We first study the thermodynamics for the radical rebound mechanism 88 of methane to methanol catalysis occurring on cluster models of the SBUs that serve as the active sites within the identified MOFs. To avoid magnetic coupling between adjacent transition metal centers, models of the SBUs with multiple transition metal centers were modified by replacing all but one transition metal center with closed-shell Mg(II) ions (Supporting Information Tables S4-S6 and Figure ). On select systems, we verified trends were qualitatively unchanged with this approach in comparison to MOFs studied with all transition metal centers present (Supporting Information Table ). Mg-substituted SBU models with equivalent connectivity are removed. Such an approach has been previously validated for MOFs with weak to moderate coupling between metal centers (e.g., Fe-MOF-74) , and we expect our MOFs to be predominantly in this coupling limit due to our criteria for including MOFs with relatively high metal-metal separation (i.e., high FSR, see Secs. 2a and 4). Using these MOF models, we first characterize reactive intermediates to estimate reaction thermodynamics for methane to methanol conversion. In this catalytic cycle, the coordinatively unsaturated transition metal center in the resting state structure (1) of the MOF SBU undergoes two-electron oxidation to form a high-valent terminal metal-oxo species (2) using triplet molecular oxygen as the source of oxygen atom (Figure ). The metal-oxo formation energy, DE(oxo), is computed as: