One challenge for the validity of V-based mimics is that C-H hydroxylation carried out by non-heme iron hydroxylases exhibits spin-state dependent reactivity , i.e., non-heme iron enzymes are known to react in the high-spin ground state. The electronic structures of Fe(IV) and V(IV) 100 in the key metal-oxo intermediate are different, i.e., Fe(IV) and V(IV) have d and d 1 electronic configurations, respectively. This results in different accessible spin states for Fe(IV)=O and V(IV)=O intermediates, where ferryl intermediates can access three spin states, i.e., high-spin (HS), intermediate-spin (IS), and low-spin (LS), while vanadyl intermediate can only access the LS state. Differences in spin states are also observed for other intermediates along the catalytic cycle, with Fe intermediates accessing all three spin states while V-based mimics are limited to either the LS, or IS and LS states. While it is unknown whether the spin would be conserved across hydroxylation intermediates in a vanadium-containing enzyme, a prior computational study of halogenases showed that the ground spin states of vanadium active sites vary across intermediates.