Preparation method and application of viscosity-sensitive heterocyclic compound

Abstract

The present invention discloses a method for preparing and applying a viscosity-sensitive heterocyclic compound. The fluorescent dye has the following structure: #imgabs0#, wherein the substituent R is selected from N,N-diphenylamine and cyano. The dye is prepared by a one-step condensation reaction of a para-substituted benzaldehyde and a seven-membered fluoroboron dipyrrole compound under the catalysis of piperidine and acetic acid. The synthesis method is simple, separation and purification are convenient, and the yield is high. The introduction of the aromatic ring substituent increases the conjugation of the molecule, red-shifting the absorption and emission spectra, enabling monitoring of viscosity changes.

Description

Technical Field

[0001] The present invention relates to a heterocyclic compound, and more specifically to a preparation method and application of a viscosity-sensitive heterocyclic compound. The compound has a certain response to viscosity. At low viscosity, the fluorescence is weak, and as the viscosity increases, the fluorescence increases. Background Art

[0002] The viscosity of body fluids is a definitive biomarker of pathological conditions. When cells are subjected to external pressure, cell viscosity becomes abnormal. As small molecule fluorescent probes that respond to viscosity, BOPYIN probes have the advantages of high sensitivity, low biophotodamage, good biocompatibility, and real-time detection. Therefore, they can perform highly sensitive detection of abnormal changes in the intracellular microenvironment. For example, increased viscosity manifested by mitochondrial swelling is associated with many diseases, such as the neurodegenerative diseases Parkinson's disease, Alzheimer's disease, and atherosclerosis. At the same time, as a probe with a large conjugated system, it has the advantages of low fluorescence background signal and large photon penetration depth, which is of great significance for the analysis of living organisms and shows great potential in clinical medical applications.

[0003] Fluorescent probes have attracted widespread attention due to their potential convenience and high spatiotemporal resolution for microscopic monitoring of microbial samples. It is highly desirable to find small molecule probes that monitor viscosity for disease diagnosis and basic research. Dyes with rotatable substituents exhibit viscosity-responsive fluorescence enhancement, and having a large conjugated system makes the probe more penetrable. Typically, log(viscosity) is linearly proportional to log(fluorescence intensity). In liquid environments with low viscosity, the intramolecular rotatable bonds of the probe can rotate at high speed, thus generating a very low background fluorescence signal; in liquid environments with high viscosity, molecular rotation is hindered, and the molecule emits a strong fluorescence signal. With increasing viscosity, the probe luminescence enhancement can be as much as 7.5 times.

[0004] The present invention provides a preparation method and application of a viscosity-sensitive heterocyclic compound. The probe exhibits weak fluorescence on its own, but gradually increases with increasing viscosity. The viscosity sensitivity coefficient is 3.76 to 4.70, and the maximum fluorescence enhancement upon viscosity is 2.7 to 7.5 times the original fluorescence intensity. Summary of the Invention

[0005] The main purpose of the present invention is to provide a preparation method and application of a viscosity-sensitive heterocyclic compound.

[0006] The technical solutions of the present invention are as follows:

[0007] A preparation method and application of a viscosity-sensitive heterocyclic compound, wherein the chemical structural formula of the compound is:

[0008]

[0009] Wherein, the substituent R is any one selected from N,N-diphenylamino and cyano groups. As a preferred embodiment,

[0010] The chemical structural formula of the viscosity-sensitive heterocyclic compound is:

[0011]

[0012] Any one of .

[0013] The preparation method and application of the viscosity-sensitive heterocyclic compound are synthesized, and the method includes the following synthesis path:

[0014]

[0015] The method comprises the following steps:

[0016] (1) Add compound 1 and toluene to a reaction flask at room temperature, stir to dissolve, then add compound 2, piperidine, and acetic acid, and heat under reflux to obtain a reaction solution;

[0017] (2) The reaction solution in step (1) is subjected to rotary evaporation, and then separated by silica gel column chromatography to obtain product I, i.e., a seven-membered fluoroborane dipyridine derivative.

[0018] Compound 1 is a seven-membered fluoroborane dipyrrole compound, and compound 2 is a para-derivative of benzaldehyde; the molar ratio of compound 1 to compound 2 is 1:1 to 10. The order of feeding in step (1) is compound 1, toluene, compound 2, piperidine, and acetic acid.

[0019] Acetic acid deprotonates the methylene compound, generating a resonance-stabilized enolate, a carbonyl compound, and an iminium ion derived from the amine in the piperidine. The enolate and iminium ion form a tetrahedral intermediate, which undergoes 1,2-elimination to yield the desired α,β-unsaturated dicarbonyl or related compound. Acetic acid and piperidine both act as activating reactants and must be added last. The molar ratio of compound 1 to piperidine is 1:1-10, and the molar ratio of compound 1 to acetic acid is 1:1-10.

[0020] The heating temperature of step (1) is 30-150°C, and the heating time is 2-18 hours. The reaction temperature and time vary depending on the reactants. When the temperature rises above 120°C, the yield decreases; when the temperature drops to 60°C, it becomes difficult to start the reaction, resulting in an increase in reaction time.

[0021] The invention discloses an application of a seven-membered fluoroboron dipyrrole heterocyclic compound in detecting liquid viscosity.

[0022] The liquid is selected from any one or more of DMF, DME, DMSO, ethylene glycol, ethanol, n-butanol, isopropanol, and PBS.

[0023] The viscosity range of the liquid is 0.1-400 mPa·s; more preferably 0.1-320 mPa·s; more preferably 0.1-300 mPa·s; more preferably 0.1-280 mPa·s; more preferably 0.1-270 mPa·s; more preferably 0.1-250 mPa·s; more preferably 0.1-200 mPa·s; more preferably 0.1-150 mPa·s.

[0024] The heterocyclic compounds of the present invention exhibit weak fluorescence at low viscosity due to energy consumption in the non-radiative pathway of free rotation. At high viscosity, free rotation is blocked, and strong fluorescence is generated in the negligible non-radiative pathway. Fluorescence intensity increases with increasing viscosity. When the viscosity rises above 400 mPa·s, free rotation is maximally restricted, and fluorescence intensity no longer increases.

[0025] The beneficial effects of the present invention are as follows:

[0026] (1) The compound of the present invention has a certain response to viscosity. The fluorescence of the compound itself is weak. As the viscosity increases, the fluorescence gradually increases, and the maximum fluorescence enhancement to viscosity is 7.5 times.

[0027] (2) The synthesis reaction conditions of the present invention are easy to control, the product purification is simple, and it has universal applicability.

[0028] (3) The synthesis steps of the present invention are simple and the reaction conditions are mild. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 1 is a fluorescence spectrum of compound I-1 obtained in Example 1 in DMF-glycerol mixtures of different proportions.

[0030] Figure 2 is the fluorescence intensity logI of compound I-1 obtained in Example 1 729nm Linear relationship with logη.

[0031] Figure 3 1 is a fluorescence spectrum of compound I-2 obtained in Example 8 in DMF-glycerol mixtures of different proportions.

[0032] Figure 4 is the fluorescence intensity logI of compound I-2 obtained in Example 8 586nm Linear relationship with logη. DETAILED DESCRIPTION

[0033] The present invention is further described below with reference to the following examples. However, the scope of protection claimed in the present invention is not limited to the scope described in the examples.

[0034] Example 1

[0035] Weigh compound 1 (399 mg, 1 mmol) of heptafluoroborane dipyrrole and dissolve it in 30.00 mL of toluene. Then add 4-diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) in sequence. Heat and stir at 90 ° C for 8 hours until the reaction is complete. The reactant is rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (196.9 mg) with a yield of 30.1%.

[0036] Example 2

[0037] Compound 1 (399 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (546 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated at 90°C with stirring for 8 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (306.1 mg) with a yield of 46.8%. When the amount of 4-cyanobenzaldehyde was doubled compared to Example 1, the yield increased by 16.7%.

[0038] Example 3

[0039] Compound 1 (7-membered fluoroborane dipyrrole) (399 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.18 mL, 2 mmol), and acetic acid (0.12 mL, 2 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until complete reaction. The reactants were rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (175.9 mg) with a yield of 26.9%. When the amounts of piperidine and acetic acid were doubled compared to Example 1, the yield did not change significantly.

[0040] Example 4

[0041] Compound 1 (7-membered fluoroborane dipyrrole) (399 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was stirred at 120°C for 6 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (428.4 mg) with a yield of 65.5%. When the reaction temperature was increased by 30°C relative to Example 1, the reaction time was reduced by 2 hours, resulting in a 35.4% increase in yield.

[0042] Example 5

[0043] Compound 1 (399 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 140°C for 6 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (106.6 mg) with a yield of 16.3%. When the reaction temperature was increased by 50°C relative to Example 1 and the reaction time was reduced by 2 hours, the yield decreased by 13.8%.

[0044] Example 6

[0045] Compound 1 (399 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 60°C for 12 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (123.6 mg) with a yield of 18.9%. When the reaction temperature was reduced by 30°C and the reaction time was increased by 4 hours compared to Example 1, the yield decreased by 11.2%.

[0046] Example 7

[0047] Compound 1 (399 mg, 1 mmol) was weighed and dissolved in 60.00 mL of toluene. 4-Diphenylaminobenzaldehyde (273 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to obtain a purple solid I-1 (179.2 mg) with a yield of 27.4%. When the volume of toluene was doubled relative to Example 1, the yield decreased by 2.7%.

[0048] Example 8

[0049] Weigh compound 1 (399 mg, 1 mmol) of heptafluoroborane dipyrrole and dissolve it in 30 mL of toluene. Then add 4-cyanobenzaldehyde (131 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) in sequence. Heat and stir at 90 ° C for 8 hours until the reaction is complete. The reactant is rotary evaporated and purified by column chromatography to obtain a purple solid I-2 (228.2 mg) with a yield of 34.9%.

[0050] Example 9 - Response of Compounds I-1 and I-2 to Viscosity

[0051] Weigh compound I-1 (6.54 mg, 0.01 mmol) and dissolve it in 1 mL of DMF to prepare a 0.01 mol / L mother solution. Then, 10 μL of the mother solution was dissolved in 3 ml of a mixture of DMF and glycerol of different viscosities to prepare a 33.3 μmol / L test solution, wherein (DMF: glycerol = 10:0, such as 3 ml of DMF, the viscosity is 0.77 mPa·s), (DMF: glycerol = 9:1, such as the compound of 2.7 ml of DMF and 0.3 ml of glycerol, the viscosity is 1.5 mPa·s), (DMF: glycerol = 8:2, such as the compound of 2.4 ml of DMF and 0.6 ml of glycerol, the viscosity is 2.41 mPa·s), (DMF: glycerol = 7:3, such as the compound of 2.1 ml of DMF and 0.9 ml of glycerol, the viscosity is 4.22 mPa·s), (DMF: glycerol = 6:4, such as 1.8 ml The viscosity of the compound of DMF and 1.2 ml of glycerol is 7.36 mPa·s) (DMF: glycerol = 5:5, such as the viscosity of the compound of 1.5 ml of DMF and 1.5 ml of glycerol is 14.2 mPa·s), (DMF: glycerol = 4:6, such as the viscosity of the compound of 1.2 ml of DMF and 1.8 ml of glycerol is 19.9 mPa·s), (DMF: glycerol = 3:7, such as the viscosity of the compound of 0.9 ml of DMF and 2.1 ml of glycerol is 64.6 mPa·s) were detected respectively, and their fluorescence spectra were obtained. Figure 1 , and fitting the fluorescence intensity logI 729nm The linear relationship with logη gives Figure 2 The fluorescence of I-1 itself is weak, but with the increase of viscosity, the fluorescence gradually increases. The viscosity coefficient is 4.7, and the maximum fluorescence enhancement with viscosity is 2.7 times.

[0052] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of DME to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of DME and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (DME:glycerol = 10:0), (DME:glycerol = 9:1), (DME:glycerol = 8:2), (DME:glycerol = 7:3), (DME:glycerol = 6:4), (DME:glycerol = 5:5), and (DME:glycerol = 4:6). Fluorescence spectra increased with increasing viscosity. The detectable viscosity range was 0.1-260 mPa·s.

[0053] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of DMSO to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of DMSO and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the following solutions were measured: (DMSO:glycerol = 10:0), (DMSO:glycerol = 9:1), (DMSO:glycerol = 8:2), (DMSO:glycerol = 7:3), (DMSO:glycerol = 6:4), (DMSO:glycerol = 5:5), (DMSO:glycerol = 4:6), (DMSO:glycerol = 3:7), (DMSO:glycerol = 2:8), and (DMSO:glycerol = 1:9). Fluorescence spectra gradually increased with increasing viscosity. The detectable viscosity range was 0.1-300 mPa·s.

[0054] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethylene glycol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of ethylene glycol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (ethylene glycol:glycerol = 10:0), (ethylene glycol:glycerol = 9:1), (ethylene glycol:glycerol = 8:2), (ethylene glycol:glycerol = 7:3), (ethylene glycol:glycerol = 6:4), (ethylene glycol:glycerol = 5:5), (ethylene glycol:glycerol = 4:6), (ethylene glycol:glycerol = 3:7), and (ethylene glycol:glycerol = 2:8). Fluorescence spectra gradually increased with increasing viscosity. The detectable viscosity range was 0.1-270 mPa·s.

[0055] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of ethanol and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the following solutions were measured: (ethanol:glycerol = 10:0), (ethanol:glycerol = 9:1), (ethanol:glycerol = 8:2), (ethanol:glycerol = 7:3), (ethanol:glycerol = 6:4), (ethanol:glycerol = 5:5), (ethanol:glycerol = 4:6), and (ethanol:glycerol = 3:7). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-200 mPa·s.

[0056] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of n-butanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of n-butanol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (n-butanol:glycerol = 10:0), (n-butanol:glycerol = 9:1), (n-butanol:glycerol = 8:2), (n-butanol:glycerol = 7:3), (n-butanol:glycerol = 6:4), (n-butanol:glycerol = 5:5), and (n-butanol:glycerol = 4:6). Fluorescence spectra increased with increasing viscosity. The detectable viscosity range was 0.1-200 mPa·s.

[0057] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of isopropanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of isopropanol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (isopropanol:glycerol = 10:0), (isopropanol:glycerol = 9:1), (isopropanol:glycerol = 8:2), (isopropanol:glycerol = 7:3), (isopropanol:glycerol = 6:4), (isopropanol:glycerol = 5:5), (isopropanol:glycerol = 4:6), (isopropanol:glycerol = 3:7), and (isopropanol:glycerol = 2:8). Fluorescence spectra gradually increased with increasing viscosity. The detectable viscosity range was 0.1-250 mPa·s.

[0058] Compound I-1 (6.54 mg, 0.01 mmol) was weighed and dissolved in 1 mL of PBS to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of PBS and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the following solutions were measured: (PBS:glycerol = 10:0), (PBS:glycerol = 9:1), (PBS:glycerol = 8:2), (PBS:glycerol = 7:3), (PBS:glycerol = 6:4), (PBS:glycerol = 5:5), (PBS:glycerol = 4:6), (PBS:glycerol = 3:7), and (PBS:glycerol = 2:8). Fluorescence spectra gradually increased with increasing viscosity. The detectable viscosity range was 0.1-250 mPa·s.

[0059] Weigh compound I-2 (5.12 mg, 0.01 mmol) and dissolve it in 1 mL of DMF to prepare a 0.01 mol / L mother solution. Then, 10 μL of the mother solution was dissolved in 3 ml of a mixture of DMF and glycerol of different viscosities to prepare a 33.3 μmol / L test solution, wherein (DMF: glycerol = 10:0, such as 3 ml of DMF, the viscosity is 0.77 mPa·s), (DMF: glycerol = 9:1, such as the compound of 2.7 ml of DMF and 0.3 ml of glycerol, the viscosity is 1.5 mPa·s), (DMF: glycerol = 8:2, such as the compound of 2.4 ml of DMF and 0.6 ml of glycerol, the viscosity is 2.41 mPa·s), (DMF: glycerol = 7:3, such as the compound of 2.1 ml of DMF and 0.9 ml of glycerol, the viscosity is 4.22 mPa·s), (DMF: glycerol = 6:4, such as 1.8 ml The viscosity of the compound of DMF and 1.2 ml of glycerol is 7.36 mPa·s) (DMF: glycerol = 5:5, such as the viscosity of the compound of 1.5 ml of DMF and 1.5 ml of glycerol is 14.2 mPa·s) was detected respectively. Figure 3 , and fitting the fluorescence intensity logI 586nm The linear relationship with logη gives Figure 4 The fluorescence of I-2 itself is weak, but with the increase of viscosity, the fluorescence gradually increases. The viscosity coefficient is 3.76, and the maximum fluorescence enhancement with viscosity is 7.5 times.

[0060] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of DME to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of DME and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the following solutions were measured: (DME:glycerol = 10:0), (DME:glycerol = 9:1), (DME:glycerol = 8:2), (DME:glycerol = 7:3), (DME:glycerol = 6:4), (DME:glycerol = 5:5), (DME:glycerol = 4:6), (DME:glycerol = 3:7), and (DME:glycerol = 2:8). Fluorescence spectra gradually increased with increasing viscosity. The detectable viscosity range was 0.1-320 mPa·s.

[0061] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of DMSO to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of DMSO and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the solutions were measured at (DMSO:glycerol = 10:0), (DMSO:glycerol = 9:1), (DMSO:glycerol = 8:2), (DMSO:glycerol = 7:3), (DMSO:glycerol = 6:4), (DMSO:glycerol = 5:5), (DMSO:glycerol = 4:6), (DMSO:glycerol = 3:7), and (DMSO:glycerol = 2:8). Fluorescence spectra increased with increasing viscosity. The detectable viscosity range was 0.1-280 mPa·s.

[0062] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethylene glycol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of ethylene glycol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (ethylene glycol:glycerol = 10:0), (ethylene glycol:glycerol = 9:1), (ethylene glycol:glycerol = 8:2), (ethylene glycol:glycerol = 7:3), (ethylene glycol:glycerol = 6:4), (ethylene glycol:glycerol = 5:5), (ethylene glycol:glycerol = 4:6), (ethylene glycol:glycerol = 3:7), (ethylene glycol:glycerol = 2:8), and (ethylene glycol:glycerol = 1:9). Fluorescence spectra of these solutions increased with increasing viscosity. The detectable viscosity range was 0.1-300 mPa·s.

[0063] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of ethanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of ethanol and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the solutions were measured at (ethanol:glycerol = 10:0), (ethanol:glycerol = 9:1), (ethanol:glycerol = 8:2), (ethanol:glycerol = 7:3), (ethanol:glycerol = 6:4), (ethanol:glycerol = 5:5), and (ethanol:glycerol = 4:6). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-230 mPa·s.

[0064] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of n-butanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of n-butanol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (n-butanol:glycerol = 10:0), (n-butanol:glycerol = 9:1), (n-butanol:glycerol = 8:2), (n-butanol:glycerol = 7:3), (n-butanol:glycerol = 6:4), (n-butanol:glycerol = 5:5), (n-butanol:glycerol = 4:6), and (n-butanol:glycerol = 3:7). Fluorescence spectra increased with increasing viscosity. The detectable viscosity range was 0.1-180 mPa·s.

[0065] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of isopropanol to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of a mixture of isopropanol and glycerol of varying viscosities to prepare a 33.3 μmol / L test solution. Fluorescence spectra of the following solutions were measured: (isopropanol:glycerol = 10:0), (isopropanol:glycerol = 9:1), (isopropanol:glycerol = 8:2), (isopropanol:glycerol = 7:3), (isopropanol:glycerol = 6:4), (isopropanol:glycerol = 5:5), (isopropanol:glycerol = 4:6), (isopropanol:glycerol = 3:7), and (isopropanol:glycerol = 2:8). Fluorescence spectra increased with increasing viscosity. The detectable viscosity range was 0.1-250 mPa·s.

[0066] Compound I-2 (5.12 mg, 0.01 mmol) was weighed and dissolved in 1 mL of PBS to prepare a 0.01 mol / L stock solution. 10 μL of each stock solution was then dissolved in 3 mL of PBS and glycerol mixtures of varying viscosities to prepare 33.3 μmol / L test solutions. Fluorescence spectra of the solutions were measured at (PBS:glycerol = 10:0), (PBS:glycerol = 9:1), (PBS:glycerol = 8:2), (PBS:glycerol = 7:3), (PBS:glycerol = 6:4), and (PBS:glycerol = 5:5). Fluorescence gradually increased with increasing viscosity. The detectable viscosity range was 0.1-150 mPa·s.

[0067] The above embodiments are merely preferred technical solutions of the present invention and should not be construed as limiting the present invention. The embodiments and features in the embodiments of this application may be arbitrarily combined with each other unless they conflict. The scope of protection of the present invention shall be the technical solutions described in the claims, including equivalent alternatives to the technical features of the technical solutions described in the claims. Equivalent alternatives and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. An application of a seven-membered fluoroboron dipyrrole heterocyclic compound in detecting liquid viscosity, wherein the liquid is selected from any one or more of DMF, DME, DMSO, ethylene glycol, ethanol, and isopropanol, and the structural formula of the seven-membered fluoroboron dipyrrole heterocyclic compound is: I in, The substituent R is a cyano group.

2. The use according to claim 1, characterized in that The application includes the following synthetic routes: (1) Add compound 1 and toluene to a reaction flask at room temperature, stir and dissolve, then add compound 2, piperidine, and acetic acid, heat and reflux to obtain a reaction solution, where compound 2 is 4-cyanobenzaldehyde; (2) The reaction solution in step (1) is subjected to rotary evaporation and then separated by silica gel column chromatography to obtain product I, i.e., a seven-membered fluoroboranedipyrrole heterocyclic compound.

3. The use according to claim 2, characterized in that In the step (1), the molar ratio of compound 1 to compound 2 is 1:1-10.

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