Control of the Iron State in Pharmaceuticals Used for Treatment and Prevention of Iron Deficiency Using Mössbauer Spectroscopy.

Various iron-containing medicaments, vitamins and dietary supplements are used or developed for treatment and prevention of the iron deficiency anemia which is very dangerous for human and may cause various disorders. From the other hand, blood losses, iron poor diet, microelements (co-factors) deficiency, metabolic failures, absorption problems, etc. can change the iron status and affect the health. These pharmaceuticals contain iron compounds in the ferrous and ferric states. It is known that ferrous salts are more suitable for the intestinal intake than ferric ones. On the other hand, pharmaceutically important ferritin analogues contain ferric hydrous oxides and appear to be effective for both injections and peroral administration. 57Fe Mössbauer spectroscopy is a unique physical technique which allows one to study various iron-containing materials including pharmaceuticals. Therefore, this technique was applied to study iron-containing pharmaceuticals for the analysis of the iron state, identification of ferric and ferrous compounds, revealing some structural peculiarities and for detection of aging processes in relation to the iron compounds. This review considers the main results of a long experience in the study of iron-containing pharmaceuticals by Mössbauer spectroscopy with critical analysis that may be useful for pharmacists, biochemists, biophysicists, and physicians.

Comparative study of iron oxide nanoparticles as-prepared and dispersed in Copaiba oil using Mössbauer spectroscopy with low and high velocity resolution.

Iron oxide nanoparticles, probably magnetite, as-prepared and dispersed in Copaiba oil were studied by Mössbauer spectroscopy using two different spectrometers: with a low velocity resolution (512 channels) for measurements at 295 and 21K and with a high velocity resolution (4096 channels) for measurements at 295 and 90K. The fitting of all measured spectra demonstrated that usual models applied to fit Mössbauer spectra of magnetite and maghemite particles were not suitable. Therefore, the recorded spectra were fitted using a large number of spectral components on the basis of better quality of the fit and linearity of differential spectra. The number of components obtained for the better fit appeared to be different for spectra measured with a low and a high velocity resolution. However, these results demonstrated differences of Mössbauer parameters for iron oxide nanoparticles as-prepared and dispersed in Copaiba oil at applied temperatures. The effect of Copaiba oil molecules on Mössbauer parameters may be a result of the interactions of polar molecules such as kaurinic acid with nanoparticles' surface.

Iron-oxide aerogel and xerogel catalyst formulations: characterization by 57Fe Mössbauer and XAFS spectroscopies.

Iron in various iron-oxide aerogel and xerogel catalyst formulations (> or =85% Fe(2)O(3); < or =10% K, Co, Cu, or Pd) developed for possible use in Fischer-Tropsch synthesis (FTS) or the water-gas-shift (WGS) reaction has been examined by (57)Fe Mössbauer spectroscopy. The seventeen samples consisted of both as-prepared and calcined aerogels and xerogels and their products after use as catalysts for FTS or the WGS reaction. Complementary XAFS spectra were obtained on the occurrence of the secondary elements in some of the same materials. A broad, slightly asymmetric, two-peak Mössbauer spectrum was obtained from the different as-prepared and calcined catalyst formulations in the majority of cases. Such spectra could only be satisfactorily fit with three quadrupole doublet components, but no systematic trends in the isomer shift and quadrupole splitting parameters and area ratios of the individual components could be discerned that reflected variations in the composition or preparation of the aerogel or xerogel materials. However, significant reductions were noted in the Mössbauer effective thickness (recoilless absorption effect per unit mass of iron) parameter, chi(eff)/g, determined at room temperature, for aerogels and xerogels compared to bulk iron oxides, reflecting the openness and lack of rigidity of the aerogel and xerogel structures. Mössbauer measurements for two aerogels over the range from 15 to 292K confirmed the greatly diminished nature of this parameter at room temperature. Major increases in the effective thickness parameter were observed when the open structure of the aerogel or xerogel collapsed during calcination resulting in the formation of iron oxides (hematite, spinel ferrite). Similar structural changes were indicated by increases in this parameter after use of iron-oxide aerogels as catalysts for FTS or the WGS reaction, during which the iron-oxide aerogel was converted to a mixture of nonstoichiometric magnetite and the Hägg carbide, chi-Fe(5)C(2), or nonstoichiometric magnetite, respectively.

Reduction of Tc(VII) by Fe(II) sorbed on Al (hydr)oxides.

Under oxic conditions, Tc exists as the soluble, weakly sorbing pertechnetate [TcO4-] anion. The reduced form of technetium, Tc(IV), is stable in anoxic environments and is sparingly soluble as TcO2 x nH2O(s). Here we investigate the heterogeneous reduction of Tc(VII) by Fe(II) adsorbed on Al (hydr)oxides [diaspore (alpha-AlOOH) and corundum (alpha-Al2O3)]. Experiments were performed to study the kinetics of Tc(VII) reduction, examine changes in Fe surface speciation during Tc(VII) reduction (Mössbauer spectroscopy), and identify the nature of Tc(IV)-containing reaction products (X-ray absorption spectroscopy). We found that Tc(VII) was completely reduced by adsorbed Fe(II) within 11 (diaspore suspension) and 4 days (corundum suspension). Mössbauer measurements revealed thatthe Fe(II) signal became less intense with Tc(VII) reduction and was accompanied by an increase in the intensity of the Fe(III) doublet and magnetically ordered Fe(III) sextet signals. Tc-EXAFS spectroscopy revealed that the final heterogeneous redox product on corundum was similar to Tc(IV) oxyhydroxide, TcO2 x nH2O.

Use of rapid kinetics methods to study the assembly of the diferric-tyrosyl radical cofactor of E. coli ribonucleotide reductase.

The SF-Abs, RFQ-EPR, and RFQ-Möss data on the R2 reconstitution reaction are all consistent with the mechanism of Scheme I, in which the intermediate X is the immediate precursor to the product cofactor, and illustrate how the continuous SF approach and the discontinuous RFQ methods can be complementary. Given the inherent differences in the methods, it should not be taken for granted that data from the two will be consistent. A number of problems can be associated with the RFQ approach. For example, isopentane could conceivably interfere with or alter the chemistry to be studied. A second potential problem involves temperature-dependent equilibria among different intermediate species. This problem has been encountered by Dooley et al. with the 6-hydroxydopa-requiring protein, plasma amine oxidase and was previously observed with the adenosylcobalamin-dependent ribonucleotide reductase by Blakley and co-workers. This potential complication should be considered when discrepancies arise between SF and RFQ data and in low temperature structural studies of reactive intermediates in general. Each of the three methods employed can yield time-resolved quantitation of reaction components. In this regard, SF-Abs has the disadvantage of poor resolution, such that quantitation of individual components most often requires sophisticated mathematical analysis. Obvious advantages to the RFQ-Möss method are the presence of an internal standard (the known amount of 57Fe being proportional to the total absorption area) and the spectroscopic activity of all reaction components which contain iron. In our hands, quantitation by RFQ-EPR was most problematic and least reproducible. This irreproducibility most likely relates to heterogeneity among samples in terms of volume and density. As discussed in detail by Ballou and Palmer, the packing factor, which relates to the fraction of a sample made up by the reaction solution (the remainder being frozen isopentane), is dependent on the investigator. Given this caveat, it is not surprising that the RFQ-EPR data had the greatest uncertainty in our hands. Placing a chemically unreactive, EPR active standard in each reaction mixture could help alleviate this problem. Time-resolved Möss methods can be extremely powerful if excellent, nonoverlapping reference spectra of starting materials, products, and intermediates are available. All of the iron centers can be examined simultaneously. The problems associated with Möss arise from its extreme insensitivity. It takes millimolar solutions of proteins and several days for data collection of each time point.(ABSTRACT TRUNCATED AT 400 WORDS)

Complementary Mössbauer and EPR studies of iron(III) in diferric human serum transferrin with oxalate or bicarbonate as synergistic anions.

The spectral and magnetic properties of iron(III) bound in the metal binding sites of human serum transferrin with oxalate or bicarbonate as synergistic anions has been studied with Mössbauer spectroscopy and electron paramagnetic resonance (EPR). The Mössbauer spectra of the iron(III) in diferric transferrin with oxalate have been described using a spin Hamiltonian with the values of the zero field splitting parameter, D = 0.55 +/- 0.05 cm-1, and the rhombicity of the crystal field, E/D = 0.045 +/- 0.005. The EPR spectrum can be described with D = 0.58 cm-1 and E/D = 0.057, using a g-strain model for the lineshape that is based on a Gaussian distribution of D and E/D with Gaussian widths sigma(D) = 0.35 cm-1 and sigma(E/D) = 0.013, respectively. The rhombicity of the iron surroundings for the transferrin-oxalate complex is almost one order of magnitude smaller than for the bicarbonate complex and the zero field splitting parameter is twice as large in the oxalate as in the bicarbonate complex. We conclude that the crystal field symmetry of the iron site is almost tetragonal in the oxalate complex but rhombohedral in the bicarbonate complex, reflecting the different geometries of the oxalate and bicarbonate coordination. The isomer shift delta = 0.56 +/- 0.01 mm s-1 and the quadrupole splitting delta EQ = 0.2 +/- 0.1 mm s-1, on the other hand, are very close to the values found for the bicarbonate complex. No differences between the Mössbauer spectra of the two iron(III) ions in diferric transferrin with oxalate were found. The homogeneity of the diferric transferrin samples was controlled by capillary zone electrophoresis in the presence of urea.

Identification and characterization of the iron compounds in bone marrow by means of Mössbauer spectrometry.

In order to determine and to demonstrate the cellular iron molecular states in hematopoietic bone marrow, direct investigations were performed by means of different and complementary spectroscopic techniques: optical absorption, electron spin resonance and Mössbauer spectrometry. In fact, the latter appears to have been the most informative. In addition to the hemoglobin forms, five- and six-coordination ligand protoporphyrins IX (monomeric and polymeric stacking, respectively) were observed. A small amount of non-hemic high-spin iron III storage component (ferritin) was measured. No diferric transferrin was detected. A ferrous compound was also observed and attributed to the mitochondrial iron pool.