A new copper-oxo player in methane oxidation.

I n this issue of PNAS, Schoonheydt, Solomon, and coworkers (1) definitively characterize the structure of the Cu-ZSM-5 site that oxidizes methane to methanol. With the successful correlation of a specific copper-oxy structure to such reactivity, the importance of this work extends beyond hydrocarbon oxidation on zeolites. This breakthrough potentially has farreaching implications in both the fundamental and applied sciences. Scientific interest focuses on the oxidation of methane as a chemical feedstock and alternative energy source (2, 3, 15). Methane constitutes the bulk of abundant natural gas, but its industrial processing requires an energyand infrastructure-intensive multistep reforming via ‘‘synthesis gas’’ (CO plus H2). C–H bond activation has long been a prime obsession of organometallic chemists, for example, and current efforts focus on finding highly active, robust catalysts for mild oxidation of methane and other alkanes (2–4, 15). Promising alkane-oxidizing inorganic compounds have been discovered, especially Pt complexes following the breakthrough Shilov catalytic system (Fig. 1) (3–5, 15). Many prominent experimental and computational researchers have made great strides on C–H bond breaking at metal centers, providing mechanistic insights and the identification of discrete compounds or materials for homoor heterogeneous catalysis. None of these systems has yet demonstrated catalytic utility for the industrial scale; all suffer from some combination of low selectivity, catalyst instability, and high temperature and pressure requirements (3, 4, 15). The holy grail of methane-oxidizing catalyst would be robust toward decomposition, rapid, selective for oxidizing methane to methanol, and active at low temperature and pressure. The Cu-ZSM-5 zeolite sets new standards in these regards while achieving selectivity in excess of 98% (6). Yet Nature far outpaces the laboratory chemist and has found not one, but two solutions to harnessing methane as an energy source and for the synthesis of the molecules required for life: the soluble methane monooxygenase (sMMO), found in the cytosol of some methane-metabolizing bacteria (7), and particulate methane monooxygenase (pMMO), a methanotrophic integral membrane protein (8). The MMOs are unique not for Nature’s choice of metals—Fe for sMMO, Cu for pMMO—but for their use of these ‘‘ordinary’’ cofactors for the extraordinary oxidation of methane C–H, at 104 kcal/mol, the strongest hydrocarbon bond (1, 9). Inorganic chemists have attempted to understand or even reproduce the reactivity of enzymes by studying smallmolecule metal complexes. Yet replication of the efficiency of Nature’s exquisitely crafted ‘‘little reactors’’ remains a near impossibility even when an enzyme’s structure and mechanism are not shrouded in mystery—the state in which current studies of pMMO are mired. sMMO appears to employ a high-valent nonheme dinuclear iron(IV) site to activate dioxygen to oxidize methane (Fig. 1) (7). For pMMO, recent crystal structures unveiled pMMO’s (possible) metal sites (Fig. 1) but have also added confusion (8). That copper is the catalytic cofactor is one point of strong agreement in the contentious argument over the location, identity, and structure of the active site. But in addition to the sites found by X-ray crystallography, trinuclear Cu clusters have been proposed to lurk within pMMO, and one such site successfully modeled into the protein manifold (Fig. 1) (10). The elucidation of the methane oxidizing site in Cu-ZSM-5, then, could potentially shed light on CH4 oxidation in pMMO. Several classes of Cux–O2 adducts demonstrate the ability to oxidize C–H bonds, but only those that are fairly weak ( 90 kcal/mol) (9, 11). The few complexes capable of oxidizing stronger C–H bonds are poorly understood, although a mixed-valent Cu–O2– CuIII core was suggested to initiate certain C–H bond abstraction reactions (9). The present contribution establishes the first specific copper-oxo structure with oxidative reactivity toward methane. With resonance-enhanced Raman (rR) spectroscopic interrogation of the Cu-ZSM-5 chromophore absorbance at 440 nm, including observation of 18Osensitive vibrations, the researchers were able to tease out the real active site, distinguishing it from the excess of spectator copper ions present. Bolstered by density functional theory (DFT) calculations and normal coordinate analysis, the spectroscopic studies conclusively determined the geometric and electronic structure of the bent CuII–O–CuII (Fig. 2) active site. Remarkably, some half-adozen variants of oxidatively capable O2or H2O2-derived complexes with the Cux–Oy(H) formula have been spectroscopically and/or structurally characterized in discrete inorganic complexes, yet none has the capacity to oxidize methane (9); and in the case of Cu-ZSM-5, the present study ruled all of them out. Complexes formulated with a CuII–O– CuII core are not entirely absent from the literature (12); however, they are not well characterized and thus far display very limited reactivity. What makes the Cu-ZSM-5 site so reactive toward C–H bonds? The first copper intermediate along the calculated reaction coordinate, a CuII–OH– CuI species, possesses a strong (90 kcal/ mol) O–H bond, making the prior C–H abstraction step from methane endo-