Enantiopure FeII4L4 cages bind steroids stereoselectively

Chiral recognition underpins many biological processes, including signaling and enzymatic transformations. Mimicry of the natural sys-tems that include these processes can provide an understanding of their fundamental mechanisms and enable the design of synthetic systems capable of achieving similar functions. However, reported synthetic hosts can only recognize small, simple chiral guests. Here, we report the self-assembly of a triazatruxene trialdehyde subcomponent into enantiopure FeII4L4 cages. Their chirotopic properties and well-enclosed cavities enable these cages to recog-nize complex steroids through non-covalent interactions, as eluci-dated by X-ray crystallography. These recognition events occur enantioselectively and diastereoselectively, spanning moderate to exclusive differentiation. Notably, one cage enantiomer binds one equivalent of canrenone, whereas the other enantiomer binds two equivalents. Microcalorimetry experiments clarify the interplay of enthalpy and entropy during enantioselective binding.

Automated summary

Chiral recognition is crucial in various biological processes and understanding its mechanism can lead to the design of synthetic systems with similar functions. However, current synthetic hosts can only recognize small chiral molecules. This study presents the self-assembly of triazatruxene trialdehyde into chiral FeII4L4 cages that can recognize complex steroids through non-covalent interactions. The recognition events are enantioselective and diastereoselective, showing different binding behaviors between the two enantiomers of the cage. Microcalorimetry experiments provide insight into the enthalpy and entropy contributions during enantioselective binding.