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High‐valent metal‐oxo species play critical roles in enzymatic catalysis yet their properties are still poorly understood. In this work we report a combined experimental and computational study into biomimetic iron(IV)‐oxo and iron(III)‐oxo complexes with tight second‐coordination sphere environments that restrict substrate access. The work shows that the second‐coordination sphere slows the hydrogen atom abstraction step from toluene dramatically and the kinetics is zeroth order in substrate. However, the iron(II)‐hydroxo that is formed has a low reduction potential and hence cannot do OH rebound favorably. The tolyl radical in solution then reacts further with alternative reaction partners. By contrast, the iron(IV)‐oxo species reacts predominantly through OH rebound to form alcohol products. Our studies show that the oxidation state of the metal influences reactivities and selectivities with substrate dramatically and that enzymes will likely need an iron(IV) center to catalyze C−H hydroxylation reactions. [ABSTRACT FROM AUTHOR]

Aryloxyalkanoate dioxygenases are unique herbicide biodegrading nonheme iron enzymes found in plants and hence, from environmental and agricultural point of view they are important and valuable. However, they often are substrate specific and little is known on the details of the mechanism and the substrate scope. To this end, we created enzyme models and calculate the mechanism for 2,4‐dichlorophenoxyacetic acid biodegradation and 2‐methyl substituted analogues by density functional theory. The work shows that the substrate binding is tight and positions the aliphatic group close to the metal center to enable a chemoselective reaction mechanism to form the C2‐hydroxy products, whereas the aromatic hydroxylation barriers are well higher in energy. Subsequently, we investigated the metabolism of R‐ and S‐methyl substituted inhibitors and show that these do not react as efficiently as 2,4‐dichlorophenoxyacetic acid substrate due to stereochemical clashes in the active site and particularly for the R‐isomer give high rebound barriers. [ABSTRACT FROM AUTHOR]