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 Pd₂L₄ 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 Pd₂L₄ cage isomers) and ranks their likelihood for forming cis-Pd₂L₄ assemblies. From this narrowed search space, we successfully synthesised four new low-symmetry, cis-Pd₂L₄ cages, with cavities of different shapes and sizes.