Bottom-up construction of chiral metal-peptide assemblies from metal cluster motifs

The exploration of artificial metal-peptide assemblies (MPAs) is one of the most exciting fields because of their great potential for simulating the dynamics and functionality of natural proteins. However, unfavorable enthalpy changes make forming discrete complexes with large and adaptable cavities from flexible peptide ligands challenging. Here, we present a strategy integrating metal-cluster building blocks and peptides to create chiral metal-peptide assemblies and get a family of enantiopure [R-/S-Ni₃L₂]_n (n = 2, 3, 6) MPAs, including the R-/S-Ni₆L₄ capsule, the S-Ni₉L₆ trigonal prism, and the R-/S-Ni₁₈L₁₂ octahedron cage. X-ray crystallography shows MPA formation reactions are highly solvent-condition-dependent, resulting in significant changes in ligand conformation and discrete cavity sizes. Moreover, we demonstrate that a structure transformation from Ni₁₈L₁₂ to Ni₉L₆ in the presence of benzopyrone molecules depends on the peptide conformational selection in crystallization. This work reveals that a metal-cluster building block approach enables facile bottom-up construction of artificial metal-peptide assemblies.