Interplay\nof Stereochemistry and Charge Governs Guest\nBinding in Flexible Zn<sup>II</sup><sub>4</sub>L<sub>4</sub> Cages

Here, we report the\nsynthesis of a family of chiral Zn<sup>II</sup><sub>4</sub>L<sub>4</sub> tetrahedral cages by subcomponent self-assembly.\nThese cages contain a flexible trialdehyde subcomponent that allows\nthem to adopt stereochemically distinct configurations. The incorporation\nof enantiopure 1-phenylethylamine produced Δ<sub>4</sub> and\nΛ<sub>4</sub> enantiopure cages, in contrast to the racemates\nthat resulted from the incorporation of achiral 4-methoxyaniline.\nThe stereochemistry of these Zn<sup>II</sup><sub>4</sub>L<sub>4</sub> tetrahedra was characterized by X-ray crystallography and chiroptical\nspectroscopy. Upon binding the enantiopure natural product podocarpic\nacid, the Zn<sup>II</sup> stereocenters of the enantiopure Δ<sub>4</sub>-Zn<sup>II</sup><sub>4</sub>L<sub>4</sub> cage retained their\nΔ handedness. In contrast, the metal stereocenters of the enantiomeric\nΛ<sub>4</sub>-Zn<sup>II</sup><sub>4</sub>L<sub>4</sub> cage\nunderwent inversion to a Δ configuration upon encapsulation\nof the same guest. Insights gained about the stereochemical communication\nbetween host and guest enabled the design of a process for acid/base-responsive\nguest uptake and release, which could be followed by chiroptical spectroscopy.