Does fluorination control the stability of the Pd₈L₁₆ square antiprism?

The controlled self-assembly of metal-organic cages (MOCs) enables access to complex supramolecular architectures, yet intermediate geometries remain elusive. Here, density functional theory elucidates the origin of selective Pd₈L₁₆ square antiprism formation from perfluorinated ligands from the pioneering work of Pilgrim and coworkers, whose X-ray structures enabled us to perform density functional theory (DFT) calculations on systems containing nearly 500 atoms. Contrary to conventional expectations, binding energies, orbital effects, and simple geometric parameters do not govern selectivity. Instead, fluorination induces dihedral twisting, modulates aromaticity, and enhances non-covalent interactions, collectively stabilizing larger assemblies. These findings establish dihedral engineering as a general strategy to access previously inaccessible supramolecular topologies.