New Product Line: NTrēons: “Newkome” Dendrons and Dendrimers:

View Dendrimer Products
Through collaboration with Prof. Newkome, one of the pioneers of dendrimer technology, “Newkome dendrimers and dendrons” are now available commercially, through Frontier Scientific, Inc. These building blocks are distinguished from the already available PAMAM-type assemblies by their 1 -> 3 C-branching pattern, allowing for greater density of functional groups and facilitating a modular approach to the construction of new materials. The branching centers of our dendrimers and dendrons are three methylene units apart, allowing facile chemical manipulation of the termini without “overcrowding”. Our initial offerings include five dendrons, the branched building-blocks for dendrimer synthesis, two being 1-> 4 core-type dendrons, and four dendrimers, generations one and two in size possessing 12 and 36 termini, respectively. To date, numerous dendrons have been created in Prof. Newkome’s laboratories; as we grow and expand into this burgeoning new market our dendron selection will also grow. Please do not hesitate to contact us with inquiries about catalog items, custom synthesis, and comments concerning this new dendron-based product line.

Critical Design Parameters in Dendrimer Construction

  • Central Core
  • Branching Centers
  • Method of Connectivity
  • Terminal Group Functionality
  • Framework Functionality

There are two methods generally accepted for the synthesis of dendrimers: the convergent approach and divergent approach. The convergent approach corresponds to dendritic construction from the “outside in” towards a suitable core. In this protocol, the number of reactions required for dendron attachment and generational growth is constant. This is depicted in Scheme 1, using FSI dendron NTN 1963 and FSI core NTN 1960.1 A divergent synthesis is essentially the opposite building from the “inside out”; starting with a multi-functional core, dendrons are added sequentially, until the desired generation is obtained. In Scheme 2, a PAMAM core is linked with FSI dendron NTN 1962 forming poly(urea-based) dendrimer.2

The dendrimer/dendron product line from FSI offers opportunities for both convergent and divergent syntheses of NTrēon dendrimers, offering comparatively more sites of functionality than currently offered PAMAM dendrimers.

Table 1. Terminal Site comparison of NTrēons to PAMAM

Generation PAMAM Terminal Sites (NAME) Terminal Sites
1 8 12
2 16 36
3 32 108*
4 64

*custom item, ask for pricing

A mix and match approach is also possible, as PAMAM type dendrimers can be divergently decorated with weisocyanate Z dendrons should more branching be desired, or conversely NTrēon dendrimers can be expanded with PAMAM units if fewer branches/terminal sites are desired. The “Newkome” dendrimer/dendron product line offered by FSI, combined with PAMAM-type dendrimers, and other already commercially available dendrons, is expected to greatly facilitate the creation of new utilitarian nanoscale materials.

Incorporation into Traditional Areas of Research

After discovery and development of dendrimeric polymers by Newkome, Tomalia, and Vögtle through the 70’s and 80’s, these unique globular molecules began to attract interest for potential use in a variety of applications due to the ease of integration with more mature areas of chemistry. These included nanotechnology, where independent functionalizable macromolecules might act as micro-factories for nanomachines capable of such phenomena as light-harvesting, red-ox catalysis, signal transduction, and electrical conduction. Medicinal chemists also perceived in dendrimers a new customizable vehicle for drug delivery, as well as functional medicinal polymers that could selectively compete for receptor sites for treatment of disease. In this field, dendritic MRI contrast reagents are also being explored because they can potentially provide better images due to their ability to encapsulate more of the MRI-active metals (gadolinium usually). Lastly, dendrimers are seeing use as modifiable additives, to break up clog-causing hydrates in oil pipelines, or as hyperbranched polyesters to improve material properties in synthetic fabrics, or coatings. Dendritic polymers are quickly becoming recognized as potential tools for solving problems and creating new inventions in the material, medicinal, and nanotechnology disciplines.

Modular Approaches to
Branched Architecture
Construction are Leading
to New Industrial Applications

For application references: specialty coatings13,14, sensors15-17, polymers and material property modification18-20, liquid crystals21

Pioneers and Milestones in the Field of Dendrimers

P. J. Flory – Evidence for Branched-Chain
Macromolecules – 1941 – 1942 (Nobel 1974) 22,23,24

J.-M. Lehn – Stepwise Strategies for Synthesis of Marcocyclic Rings – 1973 (Nobel 1987) 25

F. Vögtle – Cascade Synthesis – 1978 26

R. G. Denkwalter – Lysine-dendrimer Patent – 1981 27, 28, 29

G. R. Newkome – First Modular Dendrimer Synthesis, First Reference to Unimolecular Micelles – 1985 30, 31, 32

D. A. Tomalia – First High-Generation Dendrimers based on Linear Monomers – 1985 33

J.-M. Fréchet – First Convergent Synthesis – 1990 34, 35

P. G. DeGennes – First Theoretical Study on Dendrimers – 1983 (Nobel 1991) 36

J. S. Moore – Phenylacetylene Dendrimers – 1991 37

Wörner, Mülhaupt, De Brabander-van den
Berg, Meijer – Improved Vögtle’ Procedure and Later Developed the Dendritic Box –
1993 38-41

S. Masamune – Silicone-based Dendrimers
– 1990 42

J. –P. Marjoral – Phosphorous-based
Dendrimers – 1994 43

S. Zimmerman – Self-Assembly of
Dendrimers – 1995 44

A. D. Schlüter – Dendronized-Polymers –
1995 45,46

V. Balzani – Metallodendrimers – 1989 47,48,49

D. Seebach – Chiral Dendrimers – 1993 50

R. H. E. Hudson – DNA-based Dendrimers –
1993 51

    Application References:

  1. Young, J.K.; Baker, G.R.; G.R. Newcome; Morris, K.F.; C.S. Johnson, Macromolecules, 1994, 27, 3464-3471.
  2. G.R. Newkome; Weis, C.D.; Moorefieild, C.M., Tet. Lett, 1997, 38 (40), 7053-7056.
  3. Boas, U.; Heegaard, P. M. H. Dendrimers in drug research. Chem. Soc. Rev.2004,33 (1), 43-63.
  4. Liu, M.; Fréchet, J. M. J. Designing dendrimers for drug delivery. Pharmaceutical Science Technology Today1999,2 (10), 393-401.
  5. Newkome, G. R.; Moorefield, C. N.; Güther, R.; Baker, G. R. Novel Building Blocks for Incorporation of Molecular Recognition Sites within Cascade Polymeric Architectures. Polym. Prepr.1995,36 (1), 609-610.
  6. Newkome, G. R.; Patri, A. K.; Godínez, L. A. Design, Syntheses, Complexation, and Electrochemistry of Polynuclear Metallodendrimers Possessing Internal Metal Binding Loci. Chem. Eur. J.1999,5 (5), 1445-1451.
  7. Newkome, G. R.; Patri, A. K. Approach towards dendritic networks: design, syntheses, and metal complexes of dendritic biquinoline ligands. Polym. Mater. Sci. Eng.1999,80, 66-67.
  8. Newkome, G. R.; Narayanan, V. V.; Godínez, L. A. Anthraquinoid-based extended dendritic monomers: electrochemical comparisons. Designed Monomers and Polymers2000,3 (1), 17-24.
  9. Newkome, G. R.; Narayanan, V. V.; Godínez, L. A. Electroactive, Internal Anthraquinonoid Dendritic Cores. J. Org. Chem.2000,65, 1643-1649.
  10. Newkome, G. R.; Narayanan, V. V.; Godínez, L. A.; Pérez-Cordero, E.; Echegoyen, L. A Tailored Approach to the Syntheses of Electroactive Dendrimers Based on Diaminoanthraquinones. Macromolecules1999,32, 6782-6791.
  11. Malenfant, P. R. L.; Jayaraman, M.; Fréchet, J. M. J. Dendrimer-Supported Oligothiophene Synthesis: Aliphatic Ether Dendrimers in the Preparation of Oligothiophenes with Minimal Substitution. Chem. Mater.1999,11, 3420-3422.
  12. Apperloo, J. J.; Janssen, R. A. J.; Malenfant, P. R. L.; Groenendaal, L.; Fréchet, J. M. J. Redox States of Well-Defined  -Conjugated Oligothiophenes Functionalized with Poly(benzyl ether) Dendrons. J. Am. Chem. Soc.2000,122 (29), 7042-7051.
  13. Hong, B. J.; Shim, J. Y.; Oh, S. J.; Park, J. W. Self-Assembly of a Dendron through Multiple Ionic Interaction to Give Mesospacing between Reactive Amine Groups on the Surface. Langmuir2003,19 (6), 2357-2365.
  14. Kontturi, E.; Thüne, P. C.; Niemantsverdriet, J. W. Novel method for preparing cellulose model surfaces by spin coatings. Polymer2003,44 (13), 3621-3625.
  15. Briñas, R. P.; Troxler, T.; Hochstrasser, R. M.; Vinogradov, S. A. Phosphorescent Oxygen Sensor with Dendritic Protection and Two-Photon Absorbing Antenna. J. Am. Chem. Soc.2005,127 (33), 11851-11862.
  16. Alonso, B.; Astruc, D.; Blais, J.-C.; Nlate, S.; Rigaut, S.; Ruiz, J.; Sartor, V.; Valério, C. Metallodendrimers towards enzyme mimics and molecular electronics: new-generation catalysts, sensors and molecular batteries. C. R. Acad. Sci. Paris II,Chemie2001,4 (3), 173-180.
  17. Balzani, V.; Ceroni, P.; Gestermann, S.; Kauffmann, C.; Gorka, M.; Vögtle, F. Dendrimers as fluorescent sensors with signal amplification. Chem. Commun.2000, 853-854.
  18. Zheng, J.; Dickson, R. M. Individual Water-Soluble Dendrimer-Encapsulated Silver Nanodot Fluorescence. J. Am. Chem. Soc.2002,124 (47), 13982-13983.
  19. Andreopoulou, A. K.; Carbonnier, B.; Kallitsis, J. K.; Pakula, T. Dendronized Rigid-Flexible Macromolecular Architectures: Syntheses, Structure, and Properties in Bulk. Macromolecules2004,37 (10), 3576-3587.
  20. Newkome, G. R.; Weis, C. D.; Moorefield, C. N.; Baker, G. R.; Childs, B. J.; Epperson, J. D. Isocyanate-Based Dendritic Building Blocks: Combinatorial Tier Construction and Macromolecular Property Modification. Angew. Chem. Int. Ed.1998,37, 307-310.
  21. Chuard, T.; Béguin, M.-T.; Deschenaux, R. Ferrocene-containing liquid-crystalline dendrimers. C. R. Chimie2003,6 (8-10), 959-962.

  22. Milestone References:

  23. Flory, P. J. "Molecular Size Distribution in Three Dimensional Polymers. I. Gelation," J. Am. Chem. Soc.1941, 63(11), 3083-3090.
  24. Flory, P. J. "Molecular Size Distribution in Three Dimensional Polymers. II. Trifunctional Branching Units," J. Am. Chem. Soc.1941, 63(11), 3091-3096.
  25. Flory, P. J. "Molecular Size Distribution in Three Dimensional Polymers. III. Tetrafunctional Branching Units," J. Am. Chem. Soc.1941, 63(11), 3096-3100.
  26. Lehn, J.-M. "Design of Organic Complexing Agents. Strategies Towards Properties" In Structure and Bonding; Springer: New York , 1973; Chapter 1.
  27. Buhleier, E.; Wehner, W.; Vögtle, F. ""Cascade" and "Nonskid-Chain-like" Syntheses of Molecular Cavity Topologies," Synthesis1978, (2), 155-158.
  28. Denkewalter, R. G., Kolc, J. F., and Lukasavage, W. J. "Preparation of Lysine Based Macromolecular Highly Branched Homogeneous Compound," U.S.Pat. 4,360,646, 1979.
  29. Denkewalter, R. G., Kolc, J. F., and Lukasavage, W. J. "Macromolecular Highly Branched Homogeneous Compound Based on Lysine Units," U.S.Pat. 4,289,872, 1981.
  30. Aharoni, S. M.; Crosby, C. R., III; Walsh, E. K. "Size and Solution Properties of Globular tert-Butyloxycarbonyl-poly(  ,  -L-lysine)," Macromolecules1982, 15(4), 1093-1098.
  31. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. "Cascade Molecules: A New Approach to Micelles. A [27]-Arborol," J. Org. Chem.1985, 50(11), 2003-2004.
  32. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K.; Russo, P. S.; Saunders, M. J. "Cascade Molecules: Synthesis and Characterization of a Benzene[9] 3-Arborol," J. Am. Chem. Soc.1986, 108(4), 849-850.
  33. Newkome, G. R.; Baker, G. R.; Saunders, M. J.; Russo, P. S.; Gupta, V. K.; Yao, Z.; Miller, J. E.; Bouillion, K. "Two-directional Cascade Molecules: Synthesis and Characterization of [9]-n-[9] Arborols," J. Chem. Soc. , Chem. Commun.1986, (10), 752-753.
  34. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. "A New Class of Polymers: Starburst-Dendritic Macromolecules," Polym. J. (Tokyo)1985, 17(1), 117-132.
  35. Hawker, C. J.; Fréchet, J. M. J. "Preparation of Polymers with Controlled Molecular Architecture. A New Convergent Approach to Dendritic Macromolecules," J. Am. Chem. Soc.1990, 112(21), 7638-7647.
  36. Hawker, C.; Fréchet, J. M. J. "A New Convergent Approach to Monodisperse Dendritic Macromolecules," J. Chem. Soc. , Chem. Commun.1990, (15), 1010-1013.
  37. de Gennes, P. G.; Hervet, H. "Statistics of <> polymers," J. Phys. Lett.1983, 44, L351-L360.
  38. Moore, J. S.; Xu, Z. "Synthesis of Rigid Dendritic Macromolecules: Enlarging the Repeat Unit Size as a Function of Generation Permits Growth to Continue," Macromolecules1991, 24(21), 5893-5894.
  39. Wörner, C.; Mülhaupt, R. "Polynitrile- and Polyamine-Functional Poly(trimethylene imine) Dendrimers," Angew. Chem. , Int. Ed. Engl.1993, 32(9), 1306-1308.
  40. de Brabander-van den Berg, E. M. M.; Meijer, E. W. "Poly(propylene imine) Dendrimers: Large-Scale Synthesis via Heterogeneously Catalyzed Hydrogenation," Angew. Chem. , Int. Ed. Engl.1993, 32(9), 1308-1311.
  41. Jansen, J. F. G. A.; Meijer, E. W.; de Brabander-van den Berg, E. M. M. "The Dendritic Box: Shape-Selective Liberation of Encapsulated Guests," J. Am. Chem. Soc.1995, 117(15), 4417-4418.
  42. Jansen, J. F. G. A.; de Brabander-van den Berg, E. M. M.; Meijer, E. W. "The Dendritic Box and Bengal Rose," Polym. Mater. Sci. Eng.1995, 73, 123-124.
  43. Uchida, H.; Kabe, Y.; Yoshino, K.; Kawamata, A.; Tsumuraya, T.; Masamune, S. "General Strategy for the Systematic Synthesis of Oligosiloxanes. Silicone Dendrimers," J. Am. Chem. Soc.1990, 112(19), 7077-7079.
  44. Launay, N.; Caminade, A.-M.; Lahana, R.; Majoral, J.-P. "A General Synthetic Strategy for Neutral Phosphorus-Containing Dendrimers," Angew. Chem. , Int. Ed. Engl.1994, 33(15/16), 1589-1592.
  45. Zimmerman, S. C.; Zeng, F.; Reichert, D. E. C.; Kolotuchin, S. V. "Self-Assembling Dendrimers," Science1996, 271(5252), 1095-1098.
  46. Claussen, W.; Schulte, N.; Schlüter, A.-D. "A poly(p-phenylene) decorated with Fréchet-type dendritic fragments of the first-generation," Macromol. Rapid Commun.1995, 16(1), 89-94.
  47. Schlüter, A.-D.; Claussen, W.; Freudenberger, R. "Cylindrically shaped dendritic structures," Macromol. Symp.1995, 98, 475-482.
  48. Campagna, S.; Denti, G.; Sabatino, L.; Serroni, S.; Ciano, M.; Balzani, V. "A New Hetero-tetrametallic Complex of Ruthenium and Osmium: Absorption Spectrum, Luminescence Properties, and Electrochemical Behaviour," J. Chem. Soc. , Chem. Commun.1989, 1500-1501.
  49. Denti, G.; Serroni, S.; Campagna, S.; Ricevuto, V.; Balzani, V. "Directional energy transfer in a luminescent tetranuclear Ru(II) polypyridine complex that contains two different types of bridging ligands," Inorg. Chim. Acta1991, 182, 127-129.
  50. Serroni, S.; Denti, G.; Campagna, S.; Ciano, M.; Balzani, V. "A Decanuclear Ruthenium(II)-Polypyridine Complex: Synthesis, Absorption Spectrum, Luminescence and Electrochemical Behaviour," J. Chem. Soc. , Chem. Commun.1991, 944-945.
  51. Lapierre, J.-M.; Skobridis, K.; Seebach, D. "Preparation of Chiral Building Blocks for Starburst Dendrimer Synthesis," Helv. Chim. Acta1993, 76, 2419-2432.
  52. Hudson, R. H. E.; Damha, M. J. "Nucleic Acid Dendrimers: Novel Biopolymer Structures," J. Am. Chem. Soc.1993, 115(6), 2119-2124.
Advanced Discovery Chemicals