Enantiopure Fe^II₄L₄ cages bind steroids stereoselectively

Chiral recognition underpins many biological processes, including signaling and enzymatic transformations. Mimicry of the natural systems 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 Fe^II₄L₄ cages. Their chirotopic properties and well-enclosed cavities enable these cages to recognize complex steroids through non-covalent interactions, as elucidated 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.