Aluminum Chelates Research Articles

Ionomic analysis of Prosopis laevigata response to heavy metals: phytoremediation potential determined by wavelength-dispersive X-ray fluorescence

Prosopis laevigata (mesquite) plants can tolerate drought, thermal stress, alkalinity, salinity, and toxicity of heavy metals, making them attractive for phytoremediation. Nonetheless, most of these features have been studied under controlled laboratory conditions. In this work, the bioaccumulation of heavy metals in a free-living population of P. laevigata trees growing in a heavily metal-contaminated site (aluminum, chromium, iron, titanium, copper, and zinc) was analyzed. Furthermore, crystal phases of mineral nutrients and trace elements found in P. laevigata tissues were determined by X-ray diffraction. P. laevigata trees accumulated 705 (± 17), 47,064 (± 1459), 14,800 (± 401) and 30,000 (± 1719) mg/kg of Cu, Zn, Fe and Al, confirming the potential of these plants to hyper-accumulate metals. The X-ray diffraction analysis showed that P. laevigata trees can chelate Al3+ with phosphates to form orthorhombic crystals of aluminum phosphate (AlPO4) in the tissues. This aluminum chelation was probably a mechanism of tolerance used by the plant. The inoculation of seedlings with the endophytic Bacillus cereus MH778713 did not prevent Cr-accumulation in the plant but increased metal tolerance and seedling development. These results highlight the use of P. laevigata and B. cereus MH778713 together as tools for heavy metal bioremediation, particularly on arid and semiarid soils.

Drugs Causing Cystoid Macular Edema: Pathogenesis, Diagnosis, and Treatment

Cystoid macular edema (CME) is a disorder that usually develops in association with ocular pathologies or systemic diseases. Various topical or systemic drugs are also known to lead to the formation of cystoid macular edema. Anti-hyperlipidemic drug niacin (nicotinic acid), antineoplastic agents taxanes (paclitaxel/docetaxel), oral antidiabetic drugs glitazones, iron, and aluminum chelator deferoxamine, and fingolimod used in the treatment of multiple sclerosis are drugs used systemically and shown to be associated with macular edema. In addition, epinephrine and prostaglandin analogs are ocular agents known to be associated with CME. The purpose of this article is to provide an overview of the available scientific evidence on the development of drug-induced cystoid macular edema and to provide insight into possible pathophysiological mechanisms and therapeutic approaches.

Polychelates Based on Magnesium, Aluminum, Iron, Zirconium, and Vanadyl Acetylacetonates - Synthesis, Structure and Properties

The formation of polymeric acetylacetonates of magnesium, aluminum, iron, zirconium, and vanadyl under conditions of mechanochemical activation with subsequent condensation in boiling toluene has been investigated. The obtained compounds have been studied by the methods of gel chromatography, X-ray diffractometry, and positron annihilation and IR spectroscopy. Aluminum chelates have been studied by means of NMR spectroscopy. It has been demonstrated that the mechanochemical activation with subsequent boiling in toluene results in the formation of polymeric chelates, mostly those of iron, zirconium and, to a smaller degree, chelates of aluminum, magnesium, and vanadyl. The molecular weight of soluble high-molecular fractions is in the range 3000–5000 Da. The layered polymer structure has been revealed. Cross-section areas of polymer chains and volumes of coherent scattering regions have been calculated from the diffractometry data. The morphology of polymers consisting of spherical particles of sizes in the range 100–700 nm has been investigated. Based on the data of positron annihilation spectroscopy (PAS), density, and nitrogen low-temperature adsorption, the dependence of the chelate stability on the specific polarizing potential has been determined. A fractal structure of solid-state polychelates has been revealed.

The Labeling, Visualization, and Quantification of Hyaluronan Distribution in Tumor-Bearing Mouse Using PET and MR Imaging.

Hyaluronan (HA) based biomaterials are widely used as tissue scaffolds, drug formulations, as well as targeting ligands and imaging probes for diagnosis and drug delivery. However, because of the presence of abundant endogenous HA presented in various tissues in vivo, the pharmacokinetic behavior and biodistribution patterns of exogenously administered HAs have not been well characterized. The HA backbone was modified with Diethylenetriamine (DTPA) to enable the chelation of gadolinium (Gd) and aluminum (Al) ions. Series of PET and MR imaging were taken after the injection of HA-DTPA-Gd and HA-DTPA-Al18F while using18F-FDG and Magnevist(DTPA-Gd) as controls. The Tomographic images were analyzed and quantified to reveal the distribution and locations of HA in tumor-bearing mice. The labeled HAs had good stability in plasma. They retained binding affinity towards CD44s on tumor cell surface. The injected HAs distributed widely in various organs, but were found to be cleared quickly except inside tumor tissues where the signals were higher and persisted longer. Medical imaging tools, including MR and PET, can be highly valuable for examining biomaterial distribution non-invasively. The HA tumor accumulation properties may be explored for the development of active targeting drug carriers and molecular probes.

Major phosphorus in soils is unavailable, yet critical for plant development

Phosphorus (p) is a chemical component that has a concentration in the world’s land mass of around one gram for each kilogram. 85% to 95% of cellular phosphorus is available in the vacuole, 31p-nmr examinations uncovers the inadequacy of inorganic phosphorus (pi) efflux from the vacuole to make-up for a fast reduction of the cytosolic pi focus during phosphorus starvation. Activities of phosphorus use involve biogeochemical mechanisms of phosphorus in soil, the phosphorus cycle, chelation of iron (Fe), manganese (Mn) and aluminium (Al) and their subsequent removal from forming insoluble phosphorus compounds, transformation of phosphorus in the soil, and fixation of phosphorus in the soil. Phosphorus utilisation occur through solubilization by microbes which could be bacteria, fungi or bio-fertilizers that produce phytohormone, siderophores and antibiotics. However, factors affecting phosphorus solubilization are pH and temperature which are key predominant players for phosphorus adsorption dynamics from the soil and rhizosphere by plants, soil phosphorus transformation, spatial availability and acquisition of soil phosphorus, root architecture, bioavailability and acquisition of soil phosphorus, phosphorus cycling and bioavailability in soil-plant systems, its chemistry as well as its final uptake and utilization by plants. Overall, the phosphorus nutrition of plants is majorly monitored by phosphorus dynamics in the soil/rhizosphere-plant continuum. Given the usefulness of phosphorus to plants and its importance as a strategic resource, a better understanding of phosphorus dynamics in the soil/rhizosphere-plant continuum is necessary to lead the establishment of integrated phosphorus-management strategies involving manipulation of soil and rhizosphere activities, development of phosphorus-efficient crops, and improving phosphorus-recycling efficiency in the future.

A first-principles study on potential chelation agents and indicators of Alzheimer's disease.

Human-serum transferrin is involved in the transportation of aluminum across the blood–brain barrier. Aluminum accumulation within the neuron causes the cell to degrade. In our research, we considered 12 potential chelators of aluminum from the aluminum–human serum transferrin complex and 3 potential indicators of Alzheimer's. We performed Density Functional Theory calculations comparing the binding energies of aluminum–chelator complexes and the binding energy of the aluminum–human serum transferrin complex and determined the charge transfer of the aluminum–chelator complex. Our results showed that CDTA is the only one that has direct chelation potential, but 1-ethyl-3-hydroxypyridin-2-one, citric acid, DTPA, oxalic acid, and salicylhydroxamic acid also had a strong and stable bond with aluminum and still have the ability to be potential chelators. The charge transfer calculation further enforces that these 6 chelators have strong and stable bonds with aluminum. Furthermore, we evaluated potential indicators of Alzheimer's disease. Metals that have a similar binding affinity to human serum transferrin as that of iron prove to be potential indicators of Alzheimer's disease. Due to the minimal difference in binding energies of the gallium–human serum transferrin complex and the indium–human serum transferrin complex to the iron–human serum transferrin complex, we determined that gallium and indium could be potential indicators of Alzheimer's disease.

Insight on the chelation of aluminum(III) and iron(III) by curcumin in aqueous solution

In this work we have studied the complexation of curcumin (HCur, 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) with Al(III) and Fe(III) at 37 °C and in 0.16 M NaCl. The protonation constant of curcumin was also determined to evaluate the competition of the ligand for the metal cations and H+. Speciation profiles obtained by potentiometric titrations show that in aqueous solution a complexation occurs at 1:1 ligand-to-cations ratio. With the aim to define the coordination sites of curcumin with these metal ions a mass spectrometry and UV–Vis spectroscopy characterization was carried out. It was found that aluminum binds to the keto-enol moiety of curcumin, while iron binds to the guaiacol (2-methoxyphenol) one. This unexpected experimental evidence was supported by a thorough computational study.

In silico design of mimosine containing peptides as new efficient chelators of aluminum

The design of new and efficient chelators that can remove aluminium(iii), a metal with increasing recognition as a potential toxic agent, from biological systems is an area of high therapeutic relevance. In the present paper, we present an extensive computational study of a new promising type of these chelators based on mimosine containing peptides. The reason to choose mimosine is that the sidechain of this residue is similar to deferiprone, a ligand known to tightly interact with highly-valent metals, and in particular with Al(iii). In this article we analyze systematically, using a combination of methods that include QM/MM MD simulations, how the size and sequence of the polypeptides can alter the fundamental binding patterns to aluminum, in comparison with the binding to deferiprone. Particular attention is given towards the identification of the smallest peptide that interacts efficiently with aluminum, since polypeptide size is a fundamental factor to allow a given polypeptide to efficiently cross the cell membrane. The results indicate that the longest peptides, with 8 or 9 amino acids, show no difficulties interacting with Al(iii) in an optimum arrangement. By contrast, when the peptide contains five or six amino acids Al(iii) is pentacoordinated, reducing the stability of the resultant complex. In summary, our study demonstrates that the mimosine containing peptides can efficiently coordinate highly valent metals such as Al(iii), with a subtle dependence of the binding on the specific chain-lengths of the polypeptide. We believe that the present study sheds light on the adequacy of this new type of chelator towards aluminum binding.

Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: synthesis, solution equilibrium studies and in vivo evaluation

This paper reports the results on the study of a set of synthesized bifunctional 3-hydroxy-4-pyridinones chelators as potential aluminium sequestering agents. They were N-functionalized with alkyl-amino, -carboxylic and –(amino-carboxylic) groups, envisaging the improvement of the Al3+ sequestering capacity, in comparison with the marketed chelating drug deferiprone. The main focus of this work was given to the assessment of their binding ability towards Al3+, which was studied by potentiometric and UV–Vis spectrophotometric measurements carried out at T = 298.15 K. The speciation models were characterized by AlpLqHr(3p+r−qz) species with different stoichiometry. Depending on ligand side-chain structures and on their thermodynamic properties, different trends of stability was found. Furthermore, the sequestering ability of the ligands towards Al3+ was investigated by the calculation of pL0.5 values at different experimental conditions. These results clearly indicate that the presence of amino-carboxylic groups in the ligands increases the sequestering ability towards Al3+. The in silico evaluation of pharmacokinetic descriptors indicated no violation to the Lipinski's rule and drug-likeness properties. Furthermore, the in vivo bioassays on a model of metal-overload mice showed for three investigated ligands a higher metal-sequestering capacity than for the chelating drug deferiprone, thus suggesting their potential interest as Al-chelating drug candidates.

18F-AlF Labeled Peptide and Protein Conjugates as Positron Emission Tomography Imaging Pharmaceuticals

The clinical applications of positron emission tomography (PET) imaging pharmaceuticals have increased tremendously over the past several years since the approval of 18fluorine-fluorodeoxyglucose (18F-FDG) by the Food and Drug Administration (FDA). Numerous 18F-labeled target-specific potential imaging pharmaceuticals, based on small and large molecules, have been evaluated in preclinical and clinical settings. 18F-labeling of organic moieties involves the introduction of the radioisotope by C-18F bond formation via a nucleophilic or an electrophilic substitution reaction. However, biomolecules, such as peptides, proteins, and oligonucleotides, cannot be radiolabeled via a C-18F bond formation as these reactions involve harsh conditions, including organic solvents, high temperature, and nonphysiological conditions. Several approaches, including 18F-labeled prosthetic groups, silicon, boron, and aluminum fluoride acceptor chemistry, and click chemistry have been developed, in the past, for 18F labeling of biomolecules. Linear and macrocyclic polyaminocarboxylates and their analogs and derivatives form thermodynamically stable and kinetically inert aluminum chelates. Hence, macrocyclic polyaminocarboxylates have been used for conjugation with biomolecules, such as folate, peptides, affibodies, and protein fragments, followed by 18F-AlF chelation, and evaluation of their targeting abilities in preclinical and clinical environments. The goal of this report is to provide an overview of the 18F radiochemistry and 18F-labeling methodologies for small molecules and target-specific biomolecules, a comprehensive review of coordination chemistry of Al3+, 18F-AlF labeling of peptide and protein conjugates, and evaluation of 18F-labeled biomolecule conjugates as potential imaging pharmaceuticals.

Investigation on effect of basalin coated silver nanoparticles as antioxidant for alleviating peripheral neuropathy in mice treated with oxaliplatin

A facile, convenient, and green method for the synthesis of BAgNPs by using basalin is proposed in this work. The capping of the basalin on the surface of BAgNP was confirmed by the zeta potential and FTIR findings. Further, we have injected prepared BAgNPs into oxaliplatin-treated mice to alleviate neuropathic pain. The aluminum levels in the DRG were reduced by the chelating activity of BAgNPs. Moreover, behavioral analyses also manifested that the accumulation of aluminum on the DRG might be a reason for neuropathic hyperalgesia. These findings also recommended that the chelation of aluminum by AgNPs could provide an effective remedy to alleviate the symptoms of oxaliplatin-induced neuropathic pain in cancer patients.

A computational study on interaction of aluminum withd-glucose 6-phosphate for various stoichiometries

The interaction of aluminum with glucose 6-phosphate is thought to disrupt key processes of the glucide metabolism in cells. Complex and rich aluminum chelation chemistry is found in Aluminum-glucose 6-phosphate speciation study.

Aluminum chelates supported by β-quinolyl enolate ligands: synthesis and ROP of ε-CL.

Treatment of tautomers of β-quinolyl ketone-enaminones with AlMe3 afforded β-quinolyl enolato dialkylaluminium complexes LAlMe2 (L = [(2-C9H6N)-CH[double bond, length as m-dash]C(R)-O-], R = CH3 (), (t)Bu (), Ph (), o-tolyl (), p-tolyl (), p-OMePh ()), respectively. reacted with benzyl alcohol to generate the corresponding LAl(OBn)2 complex . Complexes and were characterized by (1)H and (13)C NMR spectroscopy, elemental analyses and single crystal X-ray diffraction analyses. All complexes were tested as catalyst precursors for ring-opening polymerization of ε-caprolactone (ε-CL). The results indicated that LAlMe2 () exhibited good activity towards the ROP of ε-CL in the presence of benzyl alcohol at 80 °C, and LAl(OBn)2 exhibited higher catalytic activity in the absence of alcohol than for the ROP of ε-CL. However, both polymerizations were less controlled. Kinetic studies showed that the polymerization reaction catalyzed by and proceeded with first-order dependence on the monomer and took place through coordination-insertion.

PP284-MON: Use of Bone Mineral Densitometry Following Aluminum Chelation in Children on Long Term Parenteral Nutrition

PP284-MON: Use of Bone Mineral Densitometry Following Aluminum Chelation in Children on Long Term Parenteral Nutrition

Mapping the affinity of aluminum(III) for biophosphates: interaction mode and binding affinity in 1 : 1 complexes.

The interaction of aluminum with biomolecular building blocks is a topic of interest as a first step to understand the potential toxic effects of aluminum in biosystems. Among the different molecules that aluminum can bind in a biological environment, phosphates are the most likely ones, due to their negatively charged nature. In the present paper, we combined DFT quantum mechanical calculations with the implicit solvent effect in order to characterize the interaction of Al(III) with these molecules. An extended set composed of a total of 59 structures was investigated, which includes various types of phosphates (monoester, diester, triester-phosphates) and various phosphate units (mono-, di- and tri-phosphate), considering various charge and protonation states, and different binding modes. The goal is to unveil the preferential interaction mode of Al(III) with phosphates in 1 : 1 complexes. Our results reveal that Al(III) prefers to form dicoordinated complexes with two phosphates, in which the interaction with each of the phosphates is of monodentate character. Our results also suggest a high affinity for binding basic phosphate groups, pointing to ATP, phosphorylated peptides, and basic diphosphates (such as 2,3-DPG) as strong aluminum chelators.

NHC Bis-Phenolate Aluminum Chelates: Synthesis, Structure, and Use in Lactide and Trimethylene Carbonate Polymerization

A novel family of Al(III) complexes supported by a tridentate, dianionic N-heterocyclic carbene bis-phenolate ligand ((OCO)2–) was prepared via various synthetic routes, and the derived compounds were all structurally characterized. The methane elimination reaction of the protio ligand N,N′-bis(2-hydroxy-3,5-di-tert-butylphenyl)-4,5-dihydroimidazolium chloride (1·H3Cl) with AlMe3 quantitatively led to the formation of the bis-phenolate imidazolinium Al zwitterion (1·H)Al(Me)(Cl) (2), whose formulation was established by X-ray diffraction studies. The deprotonation of species 2 with 1 equiv of lithium diisopropylamide (LDA) proceeded with the elimination of LiCl to afford the Al-NHC methyl derivative [(OCO)AlMe]2 (3), which was isolated as a dimer, as confirmed by X-ray diffraction studies. Alternatively, compound 3 may be accessed via a salt metathesis route involving the reaction of the NHC bis-phenolate Li salt 1·Li2, generated in situ via reaction of 1·H3Cl with 3 equiv of nBuLi (−40 °C, THF), with 1 equiv of MeAlCl2. The serendipitous hydrolysis of compound 3 allowed the X-ray characterization of the Al-oxo dinuclear species [(OCO)Al-O-Al-(OCO)] (3′), in which both Al(III) centers adopt a distorted-trigonal-monopyramidal geometry. The reaction of the salt 1·H3Cl with Al(OiPr)3 afforded the corresponding bis-phenolate imidazolinium Al zwitterion (1·H)Al(OiPr)(Cl) (4), which incorporates a four-coordinate tetrahedral Al center effectively κ2O,O-chelated by the two phenolate moieties of the OCO2– ligand. Compound 4 may be readily converted to the Al-NHC alkoxide derivative [(OCO)AlOiPr]2 (5) upon reaction with 1 equiv of LDA. Alternatively, the alcoholysis of the Al-NHC methyl species 3 with iPrOH also permitted access to the derived Al alkoxide 5 and proceeds via the formation of the kinetic product (1·H)Al(OiPr)(Me) (6) that may readily eliminate methane upon heating to produce species 5. The Al alkoxide species 5 was shown to efficiently polymerize rac-lactide and trimethylene carbonate in a highly controlled manner for the production of narrow disperse materials. The observed catalytic performances are in the range of the majority of those for group 13 metal based ROP catalysts developed thus far, and all data support the noninvolvement of the NHC moiety in these polymerization reactions.

Aluminum and its potential contribution to Alzheimer's disease (AD).

Aluminum and its potential contribution to Alzheimer's disease (AD).

Bathochromic and Hyperchromic Effects of Aluminum Salt Complexation by Anthocyanins from Edible Sources for Blue Color Development

Use of artificial food colorants has declined due to health concerns and consumer demand, making natural alternatives a high demand. The effects of Al(3+) salt on food source anthocyanins were evaluated with the objective to better understand blue color development of metalloanthocyanins. This is one of the first known studies to evaluate the effects of food source anthocyanin structures, including acylation, with chelation of aluminum. Cyanidin and delphinidin derivatives from different plants were treated with factorial excess of Al(3+) in pH 3-6 and evaluated by spectrophotometry and colorimetry over 28 days. Anthocyanin concentration, salt ratio, and pH determined final color and intensity. Pyrogallol moieties on delphinidin showed furthest bathochromic shifts, whereas acylation promoted higher chroma. Blue color developed at lower pH when acylated anthocyanins reacted with Al(3+); hue ∼270 occurred with acylated delphinidin at pH ≥ 2.5. Highest chelate stability was found with AlCl3100-500× anthocyanin concentration. This investigation showed anthocyanin-metal chelation can produce a variety of intense violet to blue colors under acidic pH with potential for food use.

Searching for new aluminium chelating agents: A family of hydroxypyrone ligands

Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminiumIII complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and 1H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog.

Evaluation of 1,2-dimethyl-3-hydroxy-4-pyridinecarboxylic acid and of other 3-hydroxy-4-pyridinecarboxylic acid derivatives for possible application in iron and aluminium chelation therapy

Four new possible chelating agents for iron and aluminium, 1,2-dimethyl-3-hydroxy-4-pyridinecarboxylic acid (DT712), 3-hydroxy-1,2,6-trimethyl-4-pyridinecarboxylic acid, 2,6-dimethyl-3-hydroxy-4-pyridinecarboxylic acid, and 2-ethyl-3-hydroxy-1-methyl-4-pyridinecarboxylic acid, were synthesized, and their complex formation with Fe(III) and Al(III) was studied by potentiometry, UV–Vis, 1H NMR, and electrospray mass spectrometry (ESI-MS). Number, stoichiometry, and stability constants of metal–ligand complexes were obtained at 25°C in aqueous (Na)Cl 0.6m. DT712 is the most promising hydroxypyridinecarboxylic acid considered so far for iron chelation therapy, as it forms the strongest Fe(III) complexes. This compound was further investigated to better clarify its possible behaviour in vivo with particular respect to iron chelation therapy. UV–Vis measurements were performed to determine the kinetics by which DT712 extracts Fe(III) from transferrin. DT712 resulted to have better kinetic properties than existing iron chelators. Ternary metal/DT712/citric acid complexes were studied by ESI-MS to check the competition with a typical low molecular weight ligand in the blood. The formation of only binary Fe(III)/DT712 and Al(III)/DT712 complexes (and ternary complexes in aged solutions), suggests that DT712 effectively compete with citric acid in the metal complexation. Standard reduction potentials of Fe(III)/DT712 complexes, and the kinetic constants of complex formation, were obtained by cyclic voltammetry. Accordingly, no redox cycling is expected to occur at in vivo conditions, and Fe(III)/DT712 complex formation should not be kinetically limited. On the basis of the present results, DT712 is proposed as candidate for iron chelation therapy.