Multi-dimensional microenvironment engineering in heteroleptic coordination cages for programmable biomimetic recognition

Abstract

Optimizing artificial receptors requires precise control over binding motif identity, quantity and spatial distribution. These parameters are notoriously difficult to coordinate in conventional systems. To address this challenge, we developed a complementary dual-cage platform (Pd₂A₃B/Pd₂A₂B₂) enabling systematic cavity engineering through site-selective endo-functionalization of heteroleptic metal–organic cages. This system integrates three programmable control dimensions: continuous quantity variation (1–4 functional groups), adjustable hetero-group ratios (1 : 3, 2 : 2, 3 : 1), and site-specific functional group mutations. Using only five functional groups, the platform constructs 53 nanocages with distinct microenvironments, achieving atomic-level cavity editing. Proof-of-concept titration experiments demonstrate 131% binding enhancement for an anionic guest in an optimized functionalized hetero-cage compared to conventional homoleptic Pd₂L₄ receptors, establishing quantitative design principles for biomimetic receptor engineering.