Search

This project seeks to develop a method to control Aromatic Oligoamide Foldamer (AOF) self-assembly in solution by providing a method to prevent multi-stranded helix formation using a reversible synthetic modification. To this end, a Diels-Alder strategy was designed by screening 1,8-diazaanthracene aromatic monomers, acting as dienes, with a range of dienophiles to that would break the extended conjugation in the monomer and could also add steric constraints to further disfavor multi-stranded helix formation [1]. By incorporating this unit into longer sequences, we showed, based on structural studies, that the Diels-Alder modification is sufficient to prevent multi-helix formation. Finally, by applying retro-Diels-Alder conditions to the oligomer, it is possible to remove the dienophile and induce multi-helix formation. Together, these reactions provide a new tool for controlling multi-helix formation in AOF and expand their potential use in the broader area of self-assembly.

Self-assembly is one of the most powerful approaches to design large functional molecular systems [1,2]. In biology, large surface area interactions allow self-assembly to occur with high selectivity and in a precise directional manner to yield asymmetric assemblies. Mimicking the types of surface interactions found in biological systems could help improve self-assembly, and foldamers are a potential tool to address this need. Notably, Aromatic Oligoamide Foldamers (AOF), due to their high stability, predictable folding, and ability to form multi-stranded helical assemblies, are particularly well suited for this purpose [3]. Nevertheless, these multi-stranded helical assemblies are usually the result of homo helices assemblies rather than the assembly of different strands. Herein, we describe the development of a strategy to drive the selective formation of hetero double helices (social self-assembly) using supramolecular driving forces such as ionic or π-stacking interactions. The use of these driving forces will provide a new tool to control the formation of AOF hetero double helices and expand their potential use in the broader area of self-assembly.

Self-assembly of secondary structural elements represent an intriguing approach for non-covalent synthesis that can potentially offer greater selectivity and orthogonality than existing methods. To this end, the ability of aromatic oligamide foldamers to hybridize into multiple helices can be seen as a powerful tool for the formation of discrete molecular cages or even networks. Still, the spontaneity of this process complicates synthetic aspects of the incorporation of multi-helical segments into larger scaffolds. In this poster we describe the synthesis of a series of diazaiptycene based aromatic monomers via Diels-Alder reaction and show that their incorporation into longer oligomers leads to structural distortions that prevent aggregation between multiple strands. Importantly the use of a TAD (triazoledione) group as dienophile opens a way to the control the oligomer topology via a Diels-Alder / retro Diels-Alder strategy and the use of thermal stimulus to trigger double helix formation. Perspectives for using this approach for the design and synthesis of larger molecular architectures formed via double helix driven self-assembly are also discussed.

This project seeks to develop a method to control Aromatic Oligoamide Foldamer (AOF) self-assembly in solution by providing a method to prevent multi-stranded helix formation using a reversible synthetic modification. To this end, a Diels-Alder strategy was designed by screening 1,8-diazaanthracene aromatic monomers, acting as dienes, with a range of dienophiles to that would break the extended conjugation in the monomer and could also add steric constraints to further disfavor multi-stranded helix formation [1]. By incorporating this unit into longer sequences, we showed, based on structural studies, that the Diels-Alder modification is sufficient to prevent multi-helix formation. Finally, by applying retro-Diels-Alder conditions to the oligomer, it is possible to remove the dienophile and induce multi-helix formation. Together, these reactions provide a new tool for controlling multi-helix formation in AOF and expand their potential use in the broader area of self-assembly.

Self-assembly is one of the most powerful approaches for designing large functional molecular systems [1,2]. In biology, large surface area interactions allow self-assembly to occur with high selectivity and in a precise directional manner to give asymmetric assemblies. Mimicking the types of surface interactions found in biological systems could help improve self-assembly, and foldamers are a potential tool to answer to this need. Notably, Aromatic Oligoamide Foldamers, because of their high stability, predictable folding, and potential to form multi-stranded helical assemblies, are particularly well-suited for this purpose [3]. Nevertheless, incorporation of these units into larger molecular architectures requires limiting the formation of multi-stranded helices until desired. Methods to achieve this are currently limited. Herein, we describe the development of a method to control Aromatic Oligoamide Foldamer self-assembly in solution by providing a method to prevent multi-stranded helix formation using a reversible synthetic modification. Since the main driving force for multi-stranded helix formation in Aromatic Oligoamide Foldamers is aromatic π-stacking between strands, this work was based on the hypothesis that disruption of this aromatic π-stacking could disfavor multi-stranded helix formation. To this end, we designed a Diels-Alder/retro-Diels-Alder strategy by screening 1,8-diazaanthracene monomers with a range of dienophiles to that would break the extended conjugation in the monomer and could also add steric constraints to further disfavor multi-stranded helix formation [4]. 4-N-phenyl-1,2,4-triazoline-3,5-dione was found to be an ideal dienophile allowing the formation of the Diels-Alder adduct with 1,8-diazaanthracenes in nearly quantitative yields at room temperature. Importantly, the retro-Diels-Alder reaction can also be induced at moderate temperatures using a dienophile scavenger. By incorporating this unit into longer sequences, we show, based on structural studies, that the Diels-Alder modification is sufficient to prevent multi-helix formation. Finally, by applying retro-Diels-Alder conditions to the oligomer, it is possible to remove the dienophile and induce multi-helix formation. Together, these reactions provide a new tool for controlling multi-helix formation in Aromatic Oligoamide Foldamers and expand their potential use in the broader area of self-assembly.