Helices and nanotubes on folding compositions and method of making same

• US 6,495,680 B1
• Filed: 03/24/2000
• Issued: 12/17/2002
• Est. Priority Date: 03/24/2000
• Status: Expired due to Fees

• Current Assignee: University of Toledo
• Original Assignee: University of Toledo
• Inventors: Gong, Bing
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US09/535,022
• Time in Patent Office: 998 Days
• Field of Search: 540/456, 564/153, 564/158
• US Class Current: 540/456
• CPC Class Codes: A61K 47/6919 the form being a ribbon or a tubule cochleate
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07C 237/42 having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
• CPC Class Codes: C08G 69/12 with both amino and carboxylic groups aromatically bound

Abstract

Helical oligomer and polymer compositions that form nanotubes are described. The compositions comprise a plurality of aromatic substituents linked by at least one amide group. The compositions have a curved backbone due to intramolecular hydrogen bonds that rigidify the amide linkage of each amide group to each aromatic substituent and due to an interaction between the aromatic substituents such that the curved backbone is stabilized. The helical compositions are formed by ridigifying the amide group, which is flanked on each side by the aromatic substituents, by introducing intramolecular hydrogen bonds into a linkage between the amide group and each aromatic substituent such that the compositions fold into a helical shape when the amide linkages are meta to each other.

Claims

1. A helical composition comprising a plurality of aromatic substituents linked by at least one amide group, the composition having a curved backbone due at least in part to intramolecular hydrogen bonds that rigidify the amide linkage of each amide group to each aromatic substituent and at least in part to an interaction between the aromatic substituents, whereby the curved backbone is stabilized, wherein the composition comprises a plurality of aromatic substituents having a Structure A:

wherein R is selected from linear and branched chain alkyl groups, aryl groups including phenyl, benzyl, napthyl, or alkyl or aryl groups with polar terminal functional ends including —

OH, —

COOH, —

NH₂, —

NH₃⁺, —

N⁺R′

₃, —

CH₂CH₂C₆H₅, CH₂C₆H₄—

p—

OH, —

CH₂COOCH₃, —

CH₂CONH₂, CH₂CH₂CONH₂, —

CH₂COOCH₂—

(3-indolyol).

2. The composition of claim 1, wherein the backbone of the composition folds back on itself and forms a left-handed helical conformation.

3. The composition of claim 1, wherein the backbone of the composition folds back on itself and forms a right-handed helical conformation.

4. The composition of claim 1, wherein the backbone comprises a structure type I as shown in

5. The composition of claim 1, wherein the composition comprises a plurality of aromatic substituents having a Structure G:

6. The composition of claim 1, wherein the composition comprises a plurality of aromatic substituents having a Structure I:

7. The composition of claim 1, wherein the composition comprises a plurality of aromatic substituents having a Structure J wherein n=0-5:

8. The composition of claim 1, wherein the composition comprises a plurality of aromatic substituents having a Structure P, wherein R₁=n-octyl and R₂=n-decyl:

9. The composition of claim 1, wherein the compositions comprise met α

disubstituted benzene derivatives.

10. The composition of claim 1, wherein the compositions comprise 1, 3 and 4 disubstituted benzene derivatives.

11. The composition of claim 1, wherein the composition has a nanosized tube-like structure.

12. The composition of claim 10, wherein a tube-like structure of the amide-linked composition has a hydrophilic interior and a hydrophobic exterior.

13. The composition of claim 1, wherein the aromatic substituent comprises a plurality of 5-amino-2,4-dihydroxybenzoic acid aromatic substituents.

14. The composition of claim 13, comprising at least 6,5-amino-2,4-dihdroxybenzoic acid aromatic substituents, whereby the composition has a helical conformation.

15. The composition of claim 13, comprising at least 12,5-amino-2,4-dihdroxybenzoic acid aromatic substituents, whereby the composition has a helical conformation.

16. The composition of claim 14, wherein the composition forms a tubular cavity having a diameter of about ˜

10 Å

.

17. The composition of claim 1, wherein the compositions comprise meta- and para-disubstituted benzene derivatives.

18. The composition of claim 17, wherein the composition has the configuration (m,m,m):

19. The composition of claim 17, wherein the composition has the configuration (m,p,m):

20. The composition of claim 17, wherein the composition has the configuration (n,p,p):

21. The composition of claim 1, wherein helical sense of the composition is induced by modifying at least one side group on the aromatic substituent.

22. The composition of claim 21, wherein the helical sense of the composition is induced by covalently linking the outer surface of the helical composition.

23. The composition of claim 22, wherein at least one side group bears free thiol groups that form disulfide bonds upon oxidative cross-linking by using I₂.

24. The composition of claim 1, wherein the composition comprises an oligomer.

25. The composition of claim 1, wherein the composition comprises an polymer.

26. The composition of claim 1, wherein the backbone comprises the Structure

27. The composition of claim 1, wherein the backbone comprises the Structure

28. The composition of claim 1, wherein the backbone comprises the Structure

29. The composition of claim 1, having the formula:

30. The composition of claim 1, wherein an inner surface of the helical conformation has a plurality of amide-O atoms, making the inner surface thereof electrostatically negative and hydrophilic.

31. The compositions of claim 1, wherein an outer surface of the helical composition has a modifiable outer surface.

32. A cytotoxic agent comprising the composition of claim 1.

33. A therapeutic reagent comprising the composition of claim 1, coupled to at least one desired tumor specific antibody.

34. The composition of claim 33, wherein the helical composition bears a free amino group which is linked to at least one Fab fragment of the tumor-specific antibodies.

35. The composition of claim 34, wherein the free amino group is linked to Fab fragments with a heterofunctional cross-linking agent, N-succinimidy 1-3-(2-pyridyidithio) propionate.

36. The helical composition of claim 1, wherein the composition acts as an ion channel for proton transport activity.

37. The composition of claim 1, wherein the helical composition has a molecular switch and defines a channel capable of being opened and closed.

38. The composition of claim 37, wherein the molecular switch is biochemical and is activated by at least one enzyme.

39. The composition of claim 37, wherein the molecular switch is chemical and is activated by binding of small molecules and ions.

40. The composition of claim 37, wherein the molecular switch is activated by at least one physical stimulus.

41. The composition of claim 40, wherein the physical stimulus comprises heat, light, and a combination thereof.

42. The composition of claim 37, wherein the molecular switch is a photoresponsive switch comprising thio indigo which undergoes a cis-trans isomerization upon irradiating by a light source with a wavelength of 550 nm (cis to trans) or 450 nm (trans to cis).

43. The composition of claim 37, wherein the molecular switch comprises at least one metal ion-chelating reagent.

44. The composition of claim 1, wherein the helical composition is used in confinement and parallel alignment of molecules.

45. The helical composition of claim 1, used as a template for producing conducting materials having a diameter in the nanometer range.

46. The composition of claim 4, wherein the side group R determines the outside surface properties of the composition.

47. The composition of claim 46, wherein the composition is a hydrophobic oligomer or polymer where R is selected from linear and branched chain alkyl groups (from one carbon to 20 and longer) and aryl groups including phenyl, benzyl, napthyl and the like.

48. The composition of claim 46, wherein the composition is a hydrophilic oligomer or polymer where R is selected from alkyl or aryl groups with polar terminal functional ends including —

OH, —

COOH, —

NH₂, —

NH₃⁺, —

N⁺R′

₃ and the like.

49. The composition of claim 46, wherein the composition is a membrane compatible oligomer or polymers where R is selected from —

CH₂CH₂C₆H₅, —

CH₂C₆H₄—

p—

OH, —

CH₂COOCH₃, —

CH₂CONH₂, —

CH₂CH₂CONH₂, or —

CH₂COOCH₂CH₂—

(3-indolyol).

50. The composition of claim 26, wherein the side group R determines the outside surface properties of the composition.

51. The composition of claim 50, wherein the composition is a hydrophobic oligomer or polymer where R is selected from linear and branched chain alkyl groups (from one carbon to 20 and longer) and aryl groups including phenyl, benzyl, napthyl and the like.

52. The composition of claim 50, wherein the composition is a hydrophilic oligomer or polymer where R is selected from alkyl or aryl groups with polar terminal functional ends including —

OH, —

COOH, —

NH₂, —

NH₃⁺, —

N⁺R′

₃ and the like.

53. The composition of claim 50, wherein the composition is a membrane compatible oligomer or polymers where R is selected from —

CH₂CH₂C₆H₅, —

CH₂C₆H₄—

p—

OH, —

CH₂COOCH₃, —

CH₂CONH₂, —

CH₂CH₂CONH₂, or —

CH₂COOCH₂CH₂—

(3-indolyol).

54. The composition of claim 27, wherein the side group R determines the outside surface properties of the composition.

55. The composition of claim 54, wherein the composition is a hydrophobic oligomer or polymer where R is selected from linear and branched chain alkyl groups (from one carbon to 20 and longer) and aryl groups including phenyl, benzyl, napthyl and the like.

56. The composition of claim 54, wherein the composition is a hydrophilic oligomer or polymer where R is selected from alkyl or aryl groups with polar terminal functional ends including —

OH, —

COOH, —

NH₂, —

NH₃⁺, —

N⁺R′

₃ and the like.

57. The composition of claim 54, wherein the composition is a membrane compatible oligomer or polymers where R is selected from —

CH₂CH₂C₆H₅, —

CH₂C₆H₄—

p—

OH, —

CH₂COOCH₃, —

CH₂CONH₂, —

CH₂CH₂CONH₂, or —

CH₂COOCH₂CH₂—

(3-indolyol).

58. The composition of claim 28, wherein the side group R determines the outside surface properties of the composition.

59. The composition of claim 58, wherein the composition is a hydrophobic oligomer or polymer where R is selected from linear and branched chain alkyl groups (from one carbon to 20 and longer) and aryl groups including phenyl, benzyl, napthyl and the like.

60. The composition of claim 58, wherein the composition is a hydrophilic oligomer or polymer where R is selected from alkyl or aryl groups with polar terminal functional ends including —

OH, —

COOH, —

NH₂, —

NH₃⁺, —

N⁺R′

₃ and the like.

61. The composition of claim 58, wherein the composition is a membrane compatible oligomer or polymers where R is selected from —

CH₂CH₂C₆H₅, —

CH₂C₆H₄—

p—

OH, —

CH₂COOCH₃, —

CH₂CONH₂, —

CH₂CH₂CONH₂, or —

CH₂COOCH₂CH₂—

(3-indolyol).