Hierarchical self-assembly of aromatic peptide conjugates into supramolecular polymers: it takes two to tango.

Supramolecular polymers are self-assembled materials displaying adaptive and responsive "life-like" behaviour which are often made of aromatic compounds capable of engaging in π-π interactions to form larger assemblies. Major advances have been made recently in controlling their mode of self-assembly, from thermodynamically-controlled isodesmic to kinetically-controlled living polymerization. Dynamic covalent chemistry has been recently implemented to generate dynamic covalent polymers which can be seen as dynamic analogues of biomacromolecules. On the other hand, peptides are readily-available and structurally-rich building blocks that can lead to secondary structures or specific functions. In this context, the past decade has seen intense research activity in studying the behaviour of aromatic-peptide conjugates through supramolecular and/or dynamic covalent chemistries. Herein, we review those impressive key achievements showcasing how aromatic- and peptide-based self-assemblies can be combined using dynamic covalent and/or supramolecular chemistry, and what it brings in terms of the structure, self-assembly pathways, and function of supramolecular and dynamic covalent polymers.

Hierarchical Self-Assembly and Multidynamic Responsiveness of Fluorescent Dynamic Covalent Networks Forming Organogels.

Smart stimuli-responsive fluorescent materials are of interest in the context of sensing and imaging applications. In this project, we elaborated multidynamic fluorescent materials made of a tetraphenylethene fluorophore displaying aggregation-induced emission and short cysteine-rich C-hydrazide peptides. Specifically, we show that a hierarchical dynamic covalent self-assembly process, combining disulfide and acyl-hydrazone bond formation operating simultaneously in a one-pot reaction, yields cage compounds at low concentration (2 mM), while soluble fluorescent dynamic covalent networks and even chemically cross-linked fluorescent organogels are formed at higher concentrations. The number of cysteine residues in the peptide sequence impacts directly the mechanical properties of the resulting organogels, Young's moduli varying 2500-fold across the series. These materials underpinned by a nanofibrillar network display multidynamic responsiveness following concentration changes, chemical triggers, as well as light irradiation, all of which enable their controlled degradation with concomitant changes in spectroscopic outputs─self-assembly enhances fluorescence emission by ca. 100-fold and disassembly quenches fluorescence emission.

A Stimuli-Responsive Macromolecular Gear: Interlocking Dynamic Helical Polymers with Foldamers.

Herein, macromolecular gears composed of helical poly(phenylacetylenes) (PPAs) bearing short oligopeptides as pendant groups are described, in which the two structural motifs (framework and substituents) are combined. These gears are obtained by polymerization of the acetylene groups introduced at the C-terminus of short oligopeptides formed by achiral (Aib)n units (n=1-3) derivatized at the N-terminus by a single enantiomer (R or S) of α-methoxy-α-trifluoromethylphenylacetic acid (MTPA, Mosher's reagent). The chiral information of the MTPA is transmitted to the achiral Aib fragments and, through either chiral tele-induction and/or chiral harvesting mechanisms, is further transferred to the polyene backbones, which adopt preferentially P or M helical senses. Moreover, these materials also show dynamic behavior and respond to the action of external stimuli by either inverting the P/M sense and/or modifying the elongation in fully reversible processes.

Chiral Overpass Induction in Dynamic Helical Polymers Bearing Pendant Groups with Two Chiral Centers.

The dynamic behavior of helical polymers bearing pendant groups with two chiral centers was studied. Controlled conformational changes at the chiral units placed either closer to or further away from the main chain promote different helical structures. Although the first residue is usually responsible for determining a specific helicity (P or M), we now found that the second chiral center is also able to induce a preferred helical sense when it is located closer in space to the main chain, thereby cancelling the order from the first chiral moiety. This result was achieved through proper coordination with a metal cation. As proof of concept, poly(phenylacetylene)s (PPAs) that bear one and two chiral amino acid units of different sizes and configuration combinations (l/d-alanine and l/d-phenylalanine) as pendants were evaluated. In total, ten polymers were studied. This constitutes the first report of axial control from a remote stereocenter in polymers bearing complex chiral pendants.