Enhancing the Solubility of 6-Mercaptopurine by Formation of Ionic Cocrystal with Zinc Trifluoromethanesulfonate: Single-Crystal-to-Single-Crystal Transformation

An antitumor drug, 6-mercaptopurine monohydrate (MP·H 2 O), 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(CF 3 SO 3 ) 2 ), [Zn(MP) 2 (H 2 O) 2 ](CF 3 SO 3 ) 2 ·2H 2 O ( 1 ) and [Zn(MP) 2 ](CF 3 SO 3 ) 2 ( 2 ), were prepared. Slow evaporation of the methanol solution containing 1 gave the crystals of [Zn(MP) 2 (H 2 O)(MeOH)](CF 3 SO 3 ) 2 ·H 2 O ( 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 (H 2 O)](CF 3 SO 3 ) 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(CF 3 SO 3 ) 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.