Nonheme iron systems

Although the [ Fe(HBpz3)(hfacac) 20] system is quite intriguing, it is unclear whether ferrous decomposition products are responsible for the observed chemistry, particularly in light of the reported reactivity properties of several less well characterized mononuclear nonheme iron systems that are capable of hydroxylating aromatic compounds (22-26). The relationship between the chemistry of these iron-based systems, such as 4 and the Gif (and modified Gif) systems (15-18) is currently unclear. 

Despite a typical substrate in the enzymatic system, protocatechuic acid was found to be oxygenated by model complexes not in organic solvents but in water. The highly selective and catalytic intradiol oxygenation of 4-fm-butylcatechol indicated that various types of catechols other than 3,5-di-fert-butylcatechol can be used as substrates in the model systems and that oxygenations by nonheme iron systems in water are attractive. The reactivity and selectivity are dependent on the substituent on catechols and pH of the solution. 

The conversion of solar energy Into chemical energy (artificial photosynthesis) may include light harvesting, charge separation, water oxidation, and water reduction [66]. High-valent nonheme iron systems have been proposed as... 

The last 20 years has seen tremendous growth in our understanding of biological and synthetic nonheme iron systems that activate dioxygen. Central to many systems is that the deavage of O2 occurs after coordination to the metal center. 

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]. 

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. 

Iron complexes or microsomal nonheme iron are undoubtedly obligatory components in the microsomal oxidation of many organic compounds mediated by hydroxyl radicals. In 1980, Cohen and Cederbaum [27] suggested that rat liver microsomes oxidized ethanol, methional, 2-keto-4-thiomethylbutyric acid, and dimethylsulfoxide via hydrogen atom abstraction by hydroxyl radicals. Then, Ingelman-Sundberg and Ekstrom [28] assumed that the hydroxylation of aniline by reconstituted microsomal cytochrome P-450 system is mediated by hydroxyl radicals formed in the superoxide-driven Fenton reaction. Similar conclusion has been made for the explanation of inhibitory effects of pyrazole and 4-methylpyrazole on the microsomal oxidation of ethanol and DMSO [29],... 

Evidence for an alternative oxidative stress protection mechanism in sulfate-reducing bacteria has begun to emerge. Table 10.1 provides data on the proteins implicated in this alternative system. All but one of these proteins contain distinctive types of nonheme iron active sites. This chapter describes recent results on three of these novel proteins DcrH, Rbo, and Rbr, all from Desulfovibrio vulgaris HUdenborough. 

The nonheme iron enzymes discussed so far in this section either utilize oxygen as a substrate or form it as a product. Other nonheme iron sites that do not bind O2 as part of their catalytic function have similar ligand environments. An example of such a system is the QFe site associated with the reaction centers of photosynthetic bacteria and with photosystem II of chloroplasts (Feher et al., 1989). 

All the internal monooxygenases that have so far been purified and characterized contain flavin coenzymes. The external hydrogen donors include reduced NAD, reduced NADP, ascorbic acid and sulfhydryl compounds. Cofactors required for the external monooxygenases are flavin, pteridine, copper, nonheme iron and heme as cytochrome P-450. In some monooxygenase reactions, enzymes and/or electron carrier systems other than monooxygenase itself are involved in the transfer of an electron or hydrogen from the external hydrogen donor to the cofactor involved. 

The biochemical importance of flavin coenzymes ap-pears to be their versatility in mediating a variety of redox processes, including electron transfer and the activation of molecular oxygen for oxygenation reactions. An especially important manifestation of their redox versatility is their ability to serve as the switch point from the two-electron processes, which predominate in cytosolic carbon metabo-lism, to the one-electron transfer processes, which predomi-nate in membrane-associated terminal electron-transfer pathways. In mammalian cells, for example, the end products of the aerobic metabolism of glucose are C02 and NADH (see chapter 13). The terminal electron-transfer pathway is a membrane-bound system of cytochromes, nonheme iron proteins, and copper-heme proteins—all one-electron acceptors that transfer electrons ultimately to 02 to produce H20 and NAD+ with the concomitant production of ATP from ADP and P . The interaction of NADH with this pathway is mediated by NADH dehydrogenase, a flavoprotein that couples the two-electron oxidation of NADH with the one-electron reductive processes of the membrane. 

A different redox system model - the model for NADH - was also described by our group. [16] As electron transfer mediators, FMN and FAD accept two electrons from NAD(P)H and transfer one electron to metal centres in heme-containing proteins, nonheme iron, or molybdenum sites. However, the transfer of electrons between reduced pyridine - dinucleotide cofactors is slow under physiological conditions and must be catalysed by enzymes. Function of these enzymes was mimicked by a modification of the cofactor by a recognition site for its counterpart and, thus, efficient electron transfer was enabled directly. Functionalised 1,4-dihydronicotinamides bearing a recognition unit for flavins were synthesised (Scheme 18). 

Aldehyde oxidase purified from maize coleoptiles is a multicomponent enzyme that contains a molybdenum cofactor, nonheme iron, and flavin adenine dinucleotide (FAD) as prosthetic groups.111 When substrate specificity of the aldehyde oxidase was tested, good activity was detected with IAAld, indole-3-aldehyde, and benzaldehyde among others. The addition of NADP and NADPH did not change the activity. In contrast, in maize endosperm, tryptophan-dependent IAA biosynthesis was dependent on an NADP/NADPH redox system, which may mean that the two tissues of maize are utilizing different pathways or different redox systems for IAA biosynthesis.112... 

Iron-sulfur systems have been intensively studied because of their relationship to nonheme iron-sulfur proteins. 

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