Development of a linkage complex photothermal reagent for reduction stress-copper apoptosis system

Abstract

The application belongs to the technical field of organic synthesis, and relates to a kind of linkage composite photothermal reagent development for reduction stress-copper apoptosis system.The application realizes a kind of linkage composite photothermal reagent development for reduction stress-copper apoptosis system, based on heptamethine cyanine skeleton, (imino) methyl phenol structure, iodine atom, nitro group are introduced, a compound is constructed.The compound can specifically recognize Cu 2+ 、S 2‑ 、SO2, can realize reduction stress response and copper apoptosis linkage, and simultaneously triggers its photothermal effect, and carries out targeted killing to cancer cells, so as to realize the treatment of cancer.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and relates to a development of a linkage composite photothermal reagent for a reduction stress-copper apoptosis system. BACKGROUND

[0002] Photothermal therapy (PTT) and photodynamic therapy (PDT) are to expose materials with high photothermal conversion efficiency or strong ROS yield to light sources of specific wavelengths, and use their target recognition technology to make the materials produce phototoxicity to specific cancer cells or disease cells to achieve therapeutic effect. PTT has the advantages of high selectivity, low invasiveness and no systemic side effects, and shows excellent anti-tumor performance. Due to the short excitation wavelength of near-infrared (NIR) dye, the penetration depth is limited, and factors such as dense extracellular matrix of tumor tissue, enrichment and deep penetration of photosensitizers in tumor tissue, and immunosuppressive microenvironment of tumor greatly affect the PTT effect, leading to easy recurrence and metastasis of tumors.

[0003] Copper ions (Cu 2+ ) are indispensable trace metal elements in mammals, widely exist in various tissues and organs, and participate in the regulation of gene expression, hematopoiesis, metabolism and various physiological processes in the body. Appropriate amount of Cu 2+ in the body promotes the health of the organism, but excessive Cu 2+ in the body will cause lipid metabolism disorder in the human body, and cause liver failure, kidney failure, shock or death.

[0004] In many physiological and pathological processes, H2S and SO2 have complex concentration and time-dependent effects. H2S and SO2 will show opposite effects at different concentrations, and high concentration of SO2 can cause damage to cancer cells. This means that the concentration of both and their killing effect on cancer cells are very important.

[0005] Cu 2+ and H2S and SO2 are important indicators in the process of cancer treatment, and there is currently no molecular probe that can specifically recognize Cu 2+ , H2S and SO2 and has photosensitivity. SUMMARY

[0006] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application realizes a development of a linkage composite photothermal reagent for a reduction stress-copper apoptosis system, designs and synthesizes a new molecular framework suitable for photothermal therapy in a cancer cell environment, and synthesizes a molecular probe that can specifically recognize Cu 2+ , S 2- , SO2, realizes linkage of reduction stress response and induction of copper apoptosis, and has a photothermal effect.

[0007] In one aspect, the present application relates to a compound having a structure as shown in formula (I),

[0008]

[0009] In another aspect, the present application provides a preparation method of the compound, which comprises:

[0010] .

[0011] Further, in the preparation method of the compound provided by the present application, the preparation of the compound shown in formula (2-1) is carried out in an oxygen-free environment.

[0012] Specifically, the preparation method of the compound shown in formula (2-1) comprises: bubbling the hydrochloric acid solution with nitrogen gas under ice bath conditions, then dissolving 4-iodoaniline in it; under stirring, the deoxygenated aqueous solution containing sodium nitrite is added dropwise into the reaction system under a closed condition, and stirring is continued for a period of time; stannous chloride dihydrate is dissolved in deoxygenated concentrated hydrochloric acid, and then added dropwise into the reaction system, and stirring is continued for a period of time; after the reaction is completed, the precipitate is filtered and dissolved in a sodium hydroxide solution; CH2Cl2 is used for extraction, the organic phase is collected, anhydrous sodium sulfate is used for drying, and the organic phase is washed under light-proof conditions and dried with nitrogen gas. In the preparation of the compound shown in formula (2-1), the oxygen is as far as possible to be isolated, which can obtain a compound shown in formula (2-1) with higher purity, and is conducive to the control of the subsequent reaction.

[0013] Further, in the preparation method of the compound provided by the present application, the preparation of the compound shown in formula (2-2) comprises: ring-closing reaction of the compound shown in formula (2-1) to generate the compound shown in formula (2-2), after the reaction system stops generating heat, ice bath treatment is carried out, then the filtrate is filtered, and NaCl aqueous solution is added to the filtrate to obtain the compound shown in formula (2-2).

[0014] Specifically, the preparation method of the compound shown in formula (2-2) comprises: the compound shown in formula (2-2) and 3-methyl-2-butanone are dissolved in anhydrous ethanol and concentrated sulfuric acid, and then reacted at high temperature for a period of time; the reaction system is cooled to room temperature, then ice bath treatment is carried out, and then filtered; NaCl aqueous solution is added to the filtrate, then CH2Cl2 is used for extraction, and NaCl aqueous solution is used to prevent the mixture of isomers; the organic phase is washed with 10% sodium bicarbonate solution and water in sequence, and then rotary dried. The use of multiple solvents for multi-phase washing makes the purity of the compound shown in formula (2-2) higher, which is conducive to the subsequent reaction.

[0015] Further, in the preparation method of the compound provided by the present application, in the preparation of the compound shown in formula (2-3), the mixture of petroleum ether and ethyl acetate is used for washing and removing impurities.

[0016] Specifically, the preparation method of the compound shown as the formula (2-3) comprises the following steps: dissolving the compound shown as the formula (2-2) and iodoethane in toluene, and reacting at high temperature for a period of time; cooling the reaction system to room temperature, and slowly precipitating the product to reduce the inclusion of photolytic impurities; and performing suction filtration, and washing the product with a mixture of petroleum ether and ethyl acetate to further remove impurities.

[0017] Specifically, the preparation method of the compound shown as the formula (2-4) comprises the following steps: dissolving the compound shown as the formula (2-3) and the compound shown as the formula (1-3) in acetic anhydride, adding sodium acetate, and reacting at high temperature for a period of time in the dark to generate sufficient intermediates; cooling the reaction solution to room temperature, washing with saturated sodium bicarbonate solution until no bubbles are generated; and then washing with water and drying and rotary evaporation; and washing the product with various solvents to make the product more pure and facilitate the subsequent reaction.

[0018] Further, in the preparation method of the compound provided by the present application, the preparation of the compound shown as the formula (I) comprises the following step: adding the compound shown as the formula (2-4) to a reaction system containing the compound shown as the formula (1-1).

[0019] Specifically, the preparation method of the compound shown as the formula (I) comprises the following steps: under the N2 atmosphere, dissolving sodium hydride and the compound shown as the formula (1-1) in anhydrous DMF, stirring at room temperature for a period of time, and fully stirring to remove residual water; dissolving the compound shown as the formula (2-4) in anhydrous DMF and injecting into the reaction system to make the substitution reaction of the chlorin more complete; continuing to stir the reaction mixture under the light-proof condition for a period of time to prevent photolysis and reduce the inclusion of photolytic impurities; after the reaction is completed, adding CH2Cl2, then washing with saturated brine and water; after the organic phase is collected, adding anhydrous sodium sulfate for drying, and rotary evaporation to obtain the crude product; and purifying the crude product with a silica gel column to obtain the compound shown as the formula (I).

[0020] On the other hand, the present application relates to a molecular probe comprising the compound shown as the formula (I).

[0021] Further, in the molecular probe provided by the present application, the compound shown as the formula (I) specifically recognizes at least one of Cu 2+ , S 2- , S 4+ .

[0022] On the other hand, the present application relates to a drug for enhancing photothermal therapy or photodynamic therapy, which comprises the compound shown as the formula (I).

[0023] On the other hand, the present application relates to an antitumor drug, which comprises the compound shown as the formula (I).

[0024] Compared with the prior art, the technical solution provided by the present application at least has the following beneficial effects or advantages:

[0025] The application provides a development of a linkage composite photothermal reagent for a reduction stress-copper apoptosis system, selects a heptamethine cyanine dye as a modification framework of a photosensitizer, introduces an (imino)methyl phenol structure in the framework, and additionally modifies an iodine atom on an indole ring, so that cross efficiency between systems is improved, more 1 O2 is generated, so that the reduction stress reaction and the copper apoptosis linkage are realized, and the photothermal effect is also realized, so that cancer cells are killed in a targeted manner.

[0026] The application provides a development of a linkage composite photothermal reagent for a reduction stress-copper apoptosis system, a nitro group is introduced above a heptamethine cyanine skeleton, an electron-withdrawing group is used to reduce the fluorescence intensity of a probe, and a way in which an excited state molecule returns to a ground state by emitting fluorescence is weakened, so that the photothermal treatment effect is enhanced; an (imino)methyl phenol structure is introduced, so that the compound has a combination ability with Cu 2+ , S 2- , S 4+ , thereby realizing specific recognition of Cu 2+ , S 2- , S 4+ .

[0027] The application provides a development of a linkage composite photothermal reagent for a reduction stress-copper apoptosis system, in which a preparation reaction is kept in a state of high efficiency and low by-products in an initial stage, meanwhile, the safety of part of operations is improved, a high-purity product is successfully prepared, and it is more beneficial to implement accurate recognition and application in a life system. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the application, the drawings involved in the embodiments will be briefly introduced below. Obviously, the drawings in the description are only some embodiments of the application, and other drawings can be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0029] Figure 1 It is a nuclear magnetic resonance spectrum of a compound shown in formula (2-1).

[0030] Figure 2 It is a nuclear magnetic resonance spectrum of a compound shown in formula (2-2).

[0031] Figure 3 It is a nuclear magnetic resonance spectrum of a compound shown in formula (2-4).

[0032] Figure 4 It is a nuclear magnetic resonance spectrum of a compound shown in formula (I).

[0033] Figure 5The fluorescence response of Cy970 to different cations.

[0034] Figure 6 The fluorescence response of Cy970 to different cations. 2+ The fluorescence response of Cy970 to different cations.

[0035] Figure 7 The fluorescence response of Cy970 to different cations. 2+ The fluorescence response of Cy970 to different cations.

[0036] Figure 8 The fluorescence response of Cy970 to different cations. 2+ The fluorescence response of Cy970 to different cations.

[0037] Figure 9 The fluorescence response of Cy970 to different cations.

[0038] Figure 10 The fluorescence response of Cy970 to different cations. 2+ The fluorescence response of Cy970 to different cations.

[0039] Figure 11 The fluorescence response of Cy970 to different cations.

[0040] Figure 12 The fluorescence response of Cy970 to different cations.

[0041] Figure 13 The fluorescence response of Cy970 to different cations.

[0042] Figure 14 The fluorescence response of Cy970 to different cations.

[0043] Figure 15 The fluorescence response of Cy970 to different cations.

[0044] Figure 16 The fluorescence response of Cy970 to different cations.

[0045] Figure 17 The fluorescence response of Cy970 to different cations.

[0046] Figure 18Fluorescence imaging of Cy970 for detecting hydrogen sulfide and sulfur dioxide in cells. Wherein, a is the collection of emission channel (650~700nm); b is bright field; c is superimposed image; excitation wavelength is 650nm, and the scale is 40µm.

[0047] Figure 19 Ratio fluorescence intensity contrast of Cy970 for detecting hydrogen sulfide and sulfur dioxide in cells.

[0048] Wherein, Cy970 is a simple name of the compound shown in formula (I). DETAILED DESCRIPTION

[0049] Hereinafter, the technical solutions of the present application are described in combination with examples, but the present application is not limited to the following examples. The experimental methods and detection methods described in each example are all conventional methods, unless otherwise specified; and the reagents and materials described, unless otherwise specified, can be purchased on the market.

[0050] Example 1

[0051] This embodiment provides the preparation of the compound shown in formula (I) (hereinafter referred to as Cy970).

[0052] The reaction route for preparing the compound shown in formula (I) is as follows:

[0053] .

[0054] Synthesis of the compound shown in formula (2-1):

[0055] Under the ice bath atmosphere, 10g (45.7mMol) 4-iodoaniline was dissolved in 50mL 20% hydrochloric acid solution. 75mL water containing 3.24g (47.0mMol) sodium nitrite was added dropwise into the reaction system within 20min under stirring, and stirring was continued for 2h. 25g (111mMol) stannous chloride dihydrate was dissolved in 35mL concentrated hydrochloric acid, and was added dropwise into the reaction system within 5min, and stirring was continued for 2h. After the reaction was completed, the precipitate was filtered, and was dissolved in 100mL sodium hydroxide solution (1mol / L). CH2Cl2extraction, collection of organic phase, anhydrous sodium sulfate drying, and rotary evaporation. Brown solid (yield 9g, yield 92%) was obtained, which was the compound shown in formula (2-1), and the nuclear magnetic resonance spectrum was as follows: Figure 1 .

[0056] Synthesis of the compound shown in formula (2-2):

[0057] 1.37 g (5.86 mmol) of the compound shown in formula (2-1) and 1.4 mL of 3-methyl-2-butanone were dissolved in 20 mL of anhydrous ethanol and 0.3 mL of concentrated sulfuric acid, and reacted at 90 °C for 11 h. The reaction system was cooled to room temperature and filtered. 50 mL of water was added to the filtrate, and the mixture was extracted with CH2Cl2. The organic phase was washed successively with 10% sodium bicarbonate solution and water, and then evaporated to dryness. An orange-yellow oil (yield 1.59 g, 93% yield) was obtained, which is the compound shown in formula (2-2). The NMR spectrum is shown below. Figure 2 .

[0058] Synthesis of the compound shown in formula (2-3):

[0059] 1.2 g (4.2 mmol) of the compound shown in formula (2-2) and 6 g (39 mmol) of iodoethane were dissolved in 30 mL of toluene and reacted at 90 °C for 9 h. The reaction system was cooled to room temperature, filtered, and washed with petroleum ether. A pink solid (yield 1.02 g, 85% yield) was given, which was the compound shown in formula (2-3).

[0060] Synthesis of the compound shown in formula (2-4):

[0061] 1.64 g (4 mmol) of the compound shown in formula (2-3) and 0.298 g (2 mmol) of the compound shown in formula (1-3) were dissolved in 20 mL of acetic anhydride, and 0.142 g (2 mmol) of sodium acetate was added. The mixture was reacted at 100 °C in the dark for 3 h. The reaction solution was cooled to room temperature, washed with saturated sodium bicarbonate solution until no bubbles were produced, washed with water, and dried by rotary evaporation. A green solid (yield 1.46 g, yield 89%) was obtained, which was the compound shown in formula (2-4). The NMR spectrum is shown in [reference needed]. Figure 3 .

[0062] Synthesis of Cy970:

[0063] Under a nitrogen atmosphere, 0.03 g (2.5 mmol) of sodium hydride and 0.61 g (2.5 mmol) of the compound shown in formula (1-1) were dissolved in anhydrous DMF and stirred at room temperature for 30 min. 1.25 mmol of the compound shown in formula (2-4) was dissolved in anhydrous DMF and injected into the reaction system. The reaction mixture was stirred for 25 h under light-protected conditions. After the reaction was complete, 50 mL of CH2Cl2 was added, followed by washing with saturated brine and then with water. The organic phase was collected, dried over anhydrous sodium sulfate, and evaporated to dryness to obtain a crude green solid (yield 0.9 g, 95% yield). The crude product was purified by silica gel column chromatography (CH2Cl2:methanol = 18:1 / v:v) to obtain a green solid (yield 0.87 g, 92% yield), designated Cy970.

[0064] Example 2

[0065] This embodiment provides Cy970 for Cu 2+ Tests on selective fluorescence response.

[0066] Add 2 μL of 10 mM Cy970 stock solution to a PE tube, and then add 4 μL of different cation solutions (K... + Na + Ca 2 + Mg 2+ Al 3+ Fe 3+ Mn 2+ Zn 2+ Cu 2+ Co 2+ Ni 2+ NH 4+ Finally, the volume was adjusted to 2 mL with acetonitrile, and the final cation concentration was 50 µM.

[0067] After thorough mixing, the mixture was scanned using a fluorescence spectrophotometer to determine the fluorescence spectrum. The results are as follows: Figure 5 As shown. All Cy970 acetonitrile solutions only required the addition of Cu. 2+ After that, the fluorescence intensity decreased significantly; while the addition of other cations had little effect on the fluorescence intensity.

[0068] Example 3

[0069] This embodiment provides Cy970 for Cu 2+ Tests on optical response concentration.

[0070] Add 2 μL of 10 mM Cy970 stock solution to a PE tube, and add 4 μL of Cu at different concentrations. 2+ The solution was diluted to 2 mL with acetonitrile. After thorough mixing and standing for 5 min, the fluorescence spectrum was measured using a fluorescence spectrophotometer. The results are as follows: Figures 6-11 As shown. Figure 6 Cy970 with different concentrations of Cu at 814 nm 2+ Graph showing the relationship between fluorescence emission intensity changes after the reaction. Figure 7 The fluorescence intensity of Cy970 after reaction at 814 nm and Cu 2+ A graph showing the relationship between concentrations. Figure 8 Cy970 with different concentrations of Cu at 814 nm 2+ Graph showing the change in UV absorption intensity after the reaction.

[0071] Depend on Figure 6 It can be seen that with Cu 2+ As the concentration increases, the fluorescence intensity of the fluorescent probe Cy970 gradually decreases, indicating that Cu... 2+There is also interaction between Cy970, so that the fluorescence is quenched. From Figure 7 It can be seen that the absorption peak position of the fluorescence probe Cy970 does not change much before and after the addition of Cu 2+ , but the absorption intensity is obviously reduced, which also corresponds to the quenching process caused by Cu 2+ . From Figure 8 it can be seen that the fluorescence intensity of the fluorescence probe at 814 nm has a concentration dependence on Cu 2+ .

[0072] Example 4

[0073] This embodiment provides a test of the concentration dependence of the photothermal effect of Cy970.

[0074] Using a laser power of 1.2 mW / cm 2 , different concentrations (0 µM, 5 µM, 10 µM, 20 µM, 30 µM) of Cy970 were irradiated to test their photothermal performance. The temperature change of the solution is shown in Figure 9 , it can be seen that under the irradiation of 808 nm (1.2 mW / cm 2 ) laser, the solution temperature of different concentrations of photosensitizer solution increases obviously. The higher the concentration of the solution, the higher the final temperature of the solution. Therefore, the photothermal effect of Cy970 is concentration dependent, and the higher the concentration, the more obvious the heating effect.

[0075] Example 5

[0076] This embodiment provides a test of the influence of the response of Cy970 to Cu 2+ on the photothermal effect.

[0077] The concentration of Cy970 was set to 20 μM, and the influence of adding different concentrations of Cu 2+ on the photothermal effect under the irradiation of 808 nm (1.2 mW / cm 2 ) laser was tested. The results show that as the concentration of Cu 2+ increases, the temperature after 480 s of irradiation gradually decreases, and the temperature of Cy970 after 480 s of irradiation first increases and then decreases.

[0078] As shown in Figure 10 , when the concentration of Cu 2+ is 0 µM, the ΔT of Cy970 after irradiation is 19.2℃; when the concentration of Cu 2+ is 30 µM, the ΔT increases to 23.2℃, and the temperature after irradiation under this Cu 2+ concentration reaches the highest value; when the concentration of Cu 2+ increases to 60 µM, the ΔT after irradiation is 20.7℃; when the concentration of Cu 2+When the concentration of Cu2+ was 90 µM, ΔT = 18.1℃ after light irradiation, and the temperature began to drop; when the concentration of Cu2+ was 120 µM, ΔT = 13℃ after light irradiation; when the concentration of Cu2+ was increased to 150 µM, ΔT dropped to 4.6℃ after light irradiation. 2+ When the concentration of Cu2+ was 90 µM, ΔT = 18.1℃ after light irradiation, and the temperature began to drop; when the concentration of Cu2+ was 120 µM, ΔT = 13℃ after light irradiation; when the concentration of Cu2+ was increased to 150 µM, ΔT dropped to 4.6℃ after light irradiation. 2+ When the concentration of Cu2+ was 90 µM, ΔT = 18.1℃ after light irradiation, and the temperature began to drop; when the concentration of Cu2+ was 120 µM, ΔT = 13℃ after light irradiation; when the concentration of Cu2+ was increased to 150 µM, ΔT dropped to 4.6℃ after light irradiation.

[0079] Therefore, the addition of Cu2+ can enhance the photothermal effect of Cy970. 2+

[0080] Example 6

[0081] This example provides a test of the selective response of Cy970 to H2S and SO2.

[0082] The effect of interferents on fluorescence intensity was tested under simulated physiological conditions (10 mM PBS, pH = 3.7, 37℃; PBS buffer: 10 mM, pH = 7.4, 10% DMSO, 37℃). The screened interferents include biological thiols (Cys, GSH), metal cations (K + , Na + , Mg 2+ , Ca 2+ ), anions (NO 2- , F - , Cl - , I - , HCO3 - , CO3 2- , CH3COO - , OH - , SO4 2- , SO3 2- , S 2- , S2O3 2- , and other substances. The experimental results are shown in Figure 11 . As can be seen from Figure 11 , Cy970 only shows specific response to hydrogen sulfide and sulfur dioxide.

[0083] The fluorescence response spectrum of 10 µM Cy970 to different concentrations of Na2S and NaHSO3 was measured under simulated physiological conditions (10 mM PBS, pH = 3.7, 37℃) and PBS buffer (10 mM, pH = 7.4, 10% DMSO, 37℃), respectively, and the results are shown in Figures 12-15 . Figure 12 is a graph showing the change in fluorescence emission intensity of Cy970 after reaction with different concentrations of Na2S. Figure 13 is a graph showing the relationship between the fluorescence intensity of Cy970 after reaction and the concentration of Na2S at 805 nm. Figure 14 is a graph showing the change in fluorescence emission intensity of Cy970 after reaction with different concentrations of NaHSO3.​Figure 15 The relationship between the fluorescence intensity of Cy970 after reaction at 805 nm and the concentration of NaHSO3.

[0084] From Figures 12-15 It can be seen that the fluorescence intensity of Cy970 gradually weakens with the increase of the concentration of Na2S; there is a linear relationship between the fluorescence emission peak intensity of Cy970 and the concentration of NaHSO3; the fluorescence intensity of Cy970 gradually weakens with the increase of the concentration of Na2S, and the correlation coefficient R 2 =0.9913 at 805 nm; the fluorescence of Cy970 continuously decreases with the increase of the concentration of NaHSO3, showing a nonlinear correlation, and the correlation coefficient R 2 =0.98287. Therefore, it can be seen that the fluorescence intensity of Cy970 gradually weakens with the increase of the concentration of Na2S, and the photothermal effect is enhanced.

[0085] Example 7

[0086] This example provides a test of the temperature change of Cy970 (20 µM) under 808 nm (1.2 mW / cm 2 ) laser irradiation at different concentrations of Na2S.

[0087] The concentration of the photosensitizer is set to 20 µM, and the influence of adding different concentrations of Na2S on the photothermal effect under 808 nm (1.2 mW / cm 2 ) laser irradiation is tested. As shown in Figure 16 , the photothermal effect of Cy970 is not affected by the concentration of Na2S.

[0088] Example 8

[0089] This example provides a cytotoxicity test of Cy970.

[0090] The phototherapy effect of Cy970 under dark and light conditions is explored using HeLa cells. The cytotoxicity results are shown in Figure 17 , it can be seen that Cy970 has almost no dark toxicity in the concentration range of 0-20 µM, so it can be applied in cells. Adding alone does not have a killing effect, and after receiving light stimulation, the killing ability is low. As shown in Figure 17 , adding Cy970 alone does not have a killing effect, but after light, the cell survival rate decreases significantly, and the higher the concentration of Cy970, the more significant the phototherapy effect.

[0091] Therefore, the photosensitizer Cy970 has good phototherapy effect in cells.

[0092] Example 9

[0093] The present embodiment provides a cell imaging test of Cy970.

[0094] HeLa cells were selected as the research object for cell imaging of Cy970. The imaging results of Cy970 are shown in Figure 18 As shown in the figure, after adding Cy970 (10 µM), fluorescence appeared in the cells; after adding Na2S (150 µM), the fluorescence intensity was weakened. When NaHSO3 (30 µM) was added, the fluorescence intensity was also significantly weakened. This conclusion can also be clearly seen from the fluorescence intensity ratio graph. Figure 19

[0095] Therefore, the present application provides the development of a linkage complex photothermal reagent for the reduction stress-copper apoptosis system. The obtained probe Cy970 can be used for the recognition of hydrogen sulfide and sulfur dioxide in cells.

[0096] The above-described embodiments are part of the embodiments of the present application, rather than all the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but to represent selected embodiments of the present application. All other embodiments obtained by related deduction and replacement made by those skilled in the art under the condition of the concept of the present application, without making creative labor, belong to the scope of protection of the present application.​

Claims

1. A compound characterized by, The compound has a structure as shown in formula (I), 2. A method of preparing a compound, characterized by, The preparation method comprises the following steps: ； The preparation of the compound shown in formula (2-2) comprises: ring-closing reaction of the compound shown in formula (2-1) to generate the compound shown in formula (2-2), after the reaction system generates heat, ice bath treatment is performed, then filtration is performed, NaCl aqueous solution is added into the filtrate, and the compound shown in formula (2-2) is obtained; When the compound shown in formula (2-3) is prepared, the mixed solution of petroleum ether and ethyl acetate is used for washing and impurity removal; The preparation of the compound shown in formula (I) comprises the following steps: the compound shown in formula (2-4) is injected into a reaction system containing the compound shown in formula (1-1) under the conditions of anhydrous, oxygen-free and light shielding, CH2Cl2 is added for treatment after the reaction is completed, and then saturated sodium chloride solution and water are used for washing. The compound of claim 1.

3. A molecular probe, characterized in that, The compound of claim 1.

4. A drug specifically recognizing at least one of Cu 2+ , S 2- , SO2 and simultaneously triggering enhanced photothermal therapy or photodynamic therapy, characterized in that, The compound of claim 1.

5. An antitumor medicament characterized by, ​

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