Synthesis and application of a class of d-a type organic near-infrared two-region light-emitting materials

Abstract

The application belongs to the field of biomedical materials, and provides preparation and application of a near-infrared two-region luminescent material with AIE property, and the structure is: wherein Ar is a group with AIE property such as triphenylamine and carbazole derivative, X is hydrogen element, fluorine element and chlorine element, etc. The near-infrared luminescent material has AIE property, is simple to synthesize, has high near-infrared luminescent efficiency, adjustable absorption and emission spectrum, good light stability, and can overcome the interference of biological tissue self-absorption and spontaneous fluorescence and the like.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, and specifically relates to the preparation of DA-type organic near-infrared II luminescent materials and their application in bioimaging and diagnosis. Background Technology

[0002] Malignant tumors, as a major public health problem, threaten human lives. With the increasing demand for accurate early diagnosis and safe treatment of tumors, non-invasive optical imaging (including fluorescence imaging and photoacoustic imaging) and phototherapy (including photothermal therapy and photodynamic therapy) have received widespread attention. In particular, the near-infrared region, especially near-infrared II light, has attracted global research interest due to its deep penetration, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Among various biomaterials, organic nanomaterials with aggregation-induced emission (AIE) properties have garnered significant attention due to their unparalleled advantages such as high brightness, good photostability, tunable photophysical properties, and good biocompatibility. Therefore, developing a novel, proprietary, highly selective, efficient, highly photostable, and low-toxicity near-infrared luminescent material system and expanding its applications in cancer imaging and diagnosis is not only a fundamental scientific problem urgently needing to be solved in this interdisciplinary field, but also an inherent requirement for seizing the future bio-diagnostic market, and an inescapable responsibility for scientists engaged in chemical and materials science research. Summary of the Invention

[0003] To address the above problems, this invention will design and synthesize near-infrared luminescent (AIE) materials with high efficiency, tunable absorption and emission spectra, and good photostability, overcoming the interference of self-absorption and autofluorescence in biological tissues. Based on a cyanoindanone framework, mechanisms such as enhancing conjugated chain length and increasing molecular steric hindrance will be utilized to achieve the preparation of highly efficient near-infrared luminescent AIE materials. Simultaneously, methods such as reducing the energy difference between singlet and triplet states will be used to improve its photodynamic efficiency, screening for near-infrared AIE materials that possess both high luminescence efficiency and high photodynamic activity.

[0004] To achieve the above objectives, the present invention provides the following technical solution: the synthesis and application of a type of DA-type organic near-infrared II luminescent material, the preparation method of which includes the following steps:

[0005] In a nitrogen atmosphere, an aldehyde-containing strong electron-donating compound and cyanoindone were added to a reactor at a molar ratio of 1.2 to 1.5:1. Chloroform was added as a solvent and pyridine as a catalyst. The mixture was stirred with a magnetic stirrer to dissolve the compound. The mixture was heated to 80 °C for 3 h. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the crude product, which was then purified by column chromatography to obtain the target compound.

[0006] structure:

[0007]

[0008] In the formula, X = fluorine or chlorine;

[0009] Ar can be any of the following groups.

[0010]

[0011] Beneficial effects of this invention:

[0012] 1. The near-infrared AIE luminescent material provided by this invention can overcome the ACQ effect of traditional luminescent materials and its light stability is improved compared with commercial luminescent materials.

[0013] 2. The near-infrared luminescent material with AIE properties provided by this invention has few synthesis steps, a simple method, and readily available raw materials.

[0014] 3. The near-infrared luminescent material with AIE properties provided by this invention has the advantages of high near-infrared luminescence efficiency, adjustable absorption and emission spectra, and overcoming the interference of self-absorption and autofluorescence in biological tissues. Attached Figure Description

[0015] Figure 1 Normalized absorption spectra of BTT-2F, MeoBTT-2F, and BTPET-2F in THF;

[0016] Figure 2 Emission spectra of the obtained materials BTT-2F, MeoBTT-2F, and BTPET-2F in THF (A) and solid state (B).

[0017] Figure 3 (A) shows the fluorescence spectra under different water content conditions. The fluorescence intensity of BTPET-2F significantly increased after water was gradually added to the THF solution. Figure 3 (B) is a graph showing the relationship between the I / I0 of 3BTPET-2F and the water content of the solvent mixture.

[0018] Figure 4 (A) shows the fluorescence spectra under different water content conditions. The fluorescence intensity of MeoBTT-2F significantly increased after water was gradually added to the THF solution. Figure 4 (B) is a graph showing the relationship between the I / I0 of MeoBTT-2F and the water content of the solvent mixture.

[0019] Figure 5 Mass spectrum of the near-infrared luminescent material BTT-2F

[0020] Figure 6 Mass spectrum of the near-infrared luminescent material MeoBTT-2F

[0021] Figure 7 Mass spectrum of the near-infrared luminescent material BTPET-2F Detailed Implementation

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, thereby making a clearer definition of the scope of protection of the present invention. The embodiments described in this invention are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0023] Example 1:

[0024] The synthesis routes for the near-infrared luminescent materials BTT-2F, MeoBTT-2F, BTPET-2F, BDFT-2F, and BCT-2F are as follows:

[0025]

[0026] BTT-2F: Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), triphenylamine 4-borate (1.62 g, 5.61 mmol), tetrakis(triphenylphosphine)palladium (0.115 g, 0.10 mmol), and potassium carbonate (0.62 g, 4.50 mmol) were added to 20 mL of a 1:1 mixture of THF and water. The reaction was carried out at 90 °C for 12 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. A yellow solid was given in 58.2% yield (0.92 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.105 g of 5,6-difluoro-3-(dicyanomethylene)indophenone (0.45 mmol), and a few drops of pyridine as a catalyst. The reaction was carried out at 70 °C for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the product was dissolved in an appropriate amount of chloroform. A large amount of methanol was added to precipitate the solid, which was then filtered to obtain a dark black solid (0.22 g) with a yield of 79.4%.

[0027] The structural characterization data of the obtained product are shown below:

[0028] 1H NMR (500 MHz, CDCl3) δ 8.86 (s, 1H), 8.62 – 8.49 (m, 1H), 7.87 (s,1H), 7.71 (t, J = 7.2 Hz, 1H), 7.38 – 7.30 (m, 7H), 7.24 – 7.11 (m, 14H), 7.07 (dd, J = 14.6, 7.5 Hz, 5H), 6.97 (d, J = 8.4 Hz, 2H).

[0029] MeOBTT-2F: Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), triphenylamine 4,4'-dimethoxy-4''-boronate (1.95 g, 5.61 mmol), tetrakis(triphenylphosphine)palladium (0.115 g, 0.10 mmol), and potassium carbonate (0.62 g, 4.50 mmol) were added to 20 mL of a 1:1 mixture of THF and water. The reaction was carried out at 90 °C for 12 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. A yellow solid was given in 46.6% (0.84 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.105 g (0.45 mmol) of 5,6-difluoro-3-(dicyanomethylene)indophenone, and a few drops of pyridine as a catalyst. The reaction was carried out at 70 °C for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the product was dissolved in an appropriate amount of chloroform. A large amount of methanol was added to precipitate the solid, which was then filtered to obtain a dark black solid (0.20 g) with a yield of 76.9%.

[0030] The structural characterization data of the obtained product are shown below:

[0031] 1 H NMR (500 MHz, CDCl3) δ 8.83 (s, 1H), 8.55 (dd, J = 8.7, 7.3 Hz,1H), 7.83 (s, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 8.5 Hz, 4H), 7.13(s, 9H), 6.90 (d, J = 8.6 Hz, 9H), 6.80 (s, 2H), 3.84 (s, 12H).

[0032] BTPET-2F: Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), [1-(4-boronylphenyl)-1,2,2-triphenyl]ethylene (2.10 g, 5.61 mmol), tetrakis(triphenylphosphine)palladium (0.115 g, 0.10 mmol), and potassium carbonate (0.62 g, 4.50 mmol) were added to 20 mL of a 1:1 mixture of THF and water. The reaction was carried out at 90 °C for 12 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. A yellow solid was given in 64.2% yield (1.22 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.105 g of 5,6-difluoro-3-(dicyanomethylene)indophenone (0.45 mmol), and a few drops of pyridine as a catalyst. The reaction was carried out at 70 °C for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the product was dissolved in an appropriate amount of chloroform. A large amount of methanol was added to precipitate the solid, which was then filtered to obtain a dark black solid (0.18 g) with a yield of 69.2%.

[0033] The structural characterization data of the obtained product are shown below:

[0034] 1 H NMR (500 MHz, CDCl3) δ 8.86 (s, 1H), 8.58 (dd, J = 11.0, 5.1 Hz,1H), 7.85 (s, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.17 (s, 3H), 7.16 – 7.13 (m,9H), 7.13 – 7.10 (m, 5H), 7.09 – 7.06 (m, 11H), 7.03 (d, J = 8.5 Hz, 5H), 7.00 (s, 2H), 6.99 (s, 2H), 6.97 (s, 1H).

[0035] BDFT-2F: Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), fluorene-2-borate pinacol ester (1.79 g, 5.61 mmol), tetrakis(triphenylphosphine)palladium (0.115 g, 0.10 mmol), and potassium carbonate (0.62 g, 4.50 mmol) were added to 20 mL of a 1:1 mixture of THF and water. The reaction was carried out at 90 °C for 12 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. A yellow solid was given in 49.1% (0.83 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.105 g of 5,6-difluoro-3-(dicyanomethylene)indophenone (0.45 mmol), and a few drops of pyridine as a catalyst. The reaction was carried out at 70 °C for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the product was dissolved in an appropriate amount of chloroform. A large amount of methanol was added to precipitate the solid, which was then filtered to obtain a dark black solid (0.18 g) with a yield of 62.0%.

[0036] The structural characterization data of the obtained product are shown below:

[0037] 1 H NMR (500 MHz, CDCl3) δ 8.96 (s, 1H), 8.63 – 8.58 (m, 1H), 8.02 (s,1H), 7.76 – 7.66 (m, 5H), 7.50 (s, 2H), 7.44 (s, 2H), 7.38 (d, J = 11.0 Hz, 5H), 7.32 (d, J = 8.3 Hz, 2H), 1.43 (s, 6H), 1.37 (s, 6H).

[0038] BCT-2F: 2,7-Dibromo-9H-carbazole (3 g, 9.23 mmol) was dissolved in acetone (60 mL) in a 250 mL round-bottom flask. Potassium hydroxide (1.55 g, 27.69 mmol) was then added to the mixture. After reflux for 30 min, bromoethane (2.07 mL, 27.69 mmol) was slowly added, and reflux was continued for 1 h. After cooling to room temperature, the reaction solvent was removed under reduced pressure to obtain the crude product, which was dissolved in ethyl acetate and washed with 2% dilute hydrochloric acid, water, and brine. The organic phase was then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography, eluting with petroleum ether / CH₂Cl₂ to give product 1 in 81% yield.

[0039] Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), product 1 (1.80 g, 5.61 mmol), tetrakis(triphenylphosphine)palladium (0.115 g, 0.10 mmol), and potassium carbonate (0.62 g, 4.50 mmol) were added to 20 mL of a 1:1 mixture of THF and water. The reaction was carried out at 90 °C for 12 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. A yellow solid was given in 47.1% (0.8 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.105 g of 5,6-difluoro-3-(dicyanomethylene)indophenone (0.45 mmol), and a few drops of pyridine as a catalyst. The reaction was carried out at 70 °C for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure, and the product was dissolved in an appropriate amount of chloroform. A large amount of methanol was added to precipitate the solid, which was then filtered to obtain a dark black solid (0.22 g) with a yield of 75.8%.

[0040] The structural characterization data of the obtained product are shown below:

[0041] 1 H NMR (500 MHz, CDCl3) δ 8.76 (s, 1H), 8.33 (s, 1H), 8.00 (s, 6H), 7.62 (s, 1H), 7.49 (s, 2H), 7.36 (d, J = 26.1 Hz, 5H), 7.24 (s, 1H), 7.20 (s,1H), 4.20 (s, 2H), 4.08 (s, 2H), 1.28 (s, 6H).

[0042] Example 2:

[0043] Absorption spectral characterization of DA-type photosensitizers (BTT-2F, MeoBTT-2F, BTPET-2F)

[0044] Figure 1 The absorption spectra of BTT-2F, MeOBTT-2F, and BTPET-2F obtained in Example 1 in THF are shown. The maximum absorption spectrum of BTT-2F in THF solution is 600 nm, that of MeOBTT-2F is 641 nm, and that of BTPET-2F is 523 nm. This indicates that the strong electron-withdrawing effect of fluorine can endow CF bond ion characteristics, which makes the CF bond highly polarized, enhances the electrostatic interaction between adjacent molecules, and promotes the red shift of the absorption wavelength.

[0045] Example 3:

[0046] Emission spectra of DA-type photosensitizers (BTT-2F, MeOBTT-2F, BTPET-2F)

[0047] Figure 2 The emission spectra of BTT-2F, MeoBTT-2F, and BTPET-2F obtained in Example 1 in THF (A) and solid state (B) are shown. The maximum emission spectrum of BTT-2F in THF solution is 961 nm, that of MeoBTT-2F in THF solution is 976 nm, and that of BTPET-2F in THF solution is 972 nm. The solid-state emission wavelength of BTT-2F is 978 nm, that of MeoBTT-2F is 992 nm, and that of BTPET-2F is 979 nm. This indicates that by enhancing the electron-donating ability of the electron-donating groups, intramolecular charge transfer in the excited state is promoted, resulting in a significant redshift in the emission spectrum, demonstrating good potential for bioimaging.

[0048] Example 4:

[0049] Figure 3 (A) shows the fluorescence spectra under different water content conditions. The fluorescence intensity of BTPET-2F significantly increased after water was gradually added to the THF solution. Figure 3 (B) is a graph showing the relationship between the I / I0 of BTPET-2F and the water content of the solvent mixture. The PL emission of BTPET-2F is quenched before the critical point (30% water content). After the critical point, the fluorescence intensity increases with the addition of water, indicating its aggregation-induced emission characteristics.

[0050] Example 5:

[0051] Figure 4 (A) shows the fluorescence spectra under different water content conditions. The fluorescence intensity of MeOBTT-2F significantly increased after water was gradually added to the THF solution. Figure 4 (B) is a graph showing the relationship between the I / I0 of MeOBTT-2F and the water content of the solvent mixture. The PL emission of MeOBTT-2F is quenched before the critical point (50% water content). After the critical point, the fluorescence intensity increases with the addition of water, indicating its aggregation-induced emission characteristics.

Claims

1. A type of DA-type organic near-infrared II luminescent material, characterized in that: The structure is as follows: In the formula, X is fluorine or chlorine; Ar is any one of the following groups: .

2. The application of the type DA-type organic near-infrared II luminescent material according to claim 1 in the preparation of near-infrared AIE materials.

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