IN A NUTSHELL: For almost two decades MMI scientists have played a leading role in dendrimer research in the world. Among many accomplishments in the field, we have contributed to the development of the first commercial dendrimer-based immunoassay to monitor for heart attack, novel approaches towards the cancer and gene therapies, the discovery of dendrimer-metal nanocomplexes and nanocomposites, better understanding of unique Newtonian dendrimer rheology, the first commercial silicon-containing dendrimers (PAMAMOS), honeycomb-like nano-structured dendrimer-based films, sheets, membranes and coatings for various materials engineering applications, etc. In addition, it was from here that the first and still the largest industrial production of dendrimers in the world started in 1992, with the foundation of Dendritech Inc., also in Midland, Michigan. Today, Dendritech sells over 60 different products from two major dendrimer families (PAMAM and PAMAMOS), in up to 11 generations and 3 different grades, including technical, diagnostic and biomedical. And the work is still in full swing: developing new products and new applications, and pushing further the boundaries of understanding of these architecturally unique macromolecules.
WHAT ARE DENDRIMERS? Dendrimers (see figure above) are globular macromolecules that consist of two or more tree-like dendrons emanating from either a single central atom or atomic group called the core. The main building blocks of dendrimer molecular architecture are the branch cells which can be considered as three-dimensional dendritic repeat units that always contain at least one branch juncture. In an ideal dendrimer structure these branch cells are organized in a series of regular, radially concentric layers (called generations) around the core. Each of these layers contains a mathematically precise number of branch cells which increases in a geometrically progressive manner from the core to the dendrimer exterior (often also referred to as the dendrimer surface). The outermost branches end with the end-groups, which can be either chemically inert or reactive. Their number depends on the particular dendrimer composition (i.e., the branching functionality at each generational level) and generation, and may range from only a few (i.e., 3 or 4 functional groups of common cores) to several hundreds or even thousands at very high generations. Because of this, high generation dendrimers may be viewed as globular, reactive, nanoscopic entities with some of the highest density of functionality known to chemistry.
Dendrimers are synthesized by the repetitive addition of branch cells in the radial molecular direction, one layer or generation at a time, either from the core to the outer surface (divergent method), or from the end-groups to the core (convergent method). With rigorous process control and purification procedures after each iterative growth step, dendrimers can be obtained in very high purities and monodispersities of shapes and sizes, even at truly “polymeric” high molecular weights, which can reach into several hundreds of thousands, or even a million. Their sizes increase with generations in a manner that leads to the crowding of the end-groups, which in turn, forces dendrimers to adopt spheroidal or globular shapes at sufficiently high generations. For most compositions, dendrimer diameters increase in a regular manner with generations in increments of up to 1 nm per generation, from about 1 to about 10 nm. As a consequence, dendrimers represent a truly unique, homologous series of compositionally identical, chemically reactive, spheroidal building blocks that increase in size in a stepwise, controllable manner, spanning the lower domain of the nanoscopic size range. Because of this, they provide unprecedented tools to manipulate this fundamentally important size domain during the bottom-up synthesis of more complex nano-structures and thus achieve control of the structural organization of matter at the nano-scale with precision that was not possible before.
THE STATE OF TECHNOLOGY: During the last two decades, dendritic polymers, particularly dendrimers and hyperbranched polymers, have become one of the fastest growing areas of interest in polymer science. This resulted in an impressive growth of the number of publications on these unique polymers, which soared from less than a dozen in the 1970’s, to over 10,000 (in scientific journals and patent literature) at present. Of many reasons that may have caused such an “explosive” interest in dendritic polymers, the following two seem especially important.
First, it has been clearly realized that after traditional linear, crosslinked and lightly branched polymers, dendritic polymers comprise a completely new class of macromolecular architecture which exhibits its own, unique, architecture-specific properties that are not found in any of the traditional classes. Among others, such properties include: unusually low polydispersities and Newtonian flow of dendrimers even at very high molecular weights, nano-scale encapsulation abilities through various host-guest interactions, much smaller hydrodynamic molecular volumes and much more compact molecules than their corresponding linear counterparts, much higher solubilities and much lower viscosities than the corresponding linear polymers of the comparable composition and molecular weights, etc. Consequently, many investigations have been directed at assembling new polymer architectures from well-known, commercially available monomers, in a desire to achieve new material properties while avoiding traditional, often painstaking, approaches based on the syntheses of compositionally new monomers followed by their polymerization.
Second, together with fullerenes, polyhedral oligosilsesquioxanes (POSS), and carbon nanotubes, dendrimers and hyperbranched polymers are among the few known chemical building blocks of truly nanoscopic size (i.e., ranging between 1 and 10 nm in the longest molecular dimension) that can be used for the directed synthesis of more complex nano-structured materials by controlled bottom-up approaches. As a consequence, with the spectacular rise of nanotechnology in the 1990s and 2000s, this, “chemical” approach to “soft” nanotechnology gained outstanding importance and popularity, and within it dendrimers have played a very important and unique role. Namely, while both fullerene spheres and POSS cubes are limited in dimensions to a diameter of about 1.5 nm and a diagonal of about 0.5 nm, respectively, a generational series of dendrimers provides not only preciseness of the molecular diameter of each of its members, but also the ability to select at will the chemical composition and the molecular size of the building block by choosing the appropriate dendrimer and its generation. In essence, this enables selection of the size domain at which one can exercise control over the composition and structure being built, which, in turn, also predefines the resulting properties of the obtained material, specific for the size and the properties of the dendrimer generation used.
OUR NOVELTIES: For almost two decades MMI scientists have played one of the major roles in the dendritic polymers research and development in the world, and some of our contributions are described in other pages on this website (See photonics, specialty coatings, delivery systems, membranes, sensors and other technologies).
In addition to these, we have published 2 books and over 100 papers in scientific journals on this subject matter, obtained several tens of U.S. and international patents in 3 major patent portfolios, and delivered numerous invited and contributed lectures and presentations at national and international scientific meetings, universities and companies in tens of different countries.
Some of our main contributions include the following:
- The Dade Behring Stratus® CKMB immunoassay to monitor the heart attack was the first dendrimer-based diagnostic tool introduced into the health market. It is based on one of our PAMAM dendrimers which enabled shortening of the critical diagnostic time in this life-threatening situation from over 40 minutes before Stratus to below 10 minutes now. The use of dendrimers in this application is under our world-wide license to in vitro human and veterinary diagnostics.
- We have originated the concept of using dendrimers and their “nano-scale container properties” as delivery agents for targeted therapeutic applications, including the cancer therapy which has attracted outstanding research attention in the biomedical world. For this purpose, Dendritech Inc., has produced and supplied kilogram quantities of the base dendrimer to Avidimer Therapeutics, the leading developer in the field.
- We have studied and described in detail in our publications in Macromolecules the dendrimer Newtonian flow behavior which makes them unique among other known high molecular weight macromolecules and suitable for unprecedented viscosity standards as nanoscopic “molecular ball bearings”.
- We have also developed the first organo-silicon radially layered copolymeric dendrimers, some of which are now being commercially produced by Dendritech Inc., under the trade-name of PAMAMOS. These dendrimers are ideal, highly precise globular building blocks for bottom-up preparation of nano-scaled honeycomb-like 3D networks which can be easily formed into elastomeric or plastomeric films, sheets, membranes or coatings on variety of substrates, including glass, metals, plastics, paper, etc.
- These unique dendrimer-based networks open the doors for dendrimers to materials science and engineering, offering exceptionally attractive possibilities for applications in nano-patterning (lithography), various types of chemical and biological sensors, decontamination materials, preparation of nano-porous dielectrics, various nanocomplexes and nanocomposites with metals or organometallic compounds, room temperature preparation of quantum dots, etc.
Some other applications are described in more detail in specific pages on this website.