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

## TL;DR

Scientists discovered a new furosemide derivative while studying zinc(II) complexes, revealing unexpected chemical transformations.

## Contribution

A new furosemide derivative with ester and amidine modifications was serendipitously discovered through zinc(II) coordination studies.

## Key findings

- A new furosemide derivative was identified with esterification and amidine functionalities.
- Zinc(II) coordination led to structural modifications of furosemide in acetonitrile solvent.
- The derivative's structure was confirmed using single-crystal X-ray analysis.

## Abstract

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.