The fate of iron nanoparticles used for treatment of iron deficiency in blood using mass-spectrometry based strategies

The release of iron from iron nanoparticles (NPs) used as parenteral formulations appears to be influenced by the size and surface properties of the colloidal iron complex and the matrix. A clinically applied product Venofer® has been used as a model formulation to establish adequate analytical strategies to evaluate the fate of iron nanoparticles (NPs) in blood. First, the preparation was characterized by high resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS) and UV-vis absorption spectroscopy. This revealed the presence of monodisperse iron NPs with a hydrodynamic diameter of ～15 nm and an iron core of ～4 nm. Venofer® was then incubated with serum and whole blood in a quantitative study on the iron bioavailability from these NPs. Iron was speciated and quantified by using inductively coupled plasma mass spectrometry (ICP-MS). Iron solubilization levels of up to 42% were found in both fluids using isotope dilution of iron for quantification within the first hour of incubation even in the absence of the reticulo-endothelial system. The monitoring of the iron-containing proteins present in serum was conducted by high-performance liquid chromatography with ICP-MS detection. It indicated that the dissolved iron ions are bound to transferrin. Quantitative speciation studies using isotope pattern deconvolution experiments concluded that the released iron saturated almost completely (up to 90%) the metal binding sites of transferrin. The remaining iron appeared also associated to albumin and, to a lesser extent, forming smaller sized particles. Thus, the methods presented here provide new insights into the fate of Venofer® nanoparticles and may be applied to other formulations.

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Graphical abstract The release of iron ions from sucrose covered iron nanoparticles used as parenteral formulations is evaluated in serum and whole blood by elemental mass spectrometry.

     

Chemical dissolution of iron in aqueous solutions

By anodic oxidation of hydrogen on the Pt ring of a metal-disk-Pt-ring rotating electrode in aqueous acid (pH 0.5–3) sulfate solutions, it is shown that during the polarization of the metal disk hydrogen coevolves by two parallel reactions. One is the well known electrochemical charge transfer process, while the other one is a direct chemical reaction of the metal, i.e. iron, with water molecules from the electrolyte. This process was proposed a long time ago by Kolotyrkin and co-workers, but their experimental results were subjected to serious criticism which is taken care of in the present paper. The chemical reaction is potential- and pH-independent and, depending on the actual conditions during the corrosion processes (actual potential, pH, etc.), can be of greater or smaller importance in the overall process. The consequences of the existence of this direct chemical reaction of metal with water molecules (i.e. H₂O-induced corrosion or chemical corrosion) on pitting and stress corrosion cracking of metals is discussed. Dedicated to the ninetieth anniversary of Ya.M. Kolotyrkin’s birth. This article was submitted by the authors in English.     

Sample handling strategies for the determination of biophenols in food and plants

The analysis of phenols in samples of plant and food origin attracts considerable attention. However, sample handling is often an ignored feature of the analysis. This review highlights the importance of sample extraction in an analysis and the problems that can arise during this step. Many questions remain unanswered and there is a need to more carefully validate extraction efficiencies. Although many new procedures have been developed the use of traditional techniques still dominates.     

Chemical protein synthesis-assisted high-throughput screening strategies for d-peptides in drug discovery

_D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,_D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One _D-peptide etelcalcetide has even entered the market that targets the calcium(Ca²⁺)-sensing recepto...     

Chemical defence strategies of higher fungi

Like plants, fungi have evolved a variety of defence strategies in order to protect themselves against feeding mammals, insects and infection with parasitic fungi. In contrast to plants little is known on the chemical ecology of fruiting bodies of higher fungi, particularly those defence mechanisms which are induced upon wounding have only occasionally been recognised. Methods both for the detection of permanently present defence compounds and for the elucidation of wound-activated chemical defence mechanisms are discussed in this concept paper.     

化学标记与蛋白质/多肽的识别检测

化学标记技术可以实现选择性地标记蛋白质/多肽分子,从而极大地提高了对蛋白质/多肽的识别效率和检测灵敏度,是突破蛋白质/多肽化学组成局限和仪器分析检测能力瓶颈的有效途径.本文对目前这一领域的研究现状扼要地进行了综述,主要包括针对蛋白质/多肽分子中内源氨基酸残基的标记策略、蛋白质/多肽分子中翻译后修饰基团的标记策略、基因编码表达肽段的标记策略以及配体/抗体亲和标记策略.透过这些研究所取得的成果,可以断定化学标记技术将会不断发展并将在蛋白质及蛋白质组学研究中发挥重要作用.     

Chemical process to separate iron oxides particles in pottery sample for EPR dating

Ancient potteries usually are made of the local clay material, which contains relatively high concentration of iron. The powdered samples are usually quite black, due to magnetite, and, although they can be used for thermoluminescene (TL) dating, it is easiest to obtain better TL reading when clearest natural or pre-treated sample is used. For electron paramagnetic resonance (EPR) measurements, the huge signal due to iron spin-spin interaction, promotes an intense interference overlapping any other signal in this range. Sample dating is obtained by dividing the radiation dose, determined by the concentration of paramagnetic species generated by irradiation, by the natural dose so as a consequence, EPR dating cannot be used, since iron signal do not depend on radiation dose. In some cases, the density separation method using hydrated solution of sodium polytungstate [Na6(H2W12O40).H2O] becomes useful. However, the sodium polytungstate is very expensive in Brazil; hence an alternative method for eliminating this interference is proposed. A chemical process to eliminate about 90% of magnetite was developed. A sample of powdered ancient pottery was treated in a mixture (3:1:1) of HCl, HNO(3) and H(2)O(2) for 4h. After that, it was washed several times in distilled water to remove all acid matrixes. The original black sample becomes somewhat clearer. The resulting material was analyzed by plasma mass spectrometry (ICP-MS), with the result that the iron content is reduced by a factor of about 9. In EPR measurements a non-treated natural ceramic sample shows a broad spin-spin interaction signal, the chemically treated sample presents a narrow signal in g=2.00 region, possibly due to a radical of (SiO(3))(3-), mixed with signal of remaining iron [M. Ikeya, New Applications of Electron Spin Resonance, World Scientific, Singapore, 1993, p. 285]. This signal increases in intensity under gamma-irradiation. However, still due to iron influence, the additive method yielded too old age-value. Since annealing at 300 degrees C, Toyoda and Ikeya [S. Toyoda, M. Ikeya, Geochem. J. 25 (1991) 427-445] states that E1'-signal with maximum intensity is obtained, while annealing at 400 degrees C E1'-signal is completely eliminated, the subtraction of the second one from 300 degrees C heat-treated sample isolate E1'-like signal. Since this is radiation dose-dependent, we show that now EPR dating becomes possible.     

Abiotic chelators and iron acquisition in living organisms: From molecular iron(III) chelators to self-assembled nanostructures

The story of the highly selective iron(III) chelating agent O-TRENSOX is presented. The promising (and somewhat unexpected in regard to partition coefficients) properties of this molecule induced the development of several tools for iron metabolism studies. The tuning of the properties of O-TRENSOX by chemical modifications of the parent molecules is also developed. Finally, fascinating perspectives are opened by amphiphilic derivatives which mimic marine siderophores from phytoplankton. The self-assembling properties of amphiphilic abiotic chelators and their iron derivatives, as well as the first results concerning iron nutrition of Erwinia chrysanthemi and some mutants, have been studied.     

Chemical reactions in electric pulse dispersion of iron in aqueous solutions

IR spectroscopy, X-ray phase, chemical, kinetic, and thermodynamic analyses were used to determine the nature of chemical reactions occurring in electric pulse dispersion of a metal (Fe) in aqueous solutions of inorganic substances (MnSO₄, NaH₂AsO₄, H₃AsO₃, K₂Cr₂O₇).     

Isotope pattern deconvolution as a tool to study iron metabolism in plants

Isotope pattern deconvolution is a mathematical technique for isolating distinct isotope signatures from mixtures of natural abundance and enriched tracers. In iron metabolism studies measurement of all four isotopes of the element by high-resolution multicollector or collision cell ICP–MS allows the determination of the tracer/tracee ratio with simultaneous internal mass bias correction and lower uncertainties. This technique was applied here for the first time to study iron uptake by cucumber plants using ⁵⁷Fe-enriched iron chelates of the o,o and o,p isomers of ethylenediaminedi(o-hydroxyphenylacetic) acid (EDDHA) and ethylenediamine tetraacetic acid (EDTA). Samples of root, stem, leaves, and xylem sap, after exposure of the cucumber plants to the mentioned ⁵⁷Fe chelates, were collected, dried, and digested using nitric acid. The isotopic composition of iron in the samples was measured by ICP–MS using a high-resolution multicollector instrument. Mass bias correction was computed using both a natural abundance iron standard and by internal correction using isotope pattern deconvolution. It was observed that, for plants with low ⁵⁷Fe enrichment, isotope pattern deconvolution provided lower tracer/tracee ratio uncertainties than the traditional method applying external mass bias correction. The total amount of the element in the plants was determined by isotope dilution analysis, using a collision cell quadrupole ICP–MS instrument, after addition of ⁵⁷Fe or natural abundance Fe in a known amount which depended on the isotopic composition of the sample.     

Photodynamic effect of iron excess on photosystem II function in pea plants

An earlier mechanistic phase of iron toxicity in photosynthetic cells was interpreted in terms of enhanced photodynamic action by the cytochrome b6/f complex (Cyt b6/f) via singlet oxygen (1O2) on the photosystem II complex (PS II). Iron excess was induced in hydroponically cultured pea (Pisum sativum L.) plants, and its effect on the function of PS II in vivo as well as in vitro was studied under high-irradiance conditions. Iron excess in plants gave rise to a significant increase in Cyt b6/f content of thylakoids. It appeared that the larger the content of Cyt b6/f, the more susceptible PS II was to photoinhibition, and the higher the rate of 1O2 photoproduction in thylakoids was. The action spectrum for degradation of the D1 protein in thylakoids revealed that photosensitization by nonporphyrin chromophore(s) was apparently associated with near UV to blue light-induced deterioration of PS II. The results are pertinent to the concept that photooxidative damage to PS 11, exacerbated by iron accumulation in thylakoid membranes in the form of Cyt b6/f, is involved in the mechanism of iron toxicity in leaf cells.     

Chemical control of competing electron transfer pathways in iron tetracyano-polypyridyl photosensitizers

Photoinduced intramolecular electron transfer dynamics following metal-to-ligand charge-transfer (MLCT) excitation of [Fe(CN)₄(2,2′-bipyridine)]²⁻ (1), [Fe(CN)₄(2,3-bis(2-pyridyl)pyrazine)]²⁻ (2) and [Fe(CN)₄(2,2′-bipyrimidine)]²⁻ (3) were investigated in various solvents with static and time-resolved UV-Visible absorption spectroscopy and Fe 2p3d resonant inelastic X-ray scattering (RIXS). This series of polypyridyl ligands, combined with the strong solvatochromism of the complexes, enables the ¹MLCT vertical energy to be varied from 1.64 eV to 2.64 eV and the ³MLCT lifetime to range from 180 fs to 67 ps. The ³MLCT lifetimes in 1 and 2 decrease exponentially as the MLCT energy increases, consistent with electron transfer to the lowest energy triplet metal-centred (³MC) excited state, as established by the Tanabe–Sugano analysis of the Fe 2p3d RIXS data. In contrast, the ³MLCT lifetime in 3 changes non-monotonically with MLCT energy, exhibiting a maximum. This qualitatively distinct behaviour results from a competing ³MLCT → ground state (GS) electron transfer pathway that exhibits energy gap law behaviour. The ³MLCT → GS pathway involves nuclear tunnelling for the high-frequency polypyridyl breathing mode (hν = 1530 cm⁻¹), which is most displaced for complex 3, making this pathway significantly more efficient. Our study demonstrates that the excited state relaxation mechanism of Fe polypyridyl photosensitizers can be readily tuned by ligand and solvent environment. Furthermore, our study reveals that extending charge transfer lifetimes requires control of the relative energies of the ³MLCT and the ³MC states and suppression of the intramolecular distortion of the acceptor ligand in the ³MLCT excited state.

Photoinduced intramolecular electron transfer in Fe tetracyano-polypyridyl complexes was investigated with static and time-resolved UV-visible absorption and resonant inelastic X-ray scattering which revealed a competition of two relaxation pathways.     

Chemical stability of sulfate ions deposited on iron oxide

Sulfate ions deposited on iron oxide were thermally stable up to ca. 770 K. When pyridine, ammonia, n-butane, and 1-butene were preadsorbed, however, they decomposed to generate gaseous SO₂ at much lower temperatures due to the reaction between these molecules and sulfate ions. Implications of these findings in characterization and catalysis of this type of superacid catalyst are discussed.

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Chemical strategies and characterization tools for the organization of single molecule magnets on surfaces

Addressing individual bistable magnetic molecules, known as Single Molecule Magnets (SMMs), is a fascinating goal at the borderline between molecular magnetism and spin electronics. This tutorial review focuses on the first step towards single-molecule experiments, namely the organization of SMMs on surfaces. Both preparation and characterization of surface-supported SMMs prove to be quite demanding and a multidisciplinary approach is necessary, which is described here using selected examples. We first illustrate the chemical strategies devised to assemble SMMs and to control their orientation on surfaces. Then, we present characterization tools, which have been selected on the basis of their relevance to address specific points, i.e. the chemical composition of the deposited SMM films, the organization of the molecules on the surface, the intramolecular arrangement of the spins, the magnetic anisotropy of SMMs, and eventually the dynamics of their magnetization on surfaces. Particular attention is devoted to techniques exploiting synchrotron light.     

Role of fulvic acids for transporting and fixing phosphate and iron ions in bean plants by radiotracer technique

Among humic substances formed by organic matter decomposition process, fulvic acids have been extensively studied because their solubility and soil fertilizer properties. This paper describes how some mineral nutrient elements are absorbed by the root as well as the foliage of bean plants and how they move in both directions depending on their association to fulvic acids. In this study, radiotracers of phosphate and iron have been used (H₂ ³²PO₄ ^-, ⁵⁹Fe²⁺). The results obtained are quantitative by instrumental detection and qualitative by autoradiography of the radiotracers. A very clear effect has been found about motion and fixation of phosphate and iron ions in bean plants brought about by fulvic acids commercially produced in Mexico by organic synthesis. This effect seems to be the more homogeneous distribution in the vegetable tissues of the mineral ions absorbed from the soil. This revised version was published online in August 2006 with corrections to the Cover Date.