Metal-oxo geometries were generated using a custom script in molSimplify by adding an oxygen atom at the active site moiety in the MOF cluster (Supporting Information Text S6 and Figure ). The DFT geometry optimization workflow begins by optimizing the metal-oxo geometry, and if this or any subsequent intermediate calculation fails, downstream intermediate optimizations are not attempted. From the optimized metal-oxo geometry, we followed protocols adapted from prior work to functionalize the metal-oxo structure with a hydrogen atom to generate initial structures for the metal-hydroxo species and removed the oxo moiety to generate initial structures for the resting state. Initial structures of the methanol-bound species were generated by adding a methyl group to the optimized metal-hydroxo structure (Supporting Information Figure ). Submission of jobs was automated by molSimplify 103, 116 with a 96-h wall-time limit per run with up to five resubmissions. Open-shell calculations that failed any of the following checks were eliminated from the entire dataset: if the expectation value of the Ŝ 2 operator deviated from its expected value of S(S + 1) by > 1 µB 2 for SBUs with only one metal center and > 1.1 µB 2 for SBUs with more than one metal center or the combined Mulliken spin density on the metal and the oxygen in the active site moiety differed from the total spin by > 1 µB. Structures whose final geometries were unreasonably distorted as observed by visual inspection were also eliminated (Supporting Information Table ).