Preparation method of phenothiazine derivative for generating singlet oxygen

Abstract

The invention provides a preparation method of phenothiazine derivatives for generating singlet oxygen. The phenothiazine derivative has a specific chemical structure, namely 2-(4 '-(10H-phenothiazine-10-yl)-[1, 1'-biphenyl]-4-yl)-3-(4 '-(1, 2, 2-tristyryl)-[1, 1'-biphenyl]-4-yl) fumaronitrile. The preparation method comprises multiple steps of reactions, including bromination of phenothiazine, esterification of boric acid, Suzuki coupling and other key steps, and finally a target compound is obtained. The derivative shows a specific absorption peak in a tetrahydrofuran solution, and has the maximum emission wavelength after excitation. In addition, the invention also provides a method for preparing nano particles from an amphiphilic molecule DSPE-PEG2000 formed by combining the phenothiazine derivative with polyethylene glycol (PEG2000) and phospholipid, wherein the amphiphilic molecule DSPE-PEG2000 is formed by combining the phenothiazine derivative with the polyethylene glycol (PEG2000) and the phospholipid. The phenothiazine derivative has relatively high singlet oxygen quantum yield, has potential application value in the fields of medicines, materials and the like, and particularly shows wide application prospects in the aspects of treating echinococcosis and long afterglow materials.

Description

Technical Field

[0001] The present invention relates to the synthesis of organic compounds, and particularly to a method for preparing phenothiazine derivatives. Background Art

[0002] Due to its unique optical and electronic properties, low cost, and easy functionalization, phenothiazine has become one of the most widely studied aromatic compounds. In recent years, phenothiazine and its derivatives have provided a versatile platform for the development of materials with a wide range of applications. The electron-rich sulfur and nitrogen atoms make phenothiazine a stronger electron donor, and its non-planar butterfly-shaped bent structure is sufficient to inhibit the formation of molecular aggregates. This unique structure endows them with unique electronic properties, in which the central nitrogen- and sulfur-containing atoms participate in the intramolecular conjugate system through lone pairs of electrons.

[0003] Phenothiazine derivatives are compounds obtained by chemical modifications such as substituting hydrogen atoms on the benzene ring based on the basic structure of phenothiazine. For example, different alkyl groups, halogen atoms, amino groups, etc. can be introduced on the benzene ring, and the introduction of these functional groups will change the physical and chemical properties of the compounds. Phenothiazine compounds have a wide range of applications in multiple fields.

[0004] In the field of medicine, Wang Weisi et al. published a patent (CN117327028A) "Phenothiazine derivatives, pharmaceutical compositions and their uses in the treatment of echinococcosis". The phenothiazine derivatives of this invention have a strong in vitro killing effect on the protoscoleces and cysts of Echinococcus granulosus and Echinococcus multilocularis, and have a good therapeutic effect on mice with Echinococcus granulosus disease and Echinococcus multilocularis disease. This invention provides phenothiazine derivatives, pharmaceutical compositions and their uses in the treatment of echinococcosis. Specifically, this invention provides a phenothiazine derivative, and its optical isomers, pharmaceutically acceptable salts or solvates can be used for the treatment and / or prevention of echinococcosis-related diseases. In the field of materials, Li Qianqian et al. from Wuhan University published a patent (CN115611826A) "Phenothiazine derivatives, their preparation methods and applications". The phenothiazine derivatives of this technical solution have a long afterglow phenomenon, and the phosphorescence lifetime is up to 384.61 ms at room temperature. This invention also provides a preparation method for the above-mentioned phenothiazine derivatives, which has simple synthesis steps, mild preparation conditions, high yield, low cost, and is suitable for large-scale production. The above-mentioned phenothiazine derivatives have different room-temperature phosphorescence properties and can be applied to the preparation of anti-counterfeiting marks, etc., and have different fluorescence properties. Summary of the Invention

[0005] The present invention provides a method for preparing a phenothiazine derivative for generating singlet oxygen, and the prepared phenothiazine derivative has good singlet oxygen generation ability ( 1 O 2 ).

[0006] The technical solution of the present invention is as follows: A phenothiazine derivative, the phenothiazine derivative is 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl) fumaronitrile, and its chemical structural formula is as follows: The preparation method of the above-mentioned phenothiazine derivative, wherein, it includes the following steps: The first step is the preparation of 10-(4-bromophenyl)-10H-phenothiazine: First, dissolve 5.0 g of phenothiazine in 1,4-dioxane, and add 17.7 g of 1,4-dibromobenzene at 100-120 °C to obtain the compound 10-(4-bromophenyl)-10H-phenothiazine; The second step is the preparation of 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine: Dissolve 1.0 g of 10-(4-bromophenyl)-10H-4-phenothiazine in 1,4-dioxane, and then add 1.08 g of bis(pinacolato)diboron and 0.2 g of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium to react to generate 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine; The third step is the preparation of 4,4,5,5-tetramethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)-1,3,2-dioxaborane: Dissolve 2.0 g of 1-(4-bromophenyl)-1,2,2-triphenylethylene in 1,4-dioxane, and then add 1.50 g of bis(pinacolato)diboron and 0.215 g of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium to react to generate 4,4,5,5-tetramethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)-1,3,2-dioxaborane; The fourth step is the preparation of 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl) fumaronitrile: Dissolve 11.94 g of 0-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine and 0.17 g of tetrakis(triphenylphosphine)palladium in tetrahydrofuran and water, and add 0.96 g of 2,3-bis(4-bromophenyl) fumaronitrile at 55-65 °C to react to generate 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl) fumaronitrile; The fifth step is the preparation of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile: 0.61 g of 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile is reacted with 0.78 g of 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine to obtain 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile.

[0007] The sixth step is to dissolve 1 mg of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile and 2 mg of the amphiphilic molecule DSPE-PEG2000 which is a combination of polyethylene glycol (PEG2000) and phospholipid (DSPE, 1,2-distearoyl-sn-glycero-3-phosphocholine) in 1 mL of tetrahydrofuran solution, and add 10 mL of deionized water to the mixture. The tetrahydrofuran and water mixture solution is sonicated for 2 minutes using a sonicator with an output power of 12 W. The resulting suspension is stirred overnight in a fume hood, the tetrahydrofuran is evaporated, and after filtration through a 0.2 μm syringe filter, it is further separated by 15 mL centrifugal filtration with a 10 KDa molecular cut-off membrane to obtain nanoparticles.

[0008] The preparation method of a phenothiazine derivative for generating singlet oxygen according to the present invention is characterized in that it exhibits three different absorption peaks in a tetrahydrofuran solution, located at 235, 315 and 400 nm respectively. After excitation, the maximum emission wavelength is 600 nm.

[0009] The present invention provides a preparation method of a phenothiazine derivative for generating singlet oxygen, and this phenothiazine derivative has a high singlet oxygen quantum yield. Description of the Drawings

[0010] Figure 1 is the 1H NMR spectrum of the compound prepared in Example 5 of the present invention.

[0011] Figure 2 is the 13C NMR spectrum of the compound prepared in Example 5 of the present invention.

[0012] Figure 3 is the mass spectrum of the compound prepared in Example 5 of the present invention.

[0013] Figure 4 It is the infrared spectrum of the compound prepared in Example 5 of the present invention.

[0014] Figure 5 It is the ultraviolet-fluorescence spectrum of the compound prepared in Example 6 of the present invention.

[0015] Figure 6 It is the ABDA absorbance degradation graph of the nanoparticles prepared in Example 6 of the present invention.

[0016] The technical solution of the present invention will be further explained according to the accompanying drawings: Figure 1 It is the 1H NMR spectrum of the compound prepared in this example: 1 HNMR (400 MHz, CDCl 3 , 298 K) δ (TMS, ppm): 7.90 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 4H), 7.36 (dd, J1 = 18.9 Hz, J2 = 18.8 Hz, 8H), 7.11 - 7.04 (m, 24H).

[0017] Figure 2 It is the 13C NMR spectrum of the compound prepared in Example 5 of this example: 13 13C NMR (100 MHz, CDCl 3 , 298 K) δ (ppm): 144.2, 143.6, 143.6, 143.5, 143.4, 142.7, 140.2, 140.1, 136.8, 132.1, 131.4, 131.4, 131.3, 129.9, 129.4, 129.2, 127.8, 127.7, 127.5, 127.4, 126.5, 126.4, 126.2, 125.1, 117.0.

[0018] Figure 3 It is the high-resolution mass spectrum of the compound prepared in Example 5 of this example: mass spectrum: 833.285.

[0019] Figure 4 It is the infrared spectrum of the compound prepared in Example 5 of this example: absorption peaks around 700 cm -1 are specific infrared absorption peaks of carbon-sulfur bonds, and absorption peaks around 947 cm -1 are C-H out-of-plane bending vibration peaks, absorption peaks between about 1500 cm -1 are specific infrared absorption peaks of carbon-nitrogen double bonds, and absorption peaks between about 1600 cm -1 are specific infrared absorption peaks of carbon-nitrogen double bonds, and absorption peaks between about 3100 cm -1The absorption peaks on the left and right are specific infrared absorption peaks of carbon-nitrogen single bonds.

[0020] Figure 5 The UV-fluorescence spectrum of the compound prepared in Example 5 shows three different absorption peaks in tetrahydrofuran (THF) solution, which are located at 235, 315 and 400 nm respectively. After excitation, the maximum fluorescence emission wavelength is 600 nm.

[0021] Figure 6 This is a graph of the ABDA absorbance degradation of the nanoparticles prepared in Example 6 of the present invention: under irradiation with a 420nm xenon lamp, the absorbance is measured every 1 minute, and the absorbance of ABDA decreases slowly, indicating that singlet oxygen is generated. Specific implementation methods

[0022] The present invention provides a method for preparing phenothiazine derivatives for generating singlet oxygen. To make the purpose, technical scheme and effect of the present invention clearer and more specific, the present invention is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. Example 1

[0023] The preparation method of 10-(4-bromophenyl)-10H-phenothiazine comprises the following steps: Phenothiazine (5.000 g, 25.00 mmol), 1,4-dibromobenzene (17.690 g, 75.00 mmol), potassium tert-butoxide (t-BuOK) (8.410 g, 75.00 mmol), tris(dibenzylethyl ketone) dipalladium (3%, 0.686 g, 0.75 mmol) and tri-tert-butylphosphine tetrafluoroborate (3%, 0.217 g, 0.75 mmol) were added to 1,4-dioxane (60 mL), degassed in a three-necked round-bottom flask, and then heated to 110 ° C with nitrogen and heated overnight. After cooling to room temperature, dichloromethane was added and the mixture was washed with water (2×100 mL). After removing the solvent, the crude product was purified by silica gel column chromatography with petroleum ether / dichloromethane (5 / 1, v / v) as the eluent to obtain a white powder (7.100 g, yield 80%). 1 HNMR (400 MHz, CDCl 3 , 298K) δ (TMS, ppm): 7.50 (S, 3H), 7.13 (d, J=7.6Hz, 4H), 6.70 (S, 3H), 6.52 (S, 2H). 13 CNMR (100MHz, CDCl 3 , 298K) δ (ppm): 143.8, 140.4, 130.4, 127.3, 127.0, 123.3, 122.8, 117.9. Example 2

[0024] A preparation method of 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine, comprising the following steps: Add 1.0 g (2.82 mmol) of 10-(4-bromophenyl)-10H-phenothiazine, 1.08 g (4.23 mmol) of bis(pinacolato)diboron, and 0.46 g (4.7 mmol) of KOAc to a three-necked round-bottom flask containing 70 mL of 1,4-dioxane. The solution is degassed and filled with nitrogen. Add Pd(dppf)Cl 2 (0.20 g, 0.15 mmol) through an equalizing funnel, and stir the mixture at 75 °C for 12 hours. After cooling to room temperature, wash the product with water, remove the solvent by rotary evaporation, and purify it by column chromatography on silica gel to obtain a white crystalline powder (0.91 g, yield 80%). 1 1H NMR (400 MHz, CDCl 3 , 298 K) δ (TMS, ppm): 7.49 (s, 2H), 7.12 (d, J = 7.2 Hz, 2H), 7.00 (t, J = 7.2 Hz, 3H), 6.91 (t, J = 7.2 Hz, 3H), 6.52 (d, J = 8 Hz, 2H), 1.26 (s, 12H). 13 13C NMR (100 MHz, CDCl 3 , 298 K) δ (ppm): 143.8, 140.4, 130.4, 127.3, 127.0, 123.3, 122.8, 117.9, 83.5, 225.0. Example 3

[0025] A preparation method of 4,4,5,5-tetramethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)-1,3,2-dioxaborane, comprising the following steps: Mix 1-(4-bromophenyl)-1,2,2-triphenylethylene (2.00 g, 4.87 mmol), bis(pinacolato)diboron (1.49 g, 5.89 mmol), and potassium acetate (1.91 g, 19.48 mmol) with 1,4-dioxane (40 mL) in a three-necked flask. The solution is degassed and filled with nitrogen. Add Pd(dppf) 2 Cl 2(5%) (215 mg, 0.3 mmol), and the reaction mixture was stirred at 85 °C for 24 h. After cooling to room temperature, the organic solvent was evaporated, and the remaining solid was dissolved in dichloromethane. The remaining solid was washed with water and the solvent was removed. The crude product was purified on a silica gel column using petroleum ether / dichloromethane (7 / 3, v / v) as the eluent to give a white crystalline powder (2.1 g, 95%). 1 HNMR (400 MHz, CDCl 3 , 298 K) δ (TMS, ppm): 7.56 (d, J = 7.88 Hz, 2H), 7.09 (dd, J1 = 6 Hz, J2 = 3.28 Hz, 10H), 7.05 - 7.02 (m, 7H), 1.32 (S, 12H). 13 CNMR (100 MHz, CDCl 3 , 298 K) δ (ppm): 146.80, 143.70, 143.60, 143.52, 141.38, 140.82, 134.09, 131.37, 131.34, 130.73, 127.74, 127.65, 126.54, 126.47, 126.45, 83.72, 24.90. Example 4

[0026] A preparation method of 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylethenyl)-[1,1'-biphenyl]-4-yl) fumaronitrile, comprising the following steps: 4,4,5,5-Tetramethyl-2-(4-(1,2,2-triphenylethenyl)phenyl)-1,3,2-dioxaborolane (1.94 g, 5.0 mmol) was carefully degassed and filled with nitrogen together with 2,3-bis(4-bromophenyl) fumaronitrile (962 mg, 2.0 mmol), THF / water (60 mL / 20 mL), K 2 CO 3 (2.76 g, 20 mmol), Pd(PPh 3 ) 4 (3%, 170 mg). Then the reaction mixture was stirred at 60 °C for 12 h. After cooling to room temperature, the reaction mixture was extracted with DCM and washed with water. The yellow solid product (0.5 g, 16%) was obtained by purification by column chromatography using petroleum ether / dichloromethane (2 / 1, v / v) as the eluent. 1 HNMR (400 MHz, CDCl 3, 298K) δ (TMS, ppm): 7.91 (d, J = 8.5 Hz, 2H), 7.72 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 1H), 7.15 - 7.05 (m, 19H). 13 13C NMR (100 MHz, CDCl 3 , 298K) δ (ppm): 144.13, 143.99, 143.60, 143.57, 143.53, 141.63, 140.21, 137.01, 132.74, 132.07, 131.35, 130.72, 129.90, 129.20, 127.86, 127.80, 127.70, 127.62, 127.49, 127.40, 126.69, 126.62, 126.35, 126.27, 126.19, 124.33, 116.93, 114.58. Mass spectrum: 640.134. Example 5

[0027] Preparation method of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl) fumaronitrile, comprising the following steps: Mix 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl) fumaronitrile (611 mg, 1.0 mmol), 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine (780 mg, 2.0 mmol), THF (60 mL) / H 2 2O (20 mL), K 2 2CO 3 3 (2.76 g, 20 mmol), Pd(PPh 3 ) 4 3 (3%) (170 mg). Carefully degas and fill with nitrogen. Stir the reaction mixture at 60 °C for 12 h, cool to room temperature, extract with DCM, and then wash again with water. Using petroleum ether / dichloromethane (1 / 1, v / v) as the eluent, purify by column chromatography to obtain a yellow solid (0.04 g, 5%). 1 1H NMR (400 MHz, CDCl 3, 298K) δ (TMS, ppm): 7.90 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 4H), 7.36 (dd, J1 = 18.9 Hz, J2 = 18.8 Hz, 8H), 7.11 - 7.04 (m, 24H). 13 13C NMR (100 MHz, CDCl 3 , 298K) δ (ppm): 144.2, 143.6, 143.6, 143.5, 143.4, 142.7, 140.2, 140.1, 136.8, 132.1, 131.4, 131.4, 131.3, 129.9, 129.4, 129.2, 127.8, 127.7, 127.5, 127.4, 126.5, 126.4, 126.2, 125.1, 117.0. Mass spectrum: 833.285. Example 6

[0028] Preparation of nanoparticles: Dissolve 1 mg of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylethenyl)-[1,1'-biphenyl]-4-yl)fumaronitrile and 2 mg of the amphiphilic molecule DSPE-PEG2000, which is a combination of polyethylene glycol (PEG2000) and phospholipid (DSPE, 1,2-distearoyl-sn-glycero-3-phosphocholine), in 1 mL of tetrahydrofuran solution. Add 10 mL of deionized water to the mixture. Use an ultrasonic instrument with an output power of 12 W to ultrasonicate the tetrahydrofuran and water mixture solution for 2 minutes. Stir the resulting suspension overnight in a fume hood. Evaporate the tetrahydrofuran. After filtering through a 0.2 μm syringe filter, separate it by 15 mL centrifugal filtration using a 10 KDa molecular cut-off membrane to obtain the nanoparticles.

Claims

1. A method for preparing a phenothiazine derivative for generating singlet oxygen, characterized in that: the phenothiazine derivative is 2-(4-(10H-phenothiazine-10-yl)-[1-biphenyl]-4-yl)-3-(4-)1,2,2-triphenylethylene)-[1,1-biphenyl]-4-yl)fumaronitrile, whose chemical structure is as follows: characterized in that the singlet oxygen is generated ( 1 O2), the preparation method comprises the following five steps: 1.1 The first step is the preparation of 10-(4-bromophenyl)-10H-phenothiazine: First, 5.0 g of phenothiazine was dissolved in 1,4-dioxane, and 17.7 g of 1,4-dibromobenzene was added at 100°C to 120°C to obtain the compound 10-(4-bromophenyl)-10H-phenothiazine; 1.2 The second step is the preparation of 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a, 5a, 9a, 10a-tetrahydro-10H-phenothiazine: 1.0 g of 10-(4-bromophenyl)-10H4-phenothiazine is dissolved in 1,4-dioxane, and then 1.08 g of biboronic acid pinacol ester and 0.2 g of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium are added to react to generate 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a, 5a, 9a, 10a-tetrahydro-10H-phenothiazine; 1.3 The third step is the preparation of 4,4,5,5-tetramethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)-1,3,2-dioxaborane: 2.0 g of 1-(4-bromophenyl)-1,2,2-triphenylethylene is dissolved in 1,4-dioxane, and then 1.50 g of biboric acid pinacol ester and 0.215 g of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium are added to react to generate 4,4,5,5-tetramethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)-1,3,2-dioxaborane; 1.4 The fourth step is the preparation of 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile: 11.94 g of 0-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine and 0.17 g of tetrakis(triphenylphosphine)palladium are dissolved in tetrahydrofuran and water, and 0.96 g of 2,3-bis(4-bromophenyl)fumaronitrile is added at 55°C to 65°C to react and generate 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4-yl)fumaronitrile; 1.5 The fifth step is the preparation of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylethylene)-[1,1'-biphenyl]-4-yl)fumaronitrile: 0.61 g of 2-(4-bromophenyl)-3-(4'-(1,2,2-triphenylethylene)-[1,1'-biphenyl]-4-yl)fumaronitrile and 0.78 g of 10-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4a,5a,9a,10a-tetrahydro-10H-phenothiazine is reacted to give 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylethylene)-[1,1'-biphenyl]-4-yl)fumaronitrile; 1.6 The sixth step is to dissolve 1 mg of 2-(4'-(10H-phenothiazin-10-yl)-[1,1'-biphenyl]-4-yl)-3-(4'-(1,2,2-triphenylethylene)-[1,1'-biphenyl]-4-yl)fumaronitrile and 2 mg of amphiphilic molecule DSPE-PEG2000 combined with polyethylene glycol (PEG2000) and phospholipid (DSPE, 1,2-eicosene-sn-glycero-3-phosphocholine) in 1 mL of tetrahydrofuran solution, and add 10 mL of deionized water to the mixture. The tetrahydrofuran and water mixture solution is sonicated for 2 minutes using an ultrasonic instrument with an output power of 12 W. The resulting suspension is stirred in a fume hood overnight, the tetrahydrofuran is evaporated, and the suspension is filtered through a 0.2 μm syringe filter and then separated by centrifugation with a 15 mL 10 KDa molecular cutoff membrane to obtain nanoparticles.

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