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X‐ray Structure Analysis of N‐Containing Nucleophilic Compounds by the Crystalline Sponge Method
Author(s) -
Sakurai Fumie,
Khutia Anupam,
Kikuchi Takashi,
Fujita Makoto
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704176
Subject(s) - nucleophile , sponge , chemistry , combinatorial chemistry , drug , stereochemistry , organic chemistry , pharmacology , catalysis , biology , botany
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 ZnCl 2 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 ZnCl 2 ‐noded CS. This demonstrates that the CS method is now a practical tool for drug‐discovery research in pharmaceutical industries.