A compound for light-controlled release of nitric oxide, its preparation and application

Abstract

A compound for light-controlled nitric oxide release, as well as its preparation and application. The compound has a molecular structure of #imgabs0#. The preparation method comprises reacting 4-bromo-N,N-dimethylaniline and 5-aldehyde-2-thiopheneboronic acid under the action of a first base and a first catalyst to generate compound 1; then reacting compound 1 with tert-butyl nitrite under the action of a second catalyst to obtain compound 2; and then reacting compound 2 with (3,5,5-trimethylcyclohex-2-enylidene)malononitrile under the action of a second base to obtain a compound for light-controlled nitric oxide release. The application of the compound for light-controlled nitric oxide release is that the molecule can controllably generate nitric oxide under the stimulation of light, and a quantitative amount of nitric oxide regulates neural differentiation in vivo, thereby promoting neural damage repair. The present invention can accurately and controllably release nitric oxide, realize controllable on-demand release of NO, and can monitor cell differentiation in real time.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and in particular relates to a compound for light-controlled release of nitric oxide, and its preparation and application. Background Art

[0002] Peripheral nerve injury is a complex disease common in young people, characterized by high morbidity, limited treatment options, and poor clinical outcomes. This disease not only causes functional and psychological impairment in patients but also places a heavy burden on society. Due to the complex microenvironmental changes in the nerve tissue at the site of injury, the repair of peripheral nerve injury remains suboptimal.

[0003] In complex and ever-changing microenvironments, nitric oxide (NO), as an important signaling molecule, has a wide range of physiological effects, including a role in tissue regeneration. Several studies have demonstrated that NO can stimulate stem cells to secrete growth factors and vesicles, regulating paracrine effects and regulating stem cell behaviors, including proliferation, differentiation, and migration. NO can also influence the microenvironment by stimulating certain signaling pathways, including regulating neurogenesis.

[0004] NO donors are widely known for their ability to release NO in vitro and in vivo and have been proposed as therapeutic tools for various diseases, such as cardiovascular disease. Currently, the two main types of NO donors are N-diazenediolates (NONOates) and nitrosothiols (RSNOs). Small molecular weight NONOates are formed by the reaction of primary or secondary amines with NO under high pressure. They produce NO through a proton-driven reaction (hydrolysis) in physiological environments, such as blood or tissue fluid, upon exposure (Biomater. Sci., 2016, 4, 1161–1183). RSNOs represent endogenous NO donors and natural transporters in tissues and blood. They are generated in acidic environments and stimulated to release NO under certain conditions, such as in the presence of transition metals or ultraviolet light (Nanoscale, 2021, 13, 444–459). Although NONOates and RSNOs have been extensively studied, these NO donors still have certain limitations in their application. They release NO through endogenous stimulation, such as in an aqueous or acidic environment. Such endogenous NO donors are usually unstable and it is difficult to achieve precise control of NO release (Adv. Healthcare Mater. 2020, 2001550). In particular, NONOates can spontaneously degrade into NO solution in physiological culture medium, resulting in poor precision of NO in regenerative medicine applications such as regulating the differentiation of stem cells into neurons.

[0005] Organic light-controlled NO-releasing molecules can achieve controlled release through external stimuli such as light. NO donors using light as a stimulus are able to avoid the risk of side effects caused by spontaneous NO release. Light control can minimize the effects of the biological environment, such as acidity, alkalinity, temperature, and ionic strength. Furthermore, organic light-controlled NO-releasing molecules have good donor stability and biocompatibility. For example, CN107459482A discloses a nitric oxide donor, its preparation, and application, 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 a compound for light-controlled release of nitric oxide has not been used in neurological diseases. Summary of the Invention

[0006] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide a compound, preparation and application of light-controlled release of nitric oxide, which can accurately and controllably release nitric oxide, realize the controlled release of NO on demand, and monitor cell differentiation in real time.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] A compound that releases nitric oxide under light-controlled conditions, the molecular structure of which is:

[0009]

[0010] A method for preparing a compound capable of light-controlled nitric oxide release comprises the following steps:

[0011] 1) 4-bromo-N,N-dimethylaniline and 5-formyl-2-thiopheneboronic acid are reacted in the presence of a first base and a first catalyst to generate compound 1, as shown in the following reaction formula:

[0012]

[0013] 2) Compound 1 and tert-butyl nitrite are reacted in the presence of a second catalyst to obtain compound 2, the reaction formula of which is as follows:

[0014]

[0015] 3) Compound 2 and (3,5,5-trimethylcyclohex-2-enylidene)malononitrile are reacted in the presence of a second base to obtain a compound capable of light-controlled release of nitric oxide, as shown in the following reaction formula:

[0016]

[0017] In step 1), the molar ratio of 4-bromo-N,N-dimethylaniline to 5-formyl-2-thiopheneboronic acid is 1:1; the first base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the first base to 4-bromo-N,N-dimethylaniline is 1:(0.2-0.5); the first catalyst is selected from any one of Pd / C powder, 1,1'-bisdiphenylphosphinoferrocene, palladium dichloride, and tetrakis(triphenylphosphine)palladium, and the molar ratio of the first catalyst to 4-bromo-N,N-dimethylaniline is 1:0.1; and the required solvent is selected from tetrahydrofuran and an aqueous solution.

[0018] The reaction conditions of step 1) are 80-85° C. and the reaction time is 24-48 hours.

[0019] In the step 2), the molar ratio of compound 1 to tert-butyl nitrosate is 1:1.5; the second catalyst is selected from tetramethylpiperidinyl oxide, and the molar ratio of the second catalyst to compound 1 is 1:0.1; and the required solvent is selected from tetrahydrofuran.

[0020] The reaction conditions of step 2) are 60-64° C. and the reaction time is 12-24 h.

[0021] In step 3), the molar ratio of compound 2 and (3,5,5-trimethylcyclohex-2-enylidene)malononitrile is 1:1; the second base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the second base to compound 2 is 1:(0.2-0.5), and the required solvent is selected from methanol or ethanol.

[0022] The reaction conditions of step 3) are 60-64° C. and the reaction time is 12-24 h.

[0023] The maximum absorption wavelength of the molecules of the compound for light-controlled nitric oxide release is about 468 nm, the maximum emission wavelength of the molecules of the compound for light-controlled nitric oxide release is about 634 nm, the molecules of the compound for light-controlled nitric oxide release have aggregation-induced luminescence characteristics, and the molecules of the compound for light-controlled nitric oxide release can quantitatively release nitric oxide under 460 nm laser irradiation. After 30 micromoles of molecules are irradiated for 15 minutes, the amount of NO released reaches 1.14 micromoles.

[0024] The application of a compound that releases nitric oxide under light-controlled conditions in promoting the repair of nerve damage. Nitric oxide, as an important gaseous signaling molecule, participates in mediating a wide range of intracellular and intercellular signaling cascades and physiological processes, and is associated with the early stages (neurogenesis) and late stages (synaptogenesis and neural graph formation) of neuronal differentiation, as well as the mechanism of developmental neurogenesis. Some studies have confirmed that nitric oxide exerts its effects by activating cGMP / PKG-dependent phosphorylation, and the cGMP-dependent mechanism can directly or indirectly promote Ca2+ Mobilization to regulate intracellular Ca 2+ level, calcium signaling plays a vital role in cell growth and neuronal signal transduction; the effect of nitric oxide is concentration-dependent. At low concentrations (<1-30nM), it mainly acts through a cGMP-dependent pathway, activating soluble guanylate cyclase (sGC) and triggering vasodilation and angiogenesis effects; when the concentration of nitric oxide increases (≥1μM), it will produce a similar apoptotic effect through protein nitrosation; therefore, the molecules of the light-controlled nitric oxide-releasing compound synthesized by the present invention can controllably generate nitric oxide under the stimulation of light, and quantitative nitric oxide regulates neural differentiation in vivo, thereby promoting the repair of neural damage.

[0025] A molecule that releases nitric oxide under light-controlled conditions has good biocompatibility and is non-toxic to target cells.

[0026] A molecule that releases nitric oxide under light-controlled conditions can be taken up by cells and has good biological imaging effects.

[0027] A molecule of a compound that releases nitric oxide under light-controlled conditions can release nitric oxide through 460nm laser irradiation, thereby achieving the purpose of controllable release of nitric oxide, and can be efficiently taken up by target cells and promote neural differentiation.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) The molecular structure of the light-controlled nitric oxide release compound designed by the present invention is stable, which can overcome the poor stability problem of existing NO donors, such as NONOates and RSNO;

[0030] (2) Since the molecule of the light-controlled nitric oxide release compound of the present invention is light-controlled to release NO through external stimulation, and the controlled release of nitric oxide is achieved by monitoring the change in the fluorescence intensity of the molecule, it can improve the shortcomings of existing NO donors that cannot accurately and controllably release NO;

[0031] (3) Since the molecule of the light-controlled nitric oxide release compound of the present invention has good biocompatibility and based on the wide range of pathophysiological effects of NO, it also has good application potential in the treatment of neurological diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the molecular 1H-NMR spectrum of the compound for light-controlled nitric oxide release according to the present invention.

[0033] Figure 2 This is the molecular ultraviolet absorption diagram of the compound for light-controlled release of nitric oxide according to the present invention.

[0034] Figure 3 This is a molecular fluorescence emission diagram of the compound that releases nitric oxide under light-controlled conditions according to the present invention.

[0035] Figure 4 This is the molecular NO release curve of the light-controlled nitric oxide-releasing compound of the present invention.

[0036] Figure 5 This is the molecular cytotoxicity result of the compound that releases nitric oxide under light control according to the present invention.

[0037] Figure 6 This is molecular cell imaging of the photocontrolled nitric oxide-releasing compound of the present invention.

[0038] Figure 7 The molecular in vitro NO release of the light-controlled nitric oxide-releasing compound of the present invention.

[0039] Figure 8 SH-SY5Y cells differentiated after being treated with the light-controlled nitric oxide-releasing compound of the present invention.

[0040] Figure 9 The figure shows the immunostaining results of βIII-tubulin in SH-SY5Y cells after treatment with the compound for light-controlled nitric oxide release of the present invention. DETAILED DESCRIPTION

[0041] The following examples further illustrate the technical solutions of the present invention. It should be understood that the following examples are merely exemplary illustrations and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope of protection intended by the present invention.

[0042] Example 1, a compound for light-controlled release of nitric oxide, the molecular structure of which is:

[0043]

[0044] A method for preparing a compound capable of light-controlled nitric oxide release comprises the following steps:

[0045] 1) Synthesis of Compound 1: Weigh 5 g (25 mmol) of 4-bromo-N,N-dimethylaniline and 4.68 g (30 mmol) of 5-formyl-2-thiopheneboronic acid into a 500 mL dry flask, dissolve in 200 mL of tetrahydrofuran and aqueous solution (V:V = 4:1), add 17.3 g (125 mmol) of potassium carbonate and 2.89 g (2.5 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 over anhydrous sodium sulfate, filter and concentrate, and purify by silica gel column chromatography to obtain a yellow solid. That is, compound 1, with a yield of >60%;

[0046] 2) 1.16 g (5 mmol) of compound 1 and 0.078 g (0.5 mmol) of tetramethylpiperidinyl oxide were dissolved in 50 mL of tetrahydrofuran, and 0.8 mL (7.5 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 was completed, the crude product was purified by silica gel column chromatography to obtain a yellow solid. That is, compound 2, with a yield of >75%;

[0047] 3) 1 g of compound 2 (3 mmol) and 0.56 g (3 mmol) of (3,5,5-trimethylcyclohex-2-enylidene)malononitrile were dissolved in 100 mL of methanol, 0.12 g (1.5 mmol) of sodium hydroxide was added, and the mixture was reacted at 60-65° C. for 24-48 h. A yellow solid precipitated, which was filtered and washed with methanol to obtain a purple solid with a yield of >60%. The purple solid is the compound that releases nitric oxide under light control. The reaction formula for this step is as follows:

[0048]

[0049] Reference Figure 1 The characterization data of the compound that releases nitric oxide under light-controlled conditions are as follows: 1H NMR (400 MHz, CDCl3): δ7.72 (d, 2H), 7.63 (d, 2H), 7.32 (d, 2H), 7.20 (t, 3H), 6.80 (d, 2H), 3.48 (s, 3H), 2.60 (s, 2H), 2.44 (s, 2H), 1.08 (s, 6H).

[0050] In order to investigate the behavior of the molecules of the light-controlled nitric oxide release compound in vitro, the Griess kit (Biyuntian, S0021S) was used for detection to obtain the molecular NO release curve. The specific experimental method is as follows: 2mL of the molecule NO-PT-MN of the light-controlled nitric oxide release compound with a concentration of 30μM was prepared, and it was continuously illuminated with a 460nm laser to release nitric oxide; referring to the instructions of the Griess kit (Biyuntian, S0021S), 50uL of the molecular solution was taken out at 0s, 1min, 5min, 10min, 30min, and 60min of illumination and added to a 96-well plate, and finally 50uL of reagent I and reagent II in the kit were added. After standing for 10min, the absorbance of the above solution at 540nm was measured with an enzyme marker. The maximum absorption wavelength of the molecule of the light-controlled nitric oxide release compound is about 468nm. Figure 2 As shown; the maximum emission wavelength of the molecule of the light-controlled nitric oxide release compound is about 634nm, as Figure 3 As shown; the light-controlled release of nitric oxide compound molecules can be quantitatively released under 460nm laser irradiation, 30 micromolecular light 15min after NO release of 1.14 micromole, such as Figure 4 shown.

[0051] In order to investigate the biocompatibility of the molecules of the light-controlled nitric oxide release compound and its cell imaging effect, the toxicity experiment of the light-controlled nitric oxide release molecule NO-PT-MN in SH-SY5Y cells (neuroblastoma) was verified. The specific experimental method is as follows: SH-SY5Y cells were placed at 37°C and 5% CO2 atmosphere by CCK8 kit detection, and SH-SY5Y cells were seeded in 96-well plates and cultured for 24 hours. Then 125uM NO-PT-MN solution was added, and after culturing in a cell culture incubator for 4 hours, the culture medium containing the molecule was removed and washed with PBS. The cells were treated with no light and light in PBS solution respectively; then fresh serum-free MEM medium was used to continue culturing for 12 and 36 hours. The culture medium was removed again and washed with PBS, and MEM medium containing fresh fetal bovine serum with CCK8 reagent was used, and cultured in a 37°C incubator for 40 minutes. Finally, the absorbance of the above solution at 450nm was measured using an enzyme reader to detect and analyze the cell activity rate of different groups. The cell analysis results are as follows Figure 5 As shown, the results show that after 36 hours of light treatment with or without the molecule NO-PT-MN, the survival rate of SH-SY5Y cells still remains above 80%, which shows that the probe of the present invention has low cytotoxicity and good cell biocompatibility.

[0052] To further investigate the cellular imaging effect of the molecules of the light-controlled nitric oxide release compound, SH-SY5Y cells were allowed to absorb the light-controlled nitric oxide release molecule NO-PT-MN, and the molecule NO-PT-MN was excited, and then cell imaging was performed. The specific experimental method is as follows: SH-SY5Y cells were placed at 37°C and 5% CO2 atmosphere, SH-SY5Y cells were seeded in a 24-well plate and cultured for 24 hours; then 125uM NO-PT-MN solution was added, and after culturing in a cell culture incubator for 4 hours, the culture medium containing the molecule was removed and washed with PBS; MEM culture medium containing fresh fetal bovine serum was used, and the cells were observed under a fluorescence microscope. The results are as follows: Figure 6 As shown, the axons of SH-SY5Y cells can be clearly observed, proving that the molecule NO-PT-MN has a good cell imaging effect.

[0053] In order to investigate the ability of NO-PT-MN, a molecule of a compound that releases nitric oxide under light control, to release nitric oxide in cells, the nitric oxide fluorescent probe DAN (AAT Bioquest, 15221) was used for detection. The specific experimental method is as follows: SH-SY5Y cells were placed at 37°C and 5% CO2 atmosphere, SH-SY5Y cells were seeded in a 24-well plate and cultured for 24 hours; then 125uM NO-PT-MN solution was added, and after culturing in a cell culture incubator for 4 hours, the culture medium containing the molecule was removed and washed with PBS, and then treated with no light and light in PBS solution respectively; then, the nitric oxide fluorescent probe DAN (AAT Bioquest, 15221) was processed according to the instructions and directly observed using a laser confocal microscope. The results are shown in FIG. Figure 7 As shown, by comparison, it was found that the fluorescence intensity of the experimental group treated with light was significantly higher than that of the experimental group not treated with light, proving that the NO-PT-MN molecule can release nitric oxide in cells through light, and can achieve controllable release of nitric oxide according to changes in fluorescence intensity.

[0054] In order to clarify the effect of NO-PT-MN, a molecule of a light-controlled nitric oxide-releasing compound, on promoting neural differentiation, the effect of SH-SY5Y cell differentiation after treatment with NO-PT-MN, a molecule of light-controlled nitric oxide-releasing compound, was verified, and neural differentiation was demonstrated by staining of the neural differentiation marker βIII-tubulin. The specific experimental method is as follows: SH-SY5Y cells were placed at 37°C and 5% CO2, and SH-SY5Y cells were seeded in a 24-well plate and cultured for 24 hours; then 125uM NO-PT-MN solution was added, and after culturing in a cell culture incubator for 4 hours, the culture medium containing the molecule was removed and washed with PBS, and then treated with no light and light in PBS solution respectively; then fresh fetal bovine serum MEM culture medium was used to continue culturing for 1, 3, 5, and 7 days respectively, and the differentiation of SH-SY5Y cells was observed under a bright field fluorescence microscope. Figure 8 As shown in the figure, it can be clearly found by comparison that the axons of SH-SY5Y cells after 7 days of culture have significantly increased.

[0055] βIII-tubulin immunostaining was performed on SH-SY5Y cells in different groups at 1, 3, 5, and 7 days. The culture medium was removed and washed with PBS. The cells were then fixed with 4% paraformaldehyde for 15 minutes, the paraformaldehyde was aspirated, and the cells were washed three times with PBS. The cells were then permeabilized with 1% TritonX-100 for 5 minutes, the Triton was aspirated, and the cells were washed three times with PBS. The cells were then blocked with a protein-free rapid blocking solution for 15 minutes. The blocking solution was also aspirated and the cells were washed three times with PBS. The cells were then stained with diluted βIII-tubulin primary antibody in a refrigerator at 4 degrees overnight. The primary antibody was recovered after 12 hours, the cells were washed three times with PBS, and the cells were incubated with diluted secondary antibody for 1-2 hours at room temperature in the dark. The secondary antibody was finally recovered and washed three times with PBS. The cell nuclei were stained with DAPI ready-to-use (Meilun Bio, MA0128), and the expression of βIII-tubulin protein was observed under a laser confocal microscope. The results are shown in Figure 2. Figure 9 As shown in the figure, the staining results showed that the experimental group treated with NO-PT-MN and irradiated with light had obvious βIII-tubulin protein expression, proving that NO-PT-MN after irradiation released nitric oxide in the cells and promoted the neural differentiation of SH-SY5Y cells.

[0056] The molar ratio of the first base to 4-bromo-N,N-dimethylaniline in step 1) of Example 1 was changed from 1:(0.2-0.5), exemplified by 1:0.2, 1:0.3, 1:0.4, and 1:0.5, the reaction conditions were changed from 80-85°C, exemplified by 80°C and 85°C, and the reaction time was changed from 24 to 48h, exemplified by 24h, 36h, and 48h; the reaction conditions in step 2) were changed from 60 to 64°C, exemplified by 60°C and 62°C. , 64°C, the reaction time is changed from 12 to 24h, exemplified by 12h and 24h; in step 3) the molar ratio of the second base to compound 2 is changed from 1:(0.2 to 0.5), exemplified by 1:0.2, 1:0.3, 1:0.4, 1:0.5, the reaction conditions are changed from 60 to 64°C, exemplified by 60°C, 62°C, and 64°C, the reaction time is changed from 12 to 24h, exemplified by 12h and 24h; the obtained effects are similar to those in Example 1.

[0057] The embodiments of the present invention are described above, but the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A compound for light-controlled release of nitric oxide, characterized in that: Its molecular structure is shown in Formula I.

2. The method for preparing a compound capable of light-controlled release of nitric oxide according to claim 1, characterized in that: The steps include: 1) 4-bromo-N,N-dimethylaniline and 5-formyl-2-thiopheneboronic acid are reacted in the presence of a first base and a first catalyst to generate compound 1, as shown in the following reaction formula: Wherein: the first catalyst is selected from any one of Pd / C powder, 1,1'-bis(diphenylphosphino)ferrocene, palladium dichloride, and tetrakis(triphenylphosphine)palladium, and the molar ratio of the first catalyst to 4-bromo-N,N-dimethylaniline is 1:0.1; 2) Compound 1 and tert-butyl nitrite are reacted in the presence of a second catalyst to obtain compound 2, the reaction formula of which is as follows: Wherein: the second catalyst is selected from tetramethylpiperidinyl oxide, and the molar ratio of the second catalyst to compound 1 is 1:0.1; 3) Compound 2 and (3,5,5-trimethylcyclohex-2-enylidene)malononitrile are reacted in the presence of a second base to obtain a compound capable of light-controlled release of nitric oxide, as shown in the following reaction formula:

3. The preparation method according to claim 2, wherein: In step 1), the molar ratio of 4-bromo-N,N-dimethylaniline to 5-formyl-2-thiopheneboronic acid is 1:1; the first base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the first base to 4-bromo-N,N-dimethylaniline is 1:(0.2-0.5); and the required solvent is selected from tetrahydrofuran and an aqueous solution.

4. The preparation method according to claim 3, wherein: The reaction conditions of step 1) are 80-85° C. and the reaction time is 24-48 hours.

5. The preparation method according to claim 2, wherein: In the step 2), the molar ratio of compound 1 to tert-butyl nitrosate is 1:1.5; the required solvent is selected from tetrahydrofuran; the reaction conditions of step 2) are 60-64° C., and the reaction time is 12-24 h.

6. The preparation method according to claim 2, wherein: In the step 3), the molar ratio of compound 2 and (3,5,5-trimethylcyclohex-2-enylidene)malononitrile is 1:1; the second base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide, and the molar ratio of the second base to compound 2 is 1:(0.2-0.5); the required solvent is selected from methanol or ethanol; the reaction conditions of step 3) are 60-64° C., and the reaction time is 12-24 h.

7. The preparation method according to claim 2, characterized in that: The maximum absorption wavelength of the molecules of the compound for light-controlled nitric oxide release is 468 nm, the maximum emission wavelength of the molecules of the compound for light-controlled nitric oxide release is 634 nm, the molecules of the compound for light-controlled nitric oxide release have aggregation-induced luminescence characteristics, and the molecules of the compound for light-controlled nitric oxide release can quantitatively release nitric oxide under 460 nm laser irradiation. After 30 micromoles of molecules are irradiated for 15 minutes, the amount of NO released reaches 1.14 micromoles.

8. Use of the compound for light-controlled nitric oxide release according to claim 1 in the preparation of a medicine, characterized in that: The molecules of compounds that release nitric oxide under light control can controllably generate nitric oxide under the stimulation of light. Quantitative nitric oxide regulates neural differentiation in the body, thereby promoting the repair of neural damage.

9. The use according to claim 8, characterized in that: A molecule of a compound that releases nitric oxide under light-controlled conditions has good biocompatibility and is not toxic to target cells; the molecule of the compound can be taken up by cells and has good bioimaging effects; the molecule of the compound can release nitric oxide through 460nm laser irradiation, achieving controllable release of nitric oxide, and can be taken up by target cells and promote neural differentiation.

Images