Showing papers on "Ferric published in 2012"

Pyochelin, a siderophore of Pseudomonas aeruginosa: Physicochemical characterization of the iron(III), copper(II) and zinc(II) complexes

Abstract: Pseudomonas aeruginosa is an opportunistic pathogen, synthesizing two major siderophores, pyoverdine (Pvd) and pyochelin (Pch), to cover its needs in iron(III). If the high affinity and specificity of Pvd toward iron(III) (pFe = 27.0) was well described in the literature, the physicochemical and coordination properties of Pch toward biologically relevant metals (Fe(III), Cu(II) or Zn(II)) have been only scarcely investigated. We report a thorough physico-chemical investigation of Pch (potentiometry, spectrophotometries, ESI/MS) that highlighted its moderate but significantly higher affinity for Fe3+ (pFe = 16.0 at p[H] 7.4) than reported previously. We also demonstrated that Pch strongly chelates divalent metals such as Zn(II) (pZn = 11.8 at p[H] 7.4) and Cu(II) (pCu = 14.9 at p[H] 7.4) and forms predominantly 1 : 2 (M2+/Pch) complexes. Kinetic studies revealed that the formation of the ferric Pch complexes proceeds through a Eigen-Wilkins dissociative ligand interchange mechanism involving two protonated species of Pch and the Fe(OH)2+ species of Fe(III). Our physico-chemical parameters supports the previous biochemical studies which proposed that siderophores are not only devoted to iron(III) shuttling but most likely display other specific biological role in the subtle metals homeostasis in microorganisms. This work also represents a step toward deciphering the role of siderophores throughout evolution.

Characterization and Evaluation of Antibacterial Activities of Chemically Synthesized Iron Oxide Nanoparticles

Abstract: The iron oxide nanoparticles have been synthesized in co-precipitation method using aqueous solution of ferric and ferrous ions with sodium salt. The synthesis of iron-oxide nanoparticles were validated by UV-Visible spectroscopy which showed higher peak at 370 nm as valid standard reference. An average size of iron oxide nanoparticle found by Diffraction Light scattering (DLS) particle size analyser, ranges approximately between 10 nm to 120 nm with mean particle size of 66 nm. The X-ray power diffraction (XRD) analysis revealed the crystallographic structure of magnetic particles. Characterization of the mean particle size and morphology of iron oxide nanoparticles confirmed that the iron oxide nanoparticles are nearly spherical and crystalline in shape. Further the antibacterial effect of iron oxide nanoparticles was evaluated against ten pathogenic bacteria which showed that the nanoparticles have moderate antibacterial activity against both Gram positive and Gram negative pathogenic bacterial strains and retains potential application in pharmaceutical and biomedical industries.

Critical conditions for ferric chloride‐induced flocculation of freshwater algae

Abstract: The effects of algae concentration, ferric chloride dose, and pH on the flocculation efficiency of the freshwater algae Chlorella zofingiensis can be understood by considering the nature of the electrostatic charges on the algae and precipitate surfaces. Two critical conditions are identified which, when met, result in flocculation efficiencies in excess of 90% for freshwater algae. First, a minimum concentration of ferric chloride is required to overcome the electrostatic stabilization of the algae and promote bridging of algae cells by hydroxide precipitates. At low algae concentrations, the minimum amount of ferric chloride required increases linearly with algae concentration, characteristic of flocculation primarily through electrostatic bridging by hydroxide precipitates. At higher algae concentrations, the minimum required concentration of ferric chloride for flocculation is independent of algae concentration, suggesting a change in the primary flocculation mechanism from bridging to sweep flocculation. Second, the algae must have a negative surface charge. Experiments and surface complexation modeling show that the surface charge of C. zofingiensis is negative above a pH of 4.0 ± 0.3 which agrees well with the minimum pH required for effective flocculation. These critical flocculation criteria can be extended to other freshwater algae to design effective flocculation systems.

Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview.

Abstract: Iron deficiency anaemia represents a major public health problem, particularly in infants, young children, pregnant women, and females with heavy menses. Oral iron supplementation is a cheap, safe, and effective means of increasing haemoglobin levels and restoring iron stores to prevent and correct iron deficiency. Many preparations are available, varying widely in dosage, formulation (quick or prolonged release), and chemical state (ferrous or ferric form). The debate over the advantages of ferrous versus ferric formulations is ongoing. In this literature review, the tolerability and efficacy of ferrous versus ferric iron formulations are evaluated. We focused on studies comparing ferrous sulphate preparations with ferric iron polymaltose complex preparations, the two predominant forms of iron used. Current data show that slow-release ferrous sulphate preparations remain the established and standard treatment of iron deficiency, irrespective of the indication, given their good bioavailability, efficacy, and acceptable tolerability demonstrated in several large clinical studies.

Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments

Abstract: Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC (59)Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without non-ferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained >90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency.

α-Synuclein expression is modulated at the translational level by iron.

Abstract: Several studies have suggested an interaction between α-synuclein protein and iron in Parkinson's disease. The presence of iron together with α-synuclein in Lewy bodies, the increase of iron in the substantia nigra and the correlation between polymorphism of the several genes implicated in iron metabolism and Parkinson's disease, support a role for iron in the neurodegeneration. Analysis of post mortem brains revealed increased amount of insoluble α-synuclein protein despite unchanged/reduced levels of α-synuclein mRNA in Parkinson's disease. Interestingly, on the basis of the presence of a putative iron responsive element in the 5'-UTR, it has been suggested that there is a possible iron-dependent translational control of human α-synuclein mRNA. Considering the similarity between the sequences present in human α-synuclein mRNA and the ferritin iron responsive element, we postulated that iron deficiency would decrease the translation of α-synuclein mRNA. Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human α-synuclein biosynthesis. We show that the amount of polysome-associated endogenous human α-synuclein mRNA decreases in presence of deferoxamine. Our data demonstrate that human α-synuclein expression is regulated by iron mainly at the translational level. This result not only supports a role for iron in the translational control of α-synuclein expression, but also suggests that iron chelation may be a valid approach to control α-synuclein levels in the brain.

Ferric, not ferrous, heme activates RNA-binding protein DGCR8 for primary microRNA processing

Abstract: The RNA-binding protein DiGeorge Critical Region 8 (DGCR8) and its partner nuclease Drosha are essential for processing of microRNA (miRNA) primary transcripts (pri-miRNAs) in animals. Previous work showed that DGCR8 forms a highly stable and active complex with ferric [Fe(III)] heme using two endogenous cysteines as axial ligands. Here we report that reduction of the heme iron to the ferrous [Fe(II)] state in DGCR8 abolishes the pri-miRNA processing activity. The reduction causes a dramatic increase in the rate of heme dissociation from DGCR8, rendering the complex labile. Electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies indicate that reduction of the heme iron is accompanied by loss of the cysteines as axial ligands. ApoDGCR8 dimers, generated through reduction and removal of the heme, show low levels of activity in pri-miRNA processing in vitro. Importantly, ferric, but not ferrous, heme restores the activity of apoDGCR8 to the level of the native ferric complex. This study demonstrates binding specificity of DGCR8 for ferric heme, provides direct biochemical evidence for ferric heme serving as an activator for miRNA maturation, and suggests that an intracellular environment increasing the availability of ferric heme may enhance the efficiency of pri-miRNA processing.

Structural Insights into the Ferroxidase Site of Ferritins from Higher Eukaryotes

Abstract: The first step of iron biomineralization mediated by ferritin is the oxidation at the ferroxidase active site of two ferrous ions to a diferric oxo/hydroxo species. Metal-loaded ferritin crystals obtained by soaking crystals of frog ferritin in FeSO(4) and CuSO(4) solutions followed by flash freezing provided X-ray crystal structures of the tripositive iron and bipositive copper adducts at 2.7 and 2.8 A resolution, respectively. At variance with the already available structures, the crystal form used in this study contains 24 independent subunits in the asymmetric unit permitting comparison between them. For the first time, the diferric species at the ferroxidase site is identified in ferritins from higher eukaryotes. Anomalous difference Fourier maps for crystals (iron crystal 1) obtained after long soaking times in FeSO(4) solution invariantly showed diferric species with a Fe-Fe average distance of 3.1 ± 0.1 A, strongly indicative of the presence of a μ-oxo/hydroxo bridge between the irons; protein ligands for each iron ion (Fe1 and Fe2) were also unequivocally identified and found to be the same in all subunits. For copper bound ferritin, dicopper(II) centers are also observed. While copper at site 1 is essentially in the same position and has the same coordination environment as Fe1, copper at site 2 is displaced toward His54, now acting as a ligand; this results in an increased intermetal distance (4.3 ± 0.4 A). His54 coordination and longer metal-metal distances might represent peculiar features of divalent cations at the ferroxidase site. This oxidation-dependent structural information may provide key features for the mechanistic pathway in ferritins from higher eukaryotes that drive uptake of bivalent cation and release of ferric products at the catalytic site. This mechanism is supported by the X-ray picture obtained after only 1 min of soaking in FeSO(4) solutions (iron crystal 2) which reasonably contain the metal at different oxidation states. Here two different di-iron species are trapped in the active site, with intermetal distances corresponding to those of the ferric dimer in crystal 1 and of the dicopper centers and corresponding rearrangement of the His54 side chain.

Microbial iron cycling in acidic geothermal springs of yellowstone national park: integrating molecular surveys, geochemical processes, and isolation of novel fe-active microorganisms.

Abstract: Geochemical, molecular, and physiological analyses of microbial isolates were combined to study the geomicrobiology of acidic iron oxide mats in Yellowstone National Park (YNP). Nineteen sampling locations from 11 geothermal springs were studied ranging in temperature from 53 to 84 °C and pH 2.4 to 3.6. All iron-oxide mats exhibited high diversity of crenarchaeal sequences from the Sulfolobales, Thermoproteales, and Desulfurococcales. The predominant Sulfolobales sequences were highly similar to Metallosphaera yellowstonensis str. MK1, previously isolated from one of these sites. Other groups of archaea were consistently associated with different types of iron oxide mats, including undescribed members of the phyla Thaumarchaeota and Euryarchaeota. Bacterial sequences were dominated by relatives of Hydrogenobaculum spp. above 65-70 °C, but increased in diversity below 60 °C. Cultivation of relevant iron-oxidizing and iron-reducing microbial isolates included Sulfolobus str. MK3, Sulfobacillus str. MK2, Acidicaldus str. MK6, and a new candidate genus in the Sulfolobales referred to as Sulfolobales str. MK5. Strains MK3 and MK5 are capable of oxidizing ferrous iron autotrophically, while strain MK2 oxidizes iron mixotrophically. Similar rates of iron oxidation were observed for M. yellowstonensis str. MK1 and Sulfolobales str. MK5 cultures, and these rates are close to those measured in situ. Biomineralized phases of ferric iron varied among cultures and field sites, and included ferric oxyhydroxides, K-jarosite, goethite, hematite, and scorodite depending on geochemical conditions. Strains MK5 and MK6 are capable of reducing ferric iron under anaerobic conditions with complex carbon sources. The combination of geochemical and molecular data as well as physiological observations of isolates suggests that the community structure of acidic Fe mats is linked with Fe cycling across temperatures ranging from 53 to 88 oC.

Novel pathway of iron‑induced blood coagulation: implications for diabetes mellitus and its complications.

Abstract: Fibrinogen (FBG) is a high-molecular-weight protein and precursor to the enzymatically formed fibrin. It has been recently discovered that FBG can be converted into an insoluble, fibrin-like polymer by a nonenzymatic action of hydroxyl radicals (HRs). These free radicals are generated due to the reaction between hydroxyl groups of water and trivalent ferric ions without the participation of any redox agent. The interaction between HRs and FBG occurs in a purified system, as well as in human plasma and in whole blood. Scanning electron microscopy (SEM) of thrombin-induced fibers and those generated with ferric chloride has shown substantial differences in their morphology and susceptibility to enzymatic degradation. Fibrin strands caused by thrombin are thick and easily digested with chymotrypsin. By contrast, the dense matted deposits formed from FBG in the presence of ferric ions are remarkably resistant to proteolytic and chemical degradations due to the presence of intermolecular hydrophobic bonds. Thus, we postulate that this iron-catalyzed reaction represents a novel blood coagulation pathway operating in degenerative diseases. By means of SEM, we showed the presence of dense fibrin-like deposits in the blood of diabetic patients. Therefore, the prothrombotic state and cardiovascular complications observed in diabetes can be explained in terms of the persistent in vivo action of free iron. This phenomenon may explain hemorheologic disturbances in patients with metabolic syndrome and other diseases caused by iron overload. Of note, HRs can be effectively scavenged by phenolic substances; therefore, certain natural polyphenolic substances, which also scavenge HRs, may be considered to have a potential antidiabetic effect. Moreover, natural or synthetic iron-binding substances may also be considered as a new class of antidiabetic drugs.

A comparative study of iron uptake mechanisms in marine microalgae: iron binding at the cell surface is a critical step.

Abstract: We investigated iron uptake mechanisms in five marine microalgae from different ecologically important phyla: the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana , the prasinophyceae Ostreococcus tauri and Micromonas pusilla , and the coccolithophore Emiliania huxleyi . Among these species, only the two diatoms were clearly able to reduce iron, via an inducible ( P. tricornutum ) or constitutive ( T. pseudonana ) ferrireductase system displaying characteristics similar to the yeast ( Saccharomyces cerevisiae ) flavohemoproteins proteins. Iron uptake mechanisms probably involve very different components according to the species, but the species we studied shared common features. Regardless of the presence and/or induction of a ferrireductase system, all the species were able to take up both ferric and ferrous iron, and iron reduction was not a prerequisite for uptake. Iron uptake decreased with increasing the affinity constants of iron-ligand complexes and with increasing ligand-iron ratios. Therefore, at least one step of the iron uptake mechanism involves a thermodynamically controlled process. Another step escapes to simple thermodynamic rules and involves specific and strong binding of ferric as well as ferrous iron at the cell surface before uptake of iron. Binding was paradoxically increased in iron-rich conditions, whereas uptake per se was induced in all species only after prolonged iron deprivation. We sought cell proteins loaded with iron following iron uptake. One such protein in O. tauri may be ferritin, and in P. tricornutum , Isip1 may be involved. We conclude that the species we studied have uptake systems for both ferric and ferrous iron, both involving specific iron binding at the cell surface.

Electronic spin states of ferric and ferrous iron in the lower-mantle silicate perovskite

Abstract: The electronic spin and valence states of iron in lower-mantle silicate perovskite have been previously investigated at high pressures using various experimental and theoretical techniques. However, experimental results and their interpretation remain highly debated. Here we have studied a well-characterized silicate perovskite starting sample [(Mg 0.9 ,Fe 0.1 )SiO 3 ] in a chemically inert Ne pressure medium at pressures up to 120 GPa using synchrotron Mossbauer spectra. Analyses of the Mossbauer spectra explicitly show a high-spin to low-spin transition of the octahedral-site Fe 3+ occurring at ~13–24 GPa, as evidenced from a significant increase in the hyperfine quadrupole splitting. Two quadrupole doublets of the A-site Fe 2+ , with extremely high-QS values of 4.1 and 3.1 mm/s, occur simultaneously with the spin transition of the octahedral-site Fe 3+ and continue to develop to 120 GPa. It is conceivable that the spin-pairing transition of the octahedral-site Fe 3+ causes a volume reduction and a change in the local atomic-site configurations that result in a significant increase of the quadrupole splitting in the dodecahedral-site Fe 2+ at 13–24 GPa. Our results here provide a coherent explanation for recent experimental and theoretical results on the spin and valence states of iron in perovskite, and assist in comprehending the effects of the spin and valence states of iron on the properties of the lower-mantle minerals.

Dioxygen Activation by a Non-Heme Iron(II) Complex: Theoretical Study toward Understanding Ferric-Superoxo Complexes.

Abstract: We present a systematic study using density functional theory (DFT) and coupled cluster (CCSD(T)) computations with an aim of characterizing a non-heme ferric-superoxo complex [(TMC)Fe(O2)](2+) (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) that was proposed to perform allylic C-H activation of cyclohexene (Lee, Y.-M. et al. J. Am. Chem. Soc.2010, 132, 10668). As such, we investigated a series of iron-O2 species without and with a sixth ligand bound to the iron ion in different O2 coordination modes (end-on and side-on) and different spin states. Most of the iron-O2 complexes were found to be iron(III)-superoxo species, Fe(III)(O2(-)), with high-spin (S = 5/2) or intermediate-spin (S = 3/2) ferric centers coupled ferromagnetically or antiferromagnetically to the superoxide anion radical. One iron(IV)-peroxo state, Fe(IV)(O2(2-)), was also examined. The preference for ferromagnetic or antiferromagnetic coupling modes between the superoxo and ferric radicals was found to depend on the FeOO angle, where a side-on tilt favors ferromagnetic coupling whereas the end-on tilt favors antiferromagnetic states. Experimental findings, e.g., the effects of solvent, spin state, and redox potential of non-heme Fe(II) complexes on O2 activation, were corroborated in this work. Solvent effects were found to disfavor O2 binding, relative to the unbound ferrous ion and O2. The potential H-abstraction reactivity of the iron(III)-superoxo species was considered in light of the recently proposed exchange-enhanced reactivity principle (Shaik, S.; Chen, H.; Janardanan, D. Nat. Chem.2011, 3, 19). It is concluded that localization and/or decoupling of an unpaired electron in the d-block of high-spin Fe(III) center in the S = 2 and 3 ferric-superoxo complexes during H abstractions enhances exchange stabilization and may be the root cause of the observed reactivity of [(TMC)Fe(O2)](2+).

A Comparison of the Biological Activities of Human Osteoblast hFOB1.19 Between Iron Excess and Iron Deficiency

Abstract: Bone metabolism has a close relationship with iron homeostasis. To examine the effects of iron excess and iron deficiency on the biological activities of osteoblast in vitro, human osteoblast cells (hFOB1.19) were incubated in a medium supplemented with 0–200 μmol/L ferric ammonium citrate and 0–20 μmol/L deferoxamine. The intracellular iron was measured by a confocal laser scanning microscope. Proliferation of osteoblasts was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apoptotic cells were detected using annexin intervention V/PI staining with a flow cytometry. Alkaline phosphatase (ALP) activity was measured using an ALP assay kit. The number of calcified nodules and mineral area was evaluated by von Kossa staining assay. The expressions of type I collagen and osteocalcin of cultured osteoblasts were detected by reverse transcriptase polymerase chain reaction and Western blot. Intracellular reactive oxygen species (ROS) was measured using the oxidation-sensitive dye 2,7-dichlorofluorescin diacetate by flow cytometry. The results indicated that excessive iron inhibited osteoblast activity in a concentration-dependent manner. Low iron concentrations, in contrast, produced a biphasic manner on osteoblasts: mild low iron promoted osteoblast activity, but serious low iron inhibited osteoblast activity. Osteogenesis was optimal in certain iron concentrations. The mechanism underlying biological activity invoked by excessive iron may be attributed to increased intracellular ROS levels.

Arsenic Removal from Water by Iron-Modified Bamboo Charcoal

Abstract: The effectiveness of a novel and low-cost adsorbent, iron-modified bamboo charcoal (BC-Fe), for arsenic removal from aqueous systems was evaluated in this study. The BC-Fe was synthesized by loading iron onto bamboo charcoal via soaking in a ferric salt solution. The BC-Fe possessed a porous structure with a surface area of 277.895 m2/g. The adsorption characteristics of arsenic onto BC-Fe were further investigated at various pHs, contact times, arsenic concentrations, and adsorbent doses in batch tests. The corresponding optimum equilibrium pH ranges for As(III) and As(V) removal were 4–5 and 3–4, respectively. The equilibrium times for As(III) and As(V) adsorption were 30 and 35.5 h, respectively. The arsenic removal was strongly dependent on the initial adsorbate concentration and adsorbent dosage. The maximum arsenic removal capacities of BC-Fe under the experimental conditions were 7.237 and 19.771 mg/g for As(III) and As(V), respectively. The pseudo-second-order kinetic model and Freundlich isotherm explained the kinetic and equilibrium of both the As(III) and As(V) adsorbent processes, respectively. Based on these results, the BC-Fe developed in this study is a promising material for the treatment of arsenic-contaminated water.