CN109369684A - A kind of electron donor-acceptor-donor fluorescent molecule and its preparation method and application - Google Patents
A kind of electron donor-acceptor-donor fluorescent molecule and its preparation method and application Download PDFInfo
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- CN109369684A CN109369684A CN201811293792.0A CN201811293792A CN109369684A CN 109369684 A CN109369684 A CN 109369684A CN 201811293792 A CN201811293792 A CN 201811293792A CN 109369684 A CN109369684 A CN 109369684A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- -1 dicarbonyl compound Chemical group 0.000 claims abstract description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 16
- 239000012046 mixed solvent Substances 0.000 claims description 11
- 238000003384 imaging method Methods 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000003827 glycol group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 239000012472 biological sample Substances 0.000 claims description 6
- 229910052711 selenium Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 238000000799 fluorescence microscopy Methods 0.000 abstract description 3
- 150000004987 o-phenylenediamines Chemical class 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000011669 selenium Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram 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
- 238000013399 early diagnosis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005622 photoelectricity Effects 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
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- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
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Abstract
The invention discloses a kind of electron donor-acceptor-donor fluorescent molecules and its preparation method and application, the present invention is using the compound of electron donor-acceptor-donor (D-A-D) type of a kind of o-phenylenediamine class as raw material, adjacent dicarbonyl compound is added and reacts into pyridine ring, to make its fluorescent emission be located at infrared window for the rigid structure further expansion of fluorescent molecule.Such molecule can be used for cell, tissue and the fluorescence imaging of organism, and have hypotoxicity, good bio-compatibility and photostability.
Description
Technical field
The invention belongs to small organic molecule fluorescence probe fields, and it is close to be related to a kind of D-A-D (electron donor-acceptor-donor)
IR fluorescence molecule, preparation method, and the application in biological sample imaging analysis.
Background technique
Fluorescent molecule development with apply the made rapid progress in nearest more than ten years, successively in chemical sensitisation, photoelectricity
Device, biological detection and disease the fields such as early diagnosis obtain great successes.Further with more and more functionality
The birth of powerful fluorescence imaging instrument, such as confocal microscope, indium gallium arsenic photodiode imager, so that fluorescence
Imaging results of the molecule for various types of cells, tissue, organism have stronger theory during probing into life science secret
Take power and biological meaning.
Since short wavelength's fluorescent molecule is used for the limitation of imaging in biological tissues depth, resolution ratio etc., and it is easy
Because autofluorescence causes false positive, the big the main direction of development of the one of fluorescent molecule is exactly longer to launch wavelength and effort, is made
It can have fluorescence in one area of infrared window or even near-infrared (700-1000nm), 2nd area of near-infrared (1000-1700nm)
Transmitting.And small organic molecule fluorescent molecule realizes the method for red shift of wavelength in addition to introducing in conventional fluorescent molecular skeleton at present
The atoms such as silicon, selenium (such as silicon substrate dye stuff of rhodamine kinds), most widely used is exactly to expand rigid structure, extends pi-electron system,
Therefore, it is necessary to people to probe into the change that a variety of reaction conditions are mild, synthetic method easy to operate has good luminous characteristic
Close object.
Summary of the invention
Electron donor-acceptor-donor (D-A-D) structural type based on Intramolecular electron transfer (ICT) mechanism of fluorescence emission
Compound has the characteristics that background fluorescent emission is low, and the object of the present invention is to provide a kind of electron donor-acceptor-donor fluorescents point
Son and preparation method and application are added adjacent using electron donor-acceptor-donor compound of a kind of o-phenylenediamine class as raw material
Dicarbonyl compound reacts cyclization, and by compound rigid structure further expansion, successful design goes out a kind of electron acceptor point
Sub- skeleton is the near-infrared fluorescent molecule of quinoxaline.
One kind electron donor-acceptor-donor fluorescent molecule provided by the invention, feature are the fluorescent molecules with as follows
General formula I or II:
In general formula I:
X is O, S or Se；
R is H, C1-C8 alkyl, the sugar of alkyl chain substitution, the substituted or non-substituted polyethylene glycol groups of different chain length；
R1And R2It is respectively independent are as follows: H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic；
In general formula II:
R3And R4Respectively stand alone as the substituted or non-substituted polyethylene glycol groups of H, C1-C8 alkyl, ester group, different chain length；R3And R4
Connection cyclization；R3And R4Simultaneously five-membered ring or simultaneously hexatomic ring are formed with the connected phenyl ring of nitrogen-atoms；
R5And R6Respectively stand alone as H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic.
A kind of preparation method of above-mentioned a kind of electron donor-acceptor-donor fluorescent molecule, this method includes walking in detail below
It is rapid:
2.1, the preparation method of general formula I:
The general formula compound I that molar ratio is 1:1-100 is reacted with adjacent dicarbonyl compound, adjacent dicarbonyl compound conduct
Acylating agent, solvent are the mixed solvent of methanol and methylene chloride, react at room temperature 1-8 hours, obtain general formula compound I；
2.2, the preparation method of general formula II:
The general formula II class compound that molar ratio is 1:1-100 is reacted with adjacent dicarbonyl compound, and adjacent dicarbonyl compound is made
For acylating agent, solvent is the mixed solvent of methanol and methylene chloride, reacts at room temperature 1-8 hours, obtains general formula II class compound.
A kind of above-mentioned a kind of electron donor-acceptor-application of the donor fluorescent molecule in biological sample imaging analysis.
Above-mentioned application, the biological sample include but is not limited to cell.
The present invention photobleaching phenomenon generally existing for organic fluorescence molecule, in the planar rigidity knot of fluorescent molecule skeleton
Structure both ends introduce flexible group, so that photobleaching phenomenon obtains certain alleviation.And the variation of both ends electron donor is to fluorescence point
The photoluminescent property of son plays a decisive role, and the specific structural modification of both ends electron donor progress can be realized using this property can
The photoluminescent property of tune.In addition, fluorescent molecule of the present invention emits with near-infrared fluorescent, and good light stability, have good
Bio-compatibility, accretion rate is fast in vivo, is the organic fluorescence molecule of a kind of great application prospect.
Detailed description of the invention
Fig. 1 is the UV absorption and fluorescent emission spectrogram of S1 fluorescent molecule of the present invention；
Fig. 2 is the Photostability experiments schematic diagram that S1 fluorescent molecule of the present invention is used for the imaging of SHSY5Y nerve cell.
Specific embodiment
An object of the present invention is to provide the D-A-D near-infrared fluorescent molecule that general formula is I:
Wherein, X O, S or Se.R is H, C1-C8 alkyl；The substituted or non-substituted polyethylene glycol groups of different chain length；Alkyl chain
Substituted sugar (such as glucose, pyranose, lactose, galactolipin)；R1And R2It respectively stands alone as H, C1-C8 alkyl, substitution or non-takes
For aromatic ring or heteroaromatic.
Preferably, X S；R is R1For methyl, R2For H or R1For H, R2For methyl.
The second object of the present invention is to provide the D-A-D near-infrared fluorescent molecule of general formula II:
Wherein, X O, S or Se.R3And R4It is respectively independent are as follows: H, C1-C8 alkyl, ester group, different chain length are substituted or non-substituted
Polyethylene glycol groups；R3And R4Connection cyclization；R3Or R4Simultaneously five-membered ring or simultaneously hexatomic ring are formed with the connected phenyl ring of nitrogen-atoms； R5And R6
Respectively stand alone as H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic.
Preferably, X S；R3Or R4Pyrrolidinyl is formed with nitrogen-atoms for methyl, ethyl or connection cyclization；R3Or R4With nitrogen
The connected phenyl ring of atom is formed and hexatomic ring, i.e.,R5For methyl, R6For H,
Or R5For H, R6For methyl.
The preferred D-A-D near-infrared fluorescent molecule in part of the invention is as follows, these embodiments are just for the present invention
It is described further, it is not intended to limit the scope of the present invention in any way.
The third object of the present invention is to provide the preparation method of D-A-D near-infrared fluorescent molecule of the present invention:
3.1, the preparation method of general formula I:
The general formula compound I that molar ratio is 1:1-1:100 is reacted with adjacent dicarbonyl compound, and adjacent dicarbonyl compound is made
For acylating agent, solvent is the mixed solvent of methanol and methylene chloride, reacts at room temperature 1-8 hours, obtains general formula compound I；
In another preferred example, R is
In another preferred example, adjacent dicarbonyl compound used is pyroracemic aldehyde (40% aqueous solution).
In another preferred example, the reaction time is 4 hours.
3.2, the preparation method of general formula II:
The general formula II class compound that molar ratio is 1:1-1:100 is reacted with adjacent dicarbonyl compound, adjacent dicarbonyl compound
As acylating agent, solvent is the mixed solvent of methanol and methylene chloride, reacts at room temperature 1-8 hours, obtains general formula II class compound.
In another preferred example, R3And R4It is methyl.
In another preferred example, adjacent dicarbonyl compound used is pyroracemic aldehyde (40% aqueous solution).
In another preferred example, the reaction time is 4 hours.
The fourth object of the present invention is to provide D-A-D near-infrared fluorescent molecule of the present invention in biological sample imaging analysis
Using
4.1, UV absorption and the fluorescent emission measurement of D-A-D near-infrared fluorescent molecule
I or II fluorescent molecule is dissolved in DMAC, 1mM/mL mother liquor is made, is placed in 4 DEG C of refrigerators and save.It is diluted when measurement, most
Whole solvent condition is 40%DMAC, 60%pH=7.4 10mM PBS, surveys absorption and fluorescence emission spectrum respectively.
4.2, photostability measurement of the D-A-D near-infrared fluorescent molecule in nerve cell
To be added to SHSY5Y intracellular for the 1%DMSO solution of I or II fluorescent molecule for being 10 μM by 5 μ L concentration, 37 DEG C,
5%CO2Under the conditions of be incubated for 1h, washed three times with PBS.In PBS, excitation light source prolonged exposure carries out co-focusing imaging to it and (swashs
Wavelength 488nm is sent out, wavelength 600-900nm is collected).
Embodiment 1
The synthesis of compound S1
Compound 1 (15.0mg, 0.027mmol) is dissolved in 1.0mL mixed solvent (methanol: methylene chloride=1: 1v/v)
In, 4h is stirred at room temperature in 0.3ml MGO aqueous solution (40%).TLC detection is concentrated under reduced pressure after completion of the reaction, prepares plate separation (two
Chloromethanes: methanol=50: 1v/v), obtain red compound S1 8mg, yield 50%.1H NMR(300MHz,CDCl3) δ8.72
(s, 1H), 7.82 (d, J=8.8Hz, 4H), 7.16 (d, J=6.8Hz, 4H), 4.31-4.25 (m, 4H), 3.98-3.90 (m,
4H),3.80–3.74(m,4H),3.65–3.58(m,4H),3.42(s,6H),2.73(s,3H).13C NMR(126MHz,
CDCl3)δ159.00(2C),154.56,153.16,152.66,147.58(2C),137.37,136.72,133.73(4C),
130.10, 129.07,127.32,114.13(4C),72.03(2C),70.82(2C),69.79(2C),67.49(2C),
59.14(2C),23.40. LR-ESI-MS:[M+H]+m/z 591.3。
Embodiment 2
The synthesis of compound S2
Compound 2 (10.0mg, 0.021mmol) is dissolved in 1.0mL in the mixed solvent (methanol: methylene chloride=1: 1v/v)
In, 4h is stirred at room temperature in 0.5ml MGO aqueous solution (40%).TLC detection is concentrated under reduced pressure after completion of the reaction, prepares plate separation (two
Chloromethanes: methanol=40: 1v/v), obtain red compound S2 4.5mg, yield 43%.1H NMR(300MHz, CDCl3)δ
8.70 (s, 1H), 7.52 (d, J=8.8Hz, 4H), 7.08 (d, J=8.8Hz, 4H), 4.22 (t, J=6.0Hz, 4H), 3.93
(t, J=5.8Hz, 4H), 2.74 (s, 3H), 2.10 (p, J=5.8Hz, 4H).
Embodiment 3
The synthesis of compound S3
Compound 3 (10.0mg, 0.017mmol) is dissolved in 1.0mL in the mixed solvent (methanol: methylene chloride=1: 1v/v)
In, 4h is stirred at room temperature in 0.5ml MGO aqueous solution (40%).TLC detection is concentrated under reduced pressure after completion of the reaction, prepares plate separation (two
Chloromethanes: methanol=40: 1v/v), obtain red compound S3 5.2mg, yield 50%.1H NMR(300MHz, CD3OD)δ
8.71 (s, 1H), 7.79 (t, J=8.7Hz, 4H), 7.14 (d, J=8.6Hz, 4H), 4.29 (t, J=4.7Hz, 4H), 3.81-
3.72(m,8H),2.94(s,4H),2.80–2.65(m,11H).LR-ESI-MS:[M+H]+m/z 613.3。
Embodiment 4
The synthesis of compound S4
Compound 4 (10.0mg, 0.0108mmol) is dissolved in 1.0mL in the mixed solvent (methanol: methylene chloride=1: 1v/
V) in, 4h is stirred at room temperature in 0.5ml MGO aqueous solution (40%).TLC detection is concentrated under reduced pressure after completion of the reaction, and C18 filler fills column
It separates (methanol: water=1: 1.5v/v), obtains red compound S4 3.9mg, yield 38%.1H NMR(300MHz, CD3OD)δ
8.72 (s, 1H), 8.29 (s, 2H), 7.78 (d, J=5.8Hz, 4H), 7.21 (d, J=8.6Hz, 4H), 5.31 (s, 4H),
4.69 (t, J=3.4Hz, 4H), 4.43-4.16 (m, 4H), 4.10-3.99 (m, 4H), 3.86 (d, J=12.4Hz, 3H),
3.69– 3.61(m,3H),3.24–3.15(m,3H),2.69(s,3H)。
Embodiment 5
The synthesis of compound S5
Compound 5 (38.0mg, 0.017mmol) is dissolved in 1.0mL in the mixed solvent (methanol: methylene chloride=1: 1v/v)
In, 4h is stirred at room temperature in 0.5mL MGO aqueous solution (40%).TLC detection is concentrated under reduced pressure after completion of the reaction, prepares plate separation (two
Chloromethanes: methanol=40:1v/v), obtain navy blue compound S5 17mg, yield 41.1%.1H NMR(400MHz, CDCl3)
δ 8.69 (s, 1H), 7.84 (dd, J=30.3,8.5Hz, 4H), 6.95 (d, J=8.5Hz, 4H), 3.08 (d, J=3.4Hz,
12H),2.72(s,3H).13C NMR(126MHz,CDCl3)δ153.90,153.39,152.90,150.43(2C),147.04,
137.33,136.71,133.54(4C),129.84,128.73,122.88(4C),111.76(2C),40.46(4C),23.32。
Embodiment 6
The performance measurement of D-A-D near-infrared fluorescent molecule
6.1, UV absorption and the fluorescent emission measurement of D-A-D near-infrared fluorescent molecule
S1 fluorescent molecule, which is dissolved in DMAC, is made 1mM/mL mother liquor, is placed in 4 DEG C of refrigerators and saves.It is diluted when measurement, it is final molten
Agent condition is 40%DMAC, 60%pH=7.4 10mM PBS, surveys absorption and fluorescence emission spectrum respectively.S1 fluorescent molecule is maximum
Absorbing wavelength is 500nm, 570-850nm of emission peak wave-length coverage, and maximum emission wavelength is 650nm；As shown in Fig. 1.
6.2, imaging applications of the D-A-D near-infrared fluorescent molecule in nerve cell
By 1%DMSO solution be added to SHSY5Y intracellular, 37 DEG C, 5% for the S1 fluorescent molecule that 5 μ L concentration are 10 μM
CO2Under the conditions of be incubated for 1h, washed three times with PBS.In PBS, excitation light source prolonged exposure carries out co-focusing imaging (excitation to it
Wavelength 488nm collects wavelength 600-900nm).It can see apparent red fluorescence, and it held with excitation light source
In the 10min of continuous irradiation, the fluorescence intensity of S1 fluorescent molecule will not be had an impact, as shown in Figure 2.This is experiments have shown that synthesized
It is very excellent as the imaging performance of the D-A-D near-infrared fluorescent molecule of representative using S1 fluorescent molecule.
Claims (4)
1. a kind of electron donor-acceptor-donor fluorescent molecule, which is characterized in that the fluorescent molecule have following general formula I or
II:
In general formula I:
X is O, S or Se；
R is H, C1-C8 alkyl, the sugar of alkyl chain substitution, the substituted or non-substituted polyethylene glycol groups of different chain length；
R1And R2It is respectively independent are as follows: H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic；
In general formula II:
R3And R4Respectively stand alone as the substituted or non-substituted polyethylene glycol groups of H, C1-C8 alkyl, ester group, different chain length；R3And R4Connection
Cyclization；R3And R4Simultaneously five-membered ring or simultaneously hexatomic ring are formed with the connected phenyl ring of nitrogen-atoms；
R5And R6Respectively stand alone as H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic.
2. a kind of electron donor-acceptor of one kind described in claim 1-donor fluorescent molecule preparation method, which is characterized in that should
Method comprising the following specific steps
2.1, the preparation method of general formula I:
The general formula compound I that molar ratio is 1:1-100 is reacted with adjacent dicarbonyl compound, and adjacent dicarbonyl compound is as acylation
Agent, solvent are the mixed solvent of methanol and methylene chloride, react at room temperature 1-8 hours, obtain general formula compound I；Wherein, X is
O, S or Se；
R is H, C1-C8 alkyl, the sugar of alkyl chain substitution, the substituted or non-substituted polyethylene glycol groups of different chain length；
R1And R2It is respectively independent are as follows: H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic；
2.2, the preparation method of general formula II:
The general formula II class compound that molar ratio is 1:1-100 is reacted with adjacent dicarbonyl compound, and adjacent dicarbonyl compound is as acyl
Agent, solvent are the mixed solvent of methanol and methylene chloride, react at room temperature 1-8 hours, obtain general formula II class compound；Wherein,
R3And R4Respectively stand alone as the substituted or non-substituted polyethylene glycol groups of H, C1-C8 alkyl, ester group, different chain length；R3And R4It connects into
Ring；R3And R4Simultaneously five-membered ring or simultaneously hexatomic ring are formed with the connected phenyl ring of nitrogen-atoms；
R5And R6Respectively stand alone as H, C1-C8 alkyl, substituted or non-substituted aromatic ring or heteroaromatic.
3. a kind of electron donor-acceptor of one kind described in claim 1-donor fluorescent molecule answering in biological sample imaging analysis
With.
4. application according to claim 3, which is characterized in that the biological sample includes but is not limited to cell.
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