Catassembly Triad: A Catalytic Framework for Enantioselective Chiral Molecular Assembly

Chiral molecular assembly represents a frontier in creating life-inspired functional materials; yet, a predictive framework for its enantioselective catalysis remains elusive. Here, we introduce the Catassembly Triad - a mechanistic paradigm for catalytic enantioselective assembly, demonstrated using chiral supramolecular cages as a model system. Combining in situ characterization, <i>ab initio</i> calculations, and machine learning, we resolve how catalysts must harmonize attachment, chiral control, and detachment to direct assembly pathways. Kinetic and structural analyses reveal that chiral diamine catalysts (e.g., cyclohexanediamine) enforce enantioselectivity by templating transient intermediates with deformation-induced affinity changes driving timely catalyst release. We establish a predictive framework based on quantitative triad metrics (Δ<i>E</i>_att, Δ<i>E</i>_ctl, and Δ<i>E</i>_det) from calculations, validated by Bayesian clustering and experimental testing. The framework achieves a perfect concordance between predicted and observed catalyst efficacy across diverse molecular classes. This framework bridges enzymatic cooperativity and supramolecular assembly, enabling programmable chirality transfer and unlocking catalyst design for adaptive chiral materials.