High-Throughput Computational Evaluation of Low Symmetry Pd₂ L₄ Cages to Aid in System Design*

Unsymmetrical ditopic ligands can self-assemble into reduced-symmetry Pd₂ L₄ metallo-cages with anisotropic cavities, with implications for high specificity and affinity guest-binding. Mixtures of cage isomers can form, however, resulting in undesirable system heterogeneity. 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 single cage isomers under constraints of geometrical mismatch. We successfully apply a collaborative computational and experimental workflow to mitigate costly trial-and-error synthetic approaches. Our rapid computational workflow constructs unsymmetrical ligands and their Pd₂ L₄ cage isomers, ranking the likelihood for exclusively forming cis-Pd₂ L₄ assemblies. From this narrowed search space, we successfully synthesised four new, low-symmetry, cis-Pd₂ L₄ cages.