Intrastrand foldamer crosslinking by reductive amination

A series of m‐phenylene ethynylene (mPE) foldamers were crosslinked in their helical conformation using a reductive amination‐based strategy. This was accomplished by placing aldehyde moieties in the backbone of the oligomer at specific residues, which allowed a diamine crosslinker to covalently link the helical loops together. Three different foldamers with crosslinks placed at different locations in the backbone were synthesized and characterized by mass spectrometry, ¹H NMR, and gel permeation chromatography. The effect of the crosslinking on the stability of the folded state was evaluated through solvent denaturation studies. These studies show a reduction in the oligomer's ability to unfold of up to 30% relative to an unmodified mPE oligomer of the same length in solvents that promote unfolding. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 927–935, 2010