A method for synthesizing an amphiphilic quasi-conjugated molecule

Abstract

The application provides a synthesis method of an amphiphilic quasi-conjugated molecule. By linking a high-activity reaction group, such as an azide group, a triple bond group and other reactive groups, at the end or side of a conjugated skeleton, efficient copolymerization and functionalization regulation of a hydrophilic component and the conjugated skeleton are realized. By using efficient chemical reactions such as click reactions, the reactivity and selectivity of the molecule are significantly improved. Meanwhile, by adjusting the reaction solvent and conditions, the self-assembly behavior of the molecule is optimized, the particle size, morphology and assembly characteristics of the nanoparticle are accurately controlled by regulating the molecular weight, chain length and structure of the molecule, so that the synthesis efficiency is improved and the photophysical properties are accurately controlled. This technology not only improves the synthesis efficiency of the material, but also provides a new strategy and idea for the design and application of functional materials such as optoelectronics and drug delivery.

Description

Technical Field

[0001] This invention belongs to the field of materials synthesis technology, specifically relating to a method for synthesizing amphiphilic quasi-conjugated molecules and a technique for controlling their photophysical properties. Background Technology

[0002] With the continuous advancements in medicine, chemistry, and pharmacy, developing novel treatments has become a crucial task for improving health. Traditional diagnostic and drug development often faces challenges such as lengthy cycles, high costs, and limited success rates, which to some extent restricts the improvement of treatment outcomes. Therefore, there is an urgent need to explore and develop new strategies that can replace or supplement traditional drug therapies. In this context, regulating the synthesis and photophysical functions of specific molecules offers a new direction for achieving efficient and precise treatment. However, many traditional photosensitizers currently have limitations in performance, such as fixed energy conversion efficiency and a lack of flexibility in functional regulation, making it difficult to avoid potential damage to healthy tissues during treatment. Therefore, innovations in molecular design and photophysical functional regulation to develop more precise and controllable treatment technologies have significant clinical application value. Summary of the Invention

[0003] To address the aforementioned problems, this invention proposes an innovative method for synthesizing amphiphilic quasi-conjugated molecules and its functional regulation. By grafting highly reactive groups, such as azide groups, triple bond groups, and other reactive groups, onto the ends or sides of the conjugated backbone, efficient copolymerization and functionalization regulation of the hydrophilic component and the conjugated backbone are achieved. Utilizing efficient chemical reactions such as click reactions significantly improves the reactivity and selectivity of the molecules. Simultaneously, by adjusting the reaction solvent and conditions, the self-assembly behavior of the molecules is optimized. By controlling the molecular weight, chain length, and structure of the molecules, the particle size, morphology, and assembly characteristics of nanoparticles can be precisely controlled, thereby improving synthesis efficiency and precisely regulating photophysical properties. This technology not only improves the synthesis efficiency of materials but also provides new strategies and ideas for the design and application of functional materials in optoelectronics, drug delivery, and other fields.

[0004] The method for synthesizing amphiphilic quasi-conjugated molecules provided by the present invention includes the following steps: copolymerizing the conjugated structure molecule shown in Formula I with the hydrophilic macromolecule shown in Formula II to obtain a conjugated polymer, i.e., an amphiphilic quasi-conjugated molecule;

[0005]

[0006] In Formula I, It is any one of the following groups: (R is H or C1-C) 10 (straight-chain or branched alkyl groups) (R = -C) m H 2m - ),

[0007] It is any one of the following groups: hydrogen, -N3, -NH2; n = integers from 1 to 10; m = integers from 1 to 10; It can be any one of the following groups: hydrogen, alkynyl, mercapto, carboxyl, and aldehyde; and Cannot both be H;

[0008] In formula II, It may be the same as or different from ○, at least one of which is any one of azide, alkynyl, mercapto, carboxyl, and aldehyde, and the other may be C1-C. 10 Alkyl groups, such as methoxy groups; n represents an integer from 10 to 50.

[0009] In the conjugated structure molecule shown in Formula I, a narrow-bandgap donor-acceptor backbone is constructed to enhance the quinone or biradical properties of the acceptor, thereby reducing the bandgap and achieving a near-infrared light response. The aggregation state is regulated by stimulating responsive molecules, thus modulating light absorption and excited-state energy levels. Furthermore, intermolecular charge transfer characteristics are used to optimize the absorption wavelength by optimizing the frontier orbital energy level, and combined with aggregation-induced emission properties, precise regulation of the light response is achieved. Groups capable of click reactions are also introduced into the molecular structure, enhancing the molecule's functionalization and regulatory capabilities.

[0010] Specifically, the conjugated molecule shown in Formula I above is any one of the following compounds:

[0011]

[0012] The hydrophilic macromolecule shown in Formula II possesses excellent solubility and self-assembly ability through the binding of polyethylene glycol (PEG) groups to the conjugated backbone. Grafting highly reactive groups, such as azide groups, triple bond groups, thiol groups, and amino groups, onto the ends of the PEG groups imparts high reactivity, enabling it to undergo various chemical reactions (such as click reactions and Markel addition reactions), thus achieving functionalization and regulation.

[0013] Specifically, the hydrophilic macromolecule shown in Formula II above is any one of the following compounds:

[0014]

[0015] Specifically, the method for synthesizing the amphiphilic quasi-conjugated molecule is as follows: a click reaction is carried out between a hydrophilic macromolecule containing an azide group and a conjugated structural molecule containing an alkyne group;

[0016] Alternatively, a click reaction can be performed between a hydrophilic macromolecule containing an alkyne group and a conjugated molecule containing an azide group to obtain an amphiphilic quasi-conjugated molecule.

[0017] Furthermore, the method for synthesizing the amphiphilic quasi-conjugated molecule is as follows: in an inert atmosphere and in the presence of an inorganic salt, a hydrophilic macromolecule containing an azide group undergoes a click reaction with a conjugated structural molecule containing an alkyne group.

[0018] Alternatively, in an inert atmosphere and in the presence of inorganic salts, a click reaction is carried out between a hydrophilic macromolecule containing an alkyne group and a conjugated molecule containing an azide group to obtain an amphiphilic quasi-conjugated molecule.

[0019] The inorganic salt may be at least one of cuprous iodide and cuprous bromide;

[0020] The molar fraction of the hydrophilic macromolecule can be 0.075 to 1.5 parts;

[0021] The molar proportions of conjugated structure molecules can be 0.100–0.380 parts;

[0022] The molar proportion of the inorganic salt can be 0.075 to 1.5 parts;

[0023] Specifically, the molar ratio of the hydrophilic macromolecule to the conjugated structural molecule and the inorganic salt can be 4:1:4;

[0024] The temperature of the click reaction can be 25-80℃, specifically 75℃, and the time can be 24-72h, specifically 48h.

[0025] The amphiphilic quasi-conjugated molecules (amphiphilic conjugated polymers) prepared by the above synthesis method are also within the scope of protection of this invention.

[0026] Specifically, the amphiphilic quasi-conjugated molecule is one of the following polymers:

[0027]

[0028] The amphiphilic conjugated polymer can spontaneously disperse in an aqueous solution to form nanoparticles.

[0029] Nanoparticles prepared from the above-mentioned amphiphilic conjugated polymers are also within the scope of protection of this invention.

[0030] The nanoparticles have a particle size ranging from 100 to 300 nanometers and exhibit excellent ultraviolet absorption properties, with their ultraviolet absorption peaks located in the 600-900 nanometer range. Under irradiation with light corresponding to these absorption peaks, the temperature of the nanoparticles can rapidly rise to 40-80 degrees Celsius, thus achieving effective photothermal conversion. Their photothermal conversion efficiency can reach 30-50%, demonstrating a strong photothermal effect and making them suitable for fields such as photothermal therapy. The structural and functional properties of these nanoparticles give them broad potential in biomedical applications.

[0031] The present invention also provides two methods for preparing the above-mentioned amphiphilic polymer nanoparticles.

[0032] One method is solvent displacement:

[0033] (1) The amphiphilic polymer is dissolved in an organic solvent, and the organic solvent is removed by vacuum distillation to form a thin film;

[0034] (2) The obtained film was added to ultrapure water, and an aqueous solution of nanoparticles was obtained by self-assembly.

[0035] (3) The obtained nanoparticles are obtained by dialysis of the aqueous solution of the nanoparticles.

[0036] In step (1) of the above method, the organic solvent may specifically be chloroform, tetrahydrofuran, 1,4-dioxane, toluene, etc.

[0037] The temperature used for vacuum distillation is 30-60℃, and the pressure is 10-300 mmHg.

[0038] The thickness of the formed film is approximately 0.5-2 mm;

[0039] In step (2) of the above method, the volume of ultrapure water can be 8-15 mL, specifically 10 mL;

[0040] In step (3) of the above method, the molecular weight cutoff of the dialysis bag is 3500 kDa.

[0041] The second method is solvent displacement:

[0042] (1) First, dissolve the amphiphilic polymer in a small amount of organic solvent to form a homogeneous solution;

[0043] (2) Quickly add the resulting solution to ultrapure water;

[0044] (3) The organic solvent interacts with the solvent in the aqueous phase by stirring, ultrasonic treatment or other methods;

[0045] (4) Finally, through the evaporation or displacement of the solvent, the nanoparticles are separated from the organic solvent to form a stable aqueous dispersion. The water is then removed to obtain the nanoparticles.

[0046] In step (1) of the method, the organic solvent may be chloroform, tetrahydrofuran, etc., and the volume of the organic solvent may be 0.2-2 ml, specifically 0.5 ml;

[0047] In step (2) of the above method, the volume of ultrapure water can be 8-15 mL, specifically 10 mL.

[0048] The advantages of this invention are:

[0049] 1. Simplified preparation process: It adopts an efficient and green preparation method, reduces the use of harmful solvents, and has low energy consumption and high production efficiency, making it suitable for large-scale production.

[0050] 2. Controllable particle size and distribution: The polymer particle size and distribution can be precisely controlled during the preparation process to ensure the stability and uniformity of nanoparticles and meet different application requirements.

[0051] 3. Excellent biocompatibility: The amphiphilic structure enhances the polymer's application potential in the biomedical field, making it suitable for drug carriers and gene therapy, and exhibiting good biocompatibility and stability.

[0052] 4. The prepared nanoparticles have uniform morphology and stable structure, effectively solving the problem of poor water solubility of conjugated polymers;

[0053] 5. This conjugated polymer has amphiphilic and self-assembly properties. After forming nanoparticles, it exhibits a red shift in the spectrum and has a stronger photothermal effect. By modifying the hydrophilic side chain groups, it can self-assemble into water-soluble photothermal nanomaterials using hydrophobic interactions.

[0054] 6. Adjustable electro-optical properties: The quasi-conjugated structure endows it with excellent electronic and optical properties, which can adjust the band gap and improve charge transfer and stability, making it suitable for optoelectronic materials, sensors and other fields.

[0055] 7. Dual functionality of structure: The polymer has an amphiphilic structure, which can self-assemble or stably disperse between aqueous and oil phases, making it suitable for various applications such as drug delivery and nanoparticle preparation. Attached Figure Description

[0056] Figure 1 This is a synthetic route diagram for preparing nanoparticles in Example 1 of the present invention.

[0057] Figure 2 The images show the ultraviolet absorption pattern (a), infrared absorption pattern (b), TEM image (c), and particle size distribution (d) of the nanoparticles 1-NP obtained in Example 1 of this invention.

[0058] Figure 3 This is a photothermal absorption diagram of the nanoparticles prepared in Example 1 of the present invention.

[0059] Figure 4 This is a synthetic route diagram for preparing nanoparticles in Example 2 of the present invention.

[0060] Figure 5 The images show the ultraviolet absorption pattern (a), infrared absorption pattern (b), TEM image (c), and particle size distribution (d) of the nanoparticles obtained in Example 2 of this invention.

[0061] Figure 6 This is the photothermal absorption diagram of the IEG-NP obtained in Example 2 of the present invention.

[0062] Figure 7 This is a synthetic route diagram for preparing nanoparticles in Example 3 of the present invention.

[0063] Figure 8 The ultraviolet absorption pattern (a), infrared absorption pattern (b), TEM image (c), and particle size diagram (d) of the nanoparticles prepared in Example 3 of this invention are shown.

[0064] Figure 9 The photothermal absorption diagram of the nanoparticles prepared in Example 3 of this invention is shown. Detailed Implementation

[0065] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0066] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0067] Example 1: Synthesis of Conjugated Polymer 1

[0068] according to Figure 1 The synthetic route shown is used to prepare conjugated polymer 1.

[0069] The specific operations include:

[0070] Synthesis of 9,9-dihexyl-9H-fluorene (compound 1): A mixture of fluorene (1 g, 0.006 mol), iodohexane (2.8 g, 0.0132 mol), and sodium hydroxide (0.72 g, 0.018 mol) was placed in DMSO (7.2 mL) and stirred overnight at 90 °C under an inert atmosphere. After cooling to room temperature, the solution was poured into cold water, and the resulting mixture was extracted with dichloromethane (50 mL). The combined organic layers were washed with water, dried overnight with anhydrous sodium sulfate, filtered, and concentrated to dryness. The crude product was purified by silica gel column chromatography using petroleum ether as the eluent to give a colorless solid. 1H NMR(400MHz,Chloroform-d)δ7.67(d,J=7.2Hz,1H),7.60-7.43(m,2H),7.28(d, J=14.8Hz,4H),1.55(s,4H),1.26(s,4H),0.88(s,1H),0.07(s,1H),0.00(s,3H).

[0071] Synthesis of 2-bromo-9,9-dihexyl-9H-fluorene (compound 2): 9,9-dihexyl-9H-fluorene (compound 1) (13 g, 46 mmol) and NBS (8.25 g, 46 mmol) were mixed in acetone (50 mL) and stirred at 80 °C for 3 h under nitrogen protection. After cooling to room temperature, the solution was poured into cold water, and the resulting mixture was extracted with dichloromethane (3500 mL). The combined organic layers were washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The crude product was purified by silica gel short column chromatography using petroleum ether as eluent to obtain a colorless solid. 1H NMR(400MHz,Chloroform-d)δ7.95(s,1H),7.73(d,J=8.3Hz,1H),7.64(s,1H),7.59(s,2H),7.54(s,2H),7.47-7.38(m,3 H),7.26(s,3H),2.01-1.79(m,15H),1.55(s,3H),1.26(s,3H),1.20-0.93(m,47H),0.79(t,J=7.0Hz,23H),0.53(s,15H).

[0072] Synthesis of 2-bromo-9,9-dihexyl-7-iodo-9H-fluorene (compound 3): 2-bromo-9,9-dihexyl-9H-fluorene (compound 2) (15.4 g, 43 mmol), iodine (6.5 g, 25.8 mmol), concentrated sulfuric acid (2.3 mL), periodic acid (1.7 g, 25.8 mmol), and water (7.7 mL) were stirred at 60 °C for 4 h in glacial acetic acid (74 mL). After cooling to room temperature, the solution was poured into ice-cold water containing a large amount of sodium sulfite. The resulting mixture was extracted with dichloromethane (100 mL). The combined organic phases were washed twice with water, dried over anhydrous sodium sulfate, and concentrated to dryness. The crude product was purified by silica gel short column chromatography using petroleum ether as eluent to give a pale yellow solid. 1HNMR(400MHz,Chloroform-d)δ7.67(s,1H),7.56(d,J=7.8Hz,1H),7.47(s,2H),7.32(s,3H) ,1.95(dt,J=11.7,5.3Hz,4H),1.22-0.94(m,14H),0.78(t,J=7.1Hz,7H),0.71-0.50(m,4H).

[0073] Synthesis of bromo-7-ethynyl-9,9-dihexyl-9H-fluorene (compound 4): 2-bromo-9,9-dihexyl-7-iodo-9H-fluorene (compound 3) (3.00 g, 6.21 mmol) was added to NEt3 triethylamine (30 mL) and deoxygenated by a three-cycle refrigeration pump-thawing system. The flask was purged with nitrogen. PdCl2(PPh3)2 (130 mg, 0.19 mmol), CuI (70 mg, 0.37 mmol), and trimethylsilylacetylene (0.92 mL, 6.46 mmol) were added, and the mixture was stirred at room temperature for 6 h. The solvent was removed under reduced pressure, and the residue was filtered by flash chromatography using silica gel column chromatography, eluted with petroleum ether. The solvent was removed to give a yellow solid. This solid was added to a mixture of deoxygenated CH2Cl2 and methanol (1:1, 30 mL). 1HNMR(400MHz,Chloroform-d)δ7.58(d,J=7.8Hz,1H),7.52(d,J=8.4Hz,1H), 7.45(d,J=6.2Hz,3H),7.41(s,1H),1.92(dd,J=11.4,5.5Hz,4H),1.51(s,1H), 1.43(s,1H),1.28(d,J=8.6Hz,3H),1.20-0.92(m,13H),0.87(dt,J=11.9,7.1H z, 2H), 0.78 (t, J = 7.2Hz, 6H), 0.56 (dq, J = 12.5, 6.7, 6.2Hz, 4H), 0.29 (s, 10H).

[0074] K₂CO₃ (1.72 g, 12.42 mmol) was added and stirred at room temperature for 5 h. The solvent was removed under vacuum, and the mixture was subjected to alumina and silica gel column chromatography sequentially. The residue was filtered. ¹H NMR (400 MHz, Chloroform-d) δ 7.61 (d, J = 7.9 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.51–7.41 (m, 4H), 7.26 (s, 3H), 3.15 (s, 1H), 2.06–1.81 (m, 5H), 1.55 (s, 5H), 1.26 (s, 4H), 1.18–0.95 (m, 14H), 0.87 (d, J = 7.6 Hz, 1H), 0.77 (t, J = 6.8 Hz, 7H), 0.55 (d, J = 14.4 Hz, 5H).

[0075] Synthesis of tributyl(2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)stanane (compound 5): Under argon protection, 3,4-ethylenedioxythiophene (8.45 g, 59.43 mmol) and anhydrous tetrahydrofuran (100 mL) were added sequentially to a 500 mL two-necked flask. The solution was cooled to -78 °C, and 26 mL of n-butyllithium (62.4 mmol, 2.4 M) was added dropwise over 1 hour. After stirring at this temperature for 1 hour, the reaction mixture was heated to -20 °C and reacted for 1 hour. The reaction mixture was then cooled to -78 °C and stirred for 30 minutes, during which tributyltin chloride (21.28 g, 65.37 mmol) was added dropwise over 30 minutes. The reaction mixture was then stirred at -78 °C for another 1 hour, slowly heated to room temperature, and stirred overnight. After the reaction is complete, the mixture is poured into 100 mL of water, extracted with dichloromethane, washed with saturated brine of the organic phase, dried with anhydrous sodium sulfate for 24 h, and the solvent is removed by vacuum distillation. The product obtained can be directly added to the next step without purification.

[0076] 5-(7-ethynyl-9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothieno[3,4-b][1,4]dioxane (compound 6): In a 25 ml double-necked flask, bromo-7-ethynyl-9,9-dihexyl-9H-fluorene (compound 4) (0.6 g, 1.3 mmol) and tributyl(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)stanane (compound 5) (2.37 g, 5.5 mmol) were dissolved in toluene (5 ml) under a protective atmosphere, and then Pd(PPh3)4 (15 mg) was added. The reaction was carried out at 110 °C for 24 h. After the reaction was completed, the mixture was cooled to room temperature. The organic phase was then washed with a saturated aqueous solution of potassium fluoride, extracted with dichloromethane, dried with anhydrous sodium sulfate for 24 h, and the solvent was removed by vacuum distillation. Finally, the crude product was purified by column chromatography using silica gel as the packing material (petroleum ether: dichloromethane = 4:1). ¹H NMR (400 MHz, Chloroform-d) δ 7.82–7.60 (m, 4H), 7.60–7.29 (m, 3H), 6.36 (d, J = 8.4 Hz, 1H), 4.45–4.16 (m, 5H), 2.04 (dq, J = 23.5, 7.3 Hz, 3H), 1.78–0.48 (m, 36H), 0.12 (s, 6H).

[0077] Tributyl(7-(7-ethynyl-9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)stanane (compound 7): In a 100 mL double-necked flask, 5-(7-ethynyl-9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)stanane (compound 6) (1 g, 2 mmol) was dissolved in 20 mL of anhydrous tetrahydrofuran under argon protection, and then dissolved at -78 °C. At ℃, lithium diisopropylamino (LDA) (2.0 M, 6 mmol) was added dropwise to the reaction system. After stirring at this temperature for 1.5 hours, tributyltin chloride (0.978 g, 3 mmol) was added. The reaction mixture was then slowly heated to room temperature and stirred overnight. After the reaction was complete, the mixture was poured into water and extracted twice with ethyl acetate. The organic phase was washed with saturated brine and dried with anhydrous sodium sulfate for 24 hours. The solvent was removed by vacuum distillation. The obtained product can be directly used in the next step without purification.

[0078] (Compound 8): Compound BBT (45 mg, 0.12 mmol Zhengzhou Alpha) and the crude product obtained above (0.3 g, 0.38 mmol) were dissolved in toluene solution (10 mL) under argon protection. Then, Pd(PPh3)4 (1.45 mg) was added, and the mixture was stirred at 110 °C for 12 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate for 24 hours. The solvent was removed by vacuum distillation. The crude product was purified by column chromatography using silica gel as the packing material (petroleum ether: ethyl acetate = 2:1). 1 H NMR(600MHz,Chloroform-d)δ7.81(d,J=7.3Hz,1H),7.74(s,1H),7.68(d,J=7.8Hz,3H),7.5 9(s,1H),7.50(d,J=18.1Hz,4H),6.33(s,1H),4.33(d,J=47.6Hz,5H),2.89(s,2H),1.96(d, J=62.3Hz,7H),1.56-1.40(m,12H),1.36(dt,J=15.3,7.3Hz,4H),1.26(s,4H),1.20-0.99(m ,20H),0.92(s,5H),0.78(d,J=7.3Hz,8H),0.70(d,J=7.5Hz,6H),0.07(s,4H),0.00(s,2H).

[0079] Synthesis of the conjugated polymer 1-NP: 1,4-dioxane (5 mL), the above compound (5 mg, 0.00314 mmol), cuprous iodide (2.38 mg, 0.01256 mmol), and methoxy polyethylene glycol azide (25.26 mg, 0.01256 mmol) (Mn = 2000) were added to a reaction flask and stirred overnight at room temperature. The organic solvent was removed by vacuum distillation to form a thin film. Subsequently, the resulting mixture was added to 10 mL of ultrapure water, and an aqueous solution of nanoparticles was obtained by self-assembly. Finally, the aqueous solution of nanoparticles was treated by dialysis (dialysis bag with a molecular weight cutoff of 3500 kDa) to obtain the nanoparticles.

[0080] Figure 1 This is the overall composite image.

[0081] Figure 2 The images show the UV absorption spectrum (a), IR absorption spectrum (b), TEM image (c), and particle size distribution (d) of the obtained nanoparticles 1-NP.

[0082] Figure 3The image shows the photothermal absorption curve of the prepared nanoparticles. The temperature rise curves of polymer 1-NP at concentrations of 0 mg / ml, 2 mg / ml, 4 mg / ml, and 8 mg / ml under irradiation with an 808 nm laser at a power of 0.8 W are also shown.

[0083] Example 2: Synthesis of the conjugated polymer IEG-NP

[0084] according to Figure 4 The synthetic route shown is used to prepare the conjugated polymer IEG-NP.

[0085] The specific operations include:

[0086] Synthesis of IEG-N3

[0087] In a nitrogen-filled two-necked flask, compound IFE-Br2 (see Chinese Patent 202410112003.8) (100 mg, 0.070 mmol) and sodium azide (46 mg, 0.7 mmol) were dissolved in DMF (10 mL). The reaction was terminated after heating at 70 °C for 3 hours, cooled to room temperature, and then a large amount of water was added and stirred until all the solids dissolved. The mixture was then extracted twice with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. Finally, the solvent was evaporated under vacuum. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give 80 mg of an orange-yellow solid, with a yield of 89.5%.

[0088] As shown in the figure, the HR-MS ESI (m / z) values ​​for the compound [C68H74N16O4S3Na]+ are 1297.5139, and the measured values ​​are 1297.5155.

[0089] Synthesis of IEG-NO:

[0090] In a 50 mL single-necked round-bottom flask, IEG-N3 (20 mg, 0.014 mmol) was added, followed by the addition of dichloromethane (10 mL) to dissolve it. Then, sodium nitrite (6 mg, 0.09 mmol) and glacial acetic acid (100 μL) were added sequentially. After stirring at room temperature for 30 minutes, the reaction mixture was poured into water and extracted twice with ethyl acetate. Finally, the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The crude product was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give 15 mg of a blue solid product, with a yield of 74.48%.

[0091] IEG-NP is synthesized by reacting IEG-NO with diyne-polyethylene glycol.

[0092] Add tetrahydrofuran (5 mL), IEG-NO compound (5 mg, 0.00385 mmol), cuprous iodide (1.82 mg, 0.00962 mmol), and diynyl polyethylene glycol (7.71 mg, 0.00771 mmol) (Mn = 2000) to a reaction flask and stir overnight at room temperature. Remove the organic solvent by vacuum distillation to form a thin film.

[0093] Subsequently, the obtained mixture was added to 10 ml of ultrapure water, and an aqueous solution of nanoparticles was obtained by self-assembly. Finally, the aqueous solution of nanoparticles was treated by dialysis (the molecular weight cutoff of the dialysis bag was 3500 kDa) to obtain nanoparticles.

[0094] Figure 4 Synthesis diagram for preparing IEG-NP.

[0095] Figure 5 The images shown are the ultraviolet absorption pattern (a), infrared absorption pattern (b), TEM image (c), particle size diagram (d), and photothermal absorption pattern of the obtained nanoparticles.

[0096] Figure 6 The image shows the photothermal absorption curve of the prepared IEG-NP. The image also shows the temperature rise curves of IEG-NP irradiated with a 650nm laser at a power of 0.8W at concentrations of 0 mg / ml, 0.25 mg / ml, 0.5 mg / ml, and 1 mg / ml.

[0097] Example 3: Synthesis of Conjugated Polymer 3

[0098] according to Figure 7 The synthetic route shown is used to prepare conjugated polymer 2.

[0099] Synthesis of 5-(9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiophene[3,4-b][1,4]dioxene (compound 10): In a 25 ml double-necked flask, bromo-9,9-dihexyl-9H-fluorene (compound 9 Aladdin) (1 g, 0.00242 mol) and tributyl(2,3-dihydrothiophene[3,4-b][1,4]dioxin-5-yl)stanane (compound 5) (4.17 g, 0.00968 mol) were dissolved in toluene (10 ml) under a protective atmosphere, and then Pd(PPh3)4 (20 mg) was added. The reaction was carried out at 110°C for 24 hours. After the reaction was completed, the mixture was cooled to room temperature. The organic phase was then washed with a saturated aqueous solution of potassium fluoride and extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate for 24 hours. The solvent was removed by vacuum distillation. Finally, the crude product was purified by column chromatography (petroleum ether: dichloromethane = 2:1) using silica gel as the packing material. 1HNMR(600MHz,Chloroform-d)δ7.63(dd,J=7.9,1.7Hz,1H),7.56(dd,J=7.9,1.8Hz ,3H),7.24-7.13(m,3H),6.18(s,1H),4.20-4.16(m,2H),4.12-4.08(m,2H),1.94-

[0100] 1.82(m,4H),1.30-1.14(m,2H),1.06-0.89(m,12H),0.80(dt,J=20.7,7 .2Hz,1H),0.65(t,J=7.3Hz,6H),0.62-0.56(m,2H),0.58-0.52(m,1H).

[0101] Tributyl(7-(9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)stanane (compound 11): In a 100 mL double-necked flask, 5-(9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxinidine (compound 10) (1 g, 2 mmol) was dissolved in 20 mL of anhydrous tetrahydrofuran under argon protection, and then dissolved at -78 °C. Under the given conditions, n-butyllithium (2.0 M, 6 mmol) was added dropwise to the reaction system. After stirring at this temperature for 1.5 hours, tributyltin chloride (0.978 g, 3 mmol) was added. The reaction mixture was then slowly heated to room temperature and stirred overnight. After the reaction was complete, the mixture was poured into water and extracted twice with ethyl acetate. The organic phase was washed with saturated brine and dried with anhydrous sodium sulfate for 24 hours. The solvent was removed by vacuum distillation. The resulting product could be directly used in the next step without purification.

[0102] Synthesis of 3,6-bis(5-(7-(9,9-dihexyl-9H-fluoren-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)thiopheno-2-yl)-2,5-bis(hexyl-5-yn-1-yl)-2,5-dihydropyrrolo[3,4-c]pyrrolo-1,4-dione (Compound 12): Compound DPP (see Chinese Patent 202410081757.1) (80 mg) 0.13 mmol) of the crude product obtained above, tributyl(7-(9,9-dihexyl-9H-fluorene-2-yl)-2,3-dihydrothiopheno[3,4-b][1,4]dioxin-5-yl)stanane (0.3 g, 0.38 mmol), was dissolved in toluene solution (3 mL) under argon protection. Then, Pd(PPh3)4 (1.45 mg) was added, and the mixture was stirred at 110 °C for 2 hours, followed by stirring at room temperature overnight. The mixture was poured into water and extracted twice with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate for 24 hours. The solvent was removed by vacuum distillation, and the crude product was purified by column chromatography using silica gel as the packing material (petroleum ether: ethyl acetate = 1:1).

[0103] Synthesis of conjugated polymer 2-NP: Chloroform (5 mL), the above compound (5 mg, 0.00385 mmol), cuprous iodide (1.82 mg, 0.00962 mmol), and methoxy polyethylene glycol azide (7.71 mg, 0.00771 mmol) (Mn = 2000) were added to a reaction flask and stirred overnight at room temperature. The organic solvent was removed by vacuum distillation to form a thin film. Subsequently, the resulting mixture was added to 10 mL of ultrapure water, and an aqueous solution of nanoparticles was obtained by self-assembly. Finally, the aqueous solution of nanoparticles was treated by dialysis (dialysis bag with a molecular weight cutoff of 3500 kDa) to obtain nanoparticles.

[0104] Figure 7 This is a diagram showing the overall synthesis of the conjugated polymer 2-NP.

[0105] Figure 8 The images show the UV absorption spectrum (a), IR absorption spectrum (b), TEM spectrum (c), and particle size distribution (d) of the obtained nanoparticles.

[0106] Figure 9 The image shows the photothermal absorption curve of the conjugated polymer 2-NP. The temperature rise curves of the conjugated polymer 2-NP under irradiation with a 650nm laser at concentrations of 0 mg / ml, 0.5 mg / ml, 1 mg / ml, and 2 mg / ml are also shown.

[0107] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. An amphiphilic quasi-conjugated molecule, said amphiphilic quasi-conjugated molecule being prepared by a method comprising the following steps: In an inert atmosphere and in the presence of inorganic salts, compound 1 or compound 3 reacts with compound 7 via a click reaction to yield an amphiphilic quasi-conjugated molecule. 。 2. The amphiphilic quasi-conjugated molecule according to claim 1, characterized in that, The inorganic salt is at least one of cuprous iodide and cuprous bromide; The molar amount of compound 7 is 0.075 to 1.5 parts; The molar amount of compound 1 or compound 3 is 0.100 to 0.380 parts; The inorganic salt is added in molar proportions of 0.075 to 1.5 parts; The click reaction is carried out at a temperature of 25-80℃ for a duration of 24-72 hours.

3. The amphiphilic quasi-conjugated molecule according to claim 1, characterized in that, The amphiphilic quasi-conjugated molecule is one of the following polymers: 。 4. Nanoparticles prepared from the amphiphilic quasi-conjugated molecules as described in claim 1.

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