Dendritic molecules and method of production

• US 5,041,516 A
• Filed: 06/21/1989
• Issued: 08/20/1991
• Est. Priority Date: 06/21/1989
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Philippides, Athena E., Hawker, Craig J., Frechet, Jean M. J.
• Primary Examiner(s): Kight, III, John
• Assistant Examiner(s): Sergent, Rabon
• Application Number:
  US07/369,270
• Time in Patent Office: 790 Days
• Field of Search: 528/425, 528/310, 528/323, 528/44, 528/45, 528/68, 528/70, 528/74, 528/85, 528/271, 528/272, 528/332, 528/363, 528/370
• US Class Current: 528/44
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 271/28 to a carbon atom of a non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 69/92 with etherified hydroxyl groups
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence
• CPC Class Codes: C08G 83/003 Dendrimers
• CPC Class Codes: C08G 85/00 General processes for preparing compounds provided for in this subclass
• CPC Class Codes: Y10S 424/16 Dendrimers and dendritic polymers

Abstract

Dendritic macromolecules and a novel convergent process for producing the same are disclosed. The convergent process enables the accurate control and design of the surface functionality of the macromolecule.

Claims

1. A process for producing a dendritic macromolecule having a polyfunctional central core connected to a periphery by a dendritic body which comprises building the macromolecule starting with the periphery, continuing through the dendritic body to form a dendritic wedge having a single reacting group at its focal point, and then attaching the wedge through the focal point group to the central core.

2. The process of claim 1, wherein the periphery is comprised of surface compounds having two parts, a non-reacting part and a reacting part.

3. The process of claim 2, wherein the reacting parts of at least two surface compounds are each reacted with a reacting group of a monomer unit which contains at least two of said reacting groups and further contains a non-reacting but activatable group to form the dendritic wedge having a single non-reacting but activatable group at its focal point.

4. The process of claim 3, wherein the non-reacting but activatable focal point groups of at least two dendritic wedges are each activated and reacted with reacting groups of an additional monomer unit to form a larger dendritic wedge having a single non-reacting but activatable group at its focal point.

5. The process of claim 4, wherein the activation of the focal point groups and reacting with reacting groups of additional monomer units is repeated until a dendritic wedge of a predetermined size is prepared.

6. The process of claim 5, wherein at least two dendritic wedges of the predetermined size are attached to the polyfunctional core by activating their respective focal point groups and reacting said groups with reacting groups of the core.

7. The process of claim 1, wherein the non-reacting part of the surface compound contains a reactive group which is non-reacting with all other compounds and reagents used and all intermediates formed in the preparation of the macromolecule.

8. The process of claim 1, wherein the periphery is comprised of at least two different surface compounds.

9. The process of claim 8, wherein the non-reacting part of at least one of the surface compounds contains a reactive group which is non-reacting with all other compounds and reagents used and all intermediates formed in the preparation of the macromolecule.

10. The process of claim 8, wherein the non-reacting parts of at least two of the surface compounds contain different reactive groups each of which is non-reacting with the other and with all other compounds and reagents used and intermediates formed in the preparation of the macromolecule.

11. The process of claim 1, wherein the macromolecule is constructed by (i) reacting a surface compound containing a surface portion which is non-reactive with all compounds and reagents used and intermediates formed in the preparation of the macromolecule and a single group which is reacting with a monomer unit containing at least two groups which are reacting with the reacting group of the surface compound and one group at its focal point which is non-reacting but may be activated to become reacting, (ii) activating the non-reacting focal point group to make it reacting, (iii) reacting the activated focal point group with an additional monomer unit containing a non-reacting group at its focal point, (iv) repeating steps (ii) and (iii) until a dendritic wedge of a predetermined size is formed, (v) activating the non-reacting focal point group of the dendritic wedge and coupling it to a polyfunctional core compound.

12. The process of claim 11, wherein the non-reactive portion of the surface compound contains at least one functional "X" group, wherein "X" is a reactive group which is non-reacting with all compounds and reagents used and intermediates formed in the process, and a reacting group.

13. The process of claim 11, wherein at least two different surface compounds are used to produce the macromolecule.

14. The process of claim 13, wherein the non-reactive portion of at least two of the surface compounds each contains a functional "X" group, wherein "X" is a reactive group which is is non-reacting with all compounds and reagents used and intermediates formed in the process, and which "X" groups are the same or different and are non-reacting with other "X" groups.

15. The process of claim 11 wherein the surface compound is a compound of the formula:

space="preserve" listing-type="equation">(s).sub.m --R--f

wherein "s" is any group which is non-reacting with any portion of all other compounds and reagents used and all intermediates formed in the preparation of the macromolecule, "m" is an integer, "R" is an organic moiety which is non-reacting with all other compounds and reagents used and intermediates formed in the preparation of the macromolecule, and "f" is a group which is non-reacting with "s" but is reacting with a group "c" of the monomer unit or of the core compound.

16. The process of claim 15, wherein at least one surface compound "s" group is substituted with a reactive "X" group which is non-reacting with all other compounds and reagents used and all intermediates formed in the preparation of the macromolecule.

17. The process of claim 16, wherein "X" is selected from the group consisting essentially of F, Cl, Br, Cn, --NO₂, --NHC(O)R² wherein R² is alkyl, aryl, O-alkyl, or O-aryl, --CONH₂, --CO₂ R³ wherein R³ is alkyl or aryl, --O--C(O)R³, --OR³, and alkyl or aryl groups substituted with any of the above functional groups.

18. The process of claim 16, wherein "X" is cyano.

19. The process of claim 11, wherein the monomer unit comprises a compound containing (i) at least two groups which are reactive with an activated focal point group of a partially formed dendritic wedge or the reacting group of the surface compound and (ii) a single non-reacting but activatable group at its focal point.

20. The process of claim 11, wherein the monomer unit is a compound of the formula:

space="preserve" listing-type="equation">(c).sub.n --R'"'"'--f'"'"'

wherein "c" is a coupling group which is non-reacting with "f'"'"'" but is reacting with an activated "f" group, "n" is an integer greater than 1, R'"'"' is an organic moiety which is non-reacting with all other compounds and reagents used and intermediates formed in the preparation of the macromolecule, and "f'"'"'" is a non-reacting group which is activatable to form reacting group "f".

21. The process of claim 11, wherein the core compound is of the formula:

space="preserve" listing-type="equation">(c).sub.x --R"

wherein "c" is a coupling group which is non-reacting with "f'"'"'" but is reacting with an activated "f" group, "x" is an integer greater than 1, and "R"" is any organic moiety which is non-reacting with all other compounds and reagents used and intermediates formed in the preparation of the macromolecule.

22. The process of claim 11, wherein the core compound is of the formula:

space="preserve" listing-type="equation">(c).sub.x --R"

wherein "c" is a protected coupling group which, after removal of the protection, is non-reacting with "f'"'"'" but is reacting with an activated "f" group, "x" is an integer greater than 1, and "R"" is an organic moiety which is non-reacting with all other compounds and reagents used and intermediates formed in the preparation of the macromolecule.

26. The process of claim 1 wherein the macromolecule has an outer surface disposed at its periphery which is non-uniformly functionalized having at least one functional group at its outer surface, which functional group is non-reacting with all compounds and reagents used and intermediates formed in preparing the macromolecule.

27. The process of claim 26, wherein the functional group is selected from the group consisting essentially of F, Cl, Br, CN, --NO₂, --NHC(O)R² wherein R² is alkyl, aryl, O-alkyl, or O-aryl, --CONH₂, --CO₂ R³, --O--C(O)R³, --OR³, wherein R³ is alkyl, aryl, and alkyl and aryl substituted with any of the other functional groups.

23. A process of forming a dendritic wedge having a single reacting group at its focal point which comprises (i) reacting a surface compound containing a surface group which is non-reacting with all compounds and reagents used and intermediates formed in the preparation of the wedge and a single reacting group which reacts with a monomer unit containing at least two groups which are reacting with the reactive group of the surface compound and one non-reacting group at its focal point, (ii) activating the non-reacting group, (iii) reacting the activated focal point group with an additional monomer unit containing a non-reacting group at its focal point, (iv) repeating steps (ii) and (iii) until a dendritic wedge of the desired size is formed.

24. The process of claim 23, wherein at least two dendritic wedges are produced and each dendritic wedge is coupled to a single core compound having at least two reacting functional sites.

25. The process of claim 23, wherein the dendritic wedge is formed by reacting the surface compound with the monomer unit to form a first generation dendrimer and then reacting at least two of the first generation dendrimers with an identical monomer unit.

28. The process of claim 23, wherein the monomer unit has n coupling sites and one focal non-reactive, activatable focal group and the r'"'"'th generation dendritic wedge contains n^r surface compounds which are the same or different.

29. The process of claim 23, wherein the dendritic wedge is constructed by (i) reacting a surface compound containing a surface portion which is non-reacting with all compounds and reagents used and intermediates formed in the preparation of the wedge and a single group which reacts with one of at least two reacting groups of a first monomer unit which further contains one reacting group at its focal point which is non-reacting with the reacting groups of the monomer to form a first generation dendrimer, (ii) reacting the focal point groups of at least two first generation dendrimers with a second monomer unit which is different from the first monomer unit and containing a non-reacting group at its focal point to form a second generation dendrimer, (iii) reacting at least two of the second generation dendrimers with a first monomer unit to form a third generation dendrimer (iv) alternately repeating steps (ii) and (iii) until the dendritic wedge of a predetermined size is formed.

30. A macromolecule comprising a core compound having at least two functional sites and at least one dendritic wedge having a single reacting functional group at its focal point through which it is attached to the core compound, said dendritic wedge having been preformed and then coupled to the core compound by reaction between one of the functional groups on the core compound and the functional group at the focal point of the dendritic wedge.

31. The macromolecules of claim 30 wherein the dendritic wedge has an outer surface disposed at the periphery of the macromolecule in which the outer surface contains at least one functional group which is non-reacting with all compounds and reagents used and intermediates formed in the preparation of the macromolecule.

32. The macromolecule of claim 30, wherein at least two dendritic wedges are coupled to the core compound.

33. The macromolecule of claim 32, wherein at least one of the dendritic wedges is different from the other.

34. The macromolecule of claim 33, wherein the dendritic wedges have outer surfaces disposed at the periphery of the macromolecule in which the outer surfaces differ in the number of functional groups thereon.

35. The macromolecule of claim 34 wherein the functional groups on the outer surface are selected from the group consisting of F, Cl, Br, CN, --NO₂, --NHC(O)R² wherein R² is alkyl, aryl, O-alkyl, or O-aryl, --CONH₂, --CO₂ R³, --O--C(O)R³, --OR³, wherein R³ is alkyl or aryl, and alkyl or aryl groups substituted with any of the other functional groups.

36. The macromolecule of claim 35 wherein the functional groups on the outer surface are cyano.

37. The macromolecule of claim 33, wherein the dendritic wedges have outer surfaces disposed at the periphery of the macromolecule in which the outer surfaces differ in the type of functional groups thereon.

38. The macromolecule of claim 37 wherein the functional groups on the outer surface are selected from the group consisting of F, Cl, Br, CN, --NO₂, --NHC(O)R² wherein R² is alkyl, aryl, O-alkyl, or O-aryl, --CONH₂, --CO₂ R³, --O--C(O)R³, --OR³, wherein R³ is alkyl or aryl, and alkyl or aryl groups substituted with any of the other functional groups.

39. The macromolecules of claim 38 wherein at least one of the functional groups on the outer surface is cyano.

40. The macromolecule of claim 32, wherein at least one of the dendritic wedges is uniformly functionalized.

41. The macromolecule of claim 30, wherein the dendritic wedge has internal linkage layers which comprise the group ##STR8##

42. The macromolecule of claim 30, wherein the dendritic wedge has internal lingage layers which comprise the group ##STR9##

43. The macromolecule of claim 30, wherein the dendritic wedge has internal linkages selected from the group consisting essentially of ether, urethane, ester, carbonate, urea, and amide linkages.

44. The macromolecule of claim 30, wherein the core compound is selected from the group consisting of compounds of the formula:

##STR10## pentaerythritol, pyromellitic anhydride, glucose, phloroglucinol, pyromellitic acid, benzenetetracarboxylic acid and anhydride, and ethylenediamine.

45. The macromolecule of claim 30, wherein the core compound is a polymer.

46. A dendrimer comprising a highly branched polymer chain which contains a single reacting group located at its focal point.

47. The dendrimer of claim 46, wherein said dendrimer is a non-uniformly functionalized molecule having at least one functional group at its outer surface which functional group is non-reacting with all compounds and reagents used and intermediates formed in the preparation of the dendrimer.

48. The dendrimer of claim 47, wherein the functional group is selected from the group consisting essentially of F, Cl, Br, CN, --NO₂, --NHC(O)R² wherein R² is alkyl, aryl, O-alkyl, or O-aryl, --CONH₂, --CO₂ R³, --O--C(O)R³, --OR³, wherein R³ is alkyl or aryl, and alkyl or aryl groups substituted with any of the other functional groups.

49. The dendrimer of claim 47, wherein the functional group is cyano.

50. The dendrimer of claim 46 containing internal linkage layers comprising the group ##STR11##

51. The dendrimer of claim 46, containing internal linkage layers comprising the group ##STR12##

52. The dendrimer of claim 46 containing internal linkages selected from the group consisting essentially of ether, urethane, ester, carbonate, urea, and amide linkages.