Texaphyrin solid supports and devices

• US 5,594,136 A
• Filed: 05/03/1995
• Issued: 01/14/1997
• Est. Priority Date: 12/21/1989
• Status: Expired due to Fees

• Current Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Thomas, Richard E., Smith, Daniel A., Kr al, Vladimir, Sessler, Jonathan L., Iverson, Brent L., Magda, Darren
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Sripada, Pavanaram K.
• Application Number:
  US08/433,573
• Time in Patent Office: 622 Days
• Field of Search: 540/472, 540/474, 540/145, 424/9.322, 534/11, 534/14, 534/15, 534/16
• US Class Current: 540/472
• 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: A61K 47/546 Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
• CPC Class Codes: A61K 47/558 the modifying agent being a chemiluminescent acceptor
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61L 27/40 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 29/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 31/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: B01J 20/223 containing metals, e.g. organo-metallic compounds, coordination complexes
• CPC Class Codes: B01J 20/289 bonded via a spacer
• CPC Class Codes: B01J 20/29 Chiral phases
• CPC Class Codes: B01J 20/3204 Inorganic carriers, supports or substrates
• CPC Class Codes: B01J 20/321 consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3212 consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3219 involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3265 with an organic functional group containing a metal, e.g. a metal affinity ligand
• CPC Class Codes: B01J 2220/4825 Polysaccharides or cellulose materials, e.g. starch, chitin, sawdust, wood, straw, cotton
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/58 Use in a single column
• CPC Class Codes: B01J 2220/62 : In a cartridge
• CPC Class Codes: B01J 2220/84 : Capillaries
• CPC Class Codes: B01J 2531/025 : Ligands with a porphyrin ring system or analogues thereof, e.g. phthalocyanines, corroles
• CPC Class Codes: B01J 2531/36 : Yttrium
• CPC Class Codes: B01J 2531/37 : Lanthanum
• CPC Class Codes: B01J 2531/38 : Lanthanides other than lanthanum
• CPC Class Codes: B01J 31/1658 : immobilised by covalent linkages, i.e. pendant complexes with optional linking groups, e.g. on Wang or Merrifield resins
• CPC Class Codes: B01J 31/1815 : with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
• CPC Class Codes: C07D 487/22 : in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07F 5/00 : Compounds containing elements of Groups 3 or 13 of the Periodic Table
• CPC Class Codes: C07H 15/26 : Acyclic or carbocyclic radicals, substituted by hetero rings
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/101 : by chromatography, e.g. electrophoresis, ion-exchange, reverse phase

Abstract

The present invention provides various novel matrix-supported texaphyrins in which a polymeric or solid matrix is covalently modified by the addition of one or more texaphyrins or texaphyrin derivatives. Described are methods of making various polymer-supported texaphyrins, including texaphyrin chromatographic supports, and devices such as catheters, as may be used, for example, in the separation of neutral and anionic species and in applications concerning phosphate ester hydrolysis, other catalytic schemes, MRI, and PDT.

Claims

1. A composition comprising a matrix-supported texaphyrin.

2. The composition of claim 1 where the matrix is a polymericor solid-support matrix.

3. The composition of claim 1 wherein the texaphyrin is complexed to a metal cation.

4. The composition of claim 3, wherein the metal cation is La(III), Nd(III), Sm(III), Sm(II), Gd(III), Tm(III), Lu(III), Eu(III), Dy(III), Y(III), In(III), Ce(III), Sc(III), Ca(II), Mn(II), Ni(II), Zn(II), Cd(II), Hg(II), Mn(III), Co(II), Co(III), Ni(III), Fe(II), Fe(III), Cu(II), Ho(III), Pr(III), Tb(III), Er(III) or Yb(III).

5. The composition of claim 3, wherein the metal cation is Sm(III), Eu(III), Gd(III) or Dy(III).

6. The composition of claim 3, wherein the metal cation is La(III), Lu(III), or Y(III).

7. The composition of claim 1 wherein the texaphyrin is joined to the matrix by a linker XY, wherein X is [--(CH₂)_n --]--NH₂ where n is an integer from 0 to 20, OH, CO₂ H, Cl, Br, I, OH, NCO, NCS, NC, C.tbd.CH, CH═

CH₂, MgCl, ZnCl, Li, a nucleotide or an oligonucleotide, and Y is [--(CH₂)_n --]--OH where n is an integer from 0 to 20, NH₂, CO₂ H, Cl, Br, I, NCO, NCS, oxirane, C.tbd.CH, MgCl, ZnCl, Li, a nucleotide or an oligonucleotide.

8. The composition of claim 1 wherein the texaphyrin is joined to the matrix by a linker XY, wherein X is [--(CH₂)_n --]--OH where n is an integer from 0 to 20, NH₂, CO₂ H, Cl, Br, I, NCO, NCS, oxirane, C.tbd.CH, MgCl, ZnCl, Li, a nucleotide or an oligonucleotide, and Y is [--(CH₂)_n --]--NH₂ where n is an integer from 0 to 20, OH, CO₂ H, Cl, Br, I, OH, NCO, NCS, NC, C.tbd.CH, CH═

CH₂, MgCl, ZnCl, Li, a nucleotide or an oligonucleotide.

9. The composition of claim 1 wherein the texaphyrin is joined to the matrix by an ether, ester, amide, amine, carbamate, urea, --CH═

CH--, --C.tbd.C--, --(CH₂)_m -- where m is an integer from 1 to 20, functionalized alkyl, aryl, or oligonucleotide linker.

10. The composition of claim 1 wherein the matrix is a solid-support matrix and the solid-support is silica, silica gel, amino-functionalized silica gel, alumina, clay, zeolite, glass, controlled pore glass or montmorillonite.

11. The composition of claim 1 wherein the matrix is silica gel.

12. The composition of claim 1 wherein the matrix is a polymer-support matrix and the polymer is polystyrene, polyethylene, polyacrylamide, polypropylene, polyamide, Merrifield resin, sepharose, agarose, polystyrene, polydivinylbenzene, cellulose, alginic acid, chitosan, chitin, polystyrene-benzhydrylamine resin, an acrylic ester polymer, a lactic acid polymer, a texaphyrin multimer or a sapphyrin multimer.

13. The composition of claim 1 wherein the matrix is polyurethane, polyvinylchloride, nylon, latex, silicone rubber, a halogenated polyethylene, an organosilicone, a biocompatible ceramic, bioglass or sintered hydroxyapatite.

14. The composition of claim 1 formulated into a column.

15. The composition of claim 1 formulated into a capillary electrophoresis tube.

16. The composition of claim 1 wherein the matrix-supported texaphyrin is in the form of a medical device.

17. The composition of claim 16, wherein the medical device is implantable.

18. The composition of claim 16, where the medical device is a catheter, an orthopedic implant, an artificial joint or a part thereof.

19. The composition of claim 1, wherein the texaphyrin further comprises a D-sugar unit, an L-sugar unit, an oligosaccharide, an L-amino acid, a D-amino acid, a peptide or a polypeptide.

20. The composition of claim 1, wherein the texaphyrin further comprises a nucleobase-containing group.

41. A method of light-induced singlet oxygen production comprising subjecting a matrix-supported texaphyrin of claim 1 to light in the presence of oxygen.

44. The composition of claim 2 where the matrix is a polymeric matrix and the polymeric matrix is a texaphyrin multimer.

21. A method for separating a first molecule from a mixture of at least two molecules comprising the step of contacting a matrix-supported texaphyrin metal complex with said mixture to separate said first molecule.

22. The method of claim 21, wherein the metal is La(III), Nd(III), Sm(III), Sm(II), Gd(III), Tm(III), Lu(III), Eu(III), Dy(III), Y(III), In(III), Ce(III), Sc(III), Ca(II), Mn(II), Ni(II), Zn(II), Cd(II), Hg(II), Mn(III), Co(II), Co(III), Ni(III), Fe(II), Fe(III), Cu(II), Ho(III), Pr(III), Tb(III), Er(III) or Yb(III).

23. The method of claim 21, wherein the matrix-supported texaphyrin comprises a texaphyrin linked to a polymeric or solid-support matrix via an ether, ester, amide, amine, carbamate, urea, --CH═

CH--, --C.tbd.C--, --(CH₂)_m -- where m is an integer from 1 to 20, functionalized alkyl, aryl, or oligonucleotide linker.

24. The method of claim 21, wherein the matrix-supported texaphyrin comprises a silica, silica gel, amino-functionalized silica gel, alumina, clay, zeolite, glass, controlled pore glass, montmorillonite, polystyrene, polyethylene, polyacrylamide, polypropylene, polyamide, Merrifield resin, sepharose, agarose, polystyrene, polydivinylbenzene, cellulose, alginic acid, chitosan, chitin, polystyrene-benzhydrylamine resin, an acrylic ester polymer, a lactic acid polymer, a texaphyrin multimer, a sapphyrin multimer, polyurethane, polyvinylchloride, nylon, latex, silicone rubber, a halogenated polyethylene, an organosilicone;

or a biocompatible ceramic, bioglass or sintered hydroxyapatite polymeric or solid-support matrix.

25. The method of claim 21, wherein the matrix-supported texaphyrin is formulated into an HPLC column, a capillary electrophoresis tube or a filter cartridge.

26. The method of claim 21, wherein said mixture to be separated includes a molecule having a chloride, bromide, fluoride, pseudohalide, phosphate, phosphonate, phosphate ester, arsenate, arsenate ester, carboxylate, nitrate, sulfate, sulfonate or sugar moiety within its structure.

27. The method of claim 21, wherein said mixture to be separated includes a molecule having a phosphate, nitrate, organophosphorus or nucleotide moiety within its structure.

28. The method of claim 27, wherein said mixture to be separated includes an RNA or DNA molecule.

29. The method of claim 27, wherein said mixture includes a pesticide, an herbicide, a fungicide, or a chemical warfare agent.

30. A method for hydrolysing a phosphate ester, comprising the step of contacting a matrix-supported texaphyrin metal complex where the metal cation has catalytic activity for ester bond hydrolysis in aqueous solution with the phosphate ester to cleave the ester.

31. The method of claim 30, wherein the metal cation is Eu(III) or Dy(III).

32. The method of claim 30, wherein the phosphate ester is a nucleotide, an RNA molecule, a cofactor or a phospholipid.

33. The method of claim 32, wherein the phosphate ester is an RNA molecule.

34. A method of light-induced cleavage of a polymer of deoxyribonucleic acid, the method comprising:

contacting the polymer with a matrix-supported texaphyrin where the texaphyrin is a photosensitive texaphyrin; and

exposing the matrix-supported texaphyrin to light for a time sufficient to cleave the polymer.

35. The method of claim 34 wherein the exposing step is carried out in the presence of oxygen.

36. The method of claim 34 wherein the photosensitive texaphyrin is a texaphyrin complexed with a diamagnetic metal and the diamagnetic metal is Lu(III), La(III), In(III), Zn(II) or Cd(II).

37. A method for conducting a chemical reaction catalyzed by a lanthanide metal cation comprising the step of contacting a matrix-supported texaphyrin complexed to a metal cation, where the metal cation is a lanthanide metal cation, with a composition comprising the substrates for the chemical reaction.

38. The method of claim 37, wherein the lanthanide metal cation is La(III), Sm(III), Gd(III), Y(III), Tb(III), Lu(III), Eu(III), Ce(III) or Dy(III).

39. The method of claim 37, wherein the chemical reaction is ester hydrolysis, amide hydrolysis, phosphate ester hydrolysis, acyl transfer, hydrogenation or polymerization.

40. A method of magnetic resonance imaging of a subject, comprising:

administering a matrix-supported texaphyrin complexed to a metal cation, wherein the metal cation is a paramagnetic metal cation, to the subject; and

imaging the subject by reference to the matrix-supported texaphyrin.

42. A method of photodynamic tumor therapy comprising:

contacting a matrix-supported texaphyrin with a composition suspected of having tumor cells; and

photoirradiating the matrix-supported texaphyrin in contact with the composition.

43. A method for deactivating a retrovirus or an enveloped virus comprising

contacting a matrix-supported texaphyrin with a composition suspected of having a retrovirus or enveloped virus;

and

photoirradiating the matrix-supported texaphyrin in contact with the composition.