Ultra bright dimeric or polymeric dyes

Patent metadata

Field	Value
Publication number	US-10865310-B2
Application number	US-201615543827-A
Country	US
Kind code	B2
Filing date	May 11, 2016
Priority date	May 11, 2015
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):

including stereoisomers, salts and tautomers thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , L 1 , L 2 , L 3 , L 4 , M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

First claim

What is claimed is:

1. A compound having the following structure

or a stereoisomer, salt or tautomer thereof, wherein:
M is, at each occurrence, independently a fluorescent or colored moiety comprising three or more aryl or heteroaryl rings, or combinations thereof,
L 1 , L 2 and L 3 are, at each occurrence, independently an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;
L 4 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 and R 3 are each independently H, OH, SH, alkyl, alkoxy, alkylether, —OP(═R a )(R b )R c , Q, a linker comprising a covalent bond to Q, a linker comprising a covalent bond to an analyte molecule, a linker comprising a covalent bond to a solid support or a linker comprising a covalent bond to a further compound of structure (I), wherein: R a is O or S; R b is OH, SH, O, S, OR d or SR d ; R c is OH, SH, O, S, OR d , SR d , alkyl, alkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;
R 4 is, at each occurrence, independently OH, SH, O, S, OR d or SR d ;
R 5 is, at each occurrence, independently oxo, thioxo or absent;
Q is, at each occurrence, independently a moiety comprising a reactive group capable of forming a covalent bond with an analyte molecule, a solid support or a complementary reactive group Q′;
R d is a cation;
m is, at each occurrence, independently an integer of zero or greater, provided that at least one occurrence of m is an integer of three or greater; and
n is an integer of one or greater.

2. The compound of claim 1 , wherein the compound has the following structure (IA):

wherein x 1 , x 2 and x 3 are, at each occurrence, independently an integer from 0 to 6.

3. The compound of claim 1 , wherein the compound has the following structure (IB):

wherein:
x 1 ,x 2 and x 3 are, at each occurrence, independently an integer from 0 to 6; and
y is an integer from 1 to 6.

4. The compound of claim 1 , wherein the compound has one of the following structures (IB′) or (IB″):

5. The compound of claim 1 , wherein R 2 and R 3 are each independently OH or —OP(═R a )(R b )R c .

6. The compound of claim 1 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is Q or a linker comprising a covalent bond to Q.

7. The compound of claim 1 , wherein Q comprises a sulfhydryl, disulfide, activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or a maleimide functional group.

8. The compound of claim 1 , wherein Q comprises a moiety selected from Table 1.

9. The compound of claim 1 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is a linker comprising a covalent bond to an analyte molecule or a linker comprising a covalent bond to a solid support.

10. The compound of claim 9 , wherein the analyte molecule is an enzyme, receptor, receptor ligand, antibody, glycoprotein, aptamer or prion.

11. The compound of claim 1 , wherein m is, at each occurrence, independently an integer from 3 to 10.

12. The compound of claim 1 , wherein m is, at each occurrence, independently an integer from 7 to 9.

13. The compound of claim 1 , wherein M is, at each occurrence, independently fluorescent or colored.

14. The compound of claim 1 , wherein M is, at each occurrence, independently a dimethylaminostilbene, quinacridone, fluorophenyl-dimethyl-BODIPY, his-fluorophenyl-BODIPY, acridine, terrylene, sexiphenyl, porphyrin, benzopyrene, (fluorophenyl-dimethyl-difluorobora-diaza-indacene)phenyl, (bis-fluorophenyl-difluorobora-diaza-indacene)phenyl, quaterphenyl, bi-benzothiazole, ter-benzothiazole, bi-naphthyl, bi-anthracyl, squaraine, squarylium, 9,10-ethynylanthracene, ter-naphthyl, p-terphenyl, perylene, azobenzene, phenazine, phenanthroline, thioxanthrene, chrysene, rubrene, coronene, cyanine, perylene imide, perylene amide, coumarin dye, resorufin dye, dipyrrometheneboron difluoride dye, ruthenium bipyridyl dye, energy transfer dye, thiazole orange dye, polymethine or N-aryl-1,8-naphthalimide dye moiety.

15. The compound of claim 1 , wherein M is, at each occurrence, independently pyrene, perylene, perylene monoimide or 6-FAM or derivative thereof.

16. The compound of claim 1 , wherein M, at each occurrence, independently has one of the following structures:

17. The compound of claim 1 , wherein the compound is selected from one of the following structures:

wherein F, E and Y have the following structures:

18. A method of staining a sample, comprising adding to said sample the compound of claim 1 in an amount sufficient to produce an optical response when said sample is illuminated at an appropriate wavelength.

19. A method for visually detecting an analyte molecule, the method comprising:
(a) providing the compound of claim 1 , wherein R 2 or R 3 is a linker comprising a covalent bond to the analyte molecule; and
(b) detecting the compound by its visible properties.

20. A method for visually detecting an analyte molecule, the method comprising:
(a) admixing the compound of claim 1 , wherein R 2 or R 3 is Q or a linker comprising a covalent bond to Q, with the analyte molecule;
(b) forming a conjugate of the compound and the analyte molecule; and
(c) detecting the conjugate by its visible properties.

21. A composition comprising the compound of claim 1 and one or more analyte molecules.

22. A method for determining the presence of dead cells in a sample, the method comprising contacting the sample with a compound of claim 1 , thereby binding or associating the compound with the dead cells, and observing a fluorescent signal from the compound bound or associated with the dead cells.

Assignees

• Sony Corp
• Sony Corp America

Inventors

• Matray Tracy
• Singh Sharat

Classifications

• C09B69/101

  containing an anthracene dye · CPC title

• C09B69/103

  containing a diaryl- or triarylmethane dye · CPC title

• C09B3/14 Primary

  Perylene derivatives · CPC title

• C09B69/109 Primary

  containing other specific dyes · CPC title

• C09B69/102

  containing a perylene dye · CPC title