A New Cu²⁺‐Binding 1,3‐Benzodioxole‐Contaning N‐Acylhydrazone Protects Saccharomyces cerevisiae 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 N₂O‐ meridional tridentate ligand. The soluble cationic species [Cu(X1Diox)(OH₂)_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.