A novel organic functional dye, and a preparation method and application thereof

Abstract

The application discloses a novel organic functional dye, a preparation method and application thereof, and specifically discloses a method for preparing the novel organic functional dye by one-pot condensation of 1-acetylinindole-3-ketone and aromatic heterocyclic-2-formaldehyde under catalysis of alkali. The method has the advantages of easy availability of raw materials, simple steps and mild reaction. The obtained dye has strong absorption in a near-infrared region after being wrapped by a polymer to form nanoparticles, has a photo-thermal conversion efficiency as high as 69.2%, has low dark toxicity and good biocompatibility, and can be applied to photothermal treatment of tumors.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry, and specifically relates to a novel organic functional dye, its preparation method, and its application. Background Technology

[0002] In recent years, with the rapid development of nanotechnology, supramolecular chemistry, and phototherapy, photofunctional dyes are rapidly evolving towards functionalization, intelligence, and high-end applications. Among them, organic photofunctional dyes have attracted widespread attention due to their advantages such as high molar extinction coefficient, excellent photothermal stability, low toxicity, well-defined molecular structure, and controllable photophysical properties, showing broad application prospects in fields such as fluorescence imaging, organelle labeling, photothermal antitumor therapy, and photoacoustic imaging.

[0003] Currently, the construction strategies for novel organic photofunctional dyes mainly focus on the chemical modification and derivatization of existing classical core structures (such as porphyrins, anthocyanins, and fluoroboron dipyrroles). However, these methods generally suffer from problems such as complex synthetic routes, lengthy reaction steps, and low overall efficiency. In addition, the obtained products often face performance bottlenecks such as insufficient photostability and absorption wavelengths in the short wavelength range, making it difficult to meet application requirements such as near-infrared light absorption and high photothermal conversion efficiency.

[0004] Therefore, there is an urgent need to further develop organic functional dyes. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing a novel organic functional dye, its preparation method, and its applications. The preparation method is simple, requiring only conventional reaction equipment, operating under mild conditions, and exhibiting low equipment dependence, making it easy to scale up production and widespread application. After being nano-encapsulated, the prepared organic photofunctional dye results in nanoparticles that demonstrate excellent photothermal conversion efficiency in both aqueous systems and cellular environments, exhibiting good photothermal response performance. Based on these advantages, this nanosystem can be further used for photothermal cancer therapy, showing potential biomedical applications.

[0006] This invention is achieved through the following technical solution:

[0007] In a first aspect, the present invention provides a novel organic functional dye, the structural formula of which is shown below:

[0008]

[0009] R is selected from a conjugated aromatic heterocycle with a nitrogen atom at position 2.

[0010] Furthermore, R is selected from one of imidazole, pyridazine, pyrimidine, pyridine, thiazole, isazole, oxazole, pyrazole, and benzimidazole.

[0011] Secondly, the present invention provides a method for preparing the above-mentioned novel organic functional dyes.

[0012] This invention successfully synthesized a novel photothermal reagent with a large conjugated structure and both rigidity and planarity, using commercially available 1-acetylindole-3-one as a starting material. This photothermal reagent exhibits excellent near-infrared absorption properties and low dark toxicity.

[0013] The above-mentioned novel photothermal reagent preparation method includes:

[0014] Under a nitrogen atmosphere, 1-acetylindol-3-one (I) and formaldehyde derivative (II) were added to the reaction medium, and then alkali was added to carry out the reaction. After the reaction was completed, distilled water was added to quench the reaction, the product was dried and purified to obtain the novel organic functional dye.

[0015] The reaction formula is shown below:

[0016]

[0017] Preferably, the reaction temperature is 40~70℃ and the reaction time is 4~10 h.

[0018] Preferably, the alkali is selected from any one or a mixture of two of potassium carbonate, triethylamine, diethylamine, and N,N-diisopropylethylamine, and is used in an amount sufficient to allow the solute to react completely. Triethylamine is more preferred.

[0019] Preferably, the molar ratio of the formaldehyde derivative shown in formula (II), the 1-acetylindol-3-one shown in formula (I), and the base is 1:(1.5~3):(2~4).

[0020] Preferably, the reaction medium is selected from any one or a mixture of two of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, or N,N-dimethylformamide, and the amount used is sufficient to allow the solute to react completely. More preferably, it is N,N-dimethylformamide.

[0021] Thirdly, this invention provides the application of the above-mentioned novel organic functional dyes in the preparation of photothermal diagnostic and therapeutic reagents for tumor cells.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] (1) The present invention is prepared by a one-pot method, which is simple and efficient. All raw materials used are common commercial reagents, and the synthesis can be completed in one step. The reaction conditions are mild, the equipment requirements are low, the target product has a high yield and is easy to separate, which is suitable for large-scale production and has good industrialization prospects.

[0024] (2) Excellent spectral performance. This organic photothermal reagent has excellent near-infrared maximum absorption wavelength, which is easy to match with commercial lasers and facilitates practical application. It has shown excellent phototherapy effects in aqueous systems, cells and mouse models.

[0025] (3) Novel structural design and good biocompatibility. The design strategy of this type of organic photothermal reagent is novel, and its nanoparticles have excellent photothermal stability and low dark toxicity.

[0026] (4) High photothermal conversion efficiency. Its photothermal conversion efficiency can reach 69.2%, demonstrating highly efficient photothermal performance. Attached Figure Description

[0027] Figure 1 (A) shows the UV absorption spectra of 1 in tetrahydrofuran and 1-NPs in water; (B) shows the DLS and TEM images of the size distribution of the nanoparticles.

[0028] Figure 2 In Figure (A), different concentrations of 1-NPs are subjected to a 755 nm laser (0.96 W·cm⁻¹). −2 (A) Photothermal effect after irradiation for 1500 s; (B) 30 μmol / L 1-NPs under different laser power lasers at 755 nm (0.96 W•cm). −2 (C) Photothermal effect after irradiation for 1500s; (D) Three consecutive heating and cooling processes of 30 μmol / L 1-NPs; (E) Negative logarithm and linear fitting curve of cooling time versus temperature of 1-NPs.

[0029] Figure 3 (A) shows the results of the CCK-8 cytotoxicity assay for 1-NPs; (B) shows the results of intratumoral injection of 1-NPs (100 μM, λ). ex =755 nm, 0.96 W•cm −2 Afterwards, the tumor-bearing mice underwent thermal imaging after being irradiated with laser for 6 minutes. Detailed Implementation

[0030] The present invention will be further described in detail below through examples, and all raw materials used in the examples are commercially available.

[0031] Example 1

[0032] In a 20 mL round-bottom flask, imidazole-2-carboxaldehyde (96 mg, 1.0 mmol) and 1-acetyl-3-indololinone (350 mg, 2.0 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 45°C water bath, followed by the addition of triethylamine (0.4 mL) and vigorous stirring for 6 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (250 mg) as a blue solid, namely compound 1, with a yield of 65%.

[0033] 1 H NMR (400 MHz, THF-d8) δ 10.88 (s, 1H), 8.05 (d, J = 8 Hz, 2H), 8.02(s, 1H), 7.79 (d, J = 8 Hz, 2H), 7.49 (s, 2H), 7.44 (t, J = 8 Hz, 2H), 7.06(t, J = 8 Hz, 2H), 1.65 (s, 3H)

[0034] 13 C NMR (101 MHz, THF-d8) δ 166.95, 143.37, 131.94, 124.20, 123.29,122.69, 120.88, 119.17, 114.86, 95.93, 21.52, 14.24.

[0035] HRMS-ESI: m / z: calcd for [C 22 H 16 N4O3] + : 384.1222, found: 384.1206.

[0036] The synthesis reaction equation is as follows:

[0037]

[0038] Example 2

[0039] In a 20 mL round-bottom flask, pyridazine-3-carboxaldehyde (108 mg, 1.0 mmol) and 1-acetyl-3-indololinone (350 mg, 2.0 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 45 °C water bath, followed by the addition of triethylamine (0.42 mL) and vigorous stirring for 7 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (241 mg) as a blue solid, namely compound 2, with a yield of 61%.

[0040] The structural formula of compound 2 is as follows:

[0041]

[0042] 1 H NMR (400 MHz, THF-d8) δ 10.71 (s, 1H), 8.91 (s, 1H), 8.04 (d, J = 8Hz, 2H), 7.95 (d, J = 8 Hz, 1H), 7.78 (d, J = 8 Hz, 2H), 7.71 (t, J = 8 Hz,1H), 7.43 (t, J = 8 Hz, 2H), 7.39 (d, J = 8 Hz, 1H), 7.05 (t, J = 8 Hz, 2H), 1.63 (s, 3H).

[0043] 13 C NMR (101 MHz, THF-d8) δ 166.60, 152.37, 146.82, 135.76, 132.12,128.94, 124.26, 123.38, 121.00, 119.29, 114.95, 96.05, 21.62, 14.37.

[0044] HRMS-ESI: m / z: calcd for [C 23 H 16 N4O3] + 396.1222, found: 396.1214.

[0045] Example 3

[0046] In a 20 mL round-bottom flask, 130 mg (1.2 mmol) of 2-pyrimidinecarboxaldehyde and 350 mg (2.0 mmol) of 1-acetyl-3-indololinone were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added and stirred for 10 minutes, and the mixture was placed in a 50 °C water bath. Triethylamine (0.44 mL) was then added and the mixture was stirred vigorously for 8 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (249 mg) as a blue solid, with structural formula (3), yield 63%.

[0047] The structural formula of compound 3 is as follows:

[0048]

[0049] 1 H NMR (400 MHz, THF-d8): δ ppm 10.29 (s, 1H), 8.68 (d, J = 4 Hz, 2H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.32(t, J = 4 Hz, 1H), 7.05 (t, J = 8 Hz, 2H), 1.66 (s, 3H).

[0050] 13 C NMR (100 MHz, THF-d8) δ ppm 166.50, 162.37, 157.14, 132.00,124.18, 123.30, 121.26, 120.92, 119.21, 114.87, 95.97, 21.56, 14.31.

[0051] HRMS-ESI: m / z: calcd for [C 23 H 16 N4O3]: 396.1222, found: 396.1234.

[0052] Example 4

[0053] In a 20 mL round-bottom flask, 4-pyrimidinecarboxaldehyde (96 mg, 1.0 mmol) and 1-acetyl-3-indololinone (263 mg, 1.5 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added and stirred for 10 minutes, and the mixture was placed in a 60 °C water bath. Potassium carbonate (318 mg) was then added and the mixture was stirred vigorously for 10 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (166 mg) as a blue solid, with structural formula (4), yield 42%.

[0054] The structural formula of compound 4 is as follows:

[0055]

[0056] 1 H NMR (400 MHz, THF-d8): δ ppm 10.68 (s, 1H), 9.10 (s, 1H), 8.75 (s,1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.38 (d, J = 4 Hz, 1H), 7.05 (t, J = 8 Hz, 2H), 1.68 (s, 3H).

[0057] 13 C NMR (100 MHz, THF-d8): δ ppm 166.48, 158.72, 155.36, 132.14,129.75, 124.28, 123.40, 121.02, 119.31, 114.97, 96.07, 21.64, 14.39.

[0058] HRMS-ESI: m / z: calcd for [C 23 H 16 N4O3]: 396.1222, found: 396.1220.

[0059] Example 5

[0060] In a 20 mL round-bottom flask, pyridine-2-carboxaldehyde (107 mg, 1.0 mmol) and 1-acetyl-3-indololinone (350 mg, 2.0 mmol) were added, nitrogen gas was introduced, dichloromethane (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 40 °C water bath, followed by the addition of triethylamine (0.44 mL) and vigorous stirring for 6 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (201 mg) as a blue solid, namely compound 5, in 51% yield.

[0061] The structural formula of compound 5 is as follows:

[0062]

[0063] 1 H NMR (400 MHz, THF-d8): δ ppm 10.49 (s, 1H), 8.63 (d, J = 4 Hz, 1H), 8.41 (d, J = 8 Hz, 1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.80(td, J = 8, 4 Hz, 1H), 7.43 (t, J = 8 Hz, 2H), 7.32 (dd, J = 8, 4 Hz, 1H), 7.05 (t, J = 8 Hz, 2H), 1.68 (s, 3H).

[0064] 13 C NMR (100 MHz, THF-d8): δ ppm 166.77, 158.21, 149.83, 137.64,132.14, 124.36, 123.48, 122.89, 121.10, 119.39, 115.05, 96.14, 21.69, 14.43.

[0065] HRMS-ESI: m / z: calcd for [C 24 H 17 N3O3]: 395.1270, found: 395.1276.

[0066] Example 6

[0067] In a 20 mL round-bottom flask, thiazolium-4-carboxaldehyde (113 mg, 1.0 mmol) and 1-acetyl-3-indololinone (438 mg, 2.5 mmol) were added, nitrogen gas was introduced, tetrahydrofuran (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 65 °C water bath, followed by the addition of diethylamine (0.45 mL) and vigorous stirring for 4 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (209 mg) as a blue solid, namely compound 6, with a yield of 52%.

[0068] The structural formula of compound 6 is as follows:

[0069]

[0070] 1 H NMR (400 MHz, THF-d8): δ ppm 10.67 (s, 1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.71 (s, 1H), 7.43 (t, J = 8 Hz, 2H), 7.24 (s, 1H), 7.05 (t, J = 8 Hz, 2H), 1.78 (s, 3H).

[0071] 13 C NMR (100 MHz, THF-d8): δ ppm 166.67, 148.53, 132.19, 131.46,129.02, 125.14, 124.37, 123.49, 121.11, 119.40, 115.04, 96.16, 21.70, 14.33.

[0072] HRMS-ESI: m / z: calcd for [C 22 H 15 N3O3S]: 401.0834, found: 401.0845.

[0073] Example 7

[0074] In a 20 mL round-bottom flask, 2-aldehydethiazole (113 mg, 1.0 mmol) and 1-acetyl-3-indololinone (525 mg, 3.0 mmol) were added, nitrogen gas was introduced, 1,2-dichloroethane (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in an 80 °C water bath, followed by the addition of DIPEA (0.46 mL) and vigorous stirring for 10 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (244 mg), namely compound 7, as a blue solid, with a yield of 61%.

[0075] The structural formula of compound 7 is as follows:

[0076]

[0077] 1 H NMR (400 MHz, THF-d8): δ ppm 11.09 (s, 1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.56 (d, J = 4 Hz, 1H), 7.43 (t, J = 8 Hz, 2H), 7.18(d, J = 4 Hz, 1H), 7.05 (t, J = 8 Hz, 2H), 1.87 (s, 3H).

[0078] 13 C NMR (100 MHz, THF-d8): δ ppm 166.75, 147.22, 132.08, 130.15,129.63, 125.87, 124.29, 123.41, 121.03, 119.32, 114.96, 96.08, 21.65, 14.47.

[0079] HRMS-ESI: m / z: calcd for [C 22 H 15 N3O3S]: 401.0834, found: 401.0850.

[0080] Example 8

[0081] In a 20 mL round-bottom flask, 3-formylisoazole (97 mg, 1.0 mmol) and 1-acetyl-3-indololinone (402 mg, 2.3 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 54 °C water bath, followed by the addition of triethylamine (0.42 mL) and vigorous stirring for 8 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (231 mg) as a blue solid, namely compound 8, with a yield of 60%.

[0082] The structural formula of compound 8 is as follows:

[0083]

[0084] 1 H NMR (400 MHz, THF-d8): δ ppm 10.63 (s, 1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.32 (d, J = 4 Hz, 1H), 7.05(t, J = 8 Hz, 2H), 6.28 (d, J = 4 Hz, 1H), 1.64 (s, 3H).

[0085] 13 C NMR (100 MHz, THF-d8): δ ppm 166.72, 152.64, 131.96, 127.58,124.15, 123.27, 120.83, 119.12, 114.76, 104.89, 95.81, 21.44, 14.18.

[0086] HRMS-ESI: m / z: calcd for [C 22 H 15 N3O4]: 385.1063 found: 385.1052.

[0087] Example 9

[0088] In a 20 mL round-bottom flask, oxazol-4-carboxaldehyde (97 mg, 1.0 mmol) and 1-acetyl-3-indololinone (525 mg, 3.0 mmol) were added, nitrogen gas was introduced, 1,2-dichloroethane (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 75°C water bath, followed by the addition of triethylamine (0.46 mL) and vigorous stirring for 5 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (208 mg) as a blue solid, namely compound 9, in 54% yield.

[0089] The structural formula of compound 9 is as follows:

[0090]

[0091] 1 H NMR (400 MHz, THF-d8): δ ppm 810.32 (s, 1H), 8.04 (d, J = 8 Hz,2H), 7.82 (s, 1H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.05 (t, J= 8 Hz, 2H), 7.02 (s, 1H), 1.61 (s, 3H).

[0092] 13 C NMR (100 MHz, THF-d8): δ ppm 166.93, 150.17, 141.25, 132.04,125.38, 124.22, 123.34, 120.92, 119.21, 114.83, 95.97, 21.57, 14.42.

[0093] HRMS-ESI: m / z: calcd for [C 22 H 15 N3O4]: 385.1063, found: 385.1068.

[0094] Example 10

[0095] In a 20 mL round-bottom flask, azole-2-carboxaldehyde (97 mg, 1.0 mmol) and 1-acetyl-3-indololinone (315 mg, 1.8 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 55 °C water bath, followed by the addition of triethylamine (0.48 mL) and vigorous stirring for 8 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (223 mg), namely compound 10, as a blue solid, with a yield of 58%.

[0096] The structural formula of compound 10 is as follows:

[0097]

[0098] 1 H NMR (400 MHz, THF-d8): δ ppm 10.40 (s, 1H), 8.04 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.36 (d, J = 4 Hz, 1H), 7.05(t, J = 8 Hz, 2H), 6.72 (d, J = 4 Hz, 1H), 1.61 (s, 3H).

[0099] 13 C NMR (100 MHz, THF-d8): δ ppm 167.21, 152.38, 132.27, 128.09,124.46, 123.58, 121.17, 119.49, 115.08, 109.87, 96.19, 21.76, 14.35.

[0100] HRMS-ESI: m / z: calcd for [C 22 H 15 N3O4]: 385.1063, found: 385.1073.

[0101] Example 11

[0102] In a 20 mL round-bottom flask, 4-imidazolium carboxaldehyde (96 mg, 1.0 mmol) and 1-acetyl-3-indololinone (438 mg, 2.5 mmol) were added, nitrogen gas was introduced, dichloromethane (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 45 °C water bath, followed by the addition of potassium carbonate (424 mg) and vigorous stirring for 10 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (127 mg) as a blue solid, namely compound 11, in 33% yield.

[0103] The structural formula of compound 11 is as follows:

[0104]

[0105] 1 H NMR (400 MHz, CD2Cl2) δ ppm 10.67 (s, 1H), 8.92 (s, 1H), 8.04 (d, J= 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.68 (s, 1H), 7.43 (t, J = 8 Hz, 2H), 7.24 (s, 1H), 7.05 (t, J = 8 Hz, 2H), 1.75 (s, 3H).

[0106] 13 C NMR (126 MHz, THF-d8) δ ppm 166.41, 138.65, 135.21, 132.04,124.20, 123.32, 121.74, 120.94, 119.23, 114.89, 95.99, 21.58, 14.33.

[0107] HRMS-ESI: m / z: calcd for [C 22 H 16 N4O3] + 384.1222, found: 384.1237.

[0108] Example 12

[0109] In a 20 mL round-bottom flask, 1H-pyrazole-3-carboxaldehyde (96 mg, 1.0 mmol) and 1-acetyl-3-indololinone (350 mg, 2.0 mmol) were added, nitrogen gas was introduced, tetrahydrofuran (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 60 °C water bath, followed by the addition of diethylamine (0.48 mL) and vigorous stirring for 9 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (227 mg) as a blue solid, namely compound 12, in 59% yield.

[0110] The structural formula of compound 12 is as follows:

[0111]

[0112] 1 H NMR (400 MHz, CD2Cl2) δ ppm 11.49 (s, 1H), 8.04 (d, J = 8 Hz, 2H), 7.85 (s, 1H), 7.78 (d, J = 8 Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.05 (t, J = 8Hz, 2H), 6.79 (d, J = 4 Hz, 1H), 6.21 (d, J = 4 Hz, 1H), 1.84 (s, 3H).

[0113] 13 C NMR (126 MHz, THF-d8) δ ppm 166.82, 145.17, 131.83, 132.05,124.12, 123.21, 120.80, 119.09, 114.68, 105.34, 95.83, 21.43, 14.28.

[0114] HRMS-ESI: m / z: calcd for [C 22 H 16 N4O3] + : 384.1222, found: 384.1211.

[0115] Example 13

[0116] In a 20 mL round-bottom flask, benzimidazole-2-carboxaldehyde (146 mg, 1.0 mmol) and 1-acetyl-3-indololinone (263 mg, 1.5 mmol) were added, nitrogen gas was introduced, N,N-dimethylformamide (7 mL) was added, and the mixture was stirred for 10 minutes. The flask was placed in a 50 °C water bath, followed by the addition of triethylamine (0.50 mL) and vigorous stirring for 5 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the concentrate was purified by silica gel chromatography (tetrahydrofuran / petroleum ether = 2:8) to give a pure product (226 mg), namely compound 13, as a blue solid, with a yield of 52%.

[0117] The structural formula of compound 13 is as follows:

[0118]

[0119] 1 H NMR (400 MHz, CD2Cl2) δ ppm 7.69 (d, J = 8 Hz, 2H), 7.47 (dd, J =4, 4 Hz, 2H), 7.33 – 7.27 (m, 4H), 7.20 – 7.11 (m, 2H), 6.73 (t, J = 8 Hz,2H), 1.59 (s, 3H)

[0120] 13 C NMR (126 MHz, THF-d8) δ ppm 167.29, 149.24, 143.48, 136.71,132.40, 125.21, 124.10, 123.46, 121.26, 120.47, 116.71, 115.64, 114.97,95.88, 21.74, 15.49.

[0121] HRMS-ESI: m / z: calcd for [C 26 H 18 N4O3] + : 434.1379, found: 434.1365.

[0122] Test Example 1: Photophysical Properties Test of Photofunctional Dyes

[0123] Dissolve any of the newly prepared compounds from Examples 1 to 13 above in tetrahydrofuran solution to prepare a solution with a molar concentration of 10. -5 Moles per liter of test solution.

[0124] First, the absorption characteristics and photostability of the novel functional dyes were studied. Taking functional dye 1 as an example, ... Figure 1 As shown in (A), its maximum absorption peak in dichloromethane is located at approximately 600 nm, exhibiting good red light and near-infrared absorption capabilities. Based on its strong near-infrared absorption characteristics, compound 1 was selected as the subject of subsequent research, and its nanoparticles were prepared using a polymer encapsulation method to further evaluate its photothermal properties.

[0125] Specifically, compound 1 (1×10 -4 A tetrahydrofuran solution (0.25 mL) containing 1 mmol was rapidly added to an aqueous solution (2 mL) containing F-127 (1 mg, polyoxyethylene-polyoxypropylene block copolymer), and the mixture was sonicated at 40 °C for 5 min. The tetrahydrofuran was then removed by nitrogen purging at a constant temperature of 55 °C. After centrifugation and filtration, a stable 1-NPs aqueous solution was obtained.

[0126] High-resolution transmission electron microscopy (HRTEM) results showed that the obtained nanoparticles had an average particle size of approximately 98 ± 5 nm and a relatively uniform particle size distribution. Dynamic light scattering (DLS) measurements indicated that the hydrodynamic particle size was approximately 111 ± 5 nm, which is consistent with the TEM results, further demonstrating that the nanosystem possesses good dispersibility and uniformity. Figure 1 As shown in (B), compared with the absorption spectrum of compound 1 in tetrahydrofuran, the absorption peak of 1-NPs shows significant broadening and redshift, with the tail of the absorption wavelength approaching 800 nm. The maximum absorption wavelength has good matching with commercial 755 nm lasers, which is beneficial to improving the light energy utilization efficiency and enhancing the photothermal conversion effect.

[0127] Subsequently, the photothermal performance of 1-NPs at different concentrations and under different laser powers was investigated. The specific operational steps were as follows: 3 mL of the sample to be tested was prepared at different concentrations (0, 5, 10, 20, 30 µM), and 2 mL of each was placed in a cuvette and fixed on a special support. A 755 nm laser was used, and its power density was adjusted to 0.96 W / cm². 2 Irradiate the sample, recording the temperature every 60 seconds for 25 minutes. Take 2 mL of the 30 µM sample and place it in a cuvette. Fix the test position and use different powers (0.25, 0.5, 0.75, 0.96 W / cm²). 2 The sample was irradiated with a 755 nm laser, and the temperature was recorded every 60 seconds for ten minutes. For the photothermal efficiency test, a 30 µM sample was selected, and a 755 nm laser (0.96 W / cm²) was used. 2The laser was used for irradiation, and the entire process from the initial temperature to the maximum temperature and then naturally cooling back to the initial temperature was recorded. Photothermal cycling stability testing was conducted under the same conditions, with three repeated temperature increases and decreases. The results are shown in [Figure number missing]. Figure 2 .

[0128] The results showed that the temperature rise of the system was positively correlated with both the nanoparticle concentration and the laser power. Under conditions of 30 μmol / L, the system was heated by a 755 nm laser (0.96 W·cm⁻¹). -2 After continuous irradiation for 1500 s, the system temperature reached a maximum of 57 °C. Furthermore, repeated heating-cooling cycle experiments demonstrated that 1-NPs exhibit good photothermal stability. Based on the photothermal response curve and time constant, its photothermal conversion efficiency (η) was calculated to be 69.2%, higher than some common photothermal materials, such as Cu9S5 nanoparticles and indocyanine green (ICG). These results indicate that 1-NPs possess good photothermal conversion capabilities and have potential application in tumor photothermal therapy.

[0129] To further evaluate the biosafety and photothermal therapeutic effect of 1-NPs, a cytotoxicity assay was performed using the CCK-8 assay. Different concentrations of 1-NPs were co-incubated with HeLa cells and divided into a light-illuminated group (1-NPs + L) and a non-light-illuminated group (1-NPs). The light-illuminated group used a 755 nm laser (0.96 W·cm²). -2 Experimental results showed that under no-light conditions, the cell survival rate of each concentration treatment group was higher than 96%, indicating that 1-NPs itself had low cytotoxicity. However, under laser irradiation conditions, when the concentration of 1-NPs was 20 μg / mL, the cell survival rate decreased to 12%, indicating that it could effectively kill tumor cells under light irradiation. Based on the good photothermal properties exhibited by 1-NPs in in vitro experiments, further in vivo imaging-guided photothermal therapy research was conducted. HeLa tumor mice were randomly divided into PBS group and 1-NPs group, and injected with PBS or 1-NPs (100 μM), respectively. Subsequently, the tumor site was irradiated with a 755 nm laser for 0-10 min, and the temperature change of the tumor area was monitored in real time using an infrared thermal imager. The results showed that the temperature of the tumor site in the 1-NPs group increased rapidly after laser irradiation, reaching its maximum value at about 6 min. Compared with the PBS group, the temperature of the tumor area in the 1-NPs treatment group increased by about 30 °C, indicating that the nanosystem has a significant in vivo photothermal response capability and can be used for tumor photothermal therapy research. Figure 3 ).

Claims

1. A novel organic functional dye, characterized in that, Its structural formula is shown below: R is selected from a conjugated aromatic heterocycle with a nitrogen atom at position 2.

2. The novel organic functional dye according to claim 1, characterized in that, R is selected from one of imidazole, pyridazine, pyrimidine, pyridine, thiazole, isazole, oxazole, pyrazole, and benzimidazole.

3. A method for preparing a novel organic functional dye as described in claim 1 or 2, characterized in that, Includes the following steps: Under a nitrogen atmosphere, 1-acetylindol-3-one (I) and formaldehyde derivative (II) were added to the reaction medium, and then an alkali was added to carry out the reaction. After the reaction was completed, distilled water was added to quench the reaction, the product was dried and purified to obtain the novel organic functional dye. The reaction formula is shown below: 。 4. The preparation method according to claim 3, characterized in that, The reaction temperature is 40~70℃, and the reaction time is 4~10h.

5. The preparation method according to claim 3, characterized in that, The alkali is selected from any one or two of potassium carbonate, triethylamine, diethylamine, and N,N-diisopropylethylamine.

6. The preparation method according to claim 3, characterized in that, The molar ratio of the formaldehyde derivative shown in formula (II), the 1-acetylindol-3-one shown in formula (I), and the base is 1:(1.5~3):(2~4).

7. The preparation method according to claim 3, characterized in that, The reaction medium is selected from any one or a mixture of two of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, or N,N-dimethylformamide.

8. The application of the novel organic functional dye as described in claim 1 or 2 in the preparation of photothermal diagnostic and therapeutic reagents for tumor cells.

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