Chelating Agents For Metal Ions Research Articles

Erythrocyte membrane coated with nitrogen-doped quantum dots and polydopamine composite nano-system combined with photothermal treatment of Alzheimer's disease

Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of β-amyloid (Aβ) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu2+), effectively preventing Cu2+-mediated aggregation of Aβ. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aβ fibers and enhance the blood–brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.

DL‐malic acid for inhibiting the re‐ignition of long‐flame coal and its micro‐reaction mechanism

AbstractTo study the metal ion chelating agent (DL‐malic acid) inhibiting oxidation characteristics of residual coal in goaf, the microscopic thermal transformation characteristics of the treated coal samples were obtained using apparent morphology, infrared spectroscopy, free radical testing, and thermal analysis. The results demonstrate that after the addition of malic acid, the sphericity and roundness of the coal samples decrease, and the small fractured particles accumulate in the pores of the oxidized coal samples and, thereby, reduce the number of coal–oxygen contact sites. The addition of 10% malic acid promotes the conversion of functional groups (FG) and free radicals in pre‐oxidized coal, inhibits the catalytic effect of metal ions, generates more active sites, and increases the total heat release during the combustion process. There are strong endothermic points in the malic acid‐treated coal samples, and the free water evaporation blocked by small particles in the holes delays the initial heat release temperature of the coal samples. Pre‐oxidation can promote changes in the valence state of metal ions in coal, increase the adhesion between broken pre‐oxidized coal particles via malic acid chelation, and lose the catalytic effect of metal ions; this inhibits the process of oxidative re‐ignition of coal samples.

Novel metallo-β-lactamases inhibitors restore the susceptibility of carbapenems to New Delhi metallo-lactamase-1 (NDM-1)-harbouring bacteria.

The production of metallo-β-lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost-effective approach to fight infections caused by carbapenem resistant pathogens. The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo-lactamase-1 (NDM-1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP-MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time-dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy. Twelve FDA-approved compounds were initially screened to inhibit the ability of NDM-1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo-β-lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo-β-lactamases-producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM-1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM-1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models. Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo-β-lactamases-positive carbapenem resistant bacterial pathogens.

Structural Characterization of Zinc-Sucrose Complex and Its Ability to Promote Zinc Absorption in Caco-2 Monolayer Cells and Mice.

Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc-sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc-sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc-sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc-sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc-sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc-sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc-sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.

Facile synthesis of Ag-Co bimetallic nanoparticles decorated Fe3O4@EDTA nanocomposites and their enhanced catalytic activity

In this study, firstly, bimetallic Ag-Co nanoparticles with rich catalytic sites decorated on Fe3O4 magnetic carriers through metal ion chelating agent EDTA (Ag-Co@EDTA@Fe3O4 NPs) were fabricated by co-reducing agent in-situ deposition method for the first time. The synthesized nanocomposites were characterized by various techniques, including UV–vis, XRD, TEM, EDX, XPS and VSM. Secondly, the catalytic reduction performance of Ag-Co@EDTA@Fe3O4 NPs was analyzed for 2-nitrophenol in the presence of NaBH4 at 25 ℃. Results showed that the k of Ag-Co@EDTA@Fe3O4 NPs was 10.9 and 2.7 times higher than that of Co@EDTA@Fe3O4 and Ag@EDTA@Fe3O4 NPs, respectively, which considered to obey the first-order kinetics equation, proving the strong synergistic effect between Ag and Co nanoparticles. Furthermore, the significantly enhanced catalytic activity of Ag-Co@EDTA@Fe3O4 NPs was discussed. Plenty of Ag NPs were successfully anchored on Fe3O4@EDTA supports maybe the crucial factor, and the doped Co provided much more active sites in the catalytic process. Finally, the degradation efficiency of Ag-Co@EDTA@Fe3O4 NPs still remained above 95% after 5 cycles. Importantly, there was no significant difference between the fresh catalyst and after cycling for 5 times, observed by TEM and SEM. Meanwhile, the change of hydrodynamic diameter of the used Ag-Co@EDTA@Fe3O4 NPs over cycle number was measured around 230 nm which increased unobviously, making it a promising candidate for wastewater treatment in industries.

Biochemical and molecular characterization of a novel porphobilinogen synthase from Corynebacterium glutamicum.

Corynebacterium glutamicum porphobilinogen synthase (PBGS) is a metal enzyme with a hybrid active site metal binding sequence. In this study, the porphobilinogen synthase gene of C. glutamicum was cloned and heterogeneously expressed in Escherichia coli. C. glutamicum PBGS was purified, and its enzymatic characteristics were analyzed. The results showed that C. glutamicum PBGS is a Zn2+-dependent enzyme, and Mg2+ has allosteric regulation. The allosteric Mg2+ plays a vital role in forming the quaternary structure of C. glutamicum PBGS. Based on the ab initio predictive structure modeling of the enzyme and the molecular docking model of 5-aminolevulinic acid (5-ALA), 11 sites were selected for site-directed mutagenesis. When the hybrid active site metal binding site of C. glutamicum PBGS is converted into a cysteine-rich motif (Zn2+-dependent) or an aspartic acid-rich motif (Mg2+/K+-dependent), the enzyme activity is basically lost. Four residues, D128, C130, D132, and C140, in the metal binding site, were the binding sites of Zn2+ and the active center of the enzyme. The band migration, from the native PAGE, of five variants with mutations in the center of enzyme activity was the same as that of the variant enzymes as purified, individually adding two metal ion chelating agents. Their Zn2+ active center structures were abnormal, and the quaternary structure equilibrium was altered. The destroyed active center affects the construction of its quaternary structure. The quaternary structural balance between octamer and hexamer through dimers was regulated by the allosteric regulation of C. glutamicum PBGS. The enzyme activity was also affected by the change of the active site lid structure and (α β)8-barrel structure caused by mutation. Structural changes in the variants were analyzed to understand C. glutamicum PBGS better.

Electrochemical sensing interface based on the oriented self-assembly of histidine labeled peptides induced by Ni2+ for protease detection

To construct an electrochemical sensing interface which was convenient for protease recognition and cleavage, we designed a strategy for directed self-assembly of histidine-tagged peptides on the electrode led by Ni2+ ions for electrochemical detection of prostate specific antigen (PSA). The electrode surface was first functionalized using carboxylated multiwalled carbon nanotubes and then modified with the metal ion chelating agent (5 S)–N-(5-Amino-1-carboxypentyl) iminodiacetic acid (NIA). After the Ni2+ was captured by NIA, the designed immune-functional peptide could be oriented assembly to the electrode interface through the imidazole ring of histidine at the tail, completing the construction of the recognition layer. Therefore, by adding the analyte PSA to identify and shear the immune-functional peptide, the ferrocene in its head was released, resulting in a reduction in the electrical signal, enabling sensitive detection. In addition, the self-assembly layer could be removed by pickling to realize the reconstruction of the recognition layer. Under optimal conditions, the electrochemical sensor had an ultralow detection limit of 11.8 fg mL−1 for PSA, with a wide detection range from 1 pg mL−1 to 100 ng mL−1. In this work, an electrochemical sensing interface based on the histidine-tagged peptide induced by Ni2+ was formed to enable controllable oriented assembly on the electrode surface, and the recognition layer could be reconstructed via pickling, providing a potential approach for the design of repeatable interfaces.

Experimental Study on the Inhibitory Effect of Organic Phosphonic Acid Compound on Coal Spontaneous Combustion

ABSTRACT The minerals in coal contain a certain amount of metal ions, among which transition metal ions have a catalytic effect on coal spontaneous combustion (CSC). Therefore, the addition of metal ion chelating agent to coal will weaken this catalytic effect, thereby inhibiting CSC. As a class of highly effective metal ion chelating agent, two kinds of organic phosphonic acid compounds (OPAC), 1-Hydroxy Ethylidene-1,1-Diphosphonic Acid (HEDP) and 2-Hydroxyphosphonoacetic Acid (HPAA), were investigated for their inhibitory effect on CSC. First, the low-temperature oxidation experiment was performed on coal samples before and after OPAC treatment. The experimental results show that HEDP and HPAA could reduce CO generation during spontaneous combustion of coal with different metamorphic degrees. Besides, the inhibiting efficiency of HEDP on CSC is higher than that of HPAA. Then, the effects of HEDP and HPAA on the thermal properties of CSC were investigated using synchronous thermal analysis experiment. The experimental results show that HEDP and HPAA could significantly weaken the oxygen adsorption, mass loss, and heat release during the high-temperature oxidation stage of CSC and exhibit the same result that HEDP is better than HPAA. Finally, the reasons for the difference in the inhibitory effects of HEDP and HPAA were analyzed and the inhibition mechanism of them on CSC was revealed via quantum chemical calculation. The results can provide new ideas for preventing CSC and developing new inhibitors.

Tailoring buried interface of tin oxide-based n-i-p perovskite solar cells via bidirectional and multifunctional metal ion chelating agent modification

For the n-i-p perovskite solar cells hiring tin oxide (SnO2) as electron transporting material, the buried interface (SnO2/perovskite interface) acts as the working interface and growth substrate of the perovskite crystal simultaneously.

Fulvic acid mitigates cadmium toxicity-induced damage in cucumber seedlings through the coordinated interaction of antioxidant enzymes, organic acid, and amino acid.

Fulvic acid (FA) can significantly alleviate cadmium (Cd) stress, but the specific metabolic response of FA to Cd toxicity is still not clarified. In the present study, we used untargeted metabolomic [gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)] analysis to profile cucumber metabolism in response to Cd stress after spray application of FA. Our results showed that 331 differentially enriched metabolites (DEMs) were identified in leaf materials. These DEMs were enriched in 21 shared pathways in comparative groups of "Cd treatment vs. the control treatment" and "FA + Cd treatment vs. the Cd treatment." Specifically, treatment with FA significantly enhanced the organic acid content (citric acid, isocitric acid, 2-oxoglutaric acid, fumaric acid, and malic acid), which would contribute to provide sufficient substrates for the tricarboxylic acid (TCA) cycle and amino acid biosynthesis, thereby ensuring the normal production of energy and amino acid. At the same time, FA significantly increased the amino acid content (aspartate, citrulline, histidine, leucine, and phenylalanine). The accumulation of organic acid and amino acid can act as chelating agents for heavy metal ions and as scavengers of reactive oxygen species (ROS), thereby reducing intracellular oxidative damage. Furthermore, the application of FA improves antioxidant enzymes and accelerates ROS clearance. The improved contents of organic acid and amino acid, and the increased activity of antioxidant enzymes both played a central role in the reduction of malondialdehyde (MDA, 14.08%), hydrogen peroxide (H2O2, 61.70%) contents, and superoxide anion radical (O2-, 30.41%) production rate in plants under Cd stress. Taken together, the present study demonstrates the effects of FA on the antioxidant capacity and carbohydrate and amino acid metabolism of cucumber seedlings exposed to Cd stress, which provides comprehensive insights into the regulation of plants' response to Cd toxicity with FA was applied in cucumber.

Simultaneous analysis of 16 metal ions by ion‐pairing high‐performance liquid chromatography‐electrospray ionization tandem mass spectrometry

AbstractMetal ions can be analyzed by ESI‐MS with chelating agents. However, matrix effect and the marginal difference in atomic weight of the isotopes of some metal ions make the analysis of a metal ion mixture not feasible. In this paper, we present the use of IP‐HPLC in conjunction with a metal ion chelating agent to analyze the metal ion mixtures. Hydrophobic (±)‐trans‐1,2‐cyclohexylenedinitrilotetraacetic acid (CDTA) was used to chelate 16 metal ions. The chelates were then separated by IP‐HPLC followed by ESI‐MS analysis. For IP‐HPLC, different combinations of primary amines and their salts were employed as the ion‐pairing reagent in eluent on a high‐pH resistant C‐18 column under basic conditions. For ESI‐MS, Q‐Exactive Focus system was used. Among the metal ions, the results indicated that Al3+ showed the lowest LOD (3.88 × 10−3 μM) while Zn2+ showed the highest (0.227 μM). The sensitivity was close to that of ICP‐AES. The coefficients of determination (R2) were greater than 0.995 except for Sr2+ (R2 = 0.9899), indicating the high accuracy of the method. Finally, this method was used to analyze the black soybean samples from two different sources. Eight metal ions were successfully identified with simultaneous detection of sugars, organic acids, and nucleotides.

POS0478 TOPICAL CALCIUM CHELATORS FOR TARGETING CUTANEOUS CALCIFICATION: PRECLINICAL EVIDENCE OF EFFICACY

BackgroundCutis calcinosis, defined as sub-epidermal deposition of calcium salts, is a painful, disabling, disfiguring, problem in 20-40% of patients with systemic sclerosis. Its pathogenesis remains poorly understood and currently there is no effective disease-modifying pharmacotherapy. One potential strategy is topical application of calcium chelating agents, able to penetrate the epidermal barrier and dissolve subcutaneous calcinotic deposits in situ. To date, the only compound reported for this application has been sodium thiosulfate (STS), with often-contradictory results.ObjectivesTo test the hypothesis, in pre-clinical studies, that polycarboxylic acids can induce calcium dissolution without skin toxicity, with the long-term aim of developing an effective topical treatment for cutis calcinosis.MethodsWe compared the metal ion-chelating agents citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) - polycarboxylic acids with well-characterised chelation profiles – to STS for their ability to chelate calcium, without inducing cytotoxicity or inflammation (pro-inflammatory cytokine expression and release), using in vitro 2D (keratinocyte [HaCaT]; fibroblast ([HCA2]) and recombinant human epidermal (RHE) models. The resultant data was subsequently used to predict therapeutic concentrations for assessment in a validated skin irritation model (SkinEthicTM; Episkin SA) and to assay maximal percutaneous absorption. At relative dermal concentrations, the dissolution performance of each chelator was further assessed using two different models of calcinosis: 1) pharmaceutical dissolution of a hydroxyapatite (HAp) tablet (1) and; 2) dissolution of a calcified extracellular matrix laid down by mineralising SaOS2 in vitro monolayer culture (2).ResultsIncubation with CA, EDTA and STS induced cytotoxicity in both in vitro cell lines studied at concentrations of >10 mM; only EDTA (10 mM) resulted in inflammatory cytokine release (IL8) from cells at these higher concentrations (cf positive control, Lipopolysaccharide 10 mg/mL). When applied topically to RHE models as near-saturated solutions, none of the chelators were categorised as skin irritants. Due to differences in their relative aqueous solubility, higher concentrations of CA (1600 mM) and STS (1200 mM) could be delivered through the RHE model than EDTA (200 mM). Using a simple linear regression model, the rate of compound absorption was: CA, 0.43 ± 0.05; STS, 0.26 ± 0.03 and; EDTA, 0.05 ± 0.01 g/L/hr. At each time-point, the cumulative concentration of compound in the receptor media was CA > STS > EDTA. Incubation with chelators had no effect on the integrity of the RHE by standard histology. Based on the rate of percutaneous absorption, the dissolution performance of each chelator was tested at relative dermal concentrations for phosphate dissolution (nmoles) of HAp (CA, 9.61 ±0.97; EDTA, 5.38 ± 0.28; 3.78 ± 0.58) and in the calcified in vitro model (Figure 1; CA, 3285 ± 105, STS, 947 ± 95, EDTA, 1174 ± 89), showing the superiority of CA in both model systems.Figure 1.Dissolution of a calcified extracellular matrix by citric acidConclusionOverall, this study highlights the promise of polycarboxylic acids, particularly CA, to target subcutaneous calcification, which are neither toxic nor inflammatory to the skin. Specifically, we have identified CA as a potentially more efficacious alternative to STS for the topical treatment of cutis calcinosis.

Hypolipidemic effect of chromium-modified enzymatic product of sulfated rhamnose polysaccharide from Enteromorpha prolifera in type 2 diabetic mice

Sulfated rhamnose polysaccharide (SRP) derived from Enteromorpha prolifera is a metal-ion chelating agent that could potentially be used to treat diabetes. The aim of our study was to determine the effect of a variant of SRP on DIABETES. First, we synthesized and characterized SRPE-3 chromium(III) [SRPE-3-Cr(III)] complex using an enzymatic method. The maximum chelation rate was 18.2% under optimal chelating conditions of pH 6.0, time 4 h, and temperature 60 °C. Fourier transform infrared spectroscopy results showed important sites for Cr(III)-binding were O–H and C=O groups. We then studied the hypolipidemic effects of SRPE-3-Cr(III) on type 2 diabetes mellitus (T2DM) induced by a high-fat, high-sucrose diet (HFSD). Decreased blood glucose content, body fat ratio, serum TG, TC, LDL-C, and increased serum HDL-C were observed after treatment with SRPE-3-Cr(III). In addition, SRPE-3-Cr(III) significantly reduced leptin, resistin, and TNF-α levels, and increased adiponectin contents relative to T2DM. Histopathology results also showed that SRPE-3-Cr(III) could alleviate the HFSD-lesioned tissues. SRPE-3-Cr(III) also improved lipid metabolism via a reduction in aspartate aminotransferase, alanine aminotransferase, fatty acid synthase, and acetyl-CoA carboxylase activities in the liver. SRPE-3-Cr(III) at low doses exhibited better lipid-lowering activities, hence, could be considered to be a novel compound to treat hyperlipidemia and also act as an anti-diabetic agent.

Improving the solubility of melanin nanoparticles from apricot kernels is a potent drug delivery system.

Melanin can be used in biomedical nanomaterials, but its solubility in water and bioavailability are low. Melanin nanoparticles were prepared and then PEG-natural melanin nanoparticles (NMNP-PEG) were obtained with good performance and optimize their (water solubility, dispersion stability, chelating metal ions, photothermal stability, drug delivery, and biocompatibility), therefore improve the water solubility of melanin and broaden its application scope in biology, medicine, food, and other fields. MFAK (melanin from apricot kernels) and NMNP-PEG were prepared and characterized using ultraviolet-visible spectrophotometry (UV-Vis), high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (NMR), and electron microscopy. The chelation rate of metal ions, photothermal effect, doxorubicin loading, and cytotoxicity (MCF-7 cells) were examined. UV-Vis, HPLC, FTIR, and NMR indicated that NMNPs contained melanin. NMNPs could be successfully modified using PEG. Under physiological pH conditions (pH 7.4), the metal ion chelation rate of NMNP-PEG increased with time and peaked at 12 h. The photothermal assay showed a temperature enhancement of 26.3°C with 1 mg/mL NMNP-PEG, compared with 1.9℃ with water. The NMNP-PEGs had a typical peak for doxorubicin in the FTIR spectrum, and the peak intensity was proportional to the drug loading. The release of doxorubicin in an acidic buffer was 40.8% at 24 h, almost threefold that in a neutral buffer (11.9%). There was no obvious cytotoxicity from NMNP-PEG. NMNP-PEG displays good stability, high metal ion chelation ability, efficient photothermal conversion potential, drug-retaining capability, sustained controlled drug release, and biocompatibility. This study provides a theoretical basis for NMNP-PEG applications in medicine (targeting specific sites to diagnose and treat diseases), food (extending the shelf life of food), and biology (as metal ion chelating agents to remove heavy metals from wastewater).

Metal ion chelation enhances tissue plasminogen activator (tPA)-induced thrombolysis: an in vitro and in vivo study.

Stroke is the third leading cause of death in the United States and the leading cause of adult disability. Despite enormous research efforts including many clinical trials, tissue plasminogen activator (tPA) remains the only FDA-approved treatment for acute ischemic stroke. Unfortunately, only 1-3% of stroke patients in the US receive this therapy because of the narrow time window and severe side effects for using tPA. The most deadly and damaging side effect is the risk of intracranial bleeding or hemorrhage. For that reason, the dose of tPA and its overall administration are under tight control, which may compromise the effect of thrombolysis. Studies have been focused on improving the effectiveness of tPA for higher rate of reperfusion, and the safety for less adverse bleeding episode. We studied how metal ions (zinc & iron) affect tPA-induced thrombolysis in vitro and in vivo, and proposed a method to improve the rate of thrombolysis. The amount of hemoglobin in the blood clot lysis was measured by a spectrophotometer. The tPA-induced thrombolysis was measured in vivo in femoral artery. Our results showed that Zn2+, Fe3+ and Fe2+ inhibited tPA-induced thrombolysis, with Zn2+ and Fe2+ being the most effective. Metal ion chelating agent EDTA when it was co-applied with tPA significantly enhanced the tPA-induced thrombolysis. The chelation alone did not have noticeable thrombolytic effect. In in vivo study of tPA-induced thrombosis following femoral artery thrombosis, the co-application of tPA and EDTA achieved significant higher rate of reperfusion than that by tPA treatment alone, suggesting that ion chelation facilitates tPA-induced thrombolysis and potentially improves the safety of tPA application by reducing the necessary dose of tPA application. Our results suggest that the co-application of a chelator and tPA improves the efficacy and, potentially, safety of tPA application, by reducing the necessary dose of tPA for thrombolysis.

Synthesis and properties of hydrophobically associating polymer fracturing fluid

The double tailed hydrophobic monomer PMB-16 was synthesized by the reaction of phenylethylamine,1-bromohexadecane and methacryloyl chloride. The ternary hydrophobic association polymer (PADM) was synthesized by free radical copolymerization of PMB-16 with acrylamide (AM) and methacryloyloxyethyl trimethylammonium chloride (DMC). The optimum synthesis conditions were as follows, the mass ratio of m (AM):m (DMC):m (PMB-16) was 80:19.6:0.4, the total monomer concentration was 35.0 wt%, the amount of initiator (V50) was 0.1 wt% of the total mass of monomer, the reaction temperature was 55 °C, the reaction time was 6.0 h, the system pH was 7, and the amount of metal ion chelating agent (EDTA-4Na) was 0.01 wt% of the total mass of monomer. The results of performance evaluation showed that PADM aqueous solution had excellent temperature and salt resistance. Using zirconium acetylacetonate as crosslinking agent, the mass crosslinking ratio of PADM solution to zirconium acetylacetonate was 100:0.9, the crosslinking temperature was 60 °C, and the pH value was 6.0. The system presented good thickening, temperature resistance, shear stability and low residue content, so it was a low damage fracturing fluid.

Structural modification and biological activities of carboxymethyl Pachymaran.

Polysaccharides are good chelating agents for metal ions, which are often used to synthesize polysaccharide metal ion complexes. With carboxymethyl pachymaran (CMP) as the substrate, carboxymethyl pachymaran iron (CMPF), carboxymethyl pachymaran selenium (CMPS), and carboxymethyl pachymaran zinc (CMPZ) were synthesized by response surface methodology, and their biological characteristics were studied. The results showed that the CMP was a β‐polysaccharide, and the degree of carboxymethylation was 0.6352. The polysaccharide metal ion complexes were characterized by physicochemical methods, scanning electron microscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and nuclear magnetic resonance spectroscopy. All the polysaccharides and complexes possessed antioxidant activity in vitro with scavenging activities to ABTS, superoxide anions, and ferrous ions. CMPF, CMPS, and CMPZ caused significant inhibition of A2780 cell proliferation, promoted the production of reactive oxygen species, and induced apoptosis in a human ovarian cancer cell line (A2780 cells). These results suggest that the CMP complex may be an effective candidate drug for cancer treatment in the field of functional food and pharmacology.

Controllable preparation and performance of bio-based poly(lactic acid-iminodiacetic acid) as sustained-release Pb2+ chelating agent

SummaryThe bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

Synthesis of Novel 8‐cyclo‐1,5,3,7‐Diazadiphosphocine Derivatives Via [4 + 2] Cycloaddition

As part of our research program into pharmacologically valuable compounds and chelating agents for transition metal ions, novel 8‐cyclo‐1,5,3,7‐diazadiphosphocines (5–16) were successfully synthesized in good yields via [4 + 2] cycloaddition reaction between 8‐cyclo‐1,5,3,7‐diazadiphosphocines (4a‐c) with dienophiles (dimethyl acetylenedicarboxylate [DMAD], diethyl acetylenedicarboxylate [DEAD], diethyl diazene‐1,2‐dicarboxylate [DEDAD], and diisopropyl diazene‐1,2‐dicarboxylate [DIPDAD]). The core precursor scaffolds (4a‐c) were prepared via a one‐pot reaction between heteroaromatic amine analogs (1a‐c), paraformaldehyde and hypophosphorous acid in the presence of 6 M HCl. The biological activity of all synthesized 8‐cyclo‐1,5,3,7‐diazadiphosphocines (4a‐c, and 5–16) was evaluated against several cancer cell lines.

Magnetic Multiwall Carbon Nanotube Decorated with Novel Functionalities: Synthesis and Application as Adsorbents for Lead Removal from Aqueous Medium

Water pollution is one of the major challenges facing modern society because of industrial development and urban growth. This study is directed towards assessing the use of multiwall carbon nanotube, after derivatization and magnetization, as a new and renewable absorbent, to remove toxic metal ions from waste streams. The adsorbents were prepared by, first oxidation of multiwall carbon nanotube, then derivatizing the oxidized product with hydroxyl amine, hydrazine and amino acid. The adsorbents were characterized by various techniques. The adsorption efficiency of the multiwall carbon nanotube adsorbents toward Pb(II) was investigated. The effect of adsorbent’s dose, temperature, pH, and time on the adsorption efficiency were studied and the adsorption parameters that gave the highest efficiency were determined. The derivatives have unique coordination sites that included amine, hydroxyl, and carboxyl groups, which are excellent chelating agents for metal ions. The thermodynamic and kinetic results analysis results indicated spontaneous adsorption of Pb(II) by the multiwall carbon nanotube adsorbents at room temperature. The adsorption process followed pseudo-second-order and Langmuir isotherm model. The adsorbents were regenerated using 0.1 N HCl.