Examination of Fe(IV)=O isomers in the HS state reveals that all bidentate succinate isomers are comparable in energy and more favorable than the monodentate succinate isomers by ca. 3 kcal/mol for intermediates containing fluoride and chloride (Figure and Supporting Information Table and Figure ). The monodentate succinate isomer with fluoride in the active site was obtained using additional constraints on Fe and oxygen atoms of succinate to ensure monodentate coordination. In the absence of these constraints, this monodentate isomer optimizes to a bidentate succinate isomer, indicating that for fluoride intermediates, interactions with the greater protein environment, such as a hydrogen bond to either the proximal or distal succinate carboxylate groups that would pull the co-substrate away from iron, are likely necessary to facilitate monodentate succinate coordination. In contrast, for bromide intermediates, the monodentate succinate isomer is more favorable than two bidentate succinate isomers by ca. 1-2 kcal/mol (Figure ). We find that the most stable Fe(IV)=O isomer is different for each halogen element (Figure ). However, the range of relative isomer energetics is consistent, i.e., for a given halide, all isomers differ in energy by less than 3.5 kcal/mol, suggesting that isomerization of Fe(IV)=O is feasible for all halides (Figure and Supporting Information Table and Figure ). ) oxo, axial (ax.) X, bidentate (bident.) succinate (succ.); axial oxo and equatorial X, bidentate succinate; axial oxo, equatorial X, monodentate (monodent.) succinate; equatorial oxo and X, bidentate succinate. (Top to bottom, right) Isomers are equatorial OH, axial X, monodentate succinate; axial OH, equatorial X, monodentate succinate; equatorial OH and X, bidentate succinate; axial OH, equatorial X, bidentate succinate; equatorial OH, axial X, bidentate succinate. The dashed blue line corresponds to an estimated DLPNO/CBS energy. Hydrogen, carbon, nitrogen, oxygen, iron, and bromine are shown in white, gray, blue, red, brown, and maroon, respectively.