The mechanism of water oxidation performed by a recently discovered manganese pyridinophane catalyst [Mn((Py2NBu2)-Bu-t)(H2O)(2)](2+) is studied using density functional theory methods. A complete catalytic cycle is constructed and the catalytically active species is identified to consist of a Mnv- bis(oxo) moiety that is generated from the resting state by a series of proton-coupled electron transfer reactions. Whereas the electronic ground state of this key intermediate is found to be a triplet, the most favorable pathway for O-O bond formation is found on the quintet potential energy surface and involves an intramolecular coupling of two oxyl radicals with opposite spins bound to the Mn-center that adopts an electronic structure most consistent formally with a high-spin Mnill ion. Therefore, the thermally accessible high-spin quintet state that constitutes a typical and innate property of a first-row transition metal center plays a critical role for catalysis. It enables facile electron transfer between the oxo moieties and the Mn-center and promotes O-O bond formation via a radical coupling reaction with a calculated reaction barrier of only 14.7 kcal mol(-1). This mechanism of O-O coupling is unprecedented and provides a novel possible pathway to coupling two oxygen atoms bound to a single metal site.