In section 3.2, when we investigate multiple configurations of the same reactive event, we used a slightly different set of Si-Min clusters: three of them are from the original set, while the rest are different to include a larger variety of active site structures. All of the Si-Min models are carved out from pre-optimized Si-12Å clusters as described above. The new set contains 11 Si-Min clusters of three types depending on the structure of the binding silica, shown in Figure . Using the notation in Ref. 25, where the ring structure in the silica framework was denoted by the number of O centers in the ring, the first site type has the Nb bound to a two-member ring (called 2M site); in the second type, the Nb is bound to a threemember ring (3M site); in the third type, the Nb is bound to a larger-size ring that extends beyond the Si-Min framework (this is denoted an isolated or ISO site). In total, there are one 2M, five 3M, and five ISO sites. The full geometry of the fifteen Si-Min clusters is reported in the SI. The calculations were performed with a similar model chemistry as in our previous work, because it provides reliable results. The B3LYP hybrid functional with D3 dispersion corrections was used for all calculations. The basis set was the same for the Si-12Å and Si-10Å clusters: Def2TZVP and Stuttgart's pseudopotentials for Nb, 6-31++G(d,p) for the hydroxyls within the relaxed region, 6-31G(d) for the remaining atoms in the relaxed zone, and 3-21G for the peripheral region (>9 Å) that is kept frozen past the initial pre-optimization. In the Si-Min clusters, the basis set for Nb is the same, and 6-31++G(d,p) was used for Si, O, and OH. However, 6-31G was used for the capping F centers to mimic the electronegativity of the silica framework, as suggested in Ref The reaction mechanism of ethylene epoxidation was studied by Patel et al., and it is reproduced in Figure . The initial step (S1) is the H 2 O 2 adsorption on the Nb-center, followed by ethylene adsorption (S2); the catalytic cycle passes through a transition state (S3) to form ethylene epoxide and water (S4); the final steps are the desorption of ethylene epoxide (S5) and water (S6) to regenerate the bare active site. We focus on steps S1-S4 to investigate the modeling of the key processes and related energetics. The adsorption energies for steps S1 and S2 were calculated as: