Alternative Mechanism for O₂ Formation in Natural Photosynthesis via Nucleophilic Oxo-Oxo Coupling

O₂ formation in photosystem II (PSII) is a vital event on Earth, but the exact mechanism remains unclear. The presently prevailing theoretical model is "radical coupling" (RC) involving a Mn(IV)-oxyl unit in an "open-cubane" Mn₄CaO₆ cluster, which is supported experimentally by the S₃ state of cyanobacterial PSII featuring an additional Mn-bound oxygenic ligand. However, it was recently proposed that the major structural form of the S₃ state of higher plants lacks this extra ligand, and that the resulting S₄ state would feature instead a penta-coordinate dangler Mn(V)=oxo, covalently linked to a "closed-cubane" Mn₃CaO₄ cluster. For this proposal, we explore here a large number of possible pathways of O-O bond formation and demonstrate that the "nucleophilic oxo-oxo coupling" (NOOC) between Mn(V)=oxo and μ₃-oxo is the only eligible mechanism in such a system. The reaction is facilitated by a specific conformation of the cluster and concomitant water binding, which is delayed compared to the RC mechanism. An energetically feasible process is described starting from the valid S₄ state through the sequential formation of peroxide and superoxide, followed by O₂ release and a second water insertion. The newly found mechanism is consistent with available experimental thermodynamic and kinetic data and thus a viable alternative pathway for O₂ formation in natural photosynthesis, in particular for higher plants.