Role of copper chelating agents: between old applications and new perspectives in neuroscience

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Polarizable Additive with Intermediate Chelation Strength for Stable Aqueous Zinc‑Ion Batteries

Aqueous zinc-ion batteries are promising due to inherent safety,low cost,low toxicity,and high volumetric capacity.However,issues of dendrites and side reactions between zinc metal anode and the electrolyte need to be solved for extended storage and cycle life.Here,we proposed that an electrolyte additive with an intermediate chelation strength of zinc ion—strong enough to exclude water molecules from the zinc metal-electrolyte interface and not too strong to cause a significant energy barrier for zinc ion dissociation—can benefit the electrochemical stability by suppressing hydrogen evolution reaction,overpotential growth,and den-drite formation.Penta-sodium diethylene-triaminepentaacetic acid salt was selected for such a purpose.It has a suitable chelating ability in aqueous solutions to adjust solvation sheath and can be readily polarized under electrical loading conditions to further improve the passivation.Zn||Zn symmetric cells can be stably operated over 3500 h at 1 mA cm^(-2).Zn||NH4V4O10 full cells with the additive show great cycling stability with 84.6%capacity retention after 500 cycles at 1 A g^(-1).Since the additive not only reduces H2 evolution and corrosion but also modifies Zn2+diffusion and deposition,highlyreversible Zn electrodes can be achieved as verified by the experimental results.Our work offers a practical approach to the logical design of reliable electrolytes for high-performance aqueous batteries.

Electrode/Electrolyte Interfacial Chemistry Modulated by Chelating Effect for High-Performance Zinc Anode

Although Zn metal has been regarded as the most promising anode for aqueous batteries,its practical application is still restricted by side reactions and dendrite growth.Herein,an in-situ solid electrolyte interphase(SEI)film formed on the interface of electrode/electrolyte during the plating/stripping of zinc anodes by introducing trace amounts of multidentate ligand sodium diethyldithiocarbamate(DDTC)additive into 1 M ZnSO_(4).The synergistic effect of in-situ solid electrolyte interphase forming and chelate effect endows Zn^(2+)with uniform and rapid interface-diffusion kinetics against dendrite growth and surface side reactions.As a result,the Zn anode in 1 M ZnSO_(4)+DDTC electrolytes displays an ultra-high coulombic efficiency of 99.5%and cycling stability(more than 2000 h),especially at high current density(more than 600 cycles at 40 mA cm^(-2)).Moreover,the Zn//MnO_(2)full cells in the ZnSO_(4)+DDTC electrolyte exhibit outstanding cyclic stability(with 98.6%capacity retention after 2000 cycles at 10 C).This electrode/electrolyte interfacial chemistry modulated strategy provides new insight into enhancing zinc anode stability for high-performance aqueous zinc batteries.

Influence of pH value and chelating reagent on performance of Li_3V_2(PO_4)3/C cathode material

The Li3V2（PO4）3/C composite cathode material was synthesized via sol-gel method using three different chelating agents （citric acid, salicylic acid and polyacrylic acid） at pH value of 3 or 7. The crystal structure, morphology, specific surface area and electrochemical performance of the prepared samples were investigated by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, cyclic voltammetry （CV）, electrochemical impedance spectroscopy （EIS） and galvanostatic charge/discharge test. The results show that the effects of pH value on the performance of the prepared materials are greatly related to the chelating agents. With salicylic acid or polyacrylic acid as the chelating reagent, the structure, morphology and electrochemical performance of the samples are greatly influenced by the pH values. However, the structure of the materials with citric acid as the chelating agent does not change as pH value changes, and the materials own uniform particle size distribution and good electrochemical performance. It delivers an initial discharge capacity of 113.58 mA·h/g at 10C, remaining as high as 108.48 mA·h/g after 900 cycles, with a capacity retention of 95.51%.

A Novel Approach to Synthesizing Porous ZnO Films: Inorganic Chelating Sol-Gel Method

Porous ZnO films are synthesized by inorganic chelating sol-gel method,which is a novel sol-gel technique using zinc nitrate as starting materials and citric acid as the chelating reagent.The crystal structure,surface morphology,porous and optical properties of the deposited films are investigated.X-ray diffraction pattern analysis shows that crystal structure of the ZnO films is hexagonal wurtzite.Scanning electron microscopy (SEM) shows that the ZnO film is porous.The curve of pore size distribution has two peak values at about 2.02nm and 4.97nm and BET surface area of the ZnO film is 27.57m2/g.In addition,the transmittance spectrum gives a high transmittance of 85% in the visible region and optical bandgap of the ZnO film (fired at 500℃) is 3.25eV.

Effect of Combined Treatments of Phytohormones and Chelating Agents on the Accumulation Capacity of Amaranth

[Objective] To explore a high efficient phytoremediation technology for soil pollution. [Method] Foliage application and root irrigation were carried out to study the influence on amaranth repair efficiency by using combined treatments of phytohor- mones （IAA, GA3 SA） and chelating agents （EDTA）. [Result] The combined treatment increased the biomass of amaranth under 133Cs, 88Sr, Cr stress The 133Cs, 88Sr, Cr enrich- ment in amaranth by root irrigation were obviously higher than that by foliage appli- cation. The phytoextraction efficiency of phytohormones and chelating agents from best to poor was as following： 100 mg/L SA＋1.5 mg/kg EDTA, 500 mg/L GA3＋1.5 mg/kg EDTA, 100 mg/L IAA＋1.5 mg/kg EDTA. [Conclusion] The most appropriate treatment was the combined treatment of 100 mg/L SA＋l.5mg/kg EDTA by soil irri- gation, which could make the total absorption doses of 133Cs, 88Sr, Cr per plant achieve the maximum.

Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)in longterm iron loading β-thalassemic mice

Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) mice.Methods:The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1|50 mg/(kg·day)| for 6 months.Blood levels of non-transferrin hound iron,labile plasma iron.ferritin(Ft) and malondialdehyde were determined.Results:The BKO mice were fed with an iron diet for 8 months which resulted in iron overload.Interestingly,the mice showed a decrease in the non—transferrin bound iron,labile plasma iron and malondialdehyde levels,but not the Ft levels after continuous CM1 treatment.Conclusions:CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β—thalassemic mice.

Superior growth performance in broiler chicks fed chelated compared to inorganic zinc in presence of elevated dietary copper

Background： The goal of this study was to compare the antagonism of elevated dietary Cu （250 mg/kg） from CuS04 on three different Zn sources （ZnS04. H20; [Zn bis（-2-hydroxy-4-（methylthio）butanoic acid）], Zn（HMTBa）2 a chelated Zn methionine hydroxy analogue; and Zn-Methionine）, as measured using multiple indices of animal performance in ROSS 308 broilers. Methods： Three experiments were conducted in broiler chicks fed a semi-purified diet. All birds were fed a Zn-deficient diet （8.5 mg/kg diet） for 1 wk, and then provided with the experimental diets for 2 wks. Results： Experiment 1 was a 2 x 2 factorial design with two levels of Cu （8 vs. 250 mg/kg diet from CuSO4） and two Zn sources at 30 mg/kg [ZnSO4. H20 vs. Zn（HMTBa）2]. Elevated Cu impaired growth performance only in birds fed ZnSO4. Compared to ZnSO4. H20, Zn（HMTBa）2 improved feed intake （12 %; P 〈 0.001） and weight gain （12 %, P 〈 0.001） and the benefits were more pronounced in the presence of 250 mg/kg diet Cu. Experiment 2 was a dose titration of ZnSO4- H20 and Zn（HMTBa）2 at 30, 4,5, 60, and 75 mg/kg diet in the presence of 250 mg/kg CuSO4. Feed：gain was decreased and tibia Zn was increased with increasing Zn levels from 30 to 75 mg/kg. Birds fed Zn（HMTBa）2 consumed more food and gained more weight compared to birds fed ZnSO4, especially at lower supplementation levels （30 and 45 mg/kg; interaction P 〈 0,05）. Experiment 3 compared two organic Zn sources （Zn（HMTBa）2 vs. Zn-Methionine） at 30 mg/kg with or without 250 mg/kg CuSO4. No interactions were observed between Zn sources and Cu levels on performance or tissue mineral concentrations. High dietary Cu decreased weight gain （P 〈 0.01）. Tibia Cu and liver Cu were significantly increased with 250 mg/kg dietary Cu supplementation （P 〈 0.01）. No difference was observed between the two Zn sources. Conclusions： Dietary 250 mg/kg Cu significantly impaired feed intake and weight gain in birds fed ZnSO4. H20, but had less impact in birds fed Zn（HMTBa）2. No difference was observed between the two organic zinc sources These results are consistent with the hypothesis that chelated organic Zn is better utilized than inorganic zinc in the presence of elevated Cu.

Processing and Microstructure of LaCrO_3 Thin Film Derived from Chelating Precursors

LaCrO 3 thin films were successfully prepared at lower temperatures by the sol gel process based on organic chelating precursors. The formation and transition of the gel derived from the chelate solution were analyzed by means of IR, DTA TG, XRD and TEM. In addition, the formation and microstructure of thin films were investigated by SEM and XRD. The results show that the gel formed by the condensation reaction is decomposed at about 195 ℃, transformed into a great quantity of LaCrO 3 by heat treating at 200 ℃ for 1 h, and the complexing ways in the gel have an important influence upon the formation of LaCrO 3. The formation process of thin film includes the nucleation and growth on the substrate, the formation of polycrystalline islands and the continuous film by repeating the dip coating process. Higher heat treatment temperature gives rise to larger granules in the thin film.

Progress on Study of Luminescence of Rare Earth Organic Chelates

Based on the investigation of the luminescence of a series of rare earth organic chelates, some relationships between luminescence and the structure of the chelates were proposed: the intensity of sensitized luminescence of central lanthanide ions(Ln 3+ ) in a rare earth organic chelate depends on (1)the suitability of the energy gap between the excited triplet energy level of the ligands and the lowest excited energy level of Ln 3+ ions; (2)the rigidity and planarity of the structure of the chelate molecule; (3)the existence of a suitable secondary ligand which may increase rigidity and the stability of the chelate molecule; and (4) the existence of a suitable π conjugated system in the chelate molecule. According to the above relationships, 25 novel organic ligands were designed and synthesized, and their lanthanide chelates were prepared. Investigation of the photoluminescence for the new chelates shows that some of the chelates are strongly luminescent, and are applied to fluoroimmunoassay for determination of human immunoglobulin(IgG), to preparation of fluorescent plastics, and to determination of growth hormone for plants. Two novel spectroscopy probe techniques for structure of coordination compounds and biological molecules were proposed and developed based on vibronic spectroscopy of Tb 3+ complexes and fluorescence of Ce 3+ .

Synthesis of novel silica-supported chelating resin containing tert-butyl 2-picolyamino-N-acetate and its properties for selective adsorption of copper from simulated nickel electrolyte

A novel silica-supported tert-butyl 2-picolyamino-N-acetate chelating resin (Si-AMPY-1) was successfully synthesized and characterized by elemental analysis, FT-IR, SEM and 13 C CP/MAS NMR. The adsorption behaviors of the Si-AMPY-1 resin for Cu(Ⅱ) and Ni(Ⅱ) were studied with batch and column methods. The batch experiments indicated that the Si-AMPY-1 resin adsorbed Ni(Ⅱ) mainly via physisorption, while adsorbed Cu(II) via chemisorption. The column dynamic breakthrough curves revealed thatthe Si-AMPY-1 resin can efficiently separate Cu(Ⅱ) from the simulated nickel electrolyte before the breakthrough point. Moreover, the concentration of Cu(Ⅱ) in the column effluent was decreased to be less than 3 mg/L within the first 43 BV (bed volumes), and the mass ratio of Cu/Ni was 21:1 in the saturated resin, which completely satisfied the industrial requirements of the nickel electrorefining process. Therefore, it was concluded that the Si-AMPY-1 resin can be a promising candidate for the deep removal of Cu(Ⅱ) from the nickel electrolyte.

A new synthetic chelating collector for the flotation of oxidized-lead mineral

A new synthetic reagent DPTUHP [diphenyl α-（3-phenylthioureido） hexylpbosphonate] containing a hydrocarbon chain nonpolar group, a thioureido, and a phosphonate easter chelating group, has proven to be an effective collector for the flotation of cerussite mineral. The synthetic method utilized the Mannich-type reaction of an N-monosubstituted thiourea, an aldehyde, and triphenyl phosphate in glacial acetic acid solution. The experimental results of flotation of the cerussite mineral show that the collector has stronger collecting ability and higher selectivity in a neutral and a slightly alkaline medium, especially in the pulp of pH=8. Using the measurements by infrared spectroscopy （IR） and X-ray photoelectron spectroscopy （XPS） of the cerussite mineral, the collector, as well as the cerussite treated with the collector, the flotation mechanism of cerussite has been discussed. It is concluded that the adsorption of collector on cerussite is a chemical adsorption through the electron donor atoms of the collector chelating the Pb （ Ⅱ ） of cerussite to form chelate.

Air-Stable Ultrabright Inverted Organic Light-Emitting Devices with Metal Ion-Chelated Polymer Injection Layer

Here,this work presents an air-stable ultrabright inverted organic lightemitting device(OLED)by using zinc ionchelated polyethylenimine(PEI)as electron injection layer.The zinc chelation is demonstrated to increase the conductivity of the PEI by three orders of magnitude and passivate the polar amine groups.With these physicochemical properties,the inverted OLED shows a record-high external quantum efficiency of 10.0% at a high brightness of 45,610 cd m^(-2) and can deliver a maximum brightness of 121,865 cd m^(-2).Besides,the inverted OLED is also demonstrated to possess an excellent air stability(humidity,35%)with a half-brightness operating time of 541 h@1000 cd m^(-2) without any protection nor encapsulation.

Selection of Chelated Fe(Ⅲ)/Fe(Ⅱ) Catalytic Oxidation Agents for Desulfurization Based on Iron Complexation Method

Optimization of factors influencing the experiments on reactions involving 8 different chelating agents and soluble Fe(III)/Fe(II) salts was carried out to yield chelated iron complexes. A combination of optimized influencing factors has resulted in a Fe chelating capacity of the iron-based desulfurization solution to be equal to 6.83—13.56 g/L at a redox potential of 0.185—0.3. The desulfurization performance of Fe(III)/Fe(II) chelating agents was investigated on a simulated sulfur-containing industrial gas composed of H2 S and N2 in a cross-flow rotating packed bed. Test results have revealed that the proposed iron-based desulfurization solution showed a sulfur removal efficiency of over 99% along with a Fe chelating capacity exceeding 1.35 g/L. This desulfurization technology which has practical application prospect is currently in the phase of commercial scale-up study.

SYNTHESES AND ADSORPTION PROPERTIES OF PHENOL-FORMALDEHYDE-TYPE CHELATING RESINS BEARING THE FUNCTIONAL GROUP OFTAR TARIC ACID

Several kinds of novel chelating resins bearing the functional group of tartaric acid (TTA-FQ-12, TTA-FQ-23, and TTA-FQ-34) were synthesized by reacting epoxy maleic anhydride, which was prepared through the oxidization reaction of maleic anhydride by hydrogen peroxide, with phenol-formaldehyde resin containing polyamine (FQ resins series). The effects of such factors as reaction time, reaction temperature and pH value on the loading capacity of TTA in resins were investigated. The results showed that the optimum reaction conditions are as follows: time 9-12 h; temperature 90-105'C; pH value 6-10. The loading capacities of TTA can reach 0.15, 0.14, and 0.11 mmol/g-1 when the functional group of FQ resin was - OCH2CH2NHC2H4NH2, - O(CH2CH2NH)2C2H4NH2 and - O(CH2CH2NH)3C2H4NH2), respectively. The structures of resins were characterized by FTIR spectra. The primary study on the adsorption properties of the resins for metal ions showed that there are two kinds of adsorption mechanisms i.e. ion exchange and chelate in the adsorption process. TTA-FQ resins have much higher adsorption selectivity for Pb2+and Zn2+ than for Cu2+ and Ni2+. These resins can probably be used for separating Pb2+ or Zn2+ in the mixture of metal ions or for treating wastewater containing heavy metal ions.

Synthesis and Adsorption Properties of Polystyrene-supported Chelating Resins Containing Heterocyclic Functional Groups

A series of new chelating resins with incorporating heterocyclic functional groups： pyridine, thiadizole, benzothizole into macroporous chloromethylated polystyrene were synthesized via hydrophilic spacer arm of polyethylene glycol containing sulfur. These chelating resins were found to show high adsorption capacities for Ag^＋, Hg^2＋, Au^3＋ and Pd^2＋, and the presence of spacer arm can enhance adsorption ability due to increase the hydrophilicity of the chelating resins.

The effect of chelating agent on hydrodesulfurization reaction of ordered mesoporous alumina supported Ni Mo catalysts

In this paper,ordered mesoporous alumina(OMA)support with the high surface area(328 m^(2)g^(-1))and the large pore volume 0.74(cm^(3)·g^(-1))was synthesized by homogeneous precipitation method.And the influence of EDTA on the physical and chemical properties of the modified catalysts was also studied.The characteristic results showed that the addition of EDTA could adjust the metal-support interaction and improved the acidity of the corresponding catalyst.Combined with the catalytic performance results,the EDTA-modified Ni Mo E(1.0)/OMA catalyst displays the highest DBT hydrodesulfurization conversion(97.7%).

Copper-chelating therapeutic effect in Wilson disease with different clinical phenotypes and polymorphisms of ATP7B gene

AIM To investigate the copper-chelating therapeutic effect in Wilson disease (WD) with different clinical phenotypes and polymorphisms of ATP7B gene.METHODS One hundred and twenty-two WD patients with different clinical phenotypes were given DMPS intravenously and Gandou copper-chelating tablet orally for one month. The therapeutic effect was judged by modified Goldstein mothod. Exon 18 of ATP7B gene extracted from the DNA of patients and 20 healthy volunteers was amplified with PCR mutation and polymorphism were screened with SSCP technique.RESULTS Four kinds of abnormal migration bands in PCR-SSCP were observed in 37 WD patients, mutation frequencies of three different disease phenotypes, and curative effect between mutation group and non-mutation group showed no statistically significant difference (P＞0.05), but the total effectiveness rates in patients with Wilson type or pseudosclerosis type were significantly higher than those of patients with hepatic type (X2=6.17, P＜0.05).CONCLUSION Most WD patients are compound heterozygotes, the patients with different clinical phenotypes have different response to copper-chelating therapy. Specific mutation, at least in part, plays a role in influencing the disease phenotypes and therapeutic effect.

New developments and controversies in iron metabolism and iron chelation therapy

Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies.