Metal clusters as ligands: substitution of Fe ions in Fe/Mo/S clusters by thiophilic Cu(I) ions to give clusters with [Cu4Mo2Fe2S8]4+ and [Cu5Mo3Fe4S11]6+ cores.
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In an attempt to delineate the capacity of aluminum (Al) to promote pro-oxidant events, several indices of oxidative stress have been determined in brains and livers of rats exposed to an Al salt, either alone or in combination with an iron (Fe) compound. Treatment with Al over a 3-wk period increased both cortical levels of glutathione (GSH) and the rates of generation of reactive oxygen species (ROS). Dosing with an Fe compound resulted in no parallel changes, and concurrent exposure to Fe together with Al prevented these elevations. Both Fe and Al dosing elevated glutamine synthetase activity in the cortex. Levels of creatine kinase, another enzyme susceptible to oxidative stress, were also elevated in cortices of Al-treated rats. These data are in contrast to the changes found in liver fractions where exposure to Fe greatly enhanced hepatic pro-oxidant events as judged by changes in all three of the test indices used. Concurrent treatment with Al did not potentiate the pro-oxidant effects of Fe in liver. Al treatment had very minor effects on hepatic parameters of oxidative events. The results suggest that the presence of Al may exert deleterious pro-oxidant changes within the brain, which may be related to induction of oxidant species. These changes are tissue-specific and appear to be independent of any promotion of pro-oxidant status induced by exogenous Fe.
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A series of sulfate, different metal promoted SO(4)(2-)/Fe(2)O(3) catalysts were prepared and investigated by means of Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS). All catalysts exhibit good catalytic activity for the electrochemical reaction of toluene with methanol assisted with a pair of porous graphite plane electrodes and chemical conversion higher than 80% was observed. In particular, molybdate promoted catalysts exhibited excellent catalytic activity.
We outline a spectroscopic method for probing the effective magnetic field B on the surface of crystals of the single molecule magnet (SMM) [(C6H15N3)6Fe8(mu3-O)2(mu2-OH)12]Br7(H2O)Br.H2O, (Fe8Br8). This technique utilizes the line shape changes in the EPR spectra of the organic radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) (g = 2.0036, single peak) adsorbed onto the sample. The temperature dependence of the EPR line shifts scale with the sample's magnetization as measured by a SQUID magnetometer. Analysis of the line shape in terms of dipolar coupling between the DPPH and the SMM molecules on the surface, yields their average dipolar distance. The method's potential for measuring the magnetization fluctuation dynamics is briefly pointed out using the SMM [Mn12O12(CH3COO)16(H2O)4].2CH3COOH.4H2O (Mn12-acetate).
The main theme of this chapter concerns the precise biochemical mechanisms involved in stages up to, and including, gastrointestinal absorption of vitamins and certain selected minerals. Essential data regarding sequential events, immediately following absorption of these micronutrients, are also included. There is reference to water-soluble vitamins that are, in general, either coenzymes in various metabolic reactions or carriers of certain biochemical groupings. In contrast, fat-soluble vitamins frequently function as integral components of cell membranes; they, too, receive ample attention. It is appropriate, nevertheless, to recognize that some minerals required in very small amounts are closely allied biochemically with particular vitamins; these specific associations are apportioned emphasis at relevant places in the text. Although predominant discussion centres on the physiological state, clinical reference is necessarily made to gastrointestinal disorders in which imbalance of vitamins and minerals consequently results in an additional detrimental impact on health.
Alcaligenes eutrophus containing intracellular poly(3-hydroxybutyrate) was recovered from fermentation broth by centrifugation and filtration after pretreatment with Al- and Fe-based coagulants. Coagulation efficiency was largely affected by pH, and the optimum pH's for cell recovery were about 4.6-5.6 for the Al-based coagulants and about 5-8 for the Fe-based coagulants. Ammonium ions that combined with metals to form complex compounds increased the coagulant requirement, and the additional requirement of coagulant was found to be proportional to the ammonium concentration. In addition, various ligands in addition to ammonium ions contained in the culture medium interfered with the coagulation reaction and increased the coagulant requirement also. The coagulant requirement increased with the cell concentration regardless of coagulant type. The polymeric coagulants such as PACS, Hi-PAX, and Ferix-3 were more effective than nonpolymeric coagulants of aluminum sulfate and ferrous sulfate. The optimum dosages of the coagulants tested were determined over a broad range of cell concentration of 20.5-210 g/L. It was observed that the energy requirement for centrifugation could be greatly reduced with cell coagulation.
Dioxygen activation by enzymes such as methane monooxygenase, ribonucleotide reductase, and fatty acid desaturases occurs at a nonheme diiron active site supported by two histidines and four carboxylates, typically involving a (peroxo)diiron(III,III) intermediate in an early step of the catalytic cycle. Biomimetic tetracarboxylatodiiron(II,II) complexes with the familiar "paddlewheel" topology comprising sterically bulky o-dixylylbenzoate ligands with pyridine, 1-methylimidazole, or THF at apical sites readily react with O(2) to afford thermally labile peroxo intermediates that can be trapped and characterized spectroscopically at low temperatures (193 K). Cryogenic stopped-flow kinetic analysis of O(2) adduct formation carried out for the three complexes reveals that dioxygen binds to the diiron(II,II) center with concentration dependences and activation parameters indicative of a direct associative pathway. The pyridine and 1-methylimidazole intermediates decay by self-decomposition. However, the THF intermediate decays much faster by oxygen transfer to added PPh(3), the kinetics of which has been studied with double mixing experiments in a cryogenic stopped-flow apparatus. The results show that the decay of the THF intermediate is kinetically controlled by the dissociation of a THF ligand, a conclusion supported by the observation of saturation kinetic behavior with respect to PPh(3), inhibition by added THF, and invariant saturation rate constants for the oxidation of various phosphines. It is proposed that the proximity of the reducing substrate to the peroxide ligand on the diiron coordination sphere facilitates the oxygen-atom transfer. This unique investigation of the reaction of an O(2) adduct of a biomimetic tetracarboxylatodiiron(II,II) complex provides a synthetic precedent for understanding the electrophilic reactivity of like adducts in the active sties of nonheme diiron enzymes.
Mechanistic and energetic aspects for the conversion of camphor to 5-exo-hydroxycamphor by the compound I iron-oxo species of cytochrome P450 are discussed from B3LYP DFT calculations. This reaction occurs in a two-step manner along the lines that the oxygen rebound mechanism suggests. The activation energy for the first transition state of the H atom abstraction at the C5 atom of camphor is computed to be more than 20 kcal/mol. This H atom abstraction is the rate-determining step in this hydroxylation reaction, leading to a reaction intermediate that involves a carbon radical species and the iron-hydroxo species. The second transition state of the rebound step that connects the reaction intermediate and the product alcohol complex lies a few kcal/mol below that for the H atom abstraction on the doublet and quartet potential energy surfaces. This energetic feature allows the virtually barrierless recombination in both spin states, being consistent with experimentally observed high stereoselectivity and brief lifetimes of the reaction intermediate. The overall energetic profile of the catalytic mechanism of camphor hydroxylation particularly with respect to why the high activation energy for the H atom abstraction is accessible under physiological conditions is also considered and calculated. According to a proton source model involving Thr252, Asp251, and two solvent water molecules (Biochemistry 1998, 37, 9211), the energetics for the conversion of the iron-peroxo species to compound I is studied. A significant energy over 50 kcal/mol is released in the course of this dioxygen activation process. The energy released in this chemical process is an important driving force in alkane hydroxylation by cytochrome P450. This energy is used for the access to the high activation energy for the H atom abstraction.
Iron is an essential element for nearly all organisms. In mammals, iron is transported to body tissues by the serum glycoprotein transferrin. Transferrin-iron is internalized by binding to specific receptors followed by endocytosis. In vitro, Neisseria meningitidis and Neisseria gonorrhoeae can use iron from a variety of iron-containing compounds, including human transferrin. In vivo, transferrin is an important source of iron for N. gonorrhoeae: a mutant that is unable to bind and use transferrin-iron is unable to colonize the urethra of men or initiate disease at this site. As pathogenic Neisseria and its human host derive much of their iron from transferrin, we reasoned that a competition may exist between microbe and host epithelial cells for transferrin-iron at certain stages of infection. We therefore tested the hypothesis that N. meningitidis and N. gonorrhoeae may actively interfere with host transferrin-iron metabolism. We report that Neisseria-infected human epithelial cells have reduced levels of transferrin receptor messenger RNA and cycling transferrin receptors. The ability of infected cells to internalize transferrin receptor is also reduced. Finally, the relative distribution of surface and cycling transferrin receptors is altered in an infected cell. We conclude that Neisseria infection alters epithelial cell transferrin-iron homeostasis at multiple levels.
Ferritins play an essential role in iron homeostasis by sequestering iron in a bioavailable and non-toxic form. In plants, ferritin mRNAs are highly and quickly accumulated in response to iron overload. Such accumulation leads to a subsequent ferritin protein synthesis and iron storage, thus avoiding oxidative stress to take place. By combining pharmacological and imaging approaches in an Arabidopsis cell culture system, we have identified several elements in the signal transduction pathway leading to the increase of AtFer1 transcript level after iron treatment. Nitric oxide quickly accumulates in the plastids after iron treatment. This compound acts downstream of iron and upstream of a PP2A-type phosphatase to promote an increase of AtFer1 mRNA level. The AtFer1 gene transcription has been previously shown to be repressed under low iron conditions with the involvement of the cis-acting element iron-dependent regulatory sequence identified within the AtFer1 promoter sequence. We show here that the repressor is unlikely a transcription factor directly bound to the iron-dependent regulatory sequence; such a repressor is ubiquitinated upon iron treatment and subsequently degraded through a 26 S proteasome-dependent pathway.
NaFe(III)EDTA is a promising iron (Fe) compound for food fortification programs because of its high Fe bioavailability from meals containing dietary inhibitors of Fe absorption such as phytic acid. However, this Fe compound is not currently used in any large-scale fortification program because of concern over its possible negative influence on the metabolism of other essential minerals or its possible influence on the absorption of potentially toxic elements, such as manganese (Mn). In this study, Mn absorption and urinary excretion were studied in adults after intake of an Fe-fortified weaning cereal labeled with 54Mn. In a crossover design, the fortification of the weaning cereal with Fe as NaFeEDTA was compared with ferrous sulfate. Manganese absorption was measured by extrapolation from whole-body retention data 10-30 d after intake, and urinary excretion of 54Mn was measured over 7 d. No significant differences in 54Mn absorption or urinary excretion were found; 1.1 +/- 0.15 and 0.91 +/- 0.35% of the ingested dose was absorbed from the cereal fortified with NaFe(III)EDTA and FeSO4, respectively. Urinary excretion of 54Mn was very low; the total radioactivity in urine represented 1.1 +/- 0.55% of the absorbed dose with NaFe(III)EDTA and 0.72 +/- 0.53% of the absorbed dose with FeSO4. Until now, Fe-fortification programs have met with only limited success. The introduction of NaFeEDTA as a food fortificant could be a useful tool to provide bioavailable Fe to vulnerable groups in the population and thus aid in combating Fe deficiency.
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