Closing Kok’s cycle of nature’s water oxidation catalysis

Abstract The Mn 4 CaO 5(6) cluster in photosystem II catalyzes water splitting through the S i state cycle ( i = 0–4). Molecular O 2 is formed and the natural catalyst is reset during the final S 3 → (S 4 ) → S 0 transition. Only recently experimental breakthroughs have emerged for this transition but without explicit information on the S 0 -state reconstitution, thus the progression after O 2 release remains elusive. In this report, our molecular dynamics simulations combined with density functional calculations suggest a likely missing link for closing the cycle, i.e., restoring the first catalytic state. Specifically, the formation of closed-cubane intermediates with all hexa-coordinate Mn is observed, which would undergo proton release, water dissociation, and ligand transfer to produce the open-cubane structure of the S 0 state. Thereby, we theoretically identify the previously unknown structural isomerism in the S 0 state that acts as the origin of the proposed structural flexibility prevailing in the cycle, which may be functionally important for nature’s water oxidation catalysis.