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Formation of superoxide radicals after FeCl3 injection into rat isocortex.

Subpial injection of aqueous solutions of iron salts into rat isocortex induces recurrent epileptiform discharges with focal brain edema, cavitary necrosis and gliosis. Since aqueous iron or heme compounds cause peroxidation of lipids, we studied the sequence of changes in the formation of free radicals, and superoxide radicals, in rat isocortex injected with 5 microliter of 100 mM FeCl3. Electron spin resonance measurements of whole rat brain showed a transient increase in heme-bound Fe3+. Superoxide radicals were increased in a cylinder of tissue obtained at the injection site 5 min and 15 min after completion of the injection. This study shows that iron salts injected into rat isocortex cause transient formation of free radicals. We suggest that decompartmentalization of iron compounds may be of importance in trauma-related brain injury responses.

Animals↗

New class of steroidal alkaloids from Fritillaria imperialis.

Two members of a new class of C-nor-D-homo steroidal alkaloids, impranine (1). and dihydroimpranine (2). along with a new pyridyl-pregnane-type steroidal alkaloid, fetisinine (3). and a known base, korsevine (4). were isolated from the bulbs of Fritillaria imperialis. The structures of the compounds were established on the basis of spectroscopic techniques and some chemical transformations. Compounds 1 and 2 form a new class of steroidal alkaloids, named as "impranane."

Alkaloids↗

Long-range magnetic ordering in iron jarosites prepared by redox-based hydrothermal methods.

The iron jarosites, plumbojarosite, Pb0.5Fe3(OH)6(SO4)2, argentojarosite, AgFe3(OH)6(SO4)2, and thallium jarosite, TlFe3(OH)6(SO4)2, along with the selenate-capped jarosite analogues of potassium, KFe3(OH)6(SeO4)2, and rubidium, RbFe3(OH)6(SeO4)2, have been prepared in their analytically pure forms by employing redox-based hydrothermal methods. The crystal structures of these materials have been determined, and all are found to be essentially isostructrual including Pb0.5Fe3(OH)6(SO4)2, which is distinct from the structure reported for naturally mined samples. All iron jarosites show long-range order (LRO), signified by a sharp transition temperature, T(N), which falls in the narrow temperature range of 61.4 +/- 5 K. The mechanism responsible for this ordering has been established by examining magnetostructural correlations for the jarosites possessing various interlayer cation and capping groups. We show that all magnetic properties of jarosites, including LRO, find their origin in the basic magnetic unit, the intralayer Fe3(mu-OH)3 triangle. Field-dependent magnetization experiments are consistent with the antiferromagnetic stacking of an out of plane moment developed from spin canting within Fe3(mu-OH)3 triangles. Together with the previously reported AFe3(OH)6(SO4)2 (A = Na+, K+, Rb+ and NH4+) jarosites, these compounds provide a framework for probing magnetic ordering in a spin frustrated lattice of the largest series of isoelectronic and isostructural kagomé systems yet discovered.

Ferric Compounds↗

Comparison of the binding and reactivity of plant and mammalian peroxidases to indole derivatives by computational docking.

The oxidation of melatonin by the mammalian myeloperoxidase (MPO) provides protection against the damaging effects of reactive oxygen species. Indole derivatives, such as melatonin and serotonin, are also substrates of the plant horseradish peroxidase (HRP), but this enzyme exhibits remarkable differences from MPO in the specificity and reaction rates for these compounds. A structural understanding of the determinants of the reactivity of these enzymes to indole derivatives would greatly aid their exploitation for biosynthetic and drug design applications. Consequently, after validation of the docking procedure, we performed computational docking of melatonin and serotonin to structural models of the ferric and compound I and II (co I and co II, respectively) states of HRP and MPO. The substrates dock at the heme edge on the distal side, but with different orientations in the two proteins. The distal cavity is larger in MPO than in HRP; however, in MPO, the substrates make closer contacts with the heme involving ring stacking, whereas in HRP, no ring stacking is observed. The observed differences in substrate binding may contribute to the higher reaction rates and lower substrate specificity of MPO relative to those of HRP. The docking results, along with the previously measured heme-protein reduction potentials, suggest that the differentially lowered reaction rates of co II of HRP and MPO with respect to those of co I could stem from as yet undetermined conformational or electrostatic differences between the co I and co II states of MPO, which are absent in HRP.

Animals↗

Toxicological profile, current use, and regulatory issues on EDTA compounds for assessing use of sodium iron EDTA for food fortification.

The U.S. Food and Drug Administration (FDA) has approved the use of disodium and calcium disodium ethylenediaminetetraacetate (EDTA) for direct addition to food. The international nutrition community is interested in obtaining approval for the use of sodium iron(III) EDTA (NaFeEDTA) for dietary iron fortification because of its high iron bioavailability, its enhancement of intrinsic food iron uptake, and its stability under storage and food preparation conditions. A major concern in the United States has been the presumed extensive use of EDTA in the American food supply. Recently, an update of the estimated exposure to EDTA suggests that the exposure is much lower than previously assumed. This reduction may allow new uses of NaFeEDTA in food. The following issues are discussed in relation to the possible use of NaFeEDTA: toxicological profile of EDTA compounds, acceptable daily intake of EDTA, and estimated daily intake of EDTA in the United States.

Edetic Acid↗

Hydroperoxidase activities of ferrihemes: heme analogues of peroxidase enzyme intermediates.

By reaction of deuteroferriheme (DFH) with peroxo acids, spectroscopically distinct and peroxidatically active deuteroferriheme-peroxide compounds (DPC) are formed. These species closely resemble, and are probably identical with, the species formed by reaction of DFH with H2O2, which has previously been considered to be an analogue of peroxidase compound I. Stopped-flow spectrophotometric titration studies imply: (a) that DPC is formed by reaction of 1.9 +/- 0.2 mol of DFH with 1 mol of peroxo acid; (b) that the spectral change accompanying formation of DPC is independent of the peroxo acid oxidant used. Titration of the oxidizing power of DPC formed with H2O2 implies that submaximal yields of DPC are obtained, a result that could implicate DPC species as analogues of catalase compound I in the catalase action of ferrihemes. Preliminary results suggest that DPC may involve both monomeric and dimeric heme components.

Catalase↗

Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2-hydroxy estradiol.

Catechol estrogens, 2-hydroxy estrone, 2-hydroxy estradiol and 2-hydroxy estriol, were tested as possible antioxidants of phospholipid peroxidation induced by Fe3+-ADP-adriamycin, using phospholipid liposomes as lipid source and alpha-tocopherol or other steroids as reference compounds. The parameters of antioxidant activities were: elongation of induction period, inhibition of O2 consumption required for lipid peroxidation and inhibition of peroxidative cleavage of unsaturated phospholipid. Of the tested compounds, 2-hydroxy estradiol or 2-hydroxy estrone had more potent activity than that of tocopherol.

Adenosine Diphosphate↗

Geobacter hydrogenophilus, Geobacter chapellei and Geobacter grbiciae, three new, strictly anaerobic, dissimilatory Fe(III)-reducers.

Recent studies on the diversity and ubiquity of Fe(III)-reducing organisms in different environments led to the isolation and identification of four new dissimilatory Fe(III)-reducers (strains H-2T, 172T, TACP-2T and TACP-5). All four isolates are non-motile, Gram-negative, freshwater, mesophilic, strict anaerobes with morphology identical to that of Geobacter metallireducens strain GS-15T. Analysis of the 16S rRNA sequences indicated that the new isolates belong to the genus Geobacter, in the delta-Proteobacteria. Significant differences in phenotypic characteristics, DNA-DNA homology and G+C content indicated that the four isolates represent three new species of the genus. The names Geobacter hydrogenophilus sp. nov. (strain H-2T), Geobacter chapellei sp. nov. (strain 172T) and Geobacter grbiciae sp. nov. (strains TACP-2T and TACP-5) are proposed. Geobacter hydrogenophilus and Geobacter chapellei were isolated from a petroleum-contaminated aquifer and a pristine, deep, subsurface aquifer, respectively. Geobacter grbiciae was isolated from aquatic sediments. All of the isolates can obtain energy for growth by coupling the oxidation of acetate to the reduction of Fe(III). The four isolates also coupled Fe(III) reduction to the oxidation of other simple, volatile fatty acids. In addition, Geobacter hydrogenophilus and Geobacter grbiciae were able to oxidize aromatic compounds such as benzoate, whilst Geobacter grbiciae was also able to use the monoaromatic hydrocarbon toluene.

Base Composition↗

Lack of production of electron-shuttling compounds or solubilization of Fe(III) during reduction of insoluble Fe(III) oxide by Geobacter metallireducens.

Studies with the dissimilatory Fe(III)-reducing microorganism Geobacter metallireducens demonstrated that the common technique of separating Fe(III)-reducing microorganisms and Fe(III) oxides with semipermeable membranes in order to determine whether the Fe(III) reducers release electron-shuttling compounds and/or Fe(III) chelators is invalid. This raised doubts about the mechanisms for Fe(III) oxide reduction by this organism. However, several experimental approaches indicated that G. metallireducens does not release electron-shuttling compounds and does not significantly solubilize Fe(III) during Fe(III) oxide reduction. These results suggest that G. metallireducens directly reduces insoluble Fe(III) oxide.

Deltaproteobacteria↗

Preparation and initial characterization of the compound I, II, and III states of iron methylchlorin-reconstituted horseradish peroxidase and myoglobin: models for key intermediates in iron chlorin enzymes.

To better understand the spectral properties of high valent and oxyferrous states in naturally occurring iron chlorin-containing proteins, we have prepared the oxoferryl compound I derivative of iron methylchlorin-reconstituted horseradish peroxidase (MeChl-HRP) and the compound II and oxyferrous compound III states of iron MeChl-reconstituted myoglobin. Initial spectral characterization has been carried out with UV-visible absorption and magnetic circular dichroism. In addition, the peroxidase activity of iron MeChl-HRP in pyrogallol oxidation has been found to be 40% of the rate for native HRP. Previous studies of oxoferryl chlorins have employed tetraphenylchlorins in organic solvents at low temperatures; stable oxyferrous chlorins have not been previously examined. The present study describes the compound I, II, and III states of histidine-ligated iron chlorins in a protein environment for the first time.

Animals↗

Preparation of nanomagnetic absorbent for partition coefficient measurement.

In this paper, we report a new method based on supercritical carbon dioxide (scCO(2)) to fill and distribute the porous magnetic nanoparticles with n-octanol in a homogeneous manner. The high solubility of n-octanol in scCO(2) and high diffusivity and permeability of the fluid allow efficient delivery of n-octanol into the porous magnetic nanoparticles. Thus, the n-octanol-loaded magnetic nanoparticles can be readily dispersed into aqueous buffer (pH 7.40) to form a homogenous suspension consisting of nano-sized n-octanol droplets. We refer this suspension as the n-octanol stock solution. The n-octanol stock solution is then mixed with bulk aqueous phase (pH 7.40) containing an organic compound prior to magnetic separation. The small-size of the particles and the efficient mixing enable a rapid establishment of the partition equilibrium of the organic compound between the solid supported n-octanol nano-droplets and the bulk aqueous phase. UV-vis spectrophotometry is then applied to determine the concentration of the organic compound in the aqueous phase both before and after partitioning (after magnetic separation). As a result, logD values of organic compounds of pharmaceutical interest determined by this modified method are found to be in excellent agreement with the literature data.

1-Octanol↗

[Dynamics of changes in the electroretinogram of isolated frog and turtle retinas during rhythmic photic stimulation in conditions of induced lipid peroxidation].

Comparative study of isolated retinas of frogs and turtles exposed to rhythmical photostimulation was conducted. It was shown that there are marked differences between the responses of isolated retinas of frogs and turtles to the rhythmical photostimulation. A considerable depression of the total amplitude of the rhythmical electroretinogram was observed under the conditions of induced lipid peroxidation. Introduction of a selenium compound to the superfusing medium increased to a certain extent both the single and rhythmical responses of isolated retinas of the animals.

Animals↗

The effect of pH on yields of hydroxyl radicals produced from superoxide by potential biological iron chelators.

The efficiency of conversion of superoxide to hydroxyl radicals was measured by determining the yields of fluorescent hydroxybenzoates. A variety of iron-containing catalysts were tested. Citrate was the only organic salt which showed catalytic activity at neutral pH. Adenine nucleotides had little or no activity under similar conditions. Heme proteins were inactive and any catalytic activity measured with transferrin, lactoferrin, and conalbumin could be explained by free Fe3+ released by the former two at acid pH. Many of the potential catalysts tested showed maximum activity near pH 4.8, where the rate of dismutation of O2-. is highest. This suggests that in most systems the rate-controlling step in the superoxide-driven Fenton process was the formation of H2O2. It was concluded that, with the exception of citrate, none of the biological compounds tested were able to assist the conversion of O2-. to HO. with significant efficiency at neutral pH in homogeneous solutions.

Benzoates↗

Eta4-pyrone iron(0)carbonyl complexes as effective CO-releasing molecules (CO-RMs).

The CO-releasing properties of iron(0)tricarbonyl complexes bearing a 2-pyrone ligand have been evaluated. In this report, we demonstrate that the intrinsic stability of the (eta4-2-pyrone)Fe(CO)3 complex influences the extent and rate of CO release, which is affected by the presence of a halogen substituent on the 2-pyrone ring. The cell viability index has been highlighted for the active carbon monoxide-releasing molecules (CO-RMs), demonstrating that these complexes and related derivatives are a promising new class of compounds with potential therapeutic applications.

Animals↗

Metal complexes of the trans-influencing ligand thiomaltol.

The wide use of the ligand 3-hydroxy-2-methyl-4-pyrone (maltol) in bioinorganic chemistry has prompted an effort to further exploit this ligand class by achieving an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol). Complexes of thiomaltol with nickel(II) and iron(III) have been prepared and studied by using UV-visible spectroscopy and electrochemical methods. In addition, both complexes as well as the free thiomaltol ligand have been structurally characterized by using single-crystal X-ray diffraction methods. The ligand is found to exert a strong trans influence on the structure of the complexes in the solid state with the nickel(II) and iron(III) complexes demonstrating a cis and fac geometry, respectively. The compounds described here should significantly expand the scope and utility of O,S-donor ligands derived from maltol and related precursors.

Crystallography, X-Ray↗

Inhibition of acetylcholinesterase by three new pyridinium compounds and their effect on phosphonylation of the enzyme.

Three new mono-pyridinium compounds were prepared: 1-phenacyl-2-methylpyridinium chloride (1), 1-benzoylethylpyridinium chloride (2) and 1-benzoylethylpyridinium-4-aldoxime chloride (3) and assayed in vitro for their inhibitory effect on human blood acetylcholinesterase (EC 3.1.1.7, AChE). All the three compounds inhibited AChE reversibly; their binding affinity for the enzyme was compared with their protective effect (PI) on AChE phosphonylation by soman and VX. Compound 1 was found to bind to both the catalytic and the allosteric (substrate inhibition) sites of the enzyme with estimated dissociation constants of 6.9 microM (Kcat) and 27 microM (Kall), respectively. Compound 2 bound to the catalytic site with Kcat = 59 microM and compound 3 only to the allosteric site with Kall = 328 microM. PI was evaluated from phosphonylation measured in the absence and in presence of the compounds applied in a concentration corresponding to their Kcat or Kall value, and was also calculated from theoretical equations deduced from the reversible inhibition of the enzyme. Compounds 1 and 3 protected the enzyme from phosphonylation by soman and VX, whereas no protection was observed in the presence of compound 2 under the same conditions. Irrespective of the binding sites to AChE, PI for compounds 1 and 3 evaluated from phosphonylation agreed with PI calculated from reversible inhibition. Compound 3 was found to be a weak reactivator of methylphosphonylated AChE with Kr = 1.1 x 10(2) L mol-1 min-1.

Acetylcholinesterase↗

Antioxidant capacity of selected wines.

BACKGROUND: Recent studies indicate that regular consumption of red wine reduces the risk of atherosclerosis and coronary heart disease. This effect is attributed in part to the antioxidant properties of polyphenolic compounds. The purpose of our study was to examine the antioxidant potential of selected wines under in vitro conditions. MATERIAL AND METHODS: We examined the total antioxidant capacity of 10 selected wines using the recently developed FRAP method. This method measures the capacity of the antioxidants contained in the analyzed solution to reduce ferric-tripiridyltriazine (Fe3+-TPTZ) to a ferrous form (Fe2+) which absorbs light at 593 nm. RESULTS: All the analyzed wines had strong antioxidant potential in the FRAP test. Red wines demonstrated higher antioxidant capacity than white wines, and dry wines higher than sweet wines. Neither ethanol (1-100%) nor glucose had any capacity to reduce Fe3+, indicating that these substances are not responsible for the antioxidant properties of wine. Red grape juice demonstrated an antioxidant capacity similar to that of sweet wines, whereas white grape juice had no antioxidant properties. CONCLUSIONS: These results indicate that wine demonstrates antioxidant activity in vitro and that the FRAP test can be used for to analyze this activity.

Antioxidants↗