Crystalline Sponge Method: X‐ray Structure Analysis of Small Molecules by Post‐Orientation within Porous Crystals—Principle and Proof‐of‐Concept Studies

Abstract This Review discusses, along with the historical background, the principles as well as proof‐of‐concept studies of the crystalline sponge (CS) method, a new single‐crystal X‐ray diffraction (SCXRD) method for the analysis of the structures of small molecules without sample crystallization. The method uses single‐crystalline porous coordination networks (crystalline sponges) that can absorb small guest molecules within their pores. The absorbed guest molecules are ordered in the pores through molecular recognition and become observable by conventional SCXRD analysis. The complex {[(ZnI2)3(tpt)2]⋅x(solvent)}n (tpt=tris(4‐pyridyl)‐1,3,5‐triazine) was first proposed as a crystalline sponge and has been most generally used. Crystalline sponges developed later are also discussed here. The principle of the CS method can be described as “post‐crystallization” of the absorbed guest, whose ordering is templated by the pre‐latticed cavities. The method has been widely applied to synthetic chemistry as well as natural product studies, for which proof‐of‐concept examples will be shown here.