A thionaphthalene imide photosensitizer, its preparation method and application

Abstract

This invention provides a thionaphthalene imide photosensitizer, its preparation method, and its applications, relating to the field of organic synthesis technology. The thionaphthalene imide photosensitizer of Formula I provided by this invention exhibits excellent absorption at 530 nm, demonstrates strong reactive oxygen species generation capability under white light irradiation, and possesses excellent optical, thermal, and chemical stability. Its ultraviolet absorption tail peak reaches the near-infrared region, indicating good photodynamic therapeutic efficacy. Furthermore, the preparation method provided by this invention utilizes readily available raw materials, employs a simple synthesis process, and facilitates product purification.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a thionaphthalene imide photosensitizer, its preparation method, and its application. Background Technology

[0002] Photodynamic therapy (PDT) is a non-destructive tumor treatment method that has developed in recent years. It boasts advantages such as high spatiotemporal resolution, minimal damage to normal tissue, no drug resistance, and the ability to be repeated. Compared to traditional therapies, PDT offers faster healing, fewer side effects, and a shorter treatment cycle. The basic principle of PDT is that under illumination, a photosensitizer absorbs photons and transitions from the ground state to a singlet excited state. This transition occurs through intersystem crossing and decays to a triplet excited state. The photosensitizer in the triplet excited state transfers its excitation energy to oxygen molecules surrounding the tumor, leading to the generation of highly reactive singlet oxygen or other reactive oxides with cytotoxicity. This causes permanent damage to cancer cells and tissues, thus achieving a therapeutic effect. Therefore, the selection of a suitable photosensitizer directly impacts the treatment outcome. However, commonly used small-molecule photosensitizers such as porphyrin, methylene blue, and BODIPY suffer from low reactive oxygen species generation efficiency, hindering the achievement of optimal therapeutic results. A solution to address this issue is urgently needed. Summary of the Invention

[0003] The purpose of this invention is to provide a thionaphthalene imide photosensitizer, its preparation method, and its application.

[0004] In a first aspect, the present invention provides a thionaphthalene imide photosensitizer with the general formula shown in Formula I:

[0005]

[0006] R1 is a dimethylamino group or a triphenylamino group.

[0007] Secondly, the present invention also provides a method for preparing a thionaphthalene imide photosensitizer of general formula I, comprising: compound 2 undergoing a pyridine salt-forming reaction after R1 grouping to generate a pyridinium salt, followed by carbonyl thiolation to obtain the thionaphthalene imide photosensitizer; wherein R1 is a dimethylamino group or a triphenylamino group, and the structural formula of compound 2 is:

[0008]

[0009] Optionally, compound 2 is generated by reacting compound 1 with 3-aminopyridine, and the structural formula of compound 1 is:

[0010]

[0011] Optionally, the process includes the following steps: reacting compound 2 with an amine hydrogen compound having R1 to generate compound 3; reacting compound 3 with an iodine compound to form a pyridine salt to generate a pyridinium salt compound 4; and reacting compound 4 with Lawson's reagent to form a thionaphthalene imide as shown in Formula I.

[0012] Optionally, when compound 2 is reacted with an amine hydrogen compound having R1 to generate compound 3, the molar ratio of compound 2 to the amine hydrogen compound is 1:(1-3).

[0013] Optionally, when compound 2 is reacted with an amine hydrogen compound having R1 to generate compound 3, the structural formula of compound 3 is:

[0014]

[0015] Alternatively, the reaction formula is:

[0016]

[0017] Optionally, when compound 3 reacts with the iodine compound to form a pyridinium salt compound 4, the molar ratio of compound 3 to the iodine compound is 1:(1-3).

[0018] Optionally, the structural formula of compound 4 is:

[0019]

[0020] Alternatively, the reaction formula is:

[0021]

[0022] Optionally, when compound 4 is carbonyl thiolated with Lawson's reagent, the molar ratio of compound 4 to Lawson's reagent is 1:(1-9).

[0023] Alternatively, the reaction formula is:

[0024]

[0025] Optionally, when R1 is triphenylamine, the process includes the following steps: in a first solvent and a non-oxidizing atmosphere, under alkaline conditions and with the aid of a catalyst, compound 2 reacts with a borate-modified triphenylamine compound at 75-85°C to generate compound 3; in a second solvent and a non-oxidizing atmosphere, compound 3 reacts with an iodine compound at 80-90°C to undergo a pyridine salt formation reaction to generate compound 4; and in a third solvent and a non-oxidizing atmosphere, compound 4 reacts with a Lawson reagent at 100-120°C to undergo a carbonyl thiothioimide reaction to generate a triphenylamine-substituted thionaphthalene imide.

[0026] Optionally, when R1 is a dimethylamine group, the process includes the following steps: in a fourth solvent and a non-oxidizing atmosphere, compound 2 reacts with a dimethylamine compound at 110-130°C to generate compound 3; in a fifth solvent and a non-oxidizing atmosphere, compound 3 reacts with an iodine compound at 80-90°C to undergo a pyridine salt formation reaction to generate compound 4; and in a sixth solvent and a non-oxidizing atmosphere, compound 4 reacts with Lawson's reagent at 100-120°C to undergo a carbonyl thiothioimide reaction to generate a trimethylamine-substituted thionaphthaleneimide.

[0027] Thirdly, the present invention also provides an application of the thionaphthaleneimide photosensitizer.

[0028] Optionally, this includes preparing a photodynamic agent for killing cancer cells. Attached Figure Description

[0029] Figure 1 The 1H NMR spectrum of compound 2 synthesized in Example 1 of this invention;

[0030] Figure 2 The 1H NMR spectrum of compound 3 synthesized in Example 1 of this invention;

[0031] Figure 3 The 1H NMR spectrum of compound 4 synthesized in Example 1 of this invention;

[0032] Figure 4 The above is the 1H NMR spectrum of the TNDS synthesized in Example 1 of this invention;

[0033] Figure 5 The 1H NMR spectrum of the TNDS synthesized in Example 2 of this invention;

[0034] Figure 6 The following are the ultraviolet absorption spectra of compound 4 synthesized in Example 1 of this invention in different solvents;

[0035] Figure 7 The following are the UV absorption spectra of TNDS synthesized in Example 1 of this invention in different solvents;

[0036] Figure 8 The fluorescence spectrum of total reactive oxygen species in compound 4 synthesized in Example 1 of this invention is shown.

[0037] Figure 9 The fluorescence spectrum of total reactive oxygen species in TNDS synthesized in Example 1 of this invention is shown. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise defined, the technical or scientific terms used herein should have the ordinary meaning understood by those skilled in the art to which this invention pertains.

[0039] This invention provides a thionaphthalene imide photosensitizer, the general formula of which is shown in Formula I:

[0040]

[0041] R1 is a dimethylamino group or a triphenylamino group.

[0042] Specifically, when R1 is dimethylamino, the structural formula of the thionaphthaleneimide photosensitizer is:

[0043]

[0044] Specifically, when R1 is a triphenylamine group, the structural formula of the thionaphthaleneimide photosensitizer is:

[0045]

[0046] In fact, the thionaphthalene imide photosensitizer provided by this invention has a strong electron donor and an electron-deficient naphthalene imide core in its entire molecule. The introduction of pyridinium forms a strong push-pull electron effect, which is beneficial for reducing the band gap and promoting intersystem crossing. At the same time, since the thio-based photosensitizer hardly shows fluorescence, it has highly efficient ISC (intersystem crossing) and other non-radiative processes that simultaneously cause a red shift in ultraviolet absorption. These are beneficial for promoting the generation of reactive oxygen species.

[0047] The present invention also provides a method for preparing a thionaphthalene imide photosensitizer as shown in Formula I, comprising: after compound 2 undergoes R1 grouping, a pyridine salt formation reaction occurs to generate a pyridinium salt, followed by carbonyl thiolation to obtain the thionaphthalene imide photosensitizer.

[0048] Specifically, the structural formula of compound 2 is as follows:

[0049]

[0050] In fact, compound 2 is generated by the reaction of compound 1 with 3-aminopyridine, wherein the structural formula of compound 1 is:

[0051]

[0052] Specifically, the CAS number of compound 1 is 81-86-7, and compound 1 can be obtained from commercially available conventional products or synthesized in the laboratory. In fact, the reaction of compound 1 with 3-aminopyridine to generate compound 2 includes: dissolving compound 1 and 3-aminopyridine at room temperature to obtain a mixed solution; refluxing the mixed solution under a nitrogen atmosphere at 100-120°C for 10-14 hours, followed by concentration and purification to obtain compound 2.

[0053] In some embodiments, after dissolving compound 1 in a mixture, the molar mixing ratio of compound 1 to 3-aminopyridine is 1:(1-2). In fact, setting an excess of 3-aminopyridine is beneficial for the forward reaction, thereby increasing the yield of compound 2.

[0054] In some embodiments, when purifying compound 2, the mixture after reflux reaction is concentrated under reduced pressure to separate crude compound 2, and crude compound 2 is dissolved and recrystallized using ethanol, and the precipitate is collected to obtain pure compound 2.

[0055] In fact, when compound 1 reacts with 3-aminopyridine to form compound 2, the reaction equation is as follows:

[0056]

[0057] In some embodiments, the preparation method of the thionaphthaleneimide photosensitizer provided by the present invention includes the following steps:

[0058] S1. Compound 1 is reacted with 3-aminopyridine to generate compound 2;

[0059] S2. Compound 2 is reacted with an amine hydrogen compound having R1 to generate compound 3;

[0060] S3 and compound 3 react with iodine compound to form pyridinium salt compound 4;

[0061] S4 and compound 4 are reacted with Lawson's reagent to undergo carbonyl thiosulfate reaction to produce thionaphthalene imide as shown in formula I.

[0062] In some embodiments, during step S2, the molar mixing ratio of compound 2 to the amine hydrogen compound is 1:(1-3) to ensure an excess of the amine hydrogen compound, thereby promoting the forward reaction and increasing the yield of compound 3. Furthermore, when R1 is a triphenylamine group, the amine hydrogen compound may specifically be a borate-modified triphenylamine compound; when R1 is a dimethylamine group, the amine hydrogen compound may specifically be a dimethylamine compound.

[0063] Specifically, after performing step S2, the structural formula of the resulting compound 3 is as follows:

[0064]

[0065] Specifically, the reaction that occurs during step S2 is as follows:

[0066]

[0067] In some embodiments, during step S3, the molar ratio of compound 3 to the iodine compound is 1:(1-3). Specifically, the iodine compound can be iodomethane, CAS number 74-88-4, which can be a commercially available conventional product and can be synthesized in a laboratory.

[0068] Specifically, after performing step S3, the structural formula of the resulting compound 4 is as follows:

[0069]

[0070] Specifically, the reaction that occurs during step S3 is as follows:

[0071]

[0072] In some embodiments, when performing step S4, the molar ratio of compound 4 to Lawesson's reagent is 1:(1-9), wherein the CAS number of Lawesson's reagent is 19172-47-5, and commercially available conventional products can be used, while also being synthesized in-house.

[0073] Specifically, the reaction that occurs during step S4 is as follows:

[0074]

[0075] In some embodiments, when R1 is a triphenylamine group, the preparation method of the thionaphthaleneimide photosensitizer includes the following steps:

[0076] S2. In the first solvent and non-oxidizing atmosphere, under alkaline conditions and with the action of a catalyst, compound 2 reacts with a borate-modified triphenylamine compound at 75-85°C to generate compound 3.

[0077] S3. In the second solvent and a non-oxidizing atmosphere, compound 3 reacts with iodine compound at 80-90℃ to form compound 4 after a pyridine salt formation reaction.

[0078] S4. In a third solvent and a non-oxidizing atmosphere, compound 4 reacts with Lawson's reagent at 100-120°C to undergo a carbonyl thiosulfate reaction to generate a triphenylamine-substituted thionaphthalene imide.

[0079] In fact, the first solvent, the second solvent, and the third solvent used in steps S2 to S4 are independently selected from toluene, anhydrous tetrahydrofuran, and acetonitrile. The non-oxidizing atmosphere used in steps S2 to S4 can be the same or different. Specifically, the non-oxidizing atmosphere includes either a nitrogen atmosphere or an inert atmosphere.

[0080] In practice, the alkaline regulator used in step S2 to adjust the alkaline environment can be at least one of organic and inorganic bases; specifically, potassium carbonate can be used to adjust the alkaline environment of the reaction. In fact, the catalyst used in Example 1 can be Pd(PPh3)4.

[0081] In fact, the borate-modified triphenylamine compound used in step S2 can be 4-(diphenylamino)phenylboronic acid pinacol ester, CAS number 267221-88-5, and can be a commercially available product. In step S2, compound 2 and the borate-modified triphenylamine compound are refluxed at 75-85°C.

[0082] In some embodiments, when R1 is a dimethylamino group, the preparation method of the thionaphthaleneimide photosensitizer includes the following steps:

[0083] In S2, the fourth solvent, and a non-oxidizing atmosphere, compound 2 reacts with dimethylamine compounds at 110-130℃ to generate compound 3;

[0084] S3. In the fifth solvent and a non-oxidizing atmosphere, compound 3 reacts with iodine compound at 80-90℃ to form compound 4 after a pyridine salt formation reaction.

[0085] S4. In the sixth solvent and a non-oxidizing atmosphere, compound 4 reacts with Lawson's reagent at 100-120°C to undergo a carbonyl thiosulfate reaction to generate a trimethylamino-substituted thionaphthalene imide.

[0086] In fact, the fourth, fifth, and sixth solvents used in steps S2 to S4 are independently selected from anhydrous 2-methoxyethanol, toluene, and acetonitrile. The non-oxidizing atmosphere used in steps S2 to S4 can be the same or different. Specifically, the non-oxidizing atmosphere includes either a nitrogen atmosphere or an inert atmosphere.

[0087] In fact, the dimethylamine compound used in step S2 can be dimethylamine, whose CAS number is 124-40-3.

[0088] Specifically, after performing step S2 to generate compound 3, step S3 to generate compound 4, and step S4 to generate thionaphthalene imide, compound 3, compound 4, and thionaphthalene imide can be purified using purification and separation methods commonly used in the art.

[0089] Example 1

[0090] This embodiment 1 provides a method for preparing thionaphthalene imide, comprising the following steps:

[0091] S1. At room temperature, 1 g (3.61 mmol) of compound 1 (CAS: 81-86-7) and 0.51 g (5.42 mmol) of 3-aminopyridine were mixed and dissolved in 30 mL of toluene. The mixture was refluxed at 110 °C under a nitrogen atmosphere for 12 h. After filtration under reduced pressure, the crude product was obtained by drying. The crude product was then recrystallized from ethanol and the gray solid was collected to obtain 1.01 g of compound 2. The yield was calculated to be 80%.

[0092] S2. Under a nitrogen atmosphere, 0.5 g (1.41 mmol) of compound 2, 0.57 g (1.55 mmol) of 4-(diphenylamino)phenylboronic acid pinacol ester (CAS: 267221-88-5), 0.97 g (7.05 mmol) of potassium carbonate and 0.32 g (0.282 mmol) of Pd(PPh3)4 were added sequentially to a side-mounted flask. Then, 30 mL of anhydrous tetrahydrofuran (THF) was added and the mixture was stirred. The side-mounted flask was refluxed in an 80 °C water bath for 24 h and then cooled to room temperature. Cold water was added to the reaction system in the side-mounted flask and the mixture was extracted with dichloromethane. After separating the organic phase, the mixture was dried with anhydrous sodium sulfate and concentrated by rotary evaporation to obtain the crude product. The crude product was separated by column chromatography and eluted with dichloromethane / petroleum ether eluent at a volume ratio of 3:1 to obtain 0.59 g of compound 3 as a yellow solid. The yield was calculated to be 81%.

[0093] S3. Under a nitrogen atmosphere, 0.3 g (0.58 mmol) of compound 3 and 0.16 g (1.16 mmol) of iodomethane were added sequentially to a single-necked flask, followed by the addition of 20 mL of acetonitrile. The single-necked flask was refluxed in a water bath at 85 °C for 24 h. After rotary evaporation and concentration, the mixture was separated by silica gel column chromatography and eluted with a dichloromethane / methanol eluent at a volume ratio of 20:1 to obtain 0.28 g of compound 4 as a red solid. The yield was calculated to be 70%.

[0094] S4. Under a nitrogen atmosphere, 0.25 g (0.38 mmol) of compound 4 and 0.76 g (1.9 mmol) of Lawson's reagent were added to a side-mounted flask, followed by the addition of 15 mL of toluene. The mixture was stirred and stirred, and the side-mounted flask was refluxed at 110 °C for 36 h. The crude product was then concentrated by rotary evaporation. The crude product was separated by silica gel column chromatography and eluted with dichloromethane / methanol at a volume ratio of 10:1 to obtain 0.09 g of thionaphthalene imide (TNDS) as a purple-red solid. The yield was calculated to be 36%.

[0095] Compound 2 prepared in Example 1 was characterized by 1H NMR spectroscopy as follows: Figure 1 The characterization data are as follows: ¹H NMR (400MHz, DMSO-d⁶) δ 8.64 (d, J = 4.8Hz, ¹H), 8.60 (d, J = 2.7Hz, ¹H), 8.58 (t, J = 2.5Hz, ¹H), 8.56 (s, ¹H), 8.32 (dd, J = 7.8, 2.2Hz, ¹H), 8.22 (dd, J = 7.9, 2.2Hz, ¹H), 8.05–7.96 (m, ¹H), 7.91–7.83 (m, ¹H), 7.63–7.55 (m, ¹H).

[0096] Compound 3 prepared in Example 1 was characterized by 1H NMR spectroscopy as follows: Figure 2 As shown, the characterization data is as follows: 1 H NMR (400MHz, Chloroform-d) δ8.72 (d, J=4.9Hz, 1H), 8.69 (s, 1H), 8.67 (s, 1H), 8.63 (s, 1H), 8.50 (d, J=8.5Hz, 1H), 7.78 (s, 1H), 7.76 (s, 1H) ), 7.72 (d, J=8.3Hz, 1H), 7.51 (t, J=6.9Hz, 1H), 7.40 (d, J=8.1Hz, 2H), 7.33 (t, J=7.7Hz, 4H), 7.22 (d, J=7.9Hz, 6H), 7.12 (d, J=7.2Hz, 2H).

[0097] Compound 4 prepared in Example 1 was characterized by 1H NMR spectroscopy as follows: Figure 3 The characterization data are as follows: ¹H NMR (400MHz, DMSO-d⁶) δ 9.32 (s, ¹H), 9.13 (d, J = 6.1Hz, ¹H), 8.80 (d, J = 8.4Hz, ¹H), 8.61 (t, J = 7.8Hz, 2H), 8.52 (d, J = 8.5Hz, 1H), 8.41–8.35 (m, ¹H), 7.96 (t, J = 7.8Hz, 1H), 7.90 (d, J = 7.5Hz, 1H), 7.52 (d, J = 8.1Hz, 2H), 7.38 (t, J = 7.6Hz, 4H), 7.16 (d, J = 7.2Hz, 6H), 7.13 (d, J = 7.2Hz, 2H), 4.47 (s, 3H).

[0098] The TNDS of the thionaphthalene imide prepared in Example 1 was characterized by 1H NMR spectroscopy as follows: Figure 4 As shown, the characterization data is as follows: 1H NMR (400MHz, DMSO-d6) δ9.30 (s, 1H), 9.07 (s, 1H), 8.90 (s, 2H), 8.74 (s, 1H), 8.58 (s, 1H), 8.37 ( s, 1H), 7.90 (s, 2H), 7.58 (s, 2H), 7.39 (s, 4H), 7.17 (d, J=10.7Hz, 6H), 6.98 (s, 2H), 4.44 (s, 3H).

[0099] Specifically, the reaction that occurred in Example 1 is as follows:

[0100]

[0101] Example 2

[0102] Example 2 provides a method for preparing a thionaphthalene imide photosensitizer, which differs from Example 1 in that:

[0103] S2. Under a nitrogen atmosphere, 0.5 g (1.41 mmol) of compound 2 and 0.19 g (4.23 mmol) of dimethylamine were added to a side-necked flask, followed by the addition of 30 mL of anhydrous 2-methoxyethanol. After stirring and dissolving, the mixture was refluxed at 120 °C for 24 h and then cooled to room temperature. The precipitate was separated by filtration and washed with n-hexane to obtain 0.22 g of compound 3 as a bright yellow solid. The yield was calculated to be 50%.

[0104] S3. Under a nitrogen atmosphere, 0.2 g (0.63 mmol) of compound 3 and 0.17 g (1.26 mmol) of iodomethane were added sequentially to a single-necked flask, followed by 20 mL of acetonitrile. The single-necked flask was refluxed in a water bath at 85 °C for 24 h. After rotary evaporation and concentration, the mixture was separated by silica gel column chromatography and eluted with a dichloromethane / methanol eluent at a volume ratio of 15:1 to obtain 0.2 g of compound 4 as a red solid. The yield was calculated to be 70%.

[0105] S4. Under a nitrogen atmosphere, 0.2 g (0.43 mmol) of compound 4 and 0.86 g (2.15 mmol) of Lawson's reagent were added to a side-mounted flask, followed by the addition of 15 mL of toluene. The mixture was stirred and stirred. The side-mounted flask was refluxed at 110 °C for 36 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was evaporated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography and eluted with dichloromethane / methanol at a volume ratio of 8:1 to obtain 0.06 g of thionaphthalene imide (TDNS) as a purple-black solid. The yield was calculated to be 30%.

[0106] The 1H NMR characterization data of compound 3 prepared in Example 2 are as follows: 1H NMR (400MHz, Chloroform-d) 68.70-8.65 (m, 1H), 8.61 (s, 1H), 8.59 (d, J = 3.3 Hz, 1H), 8.52-8.50 (m, 1H), 8.49 (d, J = 3.0 Hz, 1H), 7.73-7.64 (m, 2H), 7.47 (dd, J = 8.1, 4.9 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 3.15 (s, 6H).

[0107] The 1H NMR characterization data of compound 4 prepared in Example 2 are as follows: 1H NMR (400MHz, DMSO-d6) δ 9.28 (s, 1H), 9.08 (d, J = 6.1Hz, 1H), 8.75 (d, J = 8.3Hz, 1H), 8.62 (d, J = 8.5Hz, 1H), 8.51 (d, J = 7.3Hz, 1H), 8.40-8.30 (m, 2H), 7.80 (t, J = 7.9Hz, 1H), 7.24 (d, J = 8.5Hz, 1H), 4.44 (s, 3H), 3.15 (s, 6H).

[0108] The thionaphthalene imide prepared in Example 2 was characterized by 1H NMR spectroscopy as follows: Figure 5 The characterization data are as follows: ¹H NMR (400 MHz, Methanol-d⁴) δ 9.13 (d, J = 23.7 Hz, ¹H), 9.07–8.99 (m, ¹H), 8.98 (s, ¹H), 8.88 (s, ¹H), 8.73–8.60 (m, ¹H), 8.60–8.45 (m, ¹H), 8.24 (dd, J = 17.4, 7.0 Hz, ¹H), 7.69 (dt, J = 24.3, 8.1 Hz, ¹H), 7.21 (dd, J = 24.3, 9.6 Hz, ¹H), 4.89 (s, 3H), 3.44 (s, 6H).

[0109] Specifically, the reaction that occurs in Example 2 is as follows:

[0110]

[0111] Performance testing

[0112] Using dimethyl sulfoxide (DMSO) as a solvent, compound 4 prepared in Example 1 and TNDS were respectively prepared to a concentration of 2 × 10⁻⁶. -310 μL of the mother liquor of compound 4 and TNDS were transferred to cuvettes, and 19980 μL of N,N-dimethylformamide (DMF), acetic acid (AC), tetrahydrofuran (THF), ethyl acetoacetate (EA), methanol (MeOH), acetonitrile (MeCN), toluene, dimethyl sulfoxide (DMSO), and deionized water (H2O) were added to each cuvette for dilution. UV-Vis absorption spectra were then measured. The UV spectra of compound 4 in different solvents are shown below. Figure 6 As shown, the UV spectra of TNDS in different solvents are as follows: Figure 7 As shown.

[0113] from Figure 6 and Figure 7 As can be seen, the maximum absorption peak of compound 4 is at 435 nm, while the maximum absorption peak of TNDS after carbonyl thiolation in DMSO is at 530 nm. At the same time, with the increase of solvent polarity, the absorption of both compound 4 and TNDS shows a slight red shift, and the maximum UV absorption of TNDS is 95 nm red shifted compared to compound 4.

[0114] Because the reactive oxygen species indicator 2',7'-dichlorodihydrofluorescein (DCFH) can be oxidized by reactive oxygen species to a 2',7'-dichlorofluorescein hydrogen ionization probe (DCF) with strong green fluorescence emission (EX / E). m =504nm / 529nm), therefore, 10μL of solution with a concentration of 1×10⁻⁶ nm was used. S The mol / L compound 4 dilution and the TNDS (Example 1) dilution were transferred to cuvettes respectively, and 10 μL of a 2×10 mol / L concentration was added to the cuvettes. -3 Immediately after applying DCFH at a concentration of mol / L, the fluorescence emission intensity was measured using a power density of 10 W / cm². 2 After 10 seconds of white light irradiation, the irradiation was stopped and the fluorescence emission intensity was immediately measured. Irradiation was repeated after a 5-second interval, and this cycle was repeated until the fluorescence emission intensity remained constant. The fluorescence emission intensity of compound 4 under irradiation was as follows: Figure 8 As shown, the fluorescence emission intensity of TNDS under illumination is as follows: Figure 9 As shown.

[0115] from Figure 8 As can be seen, under illumination, the fluorescence emission of compound 4 is enhanced within 40s, while the fluorescence emission intensity of TNDS is significantly enhanced within 130s, which is 1.7 times higher than that of compound 4. This indicates that the TNDS provided in Example 1 has excellent ROS generation ability, showing a significant photodynamic effect and good application prospects.

[0116] While embodiments of the present invention have been described in detail above, it will be apparent to those skilled in the art that various modifications and variations can be made to these embodiments. However, it should be understood that such modifications and variations fall within the scope and spirit of the invention as set forth in the claims. Furthermore, the invention described herein may have other embodiments and can be implemented or carried out in various ways.

Claims

1. A thionaphthalene imide photosensitizer of the general formula as shown in Formula I, ； in, R1 is a dimethylamino group or a triphenylamino group.

2. A method for preparing the thionaphthalene imide photosensitizer as described in claim 1, characterized in that, Compound 2 undergoes a pyridine salt formation reaction after R1 grouping to generate a pyridinium salt, which is then carbonyl thiolated to obtain a thionaphthalene imide photosensitizer; wherein R1 is a dimethylamino group or a triphenylamino group, and the structural formula of compound 2 is: 。 3. The preparation method according to claim 2, characterized in that, Compound 2 is generated by reacting compound 1 with 3-aminopyridine. The structural formula of compound 1 is: 。 4. The preparation method according to claim 2 or 3, characterized in that, Includes the following steps: Compound 2 is reacted with an amine hydrogen compound having R1 to generate compound 3; compound 3 is reacted with an iodine compound to form a pyridine salt compound 4; compound 4 is reacted with Lawson's reagent to form a thionaphthalene imide as shown in formula I.

5. The preparation method according to claim 4, characterized in that, When compound 2 reacts with an amine hydrogen compound having R1 to generate compound 3: The molar ratio of compound 2 to the amine hydrogen compound is 1:(1-3); Alternatively, the structural formula of compound 3 is: ； Alternatively, the reaction formula is: 。 6. The preparation method according to claim 4, characterized in that, When compound 3 reacts with an iodine compound to form a pyridinium salt compound 4: The molar ratio of compound 3 to the iodine compound is 1:(1-3); Alternatively, the structural formula of compound 4 is: ； Alternatively, the reaction formula is: 。 7. The preparation method according to claim 4, characterized in that, When compound 4 undergoes carbonyl thiolation with Lawson's reagent: The molar ratio of compound 4 to Lawson's reagent is 1:(1-9); Alternatively, the reaction formula is: 。 8. The preparation method according to claim 4, characterized in that, When R1 is triphenylamine, the process includes the following steps: In a first solvent and a non-oxidizing atmosphere, under alkaline conditions and with the aid of a catalyst, compound 2 reacts with a borate-modified triphenylamine compound at 75-85°C to generate compound 3; In a second solvent and a non-oxidizing atmosphere, compound 3 reacts with an iodine compound at 80-90°C to undergo a pyridine salt formation reaction to generate compound 4; In a third solvent and a non-oxidizing atmosphere, compound 4 reacts with Lawson's reagent at 100-120°C to undergo a carbonyl thiothioimide reaction to generate a triphenylamine-substituted thionaphthalene imide. Alternatively, when R1 is dimethylamine, the process includes the following steps: in a fourth solvent and a non-oxidizing atmosphere, compound 2 reacts with a dimethylamine compound at 110-130°C to generate compound 3; in a fifth solvent and a non-oxidizing atmosphere, compound 3 reacts with an iodine compound at 80-90°C to undergo a pyridine salt formation reaction to generate compound 4; and in a sixth solvent and a non-oxidizing atmosphere, compound 4 reacts with Lawson's reagent at 100-120°C to undergo a carbonyl thiosulfate reaction to generate a trimethylamine-substituted thionaphthaleneimide.

9. The application of a thionaphthalene imide photosensitizer as described in claim 1 or a thionaphthalene imide photosensitizer prepared by any one of claims 2 to 8, characterized in that, The thionaphthaleneimide photosensitizer is used to prepare a photodynamic reagent for killing cancer cells.

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