In this review, we highlight recent approaches that facilitate integrative self-sorting of ’naked’ metal ions and ligands to form multi-component, heteroleptic cage structures.

Control over the integrative self‐sorting of metallo‐supramolecular assemblies opens up possibilities for introducing increased complexity and function into a single self‐assembled architecture. Herein, the relationship between the geometry of three ligand components and morphology of three self‐sorted heteroleptic [Pd₂L₂L′₂]⁴⁺ cages is examined. Pd‐mediated assembly of two bis‐monodentate pyridyl ligands with native bite angles of 75° and 120° affords a cis‐[Pd₂L₂L′₂]⁴⁺ cage while the same reaction with two ligands with bite angles of 75° and 60° gives an unprecedented, self‐penetrating structural motif; a trans‐[Pd₂(anti‐L)₂L′₂]⁴⁺ heteroleptic cage with a “doubly bridged figure eight” topology. Each heteroleptic assembly can be formed by cage‐to‐cage conversion of the homoleptic precursors and morphological control of [Pd₂L₂L′₂] cages is achieved by selective ligand displacement transformations in a system of three ligands and at least six possible cage products.

A donor‐site engineering approach facilitates the formation of heteroleptic [Pd₂L₂L′₂]⁴⁺ cage structures through a favored cis‐′in₂/out₂′ spatial configuration of the methyl groups of 5‐ and 3‐substituted bis‐monodentate picolyl ligands with flat acridone and bent phenothiazine backbones. The heteroleptic cages were confirmed by ESI‐MS and 2D NMR experiments as well as DFT calculations, which pointed toward a cis‐configuration being energetically favored. This was further supported by the synthesis and X‐ray structure of a previously unreported cis‐[Pd(2‐picoline)₄]²⁺ complex. The formation of homoleptic structures, however, was met with considerable steric hindrance at the Pd^II centers, as observed by the formation of [Pd₂L₃(solvent)₂]⁴⁺ and [Pd₂L₂(solvent)₄]⁴⁺ species when only one type of acridone‐based ligand was offered. In contrast, bent phenothiazine ligands with outside‐pointing methyl groups showed the ability to form interpenetrated double‐cages, as revealed by X‐ray crystallography. The general route presented herein enables the assembly of uniform cis‐[Pd₂L₂L′₂]⁴⁺ coordination cages, thus furthering the possibility to increase structural and functional complexity in supramolecular systems.