Second-Generation Crystalline Sponge: Realizing Simple and Versatile Structural Analysis for Medium-Sized Pharmaceutical Compounds

Single crystal X-ray diffraction remains the gold standard for revealing precise three-dimensional molecular structures. In 2013, Prof. Fujita’s group introduced the crystalline sponge (CS) method, which bypasses the need for crystallizing the analyte. A small porous crystal is soaked in a solution of the target compound, allowing the molecule to be absorbed and aligned within its ordered pores for the X-ray analysis. However, the conventional CS method is limited by the size and polarity of the compounds that can be analyzed. Addressing these challenges, a team led by Distinguished Professor Makoto Fujita and Project Lecturer Hiroki Takezawa has synthesized a new crystalline sponge by immobilizing a cage molecule—renowned for its exceptional molecular capturing ability—within its framework. This breakthrough “second-generation CS method” significantly expands the range of analyzable compounds, now including water-soluble molecules and large amphiphilic compounds (MW > 1000). Moreover, by integrating crystallization techniques within glass capillaries, the required sample amount has been reduced to the microgram level, streamlining operations and enhancing reproducibility.