Coordination of Biocompatible Metals with Selenoesters: A New Route for Enhanced Antimicrobial Agents

Abstract

The aim of this work was to assess how the antimicrobial activity of selenoesters is modulated by coordination with biocompatible metals. Liquid-assisted grinding (LAG) was used to prepare coordination derivatives of carboxylic acid- and amide-containing selenoesters with Mg2+ and Zn2+. While the strategy was unsuccessful for coordinating acid-containing selenoestersresulting in hydrolysis and the unexpected formation of a magnesium(II)-based MOF with a diselenide linkerit revealed a promising and sustainable route for synthesizing novel selenium-based materials. In contrast, LAG-mediated synthesis successfully yielded a zinc(II) complex with an amide-containing selenoester by selectively coordinating the oxygen atom of the amide group with the metal center. Subsequent antimicrobial assays revealed that complexation with zinc(II) substantially broadened the antimicrobial spectrum compared to both parent selenoester and ZnCl2, indicating that its biological activity is not merely due to a synergistic effect of its precursors. Thus, while the non-complexed selenoester demonstrated activity exclusively against Gram-positive S. aureus, complexation with Zn2+ enhanced its activity against Gram-negative bacteria (P. aeruginosa and E. coli) and pathogenic fungal species of the Candida genus. The difference in activity against these different microbial species might reflect a different interaction with the cell envelope of these cells (known to be structurally different) and that might impact the access of the molecules to the microbial cell. This study highlights the potential of mechanochemical synthesis to generate novel organoselenium−metal architectures with promising antimicrobial properties, thereby expanding the chemical space for this type of interaction and encouraging further exploration of their biological mechanisms.