High?Throughput Computational Evaluation of Low Symmetry Pd ₂ L ₄ Cages to Aid in System Design**

Unsymmetrical ditopic ligands can self-assemble into reduced-symmetry Pd2L4 metallo-cages with anisotropic cavities, implications for high specificity and affinity guest-binding. Mixtures of cage isomers form, however, resulting in undesirable system heterogeneity. It is paramount to be able design components that preferentially form a single isomer. Previous data suggested computational methods could predict reasonable accuracy whether unsymmetrical would under constraints geometrical mismatch. We successfully apply collaborative experimental workflow mitigate costly trial-and-error synthetic approaches. Our rapid constructs their isomers, ranking the likelihood exclusively forming cis-Pd2L4 assemblies. From this narrowed search space, we synthesised four new, low-symmetry, cages.