Enhancing the Solubility of 6‑Mercaptopurine by Formation of Ionic Cocrystal with Zinc Trifluoromethanesulfonate: Single-Crystal-to-Single-Crystal Transformation
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An antitumor drug, 6-mercaptopurine monohydrate (MP·H2O), has a low oral bioavailability due to its poor aqueous solubility. In order to improve its solubility, two ionic cocrystals of 6-mercaptopurine with zinc trifluoromethanesulfonate (Zn(CF3SO3)2), [Zn(MP)2(H2O)2](CF3SO3)2·2H2O (1) and [Zn(MP)2](CF3SO3)2 (2), were prepared. Slow evaporation of the methanol solution containing 1 gave the crystals of [Zn(MP)2(H2O)(MeOH)](CF3SO3)2·H2O (1a). Single-crystal-to-single-crystal transformation occurred under certain conditions, in which 1a transformed to 1 in the open air around 10 °C, and 1 further transformed to [Zn(MP)2(H2O)](CF3SO3)2 (1b) at room temperature (∼25 °C) and low RH%. The structures of 1, 1a, and 1b were determined by single crystal X-ray diffraction, in which MP and Zn(CF3SO3)2 were assembled via coordination bonds and hydrogen bonds, and the coordination geometry of Zn(II) changed from octahedron in 1 and 1a to square pyramid in 1b. After the formation of ionic cocrystals of 1 and 2, both the apparent solubility and dissolution rate were increased.
