Supramolecular assembly of materials based on orthogonal, multivalent interactions

The main aim of the proposed research is the preparation of hybrid, multilayered materials with a complex architecture. This will be achieved through the supramolecular, bottom-up assembly of building blocks employing multivalent, orthogonal interactions. Such building blocks with multiple interaction motifs will not only allow the nanofabrication of more complex materials, but also give rise to new assembly methods. Basically, the project is proposed to lead to a one-pot procedure employing a complex mixture of building blocks that all find their correct position in the designed multilayer architecture by the interaction information built into them. A general method to prepare layered architectures with a nanometer thickness control is the so-called layer-by-layer assembly. Although precision and control regarding layer composition and thickness are excellent in this procedure, and aggregation in solution is avoided by the complete elimination of contact between the building blocks when they are still in solution, the procedure is rather slow since it requires separate assembly steps for every layer of a building block, and rinsing between the assembly steps is essential to avoid the solution aggregation process. A major question is therefore how uncontrolled aggregation in solution can be suppressed when building blocks are employed together in solution. The keys to this question are both multivalency and orthogonal, heterotopic interactions. Multivalency, which is the interaction between building blocks employing multiple interacting sites, is governed by the so-called effective concentration. When two multivalent entities interact, the first binding event is a common intermolecular binding step. Subsequent steps, however, are intramolecular, and the probabilities of interaction are determined by the effective concentration, which can be viewed as a concentration of a, still uncomplexed, interacting site in a probing volume as it is experienced by the complementary interaction site. Previous work by us has shown that effective concentrations at self-assembled monolayers of, for example, a receptor molecule, can be orders of magnitude higher than for multivalent host molecules of the same type in solution. This leads to significantly higher binding constants at such monolayers, whereas the binding strength of an individual interaction pair remains unchanged. Heterotopic, orthogonal interactions can lead to higher stoichiometries, better specificities, and more complex architectures. In an elementary system, we were already able to show that a doubly divalent complex constituted of five building blocks was formed selectively and exclusively at an interface whereas the corresponding complex in solution was only a very minor species. The enhancement factor obtained here (>100) is expected to be increased vastly by increasing the valency of the building blocks. The combination of these principles is proposed to lead to a new, powerful paradigm for materials assembly. Multivalent building blocks with orthogonal interaction motifs will be designed and synthesized. Their assembly in solution and at interfaces (self-assembled monolayers of a component of an interacting motif) will be probed using established methods, and the quantitative stability data will be established into a complex equilibrium model. This model will then be used to predict and verify experimental conditions for which assembly of a complex mixture of such building blocks in solution is suppressed, while the bottom-up assembly at the interface is promoted by the higher effective concentration. This is intended to lead to the proposed new assembly routes for complex, hybrid materials of (bio)molecules, polymers, and nanoparticles, in which the number of assembly steps is greatly reduced compared to the more traditional layer-by-layer assembly scheme. Furthermore, the integration of such assembly routes into more complex nanofabrication schemes, also employing top-down methods such as nanoimprint lithography, will provide truly 3D nanostructures with a complex, multilayered architecture.