CN111533761B - Ratio type pH probe with organelle or protein targeting function and application thereof - Google Patents
Ratio type pH probe with organelle or protein targeting function and application thereof Download PDFInfo
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- 210000003463 organelle Anatomy 0.000 title claims abstract description 32
- 239000000523 sample Substances 0.000 title claims abstract description 24
- 230000018883 protein targeting Effects 0.000 title claims abstract description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 40
- 210000004027 cell Anatomy 0.000 abstract description 15
- 230000008685 targeting Effects 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 5
- 230000002438 mitochondrial effect Effects 0.000 abstract description 4
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 210000003712 lysosome Anatomy 0.000 abstract description 2
- 230000001868 lysosomic effect Effects 0.000 abstract description 2
- 238000006862 quantum yield reaction Methods 0.000 abstract description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract 2
- 238000001228 spectrum Methods 0.000 abstract 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 abstract 2
- 230000008033 biological extinction Effects 0.000 abstract 1
- 238000012984 biological imaging Methods 0.000 abstract 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 230000000007 visual effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 238000004896 high resolution mass spectrometry Methods 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 15
- 238000012650 click reaction Methods 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 235000010378 sodium ascorbate Nutrition 0.000 description 9
- 229960005055 sodium ascorbate Drugs 0.000 description 9
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 9
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000001308 synthesis method Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- 101100545272 Caenorhabditis elegans zif-1 gene Proteins 0.000 description 1
- 101100463806 Mus musculus Pglyrp1 gene Proteins 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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Abstract
A ratio type pH probe with organelle or protein targeting function and application thereof belong to the field of fine chemical engineering. In the field of biological imaging, the visual study of cell activities is of great significance. The ratio pH probe positioned in an organelle mainly realizes organelle targeting by connecting specific Tag, for example, morpholine is introduced to realize positioning of a lysosome, triphenylphosphine is introduced to realize mitochondrial targeting, and Hoechst is used for realizing DNA targeting. And a series of problems of increased synthesis steps, increased separation difficulty and the like exist by directly introducing a Tag site on the basis of a ratio pH probe, so that the development of a general platform is very important. The BODIPY and rhodamine molar extinction coefficient and fluorescence quantum yield are high, the spectrum is narrow, the spectrum matching and other advantages are very suitable for constructing a ratio pH probe of a FRET mechanism, and the compounds have high biocompatibility, can be specifically combined with the ratio pH and have the organelle targeting function.
Description
Technical Field
The invention relates to a ratio type pH probe with a cell organelle or protein targeting function and application thereof, belonging to the field of fine chemical engineering.
Background
Organelles play different roles in maintaining normal physiological activities of cells, however, the normal exertion of physiological functions needs to be carried out within a certain pH range, abnormal pH often causes a series of physiological diseases, for example, lysosome pH is about 4-6, which is a necessary condition for ensuring various enzyme activities and plays a crucial role in degrading intracellular aged organelles and various substances, and once abnormal pH is reached, the activity of hydrolytic enzyme is reduced or even inactivated, the corresponding physiological functions are destroyed.
In the biological field, the visualization research of the pH of organelles is of great significance for the activity of cells. The traditional ratiometric pH probes achieve organelle targeting by additionally introducing corresponding Tag groups, which increases the synthetic difficulty. In order to reduce the synthesis difficulty and improve the performance of the probe, the synthesis of a functional organelle targeting dye with high biocompatibility has important research value.
Disclosure of Invention
In order to search a fluorescent dye with excellent organelle targeting property, realize the visualization of organelles and research the influence of the pH of the organelles on the physiological activities of cells, the invention provides a ratio type pH probe with an organelle or protein targeting function and application thereof.
The technical scheme adopted by the invention is as follows: a kind of ratio type pH probe with organelle or protein targeting function, the probe has the following structural general formula:
in the general formula (I), the compound is shown in the specification,
Y2＝
wherein:
n1n is an integer of 0 to 1120 to 5, m1N is an integer of 0 to 1130 to 11, m2N is an integer of 0 to 114Is an integer of 0 to 5, n 50 to 5, m3Is an integer of 0 to 11, Y1、Y2And Y3N in the structure1、n2、n3、n4、m1、m2And m3May be of different values.
R1，
Wherein: n is an integer of 0 to 18, m is an integer of 0 to 18, X-Is an anion, the anion being BF4 -、Cl-、Br-、I-、NO3 -、SO4 2-、ClO4 -、CH3COO-、CH3SO3 -Or CF3SO3 -. The above-mentioned
The total number of positive charges equals the total number of negative charges of the anion, R1And R2May be different groups.
R3,R4,R7,R8,R9And
or
R3,R4,R7,R8,R9And R10May be different groups.
R5,
Or a six-membered ring structure consisting of N atoms on the same side and carbon atoms on a benzene ring, wherein:
n60-18, R5And R6May be different groups.
The probe is obtained by carrying out three-step Click reaction on azido on trimesic nitrogen, BODIPY with alkynyl, rhodamine and Tag, and the preparation method comprises the following steps:
wherein: y is1、Y2、Y3And Tag is as defined in the general structural formula.
The application of a type of ratiometric pH probe with organelle or protein targeting function, which can locate organelle or target protein and is used for pH ratio test in organelle or target protein microenvironment.
The application of a ratio pH dye compound with an organelle targeting function can target a corresponding organelle so as to monitor the activity of the pH of the corresponding organelle in a living cell.
The invention has the beneficial effects that: the probe is subjected to three-step Click reaction with BODIPY, rhodamine and Tag with alkynyl through a symbenzene triazo platform to obtain ratiometric pH dye compounds with different connection modes and different chain lengths and the organelle targeting function. The compound has excellent organelle positioning performance and protein targeting performance, solves the problems of positioning to corresponding organelles and targeting target protein, provides more selectable tools for imaging biological organelles, has targeting function and can detect the pH value of a cell microenvironment. The compound is synthesized based on rhodamine, BODIPY and Tag, and can be used for cell microscopic imaging. The probe not only has higher fluorescence quantum yield, but also has the characteristic of easy functional modification. In addition, the probe has longer excitation wavelength and less damage to cells in the imaging process.
Drawings
FIG. 1 is a pH titration fluorescence plot of compound TBSR 4.
FIG. 2 is an image of the co-localization of compound TBSR4 and mitochondrial red in the mitochondria of Hela cells.
Detailed Description
The invention is illustrated but not limited by the following examples in which all parts and percentages are by weight unless otherwise indicated.
The following detailed description of the embodiments of the present invention is provided in conjunction with the technical solutions:
example 1
A first Click reaction to synthesize a compound TB 1: copper sulfate pentahydrate (515mg, 2.14mmol), sodium ascorbate (566mg, 2.86mmol), compound T (695mg, 2.86mmol) and compound B1(460mg, 1.43mmol) were dissolved in 10mL of N, N-dimethylformamide under argon, reacted at room temperature for 2h and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, the organic phase was dried over anhydrous sodium sulfate, filtered with suction, and the solvent was removed by distillation under the reduced pressure, and the crude product was purified by silica gel column chromatography to give Compound TB1(412mg, 51%). The product structure was identified by HRMS [ M ]: 565.2069.
second Click reaction, synthesisCompound TB1R 1: under the protection of argon, copper sulfate pentahydrate (141mg, 587.51. mu. mol), sodium ascorbate (233mg, 1.18mmol), TB1(332mg, 587.51. mu. mol) and R1(270mg, 587.51. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was performed to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine for 3 times, dried over anhydrous sodium sulfate for the organic phase, filtered under suction, and the solvent was removed by distillation under reduced pressure, and the crude product was purified by silica gel column chromatography to give TB1R1(290mg, 48%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1025.3771。
And thirdly, Click reaction to synthesize a compound TBSR 1. Under the protection of argon, copper sulfate pentahydrate (2.42mg, 12.20. mu. mol), sodium ascorbate (5.87mg, 24, 39. mu. mol), TB1R1(25mg, 24, 39. mu. mol) and Tag1(13.54mg, 29.27. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, dried over anhydrous sodium sulfate, filtered under suction, the solvent was removed by distillation under the reduced pressure, and the residue was purified by silica gel column chromatography to give compound TBSR1(15mg, 42%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1487.5927。
Example 2
Synthesis method referring to example 1, the compound Tag2 was used in place of Tag1, and the product structure was identified by HRMS, HRMS [ M + H ]]+：1287.5095。
Example 3
Synthesis method referring to example 1, the compound Tag3 was used in place of Tag1, and the product structure was identified by HRMS, HRMS [ M + H ]]+：1328.4534。
Example 4
A first Click reaction to synthesize a compound TB 1: copper sulfate pentahydrate (515mg, 2.14mmol), sodium ascorbate (566mg, 2.86mmol), compound T (695mg, 2.86mmol) and compound B1(460mg, 1.43mmol) were dissolved in 10mL of N, N-dimethylformamide under argon, reacted at room temperature for 2h and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, the organic phase was dried over anhydrous sodium sulfate, filtered with suction, and the solvent was removed by distillation under the reduced pressure, and the crude product was purified by silica gel column chromatography to give Compound TB1(412mg, 51%). The product structure was identified by HRMS [ M ]: 565.2069.
in the second Click reaction, compound TB1R1 was synthesized: under the protection of argon, copper sulfate pentahydrate (141mg, 587.51. mu. mol), sodium ascorbate (233mg, 1.18mmol), TB1(332mg, 587.51. mu. mol) and R1(270mg, 587.51. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was performed to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine for 3 times, dried over anhydrous sodium sulfate for the organic phase, filtered under suction, and the solvent was removed by distillation under reduced pressure, and the crude product was purified by silica gel column chromatography to give TB1R1(290mg, 48%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1025.3771。
And thirdly, Click reaction to synthesize a compound TBSR 4. Under the protection of argon, copper sulfate pentahydrate (2.42mg, 12.20. mu. mol), sodium ascorbate (5.87mg, 24, 39. mu. mol), TB1R1(25mg, 24, 39. mu. mol) and Tag4(8.87mg, 29.27. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, dried over anhydrous sodium sulfate, filtered under suction, the solvent was removed by distillation under the reduced pressure, and the residue was purified by silica gel column chromatography to give compound TBSR4(18mg, 50%). The product structure is identified by HRMS, HRMS [ M ]]+：1411.5195。
Example 5
A first Click reaction to synthesize a compound TB 1: copper sulfate pentahydrate (515mg, 2.14mmol), sodium ascorbate (566mg, 2.86mmol), compound T (695mg, 2.86mmol) and compound B2(540mg, 1.43mmol) were dissolved in 10mL of N, N-dimethylformamide under argon, reacted at room temperature for 2h and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, the organic phase was dried over anhydrous sodium sulfate, filtered with suction, and the solvent was removed by distillation under the reduced pressure, and the crude product was purified by silica gel column chromatography to give Compound TB2(435mg, 49%). The product structure was identified by HRMS [ M ]: 565.2069.
in the second Click reaction, compound TB2R2 was synthesized: under the protection of argon, copper sulfate pentahydrate (141mg, 587.51. mu. mol), sodium ascorbate (233mg, 1.18mmol), TB2(364mg, 587.51. mu. mol) and R2(250mg, 587.51. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was performed to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine for 3 times, dried over anhydrous sodium sulfate for the organic phase, filtered under suction, and the solvent was removed by distillation under reduced pressure, and the crude product was purified by silica gel column chromatography to give TB2R2(306mg, 50%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1025.3771。
And thirdly, Click reaction to synthesize a compound TBSR 5. Under the protection of argon, copper sulfate pentahydrate (2.42mg, 12.20. mu. mol), sodium ascorbate (5.87mg, 24, 39. mu. mol), TB2R2(25mg, 24.39. mu. mol) and Tag5(5.36mg, 29.27. mu. mol) were dissolved in 10mL of N, N-dimethylformamide, reacted at room temperature for 12h, and TLC was used to determine the end point. The reaction mixture was diluted with 100mL of dichloromethane, washed with 30mL of saturated brine 3 times, dried over anhydrous sodium sulfate, filtered under suction, the solvent was removed by distillation under the reduced pressure, and the residue was purified by silica gel column chromatography to give compound TBSR5(14mg, 49%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1228.5975。
Example 6
Synthesis method referring to example 5, B3 is used to replace B2, R3 is used to replace R2, and Tag6 is used to replace Tag5, and the product structure is identified by HRMS, HRMS [ M + H ]]+：1269.6968。
Example 7
Synthesis method referring to example 1, B4 is used to replace B2, R4 is used to replace R2, and Tag7 is used to replace Tag5, and the product structure is identified by HRMS, HRMS [ M + H ]]+：1388.6149。
Example 8
Synthesis method referring to example 1, B4 is used to replace B2, R5 is used to replace R2, and Tag8 is used to replace Tag5, and the product structure is identified by HRMS, HRMS [ M + H ]]+：1324.6087。
Example 9
Synthesis method referring to example 1, B5 is used to replace B2, R6 is used to replace R2, and Tag9 is used to replace Tag5, and the product structure is identified by HRMS, HRMS [ M]+：1521.6290。
Example 10
The compound TBSR4 corresponding to example 4 was subjected to a ratiometric pH titration spectroscopy experiment. Compound TBSR4 was prepared as a 5mmol/L DMSO stock solution, a 5mmol/L TBSR4 solution was diluted with PBS to a 5. mu. mol/L test solution, and 5. mu. mol/L test solution of compound TBSR4 was irradiated with 480nm excitation light to obtain fluorescence spectrum data.
FIG. 1 is a pH titration fluorescence curve diagram of compound TBSR4, wherein a is the fluorescence spectrum of TBSR4 (5. mu. mol/L) at different pH values, b is the fluorescence intensity I of compound TBSR4 at 480nm excitation at different pH values588/I522In contrast, the ratio of fluorescence of compound TBSR4 was shown to be sensitive to pH.
Example 11
The compound TBSR4 corresponding to example 4 was subjected to cell co-localization experiments.
FIG. 2 probes TBSR-CHO (5. mu. mol/L) and Mito-tracker deep red (1. mu. mol/L)
FIG. 2 is an image of co-localization of compound TBSR4 and mitochondrial red in the mitochondria of Hela cells, wherein a is an image of the cell of compound TBSR4 channel, b is an image of the cell of mitochondrial red dye channel, and c is an image of bright field cells, and it can be seen that compound TBSR4 can localize in the mitochondria of the cells.
Claims (3)
1. A ratiometric pH probe having organelle or protein targeting functions, comprising the structure:
2. the method for preparing a ratiometric pH probe with an organelle or protein targeting function according to claim 1, wherein the probe TBSR4 is prepared as follows:
the preparation method of the probe TBSR9 is as follows:
3. the use of a class of ratiometric pH probes having organelle or protein targeting functions according to claim 1, wherein the class of probes is capable of localizing organelles or targeted proteins and indicating the pH value of the microenvironment inside the organelle or targeted protein by fluorescence ratio, said use not being useful for the diagnosis and treatment of diseases.
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| CN105001856A (en) * | 2015-07-13 | 2015-10-28 | 大连理工大学 | Fluorescent probe for monitoring lipid peroxidation processes in different subcellular organelles |
| CN109456341A (en) * | 2018-10-19 | 2019-03-12 | 大连理工大学 | Sulfonamide rhodamine compound and preparation method and application of the one kind with alkynyl or the derivative site of azido |
| CN109486235A (en) * | 2018-11-10 | 2019-03-19 | 大连理工大学 | One kind has DNA dye composition and the application of cell nucleus targeting function |
| CN110204562A (en) * | 2019-07-17 | 2019-09-06 | 大连理工大学 | One kind has fluorescent chemicals and the application of protein labeling function |
| CN110256467A (en) * | 2019-07-17 | 2019-09-20 | 大连理工大学 | A kind of tracer specially fluorescence probe of azoles amine antibiotic and application |
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| CN105001856A (en) * | 2015-07-13 | 2015-10-28 | 大连理工大学 | Fluorescent probe for monitoring lipid peroxidation processes in different subcellular organelles |
| CN109456341A (en) * | 2018-10-19 | 2019-03-12 | 大连理工大学 | Sulfonamide rhodamine compound and preparation method and application of the one kind with alkynyl or the derivative site of azido |
| CN109486235A (en) * | 2018-11-10 | 2019-03-19 | 大连理工大学 | One kind has DNA dye composition and the application of cell nucleus targeting function |
| CN110204562A (en) * | 2019-07-17 | 2019-09-06 | 大连理工大学 | One kind has fluorescent chemicals and the application of protein labeling function |
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