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.
