Aromatic Oligoamide Foldamer: Dimerization Enhancement and Dynamic Covalent Chemistry

Details

Supervisors

Singleton, Michael L.

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques, à finalité approfondie

Abstract

enAromatic oligoamide foldamers (AOF) are synthetic compounds that will fold spontaneously, giving rise to stable helical conformations in solution. The overall combination of local conformational control via hydrogen bonding and dipolar preferences lead to a controlled high-fidelity folding process. Our group worked on AOF design and successfully made, among others, pyridine based heptamers. These compounds can dimerize, forming double helices mainly driven by large inter-strand π-surface interactions. Controlling multi-strand affinity and dimerization constant (Kdim) through rational design is an important but often overlooked aspect of this chemistry and will therefore be a focus in this work. To achieve this initial goal, a new series of heptamers were designed, alternating electron-rich and electron poor heteroaromatic units. The large π surface contacts between complementary π electron density of the selected strands should influence the dimerization process. The resulting dimerization constants will be calculated based on in-solution concentration studies. Three unreported pyridine-based heptamers were synthesized following standard coupling procedure between two trimers and one central functionalized pyridine monomer. In addition, among the structures, an aldehyde derivative will be used as a chemical handle for the other important goal of this project: to develop a novel strategy towards aldehyde derivatives of the aforementioned heptamers. We plan to use these aldehydes as chemical handles toform self-assembled structures thanks to dynamic covalent chemistry (DCC). Imination in the presence of a collection of amine linkers will form discrete structures and eventually a dynamic framework of heptamers AOF helices. The outcome of the reaction will be controlled thanks to careful choice of the components, since the angular relationship, rigidity/flexibility and preorganization of the units are crucial. This work will enlarge the field of non-covalent synthesis by coupling DCC with self assembly and developing new methodologies for large functional structures.