Abstract Biomimetic catalysts that rely on hollow, synthetic hosts lack the sophistication of an enzyme active site. One reason for this is that synthetic hosts, particularly those prepared using self‐assembly, are invariably highly symmetrical and therefore not tailored to achieve optimal interactions. Herein, we describe a low‐symmetry coordination cage that shows enhanced Diels–Alder catalytic proficiency compared to equivalent high‐symmetry systems. Similar to biological catalysis, this enhanced proficiency is due to the presence of non‐degenerate, distinct pockets that separately facilitate both substrate recognition and transition state stabilization, leading to higher specificity. The same low symmetry catalyst also shows emergent properties in that it can catalyze sequential chemical reactions that equivalent symmetrical cages cannot. These results pave the way to ever more elaborate catalysts that show enhanced activity and selectivity delivered solely by the tailored expression of weak non‐covalent interactions.
Maheshwari et al. (2026) studied this question.