Copper(II)-Oxyl Formation in a Biomimetic Complex Activated by Hydrogen Peroxide: The Key Role of Trans-Bis(Hydroxo) Species

Enzymes in nature, such as the copper-based lytic polysaccharide monooxygenases (LPMOs), have gained significant attention for their exceptional performance in C-H activation reactions. The use of H₂O₂ by LPMOs enzymes has also increased the interest in understanding the oxidation mechanism promoted by this oxidant. While some literature proposes Fenton-like chemistry involving the formation of Cu(II)-OH species and the hydroxyl radical, others contend that Cu(I) activation by H₂O₂ yields a Cu(II)-oxyl intermediate. In this study, we focused on a bioinspired Cu(I) complex to investigate the reaction mechanism of its oxidation by H₂O₂ using density functional theory and ab initio molecular dynamics simulations. The latter approach was found to be critical for finding the key Cu intermediates. Our results show that the highly flexible coordination environment of copper strongly influences the nature of the oxidized Cu(II) species. Furthermore, they suggest the favorable formation of <i>trans-</i>Cu(II)-(OH)₂ moieties in low-coordinated Cu(II) species. This <i>trans</i> configuration hinders the formation of Cu(II)-oxyl species, facilitating intramolecular H-abstraction reactions in line with experimentally observed ligand oxidation processes.