Photodynamic activity of sapphyrins

• US 5,120,411 A
• Filed: 12/21/1989
• Issued: 06/09/1992
• Est. Priority Date: 12/21/1989
• Status: Expired due to Term

• Current Assignee: Pharmacyclics LLC (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Harriman, Anthony, Maiya, Bhaskar G., Sessler, Jonathan L.
• Primary Examiner(s): Niebling, John F.
• Assistant Examiner(s): McAndrews, Isabelle R.
• Application Number:
  US07/454,301
• Time in Patent Office: 901 Days
• Field of Search: 204/157.61, 204/157.15
• US Class Current: 204/157.15
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: C01B 13/02 Preparation of oxygen by liquefying F25J

Abstract

The present invention includes a method to produce singlet oxygen from molecular oxygen generated by reaction with a sapphyrin compound excited at an absorbing wavelength to form a triplet species. Specifically, the sapphyrin compound is an alkylated sapphyrin, most preferably diprotonated 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin. Generation of the triplet species may be accomplished in an organic solvent, of which the most preferable solvents are chloroform, methanol or acetonitrile.

Also encompassed within the present invention is a method to selectively produce singlet oxygen in an aqueous environment. A sapphyrin compound is incorporated within a membranous vesicle, the vesicle is illuminated with exciting light and the resultant excited triplet state sapphyrin compound reacts with molecular oxygen to produce singlet oxygen. Singlet oxygen was not generated external to the vesicle where the sapphyrin compound is present in an aqueous medium.

Claims

1. A method of producing singlet oxygen, comprising:

dissolving a diprotonated sapphyrin conjugate diacid in a solvent;

exciting said diprotonated sapphyrin conjugate diacid at an absorbing wavelength to form a triplet species; and

generating singlet oxygen by reacting molecular oxygen with said triplet species.

2. The method of claim 1 wherein the sapphyrin compound is an alkylated diprotonated sapphyrin conjugate diacid.

3. The method of claim 1 wherein the diprotonated sapphyrin conjugate diacid is diprotonated 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.

4. The method of claim 1 wherein the solvent is an organic solvent.

5. The method of claim 1 wherein the exciting wavelength is in the visible range.

6. The method of claim 1 wherein the exciting wavelength is between about 450 nm and about 600 nm.

7. The method of claim 4 wherein the organic solvent is characterized as being of low polarity.

8. The method of claim 4 wherein the organic solvent is characterized as having high polarity.

9. The method of claim 1 wherein the excitation is produced by photons from a laser.

10. A method of selective production of singlet oxygen, comprising:

incorporating a diprotonated sapphyrin conjugate diacid into a suitable biological carrier in an aqueous environment;

illuminating said aqueous environment at a wavelength effective to excite said diprotonated sapphyrin conjugate diacid to triplet state species;

generating singlet oxygen by allowing molecular oxygen dissolved in said environment to react with said triplet state species; and

terminating said singlet oxygen generation by cessation of said illumination.

11. The method of claim 10 wherein the biological carrier is a positively or negatively charged liposome.

12. The method of claim 10 wherein the biological carrier is a membranous vesicle.

13. A method of modulating production of singlet oxygen in organic solvents, comprising:

dissolving a diprotonated sapphyrin conjugate diacid in an organic solvent to form a solution;

introducing molecular oxygen into said solution;

illuminating said solution sufficiently to cause excitation of said diprotonated sapphyrin conjugate diacid to excited triplet species; and

adding at least one moderator to said solution, said moderator comprising ampholytic biologically compatible materials to which said sapphyrin compound will bind.

14. The method of claim 13 wherein the moderator is a protein.

15. The method of claim 13 wherein the moderator is albumin.

16. The method of claim 13 wherein the moderator is a membranous material.

17. The method of claim 13 wherein the moderator is a positively or negatively charged liposome.

18. The method of claim 13 wherein the organic solvent is selected from a group consisting of chloroform, methanol, and acetonitrile.