Coordination Sphere Interactions Drive Isomer Selection in Heteroleptic Pd(II) Cages with Low-Symmetry Ligands

The targeted formation of low-symmetry coordination cages represents a significant design challenge, but offers the potential to engineer bespoke molecular hosts with precision. In this work, we have combined the design principles of geometric complementarity and coordination sphere engineering to direct the site- and orientation-selective self-assembly of heteroleptic Pd2LA2LB2-type coordination cages from low-symmetry ligands. The effects of different combinations of heterocyclic donors and their locations within the cage structures on isomer distributions were studied, providing insights on shifts in the balance between non-covalent interactions in the first and second coordination spheres of the cages. For cages with one low-symmetry ligand, switching between selective formation of syn- (up to 77%) or anti-isomers (up to 76%) was achieved simply through minor structural changes (swapping a hydrogen atom for a fluorine) or changing the location of heterocycles within the cage structure between the different ligand scaffolds. Furthermore, the selective (up to ~62%) assembly of particular isomers of heteroleptic cages formed from two low-symmetry ligand scaffolds was demonstrated and rationalised.