First series of N-alkylamino peptoid homooligomers: Solution phase synthesis and conformational investigation

The synthesis and conformational analysis of the first series of peptoid oligomers composed of consecutive N -alkylamino glycine units is investigated. We demonstrate that N -methylamino glycine homooligomers can be readily synthesised in solution using N -Boc- N -methylhydrazine as a peptoid submonomer and stepwise or segment coupling methodologies. Their structures were analyzed in solution by 1-D and 2-D NMR, in the solid state by X-ray crystallography (dimer 2 ) and implicit solvent QM geometry optimisations. N -methylamino peptoids were found to preferentially adopt trans amide bonds with the side chain N-H bonds oriented approximately perpendicular to the amide plane. This orientation is conducive to local backbone stabilization through intra-residue hydrogen bonds but also to intermolecular associations. The high capacity of N -methylamino peptoids to establish intermolecular hydrogen bonds was notably deduced from pronounced concentration dependent N-H chemical shift variation in 1 H-NMR, the antiparallel arrangement of mirror images molecules held together via two hydrogen bonds in the crystal lattice of dimer 2 , and self-assembling properties of dimer 2 visualized by transmission electron microscopy.