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.

Approaches to Configuration Determinations of Flexible Marine Natural Products: Advances and Prospects

“…In addition, crystalline sponges (CS), single-crystalline porous coordination networks that do not involve sample crystallization, have been proposed. They contain large and regular cavities that can absorb small molecules in the same way that sponges can and arrange them in an orderly manner so that their structures can be determined with X-ray diffraction [ 19 , 20 , 21 ].…”

The benefits of Cu Kβ radiation for the single-crystal X-ray structure determination of crystalline sponges

“…Despite the immense potential of the method and recent improvements and successes (Hoshino et al, 2016;Hayes et al, 2016;Ramadhar et al, 2015a,b;Easun et al, 2017;Cuenca et al, 2016;Cardenal & Ramadhar, 2021;Bosch et al, 2014;Goh et al, 2018;Inokuma et al, 2016Inokuma et al, , 2014Kersten et al, 2017;Lee et al, 2017;Li et al, 2019;Matsuda et al, 2016;Mitsuhashi et al, 2018;Morishita et al, 2020;Morita et al, 2020;Rissanen, 2017;Vinogradova et al, 2014;Wada et al, 2018;Waldhart et al, 2016;Yoshioka et al, 2016;Yuan et al, 2019;Zigon et al, 2015;de Poel et al, 2019;Urban et al, 2016;Sakurai et al, 2017) it is still far from being the universal way to determine the structure of troublesome compounds, because the method still faces some serious challenges: the time-consuming process of analysis is highly dependent on the analytes and must be carried out in separate batches for each sample. The obtained crystal structures are often crystallographically challenging because of the nature of the particular host-guest interactions (Cardenal & Ramadhar, 2021;Hoshino et al, 2016;Zigon et al, 2021). If this interaction between host and guest is too strong, diffusion into the cavities of the sponge is drastically hindered, if not impossible.…”

“…Many further investigations including, for example, fblock elements as building blocks for crystalline sponges also contributed to the improvement of the CS method (de Poel et al, 2016). For a more comprehensive overview, the recent reviews by Ramadhar, Cardenal and the Fujita group are recommended (Cardenal & Ramadhar, 2021;Zigon et al, 2021).…”

Organocatalytic Asymmetric Synthesis of Si-Stereogenic Silyl Ethers

“…Therefore, the “crystalline sponge method” was applied to elucidate the absolute structure by X-ray analysis (CS-XRD). 37 − 40 …”