Axial‐Chiral Vertex Integration Strategy for the Construction of a High‐Affinity, Homochiral Pd 4 L 2 Cage

ABSTRACT Metal–organic cages (MOCs) are versatile supramolecular platforms, but their modest binding affinities in aqueous solution limit practical utility. Chiral MOCs with enhanced binding capabilities are highly desirable for diverse applications, yet their synthesis remains challenging. Here, we report an “Axial‐Chiral Vertex Integration” (ACVI) strategy, which enables the construction of an enantiopure chiral cage ( MOC‐2 ) from a non‐chiral Pd 6 L 4 MOC ( MOC‐1 ) by substituting two axial Pd vertices with axially chiral BINOL units. This design strengthened the hydrophobic effect of the confined cavity, delivering ultrahigh aqueous binding affinity (up to 10 9 M −1 ) for MOCs. At the same time, the integration of a well‐defined chiral microenvironment endows MOC‐2 with notable enantioselectivity (up to 9.2) and the ability to transfer chirality to achiral guests, producing significant circularly polarized luminescence (| g lum | up to 10 −3 ). This strategy provides a powerful blueprint for designing high‐affinity chiral MOCs, unlocking opportunities in molecular recognition and advanced chiral functional materials.