Fluorescent dyes and related methods

Patent metadata

Field	Value
Publication number	US-9410947-B2
Application number	US-201314418303-A
Country	US
Kind code	B2
Filing date	Aug 6, 2013
Priority date	Aug 7, 2012
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

Fluorescent dyes with affinity for nucleic acids and related methods are provided. Dielectric or semiconducting films including fluorescent dyes with affinity for nucleic acids and related methods are also provided. Coumarin-based surfactants conjugated to the fluorescent dyes with affinity for nucleic acids and related methods are provided. Fluorescent compounds capable of interacting with DNA can be used for a variety of applications.

First claim

What is claimed is:

1. A compound having the general formula (I):

wherein
each of R 1 and R 2 are independently selected from the group consisting of hydrogen, substituted or unsubstituted, methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, substituted butyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl,
or wherein R 1 and R 2 are joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
each of R 3A , R 3B , R 3C , R 3D , R 3E and R 3F are independently selected from the group consisting of hydrogen, a halide, —OH, —NH 2 , —CN, —SH, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R 4A and R 4D are hydrogen;
each of R 4B and R 4C are independently hydrogen or —CN;
and salts and isomers thereof;
or the general formula (II):

wherein
each of R 1 and R 2 are independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, substituted butyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl,
or wherein R 1 and R 2 are joined together to form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
each of R 3A , R 3B , R 3C , R 3D , R 3E and R 3F are independently selected from the group consisting of hydrogen, a halide, —OH, —NH 2 , —CN, —SH, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R 4A , R 4D are hydrogen;
each of R 4B and R 4C are independently hydrogen or —CN;
R 5 is selected from the group consisting of a halide, —CN, —NO 2 , fluorinated alkyl, fluorinated heteroalkyl, fluorinated acyl, fluorinated alkoxy, fluorinated cycloalkyl, fluorinated heterocycloalkyl, fluorinated aryl, fluorinated heteroaryl, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted acyl, unsubstituted alkoxy, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl;
and salts and isomers thereof;
provided that
when R 4A , R 4B , R 4C and R 4D are hydrogen, R 1 and R 2 are not phenyl.

2. The compound of claim 1 , wherein each of R 1 and R 2 are independently selected from substituted or unsubstituted methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, substituted butyl, unsubstituted acyl, substituted or unsubstituted alkoxy, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, substituted or unsubstituted aryl, and unsubstituted heteroaryl.

3. The compound of claim 1 , wherein each of R 1 and R 2 are unsubstituted methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, substituted butyl, or wherein R 1 and R 2 are joined together to form a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

4. The compound of claim 1 , wherein R 5 is unsubstituted C 1 -C 10 alkyl.

5. The compound of claim 1 , wherein R 5 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, and substituted or unsubstituted aryl.

6. The compound of claim 1 , wherein the compound of general formula (II) comprises a salt including a counterion selected from the group consisting of a halide, acetate, halogen-substituted acetate and tosylate.

7. The compound of claim 1 , wherein the compound of general formula (II) comprises a salt including a counterion selected from the group consisting of a halide, acetate and trifluoroacetate.

8. The compound of claim 1 , wherein the compound of general formula (II) comprises a salt including a counterion selected from the group consisting of I − , O(C═O)CH 3 − , and O(C═O)CF 3 − .

9. The compound of claim 1 , having any one of the following formulas:

10. A method for detecting a nucleic acid molecule in a sample, the method comprising:
combining the sample and a compound to form a complex including the compound and the nucleic acid molecule; and
detecting the nucleic acid molecule the complex including the compound and the nucleic acid molecule, thereby detecting the nucleic acid molecule,
wherein the compound has the genera formula (I):

wherein
each of R 1 and R 2 are independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, substituted butyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl,
or wherein R 1 and R 2 are joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
each of R 3A , R 3B , R 3C , R 3D , R 3E and R 3F are independently selected from the group consisting of hydrogen, a halide, —OH, —NH 2 , —CN, —SH, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R 4A , R 4D are hydrogen;
each of R 4B and R 4C are independently hydrogen or —CN;
and salts and isomers thereof;
or the general formula (II):

wherein
each of R 1 and R 2 are independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl

Assignees

• Univ Washington Through Its Center For Commercialization

Inventors

• Johnson Lewis E
• Cattolico Rose Ann
• Robinson Bruce H
• Latimer Luke N
• Watanabe-Gastel Zachary H
• Hardin William Robert

Classifications

• C12Q1/6806

  Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) · CPC title

• C07D213/38

  having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom · CPC title

• C09B57/02

  Coumarine dyes · CPC title

• C07D213/89

  with hetero atoms directly attached to the ring nitrogen atom · CPC title

• G01N2001/302

  Stain compositions · CPC title