Iron complexes biological systems

Iron as a cofactor in catalysis is receiving increasing attention. The most common oxidation states of iron are Fe2+ and Fe3+. Iron complexes are nearly all octahedral, and practically all are paramagnetic (as a result of unpaired electrons in the 3d orbital). The most common form of iron in biological systems is heme. Heme groups (Fe2+) and hema-tin (Fe3+) most frequently involve a complex with protoporphyrin IX (fig. 10.19). They are the coenzymes (prosthetic... 

Fe-4S] + + clusters are certainly the most ubiquitous iron-sulfur centers in biological systems. They play the role of low potential redox centers in ferredoxins, membrane-bound complexes of the respiratory... 

Iron is an essential element for the proper function of nearly all known biological systems. In living organism, iron is generally stored in the center of metallopro-teins, most important is the incorporation into heme complexes. These complexes... 

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. 

The identification and quantification of potentially cytotoxic carbonyl compounds (e.g. aldehydes such as pentanal, hexanal, traw-2-octenal and 4-hydroxy-/mAW-2-nonenal, and ketones such as propan- and hexan-2-ones) also serves as a useful marker of the oxidative deterioration of PUFAs in isolated biological samples and chemical model systems. One method developed utilizes HPLC coupled with spectrophotometric detection and involves precolumn derivatization of peroxidized PUFA-derived aldehydes and alternative carbonyl compounds with 2,4-DNPH followed by separation of the resulting chromophoric 2,4-dinitrophenylhydrazones on a reversed-phase column and spectrophotometric detection at a wavelength of378 nm. This method has a relatively high level of sensitivity, and has been successfully applied to the analysis of such products in rat hepatocytes and rat liver microsomal suspensions stimulated with carbon tetrachloride or ADP-iron complexes (Poli etui., 1985). 

Iron or copper complexes will catalyse Fenton chemistry only if two conditions are met simultaneously, namely that the ferric complex can be reduced and that the ferrous complex has an oxidation potential such that it can transfer an electron to H2O2. However, we must also add that this reasoning supposes that we are under standard conditions and at equilibrium, which is rarely the case for biological systems. A simple example will illustrate the problem whereas under standard conditions reaction (2) has a redox potential of —330 mV (at an O2 concentration of 1 atmosphere), in vivo with [O2] = 3.5 x 10 5 M and [O2 ] = 10 11 M the redox potential is +230 mV (Pierre and Fontecave, 1999). 

As mentioned previously, siderophores must selectively bind iron tightly in order to solubilize the metal ion and prevent hydrolysis, as well as effectively compete with other chelators in the system. The following discussion will address in more detail the effect of siderophore structure on the thermodynamics of iron binding, as well as different methods for measuring and comparing iron-siderophore complex stability. The redox potentials of the ferri-siderophore complexes will also be addressed, as ferri-siderophore reduction may be important in the iron uptake process in biological systems. 

This variation in complex stability with change in pH is particularly important in the context of biological systems, as it can potentially play a role in the iron uptake mechanism of some organisms. In some cases, the iron-siderophore complex is taken... 

Another factor that can possibly affect the redox potential in biological systems is the presence of secondary chelating agents that can participate in coupled equilibria (3). When other chelators are present, coupled equilibria involving iron-siderophore redox occur and a secondary ligand will cause the siderophore complex effective redox potential to shift. The decrease in stability of the iron-siderophore complex upon reduction results in a more facile release of the iron. Upon release, the iron(II) is available for complexation by the secondary ligand, which results in a corresponding shift in the redox equilibrium toward production of iron(II). In cases where iron(II) is stabilized by the secondary chelators, there is a shift in the redox potential to more positive values, as shown in Eqs. (42)—(45). 

While studying the formation kinetics of complexes gives useful mechanistic information about the reactivity of the iron center when bound to a particular siderophore, it is not necessarily a good model for how environmental iron will react in the siderophore system of interest. In biological systems,... 

Metal complexes, especially involving transition metals, are known for their role as catalysts in a broad variety of chemical processes including isomerization, oxidization, hydrogenation, and polymerization. Such catalytic reactions play an important role not only in many industrial processes, such as petroleum and polymer industries, but also in many biological systems, e.g., a variety of selective oxidation catalysts with heme (1) and nonheme (2) iron centers. The transition metals in these systems usually constitute a fundamental part of the catalyst, due to their... 

Unfortunately, the iron complexes of both chelators desferal and LI are able to catalyze the formation of oxygen radicals [394,395]. Cragg et al. [395] also showed that LI exposure markedly enhanced free radical-mediated DNA damage in iron-loaded liver cells. It has been suggested that the prooxidantrantioxidant ratio of LI activity depends on the composition of complexes formed a 1 3 Fe/Ll is supposed to be inactive in the production of free radicals while the generation of radicals is possible at lower Fe/Ll ratios [395], But it should be noted that in real biological systems there is always equilibrium between iron-chelator complexes of different composition. 

Despite intense study of the chemical reactivity of the inorganic NO donor SNP with a number of electrophiles and nucleophiles (in particular thiols), the mechanism of NO release from this drug also remains incompletely understood. In biological systems, both enzymatic and non-enzymatic pathways appear to be involved [28]. Nitric oxide release is thought to be preceded by a one-electron reduction step followed by release of cyanide, and an inner-sphere charge transfer reaction between the ni-trosonium ion (NO+) and the ferrous iron (Fe2+). Upon addition of SNP to tissues, formation of iron nitrosyl complexes, which are in equilibrium with S-nitrosothiols, has been observed. A membrane-bound enzyme may be involved in the generation of NO from SNP in vascular tissue [35], but the exact nature of this reducing activity is unknown. 

---