High‐throughput computational evaluation of low symmetry Pd2L4 cages to aid in system design

The use of unsymmetrical components in metallo-supramolecular chemistry allows for low- symmetry architectures with anisotropic cavities toward guest-binding with high specificity and affinity. Unsymmetrical ditopic ligands mixed with Pd(II) have the potential to self-assemble into reduced symmetry Pd 2 L 4 metallo-architectures. Mixtures of isomers can form, however, resulting in potentially undesirable heterogeneity within a system. Therefore it is paramount to be able to design components that preferentially form a single isomer. Previous data suggested that computational methods could predict with reasonable accuracy whether unsymmetrical ligands would preferentially self-assemble into a single isomer under constraints of geometrical mismatch. We successfully apply a collaborative computational and experimental workflow to mitigate costly trial-and-error synthetic approaches. Our low-cost computational workflow rapidly constructs new unsymmetrical ligands (and Pd 2 L 4 cage isomers) and ranks their likelihood for forming cis -Pd 2 L 4 assemblies. From this narrowed search space, we successfully synthesised four new low-symmetry, cis -Pd 2 L 4 cages, with cavities of different shapes and sizes