In the fields of supramolecular chemistry and biomimetic catalysis, metal-organic cages (MOCs) have emerged as an ideal platform for mimicking enzyme active sites and constructing artificial molecular devices, owing to their well-defined three-dimensional cavities and precisely tunable internal microenvironments. Among these, the Pd₂L₄-type "lantern-shaped" coordination cage serves as a classic model system in this domain and is widely employed in host-guest chemistry research. However, existing studies have predominantly focused on cage structures based on the 1,3-diethynylbenzene linker, while in-depth exploration of other structurally analogous cages remains relatively scarce, limiting a comprehensive understanding of structure-activity relationships and the precise modulation in such systems. In this study, we systematically investigated the recognition capabilities of three Pd₂L₄ cages featuring 1,3-diethynylbenzene, triphenylamine, and terphenyl as linkers toward three representative anionic guests (TsO^-, NO₃^-, H₂PO₄^-) and two neutral guests (1,4-benzoquinone, methyl acetoacetate) through NMR titration experiments. The catalytic performance of these MOCs was subsequently evaluated by monitoring the in situ NMR yields of Michael addition reactions conducted under identical reaction conditions. Our experimental findings demonstrate that variations in ligand backbone structures substantially alter the steric hindrance at the recognition sites within the cage cavity, thereby exerting profound influence on both guest binding affinity and catalytic activity. These comparative investigations not only furnish mechanistic explanations rooted in steric hindrance regulation for the superior performance observed in 1,3-diethynylbenzene-based Pd₂L₄ cages, but also unveil the decisive role of spatial microenvironment at recognition sites in governing the catalytic efficiency of MOCs. This fundamental insight establishes critical design principles for future development of high-performance biomimetic catalytic systems: while preserving the cavity confinement effect as an essential structural advantage, the strategic minimization of steric hindrance at recognition sites through rational molecular design represents a pivotal optimization strategy. Such an approach will concurrently enhance catalytic reaction efficiency and expand substrate scope generality, thereby opening new avenues for advancing coordination cage-based catalysis toward practical synthetic applications.

Key words: metal-organic cages, host-guest recognition, cage catalysis, Pd₂L₄