CN114874197B - Viscosity fluorescent probe capable of targeting multiple organelles - Google Patents
Viscosity fluorescent probe capable of targeting multiple organelles Download PDFInfo
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 1
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
The invention discloses a fluorescent probe (E) -3,3-dimethyl-2- (2- (2-oxo-7- (pyrrolidin-1-yl) -2H-chromen-3-yl) vinyl) -3H-benzol [ g ] with viscosity sensing property and capable of targeting various organelles]The preparation method of the compound-5-carbonitrile (DCIC) and the application thereof in the aspect of biological imaging belong to the technical field of chemical analysis and detection, and the molecular structural formula is as follows:
the probe DCIC has excellent detection performance on viscosity, and as the viscosity increases, the fluorescence intensity at the maximum emission peak of the probe gradually increases due to the rotation resistance of the carbon-carbon single bond. The fluorescence intensity increased by about 230 times, and the fluorescence quantum yield increased from 0.0085 to 0.1969. The probe can also target various organelles such as mitochondria, lysosomes, golgi apparatus, endoplasmic reticulum and the like at the same time. The probe can also be used to detect both intra-lysosomal and intra-mitochondrial viscosity changes due to its excellent multicellular localization capability. Since the fluorescence intensity of the probe is lower than that of the probe in an alkaline environment in an acidic environment, the viscosity change in the lysosome detected by the probe is more remarkable.
Description
Technical Field
The invention belongs to the technical field of chemical analysis and detection, and particularly relates to a preparation method of a fluorescent probe with viscosity sensing property and capable of targeting various organelles and application of the fluorescent probe in biological imaging.
Background
Organelles such as mitochondria, lysosomes, endoplasmic reticulum, golgi apparatus, etc., constitute the basic structure of cells, and play a vital role in maintaining normal operation of cells. Viscosity is one of the cellular microenvironment parameters and plays a key role in promoting interactions of intracellular biomolecules with chemical signals and diffusion of metabolites in living cells [ Inoue, t.; maekawa, h.; inagi, R.Kidney Int 2019,95,1318-1325.Cohen, S.; valm, a.m.; lippincott-Schwartz, J.Curr Opin Cell Biol 2018,53,84-91. Coucaine, E.M.; lu, a.; neugebauer, K.M. EMBO J2016,35,1603-1612.Chen, Q.; fang, h.; shao, x.; tian, z.; geng, s.; zhang, y; fan, h.; xiang, p.; zhang, j.; tian, x.; zhang, k; he, w; guo, z.; diao, J.Nat Commun 2020,11,6290.]. Abnormal viscosity in organelles will directly cause dysfunction of organelles and thus the development of many diseases such as lysosomal storage diseases, cellular malignancies, parkinson's disease, diabetes and alzheimer's disease etc. [ Sun, w.; shi, y. -d; ding, A.—X.; tan, z. -l; chen, h.; liu, r; wang, r.; lu, Z. -L.sensors and operators B: chemical 2018,276,238-246.Sun, M.; wang, t.; yang, x; yu, h.; wang, s.; huang, d.tanata 2021,225,121996.zhao, m.; zhu, y.; su, j.; geng, q.; tian, x.; zhang, j.; zhou, h.; zhang, s.; wu, j; tian, Y.J Mater Chem B2016,4,5907-5912. Ren, M.; zhou, k.; wang, l.; liu, k; lin, W.sensors and operators B: chemical 2018,262,452-459 ]. Thus, there is an urgent need to design and develop tools with viscosity sensing properties that can target a variety of organelles.
The link between viscosity and disease has prompted the development of various viscosity detection tools, but conventional mechanical viscometer tests are slow and do not allow measurement of the cellular microenvironment. Compared with the traditional mechanical viscometer, the fluorescent probe has the advantages of noninvasiveness, high response speed, simplicity in operation, high sensitivity, good selectivity and the like, and provides an effective method [ Gao, Y. ] for in-vivo viscosity detection; hu, y; liu, q; li, X; li, X; kim, c.y.; james, t.d.; li, J; chen, x; guo, Y.Angew Chem Int Ed Engl 2021,60,10756-10765.Tian, X.; murfin, l.c.; wu, l.; lewis, s.e.; james, t.d. chem Sci 2021,12,3406-3426, piazzolla, f; mercier, v.; assies, L.; sakai, n.; roux, a; matile, S.Angew Chem Int Ed Engl 2021,60,12258-12263. Currently, many viscosity fluorescent probes have been developed, but they are mostly single organelle targeting probes [ Wang, y.n.; zhang, x.q.; qiu, l.h.; sun, r.; xu, y.j.; ge, J.F.J Mater Chem B2021,9,5664-5669. Wang, X.; fan, l.; wang, s.; zhang, y; li, F.; zan, q.; lu, w; squang, S.; dong, C.Anal Chem 2021,93,3241-3249.Zhang, Y.; li, Z; hu, w; liu, z.animal Chem 2019,91,10302-10309 ]. There is therefore a strong need to develop a viscosity sensitive probe that can target a variety of organelles, providing an effective method for monitoring organelle viscosity changes and interactions between organelles in vivo.
Disclosure of Invention
To overcome the shortcomings of the prior art, the invention aims to provide a synthesis method of a viscosity fluorescent probe capable of targeting various organelles based on a twisted intramolecular charge transfer theory and application of the synthesis method in exploring biological imaging among organelles affected by viscosity.
The fluorescent probe has the following molecular structure:
the fluorescent probe is prepared by the following reaction, and the synthesis process is as follows:
the specific synthesis method is as follows: 4-bromo-1-naphthalenecarbonitrile (692.9 mg,3 mmol) was weighed and dissolved in 25mL of ethylene glycol monomethyl ether solution. Ultrasonic treatment for 5 min, colorless mixed solution, and pipetting N with a pipette 2 H 4 (hydrazine hydrate) (1.5 mL,30 mmol) was added dropwise to the mixture, argon was introduced under vacuum, the reaction solution was warmed to 120℃and the solution was pale yellow and refluxed under argon for 4h. After the solution was cooled to room temperature, it was poured into 50mL of ice water, a large amount of flocculent white product was precipitated, the filter cake was washed with a small amount of methylene chloride, and dried to give 4-hydrozinyl-1-naphthalonitrile (C1) (440 mg, yield 72.8%) as a white solid.
Compound C1 (402.75 mg,2.2 mmol) was weighed into 20mL of methyl isopropyl ketone, and dissolved completely by ultrasound for 2 minutes, the solution was pale yellow, 500 μl of concentrated sulfuric acid was added, the color of the solution turned orange yellow, vacuum was applied, argon was introduced, the reaction solution was heated to 115 ℃, the solution turned reddish brown gradually, and heated to reflux for 8 hours. After the solution cooled, a red solid precipitated, filtered off with suction, and washed with a small amount of dichloromethane to give a pink solid. Drying gives the pink product 2, 3-trimethyl-3H-benzol [ g ] indole-5-carbonifile (C2) (310 mg, 60.2% yield).
3-aminophenol (1.0913 g,10.0 mmol) and potassium carbonate (1.5203 g,11.0 mmol) were weighed into a 50mL three-necked flask, 10mL of N, N-Dimethylformamide (DMF) was added for ultrasonic dissolution, 1340. Mu.L of 1, 4-dibromobutane was then added thereto, and the mixture was heated to 80℃for reaction for 2 hours. After stopping the reaction, the reaction solution was cooled to room temperature, a small amount of column chromatography silica gel was added to the reaction solution, and after spin-drying the solvent, the mixture was separated and purified by column chromatography to give 3- (pyrrolidin-1-yl) phenol (D1) as a white solid (960.2 mg, yield 58.8%).
After 2mLN was measured, N-dimethylformamide was put in the flask and stirred in an ice-water bath for 15 minutes, 0.5mLPOCl was added 3 (phosphorus oxychloride) was added dropwise to the flask and stirring was continued for 30 minutes. Compound D1 (326.2 mg,2 mmol) was dissolved in N, N-dimethylformamide and added dropwise to the reaction system. And removing the ice water bath after the dripping is finished, and stirring for 1h at room temperature. The temperature was then raised to 100℃and reacted for 1 hour. Then stopping heating, cooling to room temperature, adding 10mL of water into a reaction bottle, adjusting the pH of the reaction system to be between 6 and 8 by using saturated potassium carbonate solution, and continuously stirring for 1 hour. After the completion of the reaction, the reaction mixture was extracted with methylene chloride, and then the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate overnight. The white solid product, 2-hydroxy-4- (pyrrolidin-1-yl) benzaldehyde (D2) (231.4 mg, 60.5%) was obtained by silica gel column chromatography.
Piperidine (1 drop) was added to an ethanol solution (3.75 mL) containing compound D2 (229 mg,1.2 mmol) and diethyl malonate (365 μl,2.4 mmol), the above solution was refluxed for 24 hours, ethanol was removed under reduced pressure, concentrated hydrochloric acid (3.125 mL) and glacial acetic acid (3.125 mL) were added, the resultant solution was reacted at 80 ℃ for 6 hours, cooled to room temperature, and poured into ice water, and pH was adjusted to 7 with sodium hydroxide (0.1M), to obtain a yellow precipitate, which was washed with water, and a yellow solid product 7- (pyrrolidin-1-yl) -2H-chromen-2-one (D3) (215 mg, 83.3%) was obtained through silica gel column chromatography.
POCl (point of care testing) 3 (5.0 mL) was added dropwise to N, N-dimethylformamide (5.0 mL), N 2 Under protection, a solution of compound D3 in N, N-dimethylformamide (2.5 g,10 mL) was added to the above solution under stirring at 0-5 ℃ for 30 minutes, the mixture was reacted at room temperature for 30 minutes, and further reacted at 60 ℃ for 12 hours, the reaction mixture was slowly added to ice water (100 mL) and aged for 2 hours, the pH of the solution was adjusted to 7.0 using sodium hydroxide solution (20%) to give a precipitate, and the orange solid product, 2-oxo-7- (pyrrolidin-1-yl) -2H-chromene-3-carbaldehyde (D4) (150 mg, yield 61.73%) was dried by suction filtration.
Compound D4 (81 mg,0.333 mmol) and C2 (103 mg,0.44 mmol) were weighed and dissolved in 5mL of anhydrous methanol, heated to 78℃and refluxed for 8 hours, after the solution cooled, a red solid precipitated, and the red solid product (E) -3,3-dimethyl-2- (2- (2-oxo-7- (pyrrosin-1-yl) -2H-chromen-3-yl) vinyl) -3H-benzol [ g ] indole-5-carbonitrile (DCIC) (64 mg, yield 41.87%) was obtained by suction filtration and drying.
The detection mechanism of the fluorescent probe of the invention is as follows:
the fluorescent probe consumes energy due to free rotation of carbon-carbon single bonds in a low-viscosity solution, so that the fluorescent intensity of the probe is weak, and the fluorescence quantum yield is low. In the high-viscosity solvent, the probability of non-radiative transition is reduced due to the blocking of the rotation of the carbon-carbon single bond, so that the fluorescence intensity and fluorescence quantum yield of the probe are enhanced.
The fluorescent probe has good selectivity to high-viscosity solvents (glycerin), and has larger molar extinction coefficient and Stokes shift in different solvents.
The fluorescent probe of the invention can regularly change the increase of the glycerol content in Phosphate Buffer Solution (PBS) and glycerol with different proportions. The fluorescence intensity of probe DCIC was increased by about 230-fold in 95% glycerol solution compared to pure PBS solution, respectively. When the viscosity logarithmic value is in the range of 0.83-2.07, the fluorescence probe of the invention has better detection viscosity linearity and the linear correlation coefficient is 0.9990.
The fluorescent probe has excellent stability.
The fluorescent probe has good anti-interference performance, such as in active biological small molecules (1-18): ca (Ca) 2+ ,Cu 2+ ,Fe 2+ ,Fe 3+ ,K + ,Mg 2+ ,Mn 2+ ,Na + ,Zn 2+ ,F - ,Cl - ,S 2- ,ClO - ,CO 3 2- ,HSO 3 - ,Cys,GSH,H 2 O 2 And the like, the fluorescence of the probe is basically unchanged in the coexistence.
The fluorescent probe has good cytotoxicity.
The fluorescent probe has excellent targeting ability to organelles such as mitochondria, lysosomes, endoplasmic reticulum and golgi apparatus.
Drawings
FIG. 1 shows the design concept and synthesis route of the fluorescent probe DCIC of the present invention.
FIG. 2 shows the mechanism of detecting the viscosity of a solution by using the fluorescent probe DCIC of the present invention.
FIG. 3 shows (a) the UV-visible absorption spectrum, (b) the fluorescence emission spectrum, and the corresponding photographs under natural light (c) and 365nm hand-held UV lamp (d) of the fluorescent probe DCIC of the present invention in several common solvents. Probe concentration: 10. Mu.M.
FIG. 4 shows fluorescence quantum yields of fluorescent probes of the invention in several common solvents, tested against fluorescein.
Fig. 5 shows (a) the uv-vis absorption spectrum, (b) the fluorescence emission spectrum, and the corresponding photographs under natural light (c) and 365nm hand-held uv lamp (d) of the fluorescent probe of the present invention in a mixed solution of PBS buffer solution (ph=7.4) and glycerol in different proportions. Probe concentration: 10. Mu.M.
Fig. 6 shows fluorescence emission spectra of fluorescent probes of the present invention in different proportions of PBS buffer solution (ph=7.4) and glycerol as well as the linear relationship of the maximum fluorescence intensity log value (log i) to the viscosity log η. Probe concentration: 10. Mu.M.
Fig. 7 shows fluorescence stability of fluorescent probe DCIC of the present invention in PBS buffer solution (ph=7.4) and mixed solution of 95% glycerol and 5% PBS buffer solution. Probe concentration: 10. Mu.M.
FIG. 8 shows the interference resistance of the fluorescent probe DCIC of the present invention to a portion of biological small molecules, such as Ca 2+ ,Cu 2+ ,Fe 2+ ,Fe 3+ ,K + ,Mg 2+ ,Mn 2+ ,Na + ,Zn 2+ ,F - ,Cl - ,S 2- ,ClO - ,CO 3 2- ,HSO 3 - ,Cys,GSH,H 2 O 2 . Probe concentration: 10. Mu.M.
FIG. 9 shows the change in fluorescence intensity of the fluorescent probe DCIC of the present invention in pure PBS solution and a mixed solution of 95% glycerol and 5% PBS under different pH environments. Probe concentration: 10. Mu.M.
FIG. 10 is a cytotoxicity test of the fluorescent probe of the present invention.
FIG. 11 is confocal imaging of fluorescent probes of the invention and various commercial organelle localization dyes (mitochondrial, lysosome, endoplasmic reticulum, and Golgi) in HeLa cells.
FIG. 12 is a confocal image of Dexamethasone (DXM) added to lysosomes after pretreatment with the fluorescent probe DCIC of the present invention.
FIG. 13 is a front-to-back confocal imaging of Dexamethasone (DXM) added to mitochondria after pretreatment with a fluorescent probe DCIC of the present invention.
FIG. 14 is a semi-quantitative analysis of the average fluorescence intensity before and after addition of Dexamethasone (DXM) to lysosomes and mitochondria after pretreatment with the fluorescent probe DCIC of the present invention.
Examples of the embodiments
Example 1: synthesis of Compound C1
4-bromo-1-naphthalenecarbonitrile (692.9 mg,3 mmol) was weighed and dissolved in 25mL of ethylene glycol monomethyl ether solution. Ultrasonic treatment for 5 min, colorless mixed solution, and pipetting N with a pipette 2 H 4 (1.5 mL,30 mmol) was added dropwise to the mixture, argon was introduced under vacuum, the reaction solution was warmed to 120℃and the solution was pale yellow and refluxed under argon for 4 hours. After the solution was cooled to room temperature, it was poured into 50mL of ice water, a large amount of flocculent white product was precipitated, and the cake was washed with a small amount of methylene chloride, and dried to give a white solid product C1 (440 mg, yield 72.8%).
Example 2: synthesis of Compound C2
Compound C1 (402.75 mg,2.2 mmol) was weighed into 20mL methyl isopropyl ketone and dissolved completely by sonication for 2 min, the solution was pale yellow and 500 μl of concentrated H was added 2 SO 4 The color of the solution turns to orange yellow, argon is pumped into the solution for vacuum pumping, the reaction solution is heated to 115 ℃, the solution gradually turns to reddish brown, and the solution is heated and refluxed for 8 hours. After the solution cooled, a red solid precipitated, filtered off with suction, and washed with a small amount of dichloromethane to give a pink solid. Drying gave product C2 (310 mg, 60.2% yield) as pink.
Example 3: synthesis of Compound D1
3-aminophenol (1.0913 g,10.0 mmol) and potassium carbonate (1.5203 g,11.0 mmol) were weighed into a 50mL three-necked flask, 10mL of N, N-Dimethylformamide (DMF) was added for ultrasonic dissolution, 1340. Mu.L of 1, 4-dibromobutane was then added thereto, and the mixture was heated to 80℃for reaction for 2 hours. After the reaction was stopped, the reaction solution was cooled to room temperature, a small amount of silica gel was added to the reaction solution, and after the solvent was spin-dried, the mixture was separated and purified by a column chromatography to obtain white solid D1 (960.2 mg, yield 58.8%).
Example 4: synthesis of Compound D2
After 2mLN was measured, N-dimethylformamide was put in the flask and stirred in an ice-water bath for 15 minutes, 0.5mLPOCl was added 3 Dropwise add to the flask and continue stirring for 30 minutes. Compound D1 (326.2 mg,2 mmol) was dissolved in N, N-dimethylformamide and added dropwise to the reaction system. And removing the ice water bath after the dripping is finished, and stirring for 1 hour at room temperature. The temperature was then raised to 100℃and reacted for 1 hour. Then stopping heating, cooling to room temperature, adding 10mL of water into a reaction bottle, adjusting the pH of the reaction system to be between 6 and 8 by using saturated potassium carbonate solution, and continuously stirring for 1 hour. ReactionAfter completion of the extraction with methylene chloride, the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate overnight. Silica gel column chromatography gave product D2 (231.4 mg, 60.5%) as a white solid.
Example 5: synthesis of Compound D3
Piperidine (1 drop) was added to an ethanol solution (3.75 mL) containing compound D2 (229 mg,1.2 mmol) and diethyl malonate (365 μl,2.4 mmol), the above solution was refluxed for 24 hours, ethanol was removed under reduced pressure, concentrated hydrochloric acid (3.125 mL) and glacial acetic acid (3.125 mL) were added, the resultant solution was reacted at 80 ℃ for 6 hours, cooled to room temperature, and poured into ice water, pH was adjusted to 7 with NaOH (0.1M), and a yellow precipitate was obtained, which was washed with water, and yellow solid product D3 (215 mg, 83.3%) was obtained through silica gel column chromatography.
Example 6: synthesis of Compound D4
POCl (point of care testing) 3 (5.0 mL) was added dropwise to N, N-dimethylformamide (5.0 mL), N 2 Under protection, a solution of compound D3 in N, N-dimethylformamide (2.5 g,10 mL) was added to the solution under stirring at 0-5 ℃ for 30 minutes, the mixture was reacted at room temperature for 30 minutes, and further reacted at 60 ℃ for 12 hours, the reaction mixture was slowly added to ice water (100 mL) and aged for 2 hours, the pH of the solution was adjusted to 7.0 using NaOH solution (20%) to give a precipitate, and dried by suction to give an orange solid product D4 (150 mg, yield 61.73%).
Example 7: synthesis of Probe DCIC
Compound D4 (81 mg,0.333 mmol) and C2 (103 mg,0.44 mmol) were weighed into 5mL anhydrous methanol, heated to 78℃and refluxed for 8 hours, after the solution cooled, a red solid precipitated, and the red solid product DCIC (64 mg, yield 41.87%) was obtained by suction filtration and drying. I.e. probe DCIC.
Example 8: the probe DCIC detects the viscosity in solution and biological application thereof.
And (3) detecting viscosity in solution: FIG. 3 is a graph of UV visible absorption and fluorescence emission spectra of probes in different solvents, both illustrating the response of four probes to glycerol, a high viscosity solvent; FIG. 4 shows fluorescence quantum yields of probes in different solvents, showing that the fluorescence quantum yields of probes in high viscosity solvents are clearIs obviously higher than the low-viscosity solvent and is consistent with the fluorescence emission spectrum; FIGS. 5 and 6 show the ultraviolet-visible absorption spectrum, fluorescence emission spectrum, and the linear relationship between the maximum fluorescence intensity logarithmic value and the viscosity logarithmic value of the probe in the mixed solvent of PBS and glycerol (0% -95% glycerol) in different proportions, and the result shows that the fluorescence intensity of the probe gradually increases with the increase of the viscosity, and the linear relationship between the fluorescence intensity logarithmic value of the probe and the viscosity logarithmic value is good within the range of 0.83-2.07, and the linear correlation coefficient is 0.9990; fig. 7 shows fluorescence stability of probes in PBS buffer (ph=7.4) and a mixed solution of 95% glycerol and 5% PBS buffer; FIG. 8 shows the anti-interference properties of a probe against a portion of biologically relevant active small molecules, indicating Ca for the probe 2+ ,Cu 2+ ,Fe 2+ ,Fe 3+ ,K + ,Mg 2+ ,Mn 2+ ,Na + ,Zn 2+ ,F - ,Cl - ,S 2- ,ClO - ,CO 3 2- ,HSO 3 -,Cys,GSH,H 2 O 2 The anti-interference performance is good; FIG. 9 shows the change in fluorescence intensity of the probe in PBS and 95% glycerol (5% PBS) at different pH conditions. The results show that the fluorescence intensity of the probe is weaker in the acidic environment than in the weak alkaline environment.
Viscosity detection biological application: FIG. 10 shows that the probes have higher cell viability; based on higher cell viability, we studied the ability of the probe to localize the organelles, as shown in FIG. 11. The results indicate that the probes have the ability to target multiple organelles simultaneously, such as mitochondria, lysosomes, endoplasmic reticulum, and golgi apparatus; FIG. 12 shows confocal imaging of Dexamethasone (DXM) added to lysosomes pretreated with the fluorescent probe DCIC of the present invention, indicating that the probe responds to changes in viscosity in the lysosomes; FIG. 13 is a graph showing confocal imaging of the addition of Dexamethasone (DXM) to mitochondria after pretreatment with the fluorescent probe DCIC of the present invention, indicating that the probe responds to changes in intramitochondrial viscosity. FIG. 14 is a semi-quantitative analysis of the average fluorescence intensity before and after addition of Dexamethasone (DXM) to lysosomes and mitochondria after pretreatment with the fluorescent probe DCIC of the present invention. The results show that the probe can respond to the changes of the viscosity in mitochondria and lysosomes, and the changes in lysosomes are more obvious and are consistent with the spectral test results.
To sum up: using a simple organic synthesis method we have obtained a fluorescent dye DCIC with viscosity sensing properties that is capable of targeting a variety of organelles. The prepared probe has stronger viscosity response characteristic and larger fluorescence quantum yield in a high-viscosity solvent. Cell experiments show that the prepared probe has lower cytotoxicity and good organelle positioning effect, and opens up a way for exploring pathological research of related diseases caused by lysosomes and mitochondrial internal viscosity changes. In addition, probes are expected to be simple tools for studying inter-organelle interactions.
Claims (2)
1. A fluorescent probe DCIC with viscosity sensing property capable of targeting a plurality of organelles, which has the structural formula:
2. the method for preparing the fluorescent probe DCIC according to claim 1, which is characterized by comprising the following steps:
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Non-Patent Citations (3)
| Title |
|---|
| Jingjing Cui等.Mitochondria-targeted ratiometric fluorescent probes for micropolarity and microviscosity and their applications.《Chinese Chemical Letters》.2018,第30卷第1071-1074页. * |
| Panfei Xing等.A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo.《NATURE COMMUNICATIONS》.2020,第11卷第1573（1-9）页. * |
| 朱清雅等.用于活细胞成像的黏度荧光探针研究进展.《武汉大学学报（理学版）》.2021,第67卷(第4期),第299-311页. * |
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