IP Library Granted Patent US 9,958,451
Granted Patent B2
US 9,958,451 · App. 14/969,904 · Granted May 1, 2018

Near-infrared fluorescent dyes with large stokes shifts

Inventors: Robert Michael Strongin (Portland, OR); Martha Sibrian-Vazquez (Portland, OR); Jorge Omar Escobedo-Cordova (Portland, OR); Mark Allen Lowry (Portland, OR)
Assignee: Portland State University
G01N33/582C07D311/82C07D493/10C09B11/12C09B11/22C09B11/24C09B57/00G01N21/6486G01N33/49G01N33/493Y10T436/141111
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Quick Facts
Patent No.
US 9,958,451
App. No.
14/969,904
Granted
May 1, 2018
Kind
B2
Abstract

Embodiments of near-infrared (NIR) dyes are disclosed, along with methods and kits for detecting analytes with the NIR dyes. The NIR dyes have a structure according to the general structure At least one of R 1 /R 2 , R 2 /R 3 , R 3 /R 4 , R 5 /R 6 , R 6 /R 7 , and/or R 7 /R 8 together forms a substituted or unsubstituted cycloalkyl or aryl.

Claims (23)

1. A compound having a chemical structure selected from

2. A kit for detecting an analyte, comprising at least one compound according to claim 1 , wherein the compound when combined with a sample comprising the analyte will undergo a change in its absorbance spectrum, emission spectrum, or both compared to the compound in a sample that does not comprise the analyte.

3. The kit of claim 2 , further comprising at least one buffer solution in which the compound when combined with a sample comprising the analyte will undergo a change in its absorbance spectrum, emission spectrum, or both compared to the compound combined with the buffer solution and a sample that does not comprise the analyte.

4. The kit of claim 2 , where the analyte comprises glutathione, cysteine, homocysteine, succinyl-5-amino-4-imidazolecarboxamide riboside, succinyladenosine, or a combination of succinyl-5-amino-4-imidazolecarboxamide riboside and succinyladenosine.

5. The kit of claim 2 , further comprising a plurality of disposable containers in which a reaction between the compound and the analyte can be performed.

6. The kit of claim 5 , where an amount of the compound effective to undergo a detectable change in the absorbance spectrum, the emission spectrum, or both when reacted with the analyte is premeasured into the plurality of disposable containers.

7. A method for selectively detecting an analyte in a biological fluid, comprising:

(a) combining a compound according to general formula (III) or (IV) with a biological fluid to form a solution

where each bond depicted as “ ” is a single or double bond as needed to satisfy valence requirements;

X 1 is O, S, or N(H);

R 6 is hydroxyl, amino, alkyl amino, or —NHR c when the bond between R 6 and ring A is a single bond, or R 6 is oxygen, imino, iminium, alkyl imino, or alkyl iminium when the bond between R 6 and ring A is a double bond, where R C is

R 7 is hydrogen or halogen;

R 9 -R 12 independently are hydrogen, lower alkyl, carboxyl, amino, or —SO 3 H;

R 13 is hydrogen, lower alkyl, lower alkoxy, —SO 3 H or —COOR 14 where R 14 is hydrogen or lower alkyl and the bond depicted as “ ” in ring B is a double bond, or R 13 is one or more atoms forming a ring system with rings B and D and the bond depicted as “ ” in ring B is a single bond;

R 16 and R 18 independently are hydrogen, hydroxyl, thiol, oxygen, lower alkoxy, amino, alkyl amino, or —NHR c , and at least one of R 16 and R 18 is other than hydrogen;

R 19 and R 21 independently are hydrogen, hydroxyl, thiol, oxygen, amino, alkyl amino, imino, iminium, alkyl imino, alkyl iminium, or —NHR c where R c is as defined above, and at least one of R 19 and R 21 is other than hydrogen; and

wherein if X 1 is oxygen in general formula (III), then R 6 is other than oxygen or alkyl amino, or R 13 is other than one or more atoms forming a ring system with rings B and D, or R 16 is other than hydroxyl or hydrogen, or R 18 is other than hydroxyl or hydrogen, or at least one of R 7 , R 9 , R 10 , R 11 , R 12 , R 13 is other than hydrogen, or

if the compound has a chemical structure according to general formula (IV), then at least one of R 9 -R 13 , R 16 , R 18 , R 19 , or R 21 is other than hydrogen, hydroxyl, halogen, oxygen, lower alkyl, amino, or thiol, or R 13 is one or more atoms forming a ring system with rings B and D and the bond depicted as “ ” in ring B is a single bond;

(b) exposing the solution to a light source; and

(c) detecting the analyte by detecting fluorescence from the compound, wherein the analyte comprises cysteine, homocysteine, glutathione, succinyl-5-amino-4-imidazolecarboxamide riboside, succinyladenosine, or a combination thereof.

8. The method of claim 7 where detecting fluorescence from the compound comprises detecting fluorescence at a wavelength corresponding to an emission spectrum maximum of the compound.

9. The method of claim 8 , further comprising quantitating the analyte by measuring an amount of fluorescence from the compound at a wavelength corresponding to an emission spectrum maximum of the compound.

10. The method of claim 7 where the biological fluid comprises blood or urine.

Assignments (2)
ENTITY CONVERSION Recorded Dec 18, 2015
From: THE OREGON STATE BOARD OF HIGHER EDUCATION ON BEHALF OF PORTLAND STATE UNIVERSITY
To: PORTLAND STATE UNIVERSITY
Reel/Frame 037332/0255 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 18, 2015
From: STRONGIN, ROBERT MICHAEL; SIBRIAN-VAZQUEZ, MARTHA; ESCOBEDO-CORDOVA, JORGE OMAR; LOWRY, MARK ALLEN
To: THE OREGON STATE BOARD OF HIGHER EDUCATION ON BEHALF OF PORTLAND STATE UNIVERSITY
Reel/Frame 037334/0613 →
Continuity (4)
Continuation 14129223
Provisional Application 61505038 · Jul 6, 2011
Provisional Application 61502839 · Jun 29, 2011
Related Publication 20160154001A1 · Jun 2, 2016