Nonheme iron

Iron-containing proteias are classified as either heme proteias or nonheme iron proteias. The former contain iron that is coordinated to a porphyrin... 

Iron Absorption. A very important effect of ascorbic acid is the enhancement of absorption of nonheme iron from foods. Ascorbic acid also enhances the reduction of ferric iron to ferrous iron. This is important both in increasing iron absorption and in its function in many hydroxylation reactions (140,141). In addition, ascorbic acid is involved in iron metaboHsm. It serves to transfer iron to the Hver and to incorporate it into ferritin. 

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

N-Heterocycles as ligands in dioxygen activation by enzymes containing binuclear nonheme iron clusters 96CRV2625. 

Scheme 9.38 Trichlorination of leucine with enzymes from the barbamide biosynthesis pathway (BarBl. BarB2 represent nonheme iron ketoglutarate-dependent halogenases).

Rieske, J. S. In Nonheme Iron Proteins Role in Energy Conservation San Pietro, E., Ed. The Antioch Press Yellow Springs, OH, 1965, 461-468. 

The protein from D. desulfuricans has been characterized by Mbss-bauer and EPR spectroscopy 224). The enzyme has a molecular mass of approximately 150 kDa (three different subunits 88, 29, and 16 kDa) and contains three different types of redox-active centers four c-type hemes, nonheme iron arranged as two [4Fe-4S] centers, and a molybdopterin site (Mo-bound to two MGD). Selenium was also chemically detected. The enzyme specific activity is 78 units per mg of protein. 

An additional component is the iron-sulfur protein (FeS nonheme iron) (Figure 12-6). It is associated with the flavoproteins (metallofiavoproteins) and with cytochrome b. The sulfur and iron are thought to take part in the oxidoreduction mechanism between flavin and Q, which involves only a single e change, the iron atom undergoing oxidoreduction between Fe " and Fe k... 

In addition, also nonheme iron catalysts containing BPMEN 1 and TPA 2 as ligands are known to activate hydrogen peroxide for the epoxidation of olefins (Scheme 1) [20-26]. More recently, especially Que and coworkers were able to improve the catalyst productivity to nearly quantitative conversion of the alkene by using an acetonitrile/acetic acid solution [27-29]. The carboxylic acid is required to increase the efficiency of the reaction and the epoxide/diol product ratio. The competitive dihydroxylation reaction suggested the participation of different active species in these oxidations (Scheme 2). 

The addition of acetic acid (0.5 equiv. to the substrate) to the catalyst system led to increased activity (doubling of yield) by maintaining the selectivity with 1.2 equiv. H2O2 as terminal oxidant. Advantageously, the system is characterized by a certain tolerance towards functional groups such as amides, esters, ethers, and carbonates. An improvement in conversions and selectivities by a slow addition protocol was shown recently [102]. For the first time, a nonheme iron catalyst system is able to oxidize tertiary C-H bonds in a synthetic applicable and selective manner and therefore should allow for synthetic applications [103]. 

Recently, Nam, Fukuzumi, and coworkers succeed in an iron-catalyzed oxidation of alkanes using Ce(IV) and water. Here, the generation of the reactive nonheme iron (IV) 0x0 complex is proposed, which subsequently oxidized the respective alkane (Scheme 16) [104]. With the corresponding iron(II) complex of the pentadentate ligand 31, it was possible to achieve oxidation of ethylbenzene to acetophenone (9 TON). 0 labeling studies indicated that water is the oxygen source. 

Scheme 21 Hydroxylation of benzene to phenol with nonheme iron complex 35 [142]...

In addition to nonheme iron complexes also heme systems are able to catalyze the oxidation of benzene. For example, porphyrin-like phthalocyanine structures were employed to benzene oxidation (see also alkane hydroxylation) [129], Mechanistic investigations of this t3 pe of reactions were carried out amongst others by Nam and coworkers resulting in similar conclusions like in the nonheme case [130], More recently, Sorokin reported a remarkable biological aromatic oxidation, which occurred via formation of benzene oxide and involves an NIH shift. Here, phenol is obtained with a TON of 11 at r.t. with 0.24 mol% of the catalyst. 

In the field of nonheme iron complexes, Miinck, Collins, and Kinoshita reported the oxidation of benzylic alcohols via stable p-oxo-bridged diiron(IV) TAME complexes, which are formed by the reaction of iron-28 complexes with molecular oxygen (Scheme 23) [142]. 

Subramanian V, CS Vaidyanathan (1984) Anthranilate hydroxylase from Aspergillus niger new type of NADPH-linked nonheme iron monooxygenase. J Bacteriol 160 651-655. 

The alkane hydroxylase belongs to a family of nonheme iron oxygenases. There is some structural similarity between the nucleotide sequence of the integral membrane alkane hydroxylase and... 

Rosche B, B Tshisuaka, B Hauer, F Lingens, S Fetzner (1997) 2-Oxo-l,2-dihydroquinoline 8-monooxygen-ase phylogenetic relationship to other multicomponent nonheme iron oxygenases. J Bacterial 179 3549-3554. 

The selenate reductase from Enterobacter cloacae SLDla-1 functions only under aerobic conditions, and is not able to serve as an electron acceptor for anaerobic growth, in contrast to the periplasmic enzyme from Thauera selenatis (Schroder et al. 1997). In E. cloacae there are separate nitrate and selenate reductases, both of which are membrane-bound. The selenate reductase is able to reduce chlorate and bromate though not nitrate, contains Mo, heme and nonheme iron, and consists of three subunits in an a3p3y3 configuration. 

The alkane hydroxylase belongs to a family of nonheme iron oxygenases. There is some structural similarity between the nucleotide sequence of the integral-membrane alkane hydroxylase and the subunits of the monooxygenase encoded by xylA and xylM in the TOL plasmid that are involved in hydrox-ylation of the methyl groups in toluene and xylene in Pseudomonas putida PaWl (Suzuki et al. 1991). 

The general influence of covalency can be qualitatively explained in a very basic MO scheme. For example, we may consider the p-oxo Fe(III) dimers that are encountered in inorganic complexes and nonheme iron proteins, such as ribonucleotide reductase. In spite of a half-filled crystal-field model), the ferric high-spin ions show quadrupole splittings as large as 2.45 mm s < 0, 5 = 0.53 mm s 4.2-77 K) [61, 62]. This is explained... 

An interesting example of a spin-admixed nonheme iron(lll) complex with S - (3/2, 5/2) ground state is the organometallic anion [Fe CeCls) which has four pentachloro phenyl ligands in tetrahedrally distorted planar symmetry [122]. 

The enzymatic reactions of peroxidases and oxygenases involve a two-electron oxidation of iron(III) and the formation of highly reactive [Fe O] " species with a formal oxidation state of +V. Direct (spectroscopic) evidence of the formation of a genuine iron(V) compound is elusive because of the short life times of the reactive intermediates [173, 174]. These species have been safely inferred from enzymatic considerations as the active oxidants for several oxidation reactions catalyzed by nonheme iron centers with innocent, that is, redox-inactive, ligands [175]. This conclusion is different from those known for heme peroxidases and oxygenases... 

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