Dynamic Formation of Hybrid Peptidic Capsules by Chiral Self‐Sorting and Self‐Assembly

Abstract

Owing to their versatility and biocompatibility, peptide-based self-assembled structures constitute valuable targets for complex functional designs. It is now shown that artificial capsules based on β-barrel binding motifs can be obtained by means of dynamic covalent chemistry (DCC) and self-assembly. Short peptides (up to tetrapeptides) are reversibly attached to resorcinarene scaffolds. Peptidic capsules are thus selectively formed in either a heterochiral or a homochiral way by simultaneous and spontaneous processes, involving chiral sorting, tautomerization, diastereoselective induction of inherent chirality, and chiral self-assembly. Self-assembly is shown to direct the regioselectivity of reversible chemical reactions. It is also responsible for shifting the tautomeric equilibrium for one of the homochiral capsules. Two different tautomers (keto-enamine hemisphere and enol-imine hemisphere) are observed in this capsule, allowing the structure to adapt for self-assembly.

Palladium-Mediated Catalysis Leads to Intramolecular Narcissistic Self-Sorting on a Cavitand Platform

“…17 However, to the best of our knowledge, only two studies have been recently reported on intramolecular self-sorting, which involved dynamic covalent chemistry in the syntheses of various peptido-cavitands. 18,19 Carboxamidocavitands, obtained usually by the acylation of the corresponding aminocavitands, 20,21 have strong tendency to form self-assembled dimeric capsules via intermolecular hydrogen bonds. 22 In …”

Switching of inherent chirality driven by self-assembly

“…8,9 The tautomerization proceeds in a highly regioselective manner, i.e. [8][9][10] For aliphatic chiral amines two inherently chiral M and P diastereoisomers were clearly visible in NMR spectra and chemical exchange between them was slow on the NMR timescale (EXSY, no exchange detected using a mixing time of 1.5 s). [8][9][10] For aliphatic chiral amines two inherently chiral M and P diastereoisomers were clearly visible in NMR spectra and chemical exchange between them was slow on the NMR timescale (EXSY, no exchange detected using a mixing time of 1.5 s).…”

“…[8][9][10] For aliphatic chiral amines two inherently chiral M and P diastereoisomers were clearly visible in NMR spectra and chemical exchange between them was slow on the NMR timescale (EXSY, no exchange detected using a mixing time of 1.5 s). 9 For example, (S)-2a exists as a concave monomer in a homochiral form; however, ‡ HJ performed all synthetic work, NMR, CD data interpretation and ab initio calculations. 4 95%).…”

“…9 In order to determine which of the inherently chiral diastereoisomers is induced by stereogenic centres of amino acids we have synthesised a series of iminoresorcin [4]arenes (S)-2c -(S)-2e. 9 In order to determine which of the inherently chiral diastereoisomers is induced by stereogenic centres of amino acids we have synthesised a series of iminoresorcin [4]arenes (S)-2c -(S)-2e.…”

“…Electronic circular dichroism (ECD) spectra for all iminoresorcin- [4]arenes composed of (S)-amino acids exhibit highly analogous patterns (Fig. The inherent chirality of (S)-2a in dimer ((S)-2a)((R)-2a) was unambiguously determined by X-ray crystallography as (P,S)-2a 9 and we used this geometry (as (P,S)-2f, see the ESI † for further details) for calculation of an ECD spectrum (TD DFT B3LYP). The inherent chirality of (S)-2a in dimer ((S)-2a)((R)-2a) was unambiguously determined by X-ray crystallography as (P,S)-2a 9 and we used this geometry (as (P,S)-2f, see the ESI † for further details) for calculation of an ECD spectrum (TD DFT B3LYP).…”