α-Cyanodiarylethene fluorescent materials for light-controlled release of nitric oxide, preparation and application

Abstract

Disclosed are an α-cyanodiarylethene fluorescent material for light-controlled nitric oxide release, as well as its preparation and application. The preparation method comprises the following steps: first reacting 4-(dimethylamino)benzaldehyde and tert-butyl nitrite under the action of a catalyst to generate a compound, and then reacting the resulting compound with arylacetonitrile under the action of a base to obtain the α-cyanodiarylethene fluorescent material for light-controlled nitric oxide release. The material, as a nitric oxide donor, can release nitric oxide under illumination, and has aggregation-induced luminescence properties, with a large change in the molecular emission wavelength before and after nitric oxide release. Nitric oxide release can be precisely controlled according to changes in illumination power and time. The molecular nitric oxide release behavior can be detected by changes in the molecular fluorescence signal. The material has the characteristics of a large Stokes shift, controllable nitric oxide release, and unquenched fluorescence in an aggregated state, and can achieve in vivo calibration of nitric oxide release by utilizing changes in emission wavelength and fluorescence intensity.

Description

Technical Field

[0001] The present invention belongs to the technical field of nitric oxide (NO) in pharmaceutical chemistry, and specifically relates to an α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, as well as its preparation and application. Background Art

[0002] Nitric oxide (NO), a bioactive molecule, plays a key role in many physiological and pathological processes in the human body. For example, NO can regulate physiological and pathological processes by promoting vasodilation, angiogenesis, or neurotransmission. NO produced by macrophages and neutrophils can act as an antimicrobial and anticancer agent, forming part of the body's innate immune response to foreign pathogens. Furthermore, studies have shown that NO is closely associated with tumors. Low concentrations of NO can promote tumor growth and anti-apoptotic responses, while high levels of NO can induce cellular p53 phosphorylation and nitrative stress, leading to cell apoptosis and exerting anti-tumor effects.

[0003] Research on nitric oxide donors has garnered widespread attention due to the challenges of low endogenous nitric oxide concentrations or abnormal nitric oxide metabolism. Nitric oxide donor drugs play a significant role in both basic research and the treatment of clinical diseases. Nitric oxide donors such as 5-mononitroisosorbide and nitroglycerin are widely used in the clinical treatment of cardiovascular disease. Nitric oxide donors can rapidly release high concentrations of nitric oxide under physiological conditions, exerting its physiological effects, and have become a hot topic and a frontier in biomedical research.

[0004] Nitric oxide donors can not only provide exogenous nitric oxide to assist in biological research, but also serve as carriers of nitric oxide for in vivo transport. For example, CN107459482A discloses a nitric oxide donor and its preparation and use, which discloses a compound of the following formula: A fluorophore, wherein R2 is H, a C3-C8 cycloalkyl group, or a C1-6 alkyl group optionally substituted with 1-2 substituents selected from C1-4 alkoxy, -S(O)2-OH, and hydroxyl groups, and N is connected to the benzene ring of the fluorophore molecule; the compound can be used to treat or prevent hypertension-related diseases, cancer, diabetes, cardiovascular diseases, etc., but has the disadvantage that it is based on nitric oxide donor molecules with large planar molecular structures such as naphthalene imide or rhodamine, which are prone to aggregation in the in vivo environment, resulting in a decrease in the molecular fluorescence intensity. It is difficult to calibrate the nitric oxide release based on the change in the molecular fluorescence emission intensity before and after the release of nitric oxide, and it is impossible to achieve in vivo calibration of nitric oxide release. Summary of the Invention

[0005] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide an α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, as well as its preparation and application. The material is synthesized based on an aggregation-induced emission molecular skeleton, and as a nitric oxide donor, it can release nitric oxide under light, and has the characteristics of large changes in the molecular emission wavelength before and after the release of nitric oxide, and can accurately control the release of nitric oxide according to changes in light power and time; while delivering nitric oxide, the nitric oxide release behavior of the molecule can be detected by changes in the molecular fluorescence signal; the material has the characteristics of large Stokes shift and controllable release of nitric oxide, and can realize in vivo calibration of nitric oxide release by utilizing changes in emission wavelength and fluorescence intensity.

[0006] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0007] An α-cyanodiarylethene fluorescent material that releases nitric oxide under light-controlled conditions, the molecular structure of which is:

[0008]

[0009] An α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, the molecular structure of which is

[0010]

[0011] In the formula, R is an aromatic group, specifically benzene, pyridine, or picoline iodide.

[0012] A method for preparing an α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0013] (1) 4-(dimethylamino)benzaldehyde and tert-butyl nitrite are reacted in the presence of a catalyst to generate a compound, the reaction formula of which is as follows:

[0014]

[0015] (2) reacting the compound obtained in step (1) with aryl acetonitrile in the presence of a base to obtain an α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, wherein the reaction formula is as follows:

[0016]

[0017] The solvent of step (1) is selected from tetrahydrofuran; the catalyst is selected from tetramethylpiperidinium oxide, and the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde is 1:(0.1-0.5); the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate is 1:(1.5-2).

[0018] The reaction conditions of step (1) are 60-65° C. and the reaction time is 24-48 h.

[0019] The solvent of step (2) is selected from methanol or ethanol; the base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the base to the compound obtained in step (1) is 1:(0.2-0.5); the molar ratio of the compound obtained in step (1) to the aryl acetonitrile is 1:(1-4).

[0020] The reaction conditions of step (2) are 20-65° C., and the reaction time is 2-24 h.

[0021] The aryl acetonitrile structure in the step (2) is:

[0022] The α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide releases nitric oxide under the stimulation of 365nm light and can be used to treat cardiovascular diseases, inflammation, tumors and other related diseases.

[0023] The process of the α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide releasing NO under light is as follows:

[0024]

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] Since the present invention synthesizes a material having aggregation-induced emission characteristics and capable of light-controlled release of nitric oxide based on an aggregation-induced emission molecular strategy, the material has the advantages of a large Stokes shift, high photostability, and no fluorescence quenching in an aggregated state; in vivo calibration of nitric oxide release can be achieved based on changes in molecular fluorescence emission wavelength and intensity before and after nitric oxide release.

[0027] (1) The α-cyanodiarylethene fluorescent material molecules for light-controlled release of nitric oxide of the present invention have good donor stability and biocompatibility, release NO under light, and can achieve precise spatiotemporal regulation of NO release.

[0028] (2) By utilizing the fluorescence spectrum changes of α-cyanodiarylethene fluorescent material molecules that release nitric oxide under light control before and after NO release, a reliable means is provided for calibrating NO release, thereby achieving precise light control of NO release. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Formula X in Example 1 A UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0030] Figure 2 Formula X in Example 2 B UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0031] Figure 3 Example 3 Formula X C UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0032] Figure 4 Formula X in Example 4 D UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0033] Figure 5 Example 5 Formula X E UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0034] Figure 6 Example 6 Formula X F UV-visible absorption spectrum and fluorescence emission spectrum of the compound.

[0035] Figure 7 Formula X in Example 1 A Detection of aggregation-induced emission properties of compounds.

[0036] Figure 8 Formula X in Example 2 B Detection of aggregation-induced emission properties of compounds.

[0037] Figure 9 Example 3 Formula X C Detection of aggregation-induced emission properties of compounds.

[0038] Figure 10 Formula X in Example 4 D Detection of aggregation-induced emission properties of compounds.

[0039] Figure 11 Formula X in Example 5 E Detection of aggregation-induced emission properties of compounds.

[0040] Figure 12 Formula X in Example 6 F Detection of aggregation-induced emission properties of compounds.

[0041] Figure 13 Formula X in Example 4 D NO release curves of the compounds under light irradiation.

[0042] Figure 14 Example 5 Formula X E NO release curves of the compounds under light irradiation.

[0043] Figure 15 Formula X in Example 6 F NO release curves of the compounds under light irradiation. DETAILED DESCRIPTION

[0044] The technical solutions of the present invention are described below by way of examples. It should be understood that the following examples are only provided to illustrate the present invention, but the present invention is not limited thereto.

[0045] Example 1, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X A for;

[0046]

[0047] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0048] (1) 1.04 g (7 mmol) of 4-(dimethylamino)benzaldehyde and 0.11 g (0.7 mmol) of tetramethylpiperidinium oxide were dissolved in 50 mL of tetrahydrofuran, and 1.12 mL (10.5 mmol) of tert-butyl nitrosate was slowly added dropwise. The mixture was reacted at 60° C. for 24 h and monitored by TLC. After the reaction, the crude product was distilled under reduced pressure and purified by silica gel column chromatography to obtain a yellow solid with a yield of >75%. The reaction formula for this step is as follows:

[0049]

[0050] The characterization data of the yellow solid compound are as follows: 1 H NMR (400MHz, CDCl3): δ10.04(s,1H),9.82(d,2H),9.73(d,2H),3.65(s,3H). 13 CNMR (400MHz, CDCl3): δ190.99,146.83,134.64,131.26,118.30,30.44;

[0051] Formula X A Synthesis of the compound: Weigh 1 g (6 mmol) of the compound obtained in step (1) and 0.7 g (6 mmol) of aryl acetonitrile and dissolve them in 100 mL of methanol. The structure of aryl acetonitrile is Add 0.12 g (1.5 mmol) of sodium hydroxide and react at room temperature for 2 h to precipitate a yellow solid X A , filter, and wash the solid with methanol to obtain a yellow solid with a yield of >70%. The yellow solid is an α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide; the reaction formula of this step is as follows:

[0052]

[0053] The characterization data of the α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide are as follows: 1 H NMR (400MHz, CDCl3): δ8.01(d,2H),7.70(d,2H),7.67(d,2H),7.55(s,1H),7.47(d,2H),7.43(t,1H),3.47(s,3H).ESI-HRMS, C 16 H 13 The theoretical value of ON3[M+Na]+ is 286.0948, and the measured value is 286.0948.

[0054] Example 2, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X B for;

[0055] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0056] (1) The reaction conditions were changed to 65° C., the reaction time was changed to 48 h, the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde was 1:0.2; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate was 1:1.6, and the other conditions were the same as in Example 1;

[0057] (2) Formula X B Synthesis of the compound: Weigh 1 g (6 mmol) of the compound obtained in step (1) and 1.05 g (9 mmol) of aryl acetonitrile and dissolve them in 100 mL of methanol. The structure of aryl acetonitrile is Add 0.12 g (1.5 mmol) of sodium hydroxide and react at 20°C for 4 h to precipitate a yellow solid. Filter and wash the solid with methanol to obtain a yellow solid with a yield of >70%. The yellow solid is an α-cyanodiarylethene fluorescent material that releases nitric oxide under light control. The reaction formula for this step is as follows:

[0058]

[0059] The formula X B The characterization data of the compound are as follows: 1 H NMR (400MHz, DMSO-d6): δ8.69(d,1H),8.52(s,1H),8.17(d,2H),7.97(t,1H),7.88(d,2H),7.85(d,1H),7.46(t,1H),3.47(s,3H). 13C NMR (400MHz, CDCl3): δ150.90,149.79,143.96,143.64,137.57,132.02,131.36,123.78,121.48,118.59,117.85,110.38,30.61.

[0060] Example 3, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X C for;

[0061]

[0062] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0063] (1) The reaction conditions were changed to 62° C., the reaction time was changed to 30 h, the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde was 1:0.3; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate was 1:1.7, and the rest were the same as in Example 1;

[0064] (2) Formula X C Synthesis of the compound: Weigh 1 g (8 mmol) of 2-pyridineacetonitrile and dissolve it in 50 mL of acetonitrile. Add 3 mL (24 mmol) of iodomethane dropwise under nitrogen protection. React at 85 ° C for 48 h to precipitate a yellow solid. Filter and wash the solid with acetonitrile to obtain a yellow solid aryl acetonitrile. Yield> 70%;

[0065] 1 g (6 mmol) of the compound obtained in step (1) and 1.72 g (6.6 mmol) of a yellow solid aryl acetonitrile compound were weighed and dissolved in 100 mL of methanol. 0.12 g (1.5 mmol) of sodium hydroxide was added and reacted at 60° C. for 10 h. A yellow solid was precipitated, filtered, and washed with methanol to obtain a yellow solid with a yield of >60%. The yellow solid is an α-cyanodiarylethylene fluorescent material for light-controlled release of nitric oxide. The reaction formula for this step is as follows:

[0066]

[0067] The formula X C The characterization data of the compound are as follows: 1 H NMR (400MHz, DMSO-d6): δ9.15(d,1H),8.71(t,1H),8.36(d,1H),8.20(t,1H),8.17(d,2H),8.14(s,1H),7.93(d,2H),4.41(s,3H),3.45(s,3H). 13C NMR (400MHz, DMSO-d6): δ148.75,148.16,146.92,128.26,127.48,115.67,46.44,23.40.ESI-HRMS, C 16 H 15 ON4[M+H] + Theoretical value is 280.1276, measured value is 280.1276.

[0068] Example 4, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X D for;

[0069]

[0070] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0071] (1) The reaction conditions were changed to 65° C., the reaction time was changed to 34 h, the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde was 1:0.3; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate was 1:1.8, and the other conditions were the same as in Example 1;

[0072] (2) Weigh 1 g (6 mmol) of the compound obtained in step (1) and 2.32 g (12 mmol) of aryl acetonitrile and dissolve them in 100 mL of methanol. 0.12 g (1.5 mmol) of sodium hydroxide was added and the reaction was carried out at 65° C. for 4 h to precipitate a yellow solid. The solid was filtered and washed with methanol to obtain a yellow solid with a yield of >60%. The yellow solid is an α-cyanodiarylethene fluorescent material that releases nitric oxide under light control. The reaction formula for this step is as follows:

[0073]

[0074] The formula X D The characterization data of the compound are as follows: 1 H NMR (400MHz, CDCl3): δ8.01(d,2H),7.75(d,2H),7.69(d,2H),7.67(d,2H),7.63(s,1H),7.6(d,2H),7.46(d,2H),7.38(t,1H),3.47(s,3H). 13C NMR (400MHz, CDCl3): δ143.5,142.3,140.3,139.9,133.1,132.5,130.7,129.1,128.0,127.9,127.1,126.5,118.7,118.0,111.7,30.7.ESI-HRMS, C 22 H 17 ON3[M+H] + Theoretical value is 340.1444, measured value is 340.1433.

[0075] Example 5, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X E for;

[0076]

[0077] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0078] (1) The reaction conditions were changed to 60° C., the reaction time was changed to 48 h, the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde was 1:0.4; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate was 1:1.9, and the other conditions were the same as in Example 1;

[0079] (2) Formula X E Synthesis of the compound: Weigh 5 g (25.5 mmol) of 4-bromobenzeneacetonitrile and 3.75 g (30.6 mmol) of 4-pyridineboronic acid in a 500 mL dry flask, dissolve in 200 mL of tetrahydrofuran and aqueous solution (V:V = 4:1), add 17.6 g (127.5 mmol) of potassium carbonate, 2.95 g (2.55 mmol) of tetrakistriphenylphosphine palladium, stir at 80 ° C under nitrogen protection for 24 hours, and monitor the reaction by TLC; after the reaction is completed, add 100 mL of water, extract three times with 100 mL of dichloromethane respectively, collect the organic layer, dry with anhydrous sodium sulfate, filter and concentrate, and purify by silica gel column chromatography to obtain a white solid aryl acetonitrile. Yield> 60%;

[0080] 1 g (6 mmol) of the compound obtained in step (1) and 3.48 g (18 mmol) of white solid aryl acetonitrile were weighed and dissolved in 100 mL of methanol. 0.12 g (1.5 mmol) of sodium hydroxide was added and reacted at 60° C. for 12 h to precipitate a yellow solid. The solid was filtered and washed with methanol to obtain a yellow solid with a yield of >60%. The yellow solid is an α-cyanodiarylethylene fluorescent material for light-controlled release of nitric oxide. The reaction formula of this step is as follows:

[0081]

[0082] The formula X E The characterization data of the compound are as follows: 1 H NMR (400MHz, CDCl3): δ8.69(d,2H),8.04(d,2H),7.81(d,2H),7.74(d,2H),7.69(d,2H),7.62(s,1H),7.53(d,2H),3.46(s,3H). 13 C NMR (400MHz, CDCl3):150.6,147.1,143.7,141.2,139.1,135.0,132.2,130.8,127.8,126.8,121.5,118.7,117.8,111.2,30.7.ESI-HRMS, C 21 H 16 ON4[M+H] + Theoretical value is 341.1386, measured value is 341.1396.

[0083] Example 6, a light-controlled release of nitric oxide α-cyano diarylethene fluorescent material, its molecular structure X F for:

[0084]

[0085] The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide comprises the following steps:

[0086] (1) The reaction conditions were changed to 65° C., the reaction time was changed to 24 h, the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde was 1:0.5; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate was 1:2, and the other conditions were the same as in Example 1;

[0087] (2) Formula X F Synthesis of compound: Weigh 1 g (5.1 mmol) of formula IV E The compound was dissolved in 50 mL of acetonitrile, and 3 mL (15.3 mmol) of iodomethane was added dropwise under nitrogen protection. The reaction was carried out at 85 ° C for 48 h. A yellow solid was precipitated, which was filtered and washed with acetonitrile to obtain a yellow solid aryl acetonitrile. Yield> 70%;

[0088] 1 g (6 mmol) of the compound obtained in step (1) and 8 g (24 mmol) of yellow solid aryl acetonitrile were weighed and dissolved in 100 mL of methanol. 0.12 g (1.5 mmol) of sodium hydroxide was added and reacted at 60° C. for 24 h. A yellow solid was precipitated, filtered, and washed with methanol to obtain a yellow solid with a yield of >60%. The yellow solid is an α-cyanodiarylethylene fluorescent material for light-controlled release of nitric oxide. The reaction formula of this step is as follows:

[0089]

[0090] The formula X F The characterization data of the compound are as follows: 1 H NMR (400MHz, DMSO-d6): δ9.02(d,2H),8.55(d,2H),8.31(s,1H),8.22(d,2H),8.12(d,2H),8.01(d,2H),7.84(d,2H),4.32(s,3H),3.44(s,3H). 13 C NMR (400MHz, CDCl3):170.9,153.7,146.2,144.1,137.6,134.4,132.6,131.3,129.4,127.4,124.6,119.5,109.5,60.3,21.3,14.6.ESI-HRMS, C 22 H 19 ON4[M+Na] + Theoretical value is 378.1451, and the measured value is 378.1449.

[0091] Formula X was prepared with DMSO at a concentration of 20 μM A 、X B 、X C 、X D 、X E and X F Compound solutions were irradiated with a 365 nm UV lamp, and the UV absorption and fluorescence emission spectra of these compounds were recorded intermittently; UV absorption spectra were obtained using a SHIMADZU UV-1900I spectrophotometer; fluorescence emission spectra were obtained using a PTI-QM fluorescence steady-state fluorescence spectrometer; all spectra were collected using 1 cm quartz cuvettes. Figures 1-6 The results showed that as the illumination time increased, the initial absorption peak of the α-cyanodiarylethylene fluorescent material that released nitric oxide under light-controlled conditions decreased, and a new shoulder peak appeared; further extending the illumination time caused the initial peak to disappear, leaving only the new peak; the release of NO was accompanied by changes in fluorescence intensity, and a red shift in the fluorescence emission peak occurred. Figure 1 Formula X A Absorption and fluorescence emission spectra of the compounds, XA The compound has an initial absorption peak of 345 nm and an initial emission peak of 425 nm. After illumination, the absorption peak is 385 nm and the emission peak is 445 nm. Figure 2 Formula X B Absorption and fluorescence emission spectra of the compounds, X B The compound has an initial absorption peak of 350 nm and an initial emission peak of 440 nm. After illumination, the absorption peak is 410 nm and the emission peak is 495 nm. Figure 3 Formula X C Absorption and fluorescence emission spectra of the compounds, X C The compound has an initial absorption peak of 350 nm and an initial emission peak of 435 nm. After illumination, the absorption peak is 445 nm and the emission peak is 550 nm. Figure 4 Formula X D Absorption and fluorescence emission spectra of the compounds, X D The compound has an initial absorption peak of 360 nm and an initial emission peak of 450 nm. After illumination, the absorption peak is 380 nm and the emission peak is 495 nm. Figure 5 Formula X E Absorption and fluorescence emission spectra of the compounds, X E The compound has an initial absorption peak of 352 nm and an initial emission peak of 430 nm. After illumination, the absorption peak is 400 nm and the emission peak is 540 nm. Figure 6 Formula X F Absorption and fluorescence emission spectra of the compounds, X F The initial absorption peak of the compound is 370 nm, the initial emission peak is 460 nm, the absorption peak after light irradiation is 450 nm, and the emission peak is 610 nm.

[0092] Formula X was prepared in tetrahydrofuran at a concentration of 20 μM A 、X B 、X C 、X D 、X E and X F Compound solutions, using water as a poor solvent, record the compounds at different water contents (f w ) in a tetrahydrofuran / water mixture system. Figure 7-12 The results showed that the fluorescence intensity of the α-cyanodiarylethene fluorescent material molecules that release nitric oxide under light-controlled conditions is higher in the aggregated state than in the dispersed state, and they have obvious aggregation-induced emission characteristics. Figure 7 Formula X A Compounds at different water contents (f w ) under the fluorescence emission spectrum, at f w When the fluorescence intensity reaches 80%, it reaches the maximum value; Figure 8 Formula X BCompounds at different water contents (f w ) under the fluorescence emission spectrum, when f w When the fluorescence emission is less than 90%, almost no fluorescence emission occurs. w When the fluorescence intensity reaches 99%, it reaches the maximum value; Figure 9 Formula X C Compounds at different water contents (f w ) under the fluorescence emission spectrum, at f w When the fluorescence intensity reaches 99%, it reaches the maximum value; Figure 10 Formula X D Compounds at different water contents (f w ) under the fluorescence emission spectrum, when f w When the fluorescence emission is less than 70%, almost no fluorescence emission occurs. w When the fluorescence intensity reaches 90%, it reaches the maximum value; Figure 11 Formula X E Compounds at different water contents (f w ) under the fluorescence emission spectrum, when f w When the fluorescence emission is less than 80%, almost no fluorescence emission occurs. w When the fluorescence intensity reaches 90%, it reaches the maximum value; Figure 12 Formula X F Compounds at different water contents (f w ) under the fluorescence emission spectrum, when f w When the fluorescence emission is less than 90%, almost no fluorescence emission occurs. w When the fluorescence intensity reaches 99%, the maximum value is reached. D 、X E and X F The compound solution was irradiated with a 365nm UV lamp, and the amount of nitric oxide released by the compound under different illumination times was detected using the Griess reagent. After nitric oxide is produced, it is rapidly metabolized into nitrate and nitrite in the aqueous solution. The Griess reagent contains naphthylethylenediamine dihydrochloride and sulfonamide, which can react with nitrite to form a purple azo compound with absorbance at 546nm. Figure 13-15 The results showed that this type of α-cyanodiarylethene fluorescent material molecules that release nitric oxide under light-controlled conditions can release NO under 365nm light. Figure 13 Formula X D NO release curve of the compound under light, formula X D The NO release efficiency of the compound was 27.5%; Figure 14 Formula X E NO release curve of the compound under light, formula X E The NO release efficiency of the compound was 16%; Figure 15Formula X F NO release curve of the compound under light, formula X F The NO release efficiency of the compound was 25%.

Claims

1. An α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, characterized in that: Its molecular structure is: The specific molecular structure is: In the formula, R is an aromatic group, specifically benzene, pyridine, or picoline iodide.

2. The method for preparing the α-cyanodiarylethene fluorescent material capable of light-controlled release of nitric oxide according to claim 1, characterized in that: The steps include: (1) 4-(dimethylamino)benzaldehyde and tert-butyl nitrite are reacted in the presence of a catalyst to generate a compound, the reaction formula of which is as follows: The catalyst is selected from tetramethylpiperidinyl oxide, and the molar ratio of the catalyst to 4-(dimethylamino)benzaldehyde is 1:(0.1-0.5); (2) reacting the compound obtained in step (1) with aryl acetonitrile in the presence of a base to obtain an α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide, wherein the reaction formula is as follows:

3. The preparation method according to claim 2, wherein: The solvent in step (1) is selected from tetrahydrofuran; the molar ratio of 4-(dimethylamino)benzaldehyde to tert-butyl nitrosate is 1:(1.5-2).

4. The preparation method according to claim 2, wherein: The reaction conditions of step (1) are 60-65° C. and the reaction time is 24-48 h.

5. The preparation method according to claim 2, wherein: The solvent of step (2) is selected from methanol or ethanol; the base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the base to the compound obtained in step (1) is 1:(0.2-0.5); the molar ratio of the compound obtained in step (1) to the aryl acetonitrile is 1:(1-4).

6. The preparation method according to claim 2, wherein: The reaction conditions of step (2) are 20-65° C. and the reaction time is 4-24 h.

7. The preparation method according to claim 2, characterized in that: The aryl acetonitrile structure in step (2) is:

8. The use of the α-cyanodiarylethene fluorescent material for light-controlled release of nitric oxide according to claim 1, characterized in that: It can release nitric oxide under the stimulation of 365nm light, and can achieve in vivo calibration of nitric oxide based on the change of fluorescence signal after the release of nitric oxide. It can be used to treat cardiovascular diseases, inflammation, and tumor-related diseases.

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