Adducts of N-Heterocyclic Drugs, Niacin, Allopurinol, and Amiloride, with 2,4-Pyridinedicarboxylic Acid Coformer

A co-crystallization of three drug molecules, niacin (3-pyridine-carboxylic acid = NIA), allopurinol (pyrazolo(3,4-d)pyrimidin-4-one = ALP), and amiloride (3,5-diamino-6-chloro-pyrazine-2-carbonyl)-guanidine = AMI), with the same coformer, 2,4-pyridinedicarboxylic acid (PDA), resulted in three new crystalline products, (NIA)(PDA) (1), (ALP)2(PDA)·1.5H2O (2), and (AMI)2(PDA)2(H2O)2 (3). The formation of new phases was confirmed by IR spectra and X-ray single-crystal and powder diffraction analysis. The proton transfer resulted in the zwitterionic co-crystal 1. In co-crystal 2, neutral ALP molecules existed in the oxo-tautomeric form. Compound 3 crystallizes as the salt with the guanidinium cationic part as in the started amiloride hydrochloride hydrate, and the PDA coformer as the zwitterionic pyridinium dicarboxylate anion. Thus, the diversity of the PDA coformer ionization states included the neutral, zwitterion, and zwitterion anionic forms. All compounds were layered structures where the heterocyclic molecules were linked in the H-bonded corrugated layers stabilized by the diverse conventional and charge-assisted hydrogen bonds with π-π stacking interactions between the layers supported by the mediated water molecules in 2 and 3. © 2017 American Chemical Society.