared II phototherapy agent, exhibit superior photodynamic properties in addition to the performance of traditional julodinium-substituted phototherapy agents through the introduction of innovative groups into the aza-BODIPY core, resulting in a novel conformation. This provides theoretical support for their participation in novel phototherapy modalities such as combined cancer phototherapy and drug synergistic therapy. This series of compounds is highly modifiable and is expected to promote the research and development of more structurally novel and high-performance aza-BODIPY derivatives. Attached Figure Description

[0026] Figure 1 The structural formula of the novel near-infrared phototherapy agent of this invention is BDP-MeSJ; Figure 2 This is the hydrogen spectrum of the novel near-infrared phototherapy agent BDP-MeSJ of this invention; Figure 3 This is the carbon spectrum of the novel near-infrared phototherapy agent BDP-MeSJ of this invention; Figure 4 The hydrogen spectrum of the intermediate structural formula M4 (Ar = Ar1) of this invention is shown. Figure 5 The carbon spectrum of the intermediate structure M4 (Ar = Ar1) of this invention is shown. Figure 6 The hydrogen spectrum of the intermediate structural formula M5 (Ar = Ar1) of this invention is shown. Figure 7 The carbon spectrum of the intermediate structure M5 (Ar = Ar1) of this invention is shown. Figure 8 This invention relates to the high-resolution mass spectrometry of the novel near-infrared phototherapy agent BDP-MeSJ. Figure 9 This invention relates to the single-crystal structure of the novel near-infrared phototherapy agent BDP-MeSJ. Figure 10 The absorption spectrum (λ) of the novel near-infrared phototherapy agent BDP-MeSJ of this invention is shown. abs = 850 nm in dichloromethane); Figure 11 The emission spectrum (λ) of the novel near-infrared phototherapy agent BDP-MeSJ of this invention is shown. em = 1029 nm in dichloromethane); Figure 12 This is a photothermal test diagram of the novel near-infrared phototherapy agent BDP-MeSJ NPs of the present invention; Figure 13 This is a singlet oxygen test result of the novel near-infrared phototherapy agent BDP-MeSJ of the present invention under DPBF scavenging agent; Figure 14 The image shows the ROS generation effect of the novel near-infrared phototherapy agent BDP-MeSJ of this invention under the detection of the reactive oxygen species fluorescent probe DHR-123. Figure 15 The novel near-infrared phototherapy agent BDP-MeSJ NPs of this invention was used to detect the activity of MDA-MB-231 cells and 4T1 cells using CCK8 assay. Figure 16 These are schematic diagrams of live and dead cell staining and flow cytometry of the novel near-infrared phototherapy agent BDP-MeSJ NPs of this invention. Figure 17 This is a schematic diagram of intracellular reactive oxygen species in the novel near-infrared phototherapy agent BDP-MeSJ NPs of this invention. Detailed Implementation

[0027] The present invention will now be described in detail with reference to the examples shown in the accompanying drawings.

[0028] Unless otherwise stated, the terms used herein have the following meanings.

[0029] In the general formula BDP-Me of this invention, Ar is selected from the Ar1-Ar8 groups, with 4-methylthiophenyl, phenyl, and 4-methoxyphenyl being preferred.

[0030] This invention provides a method for preparing the aforementioned phototherapy agent. The method begins by using a tetramethyljulonidine fragment M1 as a starting material, introducing an aldehyde group via a Vilsmeier-Haack reaction to obtain an aldehyde-substituted intermediate M2. M2 undergoes an aldol condensation reaction with an acetylphenyl compound to generate M4, which then undergoes a Michael addition reaction with nitromethane to obtain M5. Subsequently, M5 is further converted to obtain a dye precursor M6, and finally, M6 is complexed with boron trifluoride diethyl ether to obtain the target aza-BODIPY-type phototherapy agent product.

[0031] The specific process is as follows: (1) Synthesis of compound M2: Under nitrogen protection, compound M1 was dissolved in 1,2-dichloroethane and stirred. Meanwhile, N,N-dimethylformamide was mixed with POCl3 at low temperature (–30 °C) and stirred for 15 min. After the system solidified into a white solid, it was cooled to room temperature to dissolve. The two systems were then mixed and heated for 30–45 min. After the reaction was complete, the mixture was cooled to room temperature, and a saturated potassium carbonate solution was slowly added. The mixture was then heated under reflux for 30–45 min. Finally, the reaction solution was poured into a saturated sodium chloride solution and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:15, v / v) to obtain a pale yellow solid, M2.

[0032]

[0033] In a preferred embodiment, the heating temperature is 75 °C and the reaction time is 40 min. The molar ratio of compound M1 to N,N-dimethylformamide and POCl3 is 1:2:2.

[0034] (2) Synthesis of compound M4: Compound M2 and acetylphenyl M3 were dissolved in methanol and mixed in a round-bottom flask. Solid potassium hydroxide was added and stirred until completely dissolved. The mixture was heated under reflux for 12–24 h. After the reaction was complete, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:50, v / v) to obtain a bright yellow solid, M4.

[0035]

[0036] In M3 and M4, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0037] In a preferred embodiment, the reaction temperature is 60 °C and the reaction time is 24 h. The molar ratio of M2 to the corresponding acetylphenyl is 1:2.

[0038] (3) Synthesis of compound M5: Compound M4 was dissolved in methanol and placed in a 250 mL round-bottom flask, stirred until completely dissolved. Sodium methoxide and nitromethane were added sequentially. The mixture was heated to 90–110 °C and stirred for 3–6 h. After the reaction was complete, it was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography to obtain a reddish-brown oily substance, M5.

[0039]

[0040] In M5, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0041] In a preferred embodiment, the reaction temperature is 90 °C and the reaction time is 6 h. The molar ratio of M4 to nitromethane and sodium methoxide is 1:4:4.

[0042] (4) Synthesis of compound M6: Compound M5 and ammonium acetate were dissolved in methanol and placed in a 250 mL round-bottom flask. The mixture was heated to 110 °C and stirred for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, washed in saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain a dark blue solid, M6.

[0043]

[0044] In M6, Ar is selected from the Ar1-Ar8 groups mentioned above.

[0045] In a preferred embodiment, the reaction temperature is 110 °C and the reaction time is 24 h. The molar ratio of M5 to ammonium acetate is 1:10.

[0046] (5) Synthesis of dye BDP-Me: Under nitrogen protection, compound M6 and triethylamine were dissolved in 1,2-dichloroethane and stirred for 10 min. Then, BF3·Et2O was slowly added dropwise. The mixture was heated for 2–4 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (n-hexane / dichloromethane = 1:1, v / v) to obtain a deep blue solid, BDP-Me.

[0047]

[0048] In BDP-Me, Ar is selected from the Ar1-Ar8 groups described above; In a preferred embodiment, the reaction temperature is 70 °C, the reaction time is 3 h, and the molar ratio of compound M6 to triethylamine to boron trifluoride ether is 1:15:20.

[0049] For the compounds described above in this invention, nuclear magnetic resonance (NMR) spectra are used to include... 1 H, 13 C10 NMR nuclear magnetic spectrum, absorption spectrum (l) abs = 850 nm in CH2Cl2), fluorescence spectrum (l em Its structure was determined by high-resolution mass spectrometry and single-crystal analysis (1029 nm in CH2Cl2).

[0050] The tetramethyljulodin-substituted aza-BODIPY phototherapy agent of the present invention has the following characteristics: The most innovative aspect of the compound lies in the innovative structural design of the aza-BODIPY biomolecule, which represents a breakthrough improvement over the traditional classic azaBODIPY skeleton.

[0051] The compound exhibits excellent chemical stability and good photothermal conversion ability, demonstrating good potential for photothermal therapy.

[0052] The compound can effectively generate singlet oxygen, indicating that it has good photodynamic therapy effects.

[0053] The compound has a wide range of raw material sources, a novel structure, and a simple synthetic route, and has good operability and industrialization potential. Example 1

[0054] Prepare a tetramethyljulodin-substituted aza-BODIPY phototherapy agent, BDP-MeSJ.

[0055]

[0056] (1) Synthesis scheme of BDP-MeSJ substituted with tetramethyljulodin.

[0057] (2) Synthesis of compound M2: Under nitrogen protection, compound M1 (1.03 g, 4.5 mmol) was dissolved in 1,2-dichloroethane (15 mL) and stirred. Meanwhile, N,N-dimethylformamide (0.65 g, 9 mmol) and POCl3 (1.39 g, 9 mmol) were mixed at low temperature (–30 °C) and stirred for 15 min. After the system solidified into a white solid, it was cooled to room temperature to dissolve. The two systems were then mixed and reacted at 75 °C for 40 min. After the reaction was complete, the mixture was cooled to room temperature, and a saturated potassium carbonate solution (50 mL) was slowly injected into the system. After the system stabilized, it was refluxed at 75 °C for 40 min. Finally, the reaction solution was poured into a saturated sodium chloride solution, extracted with dichloromethane, and the organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (eluent: ethyl acetate / dichloromethane = 1:15, v / v) to give a pale yellow solid M2 (1.05 g, 4 mmol, yield 90%).

[0058] (3) Synthesis of compound M4-SJ: Compound M2 (1.05 g, 4 mmol) and 4-methylthioacetophenone M3-SJ (0.83 g, 5 mmol) were dissolved in methanol (30 mL) and placed in a 250 mL round-bottom flask. Potassium hydroxide (2.00 g) solid was added and stirred until completely dissolved. The mixture was heated to 60 °C and refluxed for 24 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane (100 mL × 3). The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (eluent: ethyl acetate / dichloromethane = 1:50, v / v) to obtain a bright yellow solid M4-SJ (1.05 g, yield 64%). 1 H NMR (400 MHz, Chloroform- d ) δ 7.94 (d, J = 8.5 Hz, 2H), 7.74 (d, J = 15.4 Hz, 1H), 7.34 (s, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.22 (d, J = 15.4 Hz, 1H), 3.32 – 3.23 (m, 4H), 2.53 (s, 3H), 1.78 – 1.72 (m, 4H), 1.31 (s, 12H).

[0059] (4) Synthesis of compound M5-SJ: Compound M4-SJ (1.05 g, 2.5 mmol) was dissolved in methanol (30 mL) in a 250 mL round-bottom flask and stirred until completely dissolved. Sodium methoxide (0.54 g, 10 mmol) and nitromethane (1 mL) were added sequentially. The mixture was heated to 90 °C and stirred for 6 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane (100 mL × 3). The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (eluent: dichloromethane) to obtain a reddish-brown oily substance M5-SJ (0.46 g, yield 40%). 1 H NMR (400MHz, Chloroform- d ) δ 7.80 (d, J = 8.6 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 6.86(s, 2H), 4.71 (ddd, J= 51.3, 12.2, 7.3 Hz, 2H), 4.03 (dt, J = 13.6, 7.2 Hz,1H), 3.39 – 3.26 (m, 2H), 3.14 – 3.04 (m, 4H), 2.50 (s, 3H), 1.75 – 1.68 (m,4H), 1.23 (s, 12H).

[0060] (5) Synthesis of compound M6-SJ: Compound M5-SJ (0.46 g, 1 mmol) and ammonium acetate (0.77 g, 10 mmol) were dissolved in methanol (30 mL) and placed in a 250 mL round-bottom flask. The mixture was heated to 110 °C and stirred for 12 h. After the reaction was completed, the mixture was cooled to room temperature, washed in saturated sodium chloride solution, and extracted with dichloromethane (100 mL × 3). The organic phases were combined, dried, and concentrated under reduced pressure to obtain a dark blue solid M6-SJ (0.12 g, yield 30%).

[0061] (6) Synthesis of dye BDP-MeSJ: Under nitrogen protection, compound M6-SJ (0.12 g, 0.15 mmol) and triethylamine (0.2 mL, 2 mmol) were dissolved in 1,2-dichloroethane (20 mL). After stirring for 10 min, BF3·Et2O (0.4 mL, 3 mmol) was slowly added dropwise. The mixture was heated to 70 °C and reacted for 3 h. After the reaction was completed, the mixture was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane (100 mL × 3). The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (eluent: n-hexane / dichloromethane = 1:1, v / v) to obtain a deep blue solid BDP-MeSJ (0.08 g, yield 60%). 1 H NMR (400 MHz, Pyridine- d 5) δ 8.39 (d, J = 8.6 Hz, 4H), 7.77 (s, 4H), 7.35 (d, J = 8.5 Hz, 4H), 7.19 (s, 2H), 3.23 (t, J = 6.0 Hz, 8H), 2.36(s, 6H), 1.72 (t, J = 6.0 Hz, 8H), 1.23 (s, 24H).

[0062] The above description, in conjunction with specific optimized embodiments, provides a further detailed explanation of the present invention and should not be construed as limiting the specific implementation of the invention to these descriptions. For those skilled in the art, based on the core concept of the present invention, several simple deductions and substitutions can be made, all of which should be considered within the scope of protection of the present invention. Furthermore, for those skilled in the art, based on the present invention, several simple inferences can be made to derive other applications of the compounds of the present invention, all of which should be considered within the scope of protection of the present invention.

Claims

1. A tetramethyljulonidine-substituted azirfluborone dipyrrole phototherapy agent, characterized in that, The tetramethyljulodin-substituted aza-BODIPY phototherapy agent has the general formula shown in BDP-Me: ； In the formula BDP-Me, Ar is selected from Ar1-Ar8 aryl groups: 。 2. A method for preparing a tetramethyljulonidine-substituted azirfluborone dipyrrole phototherapy agent, characterized in that, The method includes the following steps: (1) Synthesis of compound M2: Under nitrogen protection, compound M1 was dissolved in 1,2-dichloroethane and stirred; N,N-dimethylformamide was mixed with POCl3 at low temperature (–30 °C) and stirred for 15 min. After the system solidified to form a white solid, it was heated to room temperature to dissolve. Then the two systems were mixed and heated to react for 40 min. After the reaction was completed, it was cooled to room temperature, and saturated potassium carbonate solution was slowly added to the system. The mixture was then heated to reflux for 40 min. Finally, the reaction solution was poured into saturated sodium chloride solution and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:15, v / v) to obtain a pale yellow solid M2. ； (2) Synthesis of compound M4: Compound M2 and acetylphenyl M3 were dissolved in methanol and mixed in a round-bottom flask; potassium hydroxide (2.00 g) solid was added and stirred until completely dissolved; the mixture was heated to 60 °C and refluxed for 12–24 h (preferably 18–24 h); after the reaction was completed, it was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane; the organic phases were combined, dried and concentrated under reduced pressure to obtain crude product; the crude product was purified by rapid column chromatography (ethyl acetate / dichloromethane = 1:50, v / v) to obtain bright yellow solid M4; ； In M3 and M4, Ar is selected from the Ar1-Ar8 groups described above; (3) Synthesis of compound M5: Compound M4 was dissolved in methanol and placed in a 250 mL round-bottom flask and stirred until completely dissolved; sodium methoxide and nitromethane were added in sequence; the mixture was heated to 90 °C and stirred for 3–6 h (preferably 6 h); after the reaction was completed, it was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane; the organic phases were combined, dried and concentrated under reduced pressure to obtain the crude product; the crude product was purified by rapid column chromatography to obtain reddish-brown oily substance M5; ； In M5, Ar is selected from the Ar1-Ar8 groups described above; (4) Synthesis of compound M6: Compound M5 and ammonium acetate were dissolved in methanol and placed in a 250 mL round-bottom flask; the mixture was heated to 110 °C and stirred for 12–24 h (preferably 18–24 h); after the reaction was completed, the mixture was cooled to room temperature, washed in saturated sodium chloride solution, and extracted with dichloromethane; the organic phases were combined, dried and concentrated under reduced pressure to obtain dark blue solid M6; ； In M6, Ar is selected from the Ar1-Ar8 groups described above; (5) Synthesis of dye BDP-MeSJ: Under nitrogen protection, compound M6 and triethylamine were dissolved in 1,2-dichloroethane and stirred for 10 min. BF3·Et2O was slowly added dropwise. The mixture was heated to 70 °C and reacted for 3 h. After the reaction was completed, it was cooled to room temperature, washed with saturated sodium chloride solution, and extracted with dichloromethane. The organic phases were combined, dried, and concentrated under reduced pressure to obtain crude product. The crude product was purified by rapid column chromatography (n-hexane / dichloromethane = 1:1, v / v) to obtain dark blue solid BDP-Me. ； In BDP-Me, Ar is selected from the Ar1-Ar8 groups mentioned above.

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