Peptoids are versatile peptidomimetic molecules with wide‐ranging applications from drug discovery to materials science. An understanding of peptoid sequence features that contribute to both their three‐dimensional structures and their interactions with lipids will expand functions of peptoids in varied fields. Furthermore, these topics capture the enthusiasm of undergraduate students who prepare and study diverse peptoids in laboratory coursework and/or in faculty led research. Here, we present the synthesis and study of 21 peptoids with varied functionality, including 19 tripeptoids and 2 longer oligomers. We observed differences in fluorescence spectral features for 10 of the tripeptoids that correlated with peptoid flexibility and relative positioning of chromophores. Interactions of representative peptoids with sonicated glycerophospholipid vesicles were also evaluated using fluorescence spectroscopy. We observed evidence of conformational changes effected by lipids for select peptoids. We also summarize our experiences engaging students in peptoid‐based projects to advance both research and undergraduate educational objectives in parallel.

Cyclic polymers were produced by end-to-end coupling of telechelic linear polymers under dilute conditions in THF, using intramolecular atom transfer radical coupling or click chemistry. In addition to the expected shift to longer elution times on gel permeation chromatography (GPC) indicative of the formation of cyclic product, lower molecular weight species were consistently observed upon analysis of the unpurified cyclization reaction mixture. By systematically removing or altering single reaction components in the highly dilute cyclization reaction, it was found that THF itself was responsible for the low-molecular-weight material, forming oligomeric chains of poly(THF) regardless of the other reaction components. When the reactions were performed at higher concentrations and for shorter time intervals, conducive to intermolecular chain-end-joining reactions, the low-molecular-weight peaks were absent. Isolation of the material and analysis by 1 H NMR confirmed that poly(THF) was being formed in the highly dilute conditions required for cyclization by end-to-end coupling. When a series of mock cyclization reactions were performed with molar ratios of the reactants held constant, but concentrations changed, it was found that lower concentrations of reactants led to higher amounts of poly(THF) side product.

Monobrominated polystyrene (PSBr) was prepared by ATRP, and the resulting chain ends were activated in the presence of radical traps to induce chain end-coupling. In atom transfer radical coupling (ATRC) with radical trap assistance, to achieve significant coupling requires excess metal catalyst, ligand, and a reducing agent that is often additional metal. In this work, activators generated by electron transfer (AGET) and radical trap assistance are used in the ATRC sequence to successfully lead to chain-end coupling without the need for the oxidatively unstable copper (I) and with environmentally friendlier agents in place of copper metal. High extents of coupling (Xc) were achieved using ascorbic acid (AA) as the reducing agent and copper(II) bromide as the oxidized version of the catalyst, and when combined with AGET ATRP to prepare the PSBr precursor, only a fraction of the total metal was required compared to traditional atom transfer reactions, while still retaining similar Xc values.