Research @ Thai's Group

Dendrimers (greek dendron = tree) are hyperbranched molecules, composed of a central core, to which repetitive dendritic branches are attached. These branches are synthesized from identic building blocks via an interative synthesis strategy. Efficient nonlinear growth methodologies provide access to monodisperse high molecular globular structures with unique properties. By an accurate choice of the building blocks to be used and specific functionalization in the periphery (S), the molecular weight, monodispersity, size, shape, chirality, density, viscosity, polarity, solubility, flexibility and surface chemistry of the resulting macromolecules can be controlled. This leads to new materials with a great potential for future applications.

In fact, dendrimers have often been referred to as possible globular protein mimics. However, to fully realize dendritic structures as potential biological mimics, the ability to incorporate additional structural features is needed. Arguably, the most important of these structural requirements is the ability to selectively functionalize the concave interiors of these macromolecules, i.e., selectively direct functional groups toward the interior of the globular dendrimer. The difficulty in meeting this structural requisite arises from the flexible nature of the backbone in a globular dendrimer. In molecules with flexible backbone, attaining conformational control over the orientation of the functional groups is nontrivial. A promising approach to achieving such control involves rendering these macromolecules amphiphilic.

The concave nature of the binding sites in enzymes and nucleic acids has long inspired chemists to design new host materials with recognition sites at their concave face. The globular architecture of dendrimers presents a new scaffold for such recognition possibilities.

The amphiphilicity and globular shape of dendrimers have been combined previously, and they have been shown to exhibit useful properties. In these cases, however, since the amphiphilicity is the result of the difference in hydrophilicity between the macromolecular backbone and the peripheral moieties, the functional groups are not necessarily directed toward the interior of the globular macromolecules.

Significant effort has been devoted over the past decade to achieve molecular architectures inspired by Nature. Most biological scaffolds are macromolecular in dimension and exhibit excellent control over size, shape, and functional group displays. Dendrimers belong to a unique class of artificial structural motifs that fit the requirement of controlled size. Due to the globular shape at higher generations, dendrimers have often been referred to as possible globular protein mimics. However, exquisite control of functional group presentations in dendrimers has not been fully explored. Therefore, to further develop dendrimers as potential biomimetics, they should exhibit other important structural features beyond globular conformation and controlled molecular weight. Diversity in functional group incorporations in dendrimers can be approached in an uncontrolled or a controlled fashion.

Three different methods of incorporating functional groups in a controlled fashion have been reported recently in the literature: (i) stepwise incorporation of functionalities onto an AB2 monomer unit, where the desired monosubstituted product and the disubstituted byproduct are obtained in statistical yields; (ii) incorporation of three different molecules on to a common core unit, where the different reactivities of di-, mono-, and unsubstituted cyanuric chloride are utilized; (iii) stepwise incorporation of two different functional groups on an AB2 monomer, in which one of the B units is protected in the first step. The second functional group is incorporated following deprotection of the B moiety. A complementary and perhaps a more versatile approach is to use an ABB' monomer instead of the AB2 monomer.