CN107987014A - Pyridine sulfonic acid inner salt compound and preparation method and application thereof - Google Patents
Pyridine sulfonic acid inner salt compound and preparation method and application thereof Download PDFInfo
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- CN107987014A CN107987014A CN201711324975.XA CN201711324975A CN107987014A CN 107987014 A CN107987014 A CN 107987014A CN 201711324975 A CN201711324975 A CN 201711324975A CN 107987014 A CN107987014 A CN 107987014A
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- pyridine
- sulfonic acid
- inner salt
- acid inner
- salt compound
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- KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 title claims abstract description 16
- -1 salt compound Chemical class 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 210000002569 neuron Anatomy 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000000523 sample Substances 0.000 claims description 19
- 239000003550 marker Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 150000003053 piperidines Chemical class 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003935 benzaldehydes Chemical class 0.000 claims description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 1
- 210000005013 brain tissue Anatomy 0.000 abstract description 8
- 210000001638 cerebellum Anatomy 0.000 abstract description 6
- 210000001320 hippocampus Anatomy 0.000 abstract description 6
- 210000001259 mesencephalon Anatomy 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- 239000007850 fluorescent dye Substances 0.000 abstract description 2
- MZRTWEBOYWBGCI-UHFFFAOYSA-N 3-(4-methylpyridin-1-ium-1-yl)propane-1-sulfonate Chemical compound CC1=CC=[N+](CCCS([O-])(=O)=O)C=C1 MZRTWEBOYWBGCI-UHFFFAOYSA-N 0.000 abstract 1
- YSDDPNWGLSGZRC-UHFFFAOYSA-N 4-[bis(2-hydroxyethyl)amino]benzaldehyde Chemical compound OCCN(CCO)C1=CC=C(C=O)C=C1 YSDDPNWGLSGZRC-UHFFFAOYSA-N 0.000 abstract 1
- 238000010226 confocal imaging Methods 0.000 abstract 1
- 210000004556 brain Anatomy 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 3
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 3
- 108090001090 Lectins Proteins 0.000 description 3
- 102000004856 Lectins Human genes 0.000 description 3
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 3
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 3
- 102000011931 Nucleoproteins Human genes 0.000 description 3
- 108010061100 Nucleoproteins Proteins 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 3
- 239000002523 lectin Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 108010089814 Plant Lectins Proteins 0.000 description 2
- 239000011358 absorbing material Substances 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 125000005909 ethyl alcohol group Chemical group 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000004326 gyrus cinguli Anatomy 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003726 plant lectin Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 1
- 108700005000 Glial Fibrillary Acidic Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 102100021118 Microtubule-associated protein 2 Human genes 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- 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
-
- 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
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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
- C09K2211/1007—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
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Materials Engineering (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a pyridine sulfonic acid inner salt compound and a preparation method and application thereof, wherein the pyridine sulfonic acid inner salt compound has a structural formula as follows:the invention adopts 4- (bis (2-hydroxyethyl) amino) benzaldehyde with strong electron donating capability and higher reaction activity to react with 4-methyl-1- (3-sulfopropyl) pyridinium to prepare a pyridine sulfonic acid inner salt compound S L-Neu with a D-pi-A type conjugated structure with good water solubility and biocompatibility, and performs laser confocal imaging by taking mouse brain tissues and spinal tissues as materials, and the result shows that S L-Neu can specifically mark nerve cells distributed in a mouse body (cerebellum, midbrain, gyrus, hippocampus and spine), and can be used as a near-infrared fluorescent probe for specifically marking the nerve cells.
Description
Technical field
The present invention relates to a kind of infrared fluorescence probes and preparation method thereof, specifically a kind of pyridine-sulfonic acid inner salt chemical combination
Thing and its preparation method and application.
Background technology
Nerve cell (Neuron) is structural units and the functional unit of higher mammal nervous system, and be otherwise known as nerve
Member.Contain substantial amounts of neuron in nervous system, it is estimated that, containing about 100,000,000,000 neurons in mankind's central nervous system, only
It just there are about 14,000,000,000 in cerebral cortex.Substantial amounts of nerve cell aggregation plays receiving, integration, conduction and output in the brain
The effect of information, neuronal populations realize cognition and the analytic function of brain by the information exchange of each neuron.In recent years,
More and more researchs show：The 26S Proteasome Structure and Function of nerve cell and some central nervous systems such as Alzheimer disease, pa gold
Sen Shi diseases etc. have close contact.Therefore, a kind of fluorescence probe of energy specific marker nerve cell is designed to neurology department
Learn, molecular immunology, or even life science suffers from highly important meaning.
At present, business nerve cell fluorescent marker be mostly antibody or bioprotein (such as：NSE、NeuN、MAP-2、DCX、
GFAP etc.).Photobleaching phenomenon easily occurs for most of antibody class nerve cell fluorescent markers, utilizes high energy laser beam irradiating cell
A certain specific region, irreversible be quenched can occur for the fluorescence molecule in the region.With the development of science and technology, infrared hair
The two-photon absorbing material of light (long wave excitation) played an important role in many ambits, particularly in life science
Field.Two-photon absorbing material has that tissue autofluorescence is weak, self-absorption is few, tissue penetration is strong low with photobleaching degree etc.
Advantage, suitable for two-photon fluorescence microtechnic, can more effectively mark the nerve cell in organism.With good biological
Compatibility and it is capable of that the infrared fluorescence probes of specific marker nerve cell are also fresh for report, and there is an urgent need for probe at present.
The content of the invention
Based on considerations above, the present invention is intended to provide a kind of pyridine-sulfonic acid inner salt compound and its preparation method and application.
4- (double (2- ethoxys) amino) benzaldehydes used with strong electron donation and compared with high reaction activity and 4- methyl of the invention-
1- (3- sulfonic groups propyl group) pyridine is reacted, and is prepared with good aqueous solubility and the D-π-A types of biocompatibility conjugation
The pyridine-sulfonic acid inner salt compound (SL-Neu) of structure, and using Mice brain tissues and its vertebrae tissue laser copolymerization is carried out as material
Jiao's imaging.The results show SL-Neu being capable of (cerebellum, midbrain, gyrus, hippocampus, vertebra) distribution in specific marker Mice Body
Nerve cell, can be as a kind of near infrared fluorescent probe of specific marker nerve cell.
Pyridine-sulfonic acid inner salt compound of the present invention, is abbreviated as SL-Neu, its structural formula is：
The preparation method of pyridine-sulfonic acid inner salt compound SL-Neu of the present invention, is using absolute ethyl alcohol as solvent, in piperidines
In the presence of that 4- (double (2- ethoxys) amino) benzaldehydes are mixed with 4- methyl isophthalic acids-(3- sulfonic groups propyl group) pyridine to progress is anti-
Should, obtain target product SL-Neu.
Specifically comprise the following steps：
By 4- (double (2- ethoxys) amino) benzaldehyde (1.80g, 10mmol), 4- methyl isophthalic acids-(3- sulfonic groups propyl group) pyrrole
Pyridine (2.15g, 10mmol) is dissolved in 30mL absolute ethyl alcohols, and 5 drop piperidines are added dropwise to reaction system, stir to back flow reaction
24h, there is red solid precipitation, filters, is washed with ethanol, up to red crystalline thing SL-Neu (3.40g), yield 87%.
Synthetic route of the present invention is as follows：
The purposes of pyridine-sulfonic acid inner salt compound SL-Neu of the present invention, is as the infrared glimmering of specific marker nerve cell
The application of light probe.
Compared with the prior art, beneficial effects of the present invention are embodied in：
1st, hydroxyl and sulfonate are introduced in target molecule SL-Neu of the present invention, can both adjust intramolecular push-and-pull electronic energy
Power, so as to produce nonlinear optical property, and can largely increase the water solubility and biocompatibility of probe, be easy to implement
In the application of organism.
2nd, SL-Neu of the present invention has good permeability of cell membrane, has near infrared region (900nm) larger effective
Two photon absorption cross section, the light of this long wave excitation short wavelength emissions have the spy small to cell and tissue damage, penetrating power is strong
Point.
3rd, the nerve cell that SL-Neu can be in specific marker Mice brain tissues and vertebra.At present, there is no similar
Fluorescence probe, has stronger commercial value.
4th, the synthesis material of SL-Neu is easy to get, and cost is low, and reaction condition is gentle, and processing is simple, and possessing makes its commercialized
Advantage.
Brief description of the drawings
Fig. 1 is the crystal structure figure of SL-Neu, and No. CCDC is 1534913.It is one to illustrate pyridine-sulfonic acid inner salt SL-Neu
The clear and definite new compound of structure.
Fig. 2 is uv-visible absorption spectra and fluorescence spectrum of (a) probe in PBS buffer solutions, illustrates that SL-Neu exists
There is stronger fluorescence at 593nm.(b) effective two photon absorption cross section figure of the probe in PBS buffer solutions.Can from figure
Go out：During using 900nm as excitation wavelength, the effective two photon absorption cross sections of SL-Neu reach maximum.It is near to illustrate that SL-Neu can be used as
Infrared two-photon fluorescence probe.(c) water solubility (related coefficient) with (d) probe is tested, and is shown in figure with SL-Neu concentration
Increase, absorption intensity is sequentially increased, and water-soluble related coefficient is up to 99.95%.Illustrate probe SL-Neu good water solubilities, can be fine
Be applied to organism.
Fig. 3 is the region and each position that nerve cell is distributed in probe molecule SL-Neu specific marker Mice brain tissues
Partial enlarged view：Cerebellum (Cerebellum), midbrain (Midbrain), gyrus (Cingulate gyrus), hippocampus
(Hippocampus).Show the nerve cell being distributed in probe SL-Neu energy specific marker brain tissues.
Fig. 4 is probe SL-Neu and glial fibrillary acidic albumen (GFAP) (mark of Activation of Astrocytes
Thing), plant agglutinin of blood (Lectin) (capillary label), microtubule associated protein (MAP2) (nerve cell dendron mark
Thing), common location two-photon (900nm exciting lights) fluorescence of nerve nucleus NeuN nucleoprotein (NeuN) (nerve cell core label) shows
Micro- image, it can be found that probe only with NeuN nucleoprotein in Mouse brain and the common location kissing of spinal cord cell
Close.Show that probe plays the effect that it marks nerve cell, i.e. SL- by specifically binding nerve cell nucleoprotein NeuN
Neu can be as a kind of infrared fluorescence probes for marking nerve cell.
Embodiment
1st, the synthesis of SL-Neu
By 4- (double (2- ethoxys) amino) benzaldehyde (1.80g, 10mmol), 4- methyl isophthalic acids-(3- sulfonic groups propyl group) pyrrole
Pyridine (2.15g, 10mmol) is dissolved in 30mL absolute ethyl alcohols, and 5 drop piperidines are added dropwise to reaction system, stir to back flow reaction
24h, there is red solid precipitation, filters, is washed with ethanol, up to red crystalline thing SL-Neu (3.40g), yield 87%.
SL-Neu：1H NMR(400MHz,d6- DMSO) δ 8.76 (d, J=6.3Hz, 2H), 8.04 (d, J=6.2Hz, 2H),
7.90 (d, J=16.1Hz, 1H), 7.56 (d, J=8.4Hz, 2H), 7.14 (d, J=16.0Hz, 1H), 6.79 (d, J=
8.4Hz, 2H), 4.83 (s, 2H), 4.54 (t, J=6.6Hz, 2H), 3.72-3.46 (m, 8H), 2.43 (t, J=7.0Hz, 2H),
2.26–2.10(m,2H).13C NMR(100MHz,d6- DMSO) δ=153.64,150.27,143.53,142.10,130.38,
122.21,121.97,116.59,111.47,58.18,57.89,53.77,47.05,38.65,
27.11.Anal.Calcd.for C19H24N2O4S:C,60.62；H,6.43；N, 7.44%.Found:C,60.85；H,6.618；
N, 7.455%.IR (KBr, cm-1):3371(m),3045(m),2905(m),2871(m),1643(m),1589(s),1524
(s), 1387 (s), 1167 (s), 1040 (w), 967 (w), 837 (m) .M.p.=228 DEG C of .MALDI-TOF:m/z,cal:
376.15,found:377.07([M+H]+)。
2nd, the specific marker experiment of SL-Neu
Take mouse brain to be fixed with 4% paraformaldehyde, be put into 30% sucrose solution, utilize freezing microtome section technology, system
Into 20 μm of brain tissue slice.Add SL-Neu (10-5Mol/L 0.5h) is incubated at room temperature in brain section, is washed twice with PBS.Swash
The burnt developing result of light copolymerization shows, the nerve cell that SL-Neu can be in specific marker mouse brain；Meanwhile, it is capable to indicate to move
The region that nerve cell is distributed in thing brain tissue is such as：Cerebellum (Cerebellum), midbrain (Midbrain), gyrus
(Cingulate gyrus), hippocampus (Hippocampus).
3rd, SL-Neu and Commercial optical dyestuff common location are tested
Using mouse brain, vertebra section carry out immunofluorescence processing, by SL-Neu respectively with nerve cell core label
NeuN(1:300), nerve cell dendron label MAP2 (1:300), astrocyte marker thing GFAP (1:500) it is total to
Detection and localization.The result shows that：SL-Neu only has high coincidence factor with nerve cell core label NeuN.
4th, SL-Neu and brain tissue capillary label common location are tested
By mouse brain slice (20 μm) and plant agglutinin of blood Lectin (capillary label), containing 5%CO2Gas
0.5h is incubated at 37 DEG C in the incubator of body and 95% air, is washed twice with PBS, adds SL-Neu (10-5Mol/L) in room temperature
Lower incubation 0.5h, is washed twice with PBS.Bio-imaging, the results show are carried out using Laser Scanning Confocal：SL-Neu and blood capillary
Pipe label Lectin is without coincidence phenomenon.
Claims (4)
1. a kind of pyridine-sulfonic acid inner salt compound, it is characterised in that its structural formula is：
A kind of 2. preparation method of the pyridine-sulfonic acid inner salt compound described in claim 1, it is characterised in that：
Be using absolute ethyl alcohol as solvent, in the presence of piperidines by 4- (double (2- ethoxys) amino) benzaldehydes and 4- methyl isophthalic acids-
The mixing of (3- sulfonic groups propyl group) pyridine is reacted, and obtains target product.
3. preparation method according to claim 2, it is characterised in that specifically comprise the following steps：
4- (double (2- ethoxys) amino) benzaldehyde 10mmol, 4- methyl isophthalic acid-(3- sulfonic groups propyl group) pyridine 10mmol is molten
5 drop piperidines are added dropwise in absolute ethyl alcohol, to reaction system in solution, stir to back flow reaction 24h, there is red solid precipitation, filter, use
Ethanol washs, and it is target product to obtain red crystalline thing.
A kind of 4. purposes of the pyridine-sulfonic acid inner salt compound described in claim 1, it is characterised in that：The pyridine-sulfonic acid inner salt
Application of the compound as the infrared fluorescence probes of specific marker nerve cell.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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