CytochromecOxidase and Models

New heme–dioxygen and carbon monoxide adducts using pyridyl or imidazolyl tailed porphyrins

“…The longer term goal of our research, the main reason for synthesizing such complexes with P Py and P Im , is to utilize derived iron(II) or Fe(III)-superoxo compounds to generate new heme-Fe III -((hydro)peroxo)-Cu II species [20, 52, 53], of possible relevance to the active site chemistry occurring in cytochrome c oxidase [20, 54]. We have already shown that addition of a strong ‘base’ (e.g., dicyclohexylimidazole) to a heme-peroxo-copper assembly can have a strong influence with respect to subsequent O–O cleavage when protons and/or electrons are added (where a phenol was used as a hydrogen atom source) [19, 20].…”

Synthetic Fe/Cu Complexes: Toward Understanding Heme-Copper Oxidase Structure and Function

“…Such studies have been carried out by a number of research groups, but primarily led by Collman (and Chidsey) and co-workers (see section ). ,,, Many of these studies have benefited from advanced electrochemical techniques, such as use of rotating ring disc electrode (RRDE) instrumentation to detect H 2 O 2 evolved (as a partially reduced oxygen species, PROS), novel methods of attachment to electrode surfaces, and the ability to measurably vary electron fluxes reaching the heme–Cu catalyst.…”

Status of Reactive Non-Heme Metal–Oxygen Intermediates in Chemical and Enzymatic Reactions

“…Reductive activation of dioxygen at reduced metal cofactors generally results in a variety of two-electron oxidation processes leading to hydroxylation, halogenation, dehydrogenation, cyclization, and epoxidation products; the remaining two reducing equivalents required for the four-electron reduction of dioxygen are often provided by a cosubstrate or an exogenous electron donor. − ,− However, four-electron oxidation of substrates by a single equivalent of dioxygen without the consumption of reducing cosubstrates has also been observed in a number of oxidases and oxygenases (Figure ). − This alternative manifold for transition metal-mediated dioxygen activation would, however, require metal–superoxo species, which have been generally considered merely as pass-through points en route to high-valent metal–oxo intermediates that have been widely believed to be the only reactive species responsible for oxidation reactions. Indeed, convincing evidence for the involvement of a metal–superoxo intermediate in the C–H bond cleavage step was reported in myo -inositol oxygenase (MIOX), a mammalian enzyme that carries out the four-electron oxidation of myo -inositol to d -glucuronate (Figure , MIOX). − MIOX activates dioxygen at a mixed-valent diiron­(II/III) cluster to form an S = 1 / 2 diiron­(III)–superoxo species, which was trapped and characterized by electron paramagnetic resonance (EPR) spectroscopy .…”

“…Electrophilic reactions by metal–peroxo complexes have also been suggested in biology. One example is the diiron­(III)–peroxo species, H Peroxo , which is the first spectroscopically characterized intermediate formed upon dioxygen activation at the reduced diiron­(II) center of the hydroxylase component of soluble methane monooxygenase (sMMO). , Proton-promoted O–O bond scission and rearrangement of the diiron core in H Peroxo leads to a bis­(μ-oxo)­diiron­(IV) unit, termed Q, that is considered to be directly responsible for the oxidation of methane to methanol. , Relative reactivity studies of H Peroxo and Q with various substrates have shown that H Peroxo is a more electrophilic oxidant than Q, preferring to react by a two-electron, or a hydride abstraction, pathway (Figure , sMMO), whereas one-electron oxidation processes are preferred by Q (see Figure , sMMO). , The reactivity difference between H Peroxo and Q rather parallels the known differences between (μ-η 2 :η 2 -peroxo)­dicopper­(II) species, which react by two-electron processes, and high-valent di­(μ-oxo)­dicopper­(III) centers, ,, which prefer sequential one-electron oxidations, in the dicopper complexes. However, one major difference between the reactions of H Peroxo and Q with hydrocarbons is that large kinetic isotope effects, implicating H atom tunneling, are observed for Q but not for H Peroxo .…”

“…Key metabolic functions, such as hydroxylation of methane in methanotrophs, desaturation of fatty acids in plants, DNA and RNA repairs, biosynthesis of β-lactam antibiotics, and sensing of hypoxia in mammalian cells to signal the formation of blood vessels, all require the controlled oxidation of organic substrates by metal-mediated activation of dioxygen (O 2 ). − Dioxygen activation by transition metal complexes to facilitate oxidative transformations is also industrially important in the context of making efficient use of the naturally abundant oxidant (i.e., O 2 ) in oxidation reactions. − As a consequence, great efforts have been focused on understanding the mechanisms of dioxygen activation in a number of heme and non-heme monooxygenase enzymes containing mononuclear and homo- and heterodinuclear active sites. ,− Despite the diversity of the active sites of the enzymes, a common mechanistic hypothesis for dioxygen activation has been established. In this unified scheme (Figure ), the metal centers at the active sites first bind dioxygen to form a metal–superoxo intermediate (Figure A), thereby converting the kinetically inert ground state of O 2 to a more reactive doublet state of O 2 •– .…”