Iron Ligand Research Articles

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs) that activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and, thereby, hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression to control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than in controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating a bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

Highly Stable Alkaline All‐Iron Redox Flow Batteries Enabled by Disulfonated Ligands Chelation

AbstractAlkaline all‐iron flow batteries possess intrinsic safety and low cost, demonstrating great potential for large‐scale and long‐duration energy storage. However, their commercial application is hindered by the issue of capacity decay resulting from the decomposition of iron complexes and ligand crossovers. In this paper, an robust anolyte Fe(TEA‐2S) is reported, which is formed by chelating iron ions with the sulfonate‐enriched ligand (TEA‐2S) in alkaline environment. By skillfully designing the ligands, the binding energy of the iron complexes increases and ligand crossovers are suppressed, making the iron complexes highly stable in the charge–discharge cycles. Alkaline all‐iron flow batteries coupling with Fe(TEA‐2S) and the typical iron‐cyanide catholyte perform a minimal capacity decay rate (0.17% per day and 0.0014% per cycle), maintaining an average coulombic efficiency of close to 99.93% over 2000 cycles along with a high energy efficiency of 83.5% at a current density of 80 mA cm−2. In addition, Fe(TEA‐2S) exhibits high solubility of up to 1.85 м (with a theoretical capacity of up to 49.58 Ah L−1), even at low temperatures as extreme as −30 °C. This work demonstrates a promising pathway toward achieving long‐duration and large‐scale energy storage.

Escherichia coli alcohol dehydrogenase YahK is a protein that binds both iron and zinc.

Previous studies have highlighted the catalytic activity of Escherichia coli alcohol dehydrogenase YahK in the presence of coenzyme nicotinamide adenine dinucleotide (NAD) and metal zinc. Notably, competitive interaction between iron and zinc ligands has been shown to influence the catalytic efficiency of several key proteases. This study aims to unravel the intricate mechanisms underlying YahK's catalytic action, with a particular focus on the pivotal roles played by metal ions zinc and iron. The purified YahK protein from E. coli cells cultivated in LB medium was utilized to investigate its metal-binding properties through UV-visible absorption measurements and determination of metal content. Subsequently, the effects of excess zinc and iron on the metal-binding ability and alcohol dehydrogenase activity of the YahK protein were explored using M9 minimal medium. Furthermore, site-directed mutagenesis technology was employed to determine the iron-binding site location within the YahK protein. Polyacrylamide gel electrophoresis was conducted to examine the relationship between iron and zinc with respect to the YahK protein. The study confirmed the presence of iron and zinc in the YahK protein, with the zinc-bound form exhibiting enhanced catalytic activity in alcohol dehydrogenation reactions. Conversely, the presence of iron appears to play a pivotal role in maintaining overall stability of the YahK protein. Furthermore, experimental findings indicate that excessive zinc within M9 minimal medium can competitively bind to iron-binding sites on YahK, thereby augmenting its alcohol dehydrogenase activity. The dynamic binding of YahK to iron and zinc unveils its intricate regulatory mechanism as an alcohol dehydrogenase, thereby highlighting the possible physiological role of YahK in E. coli and its significance in governing cellular metabolic processes. This discovery provides a novel perspective for further investigating the specific impact of metal ion binding on YahK and E. coli cell metabolism.

Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(II) sandwich complexes.

Tris(pyrazolyl)methane (tpm), 2,2,2-tris(pyrazolyl)ethanol (tpmOH) and its esterification derivatives with ibuprofen and flurbiprofen (tpmIBU and tpmFLU) were used as ligands to obtain complexes of the type [Fe(tpmX)2]Cl2 (1-4). The tpmIBU and tpmFLU ligands and corresponding complexes 3 and 4 were characterized by IR and multinuclear NMR spectroscopy, and the structure of tpmIBU was elucidated by single crystal X-ray diffraction. Complexes 1-4 were also assessed for their behaviour in aqueous media (solubility in D2O, octanol/water partition coefficient, stability in physiological-like conditions). The antiproliferative activity of ligands and complexes was determined on A2780, A2780cis and A549 cancer cell lines and the non-cancerous HEK 293T and BJ cell lines. The ligands and complexes were investigated for their ability to inhibit COX-2 (cyclooxygenase) and HNE (4-hydroxynonenal) enzymes. Complexes 3 and 4 exhibited cytotoxicity that may be attributed predominantly to their bioactive fragments, while DNA binding and enhancement of ROS production do not appear to play any significant role.

Applications of the Newly Developed Force-Field Parameters Uncover a Dynamic Nature of Ω-Loop C in the Lys-Ligated Alkaline Form of Cytochrome c.

Lys-ligated cytochromes make up an emerging family of heme proteins. Density functional theory calculations on the amine/imidazole-ligated c-type ferric heme were employed to develop force-field parameters for molecular dynamics (MD) simulations of structural and dynamic features of these proteins. The new force-field parameters were applied to the alkaline form of yeast iso-1 cytochrome c to rationalize discrepancies resulting from distinct experimental conditions in prior structural studies and to provide insights into the mechanisms of the alkaline transition. Our simulations have revealed the dynamic nature of Ω-loop C in the Lys-ligated protein and its unfolding in the Lys-ligated conformer having this loop in the same position as in the native Met-ligated protein. The proximity of Tyr67 or Tyr74 to the Lys ligand of ferric heme iron suggests a possible mechanism of the backward alkaline transition where a proton donor Tyr assists in Lys dissociation. The developed force-field parameters will be useful in structural and dynamic characterization of other native or engineered Lys-ligated heme proteins.

Heme Spin Distribution in the Substrate-Free and Inhibited Novel CYP116B5hd: A Multifrequency Hyperfine Sublevel Correlation (HYSCORE) Study.

The cytochrome P450 family consists of ubiquitous monooxygenases with the potential to perform a wide variety of catalytic applications. Among the members of this family, CYP116B5hd shows a very prominent resistance to peracid damage, a property that makes it a promising tool for fine chemical synthesis using the peroxide shunt. In this meticulous study, we use hyperfine spectroscopy with a multifrequency approach (X- and Q-band) to characterize in detail the electronic structure of the heme iron of CYP116B5hd in the resting state, which provides structural details about its active site. The hyperfine dipole-dipole interaction between the electron and proton nuclear spins allows for the locating of two different protons from the coordinated water and a beta proton from the cysteine axial ligand of heme iron with respect to the magnetic axes centered on the iron. Additionally, since new anti-cancer therapies target the inhibition of P450s, here we use the CYP116B5hd system-imidazole as a model for studying cytochrome P450 inhibition by an azo compound. The effects of the inhibition of protein by imidazole in the active-site geometry and electron spin distribution are presented. The binding of imidazole to CYP116B5hd results in an imidazole-nitrogen axial coordination and a low-spin heme FeIII. HYSCORE experiments were used to detect the hyperfine interactions. The combined interpretation of the gyromagnetic tensor and the hyperfine and quadrupole tensors of magnetic nuclei coupled to the iron electron spin allowed us to obtain a precise picture of the active-site geometry, including the orientation of the semi-occupied orbitals and magnetic axes, which coincide with the porphyrin N-Fe-N axes. The electronic structure of the iron does not seem to be affected by imidazole binding. Two different possible coordination geometries of the axial imidazole were observed. The angles between gx (coinciding with one of the N-Fe-N axes) and the projection of the imidazole plane on the heme were determined to be -60° and -25° for each of the two possibilities via measurement of the hyperfine structure of the axially coordinated 14N.

Recommendations for best practice for iron speciation by competitive ligand exchange adsorptive cathodic stripping voltammetry with salicylaldoxime

The method of competitive ligand exchange followed by adsorptive cathodic stripping voltammetry (CLE-AdCSV) allows for the determination of dissolved iron (DFe) organic speciation parameters, i.e., ligand concentration (LFe) and conditional stability constant (log KFe′Lcond). Investigation of DFe organic speciation by CLE-AdCSV has been conducted in a wide range of marine systems, but aspects of its application pose challenges that have yet to be explicitly addressed. Here, we present a set of observations and recommendations to work toward establishing best practice for DFe organic speciation measurements using the added ligand salicylaldoxime (SA). We detail conditioning procedures to ensure a stable AdCSV signal and discuss the processes at play during conditioning. We also present step-by-step guidelines to simplify CLE-AdCSV data treatment and interpretation using the softwares ECDSoft and ProMCC and a custom spreadsheet. We validate our application and interpretation methodology with the model siderophore deferoxamine B (DFO-B) in a natural seawater sample. The reproducibility of our application and interpretation methodology was evaluated by running duplicate titrations on 19 samples, many of which had been refrozen prior to the duplicate analysis. Nevertheless, 50% of the duplicate analyses agreed within 10% of their relative standard deviation (RSD), and up to 80% within 25% RSD, for both LFe and log KFe′Lcond. Finally, we compared the sequential addition and equilibration of DFe and SA with overnight equilibration after simultaneous addition of DFe and SA on 24 samples. We found a rather good agreement between both procedures, with 60% of samples within 25% RSD for LFe (and 43% of samples for log KFe′Lcond), and it was not possible to predict differences in LFe or log KFe′Lcond based on the method applied, suggesting specific association/dissociation kinetics for different ligand assemblages. Further investigation of the equilibration kinetics against SA may be helpful as a potential way to distinguish natural ligand assemblages.

Hydrogen evolution driven by heteroatoms of bidentate N-heterocyclic ligands in iron(II) complexes.

While Pt is considered the best catalyst for the electrocatalytic hydrogen evolution reaction (HER), it is evident that non-noble metal alternatives must be explored. In this regard, it is well known that the binding sites for non-noble metals play a pivotal role in facilitating efficient catalysis. Herein, we studied Fe(II) complexes with bidentate 2-(2'-pyridyl)benzoxazole (LO), 2-(2'-pyridyl)benzthiazole (LS), 2-(2'-pyridyl)benzimidazole (LNH), and 2-2'-bipyridyl (Lpy) ligands - by adding trifluoroacetic acid (TFA) to their acetonitrile solution - in order to examine how their reactivity towards protons under reductive conditions could be impacted by the non-coordinating heteroatoms (S, O, N, or none). By applying this ligand series, we found that the reduction potentials relevant for HER correlate with ligand basicity in the presence of TFA. Moreover, DFT calculations underlined the importance of charge distribution in the ligand-based LUMO and LUMO+1 orbitals of the complexes, dependent on the heterocycle. Kinetic studies and controlled potential electrolysis - using TFA as a proton source - revealed HER activities for the complexes with LNH, LO, and LS of kobs = 0.03, 1.1, and 10.8 s-1 at overpotentials of 0.81, 0.76, and 0.79 V, respectively, and pointed towards a correlation between the kinetics of the reaction and the non-coordinating heteroatoms of the ligands. In particular, the activity was associated with the [Fe(LS/O/NH)2(S)2]2+ form (S = solvent or substrate molecule), and the rate-determining step involved the formation of [Fe(H-H)]+, during the weakening of Fe-H and CF3CO2-H bonds, according to the experimental and DFT results.

Ligand exchange provides new insight into the role of humic substances in the marine iron cycle

Organic complexation of iron plays a crucial role in preventing its precipitation, facilitating its transport, and modulating its reactivity and bioavailability in natural waters. Although humic substances (HS) complexes serve as the primary source of terrestrial iron reaching ocean waters, the transition from Fe-HS species to other forms of organic complexation with ocean autochthonous ligands has not yet been properly described. Taking advantage of the electrolability of Fe-HS complexes, we monitored the ligand exchange of iron-saturated Suwannee River fulvic and humic acids (SRFA and SRHA) after the addition of desferrioxamine B (DFOB) and other ligands for comparison. We observed that Fe-HS concentrations gradually decreased until reaching an apparent steady state, typical of a reversible reaction within 1 to 15 h. The dissociation kinetics and species partitioning of Fe-SRHS complexes at the equilibrium showed some features contrary to the current paradigm of HS iron complexation. The affinity of SRFA to bind iron is close to that of DFOB and for SRHA is even higher. The heterogeneity of the HS iron binding groups was confirmed, although experiments in NaCl solutions revealed that in seawater it is substantially caused by the interaction of major divalent ions. The different dissociation kinetics of Fe-SRHS complexes obtained with different competing ligands and the absence of Fe-DFOB dissociation in the presence of iron-free SRFA indicate an intimate associative mechanism of ligand exchange, with the presence of a ternary complex (SRHS-Fe-DFOB) that does not form if the departing complex is Fe-DFOB. We hypothesize that at the concentrations of HS and siderophores found in the open ocean, iron ligand exchange is limited and organic iron speciation will be close to being regulated on a “first come, first served” basis. Experiments conducted under saturation of all iron complexes support the formation of a permanent concentration of a ternary complex. Our findings show the real complexity of cation-ligand interactions in seawater, with implications for the interpretation of recent chromatographic and electrochemical measurements and for the understanding of iron partitioning in the presence of ubiquitous HS.

Advancements in Portable Voltammetry: A Promising Approach for Iron Speciation Analysis.

Iron, a crucial element in our environment, plays a vital role in numerous natural processes. Understanding the presence and concentration of iron in the environment is very important as it impacts various aspects of our planet's health. The on-site detection and speciation of iron are significant for several reasons. In this context, the present work aims to evaluate the applicability of voltammetry for the on-site determination of iron and its possible speciation using a portable voltammetric analyzer. Voltammetry offers the advantage of convenience and cost-effectiveness. For iron (III) determination, the modification of a glassy carbon electrode (GCE) with an antimony-bismuth film (SbBiFE) using the acetate buffer (pH = 4) as a supporting electrolyte was used. The technique adopted was Square Wave Adsoptive Cathodic Stripping Voltammetry (SW-AdCSV), and we used 1-(2-piridylazo)-2-naphthol (PAN) as the iron (III) ligand. Linearity, repeatability, detection limit, and accuracy were determined using synthetic solutions; then, a Standard Reference Material (SRM) of 1643f Trace Elements in Water (iron content: 93.44 ± 0.78 µg L-1) was used for validation measurements in the real matrix. the accuracy of this technique was found to be excellent since we obtained a recovery of 103.16%. The procedure was finally applied to real samples (tap, lake, and seawater), and the results obtained were compared via Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES). The amount of iron found was 207.8 ± 6.6 µg L-1 for tap water using voltammetry and 200.9 ± 1.5 µg L-1 with ICP-OES. For lake water, 171.7 ± 3.8 µg L-1, 169.8 ± 4.1 µg L-1, and 187.5 ± 5.7 µg L-1 were found using voltammetry in the lab both on-site and using ICP-OES, respectively. The results obtained demonstrate the excellent applicability of the proposed on-site voltammetric procedure for the determination of iron and its speciation in water.

Polymeric membrane with nanohybrids of Cu nanocomposites and metalloporphyrin-based nanosheets for enzyme-like catalytic degradation of Congo Red

Metalloporphyrin-based nanozymes are effective peroxidase-like catalysts for dye degradation; however, their reusability is a challenge due to the nanoscale dimensions. Membrane technology has the advantages of high efficiency, low energy consumption, and easy operation. Here, we integrate poly (vinylidene fluoride) (PVDF) membrane with nanozyme for effective decolorization of Congo Red (CR). A nanozyme (Cu@Cu-FeTCPP) is prepared by growth of copper hydroxide-copper oxide (Cu(OH)2-CuO) nanocomposites onto the metal organic framework (MOF) nanosheet consisting of tetrakis-(4-carboxyphenyl)-porphyrin iron ligands and cupric ion nodes. The functional membrane is achieved by loading Cu@Cu-FeTCPP nanozyme on the PVDF membrane surface (Cu@Cu-FeTCPP/PVDF). The as-prepared membrane shows catalytic activity for the degradation of CR. Under flow through conditions, the catalytic degradation in tangential flow plays a major role in overall decolorization of CR, far exceeding the contribution of adsorption. The membrane can rapidly catalyze the dye degradation even at different operating pressures (0.1–0.7 kPa) and feed solutions with higher CR concentrations (eg. 60 mg·L-1). Compared with the static batch catalysis and the free nanozyme catalysis, the membrane exhibits higher decolorization efficiency and outstanding reusability in the continuous flow process owing to the promoted mass transfer. After 40 min of continuous flow reaction in a feed solution containing CR (40 mg·L-1) and H2O2 (50 mM), the decolorization efficiency approaches 90% and remains above 85% after five catalytic cycles. The membrane with enzyme-mimicking ability has application prospect in wastewater treatment.

Detection of a Geminate Photoproduct of Bovine Cytochrome c Oxidase by Time-Resolved Serial Femtosecond Crystallography.

Cytochrome c oxidase (CcO) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme b group in their active sites, CcO has a unique binuclear center (BNC) composed of a copper atom (CuB) and a heme a3 iron, where O2 binds and is reduced to water. CO is a versatile O2 surrogate in ligand binding and escape reactions. Previous time-resolved spectroscopic studies of the CO complexes of bovine CcO (bCcO) revealed that photolyzing CO from the heme a3 iron leads to a metastable intermediate (CuB-CO), where CO is bound to CuB, before it escapes out of the BNC. Here, with a pump-probe based time-resolved serial femtosecond X-ray crystallography, we detected a geminate photoproduct of the bCcO-CO complex, where CO is dissociated from the heme a3 iron and moved to a temporary binding site midway between the CuB and the heme a3 iron, while the locations of the two metal centers and the conformation of Helix-X, housing the proximal histidine ligand of the heme a3 iron, remain in the CO complex state. This new structure, combined with other reported structures of bCcO, allows for a clearer definition of the ligand dissociation trajectory as well as the associated protein dynamics.

Exploring the Anti-Hypoxaemia Effect of Hydromethylthionine: A Prospective Study of Phase 3 Clinical Trial Participants.

Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO2) and lower respiratory rates in patients with severe COVID-19. We have developed a stable form of reduced methylthionine (hydromethylthionine-mesylate, HMTM) having a benign safety profile in two Phase 3 trials in Alzheimer's disease. The aim of this prospective study was to determine the effects of oral HMTM on SpO2 and methaemoglobin (metHb) levels in a cohort of patients with mild hypoxaemia not due to COVID-19. Eighteen participants randomised to a single dose of 4, 75, 100 or 125 mg doses of HMTM had SpO2 levels below 94% at baseline. Patients were routinely monitored by pulse oximetry after 4 h, and after 2 and 6 weeks of twice daily dosing. Significant ~3% increases in SpO2 occurred within 4 h and were sustained over 2 and 6 weeks with no dose differences. There were small dose-dependent increases (0.060-0.162%) in metHb levels over 2 to 6 weeks. Minimum-energy computational chemistry revealed that HMT can bind within 2.10 Å of heme iron by donating a pair of electrons from the central nitrogen of HMT to d orbitals of heme iron, but with lower affinity than oxygen. In conclusion, HMTM can increase SpO2 without reducing metHb by acting as a strong displaceable field ligand for heme iron. We hypothesise that this facilitates a transition from the low oxygen affinity T-state of heme to the higher affinity R-state. HMTM has potential as an adjunctive treatment for hypoxaemia.

Assessing spatiotemporal variability in the concentration and composition of dissolved organic matter and its impact on iron solubility in tropical freshwater systems through a machine learning approach

Dissolved organic matter (DOM) plays important roles not only in maintaining the productivity and functioning of aquatic ecosystems but also in the global carbon cycle, although the sources and biogeochemical functions of terrestrially derived DOM have not been fully elucidated, particularly in the tropics and subtropics. This study aimed to evaluate the factors influencing spatiotemporal variability in (i) the concentration and composition of DOM, including dissolved organic carbon (DOC), ultraviolet absorption coefficient at 254-nm wavelength (a254), and components identified by fluorescence excitation–emission matrix coupled with parallel factor analysis (EEM-PARAFAC), and (ii) the concentration of dissolved iron (DFe) across freshwater systems (rivers, forested streams, and dam reservoirs) on a tropical island (Ishigaki Island, Japan) based on the results of water quality monitoring at 2-month intervals over a 2-year period. Random forests (RF) machine learning algorithm was employed, with the catchment characteristics (land use, soil type) and water temperature as the predictor variables for DOM and the composition of DOM (EEM-PARAFAC components) and hydrochemistry (water temperature, pH, and concentrations of divalent cations) as the predictor variables for DFe. The RF models for DOC, a254, and three humic-like components exhibited excellent predictive performance, indicating that these DOM properties are not only seasonally variable but also strongly influenced by the compositions of land uses and soil types in the upstream watershed. Poorly drained riparian lowland soil (Gleyic Fluvisols) was identified as the most important catchment parameter that positively influences these DOM variables. The RF model also explained a large portion of the variation in DFe, while terrestrial humic-like components were the most important parameters, emphasizing their significance as organic ligands for iron. These results improve our understanding of the impacts of terrestrial DOM and iron loadings on tropical and subtropical coastal ecosystems as well as on regional and global carbon budgets.

Synergistic Binding of the Halide and Cationic Prime Substrate of l-Lysine 4-Chlorinase, BesD, in Both Ferrous and Ferryl States.

An aliphatic halogenase requires four substrates: 2-oxoglutarate (2OG), halide (Cl- or Br-), the halogenation target ("prime substrate"), and dioxygen. In well-studied cases, the three nongaseous substrates must bind to activate the enzyme's Fe(II) cofactor for efficient capture of O2. Halide, 2OG, and (lastly) O2 all coordinate directly to the cofactor to initiate its conversion to a cis-halo-oxo-iron(IV) (haloferryl) complex, which abstracts hydrogen (H•) from the non-coordinating prime substrate to enable radicaloid carbon-halogen coupling. We dissected the kinetic pathway and thermodynamic linkage in binding of the first three substrates of the l-lysine 4-chlorinase, BesD. After addition of 2OG, subsequent coordination of the halide to the cofactor and binding of cationic l-Lys near the cofactor are associated with strong heterotropic cooperativity. Progression to the haloferryl intermediate upon the addition of O2 does not trap the substrates in the active site and, in fact, markedly diminishes cooperativity between halide and l-Lys. The surprising lability of the BesD•[Fe(IV)=O]•Cl•succinate•l-Lys complex engenders pathways for decay of the haloferryl intermediate that do not result in l-Lys chlorination, especially at low chloride concentrations; one identified pathway involves oxidation of glycerol. The mechanistic data imply (i) that BesD may have evolved from a hydroxylase ancestor either relatively recently or under weak selective pressure for efficient chlorination and (ii) that acquisition of its activity may have involved the emergence of linkage between l-Lys binding and chloride coordination following the loss of the anionic protein-carboxylate iron ligand present in extant hydroxylases.

Fe, N-codoped carbon derived from different ligands for oxygen reduction reaction in air-cathode microbial fuel cells: Performance comparison and the associated mechanism

In order to clarify the effect of iron ligands on properties, catalysts with different structure through four kinds of ligands are prepared and the oxygen reduction reaction (ORR) activity and the maximum power density in microbial fuel cells (MFCs) are compared. The formed Fe single atoms, the metal-organic framework compound, the Prussia blue crystal and ethylenediamine coordination compound (Phen-Fe, PA-Fe, PB-Fe and EDA-Fe) exhibit the maximum power densities of 2041 ± 23 mW m−2, 1656 ± 32 mW m−2, 1062 ± 31 mW m−2, and 1865 ± 36 mW m−2, respectively. In addition, the electrochemical performance of four catalysts with different structures is significantly different, and the higher exchange current density and 4-electron pathway of Phen-Fe explained the kinetics of ORR. The structures and surface properties are explored through a series of characterizations. The different amounts of nitrogen functionalities, Fe ion, and high graphitization degree are thought to facilitate electron transfer, lower Rct and improve ORR activity. In sum, the iron ligands have a great influence on the structure and performance of catalysts, and the single-atom structure and ethylenediamine coordination structure are proved to be promising structures for ORR in MFCs.

Nicotianamine synthase activity affects nucleolar iron accumulation and impacts rDNA silencing and RNA methylation in Arabidopsis.

In plant cells, a large pool of iron (Fe) is contained in the nucleolus, together with that in chloroplasts and mitochondria. A central determinant for intracellular distribution of Fe is nicotianamine (NA) generated by nicotianamine synthase (NAS). Here, we characterized Arabidopsis thaliana plants with disrupted NAS genes to modify accumulation of nucleolar iron and understand its role in nucleolar functions and more specifically in rRNA gene expression. We found that nas124 triple mutant plants, which contain lower quantities of the iron ligand NA, also contain less iron in the nucleolus. This is concurrent with the expression of normally silenced rRNA genes from Nucleolar Organizer Regions 2 (NOR2). Notably, in nas234 triple mutant plants, which also contain lower quantities of NA, nucleolar iron and rDNA expression are not affected. In contrast, in both nas124 and nas234, specific RNA modifications are differentially regulated in a genotype dependent manner. Taken together the data point out the impact of specific NAS activities in RNA gene expression. We discuss the interplay between NA and nucleolar iron with rDNA functional organization and RNA methylation.

Mechanistic Studies of Iron-PyBOX-Catalyzed Olefin Amino-Oxygenation with Functionalized Hydroxylamines.

Iron-catalyzed amino-oxygenation of olefins often uses discrete ligands to increase reactivity and broaden substrate scope. This work is focused on examining ligand effects on reactivity and in situ iron speciation in a system which utilizes a bisoxazoline ligand. Freeze-trapped 57Fe Mössbauer and EPR spectroscopies as well as SC-XRD experiments were utilized to isolate and identify the species formed during the catalytic reaction of amino-oxygenation of olefins with functionalized hydroxylamines, as well as in the precatalytic mixture of iron salt and ligand. Experiments revealed significant influence of ligand and solvent on the speciation in the precatalytic mixture which led to the formation of different species which had significant influence on the reactivity. In situ experiments showed no evidence for the formation of an Fe(IV)-nitrene intermediate, and the isolation of a reactive intermediate was unsuccessful, suggesting that the use of the PyBOX ligand led to the formation of more reactive intermediates than observed in the previously studied system, preventing direct detection of intermediate species. However, isolation of the seven coordinate Fe(III) species with three carboxylate units of the hydroxylamine and spin-trap EPR experiments suggest formation of a species with unpaired electron density on the hydroxylamine nitrogen, which is in accordance with formation of a potential iron iminyl radical species, as recently proposed in literature. An observed increase in yield when substrates devoid of C-H bonds as well as isolation of a ring-closed dead-end species with substrates containing these bonds suggests the identity of the functionalized hydroxylamine can dictate the reactivity observed in these reactions.

Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer's Disease: Experimental and Computational Insights.

Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people around the world. Even though the causes of AD are not completely understood due to its multifactorial nature, some neuropathological hallmarks of its development have been related to the high concentration of some metal cations. These roles include the participation of these metal cations in the production of reactive oxygen species, which have been involved in neuronal damage. In order to avoid the increment in the oxidative stress, multifunctional ligands used to coordinate these metal cations have been proposed as a possible treatment to AD. In this review, we present the recent advances in experimental and computational works aiming to understand the role of two redox active and essential transition-metal cations (Cu and Fe) and one nonbiological metal (Al) and the recent proposals on the development of multifunctional ligands to stop or revert the damaging effects promoted by these metal cations.

Carbon dioxide sequestration by mineral carbonation via iron complexation using bipyridine chelating ligands.

An innovative mineral carbonation method was developed to synthesize iron(II) carbonate (FeCO3) by cation complexation using 2,2'-bipyridine as ligand. First, complexes of iron(II) and different ligands were theoretically analyzed and discounted in terms of their temperature and pH-dependent stabilities, iron-ligand interactions, possible by-products and difficulty of analysis, choosing 2,2'-bipyridine as the most suitable ligand. Then, the Job plot was used to verify the complex formula. The stability of [Fe(bipy)3]2+ at pH 1-12 was further monitored for 7 days using UV-Vis and IR spectroscopy. Good stability was observed between pH 3 and 8, decreasing within pH 9-12 where the carbonation reaction occurs. Finally, the reaction between Na2CO3 and [Fe(bipy)3]2+ was performed at 21, 60, and 80 °C and pH 9-12. The total inorganic carbon measured after 2 h shows that the best carbonate conversion (50%) occurred at 80 °C and pH 11, being the most suitable conditions for carbon sequestration. SEM-EDS and XRD were used to examine the effect of synthesis parameters on the morphology and composition of FeCO3. The FeCO3 particle size increased from 10 μm at 21 °C to 26 and 170 μm at 60 and 80 °C respectively with no pH dependence. In addition, EDS analysis supported the carbonate identity, whose amorphous nature was confirmed by XRD. These results would help prevent the iron hydroxide precipitation problem during mineral carbonation using iron-rich silicates. These results are promising for its application as a carbon sequestration method with a CO2 uptake of around 50% obtaining Fe-rich carbonate.