Synthesis and characterization of amphiphilic o-phenylene ethynylene oligomers

Abstract

We have previously reported the synthesis of short o-phenylene ethynylene oligomers with polar triethylene glycol side chains which adopt a helical conformation in solution with three residues per turn. Two new oligomers have been synthesized, a hexamer and a nonamer, incorporating a repeated triad motif of polar-nonpolar-polar sidechains in order to create a hydrophobic stripe in the folded conformation which we report here for the first time. Helical folding in solution was observed and, unlike the previously-reported oligomers, these new oligomers are ordered solids at room temperature. Although these oligomers were designed to assemble into helical bundle-like structures, no evidence for a quaternary-like structure was found. The difference in polarity between alkyl and triethylene glycol side chains is likely not strong enough to induce self-association of folded helices, especially since the molecules are not water soluble where the driving force for association of the nonpolar stripe would be larger. We expect that more polar side chains, granting water solubility, represent an important target for future research.

Recent advances in arylene ethynylene folding systems: Toward functioning

“…The conclusion was further supported by the ROSEY spectra. oPE oligomers up to nonamer 78 were synthesized and proven to be capable of switching between folded and unfolded states in different solvents [129]. A polymer of oPE reported by Khan and Hecht also exhibited evidence for chain folding into a helical conformation [130].…”

Versatile Bottom‐up Approach to Stapled π‐Conjugated Helical Scaffolds: Synthesis and Chiroptical Properties of Cyclic o‐Phenylene Ethynylene Oligomers

“…This fact hinders the expected chiral electron transport (ET) because of competitive ET through the π‐stacked aromatic rings, thus limiting their use as a nanocoil 5. Considering the structural features of these CNCs, we were interested in the conformationally flexible open‐chain o ‐phenylene ethynylene oligomers ( o ‐PEOs), which were mainly developed by Tew and co‐workers6 and can adopt helical arrangements by supramolecular interactions 7. Nevertheless, such arrangements are solvent dependent and may not be suitable for applications demanding a permanent shape 8.…”

Development of protein mimics for intracellular delivery

“…In addition, many researchers have explored foldamers, which are chains of molecules that can fold into organized structures, such as α‐helices and β‐sheets, in solution . Foldamers differ from other proteomimetics in that they require non‐covalent interactions, such as hydrogen bonding, π‐interactions, electrostatic interactions, van der Waal's interactions, and solvophobic effects with non‐adjacent surfaces .…”

“…These molecules have been used to mimic the folding of proteins, polysaccharides, and nucleic acids . One specific subset of foldamers, referred to as abiotic foldamers, aim to capture key features of proteins, such as secondary structure, with non‐natural materials …”

“…In addition, peptide in vivo limitations, such as proteolysis, tissue distribution, and toxicity, are overcome and robust in vivo antibacterial activity against drug resistant infections has been demonstrated, specifically with a compound in phase II clinical trials . An important new development was the demonstration that polymers could be designed with AMP‐like biological activity . Unlike proteins and peptides, which typically have a single, exact molar mass, synthetic polymers, even when termed monodisperse, are characterized by a distribution of molecular weights.…”