A Diels-Alder/retro-Diels-Alder strategy for controlling self-assembly of aromatic oligoamide multi-stranded helices

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.