Reversible Structural Isomerization of Nature’s Water Oxidation Catalyst Prior to O–O Bond Formation

[Image: see text] Photosynthetic water oxidation is catalyzed by a manganese–calcium oxide cluster, which experiences five “S-states” during a light-driven reaction cycle. The unique “distorted chair”-like geometry of the Mn(4)CaO(5(6)) cluster shows structural flexibility that has been frequently proposed to involve “open” and “closed”-cubane forms from the S(1) to S(3) states. The isomers are interconvertible in the S(1) and S(2) states, while in the S(3) state, the open-cubane structure is observed to dominate inThermosynechococcus elongatus (cyanobacteria) samples. In this work, using density functional theory calculations, we go beyond the S(3)(+)Y(z) state to the S(3)(n)Y(z)(•) → S(4)(+)Y(z) step, and report for the first time that the reversible isomerism, which is suppressed in the S(3)(+)Y(z) state, is fully recovered in the ensuing S(3)(n)Y(z)(•) state due to the proton release from a manganese-bound water ligand. The altered coordination strength of the manganese–ligand facilitates formation of the closed-cubane form, in a dynamic equilibrium with the open-cubane form. This tautomerism immediately preceding dioxygen formation may constitute the rate limiting step for O(2) formation, and exert a significant influence on the water oxidation mechanism in photosystem II.