Computational evaluation of the oxidation of superoxide to molecular dioxygen mediated by NNNN-tetradentate copper complexes

Free radicals such as superoxide are reactive species that, upon accumulation, lead to oxidative stress. The superoxide dismutase (SOD) enzyme mitigates this stress by converting superoxide into hydrogen peroxide and oxygen. However, the probable lack of SOD supplementation has driven the search for alternatives, with copper complexes emerging as promising candidates. This study employs density functional theory (DFT) to evaluate the Gibbs reaction energies of nine copper complexes, suggesting their potential to catalyze the conversion of superoxide into molecular oxygen as all complexes exhibit thermodynamically favorable mechanisms for mimicking SOD. Furthermore, a topological analysis using Bader's quantum theory of atoms in molecules (QTAIM) was conducted to investigate the present interactions between copper, superoxide, and molecular oxygen species. The latter reveals that the interaction between copper and superoxide is partially covalent and attractive, transitioning to a closed-shell interaction upon charge redistribution to form the product. These findings suggest that copper complexes could effectively mimic SOD, offering a promising approach to reducing oxidative stress, a key factor in neurodegenerative diseases like Alzheimer's Disease (AD). This work provides a robust framework for assessing copper complexes as potential therapeutic agents in combating oxidative stress-related conditions.