SELF-ASSEMBLED POLYHEDRAL MULTIMERIC CHEMICAL STRUCTURES

• US 20100297009A1
• Filed: 03/13/2008
• Published: 11/25/2010
• Est. Priority Date: 03/13/2007
• Status: Abandoned Application

• Current Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD. (Technion-Israel Institute Of Technology)
• Original Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD. (Technion-Israel Institute Of Technology)
• Inventors: Olson, Arthur, Keinan, Ehud
• Application Number:
  US12/450,114
• Publication Number:
  US 20100297009A1
• Time in Patent Office: Days
• US Class Current: 424/9.1
• CPC Class Codes: C07D 401/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Self-assembled, closed and hollow chemical multimer structures having a dodecahedral morphology, composed of chemical monomers having a structurally symmetric core which possess a 5-fold rotational symmetry, are provided. Also provided are methods of creating such chemical monomers, methods of creating such chemical multimer structures and compositions comprising these chemical multimer structures. Also provided are uses of these chemical multimer structures in applications such as drug delivery, imaging, immunization, formation of plastic crystals and nanoparticle matrices and other medical and material science applications.

Claims

1. A method of creating a closed, hollow and self-assembled chemical multimer structure having a dodecahedral morphology, the method comprising:

(a) providing a plurality of chemical monomers that form the self-assembled chemical multimer structure, wherein each of said chemical monomers comprises a structurally symmetric core having a 5-fold rotational symmetry, and a plurality of at least one type of associating groups, said plurality of associating groups being symmetrically positioned at a periphery of said structurally symmetric core, whereas said chemical monomers have structural complementarity to one another so as to form the closed, hollow and self-assembled chemical multimer structure upon occurrence of an associative proximity and orientation of said associating groups; and

(b) subjecting said plurality of said chemical monomers to conditions allowing said chemical monomers to associate therebetween via said associating groups, thereby creating the closed, hollow and self-assembled chemical multimer structure.

2. The method of claim 1, wherein said chemical monomers in said plurality of chemical monomers are identical to one another.

6. The method of claim 1, wherein said plurality of chemical monomers comprises at least two different chemical monomers.

8. The method of claim 1, wherein said plurality of chemical monomers comprises from two to four types of chemical monomers that are different from one another.

10. The method of claim 1, wherein said associating groups are selected capable of forming a directional (polar) bond.

11. The method of claim 1, where said associating groups are selected capable of forming a chemically-reversible bond.

15. The method of claim 1, wherein said structurally symmetric core comprises at least one aromatic moiety.

16. The method of claim 15, wherein said structurally symmetric core comprises a corannulene moiety.

3-5. -5. (canceled)

7. (canceled)

9. (canceled)

12-14. -14. (canceled)

17. (canceled)

18. A closed, hollow and self-assembled chemical multimer structure having a dodecahedral morphology comprising a plurality of chemical monomers, wherein each of said chemical monomers comprises a structurally symmetric core having a 5-fold rotational symmetry, and a plurality of at least one type of associating groups, said plurality of associating groups being symmetrically positioned at a periphery of said structurally symmetric core, whereas said chemical monomers have structural complementarity to one another, thus forming the closed, hollow and self-assembled chemical multimer structure via associative proximity and orientation of said associating groups.

19. The chemical multimer structure of claim 18, wherein said chemical monomers in said plurality of chemical monomers are identical to one another.

23. The chemical multimer structure of claim 18, wherein said plurality of chemical monomers comprises at least two different chemical monomers.

25. The chemical multimer structure of claim 18, wherein said plurality of chemical monomers comprises from two to four types of chemical monomers that are different from one another.

28. The chemical multimer structure of claim 18, wherein said structurally symmetric core comprises at least one aromatic moiety.

29. The chemical multimer structure of claim 28, wherein said structurally symmetric core comprises a corannulene moiety.

30. A composition comprising the closed, hollow and self-assembled chemical multimer structure of claim 18 and at least one active agent being attached to and/or encapsulated in said chemical multimer structure.

32. The composition of claim 30, wherein said at least one active agent is selected from the group consisting of a pharmaceutically active agent, a labeling agent, a surface-modifying agent, a chemical compound, a metal and a nanoparticle.

33. The composition of claim 32, wherein said pharmaceutically active agent is selected from the group consisting of a therapeutically active agent and a targeting moiety.

34. The composition of claim 33, comprising at least one therapeutically active agent encapsulated in or attached to said multimer structure and at least one targeting moiety attached to said multimer structure.

35. The composition of claim 34, wherein said associating groups in said chemical monomers forming said multimer structure are selected capable of forming a biocleavable bond.

40. The composition of claim 33, comprising at least one therapeutically active agent attached to said multimer structure, said at least one therapeutically active agent being an epitope.

41. The composition of claim 40, comprising a plurality of said epitopes.

43. The composition of claim 32, wherein said active agent is a labeling agent, the composition being identified for use in diagnosis.

46. The composition of claim 32, wherein said active agent is a chemical compound, said chemical compound being encapsulated in said multimer structure.

47. The composition of claim 46, being identified for use in an analytical method for determining a chemical feature of said chemical compound.

50. The composition of claim 32, wherein said active agent is a nanoparticle, said nanoparticle being encapsulated in said multimer structure.

51. A method of delivering an active agent selected from the group consisting of a therapeutically active agent and a labeling agent to a bodily site of a subject in need thereof, the method comprising administering to the subject a composition which comprises the closed, hollow and self-assembled chemical multimer structure of claim 18 and said active agent, said active agent being attached to and/or encapsulated in said chemical multimer structure.

52. The method of claim 51, wherein said chemical multimer structure further comprises a targeting moiety attached thereto.

55. A method of immunization comprising administering to a subject a composition which comprises the closed, hollow and self-assembled chemical multimer structure of claim 18 and a plurality of epitopes, said plurality of epitopes being attached to said chemical multimer structure.

56. A plastic crystal comprising a plurality of the closed, hollow and self-assembled chemical multimer structure of claim 18.

59. A method of preparing a composition which comprises the closed, hollow and self-assembled chemical multimer structure of claim 18 and an active agent being encapsulated in the chemical multimer structure, the method comprising:

(a) providing said plurality of chemical monomers that form the self-assembled chemical multimer structure, wherein each of said chemical monomers comprises a structurally symmetric core and a plurality of at least one type of associating groups, said plurality of associating groups being symmetrically positioned at a periphery of said structurally symmetric core, whereas said chemical monomers have structural complementarity to one another so as to form the closed, hollow and self-assembled chemical multimer structure upon occurrence of an associative proximity and orientation of said associating groups; and

(b) subjecting said plurality of said chemical monomers to conditions allowing said chemical monomers to associate therebetween via said associating groups in the presence of said active agent, thereby creating the closed, hollow and self-assembled chemical multimer structure having said active agent encapsulated therein.

60. A method of preparing a composition which comprises the closed, hollow and self-assembled chemical multimer structure of claim 18 and an active agent attached to the chemical multimer structure, the method comprising:

(a) providing said plurality of chemical monomers that form the self-assembled chemical multimer structure, wherein each of said chemical monomers comprises a structurally symmetric core and a plurality of at least one type of associating groups, said plurality of associating groups being symmetrically positioned at a periphery of said structurally symmetric core, whereas said chemical monomers have structural complementarity to one another so as to form the closed, hollow and self-assembled chemical multimer structure upon occurrence of an associative proximity and orientation of said associating groups;

(b) attaching said active agent to at least one of said chemical monomers, to thereby obtain a plurality of said chemical monomers in which at least of said chemical monomers has said active agent attached thereto; and

(c) subjecting said plurality of said chemical monomers in which at least of said chemical monomers has said active agent attached thereto to conditions allowing said chemical monomers to associate therebetween via said associating groups in the presence of said active agent, thereby creating the closed, hollow and self-assembled chemical multimer structure having said active agent attached thereto.

61. A method of preparing a composition which comprises the closed, hollow and self-assembled chemical multimer structure of claim 18 and an active agent attached to the chemical multimer structure, the method comprising:

(a) providing said plurality of chemical monomers that form the self-assembled chemical multimer structure, wherein each of said chemical monomers comprises a structurally symmetric core and a plurality of at least one type of associating groups, said plurality of associating groups being symmetrically positioned at a periphery of said structurally symmetric core, whereas said chemical monomers have structural complementarity to one another so as to form the closed, hollow and self-assembled chemical multimer structure upon occurrence of an associative proximity and orientation of said associating groups;

(b) subjecting said plurality of said chemical monomers in which at least of said chemical monomers has said active agent attached thereto to conditions allowing said chemical monomers to associate therebetween via said associating groups in the presence of said active agent, thereby creating the closed, hollow and self-assembled chemical multimer structure; and

(b) attaching said active agent to closed, hollow and self-assembled chemical multimer structure, thereby creating the closed, hollow and self-assembled chemical multimer structure having said active agent attached thereto.

70. A metal-coated chemical multimer structure comprising the closed, hollow and self-assembled chemical multimer structure of claim 18 and at least one metal deposited over at least a portion of the surface thereof.

20-22. -22. (canceled)

24. (canceled)

26-27. -27. (canceled)

31. (canceled)

36-39. -39. (canceled)

42. (canceled)

44-45. -45. (canceled)

48-49. -49. (canceled)

53-54. -54. (canceled)

57-58. -58. (canceled)

62. A method of preparing a chemical monomer capable of forming a closed, hollow and self-assembled multimer structure having a dodecahedral morphology, the method comprising:

providing a structurally symmetric core compound having a 5-fold rotational symmetry;

symmetrically attaching at a periphery of said core compound a plurality of at least one type of associating groups,

wherein said chemical monomer and said associating groups are selected such that said chemical monomer has a structural complementarity to an identical and/or different chemical monomer, which allows forming the closed, hollow and self-assembled multimer structure upon occurrence of associative proximity and orientation of said associating groups.

64. The method of claim 62, wherein said structurally symmetric core comprises at least one aromatic moiety.

65. The method of claim 64, wherein said structurally symmetric core comprises a corannulene moiety.

63. (canceled)

66. A compound having a structurally symmetric core having a 5-fold rotational symmetry, and a plurality of at least one type of associating groups symmetrically positioned at a periphery of said core.

68. The compound of claim 66, wherein said structurally symmetric core comprises at least one aromatic moiety.

69. The compound of claim 68, wherein said structurally symmetric core comprises a corannulene moiety.

67. (canceled)