CN117700341A - O (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe and preparation method and application thereof - Google Patents
O (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe and preparation method and application thereof Download PDFInfo
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- CN117700341A CN117700341A CN202311707494.2A CN202311707494A CN117700341A CN 117700341 A CN117700341 A CN 117700341A CN 202311707494 A CN202311707494 A CN 202311707494A CN 117700341 A CN117700341 A CN 117700341A
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- fluorescent probe
- benzaldehyde derivative
- hydrazine
- toluenesulfonamido
- fluorescence
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- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 68
- QLQGABDYGHEFOM-UHFFFAOYSA-N n-(2-formylphenyl)-4-methylbenzenesulfonamide Chemical class C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC=C1C=O QLQGABDYGHEFOM-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 50
- 210000004027 cell Anatomy 0.000 claims description 18
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 13
- 241000252212 Danio rerio Species 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 238000001514 detection method Methods 0.000 claims description 11
- 210000002472 endoplasmic reticulum Anatomy 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 229960003350 isoniazid Drugs 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000004060 metabolic process Effects 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 3
- KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical compound [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 2
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 claims description 2
- KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 claims description 2
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims 1
- 238000000967 suction filtration Methods 0.000 claims 1
- -1 (p-toluenesulfonamide) benzaldehyde derivative Chemical class 0.000 abstract description 22
- 239000000523 sample Substances 0.000 abstract description 16
- 230000007423 decrease Effects 0.000 abstract 1
- 238000000799 fluorescence microscopy Methods 0.000 description 31
- 238000010586 diagram Methods 0.000 description 25
- 238000012632 fluorescent imaging Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 238000001917 fluorescence detection Methods 0.000 description 4
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- 239000000975 dye Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 229910020366 ClO 4 Inorganic materials 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000036267 drug metabolism Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
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- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000004604 Blowing Agent Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 235000015842 Hesperis Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000012633 Iberis amara Nutrition 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000030583 endoplasmic reticulum localization Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 231100000003 human carcinogen Toxicity 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011897 real-time detection Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- 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
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- 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"
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- 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
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
- G01N21/6458—Fluorescence microscopy
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- 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
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
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- 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
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1014—Carbocyclic compounds bridged by heteroatoms, e.g. N, P, Si or B
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
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- Animal Behavior & Ethology (AREA)
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Abstract
The invention provides an o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe, and a preparation method and application thereof, and belongs to the technical field of fluorescent probes. The structural formula of the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe provided by the invention is
Description
Technical Field
The invention relates to the technical field of fluorescent probes, in particular to an o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe, and a preparation method and application thereof.
Background
Hydrazine (N) 2 H 4 ) Is a high-activity alkali and strong reducing agent. It is widely used in industry as a blowing agent, a preservative and a gas-generating agent, as well as fuel for satellites and rockets. It is also widely used in the production of pesticides, pharmaceuticals, emulsifiers, textile dyes and many other important chemicals. Although in common use, hydrazine is considered highly toxic because it is metabolized to toxic free radical species, which can cause serious damage to the liver, lung, kidneys and central nervous system. Due to these effects, N 2 H 4 Classified as a human carcinogen, its low Threshold Limit (TLV) is 10ppb. In addition, some medicines such as isoniazid and the like are taken excessively, and can be decomposed into hydrazine in vivo, so that the hydrazine is harmful to human bodies. Clearly, there is an urgent need to develop efficient and reliable trace hydrazine detection assay methods.
In recent years, N has been detected in vitro and in vivo 2 H 4 Has attracted considerable attention. In particular to a fluorescence analysis method based on a fluorescence probe, which has the remarkable advantages of high sensitivity, simple operation and real-time detection. Although N with high selectivity and high sensitivity has been designed 2 H 4 Fluorescent probes, but most of the probes reported are either "off-on" or "on-off" and may be affected by environmental factors such as excitation power, fluorescence decay, and probe concentration. In contrast, the ratio probe measures the fluorescence emission intensity at two wavelengths, and the ratio can be used as a built-in correction to overcome the influence of the environmental factors. However, existing N 2 H 4 The ratio fluorescent probe has complex synthesis steps and purification procedures, and limits the further popularization and application. Thus, a ratio-type fluorescent probe with simple preparation was developed for N 2 H 4 Has important significance in rapid detection. Furthermore, today N targeting endoplasmic reticulum 2 H 4 The report of fluorescent probes is very limited.
Disclosure of Invention
In view of the above, the present invention aims to provide a fluorescent probe of o (p-toluenesulfonamide) benzaldehyde derivative, and a preparation method and application thereof 2 H 4 Exhibit high ratio fluorescent recognition performance.
In order to achieve the above object, the present invention provides the following technical solutions: an o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe with a structure shown in formula I:
in the invention, the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe with the structure shown in formula I is a ratio fluorescent probe, can selectively act on hydrazine under physiological conditions, changes the fluorescent color of a solution from green to blue, and presents a typical ratio fluorescent signal.
The invention also provides a preparation method of the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe, which is characterized in that 2-nitrobenzaldehyde, sodium methane sulfinate, sodium p-toluenesulfonate and sodium bisulfate are dissolved in water for heating and stirring reaction, and after the reaction is finished, precipitation is cooled, filtered and recrystallized, and the obtained white crystal is the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe.
In some embodiments, the molar ratio of 2-nitrobenzaldehyde, sodium methane sulfinate, sodium p-toluene sulfinate, and sodium bisulfite is (1-1.01): (1-1.02): (1-1.02): (3-3.06), preferably 1:1:1:3.
in some embodiments, the molar volume ratio of 2-nitrobenzaldehyde to water is (1-1.01) mmol:2mL, preferably 1mmol:2mL.
In some embodiments, the temperature of the heated stirred reaction is 60 ℃ for 2 hours.
In some embodiments, the recrystallization is recrystallization using ethanol.
The invention also provides application of the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe in hydrazine detection.
In some embodiments, the hydrazine includes endogenous hydrazine produced by exogenous hydrazine and drug isoniazid metabolism in the endoplasmic reticulum of living cells and in zebra fish.
The invention also provides a hydrazine detection method, which utilizes the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe to detect hydrazine.
In some embodiments, the hydrazine includes endogenous hydrazine produced by exogenous hydrazine and drug isoniazid metabolism in the endoplasmic reticulum of living cells and in zebra fish.
The beneficial technical effects are as follows:
1. the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe provided by the invention has the advantages that in various objects to be detected, the fluorescent probe has the effect of detecting the N 2 H 4 Exhibit high ratio fluorescent recognition performance. Probe pair N 2 H 4 The fluorescence response with high sensitivity and selectivity can be used for dual-channel detection of intracellular N by using a fluorescence sensing method of a laser confocal imaging technology 2 H 4 The concentration and the probe can target the endoplasmic reticulum of the cell, and have wide potential application value.
2. The invention prepares the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe through one-step reaction, the raw materials are easy to obtain, and the synthesis and post-treatment methods are simple.
Drawings
FIG. 1 shows a fluorescent probe of an o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 of the present invention 1 HNMR spectrogram;
FIG. 2 shows a fluorescent probe of an o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 of the present invention 13 CNMR spectrogram;
FIG. 3 is a mass spectrum of a fluorescent probe for an o (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 of the present invention, wherein an inset shows the crystal structure of the fluorescent probe for an o (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1;
FIG. 4 is a schematic illustration of an embodiment of the present inventionFluorescent probe of o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 (1X 10) - 5 mol/L) DMSO/H 2 O solution (1:1, v:v, pH=7.4) was added to 0.5X10 respectively -4 mol/L biological thiol (Cys, hcy, gsH), common ion (Br) - ，Cl - ，ClO 4 - ，ClO-，F - ，H 2 PO 4 - ，HPO 4 2- ，HSO 3 - ，HSO 4 - ，I - ，OAc - ，PO 4 3- ，PPi - ，SO 3 2- ，SO 4 2- ，Ag + ，Na + ，Zn 2+ ，Al 3+ ，Ca 2+ ，Cd 2+ ，Co 3+ ，Cr 3+ ，Fe 3+ ，Mg 2+ ，Mn 2+ ，Ni 2+ ，Pb 2+ ) And amine (pyridine, ethylenediamine, hydroxylamine hydrochloride and diethylamine), wherein the illustration is a fluorescent probe of o (p-toluenesulfonamide) benzaldehyde derivative and a fluorescent probe of o (p-toluenesulfonamide) benzaldehyde derivative +N under a 365nm ultraviolet lamp (excitation wavelength of 360 nm) 2 H 4 A change in solution color;
FIG. 5 shows a fluorescent probe (1X 10) of an o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 of the present invention - 5 PBS buffer (1X 10) in mol/L -2 mol/L, ph=7.4) at fluorescence intensity F 460 /F 530 Is a competitive histogram of (1);
FIG. 6 a shows a fluorescent probe (1X 10) of an o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 according to the present invention -5 mol/L) DMSO/H 2 O solution (1:1, v:v, ph=7.4) titrates different concentrations of N 2 H 4 B is the fluorescence intensity ratio F 460 /F 530 With N 2 H 4 A linear trend graph of concentration (excitation wavelength 360 nm);
FIG. 7 shows 1X 10 in HpeG 2 cells -5 mol/L the fluorescent probe of o- (p-toluenesulfonamide) benzaldehyde derivative prepared in example 1 was incubated with commercial mitochondrial-positioning dye ER-Tracker Red at 37℃for 30 minFluorescence imaging was then performed using an Olympus FV500-IX70 laser confocal microscope; wherein: a is a green channel fluorescence imaging diagram; b is a red channel fluorescence imaging image; c is a picture obtained by superposing a green channel and a red channel; d is a green channel and red channel fluorescence intensity scatter plot; e is the linear region intensity profile of the green and red channels;
FIG. 8 shows the fluorescent probe of o- (p-toluenesulfonamide) benzaldehyde derivative and exogenous N in HpeG 2 cells 2 H 4 And endogenous N produced by metabolism of the drug Isoniazid (INH) 2 H 4 Is a fluorescent imaging image of (2); the fluorescence Probe comprises a Probe group, a fluorescent Probe group and a fluorescent Probe group, wherein a, b, c, d and e in the Probe group are respectively a green channel fluorescent imaging diagram, a blue channel fluorescent imaging diagram, a picture after superposition of green channel fluorescent imaging and blue channel fluorescent imaging, a bright field diagram, a picture after superposition of green channel fluorescent imaging, blue channel fluorescent imaging and bright field fluorescent imaging; n (N) 2 H 4 F, g, h, i, j in the 50. Mu.M group are each the above fluorescent probe +N 2 H 4 (5×10 -5 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture; n (N) 2 H 4 K, l, M, N, o in 100. Mu.M groups are each the above fluorescent probe +N 2 H 4 (1×10 -4 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture; in INH group, p, q, r, s, t are the above fluorescent probe+isoniazid (1×10) -3 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture;
FIG. 9 shows the fluorescent probe of o- (p-toluenesulfonamide) benzaldehyde derivative and exogenous N in zebra fish 2 H 4 And endogenous N produced by metabolism of the drug Isoniazid (INH) 2 H 4 Is a fluorescent imaging image of (2);the fluorescence Probe comprises a Probe group, a fluorescent Probe group and a fluorescent Probe group, wherein a, b, c, d and e in the Probe group are respectively a green channel fluorescent imaging diagram, a blue channel fluorescent imaging diagram, a picture after superposition of green channel fluorescent imaging and blue channel fluorescent imaging, a bright field diagram, a picture after superposition of green channel fluorescent imaging, blue channel fluorescent imaging and bright field fluorescent imaging; n (N) 2 H 4 F, g, h, i, j in the 50. Mu.M group are each the above fluorescent probe +N 2 H 4 (5×10 -5 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture; n (N) 2 H 4 K, l, M, N, o in 100. Mu.M groups are each the above fluorescent probe +N 2 H 4 (1×10 -4 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture; in INH group, p, q, r, s, t are the above fluorescent probe+isoniazid (1×10) -3 mol/L) green channel fluorescence imaging diagram, blue channel fluorescence imaging diagram, green channel and blue channel fluorescence imaging superimposed picture, bright field diagram, green channel, blue channel and bright field fluorescence imaging superimposed picture.
Detailed Description
Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the invention described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present invention. The specification and examples are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
The technical scheme of the invention is conventional in the field, and the reagents or raw materials are purchased from commercial sources or are disclosed.
Example 1
The preparation method of the o- (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe in this embodiment is as follows:
2-nitrobenzaldehyde (151 mg,1 mmol), sodium methane sulfinate (102 mg,1 mmol), sodium p-toluene sulfinate (178 mg,1 mmol) and sodium hydrogen sulfite (312 mg,3 mmol) were dissolved in 2mL of water, and the reaction was stirred at 60℃for 3 hours at 800 rpm. And after the reaction is finished, cooling to separate out precipitate, filtering and recrystallizing with absolute ethyl alcohol to obtain white crystals, namely the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe. The yield thereof was found to be 40%.
Nuclear magnetic resonance analysis is carried out on the prepared o (p-toluenesulfonamide) benzaldehyde derivative by a nuclear magnetic resonance apparatus, and the result is as follows:
1 h NMR (400 MHz, DMSO-d 6) delta 10.57 (s, 1H, NH), 10.00 (s, 1H, CH), 7.80-7.83 (dd, 1H, ar-H), 7.57-7.61 (m, 3H, ar-H), 7.32-7.37 (m, 3H, ar-H), 7.17-7.19 (d, 1H, ar-H), 2.35 (s, 3H, CH 3). The specific nuclear magnetic resonance hydrogen pattern is shown in figure 1.
13 C NMR (100 MHz, DMSO-d 6) delta 144.07,140.71,136.85,135.48,130.20,129.79,128.25,127.21,124.21,124.07,119.32,21.41. The specific nuclear magnetic resonance carbon spectrum is shown in figure 2.
Mass spectrum ESI-MS: m/z= 274.0794 (negative mode, calc.for C) 14 H 13 NO 3 S, 275.0616). The specific mass spectrum is shown in figure 3. The single crystal structure is shown in the inset of fig. 3.
Example 2
Para (p-toluenesulfonamido) benzaldehyde derivative p-N 2 H 4 Optical property measurement of (c):
fluorescent probe of o- (p-toluenesulfonamido) benzaldehyde derivative prepared in example 1 (1X 10) -5 mol/L) DMSO/H 2 O solution (1:1, v:v, pH=7.4) was added to 0.5X10 respectively -4 mol/L biological thiol (Cys, hcy, gsH), common ion (Br) - ，Cl - ，ClO 4 - ，ClO-，F - ，H 2 PO 4 - ，HPO 4 2- ，HSO 3 - ，HSO 4 - ，I - ，OAc - ，PO 4 3- ，PPi - ，SO 3 2- ，SO 4 2- ，Ag + ，Na + ，Zn 2+ ，Al 3+ ，Ca 2+ ，Cd 2+ ，Co 3+ ，Cr 3+ ，Fe 3+ ，Mg 2+ ，Mn 2+ ，Ni 2+ ，Pb 2+ ) And organic amine (pyridine, ethylenediamine, hydroxylamine hydrochloride and diethylamine), and then analyzing with a fluorescence spectrometer (excitation wavelength of 360 nm), the obtained fluorescence screening chart is shown in fig. 4, and the competition bar chart is shown in fig. 5. As can be seen from FIGS. 4 and 5, the o (p-toluenesulfonamido) benzaldehyde derivative prepared by the present invention is used as a probe for N only 2 H 4 Has a distinct ratio of fluorescence responses, and fluorescence signals can be used forN 2 H 4 And not responsive to other analytes.
N can be obtained by titration spectrum calculation in FIG. 6 2 H 4 The detection limit was 2.6nM, and the linear detection range of the fluorescence spectrum was 10-125. Mu.M. Therefore, the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative prepared by the invention can be used for N 2 H 4 And (5) fluorescence quantitative detection.
Example 3
Fluorescent probes of o- (p-toluenesulfonamido) benzaldehyde derivatives in intracellular N 2 H 4 Is to be used in the detection experiment:
HpeG 2 cells 1X 10 -5 After co-incubation of the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe prepared in example 1 above and commercial endoplasmic reticulum localization dye ER-Tracker Red at 37℃for 30 minutes, a fluorescence imaging image of HpeG 2 cells was obtained, and specifically as shown in FIG. 7, the probe green channel fluorescence and ER-Tracker Red green channel fluorescence in HpeG 2 cells were substantially identical, with an overlap factor of 0.91. Therefore, the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative prepared in the embodiment 1 of the invention can target the endoplasmic reticulum of a cell.
HpeG 2 cells 1X 10 -5 mol/L the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe prepared in example 1 above was incubated at 37℃for 30 minutes and then subjected to fluorescence imaging using an Olympus FV500-IX70 laser confocal microscope; using 1X 10 -5 After pretreatment of HpeG 2 cells with mol/L fluorescent probe for 30 minutes, 5X 10 cells were added respectively -5 mol/L and 1X 10 -4 mol/LN 2 H 4 After an additional 30 minutes incubation, fluorescence imaging was performed using an Olympus FV500-IX70 laser confocal microscope, as shown in particular in fig. 8. After incubating the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe in HpeG 2 cells, the blue channel is non-fluorescent and the green channel is strong in fluorescence. And after re-hatching, the fluorescence of the green channel is obviously reduced, the fluorescence of the blue channel is obviously enhanced, and the fluorescence of the green channel is enhanced and N 2 H 4 Concentration positive correlation, it is demonstrated that the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe prepared in example 1 of the present invention can be used for exogenous N in the endoplasmic reticulum of cells 2 H 4 Is a ratio fluorescence detection of (2). HpeG 2 cells were first incubated 1X 10 -3 mol/L endogenous N 2 H 4 The green channel has almost no fluorescence and the blue channel has strong fluorescence after the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative is hatched again by the stimulant INH, which proves that the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative prepared in the example 1 of the invention can be used for endogenous N generated by drug metabolism in the endoplasmic reticulum of the cell 2 H 4 Is a ratio fluorescence detection of (2).
Example 4
O- (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe in zebra fish body N 2 H 4 Is to be used in the detection experiment:
1X 10 zebra fish -5 mol/L the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe prepared in example 1 above was incubated at 37℃for 30 minutes and then subjected to fluorescence imaging using an Olympus FV500-IX70 laser confocal microscope; using 1X 10 -5 After the zebra fish is pretreated by mol/L fluorescent probe for 30 minutes, 5 multiplied by 10 is added -5 mol/L and 1X 10 -4 mol/LN 2 H 4 After an additional 30 minutes incubation, fluorescence imaging was performed using an Olympus FV500-IX70 laser confocal microscope, as shown in particular in fig. 9. After incubation of o- (p-toluenesulfonamide) benzaldehyde derivative fluorescent probes in zebra fish, the blue channel is non-fluorescent and the green channel is strong in fluorescence. And re-hatching N 2 H 4 The fluorescence of the post-green channel is obviously reduced, the fluorescence of the blue channel is obviously enhanced, and the fluorescence of the green channel is enhanced and N 2 H 4 Concentration positive correlation shows that the o (p-toluenesulfonamide) benzaldehyde derivative fluorescent probe prepared in the example 1 can be used for exogenous N in zebra fish body 2 H 4 Is a ratio fluorescence detection of (2). Zebra fish first hatching 1X 10 -3 mol/L endogenous N 2 H 4 The green channel has almost no fluorescence and the blue channel has strong fluorescence after the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative is hatched again by the stimulant INH, which proves that the fluorescent probe of the o (p-toluenesulfonamide) benzaldehyde derivative prepared in the example 1 of the invention can be used for endogenous N generated by drug metabolism in zebra fish bodies 2 H 4 Ratio fluorescence detection of (2)。
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. An o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe with a structure shown in formula I:
2. the method for preparing the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe according to claim 1, which is characterized in that 2-nitrobenzaldehyde, sodium methane sulfinate, sodium p-toluenesulfonate and sodium bisulfate are dissolved in water for heating and stirring reaction, and after the reaction is finished, precipitation is cooled and separated out, suction filtration and recrystallization are carried out, and the obtained white crystal is the o (p-toluenesulfonamido) benzaldehyde derivative fluorescent probe.
3. The preparation method according to claim 2, wherein the molar ratio of 2-nitrobenzaldehyde, sodium methane sulfinate, sodium p-toluene sulfinate and sodium bisulphite is (1-1.01): (1-1.02): (1-1.02): (3-3.06).
4. A process according to claim 2 or 3, characterized in that the molar volume ratio of 2-nitrobenzaldehyde to water is (1-1.01) mmol:2mL.
5. The method according to any one of claims 2 to 4, wherein the temperature of the heating and stirring reaction is 60 ℃ for 2 hours.
6. The method according to any one of claims 2 to 5, wherein the recrystallization is recrystallization using ethanol.
7. Use of the fluorescent probe of o- (p-toluenesulfonamide) benzaldehyde derivative according to claim 1 in hydrazine detection.
8. The use according to claim 7, wherein the hydrazine comprises exogenous hydrazine in the endoplasmic reticulum of living cells and endogenous hydrazine produced by metabolism of the drug isoniazid in zebra fish.
9. A method for detecting hydrazine, wherein the fluorescent probe of o- (p-toluenesulfonamido) benzaldehyde derivative according to claim 1 is used for detecting hydrazine.
10. The method of claim 9, wherein the hydrazine comprises exogenous hydrazine in the endoplasmic reticulum of living cells and endogenous hydrazine produced by metabolism of the drug isoniazid in zebra fish.
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