Heterotrifunctional molecules and methods for the synthesis of dendrimeric materials

• US 9,006,345 B2
• Filed: 03/26/2012
• Issued: 04/14/2015
• Est. Priority Date: 03/25/2011
• Status: Expired due to Fees

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Lancaster, Jeffrey, Koberstein, Jeffrey T., Turro, Nicholas J.
• Primary Examiner(s): JONES JR., ROBERT STOCKTON
• Application Number:
  US13/429,704
• Publication Number:
  US 20120264881A1
• Time in Patent Office: 1,114 Days
• Field of Search: 525/242, 525/275, 525/293, 548/255
• US Class Current: 525/275
• CPC Class Codes: C08F 2/38 Polymerisation using regulators, e.g. chain terminating agents , e.g. telomerisation
• CPC Class Codes: C08F 2438/01 Atom Transfer Radical Polymerization [ATRP] or reverse ATRP
• CPC Class Codes: C08G 83/003 Dendrimers

Abstract

In one aspect, the present invention is directed to dendrimers comprised of macromolecules and trifunctional branches. In another aspect, the invention relates to methods for generating dendrimeric compositions comprising macromolecules and trifunctional branches. In certain embodiments, the radial density of the dendrimeric composition is controlled by selective incorporation of branches.

Claims

1. A method for generating a dendrimer comprising a heterobifunctional core, a heterobifunctional macromolecule, and a heterotrifunctional branch, the method comprising:

(a) covalently linking a heterobifunctional core comprised of an α

-substituted click moiety group and an ω

-substituted click moiety group with a first heterobifunctional macromolecule or a first heterotrifunctional branch, wherein said heterobifunctional macromolecule or heterotrifunctional branch is comprised of a first click moiety group and a first terminus wherein the first terminus is comprised of a second click moiety group or a non-click functional group, and

(b) covalently linking the heterobifunctional macromolecule or heterotrifunctional branch with a second heterobifunctional macromolecule or heterotrifunctional branch.

2. The method of claim 1, wherein the first terminus is comprised of a second click moiety group.

3. The method of claim 1, wherein the first terminus is comprised of a non-click functional group.

4. The method of claim 3, further comprising a step wherein the non-click functional group is converted to a click moiety group.

5. The method of claim 3, wherein the non-click functional group is selected from the group consisting of alcohol, halide, alkylsulfonate, arylsulfonate, ester and silylether.

6. The method of claim 1, further comprising the step of repeating step (b) until a multilayer dendrimer having (i) a surface layer comprising a surface heterobifunctional macromolecule or heterotrifunctional branch, and (ii) a plurality of heterotrifunctional branches between the surface layer and the core is obtained.

7. The method of claim 1, wherein the first heterobifunctional macromolecule or first heterotrifunctional branch is comprised of a thiol or a terminal alkene.

8. The method of claim 2, wherein the second click moiety group is protected, and further comprising a step between step (a) and step (b) of deprotecting the protected second click moiety group to generate a second click moiety group.

9. The method of claim 1, wherein the macromolecule is comprised of a polymer.

10. The method of claim 1, wherein macromolecule is comprised of a polypeptide, an organic polymer, a polymer precursor, a thermoplastic polymer, a thermosetting polymer, a copolymer, a terpolymer, an oligomer, a homopolymer, a block copolymer, an alternating block copolymer, a random polymer, a random copolymer, a random block copolymer, a graft copolymer, a star block copolymer, a dendrimer or any combination thereof.

11. The method of claim 1, wherein the macromolecule is comprised of a silyl-alkyne-PS-N₃, silyl-alkyne-PtBA-N₃, silyl-alkyne-PnBA-N₃, or silyl-alkyne-PMMA-N₃ polymer.

12. The method of claim 9, wherein the polymer is α

-alkyne-trimethylsilyl-ω

-azide-poly(styrene), α

-alkyne-trimethylsilyl-ω

-azide-poly(tert-butyl acrylate), α

-alkyne-trimethylsilyl-ω

-azide-poly(n-butyl acrylate), or α

-alkyne-trimethylsilyl-ω

-azide-poly(methyl methacrylate).

13. The method of claim 9, wherein the polymer is about 10 Daltons to about 2,000,000 Daltons.

14. The method of claim 8, wherein the first click moiety group is an azide group and the protected second click moiety group is a silylated alkyne group.

15. The method of claim 8, wherein the branch is comprised of a plurality of protected second click moiety groups.

16. The method of claim 8, wherein the branch is comprised of two protected second click moiety groups.

17. The method of claim 1, wherein the core is linked to a nanoparticle.

18. The method of claim 1 wherein the heterobifunctional core is:

19. The method of claim 1, wherein the heterotrifunctional branch is comprised of an alkene and an azide.

20. The method of claim 1, wherein the heterotrifunctional branch is comprised of an azide and a thiol.