Furosemide Adducts with Hexamethylenetetramine, Amantadine, and Isoniazid: A Structural Case That Demonstrates the Effect of Carboxylic Acid Dimer and Sulfonic Acid Dimer on the Solubility

Furosemide, abbreviated as FS, is a loop diuretic drug with low solubility and permeability. Herein, three adducts derived from FS and hexamethylenetetramine (HTEM), amantadine (AMD) and isonicotinic acid hydrazide (INZ), including two salts (FS–HTEM and FS–AMD) and one cocrystal (FS–INZ), have been readily obtained. Single-crystal X-ray diffraction of three adducts revealed similar layered structures but involving different hydrogen bonding networks. The solubility of two salts is higher than the cocrystal, and FS–HTEM has the highest solubility among three adducts. The solubility of FS adducts is influenced by anion–cation interactions, coformer, and hydrogen bonds. The formation of carboxylic acid dimer and sulfonic acid dimer in FS disfavors the solvation of the FS adducts.