The design of structurally defined heteroleptic coordination cages is a challenging task, and only few examples are known to date. Here we describe a selection approach that allowed the identification of a novel hexanuclear Pd cage containing two types of dipyridyl ligands. A virtual combinatorial library of [Pd n L 2n ](BF 4 ) 2n complexes was prepared by mixing six different dipyridyl ligands with substoichiometric amounts of [Pd(CH 3 CN) 4 ](BF 4 ) 2 . Analysis of the equilibrated reaction mixture revealed the preferential formation of a heteroleptic [Pd 6 L 6 L′ 6 ](BF 4 ) 12 assembly. The complex was prepared on a preparative scale by a targeted synthesis, and its structure was elucidated by single-crystal X-ray diffraction. It features an unprecedented trigonal-antiprismatic cage structure with two triangular Pd 3 L 3 macrocycles bridged by six L′ ligands. A related but significantly larger [Pd 6 L 6 L′ 6 ](BF 4 ) 12 cage was obtained by using metalloligands instead of organic dipyridyl ligands.

Trapped ion mobility mass spectrometry shows its power as analytical tool in supramolecular chemistry by discriminating ten heteroleptic coordination cage derivatives, only differing slightly in size.

Recently developed self-assembly strategies allow to rationally reduce the symmetry of metallosupramolecular architectures. In addition, the combination of multiple ligand types without creating compound mixtures has become possible. Among several...

Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in terms of cavity shape and functional group decoration. We report a series of heteroleptic [Pd2A2B2] coordination cages that self‐assemble from a library of shape complementary bis‐monodentate ligands in a non‐statistical fashion. Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All‐atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities.