CN107253965B - FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin - Google Patents
FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin Download PDFInfo
- Publication number
- CN107253965B CN107253965B CN201710516982.3A CN201710516982A CN107253965B CN 107253965 B CN107253965 B CN 107253965B CN 201710516982 A CN201710516982 A CN 201710516982A CN 107253965 B CN107253965 B CN 107253965B
- Authority
- CN
- China
- Prior art keywords
- yellow solid
- fluorine boron
- molecule
- fret
- cumarin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002866 fluorescence resonance energy transfer Methods 0.000 title claims abstract description 29
- FXURYRWDOBBQLX-UHFFFAOYSA-N N1C=CC=C1.[B].[F] Chemical class N1C=CC=C1.[B].[F] FXURYRWDOBBQLX-UHFFFAOYSA-N 0.000 title claims abstract description 14
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims abstract description 10
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 title claims abstract description 8
- FSOGIJPGPZWNGO-UHFFFAOYSA-N Meomammein Natural products CCC(C)C(=O)C1=C(O)C(CC=C(C)C)=C(O)C2=C1OC(=O)C=C2CCC FSOGIJPGPZWNGO-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 238000010189 synthetic method Methods 0.000 title claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000007787 solid Substances 0.000 claims abstract description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 9
- 238000004440 column chromatography Methods 0.000 claims abstract description 8
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 5
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000926 separation method Methods 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000012265 solid product Substances 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910006124 SOCl2 Inorganic materials 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 238000001704 evaporation Methods 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 abstract description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 abstract description 4
- 238000001917 fluorescence detection Methods 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000975 dye Substances 0.000 description 6
- 238000012546 transfer Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 241000522215 Dipteryx odorata Species 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000010226 confocal imaging Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000006862 quantum yield reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101710094902 Legumin Proteins 0.000 description 1
- LIQLLTGUOSHGKY-UHFFFAOYSA-N [B].[F] Chemical compound [B].[F] LIQLLTGUOSHGKY-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- NEKNNCABDXGBEN-UHFFFAOYSA-L disodium;4-(4-chloro-2-methylphenoxy)butanoate;4-(2,4-dichlorophenoxy)butanoate Chemical compound [Na+].[Na+].CC1=CC(Cl)=CC=C1OCCCC([O-])=O.[O-]C(=O)CCCOC1=CC=C(Cl)C=C1Cl NEKNNCABDXGBEN-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000006081 fluorescent whitening agent Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000000990 laser dye Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000010048 yiguan Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
-
- 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
-
- 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
- A61K49/0039—Coumarin dyes
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
- C09K2211/1055—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms with other heteroatoms
-
- 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
- C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
Abstract
The present invention relates to one kind FRET molecule and its synthetic method based on fluorine boron pyrroles and cumarin.When prepared by the FRET molecule, first it is stirred at room temperature to obtain yellow solid in thionyl chloride as raw material using coumaric acid.Then in dichloromethane solution, yellow solid is further reacted with propargyl ammonia and triethylamine stirring at normal temperature, the product column chromatography for separation obtained after filtering purifies to obtain yellow solid.It further reacts to obtain final goal compound with fluorine boron pyrroles, cuprous iodide and palladium catalyst.The compound has preferable chemistry, photostability, has big stoke shift, is suitable for the intracorporal fluorescence detection of biology, can avoid autofluorescence interference in organism.This kind FRET molecule prepared by the present invention can be used for the fields such as life science and Supramolecular photochemistry, and application prospect is extensive.
Description
Technical field
The present invention relates to one kind FRET molecule based on cumarin and fluorine boron pyrroles's fluorogen.
Background technique
Fluorescence resonance energy transfer (Fluorescence resonance energy transfer, FRET) refers to two
In a different fluorogen, (generally less than when the distance between Spectral matching and two fluorogens is suitable), Ke Yiguan
The phenomenon that fluorescent energy is shifted from donor to receptor is observed, i.e., when being excited with the excitation wavelength of donor, the glimmering of receptor can be observed
Light emitting.If acceptor fluorescence quantum yield is zero, energy transfer fluorescent occurs and is quenched；If acceptor is also a kind of fluorescence
Emitter then shows the fluorescence of receptor.Molecule with fluorescence resonance energy transfer is widely used at present, it can be used for
Fluorescent molecule detection, it is small to make up conventional fluorescent probe molecule stoke shift, it is lacked vulnerable to what autofluorescence in organism interfered
It falls into；The light trapping antenna that solar energy is converted into chemical energy can also be used as, because more fluorogens make its absorption spectrum significantly
It widens.Fluorescence resonance energy transfer (FRET) molecule has manifested most important in the fields such as life science and Supramolecular photochemistry
Irreplaceable effect.Therefore, the exploitation for being able to achieve the FRET molecule of fluorescence resonance energy transfer is the previous urgent need of mesh
It wants.But building is not easy to based on the molecule of fluorescence resonance energy transfer (FRET), on the one hand to consider fluorogenic donor and receptor
Matching degree；On the other hand to consider the connection type and connection distance of two fluorogens.
Fluorine boron pyrroles's fluorochrome has very excellent photochemistry physical property, shows the following aspects: tool
There is higher molar extinction coefficient；High fluorescence quantum yield；The spectral property of dyestuff is highly stable, is not easily susceptible to solvent polarity
With the influence of pH value；The fluorescence spectrum peak width of dyestuff is relatively narrow, so that dyestuff detects more when being applied to analysis field
It is sensitive；Dyestuff photostability with higher, will not because of stimulated luminescence during fluorescence analysis irradiation and lead to dyestuff knot
The rapid light degradation of structure, to ensure that the variation of spectral signal only derived from examined sample.These excellent properties make
The fluorogen is swift and violent in the application development of organic functional material, has become develop one of fluorogen of greatest concern at present.Tonka-bean
Element is due to special molecular structure, available to have difference by the modification of different location substituent group on coumarin ring
The absorption of range and fluorescence emission wavelengths, to show different colours and the derivative with strong fluorescence, in addition to being used as extensively
Outside fluorescent whitening agent, fluorescent dye and laser dye, since with preferable photoelectric properties, coumarin kind compound goes back quilt in the recent period
Applied to the fields such as fluorescence probe in organic photosensitive dyestuff and the bioprotein research of electroluminescent material solar battery.
Most important also most crucial part is exactly the selection of donor and receptor, fluorogen fluorine boron in fluorescence resonance energy transfer
Pyrroles and the excellent photochemistry and photophysical property of cumarin make it be very suitable for as FRET molecule for receptor, and it is fragrant
Legumin launch wavelength is at 450-500 nanometer one than wider range, and fluorine boron pyrroles fluorogen has just in this position
Therefore strong absorption finds a suitable connection type and connection distance has connected cumarin with fluorine boron pyrroles's fluorogen
To make it possible to achieve the efficient transfer of fluorescence resonance energy.
Summary of the invention
The present invention provides one kind FRET molecule based on fluorine boron pyrroles and cumarin, general structure is such as shown in (I):
Wherein, R=-H or
The second object of the present invention is to provide following method to realize:
A, 7- dimethylamino -2- oxygen -2H-3- coumaric acid is dissolved in SOCl2In solution.The reaction solution is in nitrogen protection
Under the conditions of be stirred at room temperature 3 hours.Filtering, ether washing precipitating, obtains yellow solid.It is not further processed and is immediately available in next step
Reaction.
B, the yellow solid that a step obtains is dissolved in dichloromethane solvent, the propargyl ammonia of 1.1 times of moles is added
With the triethylamine of 2.2 times of moles, stirring at normal temperature, TLC determines reaction end, filtering, vacuum rotary steam.Column chromatography for separation obtains yellow
Solid product.
C, the yellow solid product for 1.2 times of moles for obtaining fluorine boron azole derivatives and b step, 0.05 times of mole
Cuprous iodide, 0.02 times of mole dichloro two (triphenyl phosphorus) palladium be added to the in the mixed solvent of triethylamine and tetrahydrofuran,
After argon gas protects 40 DEG C of oil bath heating, reaction 2 hours.Cooling, filtering, filter cake is repeatedly washed with methylene chloride, and merging filtrate subtracts
Pressure distillation.Obtained solid uses column chromatography (distillate is methylene chloride), obtains target product.
Further, the volume ratio of both mixed solvents of triethylamine and tetrahydrofuran described in step c is 1:4.
Above compound to prepare reaction equation as shown in Figure 1.
FRET molecule of the invention can be used for the fluorescent molecular probe for realizing fluorescence detection in organism, it is also possible to make too
The trapping molecule of solar ray energy can have wider absorption in absorption spectrum.
The feature that FRET molecule of the invention has is as follows:
The FRET molecule excites under the excitation wavelength of 400nm, can launch at the green fluorescence or 620nm of 510nm
Red fluorescence.Insensitive to solvent polarity, chemical stability is good.
FRET molecule of the invention is the molecule based on fluorescence resonance energy transfer, while including two kinds of fluorogens, wherein
One fluorogen as donor, a fluorogen as receptor, the absorbing wavelength energy of the launch wavelength of donor and receptor
With the connection type in range, and between two fluorogens and apart from moderate, when being possible to realize excited donor molecule, only
Having the fluorescence of receptor can emit.Therefore, the realization key for synthesizing this FRET molecule is to need to reasonably select for acceptor fluorescence
Group is allowed to collaboration matching, is possible to the transfer for realizing fluorescence resonance energy.The present invention has synthesized collection fluorescein and fluorine boron pyrroles
The FRET molecule of two different chromophories, the molecule have preferable chemistry, photostability, can be to avoid cell or group
The interference for the autofluorescence knitted has big stoke shift, small by solvent effect；FRET molecule in the present invention is based on glimmering
Photoresonance energy transfer mechanism matches the energy of two fluorogens, efficiently realizes fluorescence energy by rationally adjusting connection type
Amount transfer.Such molecule is suitable for biological vivo detection fluorescence probe, is used for the fields such as life science and Supramolecular photochemistry, application
Prospect is extensive.
Detailed description of the invention
Fig. 1 is FRET molecule synthesis route of the present invention.
Fig. 2 is that the embodiment of the present invention 1 prepares fluorescent molecule in MCF-7 (breast cancer cell) interior laser confocal imaging；
MCF-7 cell cultivates 30min under 1 fluorescent molecule of embodiment (5 μM) room temperature, is respectively 405nm, launch wavelength in excitation light source
In 450 ± 15nm and 514 ± 15nm fluorescent emission；
Wherein (a) is the overlapping of bright field and 514 ± 15nm fluorescent emission；It (b) is 450 ± 15nm fluorescent emission；(c) it is
514 ± 15nm fluorescent emission；(d) MCF-7 cell under 2 fluorescent molecule of embodiment (5 μM) room temperature cultivate 30min after, in bright field
Under picture.
Fig. 3 is that the embodiment of the present invention 2 prepares fluorescent molecule in the intracellular laser confocal imaging of MCF-7；MCF-7 cell is used
Cultivate 30min under embodiment 2 (5 μM) room temperature, respectively excitation light source be 405nm, launch wavelength 450 ± 15nm and 590 ±
25nm fluorescent emission；
The wherein overlapping of (a) bright field and 590 ± 25nm fluorescent emission；It (b) is 450 ± 15nm fluorescent emission；It (c) is 590
± 25nm fluorescent emission；(d) MCF-7 cell under 2 fluorescent molecule of embodiment (5 μM) room temperature cultivate 30min after, under bright field
Picture.
Specific embodiment
Embodiment 1
The synthesis of a compound 2 (7-N, N- dimethylamino -2- oxygen -2H-3- tonka-bean acyl chlorides): 7- dimethylamino -2-
Oxygen -2H-3- coumaric acid (2.62g, 5mmol) is added to 20mL SOCl2In solution.Reaction solution room temperature under the conditions of nitrogen protection
Stirring 3 hours.Filtering, ether washing precipitating, obtains yellow solid 2.13g, yield 76%.Immediately after for anti-in next step
It answers.
B compound 3: in the dichloromethane solution of 10 milliliters of compounds 2, addition propargyl ammonia (191mg,
0.848mmol, M=225) and triethylamine (248ml, 1.69mmol), stirring at normal temperature, TLC determine reaction end, filter, decompression
Revolving.Column chromatography for separation obtains yellow solid product.1HNMR(CDCl3) δ=9.00 (s, 1H, NH) .8.70 (s, 1H, ArH), 7.43
(d, 1H, J=8.8Hz, ArH), 6.65 (d, J=8.8Hz, ArH), 6.50 (s, 1H, ArH), 4.23 (s, 2H, CH2),3.46
(q, 4H, J=7.2Hz, CH2CH3), 2.25 (s, 1H, CH), 1.24 (t, 6H, J=7.2Hz, CH2CH3).TOF MS calcd
for C17H18N2O3 298.1317,found 298.1324
The synthesis of c compound 4: by compound 3 (158mg, 0.53mmol), 8- (4- iodophenyl) fluorine boron pyrroles
(200mg, 0.44mmol), cuprous iodide (3.5mg, 0.022mmol), dichloro two (triphenyl phosphorus) palladium (6mg, 0.0086mmol)
It is added in the mixed solvent 5mL (v:v=1:4) of triethylamine and tetrahydrofuran, argon gas protects 40 degree of oil bath heating, reacts two hours
Afterwards.Cooling, filtering, filter cake is repeatedly washed with methylene chloride, merging filtrate, vacuum distillation.Obtained solid, which uses column chromatography, (to be evaporated
Liquid is methylene chloride out), obtain solid 169mg.Yield 62%.1HNMR(CDCl3) δ=9.10 (s, 1H, NH) .8.74 (s, 1H,
), ArH 7.57 (d, 2H, J=8.0Hz, ArH), 7.44 (d, 1H, J=9.2Hz, ArH), 7.23 (d, 2H, J=8.0Hz, ArH),
6.65 (d, 1H, J=9.2Hz, ArH), 5.98 (s, 2H, ArH), 4.50 (s, 2H, CH2), 3.46 (q, 4H, J=7.2Hz,
CH2CH3),2.55(s,1H,CH3),1.40(s,1H,CH3), 1.25 (t, 6H, J=7.2Hz, CH2CH3).TOF MS calcd
for C36H35BF2N4O3Na 643.2668,found 643.2653
Embodiment 2
By the compound (156mg, 0.53mmol, M=298) generated in example 1b and fluorine boron azole derivatives B-2 (275mg,
0.44mmol, M=626), cuprous iodide 3.5mg (0.022mmol), (triphenyl phosphorus) the palladium 6mg of dichloro two (0.0086mmol) in
The mixing of triethylamine and tetrahydrofuran is molten=agent 5mL (v:v=1:4) in, argon gas protects 40 degree of oil bath heating, reaction two hours
Afterwards.Cooling, filtering, filter cake is repeatedly washed with methylene chloride, merging filtrate, vacuum distillation.Obtained solid, which uses column chromatography, (to be evaporated
Liquid is methylene chloride out), obtain solid 157mg.Yield 45%.TOF MS calcd for[C50H43BF2N4O3+Na]
819.3293,found 819.3250。
Claims (1)
1. the synthetic method of a kind of FRET molecule based on fluorine boron pyrroles and cumarin, which comprises the steps of:
A, 7- dimethylamino -2- oxygen -2H-3- coumaric acid is dissolved in SOCl2In solution, room temperature is stirred under the conditions of nitrogen protection
It mixes 3 hours, filters, ether washing precipitating obtains yellow solid, is not further processed and is immediately available for reacting in next step；
B, the yellow solid that a step obtains is dissolved in dichloromethane solvent, be added 1.1 times of moles propargyl ammonia and
The triethylamine of 2.2 times of moles, stirring at normal temperature, TLC determine reaction end, and filtering, vacuum rotary steam, it is solid that column chromatography for separation obtains yellow
Body product；
C, the yellow solid product for 1.2 times of moles for obtaining fluorine boron azole derivatives and b step, 0.05 times of mole iodine
Change the in the mixed solvent that cuprous, 0.02 times of mole dichloro two (triphenyl phosphorus) palladium is added to triethylamine and tetrahydrofuran, argon gas
40 DEG C of oil bath heating of protection, cooling after reaction 2 hours, filtering, filter cake is repeatedly washed with methylene chloride, merging filtrate, and decompression is steamed
It evaporating, obtained solid uses column chromatography, and distillate is methylene chloride, obtain the structure that target product has such as formula (I):
(I)
Wherein, R=- H or。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710516982.3A CN107253965B (en) | 2017-06-29 | 2017-06-29 | FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710516982.3A CN107253965B (en) | 2017-06-29 | 2017-06-29 | FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107253965A CN107253965A (en) | 2017-10-17 |
| CN107253965B true CN107253965B (en) | 2019-07-05 |
Family
ID=60023531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710516982.3A Active CN107253965B (en) | 2017-06-29 | 2017-06-29 | FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107253965B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776588B (en) * | 2019-01-29 | 2021-06-18 | 大连大学 | Rare earth europium complex-based ratiometric fluorescence sensor platform and preparation method thereof |
| CN110105381B (en) * | 2019-06-11 | 2021-10-29 | 青岛科技大学 | Preparation and application of beta-diketone boron fluoride fluorescent dye with coumarin as skeleton |
| CN110143977B (en) * | 2019-06-12 | 2021-09-17 | 青岛科技大学 | Coumarin heteroboron difluoride complex fluorescent dye and application thereof |
| CN110128453B (en) * | 2019-06-17 | 2021-06-01 | 大连大学 | Preparation method and application of white organic electroluminescent material based on triphenylamine and rare earth complex |
| CN110183478B (en) * | 2019-07-11 | 2021-07-23 | 青岛科技大学 | Synthesis and application of cyanine, coumarin and dicarbonyl boron fluoride hybrid fluorescent dye |
| CN113402655B (en) * | 2021-06-30 | 2022-05-10 | 大连大学 | Polymer universal fluorescence platform for FRET fluorescent probe donor and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103666456A (en) * | 2013-12-02 | 2014-03-26 | 大连理工大学 | Boron-dipyrromethene fluorescence probes, and making method and application thereof |
| CN104497056A (en) * | 2015-01-09 | 2015-04-08 | 江苏大学 | Complex as well as preparation method and applications thereof |
| CN104926846A (en) * | 2015-06-01 | 2015-09-23 | 天津师范大学 | BODIPY compound as well as preparation method and application thereof |
-
2017
- 2017-06-29 CN CN201710516982.3A patent/CN107253965B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103666456A (en) * | 2013-12-02 | 2014-03-26 | 大连理工大学 | Boron-dipyrromethene fluorescence probes, and making method and application thereof |
| CN104497056A (en) * | 2015-01-09 | 2015-04-08 | 江苏大学 | Complex as well as preparation method and applications thereof |
| CN104926846A (en) * | 2015-06-01 | 2015-09-23 | 天津师范大学 | BODIPY compound as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| Energy transfer cassettes based on organic fluorophores: construction and applications in ratiometric sensing;Jiangli Fan et al.;《Chem. Soc. Rev.》;20121011;第42卷;page: 29-43 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107253965A (en) | 2017-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107253965B (en) | FRET molecule and its synthetic method of the one kind based on fluorine boron pyrroles and cumarin | |
| Martin et al. | Near IR emitting BODIPY fluorophores with mega-stokes shifts | |
| Sonawane et al. | Synthesis and application of 2‐styryl‐6, 7‐dichlorothiazolo [4, 5‐b]‐quinoxaline based fluorescent dyes: Part 3 | |
| dos Santos et al. | Lanthanide luminescent anion sensing: evidence of multiple anion recognition through hydrogen bonding and metal ion coordination | |
| Goldstein et al. | Photophysical properties of a new series of water soluble iridium bisterpyridine complexes functionalised at the 4′ position | |
| Zhu et al. | Chiral auxiliary and induced chiroptical sensing with 5d/4f lanthanide–organic macrocycles | |
| CN111995579B (en) | Preparation method and application of tetraphenylethylene derivative containing imidazole ring structure | |
| Zhang et al. | pH-sensitive fluorescent sensors based on europium (III) complexes | |
| Liu et al. | Difluoroboron β-diketonate dye with intense red/near-infrared fluorescence in solutions and solid states | |
| CN107759504B (en) | Dual-phase organic fluorescent material with strong fluorescence in solid and liquid states and preparation method thereof | |
| EP2663554B1 (en) | Carbazole end capped bipyridine compounds and process for preparation thereof | |
| Lu et al. | Synthesis and characterization of Ag (I) and Au (I) complexes with macrocyclic hybrid amine N-heterocyclic carbene ligands | |
| Tome et al. | Novel aurone-type compounds with an extended π-system: Synthesis and optical properties | |
| Anbalagan et al. | Spectral and photophysical properties of mono and dinuclear Pt (II) and Pd (II) complexes: An unusual emission behaviour | |
| Chaurasia et al. | Synthesis and fluorescent properties of a new photostable thiol reagent “BACM” | |
| CN115724848A (en) | Novel pH fluorescent probe material and preparation method and application thereof | |
| CN114671851B (en) | Naphthalimide-tetrazine compound and preparation method and application thereof | |
| Uh et al. | Synthesis and Solid‐State, Solution, and Luminescence Properties of Near‐Infrared‐Emitting Neodymium (3+) Complexes Formed with Ligands Derived from Salophen | |
| CN110922338B (en) | Anthraquinone derivative and synthesis method and application thereof | |
| CN112341453A (en) | Fluorescent probe based on coumarin and preparation method and application thereof | |
| JP2022026256A (en) | Compound | |
| KR101255255B1 (en) | Rhodamine derivative and synthesis of the derivative | |
| CN113773254B (en) | 1,3,4, 5-tetrasubstituted pyrazole derivatives and process for preparing same | |
| Sutton et al. | Ratiometric oxygen sensors of cyclometalated iridium (iii) with enhanced quantum yields and variable dynamic ranges | |
| Yuvayapan et al. | Synthesis, Characterization, and Use of Lanthanide Chelate of β-Diketonate Based Ligand as a Luminescent Biolabel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| OL01 | Intention to license declared | ||
| OL01 | Intention to license declared |