From distinct metallopeptoid to controlled supramolecular architecture

Designed synthesis of artificial protein architecture is one of the central goals in chemistry. An established pathway to achieve this goal is self-assembly of synthetic biomimetic sequences, which is, however typically not a controlled process, limiting rational design towards the construction of functional materials with specific properties. The work I will present describes a unique route for the designed synthesis of protein-like architectures, via the self-assembly of short copper-peptoid folded duplexes. We demonstrate that alternation of one non-coordinating side-chain within peptoid scaffold enables the self-assembly process of their metal complexes. Peptoid trimers designed with 2,2’-bipyridine and pyridine ligands, together with a non-coordinating bulky group, were synthesized and reacted with Cu²⁺. Single crystal X-ray analysis of the products revealed the self-assembly of each peptoid into a folded 2:2 metallopeptoid duplex, followed by the self-assembly of multiple duplexes and their packing into a three-dimensional supramolecular architecture via non-covalent interactions. We demonstrate that the non-coordinating side-chain has a strong effect on the final supramolecular architecture formed: the metallopeptoids containing aromatic side-chain self-assembled to helical rods type structures due to π- π interaction between two metallopeptoid duplexes. However, when the non-coordinating side-chains are aliphatic, nano-channel type architecture has been observed, where the pore size could be controlled depending on the side-chain. The metallopeptoid duplexes are stable in aqueous solution as verified by various techniques including ESI-MS and CD, and their supramolecular architecture in solution was verified by Cryo-TEM analysis. Moreover, selective recognition abilities of the nano-channels for binding of biologically relevant anions and small molecules were explored.