Differential electrochemical mass spectrometry (DEMS) analysis of the oxygen isotopologues produced by O-18-labeled Co-OEC in (H2O)-O-16 reveals that water splitting catalysis proceeds by a mechanism that involves direct coupling between oxygen bound to dicobalt edge sites of Co-OEC. The edge site chemistry of Co-OEC has been probed by using a dinuclear cobalt complex. O-17 NMR spectroscopy shows that ligand exchange of OH/OH2 at Co(III) edge sites is slow, which is also confirmed by DEMS experiments of Co-OEC. In borate (B-i) and phosphate (P-i) buffers, anions must be displaced to allow water to access the edge sites for an O-O bond coupling to occur. Anion exchange in P-i is slow, taking days to equilibrate at room temperature. Conversely, anion exchange in B-i is rapid (k(assoc) = 13.1 +/- 0.4 M-1 s(-1) at 25 degrees C), enabled by facile changes in boron coordination. These results are consistent with the OER activity of Co-OEC in B-i and P-i. The Pi binding kinetics are too slow to establish a pre-equilibrium sufficiently fast to influence the oxygen evolution reaction (OER), consistent with the zero-order dependence of P-i on the OER current density; in contrast, B-i exchange is sufficiently facile such that B-i has an inhibitory effect on OER. These complementary studies on Co-OEC and the dicobalt edge site mimic allow for a direct connection, at a molecular level, to be made between the mechanisms of heterogeneous and homogeneous OER.