CN106084873A - A kind of efficient near-infrared fluorescent material and biologic applications thereof - Google Patents
A kind of efficient near-infrared fluorescent material and biologic applications thereof Download PDFInfo
- Publication number
- CN106084873A CN106084873A CN201610416587.3A CN201610416587A CN106084873A CN 106084873 A CN106084873 A CN 106084873A CN 201610416587 A CN201610416587 A CN 201610416587A CN 106084873 A CN106084873 A CN 106084873A
- Authority
- CN
- China
- Prior art keywords
- compound
- infrared fluorescent
- imaging
- fluorescent dye
- near infrared
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/14—Styryl dyes
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/14—Styryl dyes
- C09B23/141—Bis styryl dyes containing two radicals C6H5-CH=CH-
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Materials Engineering (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
One has efficient near infrared fluorescent dye and the application in the field such as bio-imaging and fluorescence labeling thereof of big Stokes (stoke) displacement, belongs to organic fluorescent dye and applied technical field.Concrete molecular structure is basic receptor structure unit with fumaric acid nitrile, be there is in one or both sides conjugation connection the donor monomer of electron repulsive ability by double bond, its structural formula is as follows, is the novel near infrared fluorescent dye of the class being synthesized by Heck, and wherein R represents donor groups.This dyestuff of research discovery can send very bright near-infrared fluorescent under ultraviolet excitation, and this material has good anti-light Bleachability and high solid state quantum efficiency.These materials also have very big Stokes shift simultaneously, and therefore it is as near-infrared fluorescent material, can be applicable to the field such as bio-imaging and fluorescence labeling.
Description
Technical field
The invention belongs to organic fluorescent dye and applied technical field, be specifically related to one and there is big Stokes
(stoke) the efficient near infrared fluorescent dye of displacement and the application in the field such as bio-imaging and fluorescence labeling thereof.
Background technology
16th century, light microscope changed people to biological understanding, had promoted biomedical fast development.
This area is known, under an optical microscope can be with the size of observation of cell and form, organelle, chromosome etc..Electron microscope
Invention open research cell ultrastructure new era, such as observe rough surfaced endoplasmic reticulum (RER), smooth surfaced endoplasmic reticulum, ribosomes, simultaneously
Coordinate Measurement for Biochemistry can also be analyzed cellular elements.With the progress of human society, iconography new in recent years
Continuing to bring out of equipment and technology, molecular imaging arises at the historic moment.Molecular imaging is one and relates to iconography and modern molecular
Biology and the emerging cross discipline of Other subjects.The unprecedented progress of modern cell biology, Protocols in Molecular Biology and development,
The molecular probe of high targeting and sensitivity, the development etc. of high-spatial and temporal resolution small animal imaging equipment provide for molecular imaging
Condition.Molecular imaging be from molecule or cellular level imaging thus reach understanding disease, illustrate the biological mistake of pathological tissues
Cheng Bianhua, sick cell gene expression, metabolic activity height, the state that whether sick cell survives and intracellular biological is movable
Science etc. purpose.Molecular imaging develop into disease early diagnosis, treatment and Mechanism Study provide real-time, dynamically believe
Breath.Conventional molecular imaging method mainly includes optical imagery, ultrasonic imaging (ultrasound), computer tomography
(computedtomography, CT), nuclear magnetic resonance (magneticresonanceimaging, MRI), positron emission imaging
(positron-emissiontomography, PET) and single photon diffraction (single-photon-
Emissioncomputedtomography, SPECT) etc..
Compared with other imaging means, optical imagery have hurtless measure, without ray radiation hazradial bundle, price is low, sensitiveness is high,
Can the advantage such as real time imagery.Fluorescent technique uses fluorescent reporter group (GFP, RFP, Cyt and dyes etc.) to targeted cells or to divide
Son is marked imaging.Optical imagery instrument can directly detect specific molecular in living body biological body, cellular activity and gene table
Reach behavior.By these technology, the growth of tumour in living animal body and transfer can be observed, disease develops, gene
Expression and the biological process such as reaction.Relative to other bioluminescence imaging technology: as common in ultrasonic, computer tomography, nuclear-magnetism
Shake, positron emission imaging, single photon diffraction etc., optical imagery has the advantage of some uniquenesses, as easy and simple to handle, result is straight
See, measure quick, highly sensitive and low cost etc..
Many organisms and self can launch fluorescence under being organized in the exciting of visible ray, severe jamming biological sample glimmering
Light detection and radiography, if the fluorescent wavelength ranges of haemocyanin in blood plasma is 325～350nm, reproducibility nicotinamide adenine two
Nucleotide phosphodiesterase enzyme (NADPH) and bilirubinic fluorescent wavelength ranges are 430～470nm, so that visible region fluorescence analysis
Sensitivity and accuracy receive very big impact.Add the impact of light scattering often to produce more serious background and do
Disturb, seriously limit the raising of XRF sensitivity, and in near-infrared fluorescent (700～1200nm) light district, in organism
The self-absorption of material and autofluorescence are more weak, and ambient interferences can be avoided to obtain higher sensitivity for analysis, can also subtract simultaneously
Few damage to life entity, is advantageously implemented In vivo detection.And owing to the biquadratic of scattered light intensity and wavelength is inversely proportional to, with
Wavelength increases, and Raman scattering reduces rapidly, makes scattering interference also be greatly reduced.In addition, little Stokes shift can cause
The problem of the self-absorption of dyestuff self-quenching, also referred to as dyestuff.This is because the absorption spectrum of the dyestuff of little Stokes shift with
Emission spectrum has very big friendship lid, and such dyestuff has part transmitting luminous energy to be absorbed by himself, thus causes fluorescence intensity to decline.
Another problem is to cause the measure error of fluorescence analysis.This is because little Stokes shift make excitation wavelength with glimmering
Light detection wavelength is too close to, and fluoroscopic examination slit is easily caused scattered light to disturb by excitation wavelength.Thus exploitation has this torr big
The fluorescent dye of gram this displacement has highly important meaning.In recent years, near-infrared fluorescent material is particularly subject to concern, and this is main
It is strong penetration capacity (Guo, Z. biological tissue not disturbed by background fluorescence due near infrared light；Park, S.；Yoon, J.；
Shin, I.Chem.Soc.Rev.2014,43,16.Yuan, L.；Lin, W.；Zheng, K.；He, L.；Huang,
W.Chem.Soc.Rev.2013,42,622.Achilefu, S.Angew.Chem.Int.Ed.2010,49,
9816.Escobedo, J.O.；Rusin, O.；Lim, S.；Strongin, R.M.Curr.Opin.Chem.Biol.2010,14,
64.Hilderbrand, S.A.；Weissleder, R.Curr.Opin.Chem.Biol.2010,14,71.Kiyose, K.；
Kojima, H.；Nagano, T.Chem.AsiaJ.2008,3,506.).
The present invention for based on fumaric acid nitrile for by body unit, can obtain having not by changing periphery donor structure unit
Near infrared fluorescent dye with near infrared emission.Which is fluorescent nano particles prepared by luminescence unit at cell imaging and biology
Application in marker field has broad prospects.
Content of the invention
It is an object of the invention to provide a kind of near infrared fluorescent dye based on fumaric acid nitrile and at bio-imaging and
Application in fluorescence labeling.
Near infrared fluorescent dye of the present invention, is with fumaric acid nitrile as basic structural unit, by double bond in side or
Both sides conjugation connects the donor monomer with electron repulsive ability, and its structural formula is as follows:
Wherein R represents donor groups, is:
This compounds is applicable to prepare efficient near infrared fluorescent dye.The feature of the compounds of this invention is to have high consolidating
State fluorescence quantum efficiency and anti-light bleaching power, big stoke displacement and Multiphoton Absorbtion cross section, and under ultraviolet excitation,
Any one above-claimed cpd all can send near-infrared fluorescent.And the fluorescent marker prepared based on this kind of compound, as
Fluorescent nano particles, fluorescence probe etc. can be used in cell imaging and biomarker.
Fumaric acid nitrile near infrared fluorescent dye synthesis step is as follows:
Step 1: at iodine, sodium methoxide catalyzed under, the benzene acetonitrile class raw material reaction of two molecules generates fumaric acid nitrile intermediate；
Step 2: carry out Heck reaction under silver carbonate, palladium catalytic condition and prepare end-product molecule.
Brief description
Fig. 1: be that UV, visible light under THF solution and solid state for the near infrared fluorescent dye prepared in embodiment 1 is inhaled
Receive emission spectra, excitation wavelength 365nm；
Fig. 2: be that UV absorption under THF solution and solid state for the near infrared fluorescent dye prepared in embodiment 2 is sent out
Penetrate spectrum, excitation wavelength 365nm；
Fig. 3: for fluorescence emission spectrum during the different near infrared fluorescent dye load capacity of preparation in embodiment 17；
Fig. 4: be embodiment 18 cell imaging figure, nano particle cultivates concentration 100 μ g/mL, excitation wavelength 408nm, capture
650～700nm fluorescence.
Detailed description of the invention
The present invention gives a class based on the synthetic method of fumaric acid nitrile near infrared fluorescent dye and at cell imaging and
Application in biomarker.
The preparation of precursor
Compound 1:
To bromobenzylcyanide (5g, 25.505mmol) and iodine (6.5734g, 25.505mmol) in 250mL reaction bulb, rush argon
Gas replace three times to no oxygen in bottle and water, add 100mL dry ether stirring and dissolving.By sodium methoxide (2.8933g,
It 5.356mmol) is dissolved in absolute methanol (8.680g, 14.613ml), deoxygenation and water, be slowly dropped under-78 degrees celsius
In above-mentioned solution, need to be always maintained at argon atmosphere during whole dropping.It after dripping, is to slowly warm up to 0 degree Celsius, continue to stir
Mix reaction 3 hours.After having reacted, with the dilute hydrochloric acid solution cancellation reaction of mass fraction 5%, then stirring reaction 12 hours.Instead
Should completely after, by solution suction filtration, filter cake methyl alcohol and washing 2 times.Gained solid is dried in vacuum drying chamber.Final products are
White powder compound 1 (3.1143g, 63% productivity).1HNMR(CDCl3, 500MHz): (ppm) 7.67-7.72 (m, 8H, 1-
benzene)。
Compound 2:
To bromobenzylcyanide (2.5g, 12.753mmol), benzene acetonitrile (1.49g, 12.753mmol) and iodine (6.5734g,
25.505mmol) in 250mL reaction bulb, rush argon gas replace three times to no oxygen in bottle and water, add 100mL be dried second
Ether stirring and dissolving.Sodium methoxide (2.8933g, 5.356mmol) is dissolved in absolute methanol (8.680g, 14.613ml), deoxygenation and
Water, is slowly dropped in above-mentioned solution under-78 degrees celsius, needs to be always maintained at argon atmosphere during whole dropping.Dropping
It after complete, is to slowly warm up to 0 degree Celsius, continue stirring reaction 3 hours.After having reacted, quenched by the dilute hydrochloric acid solution of mass fraction 5%
Go out reaction, then stirring reaction 12 hours.After reaction completely, by solution suction filtration, filter cake methyl alcohol and washing 2 times.Gained solid
Vacuum drying chamber is dried.Final products are white powder compound 2 (2.274g, 57% productivity).1HNMR(CDCl3,
500MHz): (ppm) 7.67-7.72 (m, 9H, 1-benzene).
Embodiment 1:
Take compound 2 (159.6mg, 0.52mM) respectively, to hexichol amido styrene (140mg, 0.52mM), Pd (OAc)2
(6mg, 0.026mM), Ag2CO3(85mg, 0.31mM) joins in 50mL Schlenk pipe, adds about 10mL toluene, 100 degrees Celsius
Lower heating reaction 18 hours.Having reacted rear filtering reacting liquid, filtrate is spin-dried for solvent, purifies to obtain dark red powder product through silicagel column
Compound 3, productivity 53.4%.1HNMR (500MHz, DMSO) δ 7.82 (ddd, J=13.8,8.6,6.0Hz, 9H), 7.55 (d, J
=8.7Hz, 2H), 7.43 (s, 1H), 7.39 (s, 1H), 7.33 (dd, J=8.3,7.5Hz, 4H), 7.22 (s, 1H), 7.19 (s,
1H), 7.11 7.03 (m, 6H), 6.96 (d, J=8.6Hz, 2H) .Ms (m/e): C36H25N3, calcd499.6；found499.6.
Elementary analysis experiment value (calculated value): C:86.6% (86.55%)；H:5.0% (5.04%)；N:8.4% (8.41%).
As shown in Figure 1, the tetrahydrofuran solution maximum absorption band of compound 3 is 455nm, four under 365nm exciting light
Maximum emission peak in hydrogen tetrahydrofuran solution is positioned at the near-infrared luminous region of 785nm, and its Stokes shift has reached 330nm,
This is very favorable for bio-imaging.But solution brightness ratio is relatively low, its quantum efficiency only has 1.03%, the fluorescence longevity
Life is 0.25ns.The solid maximum emission peak of compound 3, at 690nm, creates the blue shift of 95nm for solution, and this can
Can its molecular distortion change when solid-state cause greatly, the solid state fluorescence life-span of compound 3 is 4.5ns, the fluorescent quantum of solid
Efficiency has increased to 5.9%.
Compound 3
Embodiment 2:
Take compound 1 (200mg, 0.52mM) respectively, to hexichol amido styrene (280mg, 1.04mM), Pd (OAc)2
(12mg, 0.052mM), Ag2CO3(170mg, 0.62mM) joins in 50mL Schlenk pipe, adds about 10mL toluene, and 100 is Celsius
The lower heating reaction of degree 18 hours.Having reacted rear filtering reacting liquid, filtrate is spin-dried for solvent, purifies to obtain dark red powder product through silicagel column
Compounds 4, productivity 62.8%.1HNMR (500MHz, DMSO) δ 7.87 (d, J=8.6Hz, 4H), 7.82 (d, J=8.6Hz,
4H), 7.58 (d, J=8.8Hz, 4H), 7.43 (d, J=16.3Hz, 4H), 7.38 7.33 (m, 8H), 7.23 (d, J=
16.5Hz, 4H), 7.13 7.06 (m, 11H), 6.98 (d, J=8.7Hz, 4H) .Ms (m/e): C56H40N4, calcd768.33；
Found767.136. elementary analysis experiment value (calculated value): C:87.5% (87.47%)；H:5.2% (5.24%)；N:7.3%
(7.29%).
As shown in Figure 2, the maximum absorption band of compound 4 is 472nm, in the tetrahydrofuran solution under 365nm exciting light
Maximum emission peak be 770nm, we are it can also be observed that the Stokes shift of compound 4 solution has reached 300nm simultaneously.
Compound 4 solution quantum efficiency is 3.43%, and fluorescence lifetime is 1.11ns, and its solid maximum emission peak is at 698nm, relative to molten
Creating the blue shift of 72nm for liquid, this is probably what its molecular distortion change when solid-state caused greatly, and the solid of compound 4 is
Big emission peak has faint red shift than compound 3, and this prolongation being likely due to conjugated system and molecular configuration more distort and draw
Rise.The solid state fluorescence life-span of compound 4 is 3.77ns, and the fluorescence quantum efficiency of solid has increased to 19.1%.
Compound 4
Embodiment 3:
Similar with compound 3 synthesis, with to N, N-dimethyl styrene replaces to hexichol amido styrene, is prepared into chemical combination
Thing 5.Ms (m/e): 375.17, elementary analysis experiment value (calculated value): C:83.2% (83.17%)；H:5.6% (5.64%)；
N:11.2% (11.9%).
Compound 5
Embodiment 4:
Similar with compound 3 synthesis, with to N, N-diethyl replaces obtaining compound to hexichol amido styrene
6.Ms (m/e): 403.52, elementary analysis experiment value (calculated value): C:83.3% (83.34%)；H:6.3% (6.24%)；N:
10.4% (10.41%).
Compound 6
Embodiment 5:
Similar with compound 3 synthesis, with to N, N-dipropyl styrene replaces obtaining compound to hexichol amido styrene
7.Ms (m/e): 431.57, elementary analysis experiment value (calculated value): C:83.5% (83.49%)；H:6.8% (6.77%)；N:
9.7% (9.74%).
Compound 7
Embodiment 6:
Similar with compound 3 synthesis, to replace obtaining compound to hexichol amido styrene to 9-vinyl julolidine
8.Ms (m/e): 427.2, elementary analysis experiment value (calculated value): C:84.3% (84.28%)；H:5.9% (5.89%)；N:
9.8% (9.83%).
Compound 8
Embodiment 7:
Similar with compound 3 synthesis, to replace obtaining compound 9 to hexichol amido styrene to N-carbazole styrene.Ms
(m/e): 497.19, elementary analysis experiment value (calculated value): C:86.9% (86.90%)；H:4.7% (4.66%)；N:8.4%
(8.44%).
Compound 9
Embodiment 8:
Similar with compound 3 synthesis, replace obtaining compound 10 to hexichol amido styrene with 9-tri-carbazole styrene.Ms
(m/e): 827.3, elementary analysis experiment value (calculated value): C:87.0% (87.04%)；H:4.5% (4.50%)；N:8.5%
(8.46%).
Compound 10
Embodiment 9:
Similar with compound 3 synthesis, replace obtaining compound 11 to hexichol amido styrene with three (triphenylamine) base ethene.
Ms (m/e): 1037.45, elementary analysis experiment value (calculated value): C:87.9% (87.92%)；H:5.3% (5.34%)；N:
6.8% (6.75%).
Compound 11
Embodiment 10:
Similar with compound 4 synthesis, with to N, N-dimethyl styrene replaces to hexichol amido styrene, is prepared into chemical combination
Thing 12.Ms (m/e): 520.26, elementary analysis experiment value (calculated value): C:83.0% (83.04%)；H:6.2% (6.19%)；
N:10.8% (10.76%).
Compound 12
Embodiment 11:
Similar with compound 4 synthesis, with to N, N-diethyl replaces to hexichol amido styrene, is prepared into chemical combination
Thing 13.Ms (m/e): 576.77, elementary analysis experiment value (calculated value): C:83.3% (83.30%)；H:7.0% (6.99%)；
N:9.7% (9.71%).
Compound 13
Embodiment 12:
Similar with compound 4 synthesis, with to N, N-dipropyl styrene replaces obtaining compound to hexichol amido styrene
14.Ms (m/e): 632.39, elementary analysis experiment value (calculated value): C:83.5% (83.50%)；H:7.6% (7.64%)；N:
8.9% (8.85%).
Compound 14
Embodiment 13:
Similar with compound 4 synthesis, to replace obtaining compound to hexichol amido styrene to 9-vinyl julolidine
15.Ms (m/e): 624.33, elementary analysis experiment value (calculated value): C:84.6% (84.58%)；H:6.5% (6.45%)；N:
8.9% (8.97%).
Compound 15
Embodiment 14:
Similar with compound 4 synthesis, to replace obtaining compound 16 to hexichol amido styrene to N-carbazole styrene.Ms
(m/e): 764.29, elementary analysis experiment value (calculated value): C:87.9% (87.93%)；H:4.8% (4.74%)；N:7.3%
(7.32%).
Compound 16
Embodiment 15:
Similar with compound 4 synthesis, replace obtaining compound 17 to hexichol amido styrene with 9-tri-carbazole styrene.Ms
(m/e): 1424.53, elementary analysis experiment value (calculated value): C:87.6% (87.62%)；H:4.5% (4.52%)；N:
7.9% (7.86%).
Compound 17
Embodiment 16:
Similar with compound 4 synthesis, replace obtaining compound 18 to hexichol amido styrene with three (triphenylamine) base ethene.
Ms (m/e): 1844.81, elementary analysis experiment value (calculated value): C:88.5% (88.47%)；H:5.5% (5.46%)；N:
6.0% (6.07%).
Compound 18
Embodiment 17
The near infrared fluorescent dye compound 4 preparing embodiment 2 is dissolved in oxolane by the concentration of 1mg/mL, and
Configure the tetrahydrofuran solution of the amphipathic nature polyalcohol poly-(styrene-co-maleic anhydride) (PSMA) of 1mg/mL simultaneously.By Fig. 3
Shown in mass ratio take respectively compound 4 tetrahydrofuran solution (40 μ L, 36.4 μ L, 33.3 μ L, 32 μ L, 30.76 μ L,
28.6 μ L, 26.7 μ L) in the EP pipe of 2mL, then it is separately added into PSMA solution 160 μ L wherein, add oxolane and be settled to
1mL, ultrasonic makes solution mix.Being quickly poured into above-mentioned tetrahydrofuran solution in the vial containing 5mL deionized water, 40 degree surpass
Sound 6 minutes.Arrange at warm table and go toward nitrogen blowing bubbling in bottle (bottleneck will not be overflowed with bubble to be advisable) at temperature 70 degrees Celsius
Except oxolane, till being blown in bottle without oxolane taste.With 0.22 micron of filter filtering solution red nano grain
Sub-solution.Above-mentioned nano-particle solution can send very bright ruddiness under 365nm ultraviolet excitation, and its emission maximum peak position exists
Between 670～700nm (accompanying drawing 3), and its fluorescence quantum efficiency can be gradually increased with the minimizing of dye load amount, in load
Maximum fluorescence quantum efficiency 34% is reached when ratio is 1:26.
Embodiment 18
Nano particle described in embodiment 17 may be used for bio-imaging.A549 cell line is used as cell imaging, culture medium
It is DMEM culture medium and add 10% hyclone, 100U mL-1Penicillin, 100mg mL-1Streptomysin, condition of culture is volume integral
Several 5% carbon dioxide, 37 DEG C incubated.When cell length to 90mm culture dish is paved with 80% part, with 37 DEG C of trypsase
Digestion, in being transferred to the burnt culture dish of copolymerization, growth is overnight, and PBS solution rinses cell, with containing fluorescent nano particles 100 μ g/mL's
DMEM maintains culture medium (2% serum) to change liquid, after 5 hours, abandons culture medium, rinses cell 3 times with PBS, 5 points every time
Clock, microscopy photograph under Laser Scanning Confocal Microscope, 408nm excites, and capture 650～700nm fluoroscopic examination fluorescent nano particles is (as attached
Fig. 4).It will be seen that nano particle is concentrated mainly on the cytosolic domain of cell and shows very high fluorescence signal.
Claims (3)
1. the near infrared fluorescent dye based on fumaric acid nitrile, its structural formula is as follows:
Wherein R is the group shown in one of following structural formula,
2. a kind of near infrared fluorescent dye based on fumaric acid nitrile as claimed in claim 1, shown in one of its structural formula is following:
3. a kind of near infrared fluorescent dye based on fumaric acid nitrile described in claim 1 or 2 is at bio-imaging or fluorescence labeling
In application.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610416587.3A CN106084873B (en) | 2016-06-14 | 2016-06-14 | A kind of efficiently near-infrared fluorescent material and its biologic applications |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610416587.3A CN106084873B (en) | 2016-06-14 | 2016-06-14 | A kind of efficiently near-infrared fluorescent material and its biologic applications |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106084873A true CN106084873A (en) | 2016-11-09 |
| CN106084873B CN106084873B (en) | 2018-02-23 |
Family
ID=57846707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610416587.3A Active CN106084873B (en) | 2016-06-14 | 2016-06-14 | A kind of efficiently near-infrared fluorescent material and its biologic applications |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106084873B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108530419A (en) * | 2018-05-31 | 2018-09-14 | 吉林大学 | A kind of nearly feux rouges organic fluorescence materials, preparation method and applications |
| CN111978952A (en) * | 2020-08-26 | 2020-11-24 | 链行走新材料科技(广州)有限公司 | Application of unconjugated fluorescent alternating copolymer in preparation of fluorescent material |
| CN113791060A (en) * | 2021-09-18 | 2021-12-14 | 吉林大学 | Cyanostyrene derivative, preparation method and application thereof, polymer detection probe and fluorescence detection method |
| CN115260057A (en) * | 2022-08-19 | 2022-11-01 | 中国科学院大学 | Improved method for preparing functionalized cis-trans dicyanoethylene compound by 2,5-dinitrothiophene desulfurization |
| KR102491823B1 (en) * | 2022-05-31 | 2023-01-26 | 엔비에스티(주) | Pressure discolored fluorescent material and forgery prevention device using the same |
| CN115960070A (en) * | 2022-12-01 | 2023-04-14 | 浙江众立合成材料科技股份有限公司 | Method for preparing bi-five-membered cyclic carbonate by using Heck reaction |
| KR102534289B1 (en) * | 2022-05-31 | 2023-05-30 | 엔비에스티(주) | Pressure doscolored fluorescent material and forgery prevention device using the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1248143A (en) * | 1998-09-11 | 2000-03-22 | 索尼株式会社 | Organic electroluminescent device |
| KR20060080378A (en) * | 2005-01-05 | 2006-07-10 | 네오뷰코오롱 주식회사 | Red organic light-emitting compound and organic light-emitting diode including the same |
| CN101085915A (en) * | 2006-06-09 | 2007-12-12 | 上海拓引数码技术有限公司 | Divinyl double-dipole red organic electroluminescence material and preparation method thereof |
-
2016
- 2016-06-14 CN CN201610416587.3A patent/CN106084873B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1248143A (en) * | 1998-09-11 | 2000-03-22 | 索尼株式会社 | Organic electroluminescent device |
| KR20060080378A (en) * | 2005-01-05 | 2006-07-10 | 네오뷰코오롱 주식회사 | Red organic light-emitting compound and organic light-emitting diode including the same |
| CN101085915A (en) * | 2006-06-09 | 2007-12-12 | 上海拓引数码技术有限公司 | Divinyl double-dipole red organic electroluminescence material and preparation method thereof |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108530419A (en) * | 2018-05-31 | 2018-09-14 | 吉林大学 | A kind of nearly feux rouges organic fluorescence materials, preparation method and applications |
| CN111978952A (en) * | 2020-08-26 | 2020-11-24 | 链行走新材料科技(广州)有限公司 | Application of unconjugated fluorescent alternating copolymer in preparation of fluorescent material |
| CN111978952B (en) * | 2020-08-26 | 2023-08-08 | 链行走新材料科技(广州)有限公司 | Application of non-conjugated fluorescent alternating copolymer in preparation of fluorescent material |
| CN113791060A (en) * | 2021-09-18 | 2021-12-14 | 吉林大学 | Cyanostyrene derivative, preparation method and application thereof, polymer detection probe and fluorescence detection method |
| CN113791060B (en) * | 2021-09-18 | 2022-08-09 | 吉林大学 | Cyanostyrene derivative, preparation method and application thereof, polymer detection probe and fluorescence detection method |
| KR102491823B1 (en) * | 2022-05-31 | 2023-01-26 | 엔비에스티(주) | Pressure discolored fluorescent material and forgery prevention device using the same |
| KR102534289B1 (en) * | 2022-05-31 | 2023-05-30 | 엔비에스티(주) | Pressure doscolored fluorescent material and forgery prevention device using the same |
| CN115260057A (en) * | 2022-08-19 | 2022-11-01 | 中国科学院大学 | Improved method for preparing functionalized cis-trans dicyanoethylene compound by 2,5-dinitrothiophene desulfurization |
| CN115960070A (en) * | 2022-12-01 | 2023-04-14 | 浙江众立合成材料科技股份有限公司 | Method for preparing bi-five-membered cyclic carbonate by using Heck reaction |
| CN115960070B (en) * | 2022-12-01 | 2024-06-21 | 浙江众立合成材料科技股份有限公司 | Method for preparing double five-membered ring carbonate by Heck reaction |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106084873B (en) | 2018-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106084873B (en) | A kind of efficiently near-infrared fluorescent material and its biologic applications | |
| CN105732564B (en) | A kind of two-photon fluorescence probe and the application in anoxic zone nitroreductase is detected | |
| CN107043623B (en) | A kind of method of the preparation and detection ferric ion, ascorbic acid of red fluorescence carbon nano dot | |
| CN102175655B (en) | Dual-mode optical imaging probe and preparation method thereof | |
| CN110982513B (en) | Preparation method of fluorescent carbon dots and application of fluorescent carbon dots in cell imaging | |
| CN105801479B (en) | Two-photon viscosity fluorescent probe and preparation method and application thereof | |
| CN110272734A (en) | A kind of high quantum production rate carbon quantum dot preparation method and applications for NO detection | |
| CN108069908A (en) | Fluorescence probe and its application | |
| CN105733563B (en) | Coumarin-based two-photon lysosome polar probe, and preparation method and application thereof | |
| CN108117544A (en) | A kind of reversible sulfur dioxide/sulfurous acid（Hydrogen）The fluorescence probe of salt | |
| CN103896928B (en) | A kind of pH fluorescence chemical sensor and synthetic method thereof and application | |
| CN106187880A (en) | Colored cyanines fluorescent probe based on aggregation-induced emission effect and preparation method and application | |
| CN109722059A (en) | Disposable class aggregation inducible cell film targeting staining reagent based on purine skeleton and its preparation method and application | |
| CN104830318B (en) | A kind of fluorescent tag molecule of high state of aggregation fluorescent emission and preparation method thereof | |
| CN109456250B (en) | Thermal Activation Delayed Fluorescence (TADF) nano probe, preparation method thereof and application thereof in biological imaging | |
| CN105906619B (en) | Two-photon fluorescent probe and preparation method and application thereof | |
| Han et al. | A diphenylacrylonitrile conjugated porphyrin with near-infrared emission by AIE–FRET | |
| CN106892870A (en) | Lysosome targeted two-photon viscosity fluorescent probe and preparation method and application thereof | |
| CN105503831B (en) | A kind of near infrared fluorescent probe and its preparation method and application with the response of pole acid pH | |
| CN110357896A (en) | A kind of compound and preparation and its application in detection bivalent cupric ion and strong acid pH | |
| CN110194900A (en) | A kind of fluorescent dye and preparation method thereof emitting near infrared light | |
| CN107056827A (en) | One kind is based on BODIPY class singlet oxygen fluorescence probes | |
| CN106699778B (en) | A kind of preparation method and applications of near infrared fluorescent dye | |
| CN111961072B (en) | Lysosome-targeted infrared two-window emission fluorescent dye and preparation method and application thereof | |
| CN113621366A (en) | Red fluorescent carbon dot and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |