A Non‐Radical Mechanism for Methane Hydroxylation at the Diiron Active Site of Soluble Methane Monooxygenase

Abstract

We propose a non-radical mechanism for the conversion of methane into methanol by soluble methane monooxygenase (sMMO), the active site of which involves a diiron active center. We assume the active site of the MMOH(Q) intermediate, exhibiting direct reactivity with the methane substrate, to be a bis(mu-oxo)diiron(IV) complex in which one of the iron atoms is coordinatively unsaturated (five-coordinate). Is it reasonable for such a diiron complex to be formed in the catalytic reaction of sMMO? The answer to this important question is positive from the viewpoint of energetics in density functional theory (DFT) calculations. Our model thus has a vacant coordination site for substrate methane. If MMOH(Q) involves a coordinatively unsaturated iron atom at the active center, methane is effectively converted into methanol in the broken-symmetry singlet state by a non-radical mechanism; in the first step a methane C-H bond is dissociated via a four-centered transition state (TS1) resulting in an important intermediate involving a hydroxo ligand and a methyl ligand, and in the second step the binding of the methyl ligand and the hydroxo ligand through a three-centered transition state (TS2) results in the formation of a methanol complex. This mechanism is essentially identical to that of the methane-methanol conversion by the bare FeO(+) complex and relevant transition metal-oxo complexes in the gas phase. Neither radical species nor ionic species are involved in this mechanism. We look in detail at kinetic isotope effects (KIEs) for H atom abstraction from methane on the basis of transition state theory with Wigner tunneling corrections.

Quantum Chemical Studies on Dioxygen Activation and Methane Hydroxylation by Diiron and Dicopper Species as well as Related Metal–Oxo Species

“…146 Our model of Q is also supported by a proposal by Noodleman et al that the hydrogen-bond framework can create "open" coordination sites in the active site of Q. 208 In the optimized geometry of the coordinatively unsaturated diiron complex, 217 the spin densities on the iron atoms are 1.9 and ¹1.7, and those on the bridging oxygen atoms are 0.1 and ¹0.3. Because this model involves a coordinatively unsaturated ironoxo species, it can directly interact with substrate methane at the five-coordinate iron center.…”

“…We have thought much of an experimental fact that the unpaired spins on the two iron atoms are antiferromagnetically coupled in Q, 134 and along this viewpoint we first optimized the coordinatively saturated diiron model complex in the broken-symmetry singlet state, as shown in the left of Figure 23. 217 At that time computer power was inadequate for constructing a sufficiently large model.…”

“…As shown in Figure 24, a formate ligand forms a bidentate chelating interaction with the left-hand side iron atom and a single bond with the righthand side iron atom in the optimized geometry of the model complex of the MMOH red active site. 217 The FeFe distance was calculated to be 3.56 ¡. Since both iron atoms have a fivecoordination environment, the diiron complex has a vacant coordination site for the binding of dioxygen.…”

THEORETICAL STUDY ON METHANE HYDROXYLATION BY MIMIC METHANE MONOOXYGENASE WITH bis(μ-OXO)DIMANGANESE CORE

“…14 Next, for the nonradical mechanism, the first step involves one C-H bond dissociation of methane via a four-centered transition state (TS), resulting in an important intermediate involving a hydroxo ligand and a methyl ligand; and in the second step, the binding of the methyl ligand and the hydroxo ligand through a three-centered TS leads to the formation of a methanol complex. 9,10 Finally, for the nonsynchronous concerted mechanism, the O-H distance first shortens, and then the hydrogen atom rotates to make an 80-90 • angle with the C-O axis while the carbon rotates in the opposite direction towards the oxygen atom to produce a methanol complex. 12 However, the elucidation of the true mechanism of the C-H bond activation of methane catalyzed by sMMO is still an open question and requires further studies.…”

Evidence for the role of zinc on the performance of dibenzothiophene desulfurization by Gordonia alkanivorans strain 1B

“…Ohshiro et al [17] reported that the DszA activity from R. erythropolis D-1 was inhibited by EDTA, suggesting that a metal might be involved in its activity. Molecular characterization of other bacterial monooxygenases revealed that some metal ions such as zinc, copper, and iron are present in the active site of the enzymes [10,23,24]. Metal ions, as part of metalloenzymes, are essential for numerous biocatalytic processes.…”