Some examples of dendrimer synthesis
Dendrimers are highly branched macromolecules with unique structural properties. They may be thought of as core–shell type macromolecules wherein they amplify their mass and terminal groups as a function of growth stages. These growth stages are referred to as generations (i.e. G= 0, 1, 2, . . .). They possess three key architectural features: (i) a core region; (ii) interior shell zones containing cascading tiers of branch cells (generations) with radial connectivity to the initiator core; and (iii) an exterior or surface region of terminal moieties attached to the outermost generation. With this architecture, a careful choice of building blocks and functional groups can provide control over shape, dimensions, density, polarity, reactivity, and solubility. One of the earlier dendrimers made, using a divergent strategy, is the Starburst® poly(amidoamine) (PAMAM) dendrimer family (Scheme 1). This method involved assembling repeat units to introduce branch cells around the initiator core through successive chemical reactions at the periphery of the growing macromolecule. The first step of PAMAM synthesis involves Michael addition of four moles of methyl acrylate to the nucleophilic ethylenediamine core. This leads to an electrophilic carbomethoxy surface, which is then allowed to react with an excess of 1,2-diaminoethane to give a nucleophilic surface at generation zero. Reiteration of these two steps now involves addition of 8 mol of methyl acrylate to give G = 0.5 (electrophilic, carbomethoxy surface). This is followed by amidation to return to a nucleophilic surface at G = 1.0. As a result of this reiterative branch cell assembly, it is apparent that these constructions follow systematic dendritic branching rules, with radial symmetry giving a well-defined three-dimensional geometry to the final dendritic product. In general, the placement of reactive functionalities on the exterior surface of the dendrimers allows introduction of a wide variety of terminal moieties. In alternate synthetic approaches, spacer groups have been deliberately introduced to relieve the steric hindrance in order to facilitate construction of the next generation. This may provide the possibility of enhancing interior cargo spaces for ‘guest–host’ type chemistry.