By chance, not design : a new furosemide derivative from zinc(ii) complex studies

Podjed Rihtaršič, Nina (author), Cerc Korošec, Romana (author), Modec, Barbara (author)

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)$_2$(NH$_3$)$_2$]·(CH$_3$CH$_2$)$_2$O (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 NH$_2$ 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.

• Language: English
• Keywords: furosemide, amidine, zinc(II), coordination chemistry, crystal structure
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. 10614-10619
• Numbering: Vol. 11, iss. 6
• PID: 20.500.12556/RUL-179665
• UDC: 546.47
• ISSN on article: 2470-1343
• DOI: 10.1021/acsomega.5c12211
• COBISS.SI-ID: 268883459
• Publication date in RUL: 19.02.2026

Record is a part of a journal

• Title: ACS omega
• Shortened title: ACS omega
• Publisher: American Chemical Society
• ISSN: 2470-1343
• COBISS.SI-ID: 525873945

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: furosemid, amidin, cink(II), koordinacijska kemija, kristalna struktura

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0134-2022
• Name: Kemija za trajnostni razvoj

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: I0-0022-2022
• Name: Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)