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 Pd(2)L(4) 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 Pd(2)L(4) cage isomers, ranking the likelihood for exclusively 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.