Water soluble fluorescent or colored dyes and methods for their use

Patent metadata

Field	Value
Publication number	US-11434374-B2
Application number	US-202117190199-A
Country	US
Kind code	B2
Filing date	Mar 2, 2021
Priority date	Aug 22, 2013
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):including stereoisomers, salts and tautomers thereof, R1, R2, R3, L1, L2, L3, L4, L5, L6, M1, M2, A, q, w 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 (IV):

wherein:
M 1 is, at each occurrence, independently a fluorescent or colored moiety comprising two or more double bonds and at least one degree of conjugation, and at least one occurrence of M 1 is a moiety comprising three or more aryl or heteroaryl rings, or combinations thereof;
L 1 , L 3 , and L 7 are, at each occurrence, independently optional alkylene or heteroalkylene linkers;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 is phospho, thiophospho, alkylphospho, alkylthiophospho, alkyletherphospho, alkyletherthiophospho, phosphoalkyl, phosphoalkylether, thiophosphoalkyl or thiophosphoalkylether, or R 2 is a linker comprising a covalent bond to a biomolecule or microparticle;
R 3 is H, OH, SH, —NH 2 , alkyl, alkylether, hydroxylalkyl, aminoalkyl, hydroxylalkylether, sulfhydrylalkyl, sulfyhdrylalkylether, phosphate, thiophosphate, alkylphospho, alkylthiophospho, -Oalkylphospho, -Oalkylthiophospho, alkyletherphospho, alkyletherthiophospho, -Oalkyletherphospho, -Oalkyletherthiophospho phosphoalkyl, phosphoalkylether, thiophosphoalkyl, thiophosphoalkylether, -Ophosphoalkyl, O-phosphoalkylether, -Othiophosphoalkyl or -Othiophosphoalkylether;
R 4 is O − , S − , OZ, SZ or N(R 6 ) 2 , where Z is a cation and each R 6 is independently H or alkyl;
R 5 is oxo, thioxo or absent;
n is an integer from 1 to 20.

2. The compound of claim 1 , wherein R 2 is alkylphospho, alkylthiophospho, alkyletherphospho, alkyletherthiophospho, phosphoalkyl, phosphoalkylether, thiophosphoalkyl or thiophosphoalkylether, wherein R 2 is optionally substituted with a substituent selected from —OH, —NH 2 , and —SH.

3. The compound of claim 2 , wherein R 2 has one of the following structures:

wherein:
R 2a is —OH, —SH, —NH 2 , phosphate or thiophosphate;
R 4a and R 4b are independently O − , S − , OZ or SZ, where Z is a cation;
R 5a and R 5b are independently oxo, or thioxo; and
a, b and c are each independently integers from 1 to 10.

4. The compound of 1 , wherein R 3 is OH.

5. The compound of claim 1 , wherein R 3 is, phosphate, thiophosphate, phospho, thiophospho, -Oalkylphospho, -Oalkylthiophospho, -Oalkyletherphospho, -Oalkyletherthiophosp ho, -Ophosphoalkyl, -Ophosphoalkylether, -Othiophosphoalkyl or -Othiophosphoalkylether optionally substituted with a substituent selected from —OH, —NH 2 , and —SH.

6. The compound of claim 5 , wherein R 3 has one of the following structures:

wherein:
R 3a is —OH, —SH, —NH 2 , phosphate or thiophosphate;
R 4a and R 4b are independently O − , S − , OZ or SZ, where Z is a cation;
R 5a and R 5b are independently oxo, or thioxo; and
b and c are each independently integers from 1 to 10.

7. The compound of claim 1 , wherein R 4 is O − and R 5 is oxo.

8. The compound of claim 1 , wherein L 1 , L 3 and L 7 are each alkylene linkers.

9. The compound of claim 1 , wherein L 1 and L 3 are each alkylene linkers and L 7 is absent.

10. The compound of claim 8 , wherein alkylene is methylene.

11. A compound having the following structure (Ih):

wherein:
M 1 is a moiety comprising three or more aryl or heteroaryl rings, or combinations thereof;
R 1 is H, C 1 -C 6 alkyl or alkoxy;
R 2 is H, an electron pair or a cation;
R 3 is OH;
R 4 is O − , S − , OZ, SZ where Z is a cation;
R 5 is oxo or thioxo;
R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are, at each occurrence, independently H or alkyl; and
x, y and z are, at each occurrence, independently an integer from 0 to 5.

12. The compound of claim 11 , wherein x, y and z are each 1.

13. The compound of claim 11 , wherein x is 0 and y and z are each 1.

14. The compound of claim 1 , wherein at least one M 1 is, is a moiety comprising four or more aryl or heteroaryl rings, or combinations thereof.

15. The compound of claim 1 , wherein at least one M 1 is 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 or ter-naphthyl moiety.

16. The compound of claim 1 , wherein at least one M 1 is p-terphenyl, perylene, azobenzene, phenazine, phenanthroline, acridine, thioxanthrene, chrysene, rubrene, coronene, cyanine, perylene imide, or perylene amide or derivative thereof.

17. The compound of claim 1 , wherein at least one M 1 is a coumarin dye, resorufin dye, dipyrrometheneboron difluoride dye, ruthenium bipyridyl dye, energy transfer dye, thiazole orange dye, polymethine or N-aryl-1,8-naphthalimide dye.

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

19. The compound of claim 1 , wherein M 1 has one of the following structures:

20. A method for visually detecting a biomolecule, the method comprising:
(a) admixing the compound of claim 1 , with one or more biomolecules; and
(b) detecting the compound by its visible properties.

Assignees

• Sony Corp

Inventors

• Matray Tracy
• Sherif Hesham
• Battrell C Frederick

Classifications

• C09B69/103

  containing a diaryl- or triarylmethane dye · CPC title

• C09B57/08

  Naphthalimide dyes; Phthalimide dyes · CPC title

• C09B3/14 Primary

  Perylene derivatives · CPC title

• C09B11/24

  Phthaleins containing amino groups {; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes} · CPC title

• G01N33/583

  with non-fluorescent dye label · CPC title