All the intermediates formed during the catalytic cycle can potentially exist in two or more isomers. For example, in intermediates ( ) and ( ), water and molecular oxygen are represented in axial positions corresponding to their respective axial configurational isomers due to the frequency with which water is found in the axial position in crystal structures of halogenases (Figure ). However, these intermediates can also have water and molecular oxygen present in equatorial positions, corresponding to equatorial configurational isomers (Figure and Supporting Information Figure ). In the Fe(IV)=O and Fe(III)-OH intermediates, the active site can be hexacoordinated or penta-coordinated depending on whether succinate is coordinated to iron in a bidentate or monodentate configuration (Figure and Supporting Information Figure ). In the case of a hexa-coordinated iron active site with bidentate succinate, oxo or hydroxo moieties and the halide ligand can be present in axial or equatorial positions, resulting in three configurational isomers: axial oxo/hydroxo and equatorial halide, equatorial oxo/hydroxo and axial halide, and equatorial oxo/hydroxo and halide (Figure and Supporting Information Figure ). These three configurational isomers can also be observed when we have a penta-coordinated iron active site with monodentate succinate (Figure and Supporting Information Figure ). Combining the monodentate and bidentate succinate coordination cases, we potentially have a total of six configurational isomers for intermediates (3) and (4) (Figure and Supporting Information Figure ). Along with computing reaction coordinates, we will evaluate the properties and energetics for interconversion of all of these isomers to identify which ones are most likely present during catalysis.