In addition to linear transit calculations for the proton transfers, we performed calculations to estimate dissociation energies and reduction potentials. For the dissociation energies, we interchanged each of the eight QM water molecules and the relevant oxygen species bound to Cu for the reactions in light blue in Fig. , and optimized the geometries. Notably, the dissociation energies and sometimes even the electronic state of the dissociated species were found to be highly sensitive to the microsolvation. We therefore generally report averages over several micro-solvated structures whenever possible. We generally used the most stable conformer from the previously preformed geometry optimizations/ proton transfers (i.e., 2 HIE in triplet state, 3 int in open-shell singlet state, 3l red and 4f red , see Tables , S13 and S16) as starting structure and the reference to estimate the dissociation energies.