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Pharmaceuticals (Basel, Switzerland) Oct 2021The good chelating properties of hydroxypyrone (HPO) derivatives towards oxidovanadium(IV) cation, VO, constitute the precondition for the development of new...
The good chelating properties of hydroxypyrone (HPO) derivatives towards oxidovanadium(IV) cation, VO, constitute the precondition for the development of new insulin-mimetic and anticancer compounds. In the present work, we examined the VO complex formation equilibria of two kojic acid (KA) derivatives, L4 and L9, structurally constituted by two kojic acid units linked in position 6 through methylene diamine and diethyl-ethylenediamine, respectively. These chemical systems have been characterized in solution by the combined use of various complementary techniques, as UV-vis spectrophotometry, potentiometry, NMR and EPR spectroscopy, ESI-MS spectrometry, and DFT calculations. The thermodynamic approach allowed proposing a chemical coordination model and the calculation of the complex formation constants. Both ligands L4 and L9 form 1:1 binuclear complexes at acidic and physiological pHs, with various protonation degrees in which two KA units coordinate each VO ion. The joined use of different techniques allowed reaching a coherent vision of the complexation models of the two ligands toward oxidovanadium(IV) ion in aqueous solution. The high stability of the formed species and the binuclear structure may favor their biological action, and represent a good starting point toward the design of new pharmacologically active vanadium species.
PubMed: 34681261
DOI: 10.3390/ph14101037 -
Journal of Inorganic Biochemistry Aug 2023Desferoxamine (DFO) is currently the golden standard chelator for Zr, a promising nuclide for positron emission tomography imaging (PET). The natural siderophore DFO had...
Desferoxamine (DFO) is currently the golden standard chelator for Zr, a promising nuclide for positron emission tomography imaging (PET). The natural siderophore DFO had previously been conjugated with fluorophores to obtain Fe(III) sensing molecules. In this study, a fluorescent coumarin derivative of DFO (DFOC) has been prepared and characterized (potentiometry, UV-Vis spectroscopy) for what concerns its protonation and metal coordination properties towards PET-relevant ions (Cu(II), Zr(IV)), evidencing strong similarity with pristine DFO. Retention of DFOC fluorescence emission upon metal binding has been checked (fluorescence spectrophotometry), as it would - and does - allow for optical (fluorescent) imaging, thus unlocking bimodal (PET/fluorescence) imaging for Zr(IV) tracers. Crystal violet and MTT assays on NIH-3 T3 fibroblasts and MDA-MB 231 mammary adenocarcinoma cell lines demonstrated, respectively, no cytotoxicity nor metabolic impairment at usual radiodiagnostic concentrations of ZrDFOC. Clonogenic colony-forming assay performed on X-irradiated MDA-MB 231 cells showed no interference of ZrDFOC with radiosensitivity. Morphological biodistribution (confocal fluorescence, transmission electron microscopy) assays on the same cells suggested internalization of the complex through endocytosis. Overall, these results support fluorophore-tagged DFO as a suitable option to achieve dual imaging (PET/fluorescence) probes based on Zr.
Topics: Deferoxamine; Radioisotopes; Tissue Distribution; Ferric Compounds; Fluorescence; Positron-Emission Tomography; Chelating Agents; Coumarins; Cell Line, Tumor
PubMed: 37229819
DOI: 10.1016/j.jinorgbio.2023.112259 -
Molecules (Basel, Switzerland) Mar 2023Medicinal plants are an important source of bioactive compounds with a wide spectrum of practically useful properties. Various types of antioxidants synthesized in... (Review)
Review
Medicinal plants are an important source of bioactive compounds with a wide spectrum of practically useful properties. Various types of antioxidants synthesized in plants are the reasons for their application in medicine, phytotherapy, and aromatherapy. Therefore, reliable, simple, cost-effective, eco-friendly, and rapid methods for the evaluation of antioxidant properties of medicinal plants and products on their basis are required. Electrochemical methods based on electron transfer reactions are promising tools to solve this problem. Total antioxidant parameters and individual antioxidant quantification can be achieved using suitable electrochemical techniques. The analytical capabilities of constant-current coulometry, potentiometry, various types of voltammetry, and chrono methods in the evaluation of total antioxidant parameters of medicinal plants and plant-derived products are presented. The advantages and limitations of methods in comparison to each other and traditional spectroscopic methods are discussed. The possibility to use electrochemical detection of the antioxidants via reactions with oxidants or radicals (N- and O-centered) in solution, with stable radicals immobilized on the electrode surface, via oxidation of antioxidants on a suitable electrode, allows the study of various mechanisms of antioxidant actions occurring in living systems. Attention is also paid to the individual or simultaneous electrochemical determination of antioxidants in medicinal plants using chemically modified electrodes.
Topics: Plants, Medicinal; Antioxidants; Phytotherapy; Oxidation-Reduction; Oxidants
PubMed: 36903553
DOI: 10.3390/molecules28052308 -
Molecules (Basel, Switzerland) May 2023Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II),...
Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys-His and His-Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while similar CC and HH regions are found 348 and 94 times, respectively. Complex stabilities increase in the series Fe(II) < Ni(II) < Zn(II), with Zn(II) complexes dominating at physiological pH, and Ni(II) ones-above pH 9. The stabilities of Zn(II) complexes with Ac-ACHA-NH and Ac-AHCA-NH are comparable, and a similar tendency is observed for Fe(II), while in the case of Ni(II), the order of Cys and His does matter-complexes in which the metal is anchored on the third Cys (Ac-AHCA-NH) are thermodynamically stronger than those where Cys is in position two (Ac-ACHA-NH) at basic pH, at which point amides start to take part in the binding. Cysteine residues are much better Zn(II)-anchoring sites than histidines; Zn(II) clearly prefers the Cys-Cys type of ligands to Cys-His and His-Cys ones. In the case of His- and Cys-containing peptides, non-binding residues may have an impact on the stability of Ni(II) complexes, most likely protecting the central Ni(II) atom from interacting with solvent molecules.
Topics: Antimicrobial Peptides; Cysteine; Histidine; Metals; Peptides; Ferrous Compounds; Copper
PubMed: 37241727
DOI: 10.3390/molecules28103985 -
Journal of Inorganic Biochemistry Jul 2023Transition metal ions such as iron, copper, zinc, manganese or, nickel are essential in many biological processes. Bacteria have developed a number of mechanisms for...
Transition metal ions such as iron, copper, zinc, manganese or, nickel are essential in many biological processes. Bacteria have developed a number of mechanisms for their acquisition and transport, in which numerous of proteins and smaller molecules are involved. One of the representatives of these proteins is FeoB, which belongs to the Feo (ferrous ion transporter) family. Although ferrous iron transport system is widespread among microorganisms, it is still poorly described in Gram-positive pathogens, such as Staphylococcus aureus. In this work, combined potentiometric and spectroscopic studies (UV-Vis, CD and EPR) were carried out to determine Cu(II), Fe(II) and Zn(II) binding modes to FeoB fragments (Ac-IDYHKLMK-NH, Ac-ETSHDKY-NH, and Ac-SFLHMVGS-NH). For the first time iron(II) complexes with peptides were characterized by potentiometry. All studied ligands are able to form a variety of thermodynamically stable complexes with transition metal ions. It was concluded that among the studied systems, the most effective metal ion binding is observed for the Ac-ETSHDKY-NH peptide. Moreover, comparing preferences of all ligands towards different metal ions, copper(II) complexes are the most stable ones at physiological pH.
Topics: Copper; Staphylococcus aureus; Binding Sites; Ligands; Peptides
PubMed: 37018851
DOI: 10.1016/j.jinorgbio.2023.112203 -
RSC Advances Mar 2020The antioxidant capacity (AOC) of chicoric acid (ChA, the main antioxidant component of ) or an ethanol/water-extract of flowers was determined by potentiometric and...
The antioxidant capacity (AOC) of chicoric acid (ChA, the main antioxidant component of ) or an ethanol/water-extract of flowers was determined by potentiometric and UV-Vis absorption spectrophotometric titrations with ABTS˙ radical cations as the oxidizing probe. The potentiometric and spectrophotometric titration results agreed well with each other. The trolox-equivalent antioxidant capacity (TEAC) of ChA was found to be 5.00 ± 0.07 (potentiometry) and 4.81 ± 0.06 (spectrophotometry) at pH 7.4, and the TEAC value has been proven to be actually equal to the ratio of the stoichiometric ratio of the ABTS˙-ChA redox reaction to that of the ABTS˙-trolox redox reaction. The TEAC of the ethanol/water-extract of flowers, expressed in mM (trolox) per gram per liter ( extract), was found to be 0.241 ± 0.006 mmol g (potentiometry) and 0.240 ± 0.007 mmol g (spectrophotometry) at pH 7.4. The stoichiometric ratio of the ABTS˙-ChA redox reaction varied from 10.8 to 3.2, depending on the solution pH and the final ABTS˙-ChA concentration ratio. However, the stoichiometric ratio of the ABTS˙-trolox redox reaction remained 2.0 at various solution-pH values and final ABTS˙-trolox concentration ratios. The unusual stoichiometric ratio of the ABTS˙-ChA redox reaction is examined by potentiometric/spectrophotometric titrations and cyclic voltammetry, clearly revealing the new mechanism of a rapid redox process followed by a slow redox process at pH 7.4 and 9.0 when the ABTS˙-ChA molar concentration ratio is greater than 4. The electrochemistry methods coupled with spectrophotometry can conveniently and reliably provide important quantitative and qualitative information on redox chemistry, and are expected to find wider applications in accurately evaluating the redox activities of many other natural/synthesized antioxidants and oxidants.
PubMed: 35496633
DOI: 10.1039/d0ra01248c -
Scientific Reports Oct 2023The complexation of trivalent lanthanides and minor actinides (Am, Cm, and Cf) by the acyclic aminopolycarboxylate chelators...
The complexation of trivalent lanthanides and minor actinides (Am, Cm, and Cf) by the acyclic aminopolycarboxylate chelators 6,6'-((ethane-1,2-diylbis-((carboxymethyl)azanediyl))bis-(methylene))dipicolinic acid (Hoctapa) and 6,6'-((((4-(1-(2-(2-(2-hydroxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)pyridine-2,6-diyl)bis-(methylene))bis-((carboxymethyl)azanediyl))bis-(methylene)) dipicolinic acid (Hpypa-peg) were studied using potentiometry, spectroscopy, competitive complexation liquid-liquid extraction, and ab initio molecular dynamics simulations. Two studied reagents are strong multidentate chelators, well-suited for applications seeking radiometal coordination for in-vivo delivery and f-element isolation. The previously reported Hoctapa forms a compact coordination packet, while Hpypa-peg is less sterically constrained due to the presence of central pyridine ring. The solubility of Hoctapa is limited in a non-complexing high ionic strength perchlorate media. However, the introduction of a polyethylene glycol group in Hpypa-peg increased the solubility without influencing its ability to complex the lanthanides and minor actinides in solution.
PubMed: 37857726
DOI: 10.1038/s41598-023-44106-6 -
Ecotoxicology and Environmental Safety Mar 2024Deferiprone, generally, is considered an important chelating agent for Fe overload. From a literature data analysis, a lack of information on the interaction of this...
Deferiprone, generally, is considered an important chelating agent for Fe overload. From a literature data analysis, a lack of information on the interaction of this molecule toward a series of metal cations emerged, inducing to fill out the topic. The complexing ability of deferiprone toward Ca, Mg, Cd and Pb was studied by potentiometry and H NMR spectroscopy, in KCl aqueous solutions at different ionic strength values (0.1 ≤ I/mol dm ≤ 1.0) and T = 298.15 K. The same speciation model featured by the ML, ML, ML and ML(OH) (M = metal and L = deferiprone or DFP) species was obtained for Cd and Pb; the formation constants calculated at infinite dilution are: logβ = 7.23±0.02, 12.47±0.03, 16.70±0.04, and -2.53±0.04, respectively for Cd and 9.91±0.01, 15.99±0.02, 19.93±0.05 and 0.99±0.02 for Pb. Only two species, namely ML and ML, were determined for Ca and Mg, whose formation constants at infinite dilution are respectively: 3.72±0.01 and 6.50±0.02, for the first one, 5.31±0.01 and 9.58±0.01, for the second. The ligand sequestering ability and affinity toward M were evaluated by determining the pL and pM parameters at different pHs and ionic strengths. The results suggest that deferiprone has the best complexing and sequestering ability toward Pb, followed by Cd, Mg and Ca, respectively. H NMR studies confirmed the DFP affinity for Cd and Pb, and in combination with DFT calculations showed that metal cations are bound to the hydroxo-oxo moiety of the pyridinone ring. The data reported in this study provide information on the possible employment of a small molecule like deferiprone, as a chelating and sequestering agent for Pb accumulation or overload from environmental and biological matrices.
Topics: Deferiprone; Cadmium; Lead; Cations; Models, Theoretical; Chelating Agents
PubMed: 38295733
DOI: 10.1016/j.ecoenv.2024.116027 -
Inorganic Chemistry Feb 2020Protein aggregation has attracted substantial interest because of its role in causing many serious illnesses, such as neurodegenerative diseases and type II diabetes....
Protein aggregation has attracted substantial interest because of its role in causing many serious illnesses, such as neurodegenerative diseases and type II diabetes. Recent studies have shown that protein aggregation can be prevented by forming metal ion complexes with a target protein, which affects their conformation in solution and their physical properties, such as aggregation. Thus, understanding the interactions between aggregating molecules and bioactive metal ions such as Cu is beneficial for new drug discovery. Pramlintide, a synthetic peptide drug, and its natural counterpart rat amylin are known to be resistant to aggregation because of the presence of proline residues, which are usually β-sheet "breakers" within their amino acid sequence. Here, we investigate the Cu coordination properties of pramlintide and rat amylin using nuclear magnetic resonance, circular dichroism, electron paramagnetic resonance, ultraviolet-visible spectroscopy, potentiometry, and mass spectrometry. We test the influence of Cu on the aggregation properties of these amylin analogues with thioflavin T assays. We find that both peptides form stable complexes with Cu with similar affinities at a 1:1 ratio. The N-termini of both peptides are involved in Cu binding; His18 imidazole is an equally attractive binding site in the case of pramlintide. Our results show that Cu ions influence the aggregation of pramlintide, but not that of rat amylin.
Topics: Amino Acid Sequence; Animals; Binding Sites; Coordination Complexes; Copper; Islet Amyloid Polypeptide; Protein Binding; Protein Multimerization; Rats
PubMed: 32027132
DOI: 10.1021/acs.inorgchem.9b03498 -
Analytical Science Advances Jun 2021In this paper, we demonstrate the suitability, sensitivity, and precision of low-cost and easy-to-use ion-selective electrodes (ISEs) for concurrent detection of NH and...
In this paper, we demonstrate the suitability, sensitivity, and precision of low-cost and easy-to-use ion-selective electrodes (ISEs) for concurrent detection of NH and NO in soil and water by technical and non-technical end-users to enable efficient soil and water management exposed to chronic reactive nitrogen loading. We developed a simplified methodology for sample preparation followed by the demonstration of an analytical methodology resulting in improvements of sensitivity and precision of ISEs. Herein, we compared and contrasted ISEs with traditional laboratory-based technique such as Flow Injection Analysis (FIA) and portable colorimetric assay followed by comparisons of linear regression and Bayesian nonlinear calibration approaches applied on both direct potentiometry and standard addition modes of analysis in terms of in-field applications and improvement of sensitivity and precision. The ISEs were validated for sensing on a range of ambient soil and water samples representing a range of NH and NO concentrations from pristine to excessive saturation conditions. Herein developed methodology showed excellent agreement with lab-based and portable analytical techniques while demonstrating improvements in precision and sensitivity analysis illustrated by a decrease in confidence intervals by 50-60%. We also demonstrated the utilization of the entire ISE response curve thus removing the biases originating from linear approximation which is often currently employed. Therefore, we show that ISEs are robust yet low cost and an easy to use technology that can enable high-frequency measurement of mineral N and help to improve our understanding of N transformation processes as influenced by soil management, fertilization, land use, and climate change.
PubMed: 38716159
DOI: 10.1002/ansa.202000124