Peptoids (N-substituted glycine oligomers) are widely used peptidomimetics, and an enhanced understanding of their structures is needed to expand their utility, particularly in aqueous applications. We report the synthesis and structural study of four water-soluble peptoids that include strongly helix-promoting (S)-N-1-(naphthylethyl)glycine residues. Peptoid structure changes with both peptoid length and solvent composition. Multiple data support the self-association of the longest peptoid studied here, 1, via hydrophobic interactions in aqueous solutions.

Herein we describe a highly chemo-, regio-, and enantioselective bromochlorination reaction of allylic alcohols, employing readily available halogen sources and a simple Schiff base as the chiral catalyst. The application of this interhalogenation reaction to a variety of substrates, the rapid enantioselective synthesis of a bromochlorinated natural product, and preliminary extension of this chemistry to dibromination and dichlorination are reported.

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Peptoids, N-substituted glycine oligomers, can adopt stable three-dimensional structures and have found diverse application as peptide surrogates and as nanomaterials. In this report, we have expanded peptoid function to include pH sensing by coupling pH-induced peptoid conformational changes with fluorescence intensity changes. We report two new peptoids (2 and 3) that comprise carboxylic-acid functionalized side chains and undergo conformational rearrangement in response to pH. Peptoids 2 and 3 are also labeled at one side-chain with an environmentally sensitive fluorophore, 4-N,N-dimethylamino-1,8-naphthalimide (4DMN). The fluorescence intensity of 2 varies 24-fold over the pH range studied. These spectroscopic properties make 2 a sensitive, biocompatible pH sensor.

Peptoids, oligomers of N-substituted glycine, have been valuable targets for study and diverse application as peptidomimetics and as nanomaterials. Their conformational heterogeneity has made the study of peptoid structures using high-resolution analyses challenging, limiting our understanding of the physiochemical features that mediate peptoid folding. Here, we introduce a new method for the study of peptoid structure that relies on the environmentally sensitive fluorescence properties of 4-N,N-dimethylamino-1,8-naphthalimide (4-DMN). We have prepared a 4-DMN-functionalized primary amine that is compatible with the traditional submonomer peptoid synthesis methods and incorporated it sequence-specifically into 11 of 13 new peptoids. When included as a peptoid side chain modification, the fluorescence emission intensity of 4-DMN correlates with predictions of the fluorophore's local polarity within a putative structure. 4-DMN fluorescence is maximized when the fluorophore is placed in the middle of the hydrophobic face of an amphiphilic helical peptoid. When the fluorophore is placed near the peptoid terminus or on a polar face of an amphiphilic sequence, 4-DMN fluorescence is diminished. Disruption of the peptoid secondary structure or amphiphilicity also modulates 4-DMN fluorescence. The peptoids' helical secondary structures are moderately disrupted by inclusion of a 4-DMN-modified side chain as evaluated by changes in the peptoids' CD spectral features. This new method for peptoid structure evaluation should be a valuable complement to existing peptoid structural analysis tools.