The Crystalline Sponge Method: A Solvent-Based Strategy to Facilitate Noncovalent Ordered Trapping of Solid and...

A strategy that leverages solvent effects to noncovalently trap solid and unstable liquid organic compounds within a crystalline sponge ({[(ZnI₂)₃(tris(4-pyridyl)-1,3,5-triazine)₂]·x(CHCl₃)}_n) in a simple, mild, and efficient fashion for target molecule structure determination via X-ray diffraction is disclosed. Host-guest structures were obtained using third-generation synchrotron radiation, and new beamline hardware allowed rapid data collection in ~5-24 minutes. This is 40-90% faster than previously reported crystalline sponge synchrotron datasets collected by us, and approximately a 150-720-fold decrease in time versus using a typical in-house diffractometer, effectively enabling the potential for high-throughput analysis. The new target molecule inclusion method using methyl tert-butyl ether (MTBE) solvent was demonstrated by trapping (E)-stilbene, vanillin, 4-(trifluoromethyl)phenyl azide, and (+)-artemisinin (an antimalarial drug). The potential of guests to maximize intermolecular interactions with the crystalline sponge framework at the expense of attenuating intramolecular interactions (e.g., π-conjugation) was observed for (E)-stilbene. Trapping of vanillin and (+)-artemisinin elicited single-crystal-to-single-crystal transformations where space group symmetry reduced from C2/c to P1̄ and C2, respectively, and the absolute configuration of (+)-artemisinin was determined through anomalous dispersion.