By Chance, Not Design: A New Furosemide Derivative From Zinc(II) Complex Studies.

Furosemide, a sulfonamide-based diuretic, may also be of interest as a ligand capable of binding to metal ions. Our studies of zinc-(II) coordination chemistry with furosemide in organic solvents resulted in a crystalline precipitate. Initial characterization was challenging because single crystals were of insufficient quality for an unambiguous structural determination. X-ray analysis confirmed a four-coordinate zinc-(II) complex with two deprotonated furosemides (fur-) bound in a monodentate manner and two simple monodentate ligands. Complementary techniques, i.e., infrared spectroscopy, NMR spectroscopy, and thermal analysis, revealed their identity as ammonia, generated in situ from acetonitrile hydrolysis. The composition of the product is thus [Zn-(fur)2(NH3)2]·(CH3CH2)2O (1). Although our attempt to prepare better-diffracting crystals was unsuccessful, it led to the serendipitous discovery of a new furosemide derivative, labeled 2. The derivative features two structural modifications compared to the parent furosemide, namely, ester and amidine functionalities. Single-crystal analysis of 2 showed the esterification of the carboxyl group with methanol and nucleophilic addition of the sulfonamide NH2 group to the triple bond of acetonitrile, used as a solvent. These results expand the structural chemistry of furosemide and demonstrate its capacity to undergo unprecedented transformations in zinc-(II)-mediated systems.