For the individual oxidation states, the frontier orbital splittings are qualitatively similar before and after the addition of substrate (see Figure and S9): The Cu(II)/Cu(II)-Cell systems display occupied frontier MOs mainly of ligand character for Cu(II) and ligand or substrate character for Cu(II)-Cell. The β-LUMOs are in both cases metal-based orbitals of d-character (dx2-y2 as depicted in Figure ). Thus, even if the substrate binds to the Cu(II) state, i.e. before reduction, the reduction of Cu(II)-Cell will likely result in the population of the same dx2-y2 orbital as in Cu(II).