Fluorogenic pH-sensitive dyes, film and kit comprising the same

Patent metadata

Field	Value
Publication number	US-11041812-B2
Application number	US-201815870146-A
Country	US
Kind code	B2
Filing date	Jan 12, 2018
Priority date	Jan 13, 2017
Publication date	Jun 22, 2021
Grant date	Jun 22, 2021

Abstract

The present disclosure relates to a fluorogenic pH-sensitive dye and a film for detecting pH using the fluorogenic pH-sensitive dye on a polymer film. The fluorogenic pH-sensitive dye includes an aryl compound having a sulfonyl group (—SO2) and an agarose compound covalently bonded to the sulfonyl group (—SO2) of the aryl compound.

First claim

What is claimed is:

1. A fluorogenic pH-sensitive dye comprising:
an aryl compound having a sulfonyl group (—SO 2 ); and
an agarose compound covalently bonded to the sulfonyl group (—SO 2 ) of the aryl compound,
wherein the aryl compound having the sulfonyl group (—SO 2 ) is derived from an aryl compound having a sulfonate (—SO 3 Ra) group, and Ra is an anion, hydrogen or a substituent; and
wherein the aryl compound and the agarose compound are directly covalently bonded using the sulfonate group as a linker.

2. The fluorogenic pH-sensitive dye of claim 1 , wherein the agarose compound has a structure represented by Chemical Formula 1 below, and
at least one R in the Chemical Formula 1 is present at a position covalently bonded to the sulfonyl group (—SO 2 ) of the aryl compound;

wherein, in Chemical Formula 1, n is an integer of 5 or more.

3. The fluorogenic pH-sensitive dye of claim 1 , wherein the aryl compound having the sulfonate (—SO 3 Ra) group includes a compound represented by Chemical Formula 2 below:

wherein, in Chemical Formula 2, at least one of Ar 1 , Y, W, R 1 , E, X and Z 1 has a sulfonate (—SO 3 Ra) group, and the Ra is an anion, a hydrogen or a substituent,
Ar 1 is substituted or unsubstituted aryl having 6 to 20 carbon atoms or substituted or unsubstituted heteroaryl having 2 to 20 carbon atoms,
E is CR 1 or N,
Z 1 is NR 2 R 3 , OR 4 , or SR 5 ,
X is O, S, NR 8 R 9 , SiR 10 R 11 , CR 12 R 13 or Se,
Y is CR 14 R 15 , NR 16 , O, S, Se, SiR 17 R 18 or CR 19 R 20 ═CR 21 R 22 ,
W is CR 23 R 24 , CR 25 R 26 ═CR5 27 R 28 , O, —[CR 29 R 30 —CR 31 R 32 ]— or —[CR 33 R 34 —O]—,
R 23 to R 34 are the same as or different from each other and each independently hydrogen, deuterium, alkyl or acyloxy,
R 1 to R 22 and R 29 to R 41 are the same as or different from each other, and each independently any one selected from hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryloxy, substituted or unsubstituted aryloxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxyalkyl, halogen, cyano, nitro, amine, hydroxy, aldehyde, amino, amide, hydrazine, thiol, acetal, ketal, phosphoryl, phosphate, phosphonate, sulfohydroxy, sulfonyl, sulfonate, sulfate, carboxylate, amide, azido, guanidium, carbonyl, thiocarbonyl, aminothiocarbonyl, carboxyl, carboxylic acid, ketone, sulfhydryl, acyl chloride, sulfonic acid, ester, polyalkylene oxide, polyethylene glycol, and quaternary ammonium, and
A is an organic ion or an inorganic ion, and is present as an anion or a cation or is absent.

4. The fluorogenic pH-sensitive dye of claim 1 , wherein the aryl compound having a sulfonate (—SO 3 Ra) group includes a compound represented by Chemical Formula 3 below:

wherein, in Chemical Formula 3, at least one of Ar 1 , Y, W, R 1 , E, X and Z 2 has a sulfonate (—SO 3 Ra) group, and the Ra is an anion, a hydrogen or a substituent,
Ar 1 is substituted or unsubstituted aryl having 6 to 20 carbon atoms or substituted or unsubstituted heteroaryl having 2 to 20 carbon atoms,
E is CR 1 or N,
Z 2 is NR 6 , O, S, or O+R 7 ,
X is O, S, NR 8 R 9 , SiR 10 R 11 , CR 12 R 13 or Se,
Y is CR 14 R 15 , NR 16 , O, S, Se, SiR 17 R 18 or CR 19 R 20 ═CR 21 R 22 ,
W is CR 23 R 24 , CR 25 R 26 ═CR5 27 R 28 , O, —[CR 29 R 30 —CR 31 R 32 ]— or —[CR 33 R 34 —O]—,
R 23 to R 34 are the same as or different from each other and each independently hydrogen, deuterium, alkyl or acyloxy,
R 1 to R 22 and R 29 to R 41 are the same as or different from each other, and each independently any one selected from hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryloxy, substituted or unsubstituted aryloxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxyalkyl, halogen, cyano, nitro, amine, hydroxy, aldehyde, amino, amide, hydrazine, thiol, acetal, ketal, phosphoryl, phosphate, phosphonate, sulfohydroxy, sulfonyl, sulfonate, sulfate, carboxylate, amide, azido, guanidium, carbonyl, thiocarbonyl, aminothiocarbonyl, carboxyl, carboxylic acid, ketone, sulfhydryl, acyl chloride, sulfonic acid, ester, polyalkylene oxide, polyethylene glycol, and quaternary ammonium, and
A is an organic ion or an inorganic ion, and may be present as an anion or a cation or may be absent.

5. The fluorogenic pH-sensitive dye of claim 1 , wherein the aryl compound having a sulfonate (—SO 3 Ra) group includes a compound represented by Chemical Formula 4 below:

wherein, in Chemical Formula 4,
at least one of Q1 to Q10 has a sulfonate (—SO 3 Ra) group,
at least one of Q1 to Q10 that do not have the sulfonate (—SO 3 Ra) group has a hydroxyl group (—OH), and
Q1 to Q10 that do not have the sulfonate (—SO 3 Ra) group and the hydroxyl group (—OH) are hydrogen, deuterium or a substituent.

6. A film for detecting pH comprising:
the fluorogenic pH-sensitive dye of claim 1 on a polymer film.

7. A film for detecting pH comprising:
a first sub-film including the fluorogenic pH-sensitive dye of claim 1 on a polymer film; and
a second sub-film including a dye exhibiting light emission at a different wavelength band at the same pH as the fluorogenic pH-sensitive dye.

8. A method for coating a fluorogenic pH-sensitive dye comprising:
heating the fluorogenic pH-sensitive dye of claim 1 to form a solution; and
dropping the solution into each well of a plate, followed by gelling.

9. A method for detecting pH or disease in a sample comprising:
contacting the sample with the fluorogenic pH-sensitive dye of claim 1 ;
incubating the sample in contact with the fluorogenic pH-sensitive dye to form a cultured sample;
irradiating the cultured sample with light to emit light; and
detecting fluorescence emission from the sample.

10. The fluorogenic PH-sensitive dye of claim 3 , wherein:
the Ar 1 is substituted with at least one substituent, respectively, and the at least one substituent is any one selected from hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryloxy, substituted or unsubstituted aryloxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxyalkyl, halogen, cyano, nitro, amine, hydroxy, aldehyde, amino, amide, hydrazine, thiol, acetal, ketal, phosphoryl, phosphate, phosphonate, sulfohydroxy, sulfonyl, sulfonate, sulfate, carboxylate, amide, azido, guanidium, carbonyl, thiocarbonyl, aminothiocarbonyl, carboxyl, carboxylic acid, ketone, sulfhydryl, acyl chloride, sulfonic acid, ester, polyalkylen

Assignees

• Sfc Co Ltd

Inventors

• Hwang Moon-Chan
• Je Jong-Tae

Classifications

• G01N33/84

  involving inorganic compounds or pH · CPC title

• G01N27/4165

  for pH meters · CPC title

• G01N21/6486

  Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence) · CPC title

• C09B57/00

  Other synthetic dyes of known constitution · CPC title

• C09B49/00 Primary

  Sulfur dyes · CPC title