Soluble Methane Monooxygenase

Abstract

Aerobic life is possible because the molecular structure of oxygen (O2) makes direct reaction with most organic materials at ambient temperatures an exceptionally slow process. Of course, these reactions are inherently very favorable, and they occur rapidly with the release of a great deal of energy at high temperature. Nature has been able to tap this sequestered reservoir of energy with great spatial and temporal selectivity at ambient temperatures through the evolution of oxidase and oxygenase enzymes. One mechanism used by these enzymes for O2 activation has been studied in detail for the soluble form of the enzyme methane monooxygenase. These studies have revealed the step-by-step process of O2 activation and insertion into the ultimately stable C–H bond of methane. Additionally, an elegant regulatory mechanism has been defined that enlists size selection and quantum tunneling to allow methane oxidation to occur specifically in the presence of more easily oxidized substrates.

Bio‐inspired Nonheme Iron Oxidation Catalysis: Involvement of Oxoiron(V) Oxidants in Cleaving Strong C−H Bonds

“…This enzyme has an active site with two iron centers that react with O 2 to form a potent oxidant capable of hydroxylating methane to methanol. The observation that Fe III can act as Lewis acid to activate an Fe III ‐OOH raises the possibility that the second iron center in soluble methane monooxygenase may act in a similar fashion in converting the enzyme peroxo intermediate into the powerful oxidant Q that hydroxylates methane …”

“…Within a bioinorganic context, this approach is best represented by the powerful biological oxidant cytochrome P450 Cpd I, which is best described as an [Fe IV )(O)(porphyrin radical)] + species . Alternatively, metal–metal cooperativity, where multiple iron centers can carry out one‐electron processes, can also be employed to effect a net transfer of two electrons; the use of this strategy in biology is exemplified by the diiron(IV) intermediate Q of the nonheme diiron enzyme methane monooxygenase used by Nature for methane hydroxylation to methanol . Lacking either a redox‐active ligand or a second metal center, the Rieske oxygenases are proposed to utilize a mononuclear Fe V =O oxidant, but direct experimental evidence for such a species has not yet been uncovered .…”

“…Recent work shows that the addition of Lewis acids such as Sc(OTf) 3 or Fe(OTf) 3 to the Fe complex/H 2 O 2 reaction mixture can also result in the formation of highly reactive Fe V (O) species . The requirement for a “bimetallic” center to activate H 2 O 2 could have a major mechanistic implication on the role played by the second iron center in the diiron center of methane monooxygenase (MMOH) in facilitating O−O bond cleavage of the peroxodiferric intermediate P , en route to the diiron(IV) oxidant Q that hydroxylates the C−H bonds of methane . Similarly, the addition of strong acids to (N4)Fe III ‐OOH species, or even (N5)Fe III ‐OOH species, can promote the formation of Fe V (O) species, which draws parallels with the formation of Cpd I through proton‐assisted O−O bond cleavage of Cpd 0 and reveals the universal role of protons in O−O bond activation and formation of high‐valent iron oxidants …”

Structural Differences and Redox Properties of Unsymmetric Diiron PDIxCy Complexes

“…Therefore, reduction of the diiron complexes results in the formation of one‐ and two‐electron charge localized forms. The potential to access Fe IV ‐containing forms of 1 and 2 , as is common for Fe‐cyclam complexes, offers advantages for oxidation chemistry , . The unique properties of the diiron complexes bode promise for their reactivity toward a range of multi‐electron processes, and these aspects are currently being explored in ongoing studies in our lab.…”

“…Binuclear iron sites are employed by enzymes for varied biological processes that entail dioxygen activation (hemerythrin, MMO, RNRs), NO reduction (FNORs), and H 2 chemistry, and feature in the active sites of hydrolases (PAPs, GliJ) . The combination of two redox‐active iron centers in close proximity confers advantages for catalysis, including cooperative binding and activation of substrates, and the use of both metal ions for multi‐electron processes.…”