Nature uses carboxylate-bridged diiron centres at the active sites of enzymes that catalyse the selective hydroxylation of hydrocarbons to alcohols. The resting diiron(III) state of the hydroxylase component of soluble methane monooxygenase enzyme is converted by two-electron transfer from an NADH-requiring reductase into the active diiron(II) form, which subsequently reacts with O2 to generate a high-valent diiron(IV) oxo species (Q) that converts CH4 into CH3OH. In this step, C–H bond activation is achieved through a transition state having a linear C⋯H⋯O unit involving a bound methyl radical. Kinetic studies of the reaction of Q with substrates CH3X, where X=H, D, CH3, NO2, CN or OH, reveal two classes of reactivity depending upon whether binding to the enzyme or C–H bond activation is rate-limiting. Access of substrates to the carboxylate-bridged diiron active site in the hydroxylase (MMOH) occurs through a series of hydrophobic pockets. In the hydroxylase component of the closely related enzyme toluene/o-xylene monooxygenase (ToMOH), substrates enter through a wide channel in the α-subunit of the protein that tracks a course identical to that found in the structurally homologous MMOH. Synthetic models for the carboxylate-bridged diiron centres in MMOH and ToMOH have been prepared that reproduce the stoichiometry and key geometric and physical properties of the reduced and oxidized forms of the proteins. Reactions of the diiron(II) model complexes with dioxygen similarly generate reactive intermediates, including high-valent species capable not only of hydroxylating pendant C–H bonds but also of oxidizing phosphine and sulphide groups.
One contribution of 19 to a Discussion Meeting ‘Catalysis in chemistry and biochemistry’.
- © 2005 The Royal Society