Iron Chemistry Research Articles

Use of the di-2-pyridyl ketone/3,5-di-tert-butylcatechol “blend” in iron(iii) chemistry: a cationic tetranuclear cluster and an anionic trinuclear complex

The use of di-2-pyridyl ketone ((py)2CO)/3,5-di-tert-butylcatechol (H2dbcat) “blend” in iron(III) chemistry has yielded a cationic tetranuclear cluster and an anionic trinuclear complex. Both complexes were prepared under anaerobic conditions. The Fe(ClO4)3·6H2O–(py)2CO–H2dbcat–NEt3 (1 ∶ 1 ∶ 1 ∶ 2) reaction system in MeOH gives [Fe4{(py)2C(OMe)O}2{(Hpy)(py)C(OMe)O}2(dbcat)4](ClO4)21, whereas reaction of Fe(ClO4)3·6H2O with (py)2CO, H2dbcat and NEt3 (1 ∶ 1 ∶ 1 ∶ 3) in MeCN gives (HNEt3)[Fe3{(py)2C(OH)O}2(dbcat)4]·MeCN 2·MeCN. The centrosymmetric tetranuclear cation of 1 contains a zigzag array of six-coordinate FeIII ions. The inner FeIII ions are bridged by two catecholate oxygen atoms from two η1:η2:μ2 dbcat2− groups, while one η1:η2:μ2 dbcat2− group and one η1:η2:η1:μ2 (py)2C(OMe)O− ligand bridge each inner FeIII to its outer FeIII neighbour. Each outer metal is chelated by a single bidentate (+Hpy)(py)C(OMe)O− zwitterion. The trinuclear anion of 2·MeCN consists of a triangular unit, in which the Fe2 edges are bridged by two η1:η2:μ2 and one η1:η2:μ3 dbcat2− groups, and one η1:η2:η1:μ2 (py)2C(OH)O− ligand. Two FeIII ions are six-coordinate, while the third is five-coordinate. One six-coordinate FeIII centre is chelated by a bidentate dbcat2− group and the other one by a bidentate (py)2C(OH)O− ligand. Variable-temperature magnetic susceptibility studies in the 2–300 K range reveal antiferromagnetic exchange interactions in both complexes. Variable-temperature Mossbauer spectra of 1 analyse as two quadrupole-split doublets which were assigned to the two different high-spin iron(III) sites in the complex, while those of 2 analyse as one (averaged) quadrupole-split doublet.

Seasonal variation of mesospheric iron layers at Arecibo: First results from low‐latitudes

We present the annual variation of the distribution of neutral iron of the low‐latitude mesopause region measured at the Arecibo Observatory using resonance fluorescence lidar. A comparison was made between our low‐latitude measurements and similar mid‐and high‐latitude observations of Fe column abundance, centroid height, and RMS width of the layer. We find that the annual variation of the height and width of the layer are essentially anti‐correlated with previous measurements, while the column abundance lags its midlatitude counterpart by roughly three months. We suggest that the latitudinal differences in Fe layer properties result from variations in the distribution of mesospheric ozone and O2, which in turn affect the iron chemistry at the two latitudes.

Iron speciation in eutrophic and oligotrophic Mediterranean coastal waters; impact of phytoplankton and protozoan blooms on iron distribution

Speciation, distribution and temporal differences in iron chemistry are important for understanding the biological roles of iron in marine systems. This paper presents a study of iron species in different coastal systems of the northeastern Mediterranean and the observed consequences of enrichments of coastal water by major nutrients and iron. Iron species were detected by using a serial chromatographic column method in the eutrophic inner and middle, transient and oligotrophic outer section of İzmir Bay, western Turkey. In order to understand the impact of biological activity on the distribution of Fe species in coastal systems, phytoplankton densities and POC were also measured along with other relevant biological, physical and chemical variables in surface waters at different stations and seasons in İzmir Bay. A significant decrease in iron concentration was observed in the outer bay despite of a very high iron input particularly from the sediment in shallow waters of the inner and middle bay. Average colloidal iron (ColFe) was 14±7% of the total iron that could pass a filter (<0.4 μm) (TFFe) throughout the bay water, however, Chelex column-labile Fe (ClxLFe) was significantly higher (42±25% of TFFe) and reached up to 80% of TFFe, especially in the shallow inner and middle bay. A dramatic decrease in ClxLFe was observed during the phytoplankton bloom in early April in the inner and middle bay. Hydrophobic organically complexed iron (HpOFe) and ClxLFe increased with increasing protozoan activity and collapse of phytoplankton.

Iron carbonyl, nitrosyl, and nitro complexes of a tetrapodal pentadentate amine ligand: synthesis, electronic structure, and nitrite reductase-like reactivity.

The tetrapodal pentaamine 2,6-C5H3N[CMe(CH2NH2)2]2 (pyN4, 1) forms a series of octahedral iron(II) complexes of general formula [Fe(L)(1)]Xn with a variety of small-molecule ligands L at the sixth coordination site (L = X = Br, n = 1 (2); L = CO, X = Br, n = 2 (3); L = NO, X = Br, n = 2 (4); L = NO+, X = Br, n = 3 (5); L = NO2-, X = Br, n = 1 (6)). The bromo complex, which is remarkably stable towards hydrolysis and oxidation, serves as the precursor for all other complexes, which may be obtained by ligand exchange, employing CO, NO, NOBF4, and NaNO2, respectively. All complexes have been fully characterised, including solid-state structures in most cases. Attempts to obtain single crystals of 6 produced the dinuclear complex [Fe2[mu 2-(eta 1-N: eta 1-O)-NO2](1)2]Br2PF6 (7), whose bridging NO2- unit, which is unsupported by bracketing ligands, is without precedent in the coordination chemistry of iron. Compound 2 has a high-spin electronic configuration with four unpaired electrons (S = 2), while the carbonyl complex 3 is low-spin (S = 0), as are complexes 5, 6 and 7 (S = 0 in all cases); the 19 valence electron nitrosyl complex 4 has S = 1/2. Complex 4 and its oxidation product, 5 ([Fe(NO)]7 and [Fe(NO)]6 in the Feltham-Enemark notation) may be interconverted by a one-electron redox process. Both complexes are also accessible from the mononuclear nitro complex 6: Treatment with acid produces the 18 valence electron NO+ complex 5, whereas hydrolysis in the absence of added protons (in methanolic solution) gives the 19 valence electron NO. complex 4, with formal reduction of the NO2- ligand. This reactivity mimicks the function of certain heme-dependent nitrite reductases. Density functional calculations for complexes 3, 4 and 5 provide a description of the electronic structures and are compatible with the formulation of iron(II) in all cases; this is derived from the careful analysis of the combined IR, ESR and Mössbauer spectroscopic data, as well as structural parameters.

Iron absorption: biochemical and molecular insights into the importance of iron species for intestinal uptake.

Recent advances in cloning of proteins involved in intestinal iron absorption can inform design and understanding of therapeutic iron preparations. Redox chemistry of iron is particularly important in iron metabolism, both as a potential source of toxic intermediates and as an essential requirement for efficient iron transport. The initial step in iron absorption (uptake from lumen to mucosa) is particularly important and several pathways involving Fe(III) reduction or transport and Fe(II) transport have been identified. Novel genes associated with iron uptake include Dcytb, a putative iron-regulated reductase and DMT1, a Fe(II) carrier in the brush border membrane. Other mechanisms may also operate, however. We review the recent findings and apply this to understanding the absorption of Fe(III) pharmaceuticals.

Superoxide activates constitutive nitric oxide synthase in a brain particulate fraction

Nitric oxide ( NO) can act as an antioxidant by directly scavenging reactive free radicals, inhibiting the oxidative chemistry of iron, and signaling the up-regulation of antioxidant enzymes. However, the cellular utility of NO as an antioxidant requires that constitutive nitric oxide synthase (NOS) be activated rapidly by a signal(s) for oxidant formation. We report here that superoxide (O 2 − ), added directly as potassium superoxide (KO 2), produced a superoxide dismutase-sensitive and hydrogen peroxide-independent stimulation of NOS activity, measured by the conversion of [ 3H]arginine to [ 3 H] citrulline and nitrite formation, in a synaptic particulate fraction from rat brain cerebral cortex. O 2 − produced maximal activation of NOS in the presence of the antioxidant urate and ATP. Stimulation of NOS activity by O 2 − was abolished by N-monomethyl- l-arginine and by the Ca 2+ chelator EGTA but not by 7-nitroindazole, which would be expected to inhibit neuronal NOS. We propose that limited activation of NOS by O 2 − may be an important contributor to brain oxidant defenses and, more generally, a signal for cellular adaptation and survival, although excessive generation of nitrogen oxides would be expected to produce neurotoxicity.

Antioxidant protection against iron in children with meningococcal sepsis

To assess antioxidant protection against iron-catalyzed reactive oxygen species in meningococcal sepsis and to establish whether severity of illness is related to deficiencies in these antioxidant systems. Prospective, controlled study. Pediatric intensive care unit of a postgraduate teaching hospital. Twenty children aged 6 months to 15 yrs (median, 5 yrs) with meningococcal septic shock were studied. Paired convalescent samples taken 8-10 wks after discharge were available in nine children. Routine management for meningococcal sepsis. Patients were classified for disease severity using the Glasgow Meningococcal Septicaemia Prognostic Score. Paired acute and convalescent samples were compared. Transferrin level (1.77 +/- 0.08 g/L) and total iron-binding capacity (46.2 +/- 2.0 microM) were significantly decreased in acute patients compared with paired convalescent samples (2.85 +/- 0.10 g/L and 74.4 +/- 2.5 microM, respectively; p <.0001). The iron saturation of transferrin was significantly increased in acute disease (36.9% +/- 2.5%) compared with convalescence (18.8% +/- 1.5%; p =.0003). Iron-binding antioxidant protection was not significantly different in acute (81.4% +/- 1.7%) and paired convalescent samples (85.6% +/- 2.5%; p =.54). However, patients with more severe meningococcal septicemia (GMSPS, >10; n = 12) had significantly diminished protection (77.5% +/- 2.4%) compared with less severe disease (87.1% +/- 1.6%; p =.0028), and there was a significant correlation between disease severity and iron-binding antioxidant protection (R =.48; p =.00067) in acute disease. Paired ceruloplasmin levels were available in six patients and were decreased in acute disease (0.29 +/- 0.02 g/L) compared with convalescence (0.40 +/- 0.04 g/L), although not statistically significant (p =.076). However, there was a significant correlation between plasma ceruloplasmin and disease severity (Pearson product moment correlation, p =.038) in the acute patients. Iron-oxidizing antioxidant assays were performed in four paired samples and were diminished in acute patients (53.3 +/- 4.4%) compared with convalescence (67.8 +/- 3.2%; p =.015). Acute samples demonstrated a significant relationship between iron-oxidizing antioxidant protection and both disease severity (r =.30; p =.012) and plasma ceruloplasmin levels (r =.48; p =.00067). Children with meningococcal septicemia exhibit abnormal plasma iron chemistry and decreased protection against iron-catalyzed oxidative damage. Such deficiencies correlate with disease severity.

Iron coordination chemistry of N-(bis(2-pyridyl)methyl)pyridine-2-carboxamide

The amidate function participates in the coordination chemistry of iron containing biomolecules such as the anti-tumor drug bleomycin and the enzyme nitrile hydratase. Our interest in amidate coordination prompted an investigation of the iron complexes of the potentially tetradentate ligand N-(bis(2-pyridyl)methyl)pyridine-2-carboxamide (HL). A number of complexes have been isolated and structurally characterized, including [FeII(L)2] (1), [FeIII(LOCH3)Br2(CH3OH)] (3), [FeIII2(μ-OH)2(LOCH3)2Br2] (4), and [FeIII4(μ-OCH3)2(LO)2Br6] (5). In these complexes L acts as a meridional tridentate ligand, as previously observed for the corresponding [Cu(L)Cl(CH3OH)] complex (Inorg. Chem. 39 (2000) 5326). In the cases of 3 and 4, the hydrogen of the tertiary carbon has been replaced by a methoxy group in the course of complex synthesis. In the case of 5, the tertiary hydrogen is replaced by hydroxide, and this oxygen and the dangling pyridine act as a bidentate ligand to a second iron ion. When the reaction of FeBr3 and HL was carried out in acetonitrile in the presence of base but in the absence of air, the ligand was cleaved into two pieces, affording [FeIIBr2(pyridine-2-carboxamide)(di-2-pyridylketone)] (6). It is proposed that the coordination of the amide nitrogen of HL to an iron(III) center as an amidate activates the α-CH bond and results in the oxidation of the α-CNamide bond to an imine.

Paleoceanographic significance of sediment color on western North Atlantic drifts: I. Origin of color

Reflectance spectra collected during ODP Leg 172 were used in concert with solid phase iron chemistry, carbonate content, and organic carbon content measurements to evaluate the agents responsible for setting the color in sediments. Factor analysis has proved a valuable and rapid technique to detect the local and regional primary factors that influence sediment color. On the western North Atlantic drifts, sediment color is the result of primary mineralogy as well as diagenetic changes. Sediment lightness is controlled by the carbonate content while the hue is primarily due to the presence of hematite and Fe 2+/Fe 3+ changes in clay minerals. Hematite, most likely derived from the Permo-Carboniferous red beds of the Canadian Maritimes, is differentially preserved at various sites due to differences in reductive diagenesis and dilution by other sedimentary components. Various intensities for diagenesis result from changes in organic carbon content, sedimentation rates, and H 2S production via anaerobic methane oxidation. Iron monosulfides occur extensively at all high sedimentation sites especially in glacial periods suggesting increased high terrigenous flux and/or increased reactive iron flux in glacials.

Extraction of iron(III) from acidic sulfate solutions with bis(2‐ethylhexyl)phosphoric acid in PENRECO® 170 ES, a new friendly diluent

AbstractThe extraction of iron(III) from acidic sulfate solutions by bis(2‐ethylhexyl)phosphoric acid (HDEHP) is investigated by using PENRECO® 170 ES as a diluent. PENRECO® 170 ES is new diluent which offers advantages such as improved solvency power, more complete phase disengagement and reduced losses in aqueous streams, with reductions of over 50% in diluent usage after 1 year, compared with conventional paraffinic diluents. The chemical analyses performed in the present work suggest that such properties arise, at least in part, from the presence of a series of hydrophobic branched alcohols in its composition (at least 0.6 mol dm−3). In spite of the solvation effects due to these alcohols, HDEHP is dimeric in this diluent and, in the presence of an excess of HDEHP, the extraction of iron(III) takes place according to the classical equation: $Fe^{3+} + 3\overline{H_2L_2} \Leftrightarrow \overline{FeL_3 \cdot 3HL} + 3H^+$ with Kex = 105.7 ± 0.2 (at I = 1 mol dm−3). Such a value of Kex is similar to that reported for pure hexane, which shows that the presence of long chain alcohols in PENRECO® 170 ES has no perceptible influence on the thermodynamics of iron(III) extraction by HDEHP. The extraction of iron(III) by HDEHP in PENRECO® 170 ES is slightly more rapid than in kerosene, which indicates that the molecules of alcohols constituting PENRECO® 170 ES have no negative effect on the kinetics of metal extraction although they compete with the extractant molecules for adsorption at the liquid–liquid interface. Stripping of iron(III) from loaded organic solutions by sulfuric acid is easy and rapid (95% equilibrium reached within 2 min) when HDEHP is used at moderate concentrations (typically 0.1 mol dm−3). At higher HDEHP concentrations, stripping is difficult and incomplete, as found previously with other diluents. Thus, PENRECO® 170 ES is interesting in its ability to overcome some of the physical problems encountered in liquid–liquid operations, but its use does not modify significantly the chemistry of iron(III) extraction by HDEHP.© 2002 Society of Chemical Industry

What Makes Iron Attractive

No precise data on gold accumulation around ironcontaining spots in soil in the absence of cyanide ions are available. Apparently, here, it can be proposed that the reaction of iron with humic acids in soil and subsequent formation of complexes containing gold(II) or gold(III) or another metal would result in an accumulation of these metals near iron-containing places. The interest in iron(II) and iron(III) compounds with humic acids and in the properties of various derivatives of these complexes appears quite natural. It should be emphasized that in his time, Academician I.V. Tananaev devoted considerable attention to ferrocyanides [2]. The results of studies along this line have found practical application and, possibly, could be demanded in the future. One can only add that the coordination chemistry of iron, as it seems, requires considerable attention. Formerly, Professor O. E. Zvyagintsev attempted to organize investigations of iron coordination compounds at the Kurnakov Institute of General and Inorganic Chemistry of the RAS. Professor A.V. Babaeva, working at the same Institute, supported in every way works on the synthesis and study of the influence of zinc ferricitrate as a microfertilizer on plant growth. Apparently, iron coordination compounds could attract the attention of researchers as microfertilizers.

Coordination chemistry of iron(III)-porphyrin-antibody complexes.

An artificial peroxidase-like hemoprotein has been obtained by associating a monoclonal antibody, 13G10, and its iron(III)-alpha,alpha,alpha,beta-meso-tetrakis(ortho-carboxyphenyl)porphyrin [Fe(ToCPP)] hapten. In this antibody, about two-thirds of the porphyrin moiety is inserted in the binding site, its ortho-COOH substituents being recognized by amino-acids of the protein, and a carboxylic acid side chain of the protein acts as a general acid base catalyst in the heterolytic cleavage of the O-O bond of H2O2, but no amino-acid residue is acting as an axial ligand of the iron. We here show that the iron of 13G10-Fe(ToCPP) is able to bind, like that of free Fe(ToCPP), two small ligands such as CN-, but only one imidazole ligand, in contrast to to the iron(III) of Fe(ToCPP) that binds two. This phenomenon is general for a series of monosubstituted imidazoles, the 2- and 4-alkyl-substituted imidazoles being the best ligands, in agreement with the hydrophobic character of the antibody binding site. Complexes of antibody 13G10 with less hindered iron(III)-tetraarylporphyrins bearing only one [Fe(MoCPP)] or two meso-[ortho-carboxyphenyl] substituents [Fe(DoCPP)] also bind only one imidazole. Finally, peroxidase activity studies show that imidazole inhibits the peroxidase activity of 13G10-Fe(ToCPP) whereas it increases that of 13G10-Fe(DoCPP). This could be interpreted by the binding of the imidazole ligand on the iron atom which probably occurs in the case of 13G10-Fe(ToCPP) on the less hindered face of the porphyrin, close to the catalytic COOH residue, whereas in the case of 13G10-Fe(DoCPP) it can occur on the other face of the porphyrin. The 13G10-Fe(DoCPP)-imidazole complex thus constitutes a nice artificial peroxidase-like hemoprotein, with the axial imidazole ligand of the iron mimicking the proximal histidine of peroxidases and a COOH side chain of the antibody acting as a general acid-base catalyst like the distal histidine of peroxidases does.

Chemistry for an essential biological process: the reduction of ferric iron.

In biological systems, the predominant form of iron is the trivalent Fe(III) form, which is potentially not readily bioavailable because of its hydrolysis and polymerization to insoluble forms. It is also the easiest of the two predominant forms of iron to chelate selectively. In a short overview of iron chemistry, we point out some of the pitfalls using standard redox potentials, comment on the interaction of ferric complexes with hydrogen peroxide to give hydroxyl radicals and address the release of iron from ferrisiderophores. In biological systems there are two classes of ferric reductases, the soluble flavin reductases found in prokaryotes, and the membrane-bound cytochrome b-like reductases found in eukaryotes. Finally the role of dissimilatory ferric reduction in microbial respiration and biomineralization is discussed.

Iron Autoxidation and Free Radical Generation: Effects of Buffers, Ligands, and Chelators

The pH of the solution along with chelation and consequently coordination of iron regulate its reactivity. In this study we confirmed that, in general, the rate of Fe(II) autoxidation increases as the pH of the solution is increased, but chelators that provide oxygen ligands for the iron can override the affect of pH. Additionally, the stoichiometry of the Fe(II) autoxidation reaction varied from 2:1 to 4:1, dependent upon the rate of Fe(II) autoxidation, which is dependant upon the chelator. No partially reduced oxygen species were detected during the autoxidation of Fe(II) by ESR using DMPO as the spin trap. However, upon the addition of ethanol to the assay, the DMPO:hydroxyethyl radical adduct was detected. Additionally, the hydroxylation of terephthalic acid by various iron–chelator complexes during the autoxidation of Fe(II) was assessed by fluorometric techniques. The oxidant formed during the autoxidation of EDTA:Fe(II) was shown to have different reactivity than the hydroxyl radical, suggesting that some type of hypervalent iron complex was formed. Ferrous iron was shown to be able to directly reduce some quinones without the reduction of oxygen. In conclusion, this study demonstrates the complexity of iron chemistry, especially the chelation of iron and its subsequent reactivity.

Kinetic iron stable isotope fractionation between iron (-II) and (-III) complexes in solution

Iron stable isotope fractionation between tris(2,2′-bipyridine) iron-II ([Fe II(bipy) 3] 2+) and iron-III chloride complexes has been measured using plasma source mass spectrometry. The experimental protocol involves complexing Fe II ion with 2,2′-bipyridine in a Fe II/Fe III chloride solution and then separating the Fe II and Fe III solution species in 6 M HCl on an anion exchange resin. Large isotopic variations of ϵ 57Fe and ϵ 56Fe are experimentally measured in the two separated solution fractions, with isotopic fractionations increasing from Δ(Fe II-Fe III)=25 to 174 ϵ units for 57Fe/ 54Fe and 17 to 117 ϵ units for 56Fe/ 54Fe. The increase in fractionations correlates with a decrease in the mole fraction of Fe II in the solution (Fe*=(Fe II)/[(Fe II)+(Fe III)]) that results from the dissociation and breakdown of [Fe II(bipy) 3] 2+ complex in 6 M HCl solution. The data variations are mainly ascribed to a kinetic fractionation occurring during this dissociation reaction. Mass balance calculations, assuming that a Rayleigh law describes the overall isotopic trends, suggest a kinetic fractionation of ca. 1.010 (∼100 ϵ units). The magnitude of this fractionation is attributed to the rupturing of the strong covalent bonds between 2,2′-bipyridine and Fe II ion. The experimental data confirm that the coordination chemistry of iron exhibits a profound control on its isotopic behaviour and that kinetic fractionations may play an important role in its isotope geochemistry, as was also found in the pioneering experimental studies of the sulphur isotopic system in solution.

Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass

Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess ‘off-pump’ coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the ‘Octopus’ myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those ( n=9) who had one- or two- ( n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.

Speciation and Crystal Chemistry of Iron(III) Chloride Hydrolyzed in the Presence of SiO4 Ligands. 3. Semilocal Scale Structure of the Aggregates

A series of fresh and 7 day aged Fe−Si samples have been investigated at the semilocal scale by small-angle X-ray scattering (SAXS). All the scattering curves are typical of amorphous aggregates. The subunits of the precipitates could not be determined precisely. However, the trend derived from SAXS modeling indicates that almost all the Fe is within subunits smaller than 7.5 A. The high fractal dimension (Df) values of the aggregates ranging from about 2.0 to 2.7 are attributed to the presence of Si ligands. However, the value of Df as a function of pH and Si concentration varies linearly with the polymerization state of iron.

ChemInform Abstract: Synthesis, Antimalarial Activity, Biomimetic Iron(II) Chemistry, and in vivo Metabolism of Novel, Potent C‐10‐Phenoxy Derivatives of Dihydroartemisinin.

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Siderophores in marine coastal waters and their relevance for iron uptake by phytoplankton: experiments with the diatom Phaeodactylum tricornutum

Natural marine bacteria populations collected from nearshore waters produce different types of siderophores depending on the degree of iron limitation. These siderophores can facilitate iron uptake in the marine diatom Phaeodactylum tricornutum. Water samples from 15 stations along the Italian coast of the northwest Adriatic Sea were collected and filter fractionated (3.0, 0.8 and 0.2 µm). Siderophore production in the fractions was determined using cross-feeding experiments with siderophore-auxotrophic bacteria. At most stations sampled, bacteria collected in the 3.0 and 0.8 µm filters produced siderophores which stimulated growth in Morganella morganii, the indicator strain for α-keto/ α-hydroxy acids. The results suggest that MGF (ŒMorganella-Growth Factor¹) production is common among filamentous and appendaged bacteria or strains associated with particles. Natural bacteria populations grown in iron-deficient media stimulated growth of all the indicator strains in the cross-feeding tests. Examples of known MGF which supply iron to M. morganii were tested for their ability to act as iron source for the marine diatom P. tricornutum. Iron uptake from 55Fe-MGFs was measured in P. tricornutum cells grown in Fe-sufficient and Fe-deficient media. Unchelated iron (55FeCl3 ) and 55FeEDTA were used as controls. The uptake of iron from the 55Fe-MGF and 55FeCl3 by Fe-deficient cells was higher (109 to 150 pgFe mg-1) than from 55FeEDTA (34 pgFe mg-1). Similarly, Fe-sufficient P. tricornutum took up iron from the 55Fe-MGF and 55FeCl3 to the same extent (~50 pgFe mg-1) while minimal uptake (8 pgFe mg-1) was measured from FeEDTA. In growth experiments where iron-deficient diatom cells were incubated in media containing different sources of iron, e.g. FeCl3, Fe-MGF and FeEDTA, a greater increase in number was observed in cells supplied with Fe-MGF. Further experiments also show that the uptake of Fe from MGF was enhanced by light and that a reduction step was involved in the uptake process. MGF also promoted the uptake of colloidal ferrihydrites. This study gives further evidence that siderophores produced by bacteria can be utilized by phytoplankton as an iron source. We therefore suggest that these substances play an important role in increasing the availability of iron to phytoplankton in coastal waters and thus are major factors defining the chemistry of iron in the marine environment.

Synthesis, antimalarial activity, biomimetic iron(II) chemistry, and in vivo metabolism of novel, potent C-10-phenoxy derivatives of dihydroartemisinin.

The combination of TMSOTf and AgClO(4) promotes the efficient C-10-phenoxylation of dihydroartemisinin (3) in good chemical yield and excellent stereoselectivity. All of the new phenoxy derivatives have potent in vitro antimalarial activity. On the basis of the excellent yield and stereoselectivity obtained for the p-trifluoromethyl derivative 7b, this compound and the parent phenyl-substituted derivative 5b were selected for in vivo biological evaluation against Plasmodium berghei in the mouse model and for metabolism studies in rats. Compound 7b demonstrated excellent in vivo antimalarial potency with an ED(50) of 2.12 mg/kg (cf. artemether = 6 mg/kg) versus P. berghei. Furthermore, from preliminary metabolism studies, this compound was not metabolized to dihydroartemisinin; suggesting it should have a longer half-life and potentially lower toxicity than the first-generation derivatives artemether and arteether. From biomimetic Fe(II)-catalyzed decomposition studies and ESR spectroscopy, the mechanism of action of these new lead antimalarials is proposed to involve the formation of both primary and secondary C-centered cytotoxic radicals which presumably react with vital parasite thiol-containing cellular macromolecules.