CN114478518B - Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection - Google Patents
Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection Download PDFInfo
- Publication number
- CN114478518B CN114478518B CN202011262822.9A CN202011262822A CN114478518B CN 114478518 B CN114478518 B CN 114478518B CN 202011262822 A CN202011262822 A CN 202011262822A CN 114478518 B CN114478518 B CN 114478518B
- Authority
- CN
- China
- Prior art keywords
- hypochlorite
- compound
- formula
- diphenyl
- base
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N2021/6417—Spectrofluorimetric devices
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention belongs to the field of organic compound synthesis, and particularly relates to a novel hypochlorite fluorescent probe, a preparation method thereof and a method for detecting hypochlorite by using the hypochlorite fluorescent probe. Aiming at the problems that the conventional hypochlorous acid fluorescent probe is easily interfered by other related species (poor specificity) and the sensitivity is not ideal, the invention provides a compound shown in a formula I as a fluorescent probe molecule. And provides a preparation method of the compound and a method for detecting hypochlorite by using the compound. The method is suitable for hypochlorite detection in the fields of analytical chemistry and chemical biology.
Description
Technical Field
The invention belongs to the field of organic compound synthesis, and further belongs to the field of organic compound synthesis for analytical chemistry and chemical biology, and particularly relates to a novel hypochlorite fluorescent probe, a preparation method thereof, and a method for detecting hypochlorite by using the hypochlorite fluorescent probe.
Background
Hypochlorous acid (HOCl/OCl) - ) The active oxygen plays an important role in the biological immune system as one of important small molecules of active oxygen in organisms. Hypochlorous acid is a member of the Reactive Oxygen Species (ROS) family, resulting from myeloperoxidationThe enzyme (MPO) catalyzes the production, which is also induced by various soluble stimuli. It plays an important role in the human immune function system, contributing to the destruction of invading bacteria and pathogens. Studies have shown that hypochlorous acid (HOCl/OCl) - ) Participate in the immune system by the following mechanisms: firstly, hypochlorous acid reacts specifically with various protein side chains and peptide bonds to enhance innate immunity; second, hypochlorous acid can oxidize and chlorinate various biomolecules, such as cholesterol, fatty acids, proteins, DNA, and RNA. These phenomena suggest that hypochlorous acid is involved in a variety of biological processes. But the concentration of the diffusible oxidant and the chlorinating agent hypochlorous acid is in the range of 10 -5 ～10 -2 And M. High concentrations of hypochlorous acid can pose potential health hazards, including tissue damage, elevated levels of intracellular chlorotyrosine residues, and protein modification. Abnormal hypochlorous acid levels can cause oxidative stress that ultimately leads to a variety of diseases including lung injury, atherosclerosis, kidney disease, neurodegeneration and certain cancers. Therefore, it is important to detect hypochlorous acid in a biological sample rapidly, sensitively and selectively.
In recent years, fluorescent probes have been widely used as an ideal detection tool, and have unique advantages such as high sensitivity, high operability, capability of performing in vivo biological imaging analysis, and the like, compared with other detection methods. Part of the hypochlorite fluorescent probe has the following structure.
The biological role of HOCl compared to other ROS has remained largely unexplored. The development of suitable hypochlorous acid detection methods is also challenging due to the strong oxidizing properties, short lifetime, and relatively low biological concentrations of hypochlorous acid. Although many fluorescent probes have been developed using the oxidizing ability of hypochlorous acid. However, the conventional hypochlorous acid probe molecules described above are susceptible to other related species (e.g., acetate, halide, chlorite, chlorate, hydrogen phosphate, dihydrogen phosphate, carbonate, nitrate, and nitrite)Plasma anions; ag + 、Al 3+ 、Ba 2+ 、Ca 2+ 、Ni 2+ An isocationic acid; h 2 O 2 、O 2 - 、 ONOO - Isoreactive oxygen compounds), resulting in poor specificity and less than ideal sensitivity for detecting hypochlorous acid.
Disclosure of Invention
Aiming at the problems that the existing hypochlorous acid fluorescent probe is easily interfered by other related species (poor specificity) and the sensitivity is not ideal, the invention provides a novel hypochlorite fluorescent probe, a preparation method thereof and a method for detecting hypochlorite by using the hypochlorite fluorescent probe, and aims to provide a fluorescent probe which has stronger specificity and higher sensitivity for hypochlorous acid molecules.
A compound of formula I:
the invention also provides a preparation method of the compound of the formula I, which comprises the following steps;
(1) Mixing (2S, 3S) -diphenyl ethylenediamine and citric acid for reaction to obtain (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic acid;
(2) Reacting (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic acid to obtain methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic ester;
(3) Methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic ester reacts with 1, 4-dibromobutane and 4-methylpyridine in sequence to obtain the compound of the formula I.
Preferably, the reaction conditions of step (1) are: (2S, 3S) -diphenylethylenediamine and citric acid are hydrothermally synthesized at 60-180 ℃.
Preferably, the reaction temperature of the step (1) is 140 ℃; and/or the reaction time is 0.5-12h, preferably 4h; and/or the molar ratio of the citric acid to the raw material A is 1: (0.5 to 2), preferably 1:1.
preferably, the reaction conditions of step (2) are as follows: reacting with methyl iodide under the condition of adding a base into an organic solvent, wherein the organic solvent is selected from DMF, THF, DMSO or acetone, and the base is selected from inorganic base or organic base; preferably, the inorganic base is selected from K 2 CO 3 The organic base is selected from DBU.
Preferably, the reaction temperature of the step (2) is 0-40 ℃, and the reaction time is 3h.
Preferably, the step (3) specifically comprises the following steps:
(3.1) reacting methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ]]Pyridine-7-carboxylic acid ester is dissolved in an organic solvent and reacts with 1, 4-dibromobutane under the condition of adding a base, wherein the organic solvent is selected from DMF, THF, DMSO or acetone, and the base is selected from inorganic base or organic base; preferably, the inorganic base is selected from K 2 CO 3 The organic base is selected from DBU; preferably, the reaction temperature is 40-60 ℃, and the reaction time is 3-5h;
(3.2) separating the product obtained in the step (3.1), dissolving the product in MeCN or toluene, adding 4-methylpyridine to react in an inert atmosphere, and separating the product to obtain a compound shown in the formula I; preferably, the reaction time of step (3.2) is 6-12h.
The invention also provides the use of a compound of formula I for hypochlorite detection.
The invention also provides a method for detecting hypochlorite by using the compound shown in the formula I, which comprises the following steps:
(1) Adding a compound of formula I to a sample to be tested;
(2) And testing the excitation emission spectrum of the sample to be tested through the fluorescence spectrum, and calculating the hypochlorite content in the sample to be tested according to the fluorescence intensity of the emission spectrum.
Preferably, the compound of formula I is used by formulating into 10 -2 -10 -3 Adding the mother solution of M into a sample to be detected;
and/or the excitation wavelength of the excitation emission spectrum is 425-500nm.
Compared with other existing fluorescent probe molecules, the fluorescent probe molecule provided by the invention has higher specificity and sensitivity.
In addition, citric acid is used as a raw material in the synthesis process of the fluorescent probe, so that the fluorescent probe has the advantages of low price and low toxicity, and no toxic solvent or catalyst is used in the cyclization in the first step, so that the pressure of the production process on environmental protection is reduced.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 shows UV absorption spectra of fluorescent probe molecules in different solvents according to the present invention;
FIG. 2 shows fluorescence spectra of fluorescent probe molecules provided by the present invention in different solvents;
FIG. 3 shows fluorescence intensities of fluorescent probe molecules in different active oxygen solutions;
FIG. 4 shows the interference of various ions on the detection of hypochlorite by the fluorescent probe molecule provided by the present invention;
FIG. 5 is a graph showing the relationship between fluorescence intensity and different hypochlorite concentrations during the measurement of detection limit;
FIG. 6 shows the results of water sample detection in example 2 of the present invention.
Detailed Description
The invention is further illustrated by the following specific examples.
Example 1: synthesis of fluorescent Probe molecules
1. Synthesis of methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylate
The synthetic route is as follows:
hydrothermally synthesizing (2S, 3S) -diphenylethylenediamine and citric acid at 140 ℃ for 4h to obtain (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazol [1,2-a ]]Pyridine-7-carboxylic acid, process for preparing it and K 2 CO 3 (3mmol, 414mg) was dissolved in DMF (10 mL) and stirred at 40 ℃ for 30 minutes, then MeI (300mg, 1.1mmol) was added thereto and the mixture stirred at 40 ℃ for 3 hours until the reaction was complete by TLC. The reaction mixture was taken up in water, extracted with Ethyl Acetate (EA) and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with ethyl acetate/petroleum ether to give the pure product.
Methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ]]Pyridine-7-carboxylate nuclear magnetic data are characterized by: 1 H NMR(400MHz,DMSO–d 6 )δ8.52(s,1H),7.46–7.35 (m,6H),7.35–7.32(m,2H),7.26–7.21(m,2H),6.03(d,J＝1.6Hz,1H),5.93 (d,J＝1.6Hz,1H),5.34(d,J＝2.7Hz,1H),4.88(d,J＝2.7Hz,1H),3.84(s,3H). HRMS(ESI)Calcd for[C21H18N2O3+H]+346.1317；Found:347.1321.
methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylate melting point: 108.7-109.8 deg.C
2. Synthesis of fluorescent Probe molecules
Reacting methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ]]Pyridine-7-carboxylic acid ester (692mg, 2mmol) and Cs 2 CO 3 (977mg, 414mg) was dissolved in THF (10 mL) and stirred at 60 ℃ for 30 min, then 1, 4-dibromobutane (648mg, 3mmol) was added to the mixture and stirred at 40 ℃ for 3h, monitored by TLC. The reaction mixture was taken up in water, extracted with Ethyl Acetate (EA) and concentrated under reduced pressure. The crude product is chromatographed on silica gel using ethyl acetatePurification with ethyl acetate/MeOH afforded the pure product. The product was dissolved in MeCN, added with stirring an equivalent amount of 4-methylpyridine and stirred at rt under argon for 12h, monitored by TLC. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography with DCM/MeOH to give the pure product.
1- (4- ((2S, 3S) -7- (methoxycarbonyl) -5-oxo-2, 3-diphenyl-2, 3-tetrahydroimidazo [1,2-a ]]Pyridin-1 (5H) -yl) butyl) -4-pyridin-1-yl salt (9): 1 H NMR(400MHz,DMSO–d6)δ8.81(d,J ＝6.6Hz,2H),7.97(d,J＝6.3Hz,2H),7.41(m,6H),7.23(m,2H),7.19–7.15 (m,2H),6.09(d,J＝1.4Hz,1H),5.93(d,J＝1.4Hz,1H),5.31(d,J＝3.0Hz, 1H),4.79(d,J＝3.0Hz,1H),4.47(t,J＝6.7Hz,2H),3.87(s,3H),3.51(m,1H), 2.93(m,1H),2.61(s,3H),1.84–1.74(m,2H),1.43(m,2H). 13 C NMR(101 MHz,DMSO–d6)δ166.19,159.85,159.26,153.19,144.06,143.96,139.63, 139.35,129.77,129.39,129.28,128.82,128.63,126.75,126.08,106.44,79.12, 70.56,66.91,59.71,53.25,49.05,43.26,28.36,23.61,21.84.389.1496 [C31H32N3O3+]+494.2438；Found:494.2433.
example 2: fluorescent probe molecule for hypochlorite detection
1. Method for testing influence of different solvents on fluorescence (ultraviolet) properties
1) Experimental solvent: respectively selecting N' N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, water, methanol, acetone, tetrahydrofuran, acetonitrile, dichloromethane and the like as solvents, wherein the purity of the samples meets the requirement of analysis and test.
2) The experimental conditions are as follows: the experimental temperature was room temperature (25 ℃), slit width =2.5nm, sample concentration C =10 -5 M。
3) The experimental procedure comprises respectively weighing 1-2mg of sample, dissolving in different solvents to obtain a solution with a concentration of 10 -3 And (5) placing the mother solution of M in a refrigerator to be protected from light for standby. During the test, 30 mu L of the corresponding mother liquor is taken out and diluted to 3mL to obtain 10 -5 M, and (3) a solution to be detected. And (3) measuring an absorption spectrum and a maximum absorption value of the liquid to be measured on an ultraviolet spectrophotometer, and then exciting on a fluorescence instrument by using the absorption value to obtain an emission spectrum. The experiment was repeated 3 times.
The results of the experiment are shown in FIGS. 1 and 2. It can be seen that in various solvents, the ultraviolet absorption and the emitted fluorescence of the fluorescent probe molecule provided by the invention are both in the range of 400-550 nm.
2. Method for testing influence of different ions on fluorescence (ultraviolet) property
1) Experimental solvent: 0.1M PBS buffer was chosen as the experimental solvent.
2) Preparing an ionic solution:
a) The metal ions and the non-metal ions are both prepared into 0.1M ionic solution.
b) The preparation method of the active oxygen solution comprises the following steps:
O 2 ·- : with CaH 2 Predrying the DMSO overnight, then centrifuging the predryed DMSO (3000 r/min, 20 min) to obtain anhydrous DMSO, and adding KO 2 Ultrasonic dissolution (stored in a-20 ℃ refrigerator);
OH: the ferrous chloride and the excessive hydrogen peroxide are used for preparation;
ONOO - : a mixed solution of 20mL of HCl (0.6N) and hydrogen peroxide (0.7N) and 20mL of sodium nitrite solution (0.6N) were poured onto ice quickly, and 20mL of cold NaOH solution (1.2N) was poured into the ice within 1 s. The solution changed from colorless to yellow, and then 30mg MnO was added 2 Removing excessive hydrogen peroxide, sealing, and storing in refrigerator. Ultraviolet calibration of the final concentration (. Epsilon.) of the polymer 302 ＝1670 M -1 cm -1 )；
H 2 O 2 : diluting with 30% hydrogen peroxide, and ultraviolet calibrating to obtain final concentration (epsilon) 240 ＝43.6M -1 cm -1 )；
ClO - : diluting with 5% NaOCl;
TBHP (tBuOOH): the 70% TBHP solution was diluted to a final concentration of 0.1M.
3) The experimental conditions are as follows: the experimental temperature was room temperature (25 ℃), slit width =2.5nm, sample concentration C =10 -5 M
4) The experimental steps are that 1-2mg of samples are respectively weighed and dissolved in different solvents to obtain the mother liquor with the concentration of 10 -3 And M, placing the mixture in a refrigerator to be protected from light for standby. Then will be pairedThe mother solution was diluted to 3mL by taking 30. Mu.L of the mother solution to 10 -5 M is the solution to be detected. Preparing two parts of the solution to be detected, adding one part of the solution to be detected into the ionic solution prepared in the step 2), taking the other part of the solution as a blank control, measuring an absorption spectrum and a maximum absorption value of the solution to be detected on an ultraviolet spectrophotometer, and then exciting the solution to be detected by using the absorption value on a fluorescence instrument to obtain an emission spectrum.
The experiment was repeated 3 times.
The results of the experiment are shown in FIG. 3. It can be seen that only in ClO - In the solution, the fluorescence intensity of the solution to be detected is obviously reduced, which shows that the compound provided by the invention has good selectivity on ions in a PBS (phosphate buffer solution) and has specific recognition on hypochlorite.
3. Ion interference test method
The experimental procedure and experimental conditions were identical to those in experiment 2 above, but 10eq interfering ions were added first to test the fluorescence properties, and then an equivalent amount of hypochlorite was added to test the optical properties. The experiment was repeated 3 times.
The results of the experiment are shown in FIG. 4. It can be seen that various interfering ions have little interference on the detection of hypochlorite.
4. Test method for detection limit
Experimental procedure and experimental conditions were consistent with those in experiment 2 above, but 11 blank samples were first prepared and scanned for standard deviation σ =4.69, then hypochlorite was added in the order of 0.5, 1eq-10eq and tested for optical properties to determine slope k =281.7. The experiment was repeated 3 times.
The results of the experiment are shown in fig. 5, giving a detection limit DL =3 σ/k =0.425 μ M. The detection limit is far lower than the content of hypochlorite in cells.
5. Detection method of actual water sample
The experimental steps and experimental conditions are consistent with those in experiment 2, but deionized water, tap water and water in the bowl of the university of west Hua are selected as detection substances, and the tap water and the bowl water are subjected to simple filtration treatment. Adding the probe solution 10 -5 M then measured the fluorescence properties, and then 10eq of sodium hypochlorite solution was added to test the fluorescence properties. Fruit of Chinese wolfberryThe experiment was repeated 3 times.
The experimental result is shown in fig. 6, and it can be seen that the fluorescent probe molecule provided by the invention is stable in performance when detecting hypochlorite in a water sample.
In conclusion, the fluorescent probe molecule obtained by the invention has good selectivity on hypochlorite detection, is resistant to ion interference and has specificity. And the detection limit of the probe is low and reaches 0.425 mu M, which is far lower than the intracellular hypochlorite value, so that the fluorescent probe molecule has high sensitivity when being used for hypochlorite detection. And the probe solution has good performance in the detection of a reagent water sample.
Claims (13)
1. A compound of formula I:
2. a process for the preparation of a compound of formula I according to claim 1, comprising the steps of;
(1) Mixing (2S, 3S) -diphenyl ethylenediamine and citric acid for reaction to obtain (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic acid;
(2) Reacting (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic acid to obtain methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic ester;
(3) Methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylic ester reacts with 1, 4-dibromobutane and 4-methylpyridine in sequence to obtain the compound of the formula I.
3. The method of claim 2, wherein: the reaction conditions of the step (1) are as follows: (2S, 3S) -diphenylethylenediamine and citric acid are hydrothermally synthesized at 60-180 ℃.
4. The method of claim 3, wherein: the reaction temperature of the step (1) is 140 ℃; and/or the reaction time is 0.5-12h; and/or the molar ratio of the citric acid to the raw material A is 1: (0.5-2).
5. The method of claim 4, wherein: the reaction temperature of the step (1) is 140 ℃; and/or the reaction time is 4h; and/or the molar ratio of the citric acid to the raw material A is 1:1.
6. the method of claim 2, wherein: the reaction conditions of the step (2) are as follows: reacting with methyl iodide under the condition of adding a base in an organic solvent, wherein the organic solvent is selected from DMF, THF, DMSO or acetone, and the base is selected from inorganic base or organic base.
7. The method of claim 6, wherein: the reaction conditions of the step (2) are as follows: the inorganic base is selected from K 2 CO 3 And the organic base is selected from DBU.
8. The method of claim 6, wherein: the reaction temperature of the step (2) is 0-40 ℃, and the reaction time is 3-12h.
9. The method of claim 2, wherein: the step (3) specifically comprises the following steps:
(3.1) reacting methyl (2S, 3S) -5-oxo-2, 3-diphenyl-1, 2,3, 5-tetrahydroimidazo [1,2-a ] pyridine-7-carboxylate with 1, 4-dibromobutane, in an organic solvent selected from DMF, THF, DMSO or acetone, and with the addition of a base selected from an inorganic base or an organic base;
and (3.2) separating the product obtained in the step (3.1), dissolving the product in MeCN or toluene, adding 4-methylpyridine to react in an inert atmosphere, and separating the product to obtain the compound shown in the formula I.
10. The method of claim 9, wherein: the step (3) specifically comprises the following steps:
in step (3.1), the inorganic base is selected from K 2 CO 3 The organic base is selected from DBU; the reaction temperature is 40-60 ℃, and the reaction time is 3-5h;
the reaction time of the step (3.2) is 6-12h.
11. Use of a compound of formula I according to claim 1 for hypochlorite detection for non-disease diagnostic purposes.
12. A method for hypochlorite detection for non-disease diagnostic purposes using a compound of formula I according to claim 1, comprising the steps of:
(1) Adding a compound of formula I to a sample to be tested;
(2) And testing the excitation emission spectrum of the sample to be tested through the fluorescence spectrum, and calculating the hypochlorite content in the sample to be tested according to the fluorescence intensity of the emission spectrum.
13. The method of claim 12, wherein: the compound of formula I is used by formulating into 10 -2 -10 -3 Adding the mother solution of M into a sample to be detected;
and/or the excitation wavelength of the excitation emission spectrum is 425-500nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011262822.9A CN114478518B (en) | 2020-11-12 | 2020-11-12 | Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011262822.9A CN114478518B (en) | 2020-11-12 | 2020-11-12 | Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114478518A CN114478518A (en) | 2022-05-13 |
| CN114478518B true CN114478518B (en) | 2023-03-31 |
Family
ID=81489971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011262822.9A Active CN114478518B (en) | 2020-11-12 | 2020-11-12 | Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114478518B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114507230B (en) * | 2020-11-17 | 2023-07-21 | 西华大学 | Bicyclic pyridone derivative, synthesis method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104710976A (en) * | 2015-01-06 | 2015-06-17 | 南京工业大学 | Hypochlorite ion fluorescence probe, preparation method and application thereof |
| CN110885327A (en) * | 2019-11-20 | 2020-03-17 | 浙江工业大学 | Hypochlorous acid rapid response fluorescent probe and preparation method and application thereof |
-
2020
- 2020-11-12 CN CN202011262822.9A patent/CN114478518B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104710976A (en) * | 2015-01-06 | 2015-06-17 | 南京工业大学 | Hypochlorite ion fluorescence probe, preparation method and application thereof |
| CN110885327A (en) * | 2019-11-20 | 2020-03-17 | 浙江工业大学 | Hypochlorous acid rapid response fluorescent probe and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114478518A (en) | 2022-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yuan et al. | Development of an ICT-based ratiometric fluorescent hypochlorite probe suitable for living cell imaging | |
| Bao et al. | A “naked eye” and ratiometric fluorescent chemosensor for rapid detection of F− based on combination of desilylation reaction and excited-state proton transfer | |
| Zhao et al. | Transforming the recognition site of 4-hydroxyaniline into 4-methoxyaniline grafted onto a BODIPY core switches the selective detection of peroxynitrite to hypochlorous acid | |
| CN111423423B (en) | Application of ratiometric fluorescent probe in detecting peroxynitrite anion | |
| Liu et al. | A highly selective and sensitive fluorescent probe for hypochlorous acid and its lysosome-targetable biological applications | |
| CN108003869B (en) | Fluorescent probe for detecting hypochlorite with high sensitivity and synthesis method and application thereof | |
| CN112574243B (en) | Synthesis and application of hydrogen peroxide long-wavelength fluorescent probe with quick response | |
| Liu et al. | A novel NIR-emissive probe with large Stokes shift for hypochlorite detection and imaging in living cells | |
| CN106008343A (en) | Naphthalimide based mercury-ion fluorescence probe as well as preparation method and application thereof | |
| CN106905310A (en) | Hypochlorous fluorescence probe of one kind detection and its preparation method and application | |
| CN111560246B (en) | Method for preparing hypochlorous acid fluorescent probe by taking citric acid-aniline-ethylenediamine as raw material | |
| CN106810561A (en) | A kind of lysosome targeting hypochlorous acid ratio fluorescent probe and preparation method and application | |
| CN114478518B (en) | Novel hypochlorite fluorescent probe, preparation method thereof and method for hypochlorite detection | |
| CN107746406B (en) | Preparation and application of ultrasensitive high-selectivity hypochlorous acid fluorescent probe | |
| CN109897627A (en) | A kind of near infrared fluorescent probe and its preparation method and application of quick detection ONOO- | |
| Lee et al. | Naphthalimide-based probe for the detection of hypochlorite in a near-perfect aqueous solution | |
| CN114644646A (en) | Near-infrared fluorescent probe with benzylboronic acid pinacol esters as detection groups and preparation method and application thereof | |
| CN110878085B (en) | Rapid high-selectivity hypobromous acid fluorescent probe, preparation method and application | |
| Liu et al. | A simple levulinate-based ratiometric fluorescent probe for sulfite with a large emission shift | |
| CN104529936A (en) | High-sensitivity high-selectivity fluorescence probe capable of real-time responding hypochlorous acid and application of high-sensitivity high-selectivity fluorescence probe | |
| Barkovskii | Organic reagents for the identification of Bi (V) and O 2 2–in Ba–Bi–O and K–Ba–Bi–O oxides using field test methods | |
| Yuan et al. | Determination of hypochlorite by quenching the fluorescence of 1-pyrenylboronic acid in tap water | |
| CN113563257B (en) | Hypochlorite fluorescent probe, preparation method and application thereof, and hypochlorite detection method | |
| CN109734710A (en) | A kind of fluorescence probe detecting cysteine and its synthetic method and application | |
| CN109503443B (en) | Fluorescent probe for analyzing hypochlorous acid in real time with ultra-sensitivity and high selectivity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |