Preparation and application of near-infrared luminescent material based on thiophene bridging group

Abstract

The invention relates to preparation and application of a near-infrared luminescent material based on thiophene bridging groups, and the near-infrared luminescent material has the following structures I-III: an electron donor is coupled with a thiophene pi bridge, and then an acceptor unit is introduced to synthesize a series of thiophene bridging materials; and wavelength adjustment and performance optimization are carried out through regulation and control of the number and the type of electron donating groups and thiophene conjugation, so that the transmission capability of electrons or holes is improved, special electronic and optical performance is achieved, rich excited state energy is provided for molecules, adjustment of a molecular conjugation system is achieved, and the photophysical property is optimized. Meanwhile, the indole structure provides good rigidity and planarity, pi-pi accumulation is facilitated, and therefore the transmission capacity of electrons or holes is improved. More substitution sites on the molecular structure allow electron donor or acceptor groups to be introduced to regulate and control the energy level structure of the molecular structure. Through substituent group or conjugate expansion, the HOMO / LUMO energy level can be regulated and controlled, and energy level matching with other materials (such as a photosensitizer and an electrode material) is optimized.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials and provides the synthesis and application of a class of thiophene-bridged near-infrared AIE materials. Background Technology

[0002] Traditional fluorescent materials possess advantages such as high luminous efficiency and rich colors, and are widely used in chemical sensing, biomedicine, and optoelectronics. Typically, organic fluorescent materials only exhibit strong fluorescence in dilute solutions, and the fluorescence emission gradually weakens with increasing concentration, a phenomenon known as aggregation-induced emission quenching. In 2001, Academician Tang Benzhong's team synthesized a fluorescent molecule, 1-methyl-1,2,3,4,5-pentaphenylsilane, with a helical propeller structure. It emits almost no light in dilute solutions but exhibits strong emission in aggregated states. This photophysical behavior is called aggregation-induced emission. With its excellent photostability and high signal-to-noise ratio, it has revolutionized biological detection methods and become a research hotspot in the field of bioanalysis.

[0003] In recent years, thiophene bridging structures have been a key strategy for constructing high-performance near-infrared (NIR) molecules in the fields of organic optoelectronic materials and biomedical imaging. Due to its unique electronic structure, aromaticity, and conjugation properties, thiophene has been widely used in the design of D-π-A type (donor-π bridge-acceptor) molecules, significantly improving the optical, electrical, and biological properties of the materials.

[0004] From an optical performance perspective, thiophene, as a π-conjugated bridging unit, can effectively extend the degree of π-electron delocalization in molecules. By extending the conjugation length of the molecule, thiophene can significantly reduce the HOMO–LUMO band gap, causing its absorption and emission wavelengths to redshift from the visible region to the near-infrared region. In particular, the stretching effect of multi-thiophene bridging on the π-electron cloud is more significant, which is crucial in constructing NIR imaging probes with deep tissue penetration capabilities.

[0005] In biomedical applications, the thiophene bridging structure offers near-infrared molecules greater potential for functional modulation. On one hand, thiophene units can be substituted at different positions to introduce hydrophilic groups, targeting ligands, or responsive units (such as pH, enzyme, and GSH responses). This enables materials to be used for targeted imaging, disease microenvironment responses, and therapy. On the other hand, thiophene enhances the photostability and thermal stability of molecules, effectively preventing photobleaching and fluorescence quenching that occur with traditional dyes in complex biological environments, thereby improving imaging quality and treatment safety.

[0006] Secondly, in terms of electronic properties, thiophene bridging helps improve the carrier mobility and charge separation efficiency of molecules. Thiophene has excellent electron donor ability, effectively promoting the transfer of electrons from donor to acceptor in the excited state. Its aromatic ring structure also facilitates the formation of stable π–π stacking, enhancing the order and crystallinity in solid materials, thereby contributing to the formation of high-mobility carrier channels. This property is not only applicable to optoelectronic devices but also crucial for signal enhancement in biophotothermal / photoacoustic imaging agents. Summary of the Invention

[0007] In order to overcome the shortcomings and deficiencies of the prior art, the primary objective of this invention is to design and synthesize a type of near-infrared AIE material, thereby enabling the material to have better tissue penetration and signal recognition capabilities.

[0008] To achieve the above objectives, the present invention provides the following technical solution: a near-infrared AIE material based on 1,2,3,3-tetramethyl-3H-indole iodide, thiophene bridge, and triphenylamine derivative, and its application, the preparation method comprising the following steps:

[0009] Under a nitrogen atmosphere, 1,2,3,3-tetramethyl-3H-indole iodide and a triphenylamine derivative were added to a two-necked round-bottom flask in a molar ratio of 1:2. The reaction flask was evacuated under vacuum, rinsed with dry nitrogen, and ethanol was added as a solvent and ammonium acetate as a catalyst. The mixture was heated to 70°C. o The reaction was carried out at C for 24 h. After the reaction was completed, the crude product was purified by silica gel column chromatography to obtain the target compound.

[0010] The structure is as follows:

[0011]

[0012] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0013] 1. This invention is based on a combination of 1,2,3,3-tetramethyl-3H-indole iodide, thiophene bridge and triphenylamine derivative. Through molecular design optimization, the photostability and thermal stability of the molecule are increased, which can effectively avoid the photobleaching and fluorescence quenching phenomena of traditional dyes in complex biological environments.

[0014] 2. The iodide provided by this invention has a rigid molecular skeleton, which provides good rigidity and planarity, which is conducive to π-π stacking, thereby improving the transport capability of electrons or holes, enhancing ion migration or auxiliary energy level regulation, and improving luminescence efficiency.

[0015] 3. The near-infrared AIE luminescent material provided by this invention combines aggregation-induced emission (AIE) and internal charge transfer (ICT) mechanisms, overcoming the problem of ACQ (acupuncture-induced emission) in traditional dyes in the aggregated state. Through rational molecular structure design, efficient radiative emission in the aggregated state is achieved. This strategy provides a new approach for developing high-performance, stable, and highly penetrating near-infrared luminescent materials, and has broad application prospects and promotional value. Attached Figure Description

[0016] Figure 1 TT-TMI, BTT-TMI, and BTS-TMI in tetrahydrofuran solution (10 -5 The ultraviolet-visible (UV-Vis) absorption spectrum in M).

[0017] Figure 2 TT-TMI, BTT-TMI, and BTS-TMI in tetrahydrofuran solution (10 -5 The emission (PL) spectrum in M).

[0018] Figure 3 Theoretical calculations for TT-TMI, BTT-TMI, and BTS-TMI.

[0019] Figure 4 The NMR spectrum of intermediate 9. Detailed Implementation

[0020] The present invention will now be described in further detail with reference to embodiments and accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, thereby providing a clearer definition of the scope of protection of the present invention. The embodiments described herein are only a part of the embodiments of the present invention, and not all of them. 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.

[0021] Example 1: Preparation of near-infrared luminescent material TT-TMI. The synthetic route is as follows:

[0022]

[0023] TT-TMI: Under a nitrogen atmosphere, 5-aldehyde-2-bromothiophene (0.50 g, 1.34 mmol), triphenylamine 4-borate (0.81 g, 2.59 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 68.8% (0.82 g). 20 mL of ethanol was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.20 g of 1,2,3,3-tetramethyl-3H-indole iodide (0.20 g, 0.65 mmol), and 0.020 g of ammonium acetate (0.05 mmol). The mixture was reacted at 70 °C for 24 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The product was separated by column chromatography and recrystallized. The product was filtered to obtain a dark blue solid (0.22 g) with a yield of 79.4%.

[0024] Example 2: Preparation of near-infrared luminescent material BTT-TMI. The synthesis route is as follows:

[0025]

[0026] BTT-TMI: Under a nitrogen atmosphere, 4,5-dibromothiophene-2-carboxaldehyde (0.50 g, 1.87 mmol), triphenylamine 4-borate (0.81 g, 2.59 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 ethanol was added to a two-necked flask, followed by 0.20 g of the product from the previous step, 0.205 g (0.85 mmol) of 1,2,3,3-tetramethyl-3H-indole iodide, and 0.020 g (0.05 mmol) of ammonium acetate. The mixture was reacted at 70 °C for 24 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The product was separated by column chromatography and recrystallized. The product was filtered to obtain a dark blue solid (0.18 g) with a yield of 65.3%.

[0027] Example 3: Preparation of near-infrared luminescent material BTS-TMI. The synthesis route is as follows:

[0028]

[0029] BTS-TMI: Under a nitrogen atmosphere, a mixture of N,N,N-triphenyl-1,4-phenylenediamine (0.5 g, 1.48 mmol), p-bromoiodobenzene (0.42 g, 1.5 mmol), sodium tert-butoxide (0.42 g, 4.4 mmol), Pd(dba)₂ (0.013 g, 0.148 mmol), and 1,1'-bis(diphenylphosphine)ferrocene (0.0375 g, 7.4 mmol) was added to a 125 mL double-necked flask. Subsequently, 40 mL of toluene was injected into the flask, and the reaction mixture was refluxed for 12 h. After cooling to room temperature, the mixture was filtered to remove insoluble impurities. The mixture was then poured into water and extracted three times with dichloromethane. The combined organic layers were washed successively with saturated sodium bicarbonate and water, and then dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. The obtained product (0.5 g, 1 mmol), 2,5-aldehyde-2-thiopheneboronic acid (0.325 g, 2 mmol), tetrakis(triphenylphosphine)palladium (0.125 g, 1 mmol), and potassium carbonate (0.62 g, 4.5 mmol) were added to 20 mL of a 1:1 mixture of THF and water under a nitrogen atmosphere. 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. An orange-yellow solid (7) was given in 55.7% yield (0.46 g). 20 mL of chloroform was added to a two-necked flask, followed by 0.2 g of the product from the previous step, 1,2,3,3-tetramethyl-3H-indole iodide (0.185 g, 0.72 mmol), and ammonium acetate (0.020 g, 0.05 mmol). The mixture was reacted at 70 °C for 24 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The product was separated by column chromatography and recrystallized. The product was filtered to obtain a dark blue solid (0.26 g), with a yield of 59.8%.

[0030] The structural characterization data of the obtained intermediate 7 are shown below:

[0031] 1H NMR (500 MHz, C6D6) δ 9.52 (s, 1H), 7.22 (d, J = 7.35 Hz, 2H), 7.15 – 7.03 (m, 12H), 6.99 (d, J = 7.40 Hz, 2H), 6.94 – 6.90 (m, 5H), 6.87 –6.82 (m, 3H), 6.76 (d, J = 2.10 Hz, 1H). 13C NMR (125 MHz, C6D6) δ 181.46,153.48, 148.92, 147.92, 147.17, 144.15, 141.90, 141.76, 136.76, 129.46, 129.35, 127.16, 126.34, 126.23, 125.14, 124.83, 124.19, 123.54, 122.82, 122.47, 122.13.

[0032] Example 4: UV-Vis absorption spectra of TT-TMI, BTT-TMI, and BTS-TMI

[0033] Figure 1 To measure the optical properties of molecules in dilute tetrahydrofuran (THF) solution, we investigated their optical absorption characteristics by measuring the UV-Vis absorption spectra of three materials: TT-TMI, BTT-TMI, and BTS-TMI. Figure 1 The absorption spectra of three molecules in THF solution are shown. The absorption peaks of TT-TMI, BTT-TMI, and BTS-TMI are located at 560 nm, 580 nm, and 610 nm, respectively. With the construction of the D-π-A type molecular structure, the electron-donating triphenylamine chain segment is extended, and the absorption spectrum of the molecules gradually red-shifts, indicating that the molecules have strong charge transfer in the excited state.

[0034] Example 5: Emission spectra of TT-TMI, BTT-TMI, and BTS-TMI

[0035] Figure 2 The emission spectra of TT-TMI, BTT-TMI, and BTS-TMI in THF are shown. In THF solution, their maximum emission peaks correspond to wavelengths of 660 nm, 670 nm, and 654 nm, respectively, reaching the near-infrared region and demonstrating strong potential for bioimaging. Moreover, all three target products exhibit a wide emission range (600 nm-9000 nm), originating from diverse vibrational relaxation, internal conversion, and other non-radiative transition processes in the excited state, reaching as far as the near-infrared I (NIR-I) region.

[0036] Example 6: Theoretical Calculations of TT-TMI, BTT-TMI, and BTS-TMI

[0037] like Figure 3 As shown, Figure 3 A and B are the HOMO / LUMO electron cloud distribution diagrams of TT-TMI, respectively. Figure 3 C and D are the HOMO / LUMO electron cloud distribution diagrams of BTT-TMI, respectively. Figure 3 E and F are the HOMO / LUMO electron cloud distribution diagrams of BTS-TMI, respectively. According to theoretical calculations, the electrons of the lowest unoccupied molecular orbital (LUMO) are mainly delocalized on the acceptor unit, while the highest occupied molecular orbital (HUMO) is distributed on the extended triphenylamine chain segment. The carbon atoms of the extended triphenylamine chain segment exhibit a significant positive π charge due to increased electron-donating ability, while the negative π charge is mainly distributed on the indolon nucleus. This may lead to strong intramolecular charge transfer between the donor and acceptor, thereby significantly reducing the band gap and resulting in longer absorption and emission.

Claims

1. A class of near-infrared luminescent materials based on thiophene bridging groups, the molecular characteristic structures of which are shown in I-III below: 。 2. The near-infrared luminescent material based on a thiophene bridging group according to claim 1, characterized in that, Thiophene bridges possess excellent π-conjugation capabilities and can serve as bridging units to connect donor and acceptor components, constructing D-π-A structures. The addition of thiophene can effectively enhance the conjugation pathway of molecules, thereby reducing the band gap and causing the absorption and emission wavelengths to redshift to the NIR region, thus obtaining near-infrared luminescent materials and enriching the near-infrared material system.

3. The near-infrared luminescent material based on a thiophene bridging group according to claim 1, characterized in that, The D-π-A type structure can produce a significant ICT effect in the excited state, which is conducive to the efficient emission transition of excited-state molecules and significantly enhances their luminescence intensity. In addition, the thiophene structure easily forms π-π stacking in the solid state, which helps to enhance the transfer rate of electrons / holes between molecules and is often used to improve quantum yield and signal strength.

4. The near-infrared luminescent material based on a thiophene bridging group according to claim 1, characterized in that, The cationic nature of 1,2,3,3-tetramethyl-3H-indole iodide is beneficial for surface grafting of hydrophilic groups, enhancing its dispersibility in biological systems and blood stability; Specific recognition groups can be introduced to achieve active targeted imaging or treatment of cancer cells, tumor microenvironment, etc.

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