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In a fundamental process throughout nature, reduced iron unleashes the oxidative power of hydrogen peroxide into reactive intermediates. However, notwithstanding much work, the mechanism by which Fe ²⁺ catalyzes H ₂O ₂ oxidations and the identity of the participating intermediates remain controversial. Here we report the prompt formation of O=Fe ᴵⱽCl ₃⁻ and chloride-bridged di-iron O=Fe ᴵⱽ·Cl·Fe ᴵᴵCl ₄⁻ and O=Fe ᴵⱽ·Cl·Fe ᴵᴵᴵCl ₅⁻ ferryl species, in addition to Fe ᴵᴵᴵCl ₄⁻, on the surface of aqueous FeCl ₂ microjets exposed to gaseous H ₂O ₂ or O ₃ beams for <50 μs. The unambiguous identification of such species in situ via online electrospray mass spectrometry let us investigate their individual dependences on Fe ²⁺, H ₂O ₂, O ₃, and H ⁺ concentrations, and their responses to tert -butanol (an ·OH scavenger) and DMSO (an O-atom acceptor) cosolutes. We found that (i) mass spectra are not affected by excess tert -butanol, i.e., the detected species are primary products whose formation does not involve ·OH radicals, and (ii) the di-iron ferryls, but not O=Fe ᴵⱽCl ₃⁻, can be fully quenched by DMSO under present conditions. We infer that interfacial Fe(H ₂O) ₙ²⁺ ions react with H ₂O ₂ and O ₃ >10 ³ times faster than Fe(H ₂O) ₆²⁺ in bulk water via a process that favors inner-sphere two-electron O-atom over outer-sphere one-electron transfers. The higher reactivity of di-iron ferryls vs. O=Fe ᴵⱽCl ₃⁻ as O-atom donors implicates the electronic coupling of mixed-valence iron centers in the weakening of the Fe ᴵⱽ–O bond in poly-iron ferryl species.

Curcumin displays anticancer properties; however, some issues with the drug delivery mode limit its therapeutic use. Although reformulation and derivatization of curcumin have improved its bioavailability, curcumin derivatives may not retain the same anticancer properties as the parent compound. The present study investigated the anticancer properties of two curcumin complexes, the iron-curcumin [Fe(Cur)3] and boron-curcumin [B(Cur)2] complexes, in the MDA-MB-231 breast cancer cell line. The cellular localization of curcumin, B(Cur)2 and Fe(Cur)3 was determined by fluorescence microscopy. Cell proliferation, migration and invasion were also analysed. Furthermore, apoptosis-associated proteins were detected by using a proteome profiler array, and ion channel gene expression was analysed by reverse transcription-quantitative PCR. The results demonstrated that the three compounds were localized in the perinuclear and cytoplasmic regions of the cell, and displayed cytotoxicity with IC50 values of 25, 35 and 8 µM for curcumin, B(Cur)2 and Fe(Cur)3, respectively. In addition, the three compounds inhibited cell invasion, whereas only curcumin and B(Cur)2 inhibited cell migration. Furthermore, cell exposure to curcumin resulted in an increase in the relative expression of the two key proapoptotic proteins, cytochrome c and cleaved caspase-3, as well as the antiapoptotic protein haem oxygenase-1. In addition, curcumin increased the expression levels of the voltage-gated potassium channels Kv2.1 and Kv3.2. Similarly, the expression levels of the chloride channel bestrophin-1 and the calcium channel coding gene calcium voltage-gated channel auxiliary subunit γ4 were increased following exposure to curcumin. Taken together, these results indicated that Fe(Cur)3 and B(Cur)2 may display similar anticancer properties as curcumin, suggesting that chemical complexation may be considered as a strategy for improving the potency of curcumin in the treatment of breast cancer.

Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron–carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron–carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron–carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.

Anemia and iron deficiency are common in patients with heart failure, and negatively impact on symptoms and outcomes in this patient population. In this Review, Dr. van Veldhuisen and colleagues discuss the impact of anemia and iron deficiency in patients with heart failure, mechanisms of iron metabolism, and treatment strategies for these patients. Anemia and iron deficiency are common in patients with heart failure (HF), and are associated with worse symptoms and adverse outcomes in this population. Although the two can occur together, anemia in HF is often not caused by iron deficiency, and iron deficiency can be present without causing anemia. Erythropoiesis-stimulating agents have been investigated extensively in the past few years and might be of benefit in patients with HF and anemia. However, concerns have arisen regarding the safety of erythropoiesis-stimulating agents in patients with chronic kidney disease and so the results of a large mortality trial are eagerly awaited to provide information on safety in patients with HF. Iron supplementation or replacement is a much older treatment option for patients with HF and anemia, but questions about the safety of intravenous iron, and absorption problems with oral formulations have prevented its widespread use to date. In the past few years, however, new data on the importance of iron deficiency in HF have become available, and a number of studies with intravenous iron have shown promising results. Therefore, this treatment approach is likely to become an attractive option for patients with HF and iron deficiency, both with and without anemia. Key Points Anemia and iron deficiency are both common and important in the setting of heart failure Anemia is associated with increased morbidity and mortality among patients with heart failure Iron deficiency, both with and without anemia, is also associated with adverse clinical outcomes Treatment of patients with heart failure and anemia with erythropoiesis-stimulating agents could have beneficial clinical effects, but the results of a large-scale ongoing trial (RED-HF) must be awaited Intravenous, but not oral, iron supplementation might be beneficial in the treatment of patients with heart failure and iron deficiency

Time-resolved resonance Raman vibrational spectroscopy was used to study the mechanism of soluble methane monooxygenase and obtain structural information on the key reaction cycle intermediate, compound Q , which contains a unique dinuclear Fe IV cluster that breaks the strong C-H bond of methane and inserts an oxygen atom (from O 2 ) to form methanol. Greenhouse gas to liquid fuel via Q Using time-resolved resonance Raman vibrational spectroscopy, Rahul Banerjee et al . have determined the structure of 'compound Q', a key transient intermediate from the soluble methane monooxygenase (sMMO) system found in methanotrophic bacteria. Q is the strongest known biological oxidant and catalyses cleavage of the ultimately stable C–H bond of methane with insertion of oxygen to form the liquid fuel methanol. With a better understanding of the structure and mechanism of action of Q it might be possible to synthesize small molecule enzyme mimetics that could convert naturally occurring methane to methanol, thereby converting a damaging greenhouse gas into a potentially important source of liquid fuel and chemicals. Methane monooxygenase (MMO) catalyses the O 2 -dependent conversion of methane to methanol in methanotrophic bacteria, thereby preventing the atmospheric egress of approximately one billion tons of this potent greenhouse gas annually. The key reaction cycle intermediate of the soluble form of MMO (sMMO) is termed compound Q (Q). Q contains a unique dinuclear Fe IV cluster that reacts with methane to break an exceptionally strong 105 kcal mol −1 C-H bond and insert one oxygen atom 1 , 2 . No other biological oxidant, except that found in the particulate form of MMO, is capable of such catalysis. The structure of Q remains controversial despite numerous spectroscopic, computational and synthetic model studies 2 , 3 , 4 , 5 , 6 , 7 . A definitive structural assignment can be made from resonance Raman vibrational spectroscopy but, despite efforts over the past two decades, no vibrational spectrum of Q has yet been obtained. Here we report the core structures of Q and the following product complex, compound T, using time-resolved resonance Raman spectroscopy (TR 3 ). TR 3 permits fingerprinting of intermediates by their unique vibrational signatures through extended signal averaging for short-lived species. We report unambiguous evidence that Q possesses a bis-μ-oxo diamond core structure and show that both bridging oxygens originate from O 2 . This observation strongly supports a homolytic mechanism for O-O bond cleavage. We also show that T retains a single oxygen atom from O 2 as a bridging ligand, while the other oxygen atom is incorporated into the product 8 . Capture of the extreme oxidizing potential of Q is of great contemporary interest for bioremediation and the development of synthetic approaches to methane-based alternative fuels and chemical industry feedstocks. Insight into the formation and reactivity of Q from the structure reported here is an important step towards harnessing this potential.

Due to the coexistence of organic matter and iron in groundwater, a certain part of the iron is present as iron-organic complexes in the form of colloids and/or dissolved complexes. The study was conducted to evaluate the impact of the type of oxidizing agent: O2, Cl2, H2O2, or KMnO4, on the efficiency of the oxidation and removal of iron compounds from three groundwaters with significantly different contents and types of organic substances among which humic and fulvic acids occurred. This study shows that after the aeration and the oxidation with Cl2 and H2O2, the increasing content of dissolved hydrophilic organic substances containing aromatic rings in the raw water reduced the effectiveness of Fe(II) oxidation and the effectiveness of iron removal during the sedimentation process. This regularity was not found only when KMnO4 was used as the oxidant. After oxidation with H2O2, the highest number of organo-iron complexes and an increased concentration of dissolved organic carbon were found. High concentrations of organo-ferrous connections were also found in aerated water samples. The highest KMnO4 efficiency of removing iron and organic substances and reducing the color intensity and turbidity was due to the catalytic and adsorptive properties of the precipitated MnO2, which also improved the sedimentation properties of the resultant oxidation products.

Although nitrogenase enzymes routinely convert molecular nitrogen into ammonia under ambient temperature and pressure, this reaction is currently carried out industrially using the Haber–Bosch process, which requires extreme temperatures and pressures to activate dinitrogen. Biological fixation occurs through dinitrogen and reduced N x H y species at multi-iron centres of compounds bearing sulfur ligands, but it is difficult to elucidate the mechanistic details and to obtain stable model intermediate complexes for further investigation. Metal-based synthetic models have been applied to reveal partial details, although most models involve a mononuclear system. Here, we report a diiron complex bridged by a bidentate thiolate ligand that can accommodate HN=NH. Following reductions and protonations, HN=NH is converted to NH 3 through pivotal intermediate complexes bridged by N 2 H 3 – and NH 2 – species. Notably, the final ammonia release was effected with water as the proton source. Density functional theory calculations were carried out, and a pathway of biological nitrogen fixation is proposed. Although it is achieved routinely by nitrogenases, the conversion of molecular dinitrogen into ammonia under ambient conditions is proving difficult with synthetic systems. A thiolate-bridged diiron complex has now been developed that produces ammonia from coordinated N 2 H 2 through a sequence of reduction and protonation reactions that may well mimic the biological nitrogen fixation.

Background Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The aim of our study was to evaluate and compare renal functional and structural integrity in 50 infants with IDA and 50 healthy controls and to assess the relation between IDA and oxidative stress and response to iron therapy. Methods This was a prospective study in which peripheral blood samples were collected from all study subjects and the following laboratory investigations performed: serum iron profile, urinary microalbumin, urinary leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace elements (iron, copper, zinc, calcium and magnesium). All patients received oral iron therapy and were followed-up for 3 months. Results The levels of baseline urinary markers were higher among the patients with IDA than among the controls ( p  < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and magnesium levels than controls as well as higher MDA and serum copper levels ( p  < 0.05). MDA level was positively correlated to microalbumin and LAP level ( p  < 0.05). Urinary LAP concentration was positively correlated to urinary trace element concentrations ( p  < 0.05). A significant decrease in microalbumin, LAP, FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin and ferritin levels were increased ( p  < 0.05). Conclusion Among the study subjects, IDA had an adverse influence on renal functional and structural integrity which could be reversed with iron therapy. Oxidative stress played an important role in the pathogenesis of renal injury in IDA.

Schwertmannite is an Fe(III)-oxyhydroxysulfate which is common in acid mine drainage (AMD) and acid sulfate soil (ASS) environments. Natural schwertmannite is often enriched in Cr(III), yet the effects of Cr(III) substitution on schwertmannite transformation to more stable Fe(III) minerals has not been addressed. Here we examine, for the first time, the effects of Cr(III) substitution on the Fe(II)-accelerated transformation of schwertmannite. X-ray diffraction (XRD) and Fe K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy shows that Cr(III) substitution inhibits schwertmannite transformation. Substitution at a Cr(III):Fe(III) ratio of 0.025 decreased schwertmannite transformation (at pH 6.5) by 18-49% (depending on Fe(II) concentrations) relative to that of Cr(III)-free schwertmannite. Formation of crystalline secondary phases (predominantly goethite) caused associated decreases in solid-phase Fe and Cr extractability by 1 M HCl. The extractability of Cr was consistently greater than that of Fe, suggesting some accumulation of Cr(III) at the residual schwertmannite surface-a phenomenon which passivates the surface against Fe(II)/Fe(III) electron transfer and atom exchange required for the Fe(II)-accelerated transformation process. The finding that Cr(III)-substitution inhibits schwertmannite transformation implies that it may also significantly impact associated Fe, S and trace metal(loid) behaviour.

Bacterial adhesion onto mineral surfaces and subsequent biofilm formation play key roles in aggregate stability, mineral weathering and the fate of contaminants in soils. However, the mechanisms of bacteria-mineral interactions are not fully understood. Atomic force microscopy (AFM) was used to determine the adhesion forces between bacteria and goethite in water and to gain insight into the nanoscale surface morphology of the bacteria-mineral aggregates and biofilms formed on clay-sized minerals. This study yields direct evidence of a range of different association mechanisms between bacteria and minerals. All strains studied adhered predominantly to the edge surfaces of kaolinite rather than to the basal surfaces. Bacteria rarely formed aggregates with montmorillonite, but were more tightly adsorbed onto goethite surfaces. This study reports the first measured interaction force between bacteria and a clay surface and the approach curves exhibited jump-in events with attractive forces of 97 ± 34 pN between E. coli and goethite. Bond strengthening between them occurred within 4 s to the maximum adhesion forces and energies of −3.0 ± 0.4 nN and −330 ± 43 aJ (10 −18  J), respectively. Under the conditions studied, bacteria tended to form more extensive biofilms on minerals under low rather than high nutrient conditions.