One Guest or Two? A Crystallographic and Solution Study of Guest Binding in a Cubic Coordination Cage

A crystallographic investigation of a series of host–guest complexes in which small‐molecule organic guests occupy the central cavity of an approximately cubic M8L12 coordination cage has revealed some unexpected behaviour. Whilst some guests form 1:1 H⋅G complexes as we have seen before, an extensive family of bicyclic guests—including some substituted coumarins and various saturated analogues—form 1:2 H⋅G2 complexes in the solid state, despite the fact that solution titrations are consistent with 1:1 complex formation, and the combined volume of the pair of guests significantly exceeds the Rebek 55±9 % packing for optimal guest binding, with packing coefficients of up to 87 %. Re‐examination of solution titration data for guest binding in two cases showed that, although conventional fluorescence titrations are consistent with 1:1 binding model, alternative forms of analysis—Job plot and an NMR titration—at higher concentrations do provide evidence for 1:2 H⋅G2 complex formation. The observation of guests binding in pairs in some cases opens new possibilities for altered reactivity of bound guests, and also highlights the recently articulated difficulties associated with determining stoichiometry of supramolecular complexes in solution. What a bind: Despite solution titrations showing binding of one guest inside the cavity of an octanuclear cubic coordination cage, in the solid‐state many guests (such as coumarin, illustrated) bind as pairs with up to 87 % of cavity volume being occupied—amongst the highest packing coefficients known. With this knowledge from crystallography, evidence for formation of H⋅G2 species can be found in solution under forcing conditions.