Self-Association of Aromatic Oligoamide Foldamers into Double Helices in Water

Abstract

Heteromeric oligoamide foldamers composed of 8-amino-2-quinolinecarboxylic acid and 7-amino-8-fluoro-2-quinolinecarboxylic acid bearing cationic water-solubilizing side chains were prepared using solid-phase synthesis (SPS). The sequences were designed to adopt a single- or a double-helical motif depending on the nature of the solvent, DMSO or water, respectively. Self-association was demonstrated by NMR and mass spectrometry. Dimerization in water was found to be much stronger than observed previously in organic solvents for analogous oligoamide sequences.

Optimizing side chains for crystal growth from water: a case study of aromatic amide foldamers

“…These developments will be particularly useful to elucidate structures in projects where remarkable properties of foldamers have been observed in aqueous media, including endomolecular recognition and double helix formation. 31 Along this line, an investigation of helix bundles constructed from monomers bearing the new side chains is in progress in our laboratory.…”

Redox-controlled hybridization of helical foldamers

“…In particular, it was proven possible to shift the equilibrium towards the hybridized structures by increasing the concentration, lowering the temperature [12,13] or taking advantage of solvophobic effects. [14,15] Moreover, the presence of a cavity inside the loops of miscellaneous foldameric backbones has also encouraged the community to evaluate the impact of guest binding over this supramolecular process. [16,17] While it is sometimes possible to shift the equilibrium by controlling the temperature in a reversible manner, reversibility is hardly reached when diluting a solution, changing the solvent or introducing a guest, due to experimental issues.…”

Solid Phase Synthesis of Helically Folded Aromatic Oligoamides

“…(Ferrand, Chandramouli, Kendhale, Aube, Kauffmann, Grélard et al, 2012) If these quinoline caps are removed, the wider diameter of, for example, a homomeric fluoroquinoline sequence results in hybridization into double (Figure 2b, 2c) and even quadruple helices (Gan, Bao, Kauffmann, Grélard, Xiang, Liu et al 2008). This behavior has even been shown to occur in aqueous conditions, representing one of the very few examples of water-soluble synthetic double helices reported in current literature (Shang, Gan, Dawson, Rosu, Jiang, Ferrand, et al, 2014). Recent work in the Huc group has also focused on the inclusion of aliphatic units into aromatic oligoamide foldamer sequences, in particular, α-amino acids.…”

“…The synthesis of various Fmoc protected 8-amino-2-quinolinecarboxylic acid and 7-amino-8-fluoro-2-quinolinecarboxylic acid has been reported before (Baptiste et al 2010, Buratto et al 2014, Shang et al 2014)…”

“…2) Protocol 8: The fluoroquinoline amine was found to be particularly susceptible to trifluoroacetylation when undergoing cleavage from the resin (Shang et al, 2014). We therefore advise that if possible, this functionality is blocked (via acylation or otherwise) during this step.…”