Non-heme Fe(IV)-oxo intermediates

High-valent non-heme ironoxo intermediates have been proposed for decades as the key intermediates in numerous biological oxidation reactions. In the past three years, the first direct characterization of such intermediates has been provided by studies of several KG-dependent oxygenases that catalyze either hydroxylation or halogenation of their substrates. In each case, the Fe(IV)oxo intermediate is implicated in cleavage of the aliphatic CH bond to initiate hydroxylation or halogenation. The observation of non-heme Fe(IV)oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related KG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxylation. In contrast, for the KG-dependent non-heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay together, suggesting that they are in rapid equilibrium. The existence of two distinct conformers of the Fe site may be the key factor accounting for the divergence of the halogenase reaction from the more usual hydroxylation pathway after CH bond cleavage. Distinct transformations catalyzed by other mononuclear non-heme enzymes are likely also to involve initial CH bond cleavage by Fe(IV)oxo complexes, followed by diverging reactivities of the resulting Fe(III)hydroxo/substrate radical intermediates.