CN106146342A - Fluorenyl salicylide buzane analog derivative and its preparation method and application - Google Patents
Fluorenyl salicylide buzane analog derivative and its preparation method and application Download PDFInfo
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- CN106146342A CN106146342A CN201510185918.2A CN201510185918A CN106146342A CN 106146342 A CN106146342 A CN 106146342A CN 201510185918 A CN201510185918 A CN 201510185918A CN 106146342 A CN106146342 A CN 106146342A
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- GMQJPRYCRZDRMJ-UHFFFAOYSA-N CC(C)(C(C)(C)OBB1OC(C)(C)C(C)(C)O1)O Chemical compound CC(C)(C(C)(C)OBB1OC(C)(C)C(C)(C)O1)O GMQJPRYCRZDRMJ-UHFFFAOYSA-N 0.000 description 1
- NDHPWLFZRGQZMJ-UHFFFAOYSA-N CC(C)(C(C)(C)OC)OBc(cc1)cc(C=O)c1O Chemical compound CC(C)(C(C)(C)OC)OBc(cc1)cc(C=O)c1O NDHPWLFZRGQZMJ-UHFFFAOYSA-N 0.000 description 1
- LJPKPCNETFGDER-GLNSOGGISA-N Oc(cc1)c(/C=N/N=C2c3ccccc3-c3ccccc23)cc1C(c1ccccc1)=C(c1ccccc1)c1ccccc1 Chemical compound Oc(cc1)c(/C=N/N=C2c3ccccc3-c3ccccc23)cc1C(c1ccccc1)=C(c1ccccc1)c1ccccc1 LJPKPCNETFGDER-GLNSOGGISA-N 0.000 description 1
Abstract
The present invention relates to technical field of biological chemistry detection, be specifically related to a kind of fluorenyl salicylide buzane analog derivative and its preparation method and application.This compounds can free in and out cell and specific dripping at cell lactone locates enrichment, intense fluorescence is become from original unstressed configuration, simultaneously under the effect of intramolecular Excited state proton trans fer mechanism (ESIPT), present bigger Stokes shift, show as yellow, orange red or red fluorescence, compared with the solid state fluorescence of in vitro, substantially there is no displacement, probe localized sites can be judged accurately, thus realize cytolipin is dripped structure, behavior and the monitoring of physiological process, at biology, medical treatment, health and energy field, there is the most wide application prospect.
Description
Technical field
The present invention relates to technical field of biological chemistry detection, be specifically related to a kind of fluorenyl salicylide buzane class
Derivant and its preparation method and application.
Background technology
Along with the fast development of national economy and improving constantly of living standards of the people, individual is healthy
In real time monitoring, prevention and treatment of diseases be increasingly becoming the livelihood issues that people focus more on.Relatively
In retardance and the hazardness of lonizing radiation on-line checking of traditional iii vitro chemical inspection, fluorescence shows online
As advantage that technology is efficient, green, real-time with it enters into the visual field of people gradually, extensively should
For cellular immunology, microbiology, molecular biology, hereditism, neurobiology, pathology,
The fields such as the scientific research of the aspects such as oncology, Clinical laboratory medicine, medical science, botany and the people's livelihood.
The key technology of fluorescent imaging technology is exactly that fluorescent material is as label probe (or stain)
Select.Preferably probe molecule is by physically or chemically acting on, specific adsorption at specific cell and
Tissue, realizes two-dimentional or three-dimensional imaging under low-yield Optical irradation, by with fluorescence color,
Intensity and distribution situation judge the health condition of cell or tissue.Compared with common chemical staining,
The sensitivity of fluorescence staining is to be exceeded 100-1000 times, and can be realized by suitable functionalized modification
On-line analysis to live body.
It is the major storage place of intracellular neutral fat that fat drips, be widely present in antibacterial, yeast, plant,
In insecticide and zooblast.The size difference that fat drips is very big, and diameter is from 40nm to 100um.
At medical treatment, health field, it is considered as a kind of granule being similar to glycogen that fat drips always, is used only to
Storing energy, when cell needs energy, is used for supplying energy, is the cell inclusion of a 'inertia',
Thus fat is not subject to people's attention in dropping in a very long time.But, up-to-date research shows,
Fat drips the most intracellular simple energy reservoir, but complexity, movable vigorous, dynamic
The multi-functional organelle of change.Fat drips can be along cytoskeletal motor and mutual with other organelle
Effect, may be in lipid metabolism and storage, film transhipment, protein degradation, and signal conductive process
Play an important role.It addition, research is it is also shown that multiple metabolic disease, as obesity, fatty liver,
Cardiovascular disease and diabetes, the depot disease of neutral fat and Niemann Pick C disease, the most all
Exception along with lipid storage.The biological study dripped accordingly, with respect to fat is increasingly subject to the weight of people
Depending on.
Except, in addition to the application of health field, high fat drips the screening of content rudimentary plant and solving energy danger
Machine field, progressively receives publicity.Also contain in major part marine organisms, the alginite of in full hundreds of millions meters
Having substantial amounts of fat to drip structure, its structure and application are similar to " oil ", if the scale that carried out dissolves choosing
Educate, by easily, realize the inorganic energy conversion of nature rapidly being organic product, this
Solve to be extremely important in the most neighbouring energy crisis.How to filter out fat and drip content relatively
High algae is cultivated, and is also the problem that focuses more on of presently relevant research worker.
Fluorescence probe, as the effective tool of the more ripe research microcosmos of the mankind, the most progressively
It is used in structure and physiological process research that cell fat drips.Utilize under details in a play not acted out on stage, but told through dialogues, probe molecule pair
The specific identification ability of ultrastructure and photoluminescent property, observe various physiological activity intuitively
During with, fat drips pattern, moves and the process such as decomposition.
Analyzing from structure, fat drips the hydrophobic core being made up of Lipid monolayer and neutral fat and constitutes,
And surface distributed has a lot of albumen.For the environment that intracellular major part is hydrophilic, fat drips and is
The most hydrophobic oiliness region, so, a lot of fat-soluble fluorescent probes can be to cytolipin
Drip and be marked and study.But, this type of probe must is fulfilled for three primary conditions, just can become with
The most ripe fat drips research and compares.First, whether such fluorescent probe can freely come in and go out cell:
Although the coating technology of Nano grade decreases the selectivity to probe structure, but under large-scale application
Cost raise the problem being also to merit attention, so, the probe knot of the cell that self can pass in and out
Structure seems more advantage；Second, the selectivity of fluorescent probe: not all fat-soluble probe all may be used
Being identified to drip fat, this may drip with fat one layer of monolayer phospholipid molecule and various albumen outside core
Structure is relevant；3rd, the on-off ratio regulation of fluorescent probe: the fluorescent probe of major part excellent performance is all
Use " lighting " that fat is dripped object to be marked, and the organic probes enrichment that fat drips place would generally cause
The decay of fluorescence intensity, thus it is difficulty with high-resolution imaging.Wherein, thirdly becoming puzzlement should
The subject matter of class probe development.
Calendar year 2001, the 1-methyl isophthalic acid that Tang this loyalty academician finds based on it, 2,3,4,5-pentapheneyl thiophenes cough up (MPPS)
In acetonitrile solution the most luminous, and after gathering, produce " unusual " phenomenon of strong fluorescence, propose
The new concept of " aggregation-induced emission (AIE) ", by the work of " Internal Rotations of Molecules limited (RIR) "
Mechanism is well to explain this phenomenon to produce, and has obtained many experimental results and theoretical meter
The support calculated, has developed a material that post " China card ", that have independent intellectual property right and theoretical body
System.AIE class material solves traditional aromatic rings fluorescence chromophore, and to assemble quencher in water-soluble solvent glimmering
Optical issue, is capable of fluorescence imaging and the spike of high brightness in physiological buffered solution or aqueous medium,
Realize high-resolution differentiation with the most luminous or weak light unimolecule in background, be well positioned at mesh
Mark biomacromolecule." lighting (light-up) " pattern of this AIE fluorescent probe be high sensitivity,
The biological study of contrast provides possibility, has epoch-making meaning in the field such as biology, medical science.
Design concept based on this quasi-molecule, substantial amounts of " fat drips type " fluorescent molecular probe is produced and has developed
Come, and the certain commercial potential quality showed.But, these probes have a significant deficiency, it is simply that
Fluorescence behaviour (fluorescence main peak position or glow color) in fat drips is deposited with probe situation in the solid state
At notable difference, fluorescence displacement is the biggest.Because being difficult to estimate the amplitude of variation of glow color, will lead
Cause this class formation to be difficult to complicated system and process are carried out fluorescence staining and labelling, it is impossible to meet biology
Higher requirement in system.
Summary of the invention
It is an object of the invention to provide a kind of fluorenyl salicylide buzane analog derivative and preparation method thereof and answer
With, the Fluorescence behaviour (fluorescence main peak position or glow color) solved in prior art in fat drips and spy
The problem that pin situation in the solid state exists notable difference, fluorescence displacement is the biggest.
The present invention solves technical problem and be the technical scheme is that a kind of fluorenyl salicylide buzane class is spread out
Biology, its general structure is as follows:
Wherein Ar represents aromatic group or its derived structure, substituent R1～R8Be respectively selected from hydrogen, alkyl,
Hydroxyl, alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl, naphthalene
Base, furyl, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic acid
Or the carbon number of the one in carboxylic acid derivates, carbazyl or anilino-, alkyl and alkoxyl is respectively
It is 1～12.
In the fluorenyl salicylide buzane analog derivative of the present invention, described substituent R1～R8It is respectively
Hydrogen, Ar structure is phenyl ring or phenyl ring derivant, and its preferred compound structural formula is:
Wherein, A1～A4Be respectively selected from hydrogen, alkyl, hydroxyl, alkoxyl, nitro, cyano group, amino,
Sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furyl, thienyl, pyrrole radicals, pyridine
In base, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid derivates, carbazyl or anilino-
The carbon number of one, alkyl and alkoxyl is respectively 1～12.
In the fluorenyl salicylide buzane analog derivative of the present invention, described substituent R1～R8It is respectively
Hydrogen, Ar structure is the derivant of naphthalene nucleus, anthracene nucleus, phenanthrene ring or naphthalene nucleus, anthracene nucleus, phenanthrene ring, and it is preferably changed
Laminate structures formula is:
Wherein, B1～B8Be respectively selected from hydrogen, alkyl, hydroxyl, alkoxyl, nitro, cyano group, amino,
Sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furyl, thienyl, pyrrole radicals, pyridine
In base, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid derivates, carbazyl or anilino-
The carbon number of one, alkyl and alkoxyl is respectively 1～12.
In the fluorenyl salicylide buzane analog derivative of the present invention, described substituent R1～R8It is respectively
Hydrogen, Ar structure is furan, thiophene, pyrroles, pyridine, pyrans, quinoline, indole, carbazole, aniline
Base or pyrimidine radicals, or Ar structure be furan, thiophene, pyrroles, pyridine, pyrans, quinoline, indole,
The derivant of carbazole, anilino-or pyrimidine radicals, its preferred compound structure is:
In the fluorenyl salicylide buzane analog derivative of the present invention, described substituent R1～R8It is respectively
Hydrogen, Ar structure is phenylethylene structure or the derivant of phenylethylene structure, its preferred compound structure
For:
In the fluorenyl salicylide buzane analog derivative of the present invention, Ar structure is benzene ring structure or phenyl ring spreads out
Biology, described substituent R1～R8In at least one substituent group selected from alkyl, hydroxyl, alkoxyl, nitro,
Cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furyl, thienyl,
Pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid derivates, carbazyl
Or the carbon number of the one in anilino-, alkyl and alkoxyl is respectively 1～12；
Its preferred compound structure is:
In the fluorenyl salicylide buzane analog derivative of the present invention, Ar structure is phenylethylene structure or benzene
The derivant of base ethylene unit, described substituent R1～R8In at least one substituent group selected from alkyl, hydroxyl,
Alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furan
Mutter base, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid
The carbon number of the one in derivant, carbazyl or anilino-, alkyl and alkoxyl is respectively 1～12；
In above-claimed cpd structural formula, wherein R1～R8、A1～A8、B1～B8And the preferably knot of R
Structure can be the one in 29 kinds or hydrogen atom shown in figure below:
-CH3、
The present invention also provides for the preparation method of a kind of fluorenyl salicylide buzane analog derivative, including walking as follows
Rapid:
A, Fluorenone or fluorenone derivatives and hydrazine hydrate are heated in the first reaction dissolvent 20 DEG C～
150 DEG C, react 1 hour～24 hours, be then cooled to room temperature, after removing solvent, separate out crystal or powder
End, obtains intermediate buzane after carrying out recrystallization；Wherein it is preferably heated to 45 DEG C～90 DEG C, reacts 6
Hour～12 hours, the preferred oxolane of recrystallization solvent for use, ethanol, toluene, DMF etc.,
It is preferably ethanol；
B, intermediate buzane is added in the second reaction dissolvent with corresponding aryl salicylide structural compounds
Heat, to 20 DEG C～150 DEG C, is reacted 1 hour～24 hours, is then cooled to room temperature, after removing solvent
Separate out crystal or powder, by column chromatography or be recrystallized to give fluorenyl salicylide buzane analog derivative；Its
In be preferably heated to 30 DEG C～90 DEG C, react 6 hours～12 hours, recrystallization solvent for use preferably four
Hydrogen furan, ethanol, toluene, DMF etc., most preferably ethanol.
In the preparation process in accordance with the present invention, in the first reaction dissolvent in step and step B
Two reaction dissolvents are selected from methanol, ethanol, acetic acid, oxolane, toluene, benzene, chloroform, dichloromethane
Alkane, DMF (DMF), N,N-dimethylacetamide (DMAC) and N-methyl
Any one solvent in ketopyrrolidine (NMP) or the mixed solvent of any several formation；First is anti-
Solvent and the second reaction dissolvent is answered to be respectively preferably ethanol or ethanol molten with the mixing that other solvent is formed
Agent.
The fluorenyl salicylide buzane analog derivative of the present invention can drip dye as preparing intracellular specificity fat
The application of the fluorescent probe of color, this fluorescent probe is mainly used in vivo, low etc. in external and ocean
Biological determination of fat aspect and for the aspect such as pathology and curative effect of medication research.
Implement fluorenyl salicylide buzane analog derivative and its preparation method and application of the present invention, have with
Lower beneficial effect: this compounds can free in and out cell and specific dripping at cell lactone locates richness
Collection, is become intense fluorescence from original unstressed configuration, simultaneously in intramolecular Excited state proton trans fer mechanism
(ESIPT) under effect, present bigger Stokes shift, show as yellow, orange red or red
Color fluorescence, compared with the solid state fluorescence of in vitro, does not has displacement substantially, can judge accurately to visit
Pin localized sites, thus realize cytolipin dripped the monitoring of structure, behavior and physiological process, biological,
Medical treatment, healthy and energy field, have the most wide application prospect.
Particularly as follows:
(1) select buzane structure as conjugated bridge symbasis unit, on the one hand utilize single double bond form alternately
Keeping the conjugated degree of probe molecule, on the other hand the lone pair electrons of atom N have less space bit
Resistance so that it is can be the most freely rotatable from regulation spatial volume, it is ensured that it can be the most direct
Through cell membrane, intracellular substructure is selected；
(2) peripheral conjugated structure introduces the five-membered ring structure of fluorenyl so that it is electron-withdrawing power increases
Add, expand spectrum and move to the direction that wavelength is longer, in order to be applied to In vivo detection；
(3) introduce phenolic hydroxyl structure at buzane two ends, form ESIPT state with the lone pair electrons of N and (swash
Send out intramolecular proton translocation under state), effectively increase Stokes shift, prevent the self-absorption of molecule
Phenomenon, and give molecule significant AIE performance；The water solublity of phenolic hydroxyl group also is able to notable Molecular regulator
Lipid, thus increase probe and be directed through the probability of cell；
(4) fluorescent probe is caused to drip interior fluorescing matter with solid at fat due to the rigid structure that molecule is unique
Body is similar, it is simple to realize pointing out and quantitative analysis in complex system.
Accompanying drawing explanation
Figure 1A is fluorenyl salicylide buzane (FAS) solvation effect in different solvents and gathering lures
Lead luminescent effect；
Figure 1B is FAS solvation effect in the tetrahydrofuran solution of different moisture content and aggregation inducing
Luminescent effect；
Fig. 2 A is the photograph via bright field of FAS cell dyeing；
Fig. 2 B is the fluorescence photo of FAS cell dyeing；
Fig. 3 be FAS in Hela cell in fluorescence staining concentration optimization experiment photo；
Fig. 4 be FAS in Hela cell in fluorescence staining under prescribed concentration time-optimized experiment shine
Sheet.
Detailed description of the invention
Below in conjunction with the accompanying drawings and embodiment, fluorenyl salicylide buzane analog derivative and the system thereof to the present invention
Preparation Method and application are described further:
The present invention provides a kind of fluorenyl salicylide buzane analog derivative, and its general structure is as follows:
Wherein Ar represents aromatic group or its derived structure, substituent R1～R8Be respectively selected from hydrogen, alkyl,
Hydroxyl, alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl, naphthalene
Base, furyl, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic acid
Or the carbon number of the one in carboxylic acid derivates, carbazyl or anilino-, alkyl and alkoxyl is respectively
It is 1～12.
Concrete building-up process:
(1)
Fluorenone structure is prepared the fluorenone derivatives with substituent structure.
(2)
Suitable solvent and temperature is used to prepare important the product fluorenone derivatives of Fluorenone or step (1)
Midbody product fluorenyl buzane.
Concrete operations: appropriate Fluorenone or fluorenone derivatives are added in the first reaction dissolvent with hydrazine hydrate
Heat, to proper temperature, is cooled to room temperature after reaction a period of time, separates out crystalline substance after getting rid of major part solvent
Body or powder, i.e. obtain intermediate buzane, productivity after recrystallization > 90%, purity > 95%.Wherein,
One reaction dissolvent be preferably selected from methanol, ethanol, acetic acid, oxolane, toluene, benzene, chloroform, two
Chloromethanes, DMF (DMF), N,N-dimethylacetamide (DMAC) and N-
In methyl pyrrolidone (NMP) one or more formed mixed solvent, most preferred ethanol and
Mixed system with other solvent；The proper temperature being heated to preferably 20 DEG C to 150 DEG C, wherein optimum
Elect 45 DEG C to 90 DEG C as；In preferably 1 hour to 24 hours response time, the most most preferably 6 hours extremely
12 hours；The preferred oxolane of recrystallization solvent for use, ethanol, toluene, DMF etc., most preferably second
Alcohol.
(3)
The intermediate buzane that will obtain in step (2), i.e. fluorenyl hydrazine hydrate, with corresponding aryl bigcatkin willow
Target compound is prepared in aldehyde structure reaction.
Concrete operations: by appropriate intermediate buzane with corresponding aryl salicylide structure in the second reaction
Solvent is heated to proper temperature, after reaction a period of time, is cooled to room temperature, dispose major part solvent
Target product is i.e. obtained after rear precipitation crystal or powder, column chromatography or recrystallization.Wherein, the second reaction
Solvent be preferably selected from methanol, ethanol, acetic acid, oxolane, toluene, benzene, chloroform, dichloromethane,
DMF (DMF), N,N-dimethylacetamide (DMAC) and N-methylpyrrole
The mixed solvent that one or more in alkanone (NMP) are formed, most preferred ethanol and molten with other
The mixed system of agent；The proper temperature being heated to preferably 20 DEG C to 150 DEG C, the most most preferably 30 DEG C
To 90 DEG C；Preferably 1 hour to 24 hours response time, the most most preferably 6 hours to 12 hours；
The preferred oxolane of recrystallization solvent for use, ethanol, toluene, DMF etc., most preferred ethanol.
Embodiment 1: the synthesis (FAS) of fluorenyl salicylide buzane
Reflux under 100ml 4h by 10g Fluorenone and 20ml hydrazine hydrate (85%), has a large amount of after cooling
Needle-like solid separates out, and with ethyl alcohol recrystallization 2 times after filtration, obtains faint yellow pin dress crystal, purity 99%,
Productivity 95%；Take 2g hydrazine hydrate crystal and 2ml salicylide to reflux in 20ml ethanol 4h, after cooling
Obtaining faint yellow pin dress crystal, after filtration, the ethanol solution with 75% cleans, and obtains FAS structure,
Productivity 99%.MALDI-TOF(m/z):[M+]calcd.C20H14N2O,298.34；found,299.34.
Anal Calc.for C20H14N2O:C,80.52；H,4.73；N,9.39；O,5.36.Found:C,80.62；
H,4.71；N,9.19；O,5.36.
The synthesis (1) of embodiment 2:FAS derivant
Take 500mg hydrazine hydrate crystal and equimolar between hydroxyl salicylide (or bromo salicylide) spread out
Biological 60 DEG C of reaction 4h in 10ml ethanol, obtain light yellow crystal, after filtration, with 75% after cooling
Ethanol solution clean, obtain product chromatography obtain correspondence FAS derived structure, productivity > 90%.
M-FAS-OH:MALDI-TOF (m/z): [M+] calcd.C20H14N2O2,314.34；found,
315.24.Anal Calc.for C20H14N2O2:C,76.42；H,4.49；N,8.91；O,10.18.Found:
C,75.32；H,4.48；N,8.35；O,10.09.
P-FAS-Br:MALDI-TOF (m/z): [M+] calcd.C20H13BrN2O,377.23；found,
299.34.Anal Calc.for C20H13BrN2O:C,63.68；H,3.47；Br,21.18；N,7.43；O,
4.24.Found:C,63.58；H,3.40；N,7.42；O,4.19.
The synthesis (2) of embodiment 3:FAS derivant
Take 500mg hydrazine hydrate crystal with equimolar N, N-diethylamino salicylide at 10ml ethanol
In 60 DEG C reaction 4h, obtain red oil after cooling, after filtration, with 75% ethanol solution cleaning,
Obtaining product chromatography and obtain the FAS derived structure of correspondence, productivity is 85%.
P-FAS-N22:MALDI-TOF (m/z): [M+] calcd.C24H23N3O:369.18；found,
370.66；Anal Calc.for C24H23N3O:C,78.02；H,6.27；N,11.37；O,4.33.found,
C,77.93；H,6.10；N,11.25；O,4.45.
Embodiment 4: the preparation (TPE-FAS) of fluorenyl-tetraphenyl ethylene class salicylide buzane
After using Sizuki coupling to obtain tetraphenyl ethylene base salicylaldehyde derivatives structure, take 500mg hydration
Hydrazine crystal 60 DEG C of reaction 4h in 10ml ethanol therewith, obtain pale yellow powder after cooling, after filtration,
Ethanol solution with 75% cleans, and obtains product chromatography and obtains the FAS derived structure of correspondence, and productivity is
85%.
m-TPE-FAS:MALDI-TOF(m/z):[M+]calcd.C40H28N2O:552.22；found,
553.28；Anal Calc.for C40H28N2O:C,86.93；H,5.11；N,5.07；O,2.89；found,C,
86.87；H,5.01；N,5.08；O,2.79.
Embodiment 5: the optical property of fluorenyl salicylide buzane FAS and in terms of dripping dyeing at fat
Application
The basic optical character of (a) FAS: be FAS fluorescence under opposed polarity as shown in Figure 1A
Spectrum, along with the change of polarity, the alcohol of formula of FAS launches (near 450nm) and keto-acid launches (600
Near nm) ratio generation significant change, launch for typical ESIPT.And for ESIPT molecule,
State of aggregation mostly is keto-acid and launches, so we have detected the gathering luminescence phenomenon at this.As shown in Figure 1B,
In the tetrahydrofuran solvent of FAS, (dissolving single molecule level) is continuously added a certain proportion of water, FAS
Slowly be gathered into nano-particle due to solubility, fluorescence intensity is remarkably reinforced (near 600nm),
It is called AIE character.FAS has obvious ESIPT and AIE character, has the latent of fluorescent probe
Matter.
B () cell dyeing is tested: by FAS to instill cell after certain concentration solution DMSO solution
In culture fluid, select Hela cell as object of study, after cultivating a period of time, use fluorescence microscope
Its polarity is observed, finds that FAS can pass through cell wall smoothly, and orient drip place at cytolipin
Enrichment, thus demonstrate Chinese red fluorescence (near 600nm).
Fig. 2 A is Hela cell photo in light field, and the fat that bag-like is cell of wherein craming food into one's mouth drips structure；
Fig. 2 B is the fluorescence photo under the details in a play not acted out on stage, but told through dialogues of 330nm-385nm exciting light of the cell after dyeing, the two
Contrast display, cytolipin specific can be dripped and dye by FAS, and its Fluorescent peal is with solid
State fluorescence spectrum no significant difference.Illustrate that FAS can be directly entered cell without any modification and realize target
To fluorescence staining, not showing obvious fluorescence shift, AIE and ESIPT phenomenon has obtained very well
Utilization.
C () fat drips the optimization of Coloration experiment condition: as shown in Figure 3 and Figure 4, and we are to dyeing concentration
Being optimized with the time, discovery FAS concentration is at 7.5 μMs, when dyeing time is 30min, and cell
The effect that fluorescence fat drips imaging is best.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not by upper
Stating the restriction of embodiment, that is made under other any spirit without departing from the present invention and principle changes
Become, modify, substitute, combine, simplify, all should be the substitute mode of equivalence, be included in the present invention
Protection domain within
It should be appreciated that for those of ordinary skills, can be the most in addition
Improve or conversion, within all improvement or conversion broadly fall into the protection domain of claims of the present invention.
Claims (10)
1. a fluorenyl salicylide buzane analog derivative, its general structure is as follows:
Wherein Ar represents aromatic group or its derived structure, substituent R1～R8Be respectively selected from hydrogen, alkyl,
Hydroxyl, alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl, naphthalene
Base, furyl, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic acid
Or the carbon number of the one in carboxylic acid derivates, carbazyl or anilino-, alkyl and alkoxyl is respectively
It is 1～12.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that institute
State substituent R1～R8Being hydrogen respectively, Ar structure is phenyl ring or phenyl ring derivant, and structural formula is:
Wherein, A1～A4Be respectively selected from hydrogen, alkyl, hydroxyl, alkoxyl, nitro, cyano group, amino,
Sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furyl, thienyl, pyrrole radicals, pyridine
In base, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid derivates, carbazyl or anilino-
The carbon number of one, alkyl and alkoxyl is respectively 1～12.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that institute
State substituent R1～R8Be hydrogen respectively, Ar structure be naphthalene nucleus, anthracene nucleus, phenanthrene ring or naphthalene nucleus, anthracene nucleus,
The derivant of phenanthrene ring, its structural formula is:
Wherein, B1～B8Be respectively selected from hydrogen, alkyl, hydroxyl, alkoxyl, nitro, cyano group, amino,
Sulfydryl, halogen atom, phenyl, tolyl, naphthyl, furyl, thienyl, pyrrole radicals, pyridine
In base, pyranose, quinolyl, indyl, carboxylic acid or carboxylic acid derivates, carbazyl or anilino-
The carbon number of one, alkyl and alkoxyl is respectively 1～12.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that institute
State substituent R1～R8Be hydrogen respectively, Ar structure be furan, thiophene, pyrroles, pyridine, pyrans,
Quinoline, indole, carbazole, anilino-or pyrimidine radicals, or Ar structure be furan, thiophene, pyrroles,
The derivant of pyridine, pyrans, quinoline, indole, carbazole, anilino-or pyrimidine radicals.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that institute
State substituent R1～R8Being hydrogen respectively, Ar structure is spreading out of phenylethylene structure or phenylethylene structure
Biological.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that Ar
Structure is benzene ring structure or phenyl ring derivant, described substituent R1～R8In at least one substituent group selected from alkane
Base, hydroxyl, alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom, phenyl, tolyl,
Naphthyl, furyl, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinolyl, indyl, carboxylic
Acid or carboxylic acid derivates, carbazyl or anilino-in one, the carbon number of alkyl and alkoxyl divides
It is not 1～12.
Fluorenyl salicylide buzane analog derivative the most according to claim 1, it is characterised in that Ar
Structure is phenylethylene structure or the derivant of phenylethylene structure, described substituent R1～R8In at least one
Substituent group selected from alkyl, hydroxyl, alkoxyl, nitro, cyano group, amino, sulfydryl, halogen atom,
Phenyl, tolyl, naphthyl, furyl, thienyl, pyrrole radicals, pyridine radicals, pyranose, quinoline
One in base, indyl, carboxylic acid or carboxylic acid derivates, carbazyl or anilino-, alkyl and alcoxyl
The carbon number of base is respectively 1～12.
8. the preparation method of a fluorenyl salicylide buzane analog derivative, it is characterised in that include as follows
Step:
A, Fluorenone or fluorenone derivatives and hydrazine hydrate are heated in the first reaction dissolvent 20 DEG C～
150 DEG C, react 1 hour～24 hours, be then cooled to room temperature, after removing solvent, separate out crystal or powder
End, obtains intermediate buzane after carrying out recrystallization；
B, intermediate buzane is added in the second reaction dissolvent with corresponding aryl salicylide structural compounds
Heat, to 20 DEG C～150 DEG C, is reacted 1 hour～24 hours, is then cooled to room temperature, after removing solvent
Separate out crystal or powder, by column chromatography or be recrystallized to give fluorenyl salicylide buzane analog derivative.
Preparation method the most according to claim 8, it is characterised in that first in step
The second reaction dissolvent in reaction dissolvent and step B is respectively selected from methanol, ethanol, acetic acid, tetrahydrochysene furan
Mutter, toluene, benzene, chloroform, dichloromethane, DMF (DMF), N, N-dimethyl
Any one solvent or the most several in acetamide (DMAC) and N-Methyl pyrrolidone (NMP)
Plant the mixed solvent formed.
10. a fluorenyl salicylide buzane analog derivative drips the glimmering of dyeing preparing intracellular specificity fat
The application of light probe.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110498809A (en) * | 2018-05-17 | 2019-11-26 | 香港科技大学深圳研究院 | Organoboron compound and its preparation method and application based on acylhydrazone ligand class |
| CN115353460A (en) * | 2022-07-08 | 2022-11-18 | 华南理工大学 | Application of phenol-containing keto-salicylaldehyde hydrazine compound in endoplasmic reticulum imaging |
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| US2691642A (en) * | 1951-05-15 | 1954-10-12 | Distillers Co Yeast Ltd | Stabilized polyvinylidene chloride compositions containing fluorenone azines |
| US4415640A (en) * | 1981-02-19 | 1983-11-15 | Konishiroku Photo Industry Co., Ltd. | Electrophotographic element with fluorenylidene hydrazone compounds |
| WO1999040062A1 (en) * | 1998-02-05 | 1999-08-12 | Novo Nordisk A/S | Hydrazone derivatives |
| CN1577115A (en) * | 2003-06-30 | 2005-02-09 | 三星电子株式会社 | Azine-based dimeric charge transport materials |
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| US2691642A (en) * | 1951-05-15 | 1954-10-12 | Distillers Co Yeast Ltd | Stabilized polyvinylidene chloride compositions containing fluorenone azines |
| US4415640A (en) * | 1981-02-19 | 1983-11-15 | Konishiroku Photo Industry Co., Ltd. | Electrophotographic element with fluorenylidene hydrazone compounds |
| WO1999040062A1 (en) * | 1998-02-05 | 1999-08-12 | Novo Nordisk A/S | Hydrazone derivatives |
| CN1577115A (en) * | 2003-06-30 | 2005-02-09 | 三星电子株式会社 | Azine-based dimeric charge transport materials |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110498809A (en) * | 2018-05-17 | 2019-11-26 | 香港科技大学深圳研究院 | Organoboron compound and its preparation method and application based on acylhydrazone ligand class |
| CN110498809B (en) * | 2018-05-17 | 2022-04-05 | 香港科技大学深圳研究院 | Organic boron compound based on acylhydrazone ligands and preparation method and application thereof |
| CN115353460A (en) * | 2022-07-08 | 2022-11-18 | 华南理工大学 | Application of phenol-containing keto-salicylaldehyde hydrazine compound in endoplasmic reticulum imaging |
| CN115353460B (en) * | 2022-07-08 | 2023-09-26 | 华南理工大学 | Application of phenol-containing keto-salicylaldehyde hydrazine compound in endoplasmic reticulum imaging |
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