Many experimental models have suggested that life arose spontaneously; simple inorganic building blocks or monomers combined to form larger, organic clusters with new properties. For years, scientists have attempted to copy the evolutionary process, endeavoring to assemble small, identical subunits into complex macromolecules that could be manipulated to interact with and even mimic life. In this attempt, the first major class of polymers was identified in the 1930s. Staudinger linked identical monomers into a spaghetti-like string called the random-coil polymer. These polymers yielded products such as Styrofoam, polyethylene plastic, nylon, and Plexiglas, known as thermoplastics (7,8). The next decade showed progress in the making of larger molecules that constituted the second class of poly-mers—the family of cross-linked polymers or thermosets. Flory (9-11) and Stockmayer (12,13) successfully created three-dimensional structures by bridging or "cross-linking" the random-coil polymers at various sites, forming an inflexible molecule. These compounds are insoluble in most liquids due to their rigidity and therefore are used as a component of epoxies, urethanes, fiberglass, resins rubbers, and gels (7,8). The third class of polymers was developed in the 1960s. These randomly branched polymers change the bulk property of a substance such as the differences between low-density polyethylene, which is highly branched, and high-density polyethylene, which is virtually unbranched (8). A change in the properties of these polymers is accomplished by altering the types and combinations of the reagents used in the polymerization process.
The problem with the first three classes of polymers was the difficulty in predicting the precise internal structure of the polymer. In an attempt to further define the submolecular structure, a fourth class of polymers was synthesized. This class was referred to as having a dendritic macromolecular architecture due to the branching structure, similar to that of trees. Tomalia, Vogtle, and Newkome independently reported the synthesis of dendrimers. Buhleier et al. (14) and Newkome et al. (15) developed the first dendritic structures, called cascade molecules and arborols, respectively. Tomalia et al. (16) developed the first dendrimer, named the Starburst™ polyamidoa-mine (PAMAM) dendrimer because of its dendritic branches and controlled starburst growth. This macromolecule is built on an ammonia core with extending branches of alternating methyl acrylate and ethylene diamine molecules (17). The cascade is continued by adding methyl acrylate moieties onto the reactive ends of the ethylene diamine molecules and then ethylene diamine moieties onto the methyl acrylate. Each addition creates another branched layer, referred to as a generation. Each generation causes an exponential increase in the surface reactive sites that may have functional implications (7).
The prospects for the use of dendrimers were numerous and exciting. Unlike the unpredictable length, size, and shape of the previous classes of polymers, the architecture of these dendritic branched molecules can be controlled. The critical molecular design parameters of size, shape, surface chemistry, flexibility, and topology can be carefully regulated to create the complex molecule. In addition, the dendrimer possesses a remarkably celllike construction consisting of a low-density core and modifiable internal and external surfaces, making it a perfect container or scaffolding for drugs, DNA, and protein. Dendrimers show great promise for a variety of uses such as drug and gene delivery systems, imaging agents, diagnostic kits, tumor therapy, industrial catalysts, and sensors.
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