High-Valent Nonheme Iron Oxidants in Biology: Lessons from Synthetic Fe(IV)=O Complexes (original) (raw)

2013, Bulletin of Japan Society of Coordination Chemistry

Ever since Hayaishi and Mason established the existence of oxygenases in 1955, 1,2 chemists have been fascinated by the activation of dioxygen at biological metal centers that produce a powerful oxidant capable of cleaving strong C-H bonds. Within the last half century, the number of metalloenzymes found to activate O 2 has grown, with iron enzymes representing the largest subset of this class as well as the most versatile. 3 For many of these reactions, it is conjectured that O 2 binding to the metal center initiates a reaction sequence that leads to the cleavage of the O-O bond and formation of a high-valent metal-oxo species responsible for C-H bond functionalization. Dioxygen activating iron enzymes can be subdivided into two families, heme and nonheme. Due to their intense and characteristic chromophores, the heme enzymes were recognized earlier as a group, exemplified by the cytochromes P450 that play important roles in metabolism. 4 Based on detailed studies of the closely related peroxidases, a high-valent intermediate called Compound I was identified as the species responsible for the oxidative chemistry observed and subsequently described as an [Fe IV (O)(porphyrin cation radical)] species. However, owing to its high reactivity, the corresponding Compound I intermediate of cytochrome P450 proved elusive, and only recently were the appropriate conditions found that allowed its spectroscopic characterization. 5 The cytochromes P450 catalyze metabolic transformations that involve the cleavage of strong C-H bonds and were recently shown to be capable of carrying out the hydroxylation of light alkanes, including methane, in vitro. 6,7 Dioxygen activating enzymes with nonheme iron active sites emerged in the past 25 years as another family of enzymes capable of cleaving strong C-H bonds. There are two subclasses, one with diiron centers exemplified by soluble methane monooxygenase (sMMO) 8,9 and the other with monoiron sites represented by taurine:α-ketoglutarate dioxygenase (TauD). 10,11 For both subclasses, the iron centers are coordinated to a combination of imidazoles (from His residues), carboxylates (from Asp and Glu residues), and solvent-derived ligands. Reaction of the reduced enzymes with O 2 leads to the generation of high-valent intermediates that, like Compounds I in cytochromes P450, carry out the critical C-H cleavage step (Scheme 1). In the case of sMMO, this intermediate is called Q and is postulated on the basis of Mössbauer and EXAFS analysis to have an antiferromagnetically coupled high-spin diiron(IV) unit with an Fe 2 O 2 diamond core. 12,13 The corresponding TauD intermediate is called J and demonstrated to have a high-spin Fe IV =O unit. 11 Both intermediates were shown to be kinetically competent to oxidize their respective substrates