CN109422707A - Aggregation-induced emission lysosome probe and the preparation method and application thereof independent of acid pH - Google Patents
Aggregation-induced emission lysosome probe and the preparation method and application thereof independent of acid pH Download PDFInfo
- Publication number
- CN109422707A CN109422707A CN201810750124.XA CN201810750124A CN109422707A CN 109422707 A CN109422707 A CN 109422707A CN 201810750124 A CN201810750124 A CN 201810750124A CN 109422707 A CN109422707 A CN 109422707A
- Authority
- CN
- China
- Prior art keywords
- acid
- aggregation
- lysosome
- independent
- induced emission
- 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
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
-
- 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
- C09K2211/1033—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with oxygen
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6432—Quenching
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Aggregation-induced emission lysosome probe and the preparation method and application thereof independent of acid pH, preparation method, the following steps are included: phenylethylene analog derivative A and Hete rocyclic derivatives B that halogen is replaced, which carry out Buchwald-Hartwig coupling reaction, generates crude product, remove the solvent in crude product, ethyl alcohol and acetone is added to dissolve crude product, filtering, filtrate is dry, then it is purified using chloroform and methanol as eluent by silica gel column chromatography to get the aggregation-induced emission lysosome probe independent of acid pH is arrived.Bioprobe of the invention has the characteristic for not depending on acid pH variation, and has responsiveness to environment viscosity.Its mechanism of action being imaged in lysosome is that internal molecular motion caused by viscosity is limited, compared with traditional PET mechanism of action, has the characteristics that better photostability and is not influenced by microenvironment acidity.
Description
Technical field
The invention belongs to the technical fields of bio-imaging, more particularly to independent of the aggregation-induced emission lyase of acid pH
Body probe and the preparation method and application thereof.
Background technique
Lysosome is a kind of important organelle for participating in the various kinds of cell metabolic process such as cell dissociation, dysfunction and each
Kind disease is related.Since its inner cavity is always maintained at acidic environment (pH=3.8-6.6), majority is for targeting lysosome
Bioprobe usually has pH dependence, and mechanism of action depends on the photo induced electron transfer (PET) that protonation inhibits.So
And the lysosome probe with this working mechanism has low signal-to-noise ratio, shines and is changed by microenvironment acidity change,
With unstability.Therefore, the exploitation independent of the lysosome targeted probes of acid pH is very important.In addition, having
Lysosome fluorescence probe independent of acid pH can also be used to monitor simultaneously the change of some important basic microenvironment parameters
Change without the interference by pH, such as in lysosome viscosity change detection etc..
Summary of the invention
The technical problem to be solved by the present invention is to prior art bioprobes usually to have pH dependence, shine by micro-
Conditioning acid changes and changes, and has the technical issues of unstability, and solves prior art biological synthesis method complexity, raw material
The low technical problem of the material state of aggregation luminous efficiency that at high cost, synthesis obtains.
The technical solution adopted by the present invention to solve the technical problems is:
Aggregation-induced emission lysosome probe independent of acid pH, it is characterised in that: including following three chemical formula:
Wherein X is O or N-CH3。
It is further preferred that the R in three chemical formulas is H or CN, R1、R2、R3And R4For identical or different atom
Or substituent group.
Further, the R1、R2、R3And R4Be hydrogen, halogen, pseudohalogen, substituted or unsubstituted alkyl, alkoxy,
Any one in alkyl amino, alkenyl, alkynyl, aryl and heteroaryl, the pseudohalogen are OH, SH, CN, NC, CP, OCN,
NCO, SCN, NSC, OSCNS, SeCN, N3 -, NO2, C (NO2)3 -, C (CN)3 -, OTf-With Co (CO)4In any one.
Further, the aryl is substituted or unsubstituted monocycle or polycyclic aromatic base with 6-20 carbon atom
Group, the aryl are phenyl, naphthalene, anthryl, pyrenyl.
In addition, the heteroaryl is substituted or unsubstituted a selected from N, S, O hetero atom with 1-20 carbon atom, 1-4
Monocycle or polycyclic hetero-aromatic group, the heteroaryl be piperazinyl, morpholinyl, pyrrole radicals, pyridyl group, pyrimidine radicals, imidazole radicals,
Any one in thiazolyl, indyl, azepine naphthalene, azepine anthryl and azepine pyrenyl.
It is further preferred that the aggregation-induced emission lysosome probe chemical formula independent of acid pH isR1、R2、R3And R4It is H.
The preparation method of aggregation-induced emission lysosome probe independent of acid pH, which is characterized in that including following
Step: it is anti-that the phenylethylene analog derivative A and Hete rocyclic derivatives B that halogen is replaced carry out Buchwald-Hartwig coupling
Crude product should be generated, the solvent in crude product is removed, ethyl alcohol and acetone is added to dissolve crude product, filtering, filtrate is dry, then
It is purified by silica gel column chromatography using chloroform and methanol as eluent to get the aggregation-induced emission independent of acid pH is arrived
Lysosome probe.
It is further preferred that the preparation method includes changing described in chemical reaction I, chemical reaction II and chemical reaction III
Learn reaction I are as follows:
Chemically react II are as follows:
Chemically react III are as follows:
Wherein the X in above three chemical reaction is O or N-CH3。
Further, the chemical structural formula of the phenylethylene analog derivative A of the halogen substitution is
Wherein X ' is halogen, and X ' is bromo；The chemical structural formula of the Hete rocyclic derivatives B are as follows: N methyl piperazine
Or morpholine
The purposes of aggregation-induced emission lysosome probe independent of acid pH, it is characterised in that: for not by acidity
The bio-imaging of lysosome targeting and tracer that pH influences.
Implement it is provided by the invention, can achieve it is following the utility model has the advantages that
(1) the lysosome targeting and tracer of the phenylethylene derivative the invention proposes one kind containing piperazine or morpholine
MOLECULE DESIGN synthesizes new strategy, it is perfectly balanced between lipophilicity and polarity to realize such molecule, and in lysosome target
Application into the bio-imaging with tracer；
(2) the phenylethylene derivative synthesizing process of the invention based on piperazine or morpholine is simple, cost of material is low, synthesis
Obtained material state of aggregation luminous efficiency is high；
(3) bioprobe of the invention shows the property of aggregation-induced emission under UV Light, in high concentration item
Under part, biological imaging can also be carried out, and traditional fluorescent dye then has aggregation inducing fluorescence under a high concentration condition
The phenomenon that quenching, therefore effectively overcome the defect of traditional fluorescent dye；
(4) bioprobe of the invention has the characteristic for not depending on acid pH variation, and has responsiveness to environment viscosity,
Its mechanism of action being imaged in lysosome is that internal molecular motion caused by viscosity is limited, compared with traditional PET mechanism of action,
Have the characteristics that better photostability and is not influenced by microenvironment acidity.
Detailed description of the invention
Fig. 1 is the piperazinyl tetraphenylethylene nucleus magnetic hydrogen spectrum of embodiment 1 of the present invention preparation；
Fig. 2 is the piperazinyl tetraphenylethylene nuclear-magnetism carbon spectrum of embodiment 1 of the present invention preparation；
Fig. 3 is the high-resolution matter (MALDI-TOF) of piperazinyl tetraphenylethylene prepared by embodiment 1；
Fig. 4 is the mono-crystalline structures figure of piperazinyl tetraphenylethylene prepared by embodiment 1；
Fig. 5 is the solution (0.8 × 10 of piperazinyl tetraphenylethylene prepared by embodiment 1-5M) and the normalization of film is ultraviolet
Absorption spectrum (A), solution (0.8 × 10-5) and the normalization photoluminescence spectra (B) of crystalline powder M；
Fig. 6 is glycerol/methanol mixed solution of the piperazinyl tetraphenylethylene in different volumes score of the preparation of embodiment 1
(10-5M photoluminescence spectra (A) and absolute fluorescence quantum yield (B) in)；
Fig. 7 is the photoluminescence spectra (A) of the PH buffered aqueous solution of piperazinyl tetraphenylethylene prepared by embodiment 1, absolutely
To fluorescence quantum yield (B), absolute fluorescence quantum yield (C) of the different acidic buffer solutions under various viscosity, different viscosities
Acidic buffer solution and protonation film normalization photoluminescence spectra (D)；
Fig. 8 is that the piperazinyl tetraphenylethylene prepared by 1 μM by embodiment 1 and 200nMLysoTracker Red contaminate altogether
The Confocal Images (A and B) of color 15 minutes HeLa cells, the merging image (C) of (A) and (B), brightfield image (D)；
Fig. 9 is that (A and B) not after 15 minutes for the piperazinyl tetraphenylethylene incubation that is prepared with 1 μM by embodiment 1 of HeLa cell
Through processing or (C and D) with 2mL 4%PFA (paraformaldehyde) handle HeLa cell light field (A and C) and fluorescence imaging figure (B with
D)；
Figure 10 is the cell viability testing result of the HeLa cell after piperazinyl tetraphenylethylene prepared by embodiment 1 incubates
Figure；
Figure 11 is piperazinyl tetraphenylethylene prepared by embodiment 1 and the photostability of LysoTracker Red；
Figure 12 HeLa cell and 1 μM of piperazinyl tetraphenylethylene incubation prepared by embodiment 1 used 3 μM of chlorine after 15 minutes
Total focused view of the quinoline under 0 minute (A), 1 minute (B), 2 minutes (C), 3 minutes (D), 4 minutes (E), 0 and 1 minute merging image
(F), 1 and 2 minute merging image (G), 2 and 3 minutes merging images (H), 3 and 4 minutes merging images (I) merge for 0 and 4 minute
Image (J).
Specific embodiment
For a clearer understanding of the technical characteristics, objects and effects of the present invention, now control attached drawing is described in detail
A specific embodiment of the invention.Obviously, described embodiments are only a part of the embodiments of the present invention, rather than whole
Embodiment.Based on the embodiments of the present invention, those of ordinary skill in the art are obtained without making creative work
The every other embodiment obtained, shall fall within the protection scope of the present invention.
Independent of the aggregation-induced emission lysosome probe of acid pH, following three chemical formula is specifically included:
Wherein X is O or N-CH3.R in three chemical formulas is H or CN, R1、R2、R3And R4For identical or different atom or take
For group.R1、R2、R3And R4All can be hydrogen, halogen, pseudohalogen, substituted or unsubstituted alkyl, alkoxy, alkyl amino,
Any one in alkenyl, alkynyl, aryl and heteroaryl, pseudohalogen OH, SH, CN, NC, CP, OCN, NCO, SCN, NSC,
OSCNS, SeCN, N3 -, NO2, C (NO2)3 -, C (CN)3 -, OTf-With Co (CO)4In any one, aryl preferably replace or not
The monocycle or polycyclic aromatic group with 6-20 carbon atom replaced, preferably phenyl, naphthalene, anthryl, pyrenyl.Heteroaryl is excellent
It is selected as substituted or unsubstituted a selected from the heteroatomic monocycle of N, S, O or polycyclic hetero-aromatic base with 1-20 carbon atom, 1-4
Group, heteroaryl is preferably piperazinyl, morpholinyl, pyrrole radicals, pyridyl group, pyrimidine radicals, imidazole radicals, thiazolyl, indyl, azanaphthalene
Any one in base, azepine anthryl and azepine pyrenyl.
Aggregation-induced emission lysosome probe chemical formula independent of acid pH is preferably
R1、R2、R3And R4It is H.
Aggregation-induced emission lysosome probe preparation method independent of acid pH is specifically includes the following steps: by halogen
Substituted phenylethylene analog derivative A and Hete rocyclic derivatives B carries out Buchwald-Hartwig coupling reaction and generates thick produce
Object removes the solvent in crude product, ethyl alcohol and acetone is added to dissolve crude product, filtering, filtrate is dry, then with chloroform and first
Alcohol is purified by silica gel column chromatography as eluent and is visited to get to the aggregation-induced emission lysosome independent of acid pH
Needle, the chemical structural formula of phenylethylene analog derivative A that wherein halogen replaces are
Wherein X ' is halogen
Element, X ' are bromo；The chemical structural formula of the Hete rocyclic derivatives B are as follows: N methyl piperazineOr morpholine
With X ' in phenylethylene analog derivative A for bromo (Br), Hete rocyclic derivatives B isWhen, it generates independent of acid
The chemical reaction general formula of the aggregation-induced emission lysosome probe I-III of property pH is as follows:
It below will be to embodiment 1, that is, when being based on piperazinyl tetraphenylethylene bioprobe molecule (hereinafter referred to as PIP-TPE)
Synthetic method and function be described in detail, the preferred chemical formula of embodiment 1 is
Work as R1、R2、R3And R4It is H, X N-CH3When as PIP-TPE, i.e. chemical formula
Are as follows:
Synthetic route is as follows:
Specific reaction step are as follows: in two mouthfuls of flasks of 100mL round bottom, by the tertiary fourth of 0.449g (1.55mmol) tetrafluoro boric acid three
Base phosphorus (P (tBu)3HBF4), 3.600g (11.00mmol) cesium carbonate (Cs2CO3), the toluene of 20mL drying and degassing is respectively in room
It is added and stirs 1 hour under mild nitrogen atmosphere.Then 0.097g (0.43mmol) Pd (OAc) is added2, under a nitrogen will reaction
Mixture is stirred for 0.5 hour.When solution forms orange suspension, 1.000g (2.04mmol) 1,1'- (2,2- bis- is added
Phenyl vinyl) bis- (4- bromine)-benzene and 0.5mL (4.51mmol) 1- methyl piperazine, it is outstanding to form pistac for reaction solution at this time
Turbid.Reaction mixture is flowed back under nitrogen atmosphere 2 days.After reaction is cooled to room temperature, toluene is removed, 50mL EtOH is added
With 10mL acetone to dissolve crude product.Suspension is filtered, be concentrated under reduced pressure and passes through silica gel column chromatography (chloroform/MeOH=40:1)
Purifying.Obtain the yellow powder of PIP-TPE, yield: 15%, the compound spread in acetone/hexane solvent grow it is yellowish
Color bulk crystals.
The chemical structure of PIP-TPE characterizes:
Nuclear-magnetism characterization (Fig. 1: nucleus magnetic hydrogen spectrum has been carried out to the chemical structure for the PIP-TPE that synthesis obtains；Fig. 2: nuclear-magnetism carbon
Spectrum), high resolution mass spectrum characterizes (Fig. 3) and mono-crystalline structures characterization (Fig. 4).
The photophysical property of PIP-TPE characterizes:
Photophysical property research has been carried out in the solvent of opposed polarity and under solid-state to PIP-TPE.As shown in Figure 5A, scheme
5 be glycerol/methanol mixed solution (10 of the piperazine base tetraphenylethylene in different volumes score-5M photoluminescence spectra (A) in) and
Absolute fluorescence quantum yield (B), all data acquire at 25 DEG C, excitation wavelength 360nm；PIP-TPE in solvent has
Similar uv-visible absorption spectra, peak value have at 250-450nm and inhale about at 275nm, 302nm, 346nm
Take-up.The absorption peak of the film of the molecule near 277nm, 305nm and 356nm there is the bandwidth being remarkably reinforced (to reach
600nm).But it exists in neutral aqueous solution with amorphous suspension form, the purple of the aqueous solution suspension of the compound
Outer absorption has certain blue shift relative to its UV absorption in organic solvent, this can at 267nm, 290nm and 325nm
It can be due to forming hydrogen bond between the nitrogen-atoms and hydrone of piperazine primitive in PIP-TPE, so as to form the aqueous of hydrogen bonding
PIP-TPE aggregation and caused by.
In PIP-TPE, piperazine unit can be considered as to electron donor, and TPE unit is considered as electron acceptor.PIP-TPE
With very weak D-A structure.Therefore, its solvatochromic Benefit Transfer in opposed polarity solvent is faint.For example, its
430nm variation of the fluorescent emission peak value from the 413nm red shift in the 404nm in hexane, THF into DMSO in organic solvent
(Fig. 5 B).However, since PIP-TPE is in neutral H2It cannot be dissolved well in O and tend to form micron order aggregation, it
The fluorescent emission of the amorphous aggregation formed in aqueous solution has big red shift, and emission peak is at 509nm (Fig. 5).Similarly,
The emission peak of the crystalline powder of PIP-TPE is at 493nm.In addition, absolute quantum yield of the PIP-TPE in THF solution is
0.6%, and the absolute fluorescence quantum yield of film and crystalline powder is respectively 14.8% and 42.2%.With the increasing of glycerol content
Add, PIP-TPE is in glycerol/methanol mixed solution (10-5M the absolute fluorescence quantum yield in) increases (Fig. 6), and Fig. 6 is piperazine
The photoluminescence spectra (A) of the PH buffered aqueous solution of base tetraphenylethylene, (illustration is in 365nm to absolute fluorescence quantum yield (B)
Ultraviolet light irradiation under pH buffer solution photo)；Absolute fluorescence quantum of the different acidic buffer solutions under various viscosity
Yield (the C) (solution and pH=5.35 that illustration is the pH=5.59 under the ultraviolet light irradiation of 365nm and viscosity is 32.46cP
And viscosity is the solution of 7.94cP), the acidic buffer solution of different viscosities and the normalization photoluminescence spectra of protonation film
(D), all data acquire at 25 DEG C, solution concentration 0.8 × 10-5M, excitation wavelength 360nm；Compound PIP-TPE has
Aggregation-induced emission (AIE) characteristic.
The pH and viscosity sensitive of PIP-TPE:
As shown in fig. 7, Fig. 7 is the photoluminescence spectra (A) of the PH buffered aqueous solution of piperazinyl tetraphenylethylene, it is absolutely glimmering
(illustration is the photo of the pH buffer solution under the ultraviolet light irradiation of 365nm, different acidic buffer solutions to quantum yield (B)
In the absolute fluorescence quantum yield (C) under various viscosity, (illustration is pH=5.59 and viscosity under the ultraviolet light irradiation of 365nm
The solution that solution and pH=5.35 and viscosity for 32.46cP are 7.94cP), the acidic buffer solution of different viscosities and protonation
The normalization photoluminescence spectra (D) of film, data acquire at 25 DEG C, solution concentration 0.8 × 10-5M, excitation wavelength are
360nm；(emission peak is for fluorescence quantum yield (Fig. 7 B) of the PIP-TPE in the buffer solution of pH=1-6 and fluorescence intensity
420nm) (Fig. 7 A) is kept approximately constant.Fluorescence of the PIP-TPE in acidic buffer solution is weaker, and fluorescence quantum yield is less than
1%.However, significant change (fluorescence emission peak 509nm) occurs for the fluorescence of PIP-TPE in the buffer solution of pH=7.13,
Absolute fluorescence quantum yield is 1.8%, and fluorescence naked eyes are visible.PIP-TPE fluorescence intensity in the alkaline aqueous solution of pH=13.03
Increase (Fig. 7 B), absolute fluorescence quantum yield reaches maximum value 12.7%.In fact, in acid water environment, protonation
The tendency that PIP-TPE forms big aggregation is smaller.Grain of the PIP-TPE in the buffer solution that pH value is 0.85,5.05 and 13.03
Diameter is respectively 89nm, and 385nm and 24.2 μm.The PIP-TPE molecule for showing protonation cannot in the aqueous solution of acid ph value
Form big (micron order) aggregation.Since the protonation of PIP-TPE leads to intermolecular repulsion, PIP-TPE connects in viscosity and water
There is low absolute fluorescence quantum yield, this PIP-TPE for being mainly due to protonation has more preferable in close acidic environment
Dissolubility and reduced aggregation tendency.Fluorescence quantum yield of the PIP-TPE in alkaline aqueous solution it is higher mainly due to compared with
Big aggregation-induced emission effect.
In cell system, lysosome is that the highest most acid organelle of viscosity in an experiment can be by different proportion
Acidic buffer solution and a series of acid solution of viscosity gradients of glycerol composition simulate lyase vivo environment to study
Photoluminescent property of the PIP-TPE in lysosome.As viscosity increases to 438.40cP, the fluorescent quantum of PIP-TPE from 2.15cP
Yield increases to 8.2% from 0.6%, and under certain viscosity and when pH range changes to 6.94 from 2.95, PIP-TPE
Fluorescence there is no any significant variation (Fig. 7 C).For example, fluorescence volume of the PIP-TPE in the acid solution that viscosity is 7.94cP
Sub- yield is all close to 0.9%.However, the molecule obviously becomes in the fluorescence quantum yield for the acid solution that viscosity is 32.46cP
Greatly, about 1.5% (Fig. 7 C).In addition, in an acidic solution, absolute fluorescence of the PIP-TPE in the environment that viscosity is 78.90cP
Quantum yield is 2.3%, is 3.4% at 140.60cP, is 4.7% at 246.70cP.On the other hand, in similar pH but tool
There are different viscosities or difference pH but have in the solution of similar viscosity, the photoluminescence emission peak of PIP-TPE is in 410-419nm
Near.For example, PIP-TPE is in pH=5-6, the buffer solution that viscosity is 2.15-4.38.40cP and it is in pH=3.41-
6.83, it is dark blue light (Fig. 7 D) that viscosity, which is the luminescence generated by light in the buffer solution of 78.90cP,.In addition, protonation PIP-TPE is thin
The emission peak of film is at 488nm (Fig. 7 D), and similar to the emission peak of PIP-TPE crystalline powder (Fig. 5 B), this shows its PIP-TPE's
Fluorescent emission is not influenced by protonating.Above-mentioned experiment shows the protonation of PIP-TPE in its non-agglomerated state or monodisperse state
Under photophysical property do not have it is any significantly affect, but it is small-scale greatly to influence its aggregation.The fluorescence of PIP-TPE depends on
Viscosity, but it is unrelated with acid pH variation.Therefore, the absolute fluorescence quantum yield of PIP-TPE is suitable for the variation of monitoring viscosity.
The bio-imaging application of PIP-TPE:
PIP-TPE has good selectivity lysosome.Under ultraviolet excitation, which shows in lysosome
Strong fluorescence out.Hela cell and PIP-TPE and business lysosome probe LysoTrackerRed are dyed altogether at 37 DEG C
15 minutes.As shown in figure 8, Fig. 8 is to dye 15 altogether by 1 μM of piperazinyl tetraphenylethylene and 200nM LysoTracker Red
The Confocal Images (A and B) of the HeLa cell of minute, the merging image (C) of (A) and (B), bright-field (D), excitation wavelength: piperazine
Piperazine base tetraphenylethylene is 405nm, and ((lysosome red fluorescence probe) is 561nm, scale bar 20 to LysoTracker Red
Micron；PIP-TPE in Hela cell is displayed in blue fluorescence (Fig. 8 A) under the microscope, and LysoTracker Red is in 561nm
Excitation wavelength under be displayed in red fluorescence (Fig. 8 B).Merge image (Fig. 8 C) and shows two images (Fig. 8 A and Fig. 8 B) overlapping very
It is good, related coefficient 0.82, it was demonstrated that PIP-TPE can be with specific localization in the lysosome of living cells, although in PIP-TPE
Tetraphenylethylene primitive is hydrophobic, but two hydrophily piperazine primitives are introduced into tetraphenylethylene will increase its
Solubility in acidic aqueous solution, therefore the compound has good signal-to-noise ratio (Fig. 8 A) when targeting lysosome.
Since the size (100nm to 1.2 μm) of lysosome is usually submicron-scale, and the PIP-TPE molecule protonated
Big (micron order) aggregation is not easily formed in acid medium, therefore the molecule will be mainly individually to protonate in lysosome
The form of molecule and/nano-sized aggregates exists.The fluorescence of PIP-TPE is blue in lysosome under uv excitation light.Due to
Its fluorescence is not influenced by pH value variation in acidic environment, but highly sensitive to viscosity, and PIP-TPE is water-soluble in the acidity of low viscosity
It hardly fluoresces in liquid.However, the fluorescence of PIP-TPE is opened in the biggish lysosome of viscosity.Fixed cell and living cells
The comparison (Fig. 9) of experiment shows that Fig. 9 is that HeLa cell and 1 μM incubate 15 points by piperazinyl tetraphenylethylene prepared by embodiment 1
(A and B) unprocessed after clock or (C and D) handles the light field (A of HeLa cell (15 minutes) with 2mL 4%PFA (paraformaldehyde)
And C) and fluorescence imaging figure (B and D), for excitation wavelength using 330-385nm, scale bar is 20 microns；Once the bright Hela of this chart
Cell is fixed, and PIP-TPE just loses the selectivity to lysosome, and lights in entire cytoplasm.Due to cytoplasmic solution
Viscosity is low, and the PIP-TPE in Hela cell living is also spread in cytosol, without any apparent effect.Therefore, PIP-
TPE is attributable to the high viscosity of the piperazine functional group and lysosome in the molecule to the good selectivity of lysosome to intramolecular
The mechanism of action of limitation of movement, rather than protonate and inhibit electronics transfer (PET).
As biological targeting probe, low cytotoxicity and good biocompatibility are the key features of living cells imaging.
Therefore, PIP- is further studied by MTT (bromination 3- (4,5- dimethylthiazole -2- base) -2,5- diphenyltetrazoliumbromide) test
The cell viability of TPE.As a result (Figure 10) is shown, for the PIP-TPE for the 5 of incubation μM higher concentration, optimization
Dyeing concentration (1 μM) does not have apparent cytotoxicity to HeLa cell.
There is serious photobleaching phenomenon after exciting due to business lysosome probe LysoTracker Red at second, because
This business lysosome probe LysoTracker Red cannot be used for tracer lysosome.However, the lysosome in addition to specificity targets
Outside ability, PIP-TPE ratio LysoTracker Red has better photostability (Figure 11), and shows that good tracer is molten
The ability of enzyme body, chloroquine are a kind of typical lysosome drugs, for driving lysosome migration without the induction times in cell
What his apparent disorder, can be used for that lysosome is stimulated to move in HeLa cell.As shown in figure 12, in 4 minutes periods
The confocal images of interior record PIP-TPE tracer lysosome.It, can be with by merging the image that shoots in different time points
The drift bearing and moving distance (Figure 12 F-J) of lysosome is clearly viewed.Such as Figure 12 (A-E), HeLa cell is with 1 μM by implementing
Piperazinyl tetraphenylethylene prepared by example 1 uses 3 μM of chloroquines at 0 minute (A), 1 minute (B), 2 minutes (C) after incubating 15 minutes,
Total focused view under 3 minutes (D), 4 minutes (E), it is 0 and 1 minute (F), 1 and 2 minute that two different time points, which merge image,
(G), 2 and 3 minutes (H), 3 and 4 minutes (I), 0 and 4 minute (J), the direction of motion of the arrow instruction lysosome in box, excitation
Wavelength is 405nm, and scale bar is 20 microns, this chart is bright can be defined in the merging image of any two continuous time shooting
Ground shows the short-term change in displacement of lysosome (Figure 12 F-1).The experiment discloses the ability and lyase of PIP-TPE tracer lysosome
The direction that body position random drift changes.It, can be with by analyzing the merging image (Figure 12 J) shot at the 0th minute and the 4th minute
Observe the obvious big change in displacement of lysosome.The high-resolution copolymerization of this PIP-TPE for tracer lysosome is burnt
Image is due principally to the good photostability of PIP-TPE, high fluorescent yield and insignificant background fluorescence.
It is above-mentioned statistics indicate that, the present invention connects the lyase of piperazinyl or morpholinyl using phenylethylene as core on phenyl ring
Body targets group, obtains the bioprobe molecule with the lysosome targeting and traceability for not depending on acid pH.This kind of lyase
Body targeted probes molecule has aggregation-induced emission (AIE) characteristic.This kind of compound is applied on lysosome cell imaging, is led to
It crosses and carries out total dye Experimental comparison with commercial organelle dyestuff, it was confirmed that there is this kind of compound excellent organelle-specificity to dye
The targeting of effect, especially lysosome and traceability, good signal-to-noise ratio and low cytotoxicity.This kind of fluorescent molecule shines
Mechanism of action is mainly due in fluorescent molecule caused by the viscosity higher of lysosome targeting functional group and lyase vivo environment
Limitation of movement, therefore, this kind of molecule are not changed by lysosomal acid and are changed, and can be used to refer to the change of microenvironment viscosity
Change.In addition, lysosome targeted probes of the invention have photostability more better than business substitute such as LysoTrackerRed
, it can be widely applied in the bio-imaging material independent of acid pH.
The present invention is using phenylethylene as core, especially using tetraphenylethylene as core, connected on phenyl ring piperazinyl or
The lysosome of morpholinyl targets group, and gained molecule has the lysosome targeting and traceability for not depending on acid pH.Containing
The phenylethylene derivative that the tetraphenylethylene or its amino of quinoline and piperazine replace has aggregation-induced emission (AIE) characteristic.This
Class molecule consists of two parts, i.e. the amino-heterocycles such as piperazine as the phenylethylene AIE activity unit of receptor and as donor
And morpholine.For example, being the tetraphenylethylene of piperazine as model compound using two phenyl ring para-orientating groups, the compound is by supplying
Body piperazine primitive and as receptor tetraphenylethylene primitive form.The present invention is to be based on piperazinyl tetraphenylethylene bioprobe
For molecule, the photophysical property of the compound, pH and viscosity sensitive are had studied, the results showed that the molecule does not have acid pH
There is dependence, but has good responsiveness to viscosity.By carrying out total dye experiment with commercial organelle dyestuff, it was confirmed that it has
The targeting of excellent organelle-specificity dyeing effect, especially lysosome and traceability, good signal-to-noise ratio and low cell
Toxicity.The molecule to the good selectivity of lysosome be attributable to piperazine lysosome targeting functional group and lyase vivo environment compared with
Limitation of movement in fluorescent molecule caused by high viscosity, therefore, the luminous function mechanism of the fluorescent molecule is not by lysosomal acid
Change and change, and the variation of environment viscosity can be used to refer to.The working principle of this lysosome targeting, which becomes, to be had
The good lysosome tracer of photostability more better than business substitute such as LysoTracker Red.This MOLECULE DESIGN plan
It can slightly play a significant role in the lysosome targeting for synthesizing amino-containing AIE characteristic, can be widely applied to not depend on
In the bio-imaging material of pH.
The embodiment of the present invention is described with above attached drawing, but the invention is not limited to above-mentioned specific
Embodiment, the above mentioned embodiment is only schematical, rather than restrictive, those skilled in the art
Under the inspiration of the present invention, without breaking away from the scope protected by the purposes and claims of the present invention, it can also make very much
Form, all of these belong to the protection of the present invention.
Claims (10)
1. the aggregation-induced emission lysosome probe independent of acid pH, it is characterised in that: including following three chemical formula:
Wherein X is O or N-CH3。
2. as described in claim 1 independent of the aggregation-induced emission lysosome probe of acid pH, it is characterised in that: three
R in the chemical formula is H or CN, R1、R2、R3And R4For identical or different atom or substituent group.
3. as claimed in claim 2 independent of the aggregation-induced emission lysosome probe of acid pH, it is characterised in that: described
R1、R2、R3And R4It is hydrogen, halogen, pseudohalogen, substituted or unsubstituted alkyl, alkoxy, alkyl amino, alkenyl, alkynyl, virtue
Any one in base and heteroaryl, the pseudohalogen are OH, SH, CN, NC, CP, OCN, NCO, SCN, NSC, OSCNS, SeCN,
N3 -, NO2, C (NO2)3 -, C (CN)3 -, OTf-With Co (CO)4In any one.
4. as claimed in claim 3 independent of the aggregation-induced emission lysosome probe of acid pH, it is characterised in that: described
Aryl be substituted or unsubstituted monocycle or polycyclic aromatic group with 6-20 carbon atom, the aryl be phenyl, naphthalene,
Anthryl, pyrenyl.
5. as claimed in claim 3 independent of the aggregation-induced emission lysosome probe of acid pH, it is characterised in that: described
Heteroaryl is substituted or unsubstituted a selected from the heteroatomic monocycle of N, S, O or polycyclic hetero-aromatic with 1-20 carbon atom, 1-4
Group, the heteroaryl are piperazinyl, morpholinyl, pyrrole radicals, pyridyl group, pyrimidine radicals, imidazole radicals, thiazolyl, indyl, azepine
Any one in naphthalene, azepine anthryl and azepine pyrenyl.
6. as described in claim 1 independent of the aggregation-induced emission lysosome probe of acid pH, it is characterised in that: described
Aggregation-induced emission lysosome probe chemical formula independent of acid pH isR1、R2、R3And R4
It is H.
7. the system of the aggregation-induced emission lysosome probe independent of acid pH as described in claim 1~6 any one
Preparation Method, which comprises the following steps: the phenylethylene analog derivative A and Hete rocyclic derivatives B for replacing halogen are carried out
Buchwald-Hartwig coupling reaction generates crude product, removes the solvent in crude product, and ethyl alcohol and acetone is added to dissolve
Crude product, filtering, filtrate is dry, is then purified using chloroform and methanol as eluent by silica gel column chromatography to get to not
Aggregation-induced emission lysosome probe dependent on acid pH.
8. the preparation method independent of the aggregation-induced emission lysosome probe of acid pH as claimed in claim 7, special
Sign is that the preparation method includes chemical reaction I, chemical reaction II and chemical reaction III, the chemical reaction I are as follows:
Chemically react II are as follows:
Chemically react III are as follows:
Wherein the X in above three chemical reaction is O or N-CH3。
9. the preparation method independent of the aggregation-induced emission lysosome probe of acid pH as claimed in claim 8, special
Sign is: the chemical structural formula for the phenylethylene analog derivative A that the halogen replaces are as follows:
Wherein X ' is halogen,
X ' is bromo；The chemical structural formula of the Hete rocyclic derivatives B are as follows: N methyl piperazineOr morpholine
10. the use of the aggregation-induced emission lysosome probe independent of acid pH as described in claim 1~6 any one
On the way, it is characterised in that: the bio-imaging of lysosome targeting and tracer for not influenced by acid pH.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762605736P | 2017-08-25 | 2017-08-25 | |
| US62/605,736 | 2017-08-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109422707A true CN109422707A (en) | 2019-03-05 |
| CN109422707B CN109422707B (en) | 2022-08-23 |
Family
ID=65513712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810750124.XA Active CN109422707B (en) | 2017-08-25 | 2018-07-10 | Aggregation-induced emission lysosome probe independent of acidic pH (potential of Hydrogen), and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109422707B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111349070A (en) * | 2020-02-12 | 2020-06-30 | 曲阜师范大学 | Near-infrared fluorescent molecular probe for detecting biological cell viscosity and preparation method and application thereof |
| CN111434656A (en) * | 2019-11-12 | 2020-07-21 | 陕西师范大学 | Aggregation-induced photosensitive material with lysosome targeting property and preparation method and application thereof |
| CN112028871A (en) * | 2020-08-20 | 2020-12-04 | 宁波大学 | Lysosome targeted photosensitizer, synthetic method and application in biological imaging |
| CN112225721A (en) * | 2020-10-21 | 2021-01-15 | 复旦大学 | Acid-responsive near-infrared lysosome organic small-molecule fluorescent probe and preparation method and application thereof |
| CN112625006A (en) * | 2020-12-22 | 2021-04-09 | 吉林大学 | Cell lipid drop fluorescence imaging probe based on stilbene skeleton and application thereof |
| CN112851575A (en) * | 2019-11-12 | 2021-05-28 | 香港科技大学深圳研究院 | Ratio type lysosome pH probe with aggregation-induced emission property and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104877668A (en) * | 2015-04-07 | 2015-09-02 | 华东理工大学 | Leave-on near-infrared lysosome probe |
| CN107098923A (en) * | 2017-05-15 | 2017-08-29 | 天津理工大学 | One class feux rouges targets fluorescent dye and preparation method thereof and purposes near infrared emission lysosome |
-
2018
- 2018-07-10 CN CN201810750124.XA patent/CN109422707B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104877668A (en) * | 2015-04-07 | 2015-09-02 | 华东理工大学 | Leave-on near-infrared lysosome probe |
| CN107098923A (en) * | 2017-05-15 | 2017-08-29 | 天津理工大学 | One class feux rouges targets fluorescent dye and preparation method thereof and purposes near infrared emission lysosome |
Non-Patent Citations (2)
| Title |
|---|
| DUAN, XIN-FANG; ZENG, JING; LUE, JIA-WEI; ZHANG, ZHAN-BIN: "Insights into the General and Efficient Cross McMurry Reactions between Ketones", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| YUANJING CAI ET.AL.: "An acidic pH independent piperazine–TPE AIEgen as a unique bioprobe for lysosome tracing", 《CHEM. SCI.》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111434656A (en) * | 2019-11-12 | 2020-07-21 | 陕西师范大学 | Aggregation-induced photosensitive material with lysosome targeting property and preparation method and application thereof |
| CN112851575A (en) * | 2019-11-12 | 2021-05-28 | 香港科技大学深圳研究院 | Ratio type lysosome pH probe with aggregation-induced emission property and application |
| CN111434656B (en) * | 2019-11-12 | 2023-02-03 | 陕西师范大学 | Aggregation-induced photosensitive material with lysosome targeting property and preparation method and application thereof |
| CN111349070A (en) * | 2020-02-12 | 2020-06-30 | 曲阜师范大学 | Near-infrared fluorescent molecular probe for detecting biological cell viscosity and preparation method and application thereof |
| CN111349070B (en) * | 2020-02-12 | 2022-09-20 | 曲阜师范大学 | Near-infrared fluorescent molecular probe for detecting biological cell viscosity and preparation method and application thereof |
| CN112028871A (en) * | 2020-08-20 | 2020-12-04 | 宁波大学 | Lysosome targeted photosensitizer, synthetic method and application in biological imaging |
| CN112028871B (en) * | 2020-08-20 | 2021-12-28 | 宁波大学 | Lysosome targeted photosensitizer, synthetic method and application in biological imaging |
| CN112225721A (en) * | 2020-10-21 | 2021-01-15 | 复旦大学 | Acid-responsive near-infrared lysosome organic small-molecule fluorescent probe and preparation method and application thereof |
| CN112225721B (en) * | 2020-10-21 | 2021-09-17 | 复旦大学 | Acid-responsive near-infrared lysosome organic small-molecule fluorescent probe and preparation method and application thereof |
| CN112625006A (en) * | 2020-12-22 | 2021-04-09 | 吉林大学 | Cell lipid drop fluorescence imaging probe based on stilbene skeleton and application thereof |
| CN112625006B (en) * | 2020-12-22 | 2022-03-29 | 吉林大学 | Cell lipid drop fluorescence imaging probe based on stilbene skeleton and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109422707B (en) | 2022-08-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109422707A (en) | Aggregation-induced emission lysosome probe and the preparation method and application thereof independent of acid pH | |
| Oliveira et al. | Green and red fluorescent dyes for translational applications in imaging and sensing analytes: A dual‐color flag | |
| Gupta et al. | A review of mechanisms for fluorescent ‘‘turn-on’’probes to detect Al 3+ ions | |
| Yang et al. | Benzo [a] phenoxazinium-based red-emitting chemosensor for zinc ions in biological media | |
| Sheng et al. | A new colorimetric chemosensor for Hg2+ based on coumarin azine derivative | |
| Qian et al. | “Alive” dyes as fluorescent sensors: fluorophore, mechanism, receptor and images in living cells | |
| Müller et al. | Red‐to NIR‐Emitting, BODIPY‐Based, K+‐Selective Fluoroionophores and Sensing Materials | |
| Wang et al. | Biocompatible fluorescent core–shell nanoparticles for ratiometric oxygen sensing | |
| Zhou et al. | Water-soluble rhodamine-based chemosensor for Fe3+ with high sensitivity, selectivity and anti-interference capacity and its imaging application in living cells | |
| US9109155B2 (en) | Heterocycle-functionalized luminogens exhibiting aggregation-induced emission | |
| Ma et al. | Positively charged hyperbranched polymers with tunable fluorescence and cell imaging application | |
| Li et al. | A multifunctional quinoxalin-based AIEgen used for fluorescent thermo-sensing and image-guided photodynamic therapy | |
| Gao et al. | Solvent-dependent ratiometric fluorescent merocyanine dyes: Spectral properties, interaction with BSA as well as biological applications | |
| Tripathy et al. | A styrylpyridinium dye as chromogenic and fluorogenic dual mode chemosensor for selective detection of mercuric ion: Application in bacterial cell imaging and molecular logic gate | |
| Liu et al. | Silica nanoparticles based on an AIE-active molecule for ratiometric detection of RNS in vitro | |
| CN107098923A (en) | One class feux rouges targets fluorescent dye and preparation method thereof and purposes near infrared emission lysosome | |
| CN107407672A (en) | The stable AIE fluorogens of light for accurate and Sensitive Detection S phases DNA synthesis and cell propagation | |
| Dong et al. | A reversible frequency upconversion probe for real-time intracellular lysosome-pH detection and subcellular imaging | |
| CN111334078B (en) | 405nm excited high-brightness and high-stability fluorescent dye and synthetic method thereof | |
| Li et al. | Novel butterfly-shaped AIE-active pyrrolopyrrole aza-BODIPYs: synthesis, bioimaging and diamine/polyamine detection | |
| CN102702769B (en) | Green fluorescence cyanine dye and preparation method as well as application thereof | |
| Lu et al. | Microenvironment-sensitive iridium (III) complexes for disease theranostics | |
| Sarkar et al. | A recent update on rhodamine dye based sensor molecules: a review | |
| Wang et al. | A comparative study of lysosome-targetable pH probes based on phenoxazinium attached with aliphatic and aromatic amines | |
| Mohan et al. | Amino-1, 8-naphthalimide-based fluorescent chemosensors for Zn (II) ion |
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 |