A class of amphiphilic indole squaraine dyes and their application in long-term labeling of lysosomes

An indole squaraine and amphiphilic technology, applied in the field of synthesis and its application in specific lysosome labeling, can solve the problems of inability to label subcellular organelles, increase biological toxicity, and short labeling time, and achieve product Good stability, low biological toxicity, strong electrostatic effect

Active Publication Date: 2017-03-22
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The application range of commercial indocyanine dyes is limited to static cell membrane labeling and the labeling time is very short, and cannot label other subcellular organelles or be used for long-term dynamic monitoring of cells
Moreover, commercial dyes are mostly oil-soluble, which are easy to aggregate in organisms and cause fluorescence quenching.
At the same time, the dependence on organic co-solvents further increases its biological toxicity

Method used

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  • A class of amphiphilic indole squaraine dyes and their application in long-term labeling of lysosomes
  • A class of amphiphilic indole squaraine dyes and their application in long-term labeling of lysosomes
  • A class of amphiphilic indole squaraine dyes and their application in long-term labeling of lysosomes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] 1. Add 2.23g (10mmol) of 4-bromophenylhydrazine hydrochloride and 0.86g (10mmol) of 3-methyl-2-butanone into 10mL of glacial acetic acid, reflux for 12 hours, and evaporate to remove the solvent. Dissolve with dichloromethane and wash with saturated NaHCO 3 The aqueous solution was washed repeatedly until the aqueous phase was colorless and the pH was neutral, and the organic phase was removed by rotary evaporation to obtain 1.88 g (7.9 mmol) of 5-bromo-2,3,3-trimethyl-3H-ylindole with a yield of 79%. ;

[0036] 1 H NMR (400MHz, CDCl 3 )δ7.40(s,3H),2.27(s,3H),1.30(s,6H).

[0037] 2. Add 1.19g (5mmol) of 5-bromo-2,3,3-trimethyl-3H-ylindole and 1.08g (5mmol) of p-benyl bromobenzoic acid to 15mL of acetonitrile, reflux for 20 hours, and remove by rotary evaporation After the solvent was precipitated with ether and washed several times, 1.72 g (3.8 mmol) of the intermediate indoline derivative was obtained after drying, with a yield of 76%;

[0038] 1 H NMR (400MHz,Me...

Embodiment 2

[0053] 1. Add 1g (4.5mmol) of phenylhydrazine hydrochloride and 0.54 (6.3mmol) of 3-methyl-2-butanone into 10mL of glacial acetic acid, reflux for 12 hours, remove the solvent by suspension evaporation, and use dichloro Dissolved in methane and washed with saturated NaHCO 3 The aqueous solution was washed repeatedly until the aqueous phase was colorless and the pH was neutral, and the organic phase was removed by rotary evaporation to obtain 0.77 g of 2,3,3-trimethyl-3H-ylindole with a yield of 71%;

[0054] 2. Add 0.72g (3mmol) of 2,3,3-trimethyl-3H-ylindole and 0.96g (4.5mmol) of p-benyl bromobenzoic acid to 15mL of acetonitrile, reflux for 20 hours, remove the solvent by rotary evaporation and use Diethyl ether precipitated and washed several times, and after drying, 0.96 g of the intermediate indoline derivative was obtained, with a yield of 72%;

[0055] 3. Add 836mg (2mmol) of indoline derivatives and 114mg (1mmol) of 3,4-dihydroxy-3-cyclobutene-1,2-dione (squaric acid)...

Embodiment 3

[0062] 1. Add 500mg (3.2mmol) of 4-methylphenylhydrazine hydrochloride and 430mg (5mmol) of 3-methyl-2-butanone into 10mL of glacial acetic acid, reflux for 12 hours, and remove the solvent by suspension evaporation. Dissolve with dichloromethane and wash with saturated NaHCO 3 The aqueous solution was washed repeatedly until the aqueous phase was colorless and the pH was neutral, and the organic phase was removed by rotary evaporation to obtain 450 mg (2.6 mmol) of 5-methyl-2,3,3-trimethyl-3H-ylindole, with a yield of 81%. ;

[0063] 2. Add 340mg (1.96mmol) of 5-methyl-2,3,3-trimethyl-3H-ylindole and 422mg (1.96mmol) of p-benyl bromobenzoic acid to 10mL of acetonitrile, reflux for 20 hours, and rotate to evaporate After removing the solvent, it was precipitated with ether and washed several times, and after drying, 608 mg (1.57 mmol) of the intermediate indoline derivative was obtained, with a yield of 80%;

[0064] 3. Add 155 mg (0.4 mmol) of indoline derivatives and 25 mg...

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Abstract

The invention relates to synthesis of an amphiphilic indole squarylium cyanine dye and an application of the dye in the field of specific lysosome marking. In the invention, phenylhydrazine hydrochloride, of which a 4 position is substituted by bromine, hydrogen or methyl, is employed as a raw material to prepare the indole squarylium cyanine dye having the three substitutive groups and having carboxyl group functionalization, and then a condensation reaction between a carboxyl group and a primary amine is carried out to further introducing amino groups into the dye molecules. Ultraviolet absorption and fluorescent emission of the amphiphilic indole squarylium cyanine dye are both in near infrared region, so that interference due to background fluorescence in a bio-imaging process is reduced greatly. The dye is water-soluble so that the dye can be directly used in bio-imaging without any organic co-solvents, thereby achieving low bio-toxicity. The amino group in the dye is fully protonized under a lysosome acidic environment so that the electrostatic effect with lysosome membrane is more intensive. The dye can be used for marking the lysosome in living cells with marking time being capable of lasting for more than 48 h. It is the first time that the indole squarylium cyanine dye is applied in the field of lysosome marking.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis and biological labeling, and in particular relates to the synthesis of a class of amphiphilic indole squaraine dye and its application in specific lysosome labeling. Background technique [0002] With the continuous deepening of people's exploration of life sciences, life activities at the cell or even subcellular level have attracted more attention. Lysosome is an important subcellular organelle existing in eukaryotic cells and is the "digestive organ" of cells. Lysosomes are closely related to the health of organisms. Many human diseases such as silicosis and tuberculosis are related to lysosomes. Therefore, the use of bioluminescent imaging technology to observe and monitor cell lysosomes is of great significance. [0003] The current lysosome-targeting substances are mainly divided into antibodies and fluorescent dyes. Among them, antibodies are expensive and easily inactivated i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C09B23/10G01N21/64
Inventor 尹梅贞冀辰东沈杰郑洋
Owner BEIJING UNIV OF CHEM TECH
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