X-ray Structure Analysis of N-Containing Nucleophilic Compounds by the Crystalline Sponge Method

Crystalline sponges (CS) used under a set of standard conditions have often failed to give viable N-containing nucleophilic compounds. Despite the high affinity of these nucleophiles to the binding sites of the CS, N-containing compounds considerably harm the coordination framework of the CS during the guest-soaking step. Herein, it is disclosed that these compounds are efficiently absorbed into the CS, without harming the host, under mild conditions (<4 °C, <2 μg) that normally do not work for common organic guests. Moreover, the use of ZnCl₂ as the metal component of CS significantly improved the tolerance and robustness of the host framework toward N-containing compounds. Out of 22 drug (or drug-like) N-containing compounds chosen from the WHO model list of essential medicines, we succeeded in analyzing 17 analytes with the modified protocols and/or by using the ZnCl₂ -noded CS. This demonstrates that the CS method is now a practical tool for drug-discovery research in pharmaceutical industries.