A new metal-organic framework (MOF), APF-80, enables the crystalline sponge method to capture and analyze nucleophilic compounds. Alkaloids, a diverse group of biologically active compounds, usually damage MOF crystals and resist study. By incorporating multiple structural motifs, these guests are encapsulated inside APF-80, which allows high-quality crystallographic data collection. This development opens new possibilities for structural analysis, advancing drug development and biochemistry.