Balancing Ligand Flexibility versus Rigidity for the Stepwise Self‐Assembly of M₁₂L₂₄ via M₆L₁₂ Metal–Organic Cages

Non‐covalent interactions are important for directing protein folding across multiple intermediates and can even provide access to multiple stable structures with different properties and functions. Herein, we describe an approach for mimicking this behavior in the self‐assembly of metal–organic cages. Two ligands, the bend angles of which are controlled by non‐covalent interactions and one ligand lacking the above‐mentioned interactions, were synthesized and used for self‐assembly with Pd²⁺. As these weak interactions are easily broken, the bend angles have a controlled flexibility giving access to M₂(L1)₄, M₆(L2)₁₂, and M₁₂(L2)₂₄ cages. By controlling the self‐assembly conditions this process can be directed in a stepwise fashion. Additionally, the multiple endohedral hydrogen‐bonding sites on the ligand were found to play a role in the binding and discrimination of neutral guests.