Journal of Biological Inorganic Chemistry最新文献

The rise of atmospheric oxygen as a result of photosynthesis in cyanobacteria and chloroplasts has transformed most environmental iron into the ferric state. In contrast, cells within organisms maintain a reducing internal milieu and utilize predominantly ferrous iron. Ferric reductases are enzymes that transfer electrons to ferric ions, either extracellularly or within endocytic vesicles, enabling cellular ferrous iron uptake through Divalent Metal Transporter 1. In mammals, duodenal cytochrome b is a ferric reductase of the intestinal epithelium, but how insects reduce and absorb dietary iron remains unknown. Here we provide indirect evidence of extracellular ferric reductase activity in a small subset of Drosophila melanogaster intestinal epithelial cells, positioned at the neck of the midgut’s anterior region. Dietary-supplemented bathophenanthroline sulphate (BPS) captures locally generated ferrous iron and precipitates into pink granules, whose chemical identity was probed combining in situ X-ray absorption near edge structure and electron paramagnetic resonance spectroscopies. An increased presence of manganese ions upon BPS feeding was also found. Control animals were fed with ferric ammonium citrate, which is accumulated into ferritin iron in distinct intestinal subregions suggesting iron trafficking between different cells inside the animal. Spectroscopic signals from the biological samples were compared to purified Drosophila and horse spleen ferritin and to chemically synthesized BPS-iron and BPS-manganese complexes. The results corroborated the presence of BPS-iron in a newly identified ferric iron reductase region of the intestine, which we propose constitutes the major site of iron absorption in this organism.

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The following comment tries to answer why the reported removal of copper from buffer, cell culture medium, and cell extract by a supported chelator called phenPS is so selective and efficient. It is further argued that the family of PSP (phosphine sulfide-stabilized phosphines) chelators, due to their unique properties, have various potential future application in biology and medicine such as chelation therapy, copper-sensors, or tools to understand copper metabolism.

Radical increase of antibiotic resistance among microbes has become a serious problem for clinics all over the world that has led to the need for search of novel types of antimicrobial drugs. Each year, researchers synthesize a multitude of compounds in pursuit of identifying potential chemotherapeutic agents through diverse methodological evaluations. Among the vast array of biologically significant compounds, coordination compounds exhibit a broad range of activities within biological systems. Chelation, in particular, induces significant alterations in the biological properties of ligands and the metal component, contributing to their efficacy. Chelation increases the lipophilicity of metal complexes as a result of which they are easily absorbed by the microorganisms, thus leading to their easy passage across cell membrane. The research and development in the field of metallodrugs can be advantageous to overcome the problem encountered in antibiotic resistance. The multifaceted involvement of vanadium relative to other biometals within biological systems, coupled with its comparatively lower toxicity, underscores its utility in the advancement of novel metal-based therapeutic agents. This review aims to delineate the biological significance of V(V/IV/III) complexes as antimicrobial agents. The amassed data indicate a correlation between the potency of vanadium complexes as antimicrobial agents and the oxidation state of the metal, with III being the least toxic and V representing the most toxic oxidation state of vanadium.

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The onset of resistance to artemisinin for malaria treatment has stimulated the quest for novel antimalarial drugs. Herein, the gold(III) coordination complexes Aubipy [Au(bipy)Cl]⁺ (bipy = 2,2′-bipyridine), Auphen [Au(phen)Cl]⁺ (phen = phenanthroline), Auterpy [Au(terpy)Cl]²⁺ (terpy = 2,2′;6′,2″-terpyridine), and corresponding hydrolyzed species, have been investigated as inhibitors of the Plasmodium falciparum aquaglyceroporin (PfAQP) protein by computational methods. Through an in-silico approach using an Umbrella Sampling protocol to sample how Aubipy, Auphen, and Auterpy permeate through the PfAQP, their permeability coefficients were estimated using the Inhomogeneous Solubility Diffusion (ISD) model with promising results. The efficacy of the gold complexes was then probed by an in vitro assay testing the growth inhibition in chloroquine sensitive and resistant P. falciparum strains. In accordance with the computational data, Auterpy achieved the highest efficiency with an IC₅₀ in the nanomolar range (590 nM) on resistant strain cultures, additionally revealing a good selectivity as compared to its activity against the human aquaglyceroporin 3.

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In 1983, Linus Pauling and colleagues reported about enhanced antitumor activity of the Cu(II) complex of the simplest ATCUN (amino terminal Cu(II) and Ni(II)-binding motif) peptide (NH₂-Gly-Gly-His-COOH, GGH) in the presence of ascorbate as an additive. In the following 4 decades, structural modifications of this complex were implemented, however, anticancer activity could not be significantly increased. This has led to neglecting the ATCUN motif and its Cu(II) complexes as potential chemotherapeutic agents. Furthermore, the addition of ascorbate with its positive effect on the anticancer activity has fallen into oblivion. In this work, we compared Cu(II) GGH with Cu(II) ATCUN peptides bearing β-Ala instead of Gly at the 2nd position of the peptide sequence regarding their in vitro complex stability and cytotoxicity (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and annexin V-FITC (fluorescein isothiocyanate) apoptosis assay) towards three cancer cell lines (AGS, HeLa and NCI-N87). Such an exchange of amino acids led to an up to three-fold higher cytotoxic effect in the presence of ascorbate. We thus achieved a significant increase in the otherwise moderate cytotoxicity of Cu(II) ATCUN-like complexes. Lipophilicity assays (n-octanol/water coefficient, log P values) of the studied complexes were used to evaluate differences in the antiproliferative activity.

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Examples of how metalloproteins feature in electron transfer processes in biological systems are reviewed. Attention is focused on the electron transport chains of cellular respiration and photosynthesis, and on metalloproteins that directly couple electron transfer to a chemical reaction. Brief mention is also made of extracellular electron transport. While covering highlights of the recent and the current literature, this review is aimed primarily at introducing the senior undergraduate and the novice postgraduate student to this important aspect of bioinorganic chemistry.

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Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using o-cresolphthalein complexone (o-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by o-CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.

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Occupational exposure to heavy metals affects various organ systems and poses a significant health risk to workers. Consequently, its precise estimation is of clinical concern and warrants the need for an analytical method with reliable precision and accuracy. The current study aimed to develop an analytical method using inductively coupled plasma‒mass spectrometry (ICP-MS) to detect trace to elevated levels of potentially toxic elements in human blood. The sample preparation was optimized using a two-step ramp temperature microwave acid digestion program. The toxic elements were quantified using ICP-MS operating in kinetic energy discrimination (KED) mode, adjusting the data acquisition parameters and instrumental settings. The analytical method was validated using standard performance parameters. Each validation parameter was aligned with the acceptable criteria outlined in standard guidelines. The method achieved optimal linearity (r² > 0.99), recovery (85.60–112.00%), and precision (1.35–7.03%), was capable of detecting the lowest concentrations of 0.32, 0.28, 0.28, and 0.19 µg/L, and was capable of quantifying trace levels of 1.01, 0.88, 0.90, and 0.62 µg/L for arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb), respectively. Post-validation, the method was applied to estimate heavy metals in blood samples from 250 Pb-smelting plant workers, revealing potential health implications of occupational exposure. The cohort analysis revealed that demographic and employment factors were associated with elevated blood Pb levels, leading to symptoms and health risks. Clinical analysis revealed that 33.6% of the participants experienced hypertension. These findings highlight the significant health risks associated with elevated blood Pb levels. The weak but significant correlation with systolic blood pressure underscores the need for improved monitoring and workplace safety. This emphasizes the importance of continuous monitoring, targeted interventions, and enhanced occupational hygiene to protect workers’ well-being.

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Mössbauer parameters of low-spin six-coordinate [Fe(II)(Por)L₂] complexes (where Por is a synthetic porphyrin; L is a nitrogenous aliphatic, an aromatic base or a heterocyclic ligand, a P-bonding ligand, CO or CN) and low-spin [Fe(Por)LX] complexes (where L and X are different ligands) are reported. A known point charge calculation approach was extended to investigate how the axial ligands and the four porphyrinato-N atoms generate the observed quadrupole splittings (ΔE_Q) for the complexes. Partial quadrupole splitting (p.q.s.) and partial chemical shifts (p.c.s.) values were derived for all the axial ligands, and porphyrins reported in the literature. The values for each porphyrin are different emphasising the importance/uniqueness of the [Fe(PPIX)] moiety, (which is ubiquitous in nature). This new analysis enabled the construction of figures relating p.c.s and p.q.s values. The relationships presented in the figures indicates that strong field ligands such as CO can, and do change the sign of the electric field gradient in the [Fe(II)(Por)L₂] complexes. The limiting p.q.s. value a ligand can have and still form a six-coordinate low-spin [Fe(II)(Por)L₂] complex is established. It is shown that the control the porphyrin ligands exert on the low-spin Fe(II) atom limits its bonding to a defined range of axial ligands; outside this range the spin state of the iron is unstable and five-coordinate high-spin complexes are favoured. Amongst many conclusions, it was found that oxygen cannot form a stable low-spin [Fe(II)(Por)L(O₂)] complex and that oxy-haemoglobin is best described as an [Fe(III)(Por)L(O₂⁻)] complex, the iron is ferric bound to the superoxide molecule.

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