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 b-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.

Making a Right or Left Choice: Chiral Self-Sorting as a Tool for the Formation of Discrete Complex Structures

“…For example, self-assembly of 33a to form heterochiral dimer (L-33a)(D-33a) requires a change of inherent chirality of the molecules 93 while self-assembly of 33e to form homochiral dimer (L-33e) 2 requires a change of the tautomeric form of one of the hemispheres. 92 Even though the changes are substantial, in both cases chiral self-sorting proceeds effectively.…”

“…Tetraformylresorcin [4]arene 31 was used as a macrocyclic scaffold, and peptides were attached by their N-termini via the reversible imine formation reaction (Figure 19a). 92 All imines 33a−33g form self-assembled dimeric capsules in a highly regioselective and diastereoselective manner by merging of 10 components. Depending on the peptide length, the capsules form in an either homochiral or heterochiral way.…”

Selective C70 encapsulation by a robust octameric nanospheroid held together by 48 cooperative hydrogen bonds

“…Multimembered, three-dimensional chemical entities such as cages or capsules are complex architectures that can be constructed using self-assembly processes where building blocks are held together by dynamic covalent or non-covalent bonds. The continuing development of supramolecular chemistry and the improved understanding of its underlying assembly processes have led to the synthesis of increasingly complex and sophisticated three-dimensional structures such as nanotubes 1 , cages 2 3 and capsules 4 5 6 . There is a close relationship between the structure of a given architecture and its functionality, as in natural systems, and chemists have exploited this in the design of functional structures that possess desirable properties and that may be used inter alia to build molecular machines 7 .…”