Host Spin‐Crossover Thermodynamics Indicate Guest Fit

Spin‐crossover (SCO) metal‐organic cages capable of switching between high‐spin and low‐spin states have the potential to be used as magnetic sensors and switches. Variation of the donor strength of heterocyclic aldehyde subcomponents in imine‐based ligands can tune the ligand field for a FeII center, which results in both homoleptic and heteroleptic cages with diverse SCO behaviors. The tetrahedral SCO cage built from 1‐methyl‐1H‐imidazole‐2‐carbaldehyde is capable of encapsulating various guests, which stabilize different cage spin states depending on guest size. Conversely, the SCO tetrahedron exhibits different affinities for guests in different spin states, which is inferred to result from subtle structural differences of the cavity caused by the change in metal center spin state. Examination of SCO thermodynamics across a series of host–guest complexes enabled sensitive probing of guest fit to the host cavity, providing information complementary to binding‐constant determination. The degree of fit between the binding partners within a host–guest complex is crucial for a highly selective interaction, yet difficult to separate from non‐covalent interactions between the partners. The spin‐crossover of a metallo‐supramolecular host can be used to quantify guest fit, providing a new tool to describe host–guest binding that is complementary to binding constant determination.