The crystalline sponge method enables single-crystal X-ray structure analysis of trace organic compounds without crystallization by using porous metal–organic frameworks(MOFs). This review discusses the design of MOF pores as molecular recognition fields, focusing on APF-series frameworks. In particular, APF-80 employs cooperative coordination and hydrogen-bonding interactions, including structured water networks, to capture diverse guest molecules. Such pore environments allow reliable atomic-resolution structure determination of pharmaceutically relevant and nucleophilic compounds. Rational pore design is shown to be key to expanding the scope and reliability of the crystalline sponge method.
Yuki Wada (2026) studied this question.