Cytochrome oxidation catalysts

One of the most smdied examples is the mimic of the enzyme cytochrome P-450 in the pores of a faujasite zeolite [196,204,225], The iron-phthalocyanine complex was encapsulated in the FAU supercage and is used as oxidation catalyst for the conversion of cyclohexane and cyclohexanone to adipic acid, an important intermediate in the nylon production. In this case the two step process using homogeneous catalysts could be replaced by a one step process using a heterogeneous catalyst [196]. This allowed better control of the selectivity and inhibited the auto oxidation of the active compound. In order to simulate a catalyst and the reaction conditions which are close to the enzymatic process, the so obtained catalyst was embedded in a polydimethylsiloxane membrane (mimics the phospholipid membrane in the living body) and the membrane was used to limit oxygen availability. With this catalyst alkanes were oxidized at room temperature with rates comparable to those of the enzyme [205]. 

Mn complexes are not strong oxidants and must be activated in order to become good oxidation catalysts. To mimic the catalytic cycle of heme enzymes, for which the active iron-oxo species is generated from Fe and H2O2 (peroxidase) or from Fe, a source of electrons and O2 (cytochrome P450), the activation of manganese complexes into high-valent... 

Over the last three decades it has become known that certain synthetic metalloporphyrins can also act as oxidative catalysts thus mimicking the action of cytochrome P450. Transformations concerning substrates epoxidation and hydroxylation have been widely studied [ 19,55,56]. 

Studies of the epoxidation of styrene and sulfoxidation of thioanisoles by cytochrome P450, a monooxygenase of known structure, show that the absolute stereochemistry of the reaction can be predicted by molecular dynamics calculations. Extension of this approach to other reactions, and to more complicated substrates, should provide an important step towards the rationalization of oxidative metabolism and the construction of tailor made oxidative catalysts. 

Phthalocyanine complexes within zeolites have also been prepared by the ship-in-a-bottle method (see Section 6.6), and have subsequently been investigated as selective oxidation catalysts, where their planar metal-N4 centres mimic the active sites of enzymes such as cytochrome P450, which is able to oxidize alkanes with molecular oxygen. Cobalt, iron and ruthenium phthalocyanines encapsulated within faujasitic zeolites are active for the oxidation of alkanes with oxygen sources such as iodosobenzene and hydroperoxides. Following a similar route, Balkus prepared Ru(II)-perchloro- and perfluorophthalocyanines inside zeolite X and used these composites for the selective catalytic oxidation of alkanes (tert-butylhydroperoxide). The introduction of fluorinated in place of non-fluorinated ligands increases the resistance of the complex to deactivation. 

The heme-containing cytochrome P450 catalysts that hydroxylate CH bonds and are active as epoxidation catalysts are known to be monooxygenases. They utilize molecular oxygen as a source of two electrons to catalyze oxygen insertion into a CH bond. The overall electrocatalytic cycle for the oxidation reaction is shown in Scheme... 

Why do cytochrome P450 and its synthetic models easily transfer an oxygen atom to substrates, even to the most inert ones such as alkanes, which makes them excellent oxidation catalysts for these substrates ... 

Oxidation in the Presence of Oxygen. One knows from Sakuma s experiments (102) that, contrary to what was believed previously, carefully purified cysteine in neutral solution, completely free of traces of metals, is practically not oxidized by oxygen from air. On the contrary, this oxidation is very strongly catalyzed by iron, copper, and manganese (71,102, 141,143) even if the metals present are traces. In animal tissues, the role of oxidation catalyst for cysteine is accomplished by cytochrome oxidase in the presence of cytochrome c. The action of this system on cysteine has been studied in detail by Keilin (66) and by Medes (85), and is represented by ... 

Hydroxylations of fatty acids by cytochrome P450119 compound increase in rate with chain length and show no intermolecular KE in buffer. With glycerol, the rate of reaction of lauric acid increases, and a KIE is observed. Reversible formation of a non-reactive complex of a fatty acid with the cytochrome and its isomerization to a reactive one is proposed. A tandem oxidative cyclocondensation process is reported for the synthesis of 3,4-dihydropyrimidin-2(l//)-one or -thione derivatives from primary aryl alcohols, -keto esters, and urea or thiourea in the presence of aluminium nitrate nonahydrate as oxidant catalyst. ... 

Cytochrome P-450 — an effective catalyst of the oxidation of organic compounds by peroxides. D. I. Metelitsa, Russ. Chem. Rev. (Engl. Transl), 1981, 50,1058-1073 (147). 

Section 18.2). The latest generation of such catalysts (1 in Fig. 18.17) reproduces the key features of the site (i) the proximal imidazole ligation of the heme (ii) the trisi-midazole ligation of distal Cu (iii) the Fe-Cu separation and (iv) the distal phenol covalently attached to one of the imidazoles. As a result, binding of O2 to compound 1 in its reduced (Fe Cu ) state appears to result in rapid reduction of O2 to the level of oxides (—2 oxidation state) without the need for outer-sphere electron transfer steps [Collman et ah, 2007b]. This reactivity is analogous to that of the heme/Cu site of cytochrome c oxidase (see Section 18.2). 

Only three steps of the proposed mechanism (Fig. 18.20) could not be carried out individually under stoichiometric conditions. At pH 7 and the potential-dependent part of the catalytic wave (>150 mV vs. NHE), the —30 mV/pH dependence of the turnover frequency was observed for both Ee/Cu and Cu-free (Fe-only) forms of catalysts 2, and therefore it requires two reversible electron transfer steps prior to the turnover-determining step (TDS) and one proton transfer step either prior to the TDS or as the TDS. Under these conditions, the resting state of the catalyst was determined to be ferric-aqua/Cu which was in a rapid equilibrium with the fully reduced ferrous-aqua/Cu form (the Fe - and potentials were measured to be within < 20 mV of each other, as they are in cytochrome c oxidase, resulting in a two-electron redox equilibrium). This first redox equilibrium is biased toward the catalytically inactive fully oxidized state at potentials >0.1 V, and therefore it controls the molar fraction of the catalytically active metalloporphyrin. The fully reduced ferrous-aqua/Cu form is also in a rapid equilibrium with the catalytically active 5-coordinate ferrous porphyrin. As a result of these two equilibria, at 150 mV (vs. NHE), only <0.1%... 

The PDMS-membrane-occluded FePcY was the first room temperature catalytic membrane and the first solid catalyst dispersed in dense organic polymer.169 The catalytic system mimics the cytochrome P-450 enzyme and can oxidize alkanes at room temperature with rates comparable to those of the... 

---