Copper Transfer from Cu–Aβ to Human Serum Albumin Inhibits Aggregation,Radical Production and Reduces Aβ Toxicity

Amyloid‐β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper‐exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N‐terminal Cu‐binding domain of HSA) and the consequence of this exchange on Aβ‐induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu^II from Aβ rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu‐induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO^. production in vitro and ROS production in neuroblastoma cells generated by Cu–Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu–Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of Cu^II–HSA than Cu–DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu^II–Aβ interaction. The repercussion of the competition between HSA and Aβ to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.     

Modulation of Amyloid‐β Aggregation by Histidine‐Coordinating Cobalt(III) Schiff Base Complexes

Oligomers of the Aβ42 peptide are significant neurotoxins linked to Alzheimer's disease (AD). Histidine (His) residues present at the N terminus of Aβ42 are believed to influence toxicity by either serving as metal–ion binding sites (which promote oligomerization and oxidative damage) or facilitating synaptic binding. Transition metal complexes that bind to these residues and modulate Aβ toxicity have emerged as therapeutic candidates. Cobalt(III) Schiff base complexes (Co–sb) were evaluated for their ability to interact with Aβ peptides. HPLC‐MS, NMR, fluorescence, and DFT studies demonstrated that Co–sb complexes could interact with the His residues in a truncated Aβ16 peptide representing the Aβ42 N terminus. Coordination of Co–sb complexes altered the structure of Aβ42 peptides and promoted the formation of large soluble oligomers. Interestingly, this structural perturbation of Aβ correlated to reduced synaptic binding to hippocampal neurons. These results demonstrate the promise of Co–sb complexes in anti‐AD therapeutic approaches.     

Therapeutic redistribution of metal ions to treat Alzheimer's disease

Currently, therapeutics that modify Alzheimer's disease (AD)are not available. Increasing age is the primary risk factor for AD and due to an aging global population the urgent need for effective therapeutics increases every year. This Account presents the development of an AD treatment strategy that incorporates diverse compounds with a common characteristic: the ability to redistribute metal ions within the brain. Central to cognitive decline in AD is the amyloid-β peptide (Aβ) that accumulates in the AD brain. A range of therapeutic strategies have been developed based on the premise that decreasing the brain Aβ burden will attenuate the severity of the disease symptoms. Unfortunately these treatments have failed to show any positive outcomes in large-scale clinical trials, raising many questions regarding whether therapeutics for AD can rely solely on decreasing Aβ levels. An alternate strategy is to target the interaction between Aβ and metal ions using compounds with the potential to redistribute metal ions within the brain. The original rationale for this strategy came from studies showing that metal ions promote Aβ toxicity and aggregation. In initial studies using the prototype metal-chelating compound clioquinol (CQ), CQ prevented Aβ toxicity in vitro, out-competed Aβ for metal ions without affecting the activity of metal-dependent enzymes, and attenuated the rate of cognitive decline in AD subjects in a small phase II clinical trial. All these outcomes were consistent with the original hypothesized mechanism of action for CQ where prevention or reversal of the extracellular Aβ-metal interactions could prevent Aβ toxicity. Soon after the completion of these studies, a new body of work began to suggest that this hypothesized mechanism of action for CQ was simplistic and that other factors were also important for the positive therapeutic outcomes. Perhaps most significantly, it was shown that after CQ sequesters metal ions the neutral CQ-metal complex crosses cell membranes to increase intracellular levels of the metals, thereby initiating protective cell signaling cascades. The activity of CQ therefore appeared to be two-fold: it prevented toxic interactions between Aβ and metal ions outside the cell, and it redistributed the metal ions into the cell to promote healthy cell function. To determine the significance of redistributing metal ions into the cell, glyoxalbis(N(4)-methylthiosemicarbazonato)Cu(II) [Cu(II)(gtsm)] was tested in models of AD. Cu(II)(gtsm) delivers Cu into cells, but, unlike CQ, it cannot out-compete Aβ for metal ions. When tested in AD model mice, the Cu(II)(gtsm) treatment restored cognitive function back to levels expected for cognitively healthy mice. The most advanced compound from this therapeutic strategy, PBT2, can sequester metal ions from Aβ and redistribute them into the cell like CQ. PBT2 improved cognition in a phase II clinical trial with AD patients, and further clinical testing is currently underway.     

Resin I: Synthesis,characterization, and ion‐exchange properties of terpolymer resins derived from 2,4‐dihydroxypropiophenone,biuret, and formaldehyde

Terpolymers (2,4‐DHPBF) were synthesized by the condensation of 2,4‐dihydro‐xypropiophenone, biuret, and formaldehyde in the presence of acid catalyst with varying the molar ratio of reacting monomers. Terpolymer composition has been determined on the basis of their elemental analysis and their number–average molecular weight of these resin were determined by conductometric titration in nonaqueous medium. The viscosity measurements were carried out in N,N‐dimethyl formamide which indicate normal behavior. IR spectra were studied to elucidate the structure. The terpolymer resin has been further characterized by UV–visible and ¹H‐NMR spectra. The newly synthesized terpolymers proved to be selective chelating ion‐exchange terpolymers for certain metals. The chelating ion‐exchange properties of this terpolymer was studied for Fe (III), Cu (II), Hg (II), Cd (II), Co (II), Zn (II), Ni (II), and Pb (II) ions. A batch equilibrium method was employed in the study of the selectivity of metal ion uptake involving the measurement of the distribution of a given metal ion between the terpolymer sample and a solution containing the metal ion. The study was carried out over a wide pH range and in media of various ionic strengths. The terpolymer showed a higher selectivity for Fe (III), Hg (II), Cd (II), and Pb (II) ions than for Cu (II), Co (II), Zn (II), and Ni (II) ions. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis of poly(acrylamide‐co‐4‐vinylpyridine) hydrogels and their application in heavy metal removal

A series of poly(acrylamide‐co‐4‐vinylpyridine) hydrogels having varied acrylamide/4‐vinylpyridine content and different crosslink ratios of N,N′‐methylene‐bisacrylamide was prepared by using solution polymerization. The prepared hydrogel polymers were characterized by their elemental analysis, infrared spectroscopy, and equilibrium water content. The polymers were investigated toward metal ion uptake of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II). The polymers were more sensitive to Cu(II) and Ni(II) and the order of metal ion binding was Ni(II), Cu(II) > Zn(II) > Co(II) > Mn(II). Metal ion uptake by the polymers was reduced as the pH of the medium decreased. Recycling of the resins resulted in high recovery of the metal ions from their aqueous solutions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2522–2526, 2003     

Nonionic water‐soluble polymer: Preparation,characterization, and application of poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) as a polychelatogen

The free‐radical copolymerization of water‐soluble poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) was carried out with a feed monomer ratio of 75:25 mol %, and the total monomer concentration was 2.67M. The synthesis of the copolymer was carried out in dioxane at 70°C with benzoyl peroxide as the initiator. The copolymer composition was obtained with elemental analysis and ¹H‐NMR spectroscopy. The water‐soluble polymer was characterized with elemental analysis, Fourier transform infrared, ¹H‐ and ¹³C‐NMR spectroscopy, and thermal analysis. Additionally, viscosimetric measurements of the copolymer were performed. The thermal behavior of the copolymer and its complexes were investigated with differential scanning calorimetry (DSC) and thermogravimetry techniques under a nitrogen atmosphere. The copolymer showed high thermal stability and a glass transition in the DSC curves. The separation of various metal ions by the water‐soluble poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) reagent in the aqueous phase with liquid‐phase polymer‐based retention was investigated. The method was based on the retention of inorganic ions by this polymer in a membrane filtration cell and subsequent separation of low‐molar‐mass species from the polymer/metal‐ion complex formed. Poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) could bind metal ions such as Cr(III), Co(II), Zn(II), Ni(II), Cu(II), Cd(II), and Fe(III) in aqueous solutions at pHs 3, 5, and 7. The retention percentage for all the metal ions in the polymer was increased at pH 7, at which the maximum retention capacity could be observed. The interaction of inorganic ions with the hydrophilic polymer was determined as a function of the pH and filtration factor. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 178–185, 2006     

Water‐soluble copolymers of 1‐vinyl‐2‐pyrrolidone and acrylamide derivatives: synthesis,characterization, and metal binding capability studied by liquid‐phase polymer‐based retention technique

Radical copolymerizations of 1‐vinyl‐2‐pyrrolidone with acrylamide and N,N′‐dimethylacrylamide at different feed ratios were investigated. The copolymers were characterized by Fourier transform infrared spectroscopy, ¹H NMR, and ¹³C NMR spectroscopy. The copolymer composition was determined from the ¹H NMR spectra and found to be statistical. The metal complexation of poly(acrylamide‐co‐1‐vinyl‐2‐pyrrolidone) and poly(N,N′‐dimethylacrylamide‐co‐1‐vinyl‐2‐pyrrolidone) for the metal ions Cu(II), Co(II), Ni(II), Cd(II), Zn(II), Pb(II), Fe(III), and Cr(III) were investigated in an aqueous phase. The liquid‐phase polymer‐based retention method is based on the retention of inorganic ions by soluble polymers in a membrane filtration cell and subsequent separation of low‐molecular compounds from the polymer complex formed. The metal ion interaction with the hydrophilic polymers was determined as a function of the pH and the filtration factor. Poly(N,N‐dimethylacrylamide‐co‐1‐vinyl‐2‐pyrrolidone) showed a higher affinity for the metal ions than poly(acrylamide‐co‐1‐vinyl‐2‐pyrrolidone). According to the interaction pattern obtained, Cr(III) and Cu(II) formed the most stable complexes at pH 7. Pb(II) and Zn(II) were not retained. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 741–750, 1999     

Water‐soluble amine and imine polymers with the ability to bind metal ions in conjunction with membrane filtration

The commercial polymers poly(ethylene imine) (PEI), poly(ethylene imine epichlorohydrin), and poly(dimethylamine‐co‐epichlorohydrin) were purified and fractionated by ultrafiltration. Their metal‐ion‐binding properties with respect to different ligand groups and the effect of the concentration on the retention properties were investigated. The amine ligands of the polymers formed the most stable complexes with the metal ions. In general, there was an effect of the pH and polymer fraction size on the retention properties. As the pH and polymer fraction size increased, the affinity to bind metal ions also increased. PEI had the highest metal‐retention values, particularly at higher pHs, at which the amine groups were nonprotonated and could coordinate easily with the metal ions. Only Pb(II) was poorly retained. The affinity for all the metal ions, except Pb(II), increased significantly at pH 5. The metal‐ion retention decreased quickly as the filtration factor increased, except for Cu(II), Co(II), Ni(II), Cd(II), and Zn(II) ions, which were retained by over 40% at a filtration factor of 4. For other metal ions such as Pb(II), Ca(II), and Mg(II), only 10% remained bound to the polymer. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 222–231, 2005     

Synthesis,characterization, and metal complexation of poly(N‐phenylmaleimide‐co‐acrylic acid) and poly(N‐phenylmaleimide‐co‐acrylamide) as polychelatogens in aqueous solution

We carried out the free‐radical copolymerization of N‐phenylmaleimide with acrylic acid and acrylamide with an equimolar feed monomer ratio. We carried out the synthesis of the copolymers in dioxane at 70°C with benzoyl peroxide as the initiator and a total monomer concentration of 2.5M. The copolymer compositions were obtained by elemental analysis and ¹H‐NMR spectroscopy. The hydrophilic polymers were characterized by elemental analysis, Fourier transform infrared spectroscopy, ¹H‐NMR spectroscopy, and thermal analysis. Additionally, viscosimetric measurements of the copolymers were performed. Hydrophilic poly(N‐phenylmaleimide‐co‐acrylic acid) and poly(N‐phenylmaleimide‐co‐acrylamide) were used for the separation of a series of metal ions in the aqueous phase with the liquid‐phase polymer‐based retention method in the heterogeneous phase. The method is based on the retention of inorganic ions by the polymer in conjunction with membrane filtration and subsequent separation of low‐molecular‐mass species from the formed polymer/metal‐ion complex. The polymer could bind several metal ions, such as Cr(III), Co (II), Zn(II), Ni(II), Cu(II), Cd(II), and Fe(III) inorganic ions, in aqueous solution at pH values of 3, 5, and 7. The interaction of the inorganic ions with the hydrophilic polymer was determined as a function of pH and a filtration factor. Hydrophilic polymeric reagents with strong metal‐complexing properties were synthesized and used to separate those complexed from noncomplexed ions in the heterogeneous phase. The polymers exhibited a high retention capability at pH values of 5 and 7. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Controlled Production of Amyloid β Peptide from a Photo‐Triggered,Water‐Soluble Precursor “Click Peptide“

In biological experiments, poor solubility and uncontrolled assembly of amyloid β peptide (Aβ) 1–42 pose significant obstacles to establish an experiment system that clarifies the function of Aβ1–42 in Alzheimer's disease (AD). Herein, as an experimental tool to overcome these problems, we developed a water‐soluble photo‐“click peptide” with a coumarin‐derived photocleavable protective group that is based on an O‐acyl isopeptide method. The click peptide had nearly 100‐fold higher water solubility than Aβ1–42 and did not self‐assemble, as the isomerized structure in its peptide backbone drastically changed the conformation that was derived from Aβ1–42. Moreover, the click peptide afforded Aβ1–42 quickly under physiological conditions (pH 7.4, 37 °C) by photoirradiation followed by an O–N intramolecular acyl migration. Because the in situ production of intact Aβ1–42 from the click peptide could improve the difficulties in handling Aβ1–42 caused by its poor solubility and highly aggregative nature, this click peptide strategy would provide a reliable experiment system for investigating the pathological function of Aβ1–42 in AD.     

The Amyloid-β Peptide in Amyloid Formation Processes: Interactions with Blood Proteins and Naturally Occurring Metal Ions

This review describes interactions between the amyloid-β peptide (Aβ) involved in Alzheimer's disease (AD) and endogenous metal ions and proteins, with an emphasis on future potential drug therapies and targets. AD is characterised by loss of neurons, memory, and cognitive functions, and by formation of cerebral senile plaque deposits. These plaques consist mainly of aggregated Aβ peptides. AD pathology includes a) on the molecular level imbalanced concentrations of Aβ peptides and metal ions, and formation of amyloid structures, and b) on the physiological level a combination of inflammatory responses and oxidative stress effects causing neuronal death. Interestingly, certain blood proteins and metal ions can affect the Aβ amyloid aggregation process. These interactions are the topics of the present review. A deeper understanding of these interactions could facilitate new therapeutic strategies against AD. Previous therapeutic approaches and trials are also briefly described.     

Synthesis and metal ions sorption properties of styrene‐based polymers

Atactic polystyrene (PS) was chemically modified with maleic (MAH), succinic (SAH), and phtalic (PhAH) anhydrides. Styrene was copolymerized with acrylic (AA) and methacrylic acids (MA). Amount of carboxyl groups (%) bound to polymers was determined in the range of 6.9–25.9. Different modified polystyrenes (MPS) and styrene copolymers were used in the experiments to study Cu(II) and Zn(II) ions adsorption probability and their comparison. Sorption capacity of the polymers for the metal ions were investigated in aqueous media containing different amounts of these ions (5–40 mg/L) and at different pH values (2.0–6.0). Adsorption behavior of heavy metal ions could be modeled using both the Langmuir and Freundlich isotherms. It was found that the adsorption capacity is highest at pH value of 6, whereas it decreases as the pH value decreases at temperature 25°C ± 1°C for 240 min. The results obtained from the adsorption capacity experiments for Cu(II) and Zn(II) ions were 3.47–5.45 and 5.42–6.85 mg/g, respectively. The affinity order of polymers for both metal ions was observed as follows: SMAC > SAAC > MPS with MAH > MPS with SAH > MPS with PhAH. The maximum adsorption capacities of SMAC were 6.85mg/g for Zn(II) and 5.45 mg/g for Cu(II). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Metal‐ion‐retention properties of the poly(2‐acrylamido‐2‐methyl‐1‐propanosulfonic acid‐co‐4‐vinyl pyridine) resin

The water‐insoluble resin poly(2‐acrylamido‐2‐methyl‐1‐propanosulfonic acid‐co‐4‐vinyl pyridine), through a radical polymerization solution, was synthesized with ammonium persulfate as an initiator and N,N‐methylene bisacrylamide as a crosslinking reagent. The metal‐ion‐retention properties were studied by batch and column equilibrium procedures for the following metal ions: Hg(II), Cu(II), Cd(II), Zn(II), Pb(II), and Cr(III). These properties were investigated under competitive and noncompetitive conditions. The effects of the pH, maximum retention capacity, and regeneration capacity were studied. The resin showed a high retention ability for Hg(II) ions at pH 2.0. The retention of Hg(II) ions from a mixture of ions was greater than 90%. The resin showed a high selectivity for Hg(II) with respect to other metal ions. The Hg(II)‐loaded resin was able to be recovered with 4M HClO₄. The retention capacity was kept after four cycles of adsorption and desorption. The retention properties for Hg(II) were very similar with the batch and column methods. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3556–3562, 2003     

Determination of the competitive adsorption of heavy metal ions on poly(n‐vinyl‐2‐pyrrolidone/acrylic acid) hydrogels by differential pulse polarography

Poly(N‐vinyl‐2‐pyrrolidone) and poly(N‐vinyl‐2‐pyrrolidone/acrylic acid) hydrogels were prepared by gamma irradiation for the removal of heavy metal ions (i.e., lead, copper, zinc, and cadmium) from aqueous solutions containing different amounts of these ions (2.5–10 mg/L) and at different pH values (1–13). The observed affinity order in adsorption of these metal ions on the hydrogels was Zn(II) > Pb(II) > Cu(II) > Cd(II) under competitive conditions. The optimal pH range for the heavy metal ions was from 7 to 9. The adsorption of the heavy metal ions decreased with increasing temperature in both water and synthetic seawater conditions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2013–2018, 2003     

Analytical applications of newly synthesized copolymer resin derived from p‐aminophenol,dithiooxamide, and formaldehyde

A copolymer resin (p‐APDF) has been synthesized using the monomers p‐aminophenol, dithiooxamide, formaldehyde in 1 : 1 : 2M proportions in the presence of 2M HCl as catalyst. The structure of p‐APDF copolymer has been elucidated on the basis of elemental analysis and various physicochemical techniques, i.e., UV‐visible, FTIR, and ¹H‐NMR spectroscopy. The number average molecular weight of copolymer resin was determined by nonaqueous conductometric titration in DMF. Viscosity measurement were carried out in DMF indicate normal behavior. The prepared resin proved to be a selective ion exchange resin for some metal ions. The chelating ion exchange properties of this resin was studied for Fe(III) and Cu(II), Ni(II), Co(II), Zn(II), Cd(II), Pb(II) ions. A batch equilibrium method was used to study selectivity of metal ion uptake over a wide pH range and in media of various ionic strength. The resin showed a higher selectivity for Fe(III), Ni(II), Cu(II) ions than for Co(II), Pb(II), Zn(II), and Cd(II) ions. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Effect of the nature of the crosslinking agent on the metal‐ion complexation characteristics of 4 mol % DVB‐ and NNMBA‐crosslinked polyacrylamide‐supported glycines

Metal‐ion complexation behavior of glycine functions supported on divinylbenzene (DVB)‐ and N,N′‐methylene bisacrylamide (NNMBA)‐crosslinked polyacrylamide was carried out toward Co(II), Ni(II), Cu(II), and Zn(II) ions. The polymeric ligands and the derived metal complexes were characterized by IR, UV, and EPR spectra and by SEM. The metal‐ion complexation of the rigid DVB‐crosslinked system is lower than that of the semirigid NNMBA‐crosslinked system. The glycine ligands renervated after the desorption of the metal ions showed an unusual specificity toward the desorbed metal ion. The low degree of crosslinking makes the desorption process simple and shows fast rebinding kinetics. The metal‐ion‐desorbed polymeric ligands would have pockets or holes characteristic of the desorbed metal ion, resulting in its specific rebinding. The rigidity of the crosslinking also determines the kinetics of metal‐ion rebinding. The specificity and selectivity characteristics of the crosslinked polymeric ligand was found to be increased as the crosslinking agent changes from semirigid NNMBA to rigid and hydrophobic DVB. Thus, copper‐desorbed resins showed an increased specificity toward copper ions and selectively binds copper ions from a mixture of copper and cobalt ions. The metal‐ion specificity and selectivity characteristics of the metal‐ion‐desorbed system is exploited for the concentration of desorbed metal ions from a mixture of metal ions. The resin is amenable for a continuous process and can be regenerated several times. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3432–3444, 1999     

Biophysical Studies of the Amyloid β‐Peptide: Interactions with Metal Ions and Small Molecules

Alzheimer's disease is the most common of the protein misfolding (“amyloid”) diseases. The deposits in the brains of afflicted patients contain as a major fraction an aggregated insoluble form of the so‐called amyloid β‐peptides (Aβ peptides): fragments of the amyloid precursor protein of 39–43 residues in length. This review focuses on biophysical studies of the Aβ peptides: that is, of the aggregation pathways and intermediates observed during aggregation, of the molecular structures observed along these pathways, and of the interactions of Aβ with Cu and Zn ions and with small molecules that modify the aggregation pathways. Particular emphasis is placed on studies based on high‐resolution and solid‐state NMR methods. Theoretical studies relating to the interactions are also included. An emerging picture is that of Aβ peptides in aqueous solution undergoing hydrophobic collapse together with identical partners. There then follows a relatively slow process leading to more ordered secondary and tertiary (quaternary) structures in the growing aggregates. These aggregates eventually assemble into elongated fibrils visible by electron microscopy. Small molecules or metal ions that interfere with the aggregation processes give rise to a variety of aggregation products that may be studied in vitro and considered in relation to observations in cell cultures or in vivo. Although the heterogeneous nature of the processes makes detailed structural studies difficult, knowledge and understanding of the underlying physical chemistry might provide a basis for future therapeutic strategies against the disease. A final part of the review deals with the interactions that may occur between the Aβ peptides and the prion protein, where the latter is involved in other protein misfolding diseases.     

Synthesis of water‐insoluble functional copolymers containing amide,amine, and carboxylic acid groups and their metal‐ion‐uptake properties

The crosslinked poly[N‐(3‐dimethylamino)propylmethacrylamide] [P(NDAPA)] and poly[N‐(3‐dimethylamino)propylmethacrylamide‐co‐acrylic acid] [P(NDAPA‐co‐AA)] were synthesized by radical polymerization. The resins were completely insoluble in water. The metal‐ion‐uptake properties were studied by a batch equilibrium procedure for the following metal ions: silver(I), copper(II), cadmium(II), zinc(II), lead(II), mercury(II), chromium(III), and aluminum(III). The P(NDAPA‐co‐AA) resin showed a lower metal‐ion affinity than P(NDAPA), except for Hg(II), which was retained at 71% at pH 2. At pH 5, the resin showed a higher affinity for Pb(II) (80%) and Cu(II) (60%), but its affinity was very low for Zn(II) and Cr(III). The polymer ligand–metal‐ion equilibrium was achieved during the first 20 min. By changing the pH, we found it possible to remove between 60 and 70% of Cd(II) and Zn(II) ions with (1M, 4M) HClO₄ and (1M, 4M) HNO₃. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:5232–5239, 2006     

Formaldehyde-Crosslinked Nontoxic Aβ Monomers to Form Toxic Aβ Dimers and Aggregates: Pathogenicity and Therapeutic Perspectives

Alzheimer's disease (AD) is characterized by the presence of senile plaques in the brain. However, medicines targeting amyloid-beta (Aβ) have not achieved the expected clinical effects. This review focuses on the formation mechanism of the Aβ dimer (the basic unit of oligomers and fibrils) and its tremendous potential as a drug target. Recently, age-associated formaldehyde and Aβ-derived formaldehyde have been found to crosslink the nontoxic Aβ monomer to form the toxic dimers, oligomers and fibrils. Particularly, Aβ-induced formaldehyde accumulation and formaldehyde-promoted Aβ aggregation form a vicious cycle. Subsequently, formaldehyde initiates Aβ toxicity in both the early-and late-onset AD. These facts also explain why AD drugs targeting only Aβ do not have the desired therapeutic effects. Development of the nanoparticle-based medicines targeting both formaldehyde and Aβ dimer is a promising strategy for improving the drug efficacy by penetrating blood-brain barrier and extracellular space into the cortical neurons in AD patients.     

Separation and adsorption properties of poly styrene‐graft‐ethyl methacrylate copolymer for zinc,copper, and cobalt ions in water samples

In this article, separation and adsorption properties of poly styrene‐graft‐ethyl methacrylate copolymer for zinc, copper, and cobalt ions in water samples were investigated. For this aim, some experimental and analytical parameters such as solution pH, sample flow rate, type of eluting agent, and sample solution volume were optimized. The adsorbed metal ions on polymeric resin were eluted with 5 ml of 2 mol l^?1 HNO₃ and they were determined by flame atomic absorption spectrometry. In optimized conditions, the adsorption capacities for Zn, Cu, and Co were obtained as 6.8, 5.2, and 7.5 mg g^?1, respectively. The detection limits were calculated as 0.82 μg l^?1 for Zn, 1.24 μg l^?1 for Cu, and 0.68 μg l^?1 for Co from standard deviation of the blank (50 ml, pH 5.8) measurements 10 replicates. The relative standard deviation of recoveries for seven replicate analyses of Zn, Cu, and Co ions (50 ml of 0.10 mg l^?1) were found as 2.4, 2.8, and 1.5%, respectively. The accuracy of method was checked with certified reference material (NIST SRM 1643e, trace elements in water) and the developed method was successfully applied to tap water, commercial drinking water, and mineral water samples. POLYM. ENG. SCI., 54:1555–1559, 2014. © 2013 Society of Plastics Engineers