Water soluble fluorescent or colored dyes and methods for their use

Patent metadata

Field	Value
Publication number	US-9765220-B2
Application number	US-201414913675-A
Country	US
Kind code	B2
Filing date	Aug 22, 2014
Priority date	Aug 22, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

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 , L 1 , L 2 , L 3 , L 4 , L 5 , L 6 , M 1 , M 2 , 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 (III):

wherein:
M 1 and M 2 are, at each occurrence, independently a 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 , L 4 L 6 , L 7 and L 8 are, at each occurrence, independently optional alkylene or heteroalkylene linkers;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 is an electron pair, H, alkyl, alkylether, hydroxylalkyl, aminoalkyl, hydroxylalkylether, sulfhydrylalkyl, sulfyhdrylalkylether, cyanoalkyl, 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, cyanoalkyl, —Oaralkyl, phosphate, thiophosphate, alkylphospho, alkylthiophospho, —Oalkylphospho, —Oalkylthiophospho, alkyletherphospho, alkyletherthiophospho, —Oalkyletherphospho, —Oalkyletherthiophospho phosphoalkyl, phosphoalkylether, thiophosphoalkyl, thiophosphoalkylether, —Ophosphoalkyl, O-phosphoalkylether, —Othiophosphoalkyl or —Othiophosphoalkylether;
R 4 is, at each occurrence, independently 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, at each occurrence, independently oxo, thioxo or absent;
n is an integer from 2 to 20; and
q and w are each independently 0 or 1 for each integral value of n, wherein q is 1 for at least two integral values of n, or wherein q and w are each independently one for at least one integral value of n.

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

wherein:
M 1 is, at each occurrence, independently a 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 four or more aryl or heteroaryl rings, or combinations thereof;
L 1 , L 7 and L 3 are, at each occurrence, independently optional alkylene or heteroalkylene linkers;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 is H, alkyl, alkylether, hydroxylalkyl, aminoalkyl, hydroxylalkylether, sulfhydrylalkyl, sulfyhdrylalkylether, cyanoalkyl, 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, cyanoalkyl, —Oaralkyl, phosphate, thiophosphate, alkylphospho, alkylthiophospho, —Oalkylphospho, —Oalkylthiophospho, alkyletherphospho, alkyletherthiophospho, —Oalkyletherphospho, —Oalkyletherthiophospho phosphoalkyl, phosphoalkylether, thiophosphoalkyl, thiophosphoalkylether, —Ophosphoalkyl, O-phosphoalkylether, —Othiophosphoalkyl or —Othiophosphoalkylether;
R 4 is, at each occurrence, independently 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, at each occurrence, independently oxo, thioxo or absent; and
n is an integer from 2 to 10.

3. The compound of claim 1 , wherein the compound has one of the following structures (IIc), (IId), (IIe) or (IIf):

4. The compound of claim 1 , wherein the compound has the following structure (IIIb):

wherein:
R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are, at each occurrence, independently H or alkyl; and
x 1 , x 2 , y 1 , y 2 , z 1 and z 2 are, at each occurrence, independently an integer from 0 to 5.

5. The compound of claim 1 , wherein R 2 has one of the following structures:

wherein:
R 2a is —OH, —NH 2 , or —SH; and
a is an integer from 1 to 10.

6. The compound of claim 1 , 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.

7. The compound of claim 1 , wherein R 3 is OH.

8. The compound of claim 1 , 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.

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

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

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

12. The compound of claim 1 , wherein R 2 is a linker comprising a covalent bond to a biomolecule or microparticle, and R 3 is H, OH, phosphate, thiophosphate, phosphoalkyl, —Ophosphoalkyl, phosphoalkylether, —Ophosphoalkylether, thiophosphoalkyl, —Othiophospho, thiophosphoalkylether or —Othiophosphoalkylether.

13. A compound having one of the following structures:

14. A method of staining a sample, comprising adding to said sample the compound of claim 12 in an amount sufficient to produce an optical response when said sample is illuminated at an appropriate wavelength.

15. A method for visually detecting a biomolecule, the method comprising:
(a) providing the compound of claim 12 ; and
(b) detecting the compound by its visible properties.

Assignees

• Sony Corp
• Sony Corp America

Inventors

• Matray Tracy
• Sherif Hesham
• Battrell C Frederick

Classifications

• G01N33/582

  with fluorescent label · CPC title

• C09B57/001

  Pyrene dyes · CPC title

• C09B69/109

  containing other specific dyes · 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