One Ligand, Four Cages: Diverse Outcomes in Pd3L4 Metal-Peptidic Cage Self-Assembly via Subtle Oligoproline Modifications

The self-assembly of metal-organic cages enables the rapid creation of atomically defined, three-dimensional, nanoscale architectures from easily accessible building blocks. Rigid and flat aromatic panels are typically used as ligands. Building on our recent success using oligoprolines to create defined metal-peptidic Pd2L4 cages with emergent head-to-tail isomer control, we have defined a new family of metal-peptidic cages. Herein, we show that installation of an additional metal-binding motif, enabling formation of Pd3L4, dual-cavity, anisotropic ‘peanut’ cages, generates complex and emergent behavior in response to small changes in ligand isomerism. By varying the sequence isomer used, or the stereochemistry of the 4R/S hydroxyproline, we can generate four distinct self-assembly outcomes, forming: the Pd3L4 cis CCNN cage isomer, the Pd3L4 ‘All Up’ CCCC cage isomer, a mixture of all possible isomers of Pd3L4 cages, or an interpenetrated Pd6L8 cage. We show that simple and subtle changes to a peptidic ligand give rise to complex behavior in metal-peptidic cage self-assembly, further underlining the advantages of supramolecular chemistry embracing biological building blocks.