Supramolecular docking: Taming flexible alkyl chains for crystallography via active molecular recognition

A supramolecular docking strategy has been developed for the SCXRD determination of flexible alkyl-chain-containing molecules. By incorporating pillar[5]arene-based recognition units into MOFs, EtP5-MOF-2 was constructed as a supramolecular dock capable of selectively capturing and organizing alkyl-bearing guests. Through cooperative host–guest interactions, this platform reduces conformational motion and promotes molecular ordering, enabling the structural determination of 48 challenging molecules, including natural products, approved drugs, and synthetic compounds. Furthermore, supramolecular docking allows direct structural analysis of alkyl-chain-containing products derived from crude reaction mixtures without purification and enables unknown compound identification through blind experiments. This strategy also provides opportunities for reactive species stabilization and absolute configuration determination, offering a versatile platform for crystallization-assisted structural elucidation.