Near-infrared fluorescent dyes with large stokes shifts

• US 9,958,451 B2
• Filed: 12/15/2015
• Issued: 05/01/2018
• Est. Priority Date: 06/29/2011
• Status: Active Grant

• Current Assignee: Portland State University (Oregon University System)
• Original Assignee: Portland State University (Oregon University System)
• Inventors: Strongin, Robert Michael, Sibrian-Vazquez, Martha, Escobedo-Cordova, Jorge Omar, Lowry, Mark Allen
• Primary Examiner(s): Mauro, John M
• Application Number:
  US14/969,904
• Publication Number:
  US 20160154001A1
• Time in Patent Office: 868 Days
• CPC Class Codes: C07D 311/82 Xanthenes
• CPC Class Codes: C07D 493/10 Spiro-condensed systems
• CPC Class Codes: C09B 11/12 without any OH group bound to an aryl nucleus
• CPC Class Codes: C09B 11/22 containing OH groups bound to an aryl nucleus and their ethers and esters
• CPC Class Codes: C09B 11/24 Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
• CPC Class Codes: C09B 57/00 Other synthetic dyes of known constitution
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/493 urine
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y10T 436/141111 Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]

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 R¹/R², R²/R³, R³/R⁴, R⁵/R⁶, R⁶/R⁷, and/or R⁷/R⁸ together forms a substituted or unsubstituted cycloalkyl or aryl.

Claims

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

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.