Utilizing Counterion Driven Phase Transfer for the Isolation of Heteroleptic Coordination Cages

Licentiate thesis, 2026

Nature uses low symmetry to achieve high selectivity and efficiency in chemical processes, for example in the binding pockets of enzymes. This is something scientists want to mimic by creating artificial structures with enzyme-like properties. For this, scaffolds with a low symmetry are needed. A promising class of structures for these kinds of applications are heteroleptic coordination cages, assemblies of metal ions linked by two or more organic ligands. When assembling heteroleptic coordination cages multiple structures are often formed. To avoid this, various strategies have been developed to ensure that only one cage is formed in the assembly. These strategies limit the types of ligands that can be used in the assembly and often require a high synthesis effort. If heteroleptic coordination cages could instead be isolated from a mixture, they would become more accessible.

In this work a novel method for isolation of heteroleptic coordination cages with different charges via phase transfer is developed. As proof of principle, three heteroleptic coordination cages, one neutral, one anionic and one cationic were isolated. Phase transfer is a process where cages are moved between immiscible liquid phases using different counterions to modify the solubility of the cages. This strategy is well established for cationic coordination cages, but there are few examples for anionic coordination cages. Therefore, the phase transfer of two geometrically similar FeII4L6, both in isolation and from a mixture was established. The anionic cage required an order of magnitude more of the salt to drive complete phase transfer compared to the cationic cage. The ligands from the geometrically similar FeII4L6 were then combined to form libraries of heteroleptic coordination cages, and the phase transfer method developed was used to isolate three different heteroleptic species.

This work both contributes to a deeper understanding of the phase transfer process and is the first example of isolation of heteroleptic species. The method developed in this work is expected to be transferable to other types of coordination cages and will be used to access novel heteroleptic cages for different applications.