Methane monooxygenases (MMOs) mediate the facile conversion of methane into methanol in methanotrophic bacteria with high efficiency under ambient conditions. Because the selective oxidation of methane is extremely challenging, there is considerable interest in understanding how these enzymes carry out this difficult chemistry. The impetus of these efforts is to learn from the microbes to develop a biomimetic catalyst to accomplish the same chemical transformation. Here, we review the progress made over the past two to three decades toward delineating the structures and functions of the catalytic sites in two MMOs: soluble methane monooxygenase (sMMO) and particulate methane monooxygenase (pMMO). sMMO is a water-soluble three-component protein complex consisting of a hydroxylase with a nonheme diiron catalytic site; pMMO is a membrane-bound metalloenzyme with a unique tricopper cluster as the site of hydroxylation. The metal cluster in each of these MMOs harnesses O to functionalize the C-H bond using different chemistry. We highlight some of the common basic principles that they share. Finally, the development of functional models of the catalytic sites of MMOs is described. These efforts have culminated in the first successful biomimetic catalyst capable of efficient methane oxidation without overoxidation at room temperature.

Two trinuclear copper [Cu I Cu I Cu I (L)] 1؉ complexes have been prepared with the multidentate ligands (L) 3,3 -(1,4-diazepane-1,4-diyl)bis(1-((2-(dimethylamino)ethyl)(methyl)amino)propan-2-ol) (7-Me) and (3,3 -(1,4-diazepane-1,4-diyl)bis(1-((2-(diethylamino) ethyl)(ethyl) amino)propan-2-ol) (7-Et) as models for the active site of the particulate methane monooxygenase (pMMO). The ligands were designed to form the proper spatial and electronic geometry to harness a ''singlet oxene,'' according to the mechanism previously suggested by our laboratory. Consistent with the design strategy, both [Cu I Cu I Cu I (L)] 1؉ reacted with dioxygen to form a putative bis( 3-oxo)Cu II Cu II Cu III species, capable of facile O-atom insertion across the central COC bond of benzil and 2,3-butanedione at ambient temperature and pressure. These complexes also catalyze facile O-atom transfer to the COH bond of CH 3CN to form glycolonitrile. These results, together with our recent biochemical studies on pMMO, provide support for our hypothesis that the hydroxylation site of pMMO contains a trinuclear copper cluster that mediates COH bond activation by a singlet oxene mechanism. density functional theory ͉ methane monooxygenase ͉ membrane-bound or particulate methane monooxygenase ͉ soluble methane monooxygenase ͉ mass spectroscopy T here presently is considerable interest in the development of efficient catalysts for the facile conversion of methane to methanol (1). Industrially, this is a difficult process. However, two methane monooxygenases (MMO) are known to mediate this process in methanotrophic bacteria: a membrane-bound MMO called particulate MMO (pMMO) and a water-soluble form referred to as soluble MMO (sMMO) (2). pMMO is a multicopper protein (3), and sMMO is a nonheme diiron protein (4, 5). Both systems exploit metal clusters to catalyze this difficult chemistry.The pMMO is found in all methanotrophs; in contrast, the sMMO has only been isolated from certain strains of methanotrophic bacteria. As an MMO, the oxidation of the COH bond often is described by the chemical equationSeveral possible mechanisms for the catalytic function of MMO have been considered. One involves a radical mechanism, wherein an activated ''oxygen'' species abstracts a hydrogen atom from the hydrocarbon substrate, followed by radical-rebound chemistry of the alkyl radical with the ''hot'' hydroxyl radical to form product. This mechanism has been implicated for the nonheme diiron cluster at the active site of sMMO (6-8). The other mechanism suggested by our laboratory invokes oxenoid or ''singlet oxene'' insertion across the COH bond (3). Evidence for a direct insertion mechanism has been provided by the turnover chemistry mediated by pMMO (9-12). Direct insertion of a singlet oxene across a COH bond should result in facile bond closure of the COO bond after formation of the OOH bond, and the process should proceed with full retention of configuration at the carbon center oxidized.Indeed, the hydroxylation of small straight-chain alkanes (C1-C5) me...

Following recent progress towards understanding the structure of the particulate methane monooxygenase in methanotrophic bacteria, it is now possible to attempt the development of laboratory catalysts for the conversion of methane into MeOH under ambient conditions. To this end, a class of tricopper complexes that are capable of efficiently oxidizing small hydrocarbon substrates at room temperature has recently been developed. In this Minireview, we describe the development of a tricopper cluster to accomplish the catalytic conversion of methane into MeOH, as well as a number of small n‐alkanes into their corresponding alcohols and ketones, with high efficiencies. The properties of this robust catalytic system are discussed.

No abstract

Six tricopper cluster complexes of the type [CuICuICuI(L)]1+ supported by a series of multidentate ligands (L) have been developed as oxidation catalysts. These complexes are capable of mediating the facile oxygen‐atom transfer to hydrocarbon substrates like cyclohexane, benzene, and styrene (C6H12, C6H6 and C8H8) upon activation by hydrogen peroxide at room temperature. The processes are catalytic with high turnover frequencies (TOF), efficiently oxidizing the substrates to their corresponding alcohols, aldehydes, and ketones in moderate to high yields. The catalysts are robust with turnover numbers (TON) limited only by the availability of hydrogen peroxide used to drive the catalytic turnover. The TON is independent of the substrate concentration and the TOF depends linearly on the hydrogen peroxide concentration when the oxidation of the substrate mediated by the activated tricopper complex is rapid. At low substrate concentrations, the catalytic system exhibits abortive cycling resulting from competing reduction of the activated catalyst by hydrogen peroxide. This behaviour of the system is consistent with activation of the tricopper complex by hydrogen peroxide to generate a strong oxidizing intermediate capable of a facile direct “oxygen‐atom” transfer to the substrate upon formation of a transient complex between the activated catalyst and the substrate. Some substrate specificity has also been noted by varying the ligand design. These properties of the tricopper catalyst are characteristic of many enzyme systems, such as cytochrome P450, which participate in biological oxidations.