The oxygen-evolving complex (OEC) of photosystem II contains a Mn4CaOn catalytic site, in which reactivity of bridging oxidos is fundamental to OEC function. We synthesized structurally relevant cuboidal Mn3MOn complexes (M = Mn, Ca, Sc; n = 3,4) to enable mechanistic studies of reactivity and incorporation of eta(3)-oxido moieties. We found that (Mn3CaO4)-Ca-IV and (Mn3ScO4)-Sc-IV were unreactive toward trimethylphosphine (PMe3). In contrast, our (Mn2Mn2O4)-Mn-III-O-IV cubane reacts with this phosphine within minutes to generate a novel (Mn4O3)-O-III partial cubane plus Me3PO. We used quantum mechanics to investigate the reaction paths for oxygen atom transfer to phosphine from (Mn2Mn2CaO4)-Mn-III-Ca-IV and (Mn3CaO4)-Ca-IV. We found that the most favorable reaction path leads to partial detachment of the CH3COO- ligand, which is energetically feasible only when Mn(III) is present. Experimentally, the lability of metal-bound acetates is greatest for (Mn2Mn2O4)-Mn-III-O-IV. These results indicate that even with a strong oxygen atom acceptor, such as PMe3, the oxygen atom transfer chemistry from Mn3MO4 cubanes is controlled by ligand lability, with the (Mn3CaO4)-Ca-IV OEC model being unreactive. The oxidative oxide incorporation into the partial cubane, (Mn4O3)-O-III, was observed experimentally upon treatment with water, base, and oxidizing equivalents. O-18-labeling experiments provided mechanistic insight into the position of incorporation in the partial cubane structure, consistent with mechanisms involving migration of oxide moieties within the cluster but not consistent with selective incorporation at the site available in the starting species. These results support recent proposals for the mechanism of the OEC, involving oxido migration between distinct positions within the cluster.