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Incorporating a chiral non-coordinating substitution at the N-terminal end within peptoids facilitates regio-selective amide bond hydrolysis mediated by a transition metal ion and/or an acidic buffer as evident by X-ray crystallographic analysis, supported by ESI-MS. This opens up a new direction for peptidomimetic compounds towards future application in chemistry, biology and medicine.

Chelation of Cu 2+ by synthetic molecules is an emerging therapeutic approach for treating several illnesses in human body such as Wilson disease, cancer and more. Among synthetic metal chelators, those based on peptoids - N-substituted glycine oligomers - are advantageous due to their structural similarity to peptides, ease of synthesis on solid support and versatile controlled sequences. Tuning peptoid sequences, via systematically changing at least one side chain, can facilitate and control their function. Along these lines, this work aims to explore the role of the non-coordinating side chain within peptoid chelators in order to understand the factors that control the selectivity of these chelators to Cu 2+ in water medium. To this aim, a set of peptoid trimers having a pyridine group at the acetylated N-terminal, a 2,2'-bipyridine group at the second position and a non-coordinating group at the C-terminus, where the latter is systematically varied between aromatic, aliphatic, chiral or non-chiral, were investigated as selective chelators for Cu 2+ . The effect of the position of the non-coordinating group on the selectivity of the peptoid to Cu 2+ was also tested. Based on extensive spectroscopic data, we found that the choice of the non-coordinating group along with its position dramatically influences the selectivity of the peptoids to Cu 2+ . We showed that peptoids having bulky chiral groups at the C-terminus enable high selectivity to Cu 2+ . We further demonstrated the ability of one of the selective chelators to remove Cu 2+ from the natural copper binding protein metallothionein in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer medium., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A peptoid trimer incorporating terpyridine and ethanol forms an intermolecular cobalt(iii) complex, which performs as a soluble electrocatalyst for water oxidation with a minimal overpotential of 350 mV and a high turnover frequency of 108 s-1. The ethanolic group facilitates water binding thus mimicking an enzymatic second coordination sphere.

Peptoids, N-substituted glycine oligomers, represent an important class of peptidomimetics that can fold into three-dimensional structures in solution. Most of the folded peptoid structures, however, resemble helices, and this can limit their applications, specifically in asymmetric catalysis. In this work, for the first time, unique examples of pyrrolidine-based β-turn-like peptoids are described and characterized, both in the solid state, by single-crystal X-ray analysis, and in solution, by circular dichroism spectroscopy. Furthermore, their highly efficient and enantioselective catalytic activity for the production of γ-nitro aldehydes by asymmetric Michael reaction in water was demonstrated. The structural properties and DFT-D3 calculations of the new β-turn-like peptoids, as well as catalytic and spectroscopic studies on designed pyrrolidine-based helical peptoids, suggest that the β-turn structure plays a key role in the stereoselectivity of the catalytic reaction., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A practical synthesis of preorganized tripodal enterobactin/corynebactin-type ligands (consisting of a C 3 -symmetric macrocyclic peptoid core, three catecholamide coordinating units, and C 2 , C 4 , and C 6 spacers) is reported. The formation of complexes with Fe 3+ was investigated by spectrophotometric (UV-Vis) and spectrometric (ESI, negative ionization mode) methods and corroborated by theoretical (DFT) calculations. Preliminary studies revealed the intricate interplay between the conformational chirality of cyclic trimeric peptoids and metal coordination geometry of mononuclear species similar to that of natural catechol-based siderophores. Experimental results demonstrated the unexpected formation of unique dinuclear Fe 3+ complexes.

The understanding of structure-function relationships within synthetic biomimetic systems is a fundamental challenge in chemistry. Herein we report the direct correlation between the structure of short peptoid ligands-N-substituted glycine oligomers incorporating 2,2'-bipyridine groups-varied in their monomer sequence, and the photoluminescence of Ru II centers coordinated by these ligands. Based on circular dichroism and fluorescence spectroscopy we demonstrate that while helical peptoids do not affect the fluorescence of the embedded Ru II chromophore, unstructured peptoids lead to its significant decay. Transmittance electron microscopy (TEM) revealed significant differences in the arrangements of metal-bound helical versus unstructured peptoids, suggesting that only the latter can have through-space interactions with the ruthenium dye leading to its quenching. High-resolution TEM enabled the remarkable direct imaging of singular ruthenium-bound peptoids and bundles, supporting our explanation for structure-depended quenching. Moreover, this correlation allowed us to fine-tune the luminescence properties of the complexes simply by modifying the sequence of their peptoid ligands. Finally, we also describe the chiral properties of these Ru-peptoids and demonstrate that remote chiral induction from the peptoids backbone to the ruthenium center is only possible when the peptoids are both chiral and helical., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Helical peptoids bearing 2,2'-bipyridine form ruthenium complexes via intermolecular binding to linear peptoid strands or intramolecular binding to a cyclic scaffold. Ru(ii) binding promoted changes in the conformational order of the peptoids, and chiral induction from the peptoids to their metal center was observed.

Metal ions play a significant role in the activity of biological systems including catalysis, recognition and folding. Therefore, introducing metal ions into peptidomimetic oligomers is a potential way for creating biomimetic metal complexes toward applications in sensing, recognition, drug design and catalysis. Herein we report the design, synthesis and characterization of water-soluble chiral N-substituted glycine oligomers, "peptoids," with one and two distinct intramolecular binding sites for metal ions such as copper and cobalt. We demonstrate for the first time the incorporation of the chiral hydrophilic group (S)-(+)-1-methoxy-2-propylamine (Nsmp) within peptoid sequences, which provides both chirality and water solubility. Two peptoids, a heptamer, and a dodecamer bearing two and four 8-hydroxyquinoline (HQ) groups respectively as metal-binding ligands, were synthesized on solid support using the submonomer approach. Using UV-titrations and ESI-MS analysis we demonstrate the creation of a novel metallopeptoid bearing two metal ions in distinct binding sites via intramolecular chelation. Exciton couplet circular dichroism (ECCD) demonstrated chiral induction from the chiral non-helical peptoids to the metal centers., (© 2015 Wiley Periodicals, Inc.)

Metallopeptoid catalysts incorporating phenanthroline-copper and TEMPO, and at least one non-catalytic group perform in the oxidation of various benzylic, allylic and aliphatic primary alcohols with a TON of up to 16 times higher than a mixture of the two catalytic groups or the peptoid dimer that is lacking the non-catalytic group.

We describe a fast and efficient side chain-to-tail cyclization of N-substituted glycine oligomers, peptoids, on a solid support and under microwave irradiation. We demonstrate that cyclic peptoids varied in their ring size and side chains can be synthesized by a bond formation between a chloropropyl group placed anywhere along the sequence and the secondary amine at the N-terminus. This SN2 reaction leads to the formation of a new C-N bond using only one reagent (a base).

The interaction between biopolymers and metal nanoparticles (AgNPs) is a key element in the development of biomimetic nanomaterials with applications in catalysis, delivery, and recognition. Here we report a facile method for the functionalization of AgNPs by N-substituted glycine oligomers, "peptoids." Based on the established affinity between phenanthroline ligand and Ag(0), we synthesized a peptoid bearing 1,10-phenanthroline at the N-terminus (PHP). Treatment of AgNPs that were pre-stabilized by citrate ions, with PHP, leads to the formation of aggregates as suggested by UV-vis spectroscopy. Transmission electron microscopy (TEM) revealed that the replacement of citrate ions by PHP yields spherical assemblies of AgNPs. These peptoids/AgNPs hybrids, as well as the ability of functional biomimetic oligomers to mediate the assembly of metal nanoparticles, hold potential for applications in sensor materials, biology, and catalysis.