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

Abstract

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.

Catalysis of an Aldol Condensation Using a Coordination Cage

“…The combined volume of two ID guests (74%) significantly exceeded the value of 55 ± 9% of the host cavity volume (409 Å 3 ), which Rebek showed a while ago afforded optimal guest binding in solution [50,51]. However, a crystalline sponge experiment was performed under highly forcing and non-equilibrium conditions using a large excess of the guest; we [48] and others [52][53][54] have observed packing coefficients for guests inside supramolecular host cavities of >80% when favourable interactions such as π-stacking between multiple guests and favourable interactions between guests and the cage interior surface result in a particularly compact guest array. In dilute solution-the conditions under which guest binding is normally evaluated-we can imagine that for this reason, the second binding constant K 2 would be substantially smaller than the first binding constant K 1 , in which case, the single-guest binding would dominate the solution speciation behaviour [48].…”

“…A crystal structure of the cage/guest H/ID complex could be obtained using the crystalline sponge method that we have used in previous work by preparing crystals of the free host cage H by a solvothermal synthesis, followed by slow cooling [28], and immersing them in a concentrated solution of ID in MeOH for several hours, which resulted in guest uptake without loss of crystallinity [48]. Details of the structure are shown in Figures 3-5.…”

“…The X-ray crystallographic data for the H w /ID complex were collected in Experiment Hutch 1 of beamline I-19 at the UK Diamond Light Source synchrotron facility [47]. Full details of the instrumentation, methods used for data collection, and for the solution and refinement of the structure, are as recently published [48]. Crystallographic, data collection, and refinement parameters are collected in Table 1.…”

Design and Applications of Water-Soluble Coordination Cages

“…Aqueous solution studies using 37 also suggested that the multiple guest binding may occur in the presence of high guest concentrations. 171 …”

An Adaptive Resorcinarene Hemicarcerand

“…As a benchmark of this adaptation, the packing coefficient, the ratio of guest to host volume, is usually compared to Rebek's 55 % solution [21] . Only if strong intermolecular forces such as hydrogen bonds contribute to the complex’ stability, an excess of these 55±9 % is observed [22] …”