An antitumor drug, 6-mercaptopurine monohydrate, has a low oral bioavailability (about 16%) due to its poor aqueous solubility. To improve its solubility, two cocrystals of 6-mercaptopurine with 4-hydroxybenzoic acid (1) and 2,4-dihydroxybenzoic acid (2), as well as two salts with piperazine in 1:1 (3) and 2:1 (4) stoichiometry, respectively, were obtained and characterized by infrared spectra, powder and single crystal X-ray diffraction. The structures of 1-4 are assembled via N-H(pyrimidine)•O(carboxyl), N-H(pyrimidine) •N(imidazole), O-H(carboxyl)•S, O-H(hydroxyl)•N(imidazole), N-H(pyrimidine)•S, O-H(carboxyl)•O(carboxyl) and N-H(piperazine) •N(imidazole) hydrogen bonds. After the formation of cocrystals and salts, the solubility of 6-mercaptopurine monohydrate is much improved, and the apparent solubility values of 1-4 in the phosphate buffer of pH 6.8 are approximately 1.6, 2.0, 14.0, and 4.2 times as large as that of 6-mercaptopurine monohydrate. Interestingly, 3 transformed to 4 at 40 °C/75% RH within one month. © 2012 American Chemical Society.
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