The water-splitting reaction is catalyzed by the oxygen-evolving complex of photosystem II. This protein-bound inorganic complex contains four manganese ions, plus calcium and chloride ions as cofactors. Two water molecules are complexed by the manganese cluster, which then undergoes a series of four electron removals (oxidations) to replenish the reaction center of photosystem II. At the end of this cycle, free oxygen (O 2) is generated and the hydrogen of the water molecules has been converted to four protons released into the thylakoid lumen (Dolai's S-state diagrams).