Cyclohexane monooxygenase

A few of the reactions carried out by the monooxygenase system of methanotrophic bacteria are summarized in Figure 2.9, and it is on account of this that methylotrophs have received attention for their technological potential (Lidstrom and Stirling 1990). An equally wide metabolic potential has also been demonstrated for cyclohexane monooxygenase, which has been shown to accomplish two broad types of reaction one in which formally nucleophilic oxygen reacts with the substrate, and... 

Itoh et al. used Cu yd-diketiminato complexes with general formula 4, and their reactivity has been described as a functional model for pMMO (particulate methane monooxygenase). Initially, the Hgands were reacted with both Cu and Cu precursors, with a variety of species formed, depending on the specific conditions employed [111, 112]. It was then shown that both Cu and Cu complexes ultimately led to bis(/z-oxo)(Cu )2 species upon reaction with O2 and H2O2, respectively. Use of these Cu complexes as the pre-catalysts for the oxidation of alkanes (cyclohexane and adamantane) in the presence of H2O2 resulted in low yields ( 20%). 

Various alkane oxidations are catalyzed by iron complexes. Such reactions are important in view of the action of non-heme iron enzymes, such as methane monooxygenase, in hydrocarbon oxidations in biological systems. For example, the oxo-bridged complex [Fe2(TPA)2(ju,-0)(ju.-0Ac)]3+ [TPA = tris(2-pyridylmethyl)-amine] catalyzes the oxidation of cyclohexane with Bu OOH. Related complexes with an Fein2(/i-0)(/i-0Ac)2 core oxidize cyclohexane or adamantane to give a mixture of alcohols and ketones.159 Less well defined systems, e.g., FeCl3-6H20/ aldehyde/AcOH/02 are similarly active.160... 

Various iron salts and mononuclear Fe or binuclear Fe complexes with a N,0 environment, biomimetic to methane monooxygenase complexes, have been applied to the oxidation of cyclohexane with various oxidants [6u,v,7a-g], but their catalytic activity is usually modest, with the exception of a hexanuclear Fe(III) compound derived from p-nitrobenzoic acid, which gives the highest total yield to Ol/One of about 30% [7a]. Moreover, most of these complexes are often unstable and very expensive. A hexanuclear heterotrimetallic Fe/Cu/Co complex bearing two Cu(p-0)2Co(p-0)2Fe cores, prepared by self-assembly, oxidizes cyclohexane with aqueous HP, with a maximum yield to Ol/One of 45%, virtually total selectivity to the two compounds, and preferred formation of cyclohexanol [7hj. The remarkable activity of the Fe/Cu/Co cluster was associated with the synergic effect of the three metals. 

While the focus of our research is to utimately activate methane to methanol, as is readily done by methane monooxygenase, we also want to understand what types of biomimics will activate higher homologues as well (C2, C3, and cycloC ). In addition, the bond dissociation energies may play an important role in our ability to activate methane at ambient temperature, since methane has the highest C-H bond dissociation energy (kcal) of all alkanes, i.e., methane(104) ethane(98) propane(96) and cyclohexane (94). 

One additional aspect is the wide spectrum of substrates which can be metabolized by the methane monooxygenase system, and some illustrative examples are given in Figure 6.1. Attention has already been drawn in Chapter 4, Section 4.3.2 to the similarity of this enzyme to that involved in the oxidation of ammonia, while the broad substrate specificity of cyclohexane oxygenase is noted again in Section 6.1.2. 

Udenfriend suggested a simple non-enzymatic system as a possible model of monooxygenase [44]. It involves an iron(II) complex with EDTA and ascorbic acid and is capable of hydroxylating aromatic compounds. Later, Hamilton found that this system was able to hydroxylate cyclohexane (however, with very low yield) and epoxidize cyclohexene [45]. Afterwards, a number of similar systems were proposed. For example, Ullrich found two models which are more effective than the Udenfriend system. One of them includes a Sn(II) phosphate complex... 

When the py-HOAc solvent system is replaced by MeCN or 3 1 MeCN/py autoxidation to 23 is observed without oxidation of hydrocarbon substrates [150]. However, added PhNHNHPh makes the system act as a hydrocarbon monooxygenase, converting cyclohexane to cyclohexanol. The proposed explanation is that the superoxo complex (DPAH)2Fe(02) formed... 

Biomimetic oxidation of cyclohexane was performed by Fish et al. in aqueous micelle system with t-butyl hydroperoxide (TBHP) and in the presence of biomimetic methane monooxygenase (MMO) enzyme complex [Fe20( 7-H20) ( )-OAc)L2] +. While in biphasic systems or in microemulsions, obtained by vigorous stirring, the reaction did not occur, the use of cetyltrimethylammonium hydrogensulfate (CTAHS) accelerated the reaction up to the rate observed in acetonitrile. Monti and collaborators developed another biomimetic system related to cytochrome P450, based on a porphyrin derivative, and successfully used it for the... 

The enzymatic oxidation of alkanes to produce alcohols is a simplified version of the reactions that produce the adrenocortical steroid hormones. In the biosynthesis of corticosterone from progesterone (Section 4-7), two such oxidations take place successively (a, b). It is thought that the monooxygenase enzymes act as complex oxygen-atom donors in these reactions. A suggested mechanism, as applied to cyclohexane, consists of the two steps shown below the biosynthesis. 

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