Near-Infrared Heptamethine Dyes For Generation Of Singlet Oxygen

• US 20200131370A1
• Filed: 10/23/2019
• Published: 04/30/2020
• Est. Priority Date: 10/24/2018
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Jarman, John B., Dougherty, Dennis A.
• Granted Patent: US 11,702,546 B2
• Time in Patent Office: Days
• CPC Class Codes: A61N 2005/0659 infrared
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: C09B 23/0041 the substituent being bound through a nitrogen atom
• CPC Class Codes: C09B 23/0066 the polymethine chain being part of a carbocyclic ring,(e.g. benzene, naphtalene, cyclohexene, cyclobutenene-quadratic acid)
• CPC Class Codes: C09B 23/086 more than five >CH- groups

Abstract

This current disclosure is directed to charge-transfer heptamethine dyes for NIR singlet oxygen generation, each such dye comprising a near-infrared (NIR) absorbing dye having heptamethine linkages orthogonally coupled to an optionally substituted cationic heteroaryl ring moiety as a charge-transfer partner and uses thereof.

Claims

1. A compound comprising a near-infrared (NIR) absorbing dye having a heptamethine linkage coupled to an optionally substituted cationic heteroaryl ring moiety.

2. The compound of claim 1, wherein the near-infrared (NIR) absorbing dye comprises a cyanine structure, a pyrylium structure, or a thiopyrylium structure, or a combination thereof.

3. The compound of claim 1, wherein the near-infrared (NIR) absorbing dye comprises a cyanine structure.

4. The compound of claim 3, comprising a structure of:

5. The compound of claim 4, wherein the five- or six-membered nitrogen-containing heterocyclic ring of Z₁ and Z₂ independently comprise a pyrrole ring, imidazole ring, isothiazole ring, isoxazole ring, oxadiazole ring, oxazole ring, pyrazole ring, pyrimidyl, thiazole ring, selenazole ring, thiadiazole ring, triazole ring, or a pyridine ring.

6. The compound of claim 4, wherein the five- or six-membered nitrogen-containing heterocyclic ring of Z₁ and Z₂ is independently fused to a phenyl, naphthyl, pyridinyl, quinolinyl, quinoxalinyl, N-alkyl-benzoindolenine, dibenzofuranyl, or dibenzothiophenyl.

7. The compound of claim 4, wherein Z₁ and Z₂ independently comprise a benzimidazole ring, benzindole ring, benzoindolenine ring, benzoxazole ring, benzothiazole ring, furopyrrole ring, imidazole ring, imidazoquinoxaline ring, indolenine ring, indolizine ring, isoxazole ring, naphthimidazole ring, naphthothiazole ring, naphthoxazole ring, oxazolocarbazole ring, oxazole ring, oxazolodibenzofuran ring, pyrrolopyridine ring, pyridine ring, quinoline ring, quinoxaline ring, thiazole ring, or naphthoimidazole ring.

8. The compound of claim 4, whose methines not bonded to Y are otherwise not substituted.

9. The compound of claim 4, wherein one of L₁ and L₃, or L₂ and L₄, or L₃ and L₅, or L₄ and L₆, or L₅ and L₇ are linked with a C_2-4 alkylene substituent to form a 5- to 7-membered ring.

10. The compound of claim 4, comprising a structure of:

11. The compound of claim 4, comprising a structure of:

12. The compound of claim 4, comprising a structure of:

13. The compound of claim 1, wherein the near-infrared (NIR) absorbing dye comprises a pyrylium dye or a thiopyrylium dye.

14. The compound of claim 13, comprising a structure of:

15. The compound of claim 14, whose methines not bonded to Y are otherwise not substituted.

16. The compound of claim 14, comprising a structure of:

17. The compound of claim 16, wherein R_A1, R_A4, R_B1, and R_B4 are H, or an isotope thereof, and R_A2, R_A3, R_B2, and R_B3 are aryl, heteroaryl, or branched alkyl, preferably phenyl, pyridinyl, or tert-butyl.

18. The compound of claim 1, wherein the optionally substituted cationic heteroaryl is directly bonded to the heptamethine linkage.

19. The compound of claim 1, wherein the optionally substituted cationic heteroaryl ring moiety comprises an optionally substituted acridinium, benzoxazolium, benzothiazolium, imidazolium, isoxazolium, isoquinolinium, isothiazolium, naphthoimidazolium, naphthothiazolium, naphthoxazolium, oxazolium, pyrazinium, pyrazolium, pyridimium, pyridinium, quinolinium, tetrazinium, tetrazolium, thiazolium, triazinium, triazolium, benzopyrazinium, benzopyridimium, benzopyridinium, naphthopyrazinium, naphthopyridimium, benzopyridinium, benzotriazinium, naphthotriazinium moiety, pyrylium, chromenylium, xanthylium, thiopyrylium, thiochromenylium, or thioxanthylium moiety.

20. The compound of claim 1, wherein the optionally substituted cationic heteroaryl ring moiety comprises a structure:

21. The compound of claim 1, wherein the compound comprises cationic groups and the compound has a net positive charge

22. The compound of claim 21, wherein at least one associated cationic group or moiety is charge balanced by a halide ion, perchlorate, tetrafluoroborate, hexafluorophosphate, sulfate, hydrogensulfate, nitrate, trifluoroacetate, trichloroacetate, triflate, mesylate, and/or p-toluenesulfonate ion.

23. The compound of claim 1, wherein the compound comprises, is substituted with, or is conjugated to at least one element enriched in an isotope of carbon, chlorine, fluorine, hydrogen, iodine, nitrogen, or oxygen above its natural abundance.

24. The compound of claim 1, that exhibits a local λ

_max for light absorption in a range of from 750 nm to 1400 nm.

25. The compound of claim 1, that generates singlet oxygen, when the compound is irradiated in the presence of 02 at a wavelength in a range of from 750 nm to 1400 nm.

26. A composition comprising a compound of claim 1, dissolved in or suspended in or in contact with a solvent comprising a deuterated solvent.

27. An optical filter comprising a transparent support comprising a polymer film and at least one filter layer, wherein the filter layer contains a compound of claim 1.

28. A method comprising contacting a biological sample with a compound of claim 1 and irradiating the biological sample by application of light having a wavelength or range of wavelengths in the near-infrared range, optionally in the presence of oxygen.

29. The method of claim 29, wherein irradiating the biological sample comprises irradiating a target area of the biological sample with near-infrared radiation, wherein the target area comprises cancer cells or a tumor.

30. The method of claim 29, wherein the method further comprises, irradiating the compound with near-infrared radiation in the presence of oxygen, such that the irradiating generates singlet oxygen known to be detrimental to cancer cells.