We Starting from the pre-bound singlet state 5a, we obtained reaction energies and barriers for the reaction 5a→5b either employing TPSS or B3LYP. The resulting energies are given in Fig. and Tab. S1. Fig. show the structures of 5a and 5b as well as the TS. In the structures, H 2 O 2 is part of the above described H-bond network of the active site throughout the whole reaction. For the open-shell singlet state of 5b, only minor differences in energy The caged OH • species has been documented previously in several theoretical studies and aligns with experimental reactivity observed in analogous Cu model complexes involving homolytic O-O-bond breaking. The involvement of Cu(I)-catalysed O-O homolysis has also been experimentally implicated in LPMOs. We additionally investigated the reaction 5a→5b with His147 in the HIP state, which Fig. ). Formation of the oxyl species. In the next step, reaction and activation energies were calculated for the hydrogen abstraction reaction (5b→6b in Fig. ). The energies are compiled in Tab. S3. Fig. -f shows the reactant and product of the reaction 5b→6b in the triplet spin state as well as the TS connecting them. The H-bond interactions of the OH • radical to residues His147 and Gln162 and the nearby water molecules can be observed throughout the reaction, further underscoring that these residues are important to include in the QM region. The OH ). The activation of oxygen requires two electrons and protons. Therefore, as a putative proton donor, 31 His147 is kept in the doubly protonated state (HIP). We first investigate the reaction 3a→4a in Fig. , where the [CuO 2 ] + moiety is protonated.