A New Cu ²⁺ ‐Binding 1,3‐Benzodioxole‐Contaning <i>N</i> ‐Acylhydrazone Protects <i>Saccharomyces cerevisiae</i> Cells from Oxidative Stress

Abstract Copper dyshomeostasis is related to an increase in oxidative stress that, in turn, has been associated with a myriad of diseases and physiological aging. Based on this, the study of compounds with moderate affinity for this biometal is of interest. In this scenario, a new, highly stable, and non‐toxic (assessed in S. cerevisiae ) 1‐methylimidazole‐containing N ‐acylhydrazone, HX1Diox , is synthesized and characterized, including by XRD. The compound forms complexes of 1:1 and 1:2 copper(II)‐to‐ligand stoichiometries in solution, while only the non‐charged 1:2 compound, [Cu( X1Diox ) 2 ], is isolated in the solid state. In this case, each hydrazone unit is fully deprotonated and coordinates, in the iminolate X1Diox − form, as an N 2 O‐ meridional tridentate ligand. The soluble cationic species [Cu( X1Diox )(OH 2 ) x ] + and [Cu( HX1Diox )( X1Diox )] + are detected solely in solution, and stability constants of 12.49(4) and 28.42(6) are determined, respectively, for each of them. Interestingly, HX1Diox shows promising activity as a scavenger of superoxide radical anions, assessed in vitro, and eukaryotic cells by using wild‐type and SOD1‐deficient strains of S. cerevisiae yeast. Altogether, these results point to a promising copper interaction profile of HX1Diox , which, coupled with its favorable antioxidant profile, encourages further studies in the context of ROS‐related diseases.