Regulating and Deciphering the Selective Synthesis of Metallacages in Microdroplets

Supramolecular synthesis, driven by reversible noncovalent interactions, offers significant potential for creating functional materials with precise architectures. However, traditional batch synthesis often leads to kinetic trapping, producing polydisperse mixtures of intermediates and products. To address this, we utilize microdroplet reactors─femtoliter-scale confined environments with high surface-to-volume ratios and controlled flow dynamics─to enable precise control over self-assembly. By incorporating the principles of Maxwellian billiards, which describe the behavior of particles in confined spaces, we show how spatial constraints and internal flows within microdroplets enhance entropy, guiding molecular interactions toward thermodynamically stable products. Comparative experiments and simulations reveal that microdroplets favor the formation of a well-defined tetrahedral metallacage with near-perfect selectivity, unlike the heterogeneous mixtures observed in batch reactors. The confined environment accelerates reactant mixing and aligns molecular trajectories, effectively suppressing kinetic traps. Additionally, the metallacages selectively encapsulate hexane isomers, reducing the extraction time by a factor of 15 and improving the efficiency of <i>n</i>-hexane extraction compared to traditional methods. This work highlights the connection between hydrodynamic confinement, molecular entropy, and thermodynamic selectivity, demonstrating the potential of microdroplet reactors for precise material synthesis and efficient separation processes.