CN114621200A - Near-infrared fluorescent probe and preparation method and application thereof - Google Patents
Near-infrared fluorescent probe and preparation method and application thereof Download PDFInfo
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- perchlorate
- methylene
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
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Abstract
The invention belongs to the technical field of organic compounds and preparation thereof, and discloses a near-infrared fluorescent probe and a preparation method and application thereof, aiming at the defects of the existing small-molecule fluorescent probe for detecting NAD (P) H. The fluorescent probe is 3- (9- (2- ((acetoxy methoxyl) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxy methylene-4 (1H) -methylene) -1-methyl quinoline-1-perchlorate trifluoromethanesulfonate. Firstly, reacting 4-diethylamino keto acid with cyclohexanone, concentrated sulfuric acid and perchloric acid; then reacting the reaction product with 3-quinoline formaldehyde; further reacting the obtained reaction product with methyl trifluoromethanesulfonate; and finally reacting with methyl bromoacetate to generate the fluorescent probe. The probe has the advantages of simple synthetic route, easily obtained raw materials and lower cost. The probe can respond to NAD (p) H, has high selectivity to NAD (p) H, has an emission wavelength of about 745nm, and can lay a foundation for the structure optimization of a subsequent molecular probe.
Description
Technical Field
The invention belongs to the technical field of organic compounds and preparation thereof, and particularly relates to a near-infrared fluorescent probe and a preparation method and application thereof.
Background
1, 4-dihydronicotinamide adenine dinucleotide (NADH) and its phosphate ester (NADPH) are the coenzymes necessary to maintain intracellular redox homeostasis. They are used as an electron carrier, are closely related to oxidoreductase, and participate in important redox reactions in metabolic pathways such as glycolysis, citric acid cycle and beta-oxidation. NAD (P) H is an important product of energy metabolism, and is closely related to the occurrence of cancer. Therefore, it is crucial to find a suitable method for achieving detection of NAD (P) H levels.
Currently, many methods for in vitro detection of nad (p) H have been developed, such as electrophoresis, enzymatic methods, and fluorescence imaging methods, such as gene-encoded proteins, nanoparticles, small molecule probes, and the like. Among them, small molecule fluorescent probes are widely concerned because of their many advantages, such as simple preparation, convenient use, good cell permeability, low toxicity, and suitability for in vivo experiments. However, most probes are off-type fluorescent probes and cannot be applied to live cell imaging, even in vivo imaging. Therefore, it is of great importance to develop an open-type fluorescent probe that can be used for live cell imaging as well as in vivo imaging.
Disclosure of Invention
Aiming at the defects of the existing small molecular fluorescent probe for detecting NAD (P) H, the invention provides a near-infrared fluorescent probe and a preparation method and application thereof. The fluorescent probe is a small molecular probe based on benzopyran phosphonium salt framework, which is found in previous researches by the inventor of the application and can respond to NAD (P) H. Therefore, the design and synthesis of the fluorescent probe of the compound are completed through a series of organic synthesis reactions, ultraviolet absorption and fluorescence tests are carried out on the fluorescent probe, and then NAD (P) H can be detected in cell confocal and in vivo experiments.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a near-infrared fluorescent probe, which is 3- (9- (2- ((acetoxy methoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxy methylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate and has a structural formula as follows:
the invention also provides a preparation method of the near-infrared fluorescent probe, which comprises the following steps:
step 1, reacting 4-diethylamino keto acid with cyclohexanone, concentrated sulfuric acid and perchloric acid to generate 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate;
step 3, reacting the 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate salt generated in the step 2 with methyl trifluoromethanesulfonate to generate 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate;
and 4, reacting the 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate generated in the step 3 with methyl bromoacetate to generate 3- (9- (2- ((acetoxy methoxyl) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxymethylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate, and thus obtaining the near-infrared fluorescent probe.
Further, the preparation method specifically comprises the following steps:
step 1, adding cyclohexanone into concentrated sulfuric acid with the mass fraction of 98% dropwise at 0 ℃, stirring, then adding 4-diethylamino keto acid in batches, continuing stirring at 90-120 ℃, stopping the reaction after the reaction is carried out for 3-5 hours, pouring the final reaction mixture into water with the temperature of 0 ℃, adding 70% perchloric acid, carrying out suction filtration on the precipitated precipitate, and washing with water with the temperature of 0 ℃ to obtain an orange-red solid compound, namely 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate;
and 3, adding methyl trifluoromethanesulfonate into dichloromethane, adding 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate, stirring at room temperature for 3 hours, stopping reaction, cooling to separate out a purple solid, performing suction filtration, washing with dichloromethane, and drying to obtain a compound: 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate;
step 4, adding 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate and N, N-diisopropylethylamine into a reaction vessel, adding acetonitrile, uniformly mixing, then adding methyl bromoacetate into the mixed solution, stirring for 48 hours under the protection of argon, and separating by column chromatography to obtain a compound: and 3- (9- (2- ((acetoxy methoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxy methylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate to obtain the near-infrared fluorescent probe.
Further, in the step 1, cyclohexanone, 98% concentrated sulfuric acid by mass fraction, 4-diethylamino keto acid by mass fraction, and 70% perchloric acid by volume: volume: quality: volume 6.6 mL: 72 mL: 9.82 g: 7.9 mL; the final reaction mixture was poured into 200mL of 0 ℃ water.
The mass of the 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate, 3-quinolinecarboxaldehyde, piperidine and absolute ethyl alcohol in the step 2 is as follows: quality: volume: volume 2 g: 1 g: 0.04 mL: 35 mL.
The volume of the used amounts of dichloromethane, methyl trifluoromethanesulfonate and 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate in the step 3 is as follows: volume: mass 108 mL: 1.2 mL: 1.53 g.
The mass of the used amount of 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate, N-diisopropylethylamine, acetonitrile and methyl bromoacetate in the step 4 is as follows: volume: volume: volume 60 mg: 0.124 mL: 2mL of: 0.1 mL.
Further, the vacuum pump for suction filtration in step 1 and step 3 is a reduced pressure vacuum pump, and the mobile phase of the column chromatography in step 4 is dichloromethane in volume ratio: methanol 8: 1.
The invention also provides an application of the near-infrared fluorescent probe, which is used for preparing a reagent for detecting 1, 4-dihydronicotinamide adenine dinucleotide and phosphate thereof.
Compared with the prior art, the invention has the following advantages:
1. the invention provides an open type fluorescent probe which has higher signal-to-noise ratio.
2. The invention provides a small molecular probe based on a benzopyran salt skeleton, which has the advantages of simple synthetic route, easily obtained raw materials and low cost.
3. The small molecular probe can respond to NAD (P) H, has high selectivity to NAD (P) H, has an emission wavelength of about 745nm, and can lay a foundation for the structure optimization of a subsequent molecular probe.
4. The invention provides biological application of a small molecule probe, and the long emission wavelength of the small molecule probe can be utilized in cell and mouse experiments, thereby being beneficial to the subsequent research of cancer.
Drawings
FIG. 1 is a hydrogen spectrum of nuclear magnetic resonance of a probe of the present invention;
FIG. 2 is a carbon spectrum of nuclear magnetic resonance of a probe of the invention;
FIG. 3 is a high resolution mass spectrum of a probe of the invention;
FIG. 4 is a spectral test chart of a probe of the present invention;
FIG. 5 is a graphic image of a probe of the present invention detecting NAD (P) H in different living cells;
FIG. 6 is a graph of an image of Hela cells with probes of the invention at different glucose concentrations;
FIG. 7 is a photograph of a mouse in vivo image of the probe of the present invention.
Detailed Description
The technical solution of the present invention will be specifically and specifically described below with reference to the embodiments of the present invention and the accompanying drawings. It should be noted that variations and modifications can be made by those skilled in the art without departing from the principle of the present invention, and these should also be construed as falling within the scope of the present invention.
Example 1
A near-infrared fluorescent probe is prepared by the following steps:
1) preparation of Compound 2
A200 ml flask was charged with 98% by mass concentrated sulfuric acid (72ml), and cyclohexanone (6.6ml, 64mmol) was added dropwise to 98% concentrated sulfuric acid (72ml) at 0 ℃ with stirring, and then 4-diethylaminoketoacid (9.82g, 32mmol) was added in portions, and the mixture was stirred at 90 ℃. The reaction was stopped after 3 hours. The final reaction mixture was poured into 0 ℃ water (200ml), 70% by mass perchloric acid (7.9ml) was added, and the precipitated precipitate was suction-filtered by a vacuum pump under reduced pressure and washed three times with 0 ℃ water to give 2(15g) as an orange-red solid compound, i.e., 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxyperchlorate, in a yield of 98%.
2) Preparation of Compound 3
Compound 2(2g, 4.2mol), 3-quinolinecarboxaldehyde (1g, 6.3mol) and piperidine (40. mu.l) were added in this order to a 50ml flask and dissolved in a further amount of solvent, anhydrous ethanol (35ml), and the final mixture was heated to 80 ℃ for reflux, allowed to react overnight, cooled to 0 ℃ for 2 hours after the reaction was completed and the temperature returned to room temperature, to precipitate a purple solid which was then washed 3 times with tert-butyl methyl ether to give compound 3(1.5513g), 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxyperchlorate, in 61% yield after the solid was dried.
3) Preparation of Compound 4
Methyl trifluoromethanesulfonate (1200. mu.l, 10.2mol) was added to methylene chloride (108ml), followed by addition of compound 3(1.53g, 2.5mol), stirring at room temperature for 3 hours, stopping the reaction, cooling to precipitate a purple solid, suction-filtering with a vacuum pump, washing three times with methylene chloride, and drying to give compound 4(0.9133g), i.e., 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate in 58% yield.
4) Preparation of Compound 1 (Probe)
Compound 4(60mg, 0.097mmol) and N, N-diisopropylethylamine (124 μ l, 0.75mmol) were added to a 10ml round bottom flask, acetonitrile (2ml) was added and mixed well, and then methyl bromoacetate (100 μ l, 1.02mmol) was added to the mixed solution, stirred under argon for 48 hours, and separated by column chromatography (dichloromethane: methanol ═ 8:1, volume ratio) to give compound 1, i.e., 3- (9- (2- ((acetoxymethoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxymethylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate (near infrared fluorescence probe) in 22% yield.
FIG. 1 is a hydrogen spectrum of nuclear magnetic resonance of the probe of this example, which is shown in FIG. 1:
1H NMR(600MHz,CDCl3)δ9.09(s,1H),8.96(s,1H),8.39(d,J＝6.7Hz,1H),8.28(d,J＝7.8Hz,1H),8.20(t,J＝7.0Hz,1H),8.07(s,1H),7.98(t,J＝7.1Hz,1H),7.84(t,J＝7.8Hz,1H),7.73(t,J＝7.6Hz,1H),7.28(s,2H),7.26(d,J＝7.4Hz,1H),7.10(d,J＝9.7Hz,1H),7.01(d,J＝9.6Hz,1H),5.77–5.73(m,2H),4.94(s,3H),4.29(s,4H),4.20–4.11(m,2H),3.84(s,2H),3.43(s,3H),3.37(s,2H),2.24(s,6H).
FIG. 2 is a carbon spectrum of NMR of the probe of this example, as shown in FIG. 2:
13C NMR(151MHz,CDCl3)δ169.3,167.9,163.6,161.6,158.8,156.4,152.3,137.2,136.5,134.5,134.1,133.8,132.7,131.8,130.6,130.6,130.3,129.8,129.7,129.7,129.1,129.0,127.8,123.7,118.8,118.7,118.0,98.2,86.7,80.0,62.5,54.2,53.4,42.4,29.6,14.0,12.1,10.5.
FIG. 3 is a high resolution mass spectrum of the probe of this example, from FIG. 3:
HRMS(ESI)[M]2+calculated for C38H38N2O5:301.1390,found:301.1387。
example 2
The fluorescence probe prepared in example 1 was subjected to spectroscopic measurement:
the test was performed in system PBS: CH (CH)3CH2OH ═ 3: 2 (volume ratio), the concentration of the probe preparation mother liquor was 2mM, and the concentration of the NADH and NADPH mother liquor was 20 mM. (all tests were carried out at 37 ℃ C. with temperature control)
The test results are shown in fig. 4. In FIG. 4 (a) is Compound 1 (10. mu.M, PBS: CH)3CH2OH, volume ratio 3: 2) change in UV absorption over time after addition of 100. mu.M NADH; (b) is compound 1 (10. mu.M, PBS: CH)3CH2OH, volume ratio 3: 2) the fluorescence intensity of (D) varies with NADH concentration (0-100. mu.M); (λ ex 680nm, narrow)Sewing: 10nm/10 nm); (c) is compound 1 (10. mu.M, PBS: CH)3CH2OH, volume ratio 3: 2) the change of fluorescence spectrum with the increase of time after adding 100 μ M NADH; (d) is compound 1 (10. mu.M) in PBS and CH3CH2Adding 100 mu M NADH kinetic curve into OH (volume ratio 3: 2) mixed solvent; (λ ex 680nm, slit: 10nm/10 nm); (e) working curves of compound 1 (10. mu.M) in the presence of different concentrations of NADH; (f) is compound 1 (10. mu.M, PBS: CH)3CH2OH, volume ratio 3: 2) fluorescence intensity at 745nm after reacting with various ions, amino acids and enzymes in a 37 ℃ water bath for 2.5 hours; the abscissa a to w represent 200. mu. M K, respectively+，Na+，Ca2+，Mg2+，F-，Br-，NO2 -，OH-，HSO3 -，SO3 2-，SCN-，H2O2VC, Cys, Hcy, GSH, Lys, Asn, lipase, pepsin, trypsin, NADPH, NADH.
As can be seen from FIG. 4, the probe has a UV absorption peak at 556nm, a new absorption peak at 723nm after the addition of NADH, and as time goes on, the UV absorption at 556nm gradually decreases, and the UV absorption at 723nm gradually increases (a), indicating that the probe can respond to NADH. Subsequently, using 680nm as the excitation wavelength of the probe, when different concentrations of NADH (0-100. mu.M) were added, a gradual increase in fluorescence intensity at 745nm was observed (b), indicating that the probe is concentration-dependent in response to NADH, and after 100. mu.M of NADH was added, the fluorescence intensity was also gradually increased with time (c and d), indicating that the probe is correspondingly time-dependent in response to a certain concentration of NADH. R of the curve in graph (e)2The probe is proved to have good linear relation for detecting NADH, wherein the linear relation is 0.99. As can be seen from fig. (f): under the same condition, the fluorescence intensity for detecting NADPH and NADH is far higher than that of other substances, which shows that the fluorescent probe has good selectivity for NADPH and NADH. Meanwhile, the result of FIG. 4 also shows that the fluorescent probe of the present invention belongs to an open type fluorescent probe, and has a higher signal-to-noise ratio.
Example 3
Cell experiments: cell experiments were performed on the fluorescent probes prepared in example 1
(1) Confocal fluorescence detection of NAD (P) H in different living cells
FIG. 5 is an image of cells detecting NAD (P) H in different living cells. Wherein: (a) as a result of imaging after incubating normal cells (7702), human cervical cancer cells (Hela), and human liver cancer cells (HepG2) with 10. mu.M of Compound 1 for 1 hour, respectively. (b) The average fluorescence intensity of three types of cells, namely normal cells (7702), human cervical cancer cells (Hela) and human liver cancer cells (HepG 2); normal cells (7702) were defined as 1.0 as a control group and data were expressed as mean ± SD (n ═ 3).
In the cell experiment (fig. 5), when the probe was added to the normal cell (7702), the human cervical cancer cell (Hela) and the human liver cancer cell (HepG2), red fluorescence was generated, but the fluorescence intensity in the Hela and HepG2 cells was relatively higher than that in the normal cell (7702). It is demonstrated that compound 1 (the fluorescent probe of the present invention) can detect the levels of NAD (P) H in different cells, and the levels of NAD (P) H in cancer cells are found to be higher than those in normal cells.
(2) Confocal fluorescence detection of NAD (P) H in Hela cells at different glucose concentrations
FIG. 6 is an image of Hela cells at different glucose concentrations. (a) Imaging was performed after incubating Hela cells with 5, 10, 20mM glucose for 15 min, respectively, followed by 10 μ M compound 1 for 15 min; (b) the mean fluorescence intensity of Hela cells under different concentrations of glucose; the fluorescence intensity of 5mM glucose pre-incubated in the cells was defined as 1.0 as a control, and the data are expressed as mean. + -. SD (n-3).
As can be seen from fig. 6: when glucose was added at different concentrations to Hela cells having the highest average fluorescence intensity, the fluorescence intensity in Hela cells gradually increased as the glucose concentration increased. Indicating that NAD (P) H is produced during glycolysis of the cell.
From the above results it can be derived: the fluorescent probe can be used for the follow-up research of cancer.
Example 4
Mouse in vivo experiments: the mother solution was diluted to 500. mu.M with a probe having a concentration of 2mM, and 10. mu.l was aspirated and injected into mice via tail vein. Fluorescence imaging in mice was performed after 0, 20, 30 and 50 minutes, respectively.
FIG. 7 is a photograph of in vivo fluorescence imaging of mice. It can be seen from the figure that: the fluorescence intensity in the mouse gradually weakens from weak to strong along with the increase of time, which shows that the probe can detect NAD (P) H in the mouse and can be used for in vivo imaging.
Claims (9)
1. The near-infrared fluorescent probe is characterized by being 3- (9- (2- ((acetoxy methoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxy methylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate, and having a structural formula as follows:
2. the method for preparing the near-infrared fluorescent probe of claim 1, which is characterized by comprising the following steps:
step 1, reacting 4-diethylamino keto acid with cyclohexanone, concentrated sulfuric acid and perchloric acid to generate 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate;
step 2, reacting the 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate generated in the step 1 with 3-quinolinecarboxaldehyde to generate 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate;
step 3, reacting the 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate salt generated in the step 2 with methyl trifluoromethanesulfonate to generate 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate;
and 4, reacting the 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate generated in the step 3 with methyl bromoacetate to generate 3- (9- (2- ((acetoxy methoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxymethylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate, and obtaining the near-infrared fluorescent probe.
3. The method for preparing a near-infrared fluorescent probe according to claim 2, which is characterized in that the method specifically comprises the following steps:
step 1, adding cyclohexanone into concentrated sulfuric acid with the mass fraction of 98% dropwise at 0 ℃, stirring, then adding 4-diethylamino keto acid in batches, continuing stirring at 90-120 ℃, stopping the reaction after the reaction is carried out for 3-5 hours, pouring the final reaction mixture into water with the temperature of 0 ℃, adding 70% perchloric acid, carrying out suction filtration on the precipitated precipitate, and washing with water with the temperature of 0 ℃ to obtain an orange-red solid compound, namely 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate;
step 2, sequentially adding 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate, 3-quinolinecarboxaldehyde and piperidine into a reaction container, adding absolute ethyl alcohol to dissolve, heating the dissolved mixture to 80 ℃ to perform reflux, reacting overnight, cooling to 0 ℃ after the reaction is finished and the temperature is recovered to room temperature, standing for 2-4 h to precipitate a purple solid, washing the solid with tert-butyl methyl ether, and drying the solid to obtain a compound: 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate;
and 3, adding methyl trifluoromethanesulfonate into dichloromethane, adding 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate, stirring at room temperature for 3 hours, stopping reaction, cooling to separate out a purple solid, performing suction filtration, washing with dichloromethane, and drying to obtain a compound: 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate;
step 4, adding 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate and N, N-diisopropylethylamine into a reaction vessel, adding acetonitrile, uniformly mixing, then adding methyl bromoacetate into the mixed solution, stirring for 48 hours under the protection of argon, and separating by column chromatography to obtain a compound: and 3- (9- (2- ((acetoxy methoxy) carbonyl) phenyl) -6- (diethylamino) -2, 3-dihydroxy methylene-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate to obtain the near-infrared fluorescent probe.
4. The method for preparing a near-infrared fluorescent probe according to claim 3, characterized in that: in the step 1, cyclohexanone, concentrated sulfuric acid with the mass fraction of 98%, 4-diethylamino keto acid, perchloric acid with the mass fraction of 70% by volume: volume: quality: volume 6.6 mL: 72mL of: 9.82 g: 7.9 mL; the final reaction mixture was poured into 200mL of 0 ℃ water.
5. The method for preparing a near-infrared fluorescent probe according to claim 3, characterized in that: in the step 2, the mass of the 9- (2-carboxyphenyl) -6- (diethylamino) -1,2,3, 4-tetrahydroxy perchlorate, 3-quinolinecarboxaldehyde, piperidine and absolute ethyl alcohol is as follows: quality: volume: volume 2 g: 1 g: 0.04 mL: 35 mL.
6. The method for preparing a near-infrared fluorescent probe according to claim 3, characterized in that: the volume of the used amounts of dichloromethane, methyl trifluoromethanesulfonate and 9- (2-carboxyphenyl) -6- (diethylamino) -4- (quinoline-3-methylene) -1,2,3, 4-tetrahydroxy perchlorate in the step 3 is as follows: volume: mass 108 mL: 1.2 mL: 1.53 g.
7. The method for preparing a near-infrared fluorescent probe according to claim 3, characterized in that: the mass of the used amount of 3- (9- (2-carboxyphenyl) -6- (diethylamino) -2, 3-dihydroxymethyl-4 (1H) -methylene) -1-methylquinoline-1-perchlorate trifluoromethanesulfonate, N-diisopropylethylamine, acetonitrile and methyl bromoacetate in the step 4 is as follows: volume: volume: volume 60 mg: 0.124 mL: 2mL of: 0.1 mL.
8. The method for preparing a near-infrared fluorescent probe according to claim 3, characterized in that: the vacuum pump for suction filtration in the step 1 and the step 3, wherein the mobile phase of the column chromatography in the step 4 is dichloromethane: methanol 8: 1.
9. The near-infrared fluorescent probe of claim 1, which is used by: is used for preparing a reagent for detecting 1, 4-dihydronicotinamide adenine dinucleotide and phosphate thereof.
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