Controlling and directing self-assembly with aromatic oligoamide foldamer double helices

Self-assembly is one of the most important processes for the formation of organized matter and chemical structures in both biological and synthetic systems. It relies on reversible covalent or non-covalent complementary interactions as driving forces to bring molecular components together into well-defined supramolecular structures. Self-assembly has been driving life on earth for eons, therefore it is not surprising that the most sophisticated examples are found in biological systems, where complex assemblies form upon a myriad of intermolecular interactions between large complementary surface areas generated by folding into secondary structures. This is in sharp contrast to artificial assemblies, which are mostly constructed from punctual intermolecular contacts involving mostly one type of interaction. Aromatic oligoamide foldamers (AOF) fold into predictable secondary structures that are capable of self-assembling into well-defined double helices that rely on large surface contacts between folded molecules for interaction, similar to biomolecules. This doctoral research looks at studying and developing a new methodology based on the self-assembly of AOF sequences into double helices through large surface interactions and exploit this ability to bring molecular components together and ultimately, form large supramolecular structures. The fundamental concepts of orthogonality and control of the self-assembled structure based on the association into double helices are studied. Essentially, the difference in interaction surface should lead to narcissistic self-sorting and give a collection of orthogonal assembly processes. The exploration of new methods to prevent and induce double helical self-assembly with AOF constitutes a second important aspect for AOF self-assembly, by developing a reversible control of the structure through external stimulations. The strategy consists of 3D modifications on the AOF backbone, through (ir)reversible Diels-Alder reaction When incorporated into a foldamer sequence, this chemical modification was demonstrated to control the self-assembly of the strands, by preventing self-association into double helix. The second part of this thesis focuses on the application of these fundamental concepts towards the construction of large artificial systems self-assembled through surface interactions of secondary structures. Supramolecular polymers based on the association between ditopic double helix forming components were designed, synthesized and characterized. Complementary analytical techniques showed promising results suggesting that these components self-assemble into oligomers or polymers in solution. This research is thus a promising application of this secondary structural self-assembly approach.