Effects of Zinc Gluconate and 2 Other Divalent Cationic Compounds on Olfactory Function in Mice

PubMed Central

Duncan-Lewis, Christopher A; Lukman, Roy L; Banks, Robert K

2011-01-01

Intranasal application of zinc gluconate has commonly been used to treat the common cold. The safety of this treatment, however, has come into question recently. In addition to a United States recall of a homeopathic product that contains zinc gluconate, abundant literature reports cytotoxic effects of zinc on the olfactory epithelium. Additional research suggests that divalent cations (such as zinc) can block ion channels that facilitate the transduction of odors into electrical signals on the olfactory epithelium. The purpose of the current study was 2-fold: to confirm whether zinc gluconate causes anosmia and to reveal whether any other divalent cationic compounds produce a similar effect. Groups of mice underwent a buried food-pellet test to gauge olfactory function and then were nasally irrigated with 1 of 3 divalent cationic compounds. When tested after treatment, mice irrigated with zinc gluconate and copper gluconate experienced a marked increase in food-finding time, indicating that they had lost their ability to smell a hidden food source. Control mice irrigated with saline had a significantly lower increase in times. These results confirm that zinc gluconate can cause anosmia and reveal that multiple divalent cations can negatively affect olfaction. PMID:22330252

Use of MgO doped with a divalent or trivalent metal cation for removing arsenic from water

DOEpatents

Moore, Robert C; Holt-Larese, Kathleen C; Bontchev, Ranko

2013-08-13

Systems and methods for use of magnesium hydroxide, either directly or through one or more precursors, doped with a divalent or trivalent metal cation, for removing arsenic from drinking water, including water distribution systems. In one embodiment, magnesium hydroxide, Mg(OH).sub.2 (a strong adsorbent for arsenic) doped with a divalent or trivalent metal cation is used to adsorb arsenic. The complex consisting of arsenic adsorbed on Mg(OH).sub.2 doped with a divalent or trivalent metal cation is subsequently removed from the water by conventional means, including filtration, settling, skimming, vortexing, centrifugation, magnetic separation, or other well-known separation systems. In another embodiment, magnesium oxide, MgO, is employed, which reacts with water to form Mg(OH).sub.2. The resulting Mg(OH).sub.2 doped with a divalent or trivalent metal cation, then adsorbs arsenic, as set forth above. The method can also be used to treat human or animal poisoning with arsenic.

Use of MgO doped with a divalent or trivalent metal cation for removing arsenic from water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Robert C.; Larese, Kathleen Caroline; Bontchev, Ranko Panayotov

Systems and methods for use of magnesium hydroxide, either directly or through one or more precursors, doped with a divalent or trivalent metal cation, for removing arsenic from drinking water, including water distribution systems. In one embodiment, magnesium hydroxide, Mg(OH).sub.2 (a strong adsorbent for arsenic) doped with a divalent or trivalent metal cation is used to adsorb arsenic. The complex consisting of arsenic adsorbed on Mg(OH).sub.2 doped with a divalent or trivalent metal cation is subsequently removed from the water by conventional means, including filtration, settling, skimming, vortexing, centrifugation, magnetic separation, or other well-known separation systems. In another embodiment, magnesiummore » oxide, MgO, is employed, which reacts with water to form Mg(OH).sub.2. The resulting Mg(OH).sub.2 doped with a divalent or trivalent metal cation, then adsorbs arsenic, as set forth above. The method can also be used to treat human or animal poisoning with arsenic.« less

Phosphorus-31 and carbon-13 nuclear magnetic resonance studies of divalent cation binding to phosphatidylserine membranes. Use of cobalt as a paramagnetic probe

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLaughlin, A.C.

1982-01-01

The paramagnetic divalent cation cobalt has large and well-understood effects on NMR signals from ligands bound in the first coordination sphere, i.e., inner-sphere ligands, and the authors have used these effects to identify divalent cation binding sites at the surface of phosphatidylserine membranes. /sup 31/P NMR results show that 13% of the bound cobalt ions are involved in inner-sphere complexes with the phosphodiester group, while /sup 13/C NMR results show that 54% of the bound cobalt ions are involved in unidentate inner sphere complexes with the carboxyl group. No evidence is found for cobalt binding to the carbonyl groups, butmore » proton release studies suggest that 32% of the bound cobalt ions are involved in chelate complexes that contain both the carboxyl and the amine groups. All of the bound cobalt ions can thus be accounted for in terms of inner sphere complexes with the phosphodiester group or the carboxyl group. They suggest that the unidentate inner-sphere complex between cobalt and the carboxyl group of phosphatidylserine and the inner-sphere complex between cobalt and the phosphodiester group of phosphatidylserine provide reasonable models for complexes between alkaline earth cations and phosphatidylserine membranes.« less

Phosphorus-31 and carbon-13 nuclear magnetic resonance studies of divalent cation binding to phosphatidylserine membranes: use of cobalt as a paramagnetic probe

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLaughlin, A.C.

1982-09-28

The paramagnetic divalent cation cobalt has large and well-understood effects on NMR signals from ligands bound in the first coordination sphere, i.e., inner-sphere ligands, and we have used these effects to identify divalent cation binding sites at the surface of phosphatidylserine membranes. /sup 31/P NMR results show that 13% of the bound cobalt ions are involved in inner-sphere complexes with the phosphodiester group, while /sup 13/C NMR results show that 54% of the bound cobalt ions are involved in unidentate inner sphere complexes with the carboxyl group. No evidence is found for cobalt binding to the carbonyl groups, but protonmore » release studies suggest that 32% of the bound cobalt ions are involved in chelate complexes that contain both the carboxyl and the amine groups. All (i.e., 13% + 54% + 32% = 99%) of the bound cobalt ions can thus be accounted for in terms of inner sphere complexes with the phosphodiester group or the carboxyl group. We suggest that the unidentate inner-sphere complex between cobalt and the carboxyl group of phosphatidylserine and the inner-sphere complex between cobalt and the phosphodiester group of phosphatidylserine provide reasonable models for complexes between alkaline earth cations and phosphatidylserine membranes.« less

Divalent cation interactions with oligogalacturonides.

PubMed

Cescutti, P; Rizzo, R

2001-07-01

The conformational properties of high and low molecular weight galacturonides were investigated in relation to the ability of oligomers with degree of polymerization >10 to act as elicitors of plant defense mechanisms. Oligomers from polygalacturonate were obtained by means of enzymatic hydrolysis. Two fractions exhibiting high and low average degrees of polymerization were isolated by solvent fractionation and characterized by means of electrospray mass spectrometry. The conformational behaviors of the two fractions were investigated in the presence of different divalent cations using circular dichroism. Calcium, copper, and zinc ions were able to induce a conformational transition in both fractions. When in the presence of the high molecular weight fraction, copper and zinc ions were much more effective than calcium ions, whereas the efficiency was much reduced with low molecular weight oligomers.

Effect of the chelation of metal cation on the antioxidant activity of chondroitin sulfates.

PubMed

Ajisaka, Katsumi; Oyanagi, Yutaka; Miyazaki, Tatsuo; Suzuki, Yasuhiro

2016-06-01

The antioxidant potencies of chondroitin sulfates (CSs) from shark cartilage, salmon cartilage, bovine trachea, and porcine intestinal mucosa were compared by three representative methods for the measurement of the antioxidant activity; DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity. CSs from salmon cartilage and bovine trachea showed higher potency in comparison with CSs from shark cartilage and porcine intestinal mucosa. Next, CS from salmon cartilage chelating with Ca(2+), Mg(2+), Mn(2+), or Zn(2+) were prepared, and their antioxidant potencies were compared. CS chelating with Ca(2+) or Mg(2+) ions showed rather decreased DPPH radical scavenging activity in comparison with CS of H(+) form. In contrast, CS chelating with Ca(2+) or Mg(2+) ion showed remarkably enhanced superoxide radical scavenging activity than CS of H(+) or Na(+) form. Moreover, CS chelating with divalent metal ions, Ca(2+), Mg(2+), Mn(2+), or Zn(2+), showed noticeably higher hydroxyl radical scavenging activity than CS of H(+) or Na(+) form. The present results revealed that the scavenging activities of, at least, superoxide radical and hydroxyl radical were enhanced by the chelation with divalent metal ions.

Fluorescent Protein-Based Ca2+ Sensor Reveals Global, Divalent Cation-Dependent Conformational Changes in Cardiac Troponin C.

PubMed

Badr, Myriam A; Pinto, Jose R; Davidson, Michael W; Chase, P Bryant

2016-01-01

Cardiac troponin C (cTnC) is a key effector in cardiac muscle excitation-contraction coupling as the Ca2+ sensing subunit responsible for controlling contraction. In this study, we generated several FRET sensors for divalent cations based on cTnC flanked by a donor fluorescent protein (CFP) and an acceptor fluorescent protein (YFP). The sensors report Ca2+ and Mg2+ binding, and relay global structural information about the structural relationship between cTnC's N- and C-domains. The sensors were first characterized using end point titrations to decipher the response to Ca2+ binding in the presence or absence of Mg2+. The sensor that exhibited the largest responses in end point titrations, CTV-TnC, (Cerulean, TnC, and Venus) was characterized more extensively. Most of the divalent cation-dependent FRET signal originates from the high affinity C-terminal EF hands. CTV-TnC reconstitutes into skinned fiber preparations indicating proper assembly of troponin complex, with only ~0.2 pCa unit rightward shift of Ca2+-sensitive force development compared to WT-cTnC. Affinity of CTV-TnC for divalent cations is in agreement with known values for WT-cTnC. Analytical ultracentrifugation indicates that CTV-TnC undergoes compaction as divalent cations bind. C-terminal sites induce ion-specific (Ca2+ versus Mg2+) conformational changes in cTnC. Our data also provide support for the presence of additional, non-EF-hand sites on cTnC for Mg2+ binding. In conclusion, we successfully generated a novel FRET-Ca2+ sensor based on full length cTnC with a variety of cellular applications. Our sensor reveals global structural information about cTnC upon divalent cation binding.

Electrochemical Formation of Divalent Samarium Cation and Its Characteristics in LiCl-KCl Melt.

PubMed

Bae, Sang-Eun; Jung, Tae Sub; Cho, Young-Hwan; Kim, Jong-Yun; Kwak, Kyungwon; Park, Tae-Hong

2018-06-28

The electrochemical reduction of trivalent samarium in a LiCl-KCl eutectic melt produced highly stable divalent samarium, whose electrochemical properties and electronic structure in the molten salt were investigated using cyclic voltammetry, UV-vis absorption spectroscopy, laser-induced emission spectroscopy, and density functional theory (DFT) calculations. Diffusion coefficients of Sm 2+ and Sm 3+ were electrochemically measured to be 0.92 × 10 -5 and 1.10 × 10 -5 cm 2 /s, respectively, and the standard apparent potential of the Sm 2+/3+ couple was estimated to be -0.82 V vs Ag|Ag + at 450 °C. The spectroelectrochemical study demonstrated that the redox behavior of the samarium cations obeys the Nernst equation ( E°' = -0.83 V, n = 1) and the trivalent samarium cation was successfully converted to the divalent cation having characteristic absorption bands at 380 and 530 nm with molar absorptivity values of 1470 and 810 M -1 cm -1 , respectively. Density function theory calculations for the divalent samarium complex revealed that the absorption signals originated from the 4f 6 to 4f 5 5d 1 transitions. Additionally, laser-induced emission measurements for the Sm cations in the LiCl-KCl matrix showed that the Sm 3+ ion in the LiCl-KCl melt at 450 °C emitted an orange color of fluorescence, whereas a red colored emission was observed from the Sm 2+ ion in the solidified LCl-KCl salt at room temperature.

Comparison of the effects of divalent cations on the noradrenaline-evoked cation current in rabbit portal vein smooth muscle cells

PubMed Central

Aromolaran, A S; Large, W A

1999-01-01

The facilitatory effects of external Ca2+, Sr2+ and Ba2+ (Cao2+, Sro2+ and Bao2+) on the noradrenaline-evoked non-selective cation current (Icat) were compared in rabbit portal vein smooth muscle cells using patch pipette techniques. All divalent cations tested potentiated the amplitude of Icat and the potency sequence was Cao2+ > Sro2+ > Bao2+. Cao2+ and Sro2+ increased the amplitude of Icat by about eight times whereas Bao2+ produced only a threefold facilitation. The current-voltage relationship of Icat was not changed by Cao2+, Sro2+ or Bao2+. From noise analysis the single channel conductance (γ) was approximately 10 pS in divalent cation-free solution but was about 20 pS with Cao2+, Sro2+ and Bao2+. From noise and voltage-jump experiments it was apparent that at least three kinetically resolvable channel states are associated with Icat in divalent cation-free solution. Cao2+ and Sro2+ produced marked changes in the characteristics of the power spectrum and relaxations of Icat in response to voltage steps, consistent with a shift in the equilibrium between the channel states, whereas Bao2+ produced minimal effects. The data show that Cao2+, Sro2+ and Bao2+ increase the amplitude of Icat, which results in part from an increase in the single channel conductance. In addition the results suggest that Cao2+ and Sro2+ alter the kinetic behaviour of the single channels whereas Bao2+ has little effect on the equilibrium between the channel states. PMID:10545143

Binding of Divalent Cations to Polygalacturonate: A Mechanism Driven by the Hydration Water.

PubMed

Huynh, Uyen T D; Lerbret, Adrien; Neiers, Fabrice; Chambin, Odile; Assifaoui, Ali

2016-02-11

We have investigated the interactions between polygalacturonate (polyGal) and four divalent cations (M(2+) = Ba(2+), Ca(2+), Mg(2+), Zn(2+)) that differ in size and affinity for water. Our results evidence that M(2+)-polyGal interactions are intimately linked to the affinity of M(2+) for water. Mg(2+) interacts so strongly with water that it remains weakly bound to polyGal (polycondensation) by sharing water molecules from its first coordination shell with the carboxylate groups of polyGal. In contrast, the other cations form transient ionic pairs with polyGal by releasing preferentially one water molecule (for Zn(2+)) or two (for Ca(2+) and Ba(2+)), which corresponds to monodentate and bidentate binding modes with carboxylates, respectively. The mechanism for the binding of these three divalent cations to polyGal can be described by two steps: (i) monocomplexation and formation of point-like cross-links between polyGal chains (at low M(2+)/Gal molar ratios, R) and (ii) dimerization (at higher R). The threshold molar ratio, R*, between these two steps depends on the nature of divalent cations and is lower for calcium ions (R* < 0.1) than for zinc and barium ions (R* > 0.3). This difference may be explained by the intermediate affinity of Ca(2+) for water with respect to those of Zn(2+) and Ba(2+), which may induce the formation of cross-links of intermediate flexibility. By comparison, the lower and higher flexibilities of the cross-links formed by Zn(2+) and Ba(2+), respectively, may shift the formation of dimers to higher molar ratios (R*).

Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes.

PubMed Central

Smyth, C J; Möllby, R; Wadström, T

1975-01-01

Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization. Images PMID:333

The permeability of endplate channels to monovalent and divalent metal cations

PubMed Central

1980-01-01

The relative permeability of endplate channels to monovalent and divalent metal ions was determined from reversal potentials. Thallium is the most permeant ion with a permeability ratio relative to Na+ of 2.5. The selectivity among alkali metals is weak with a sequence, Cs+ greater than Rb+ greater than K+ greater than Na+ greater than Li+, and permeability ratios of 1.4, 1.3, 1.1, 1.0, and 0.9. The selectivity among divalent ions is also weak, with a sequence for alkaline earths of Mg++ greater than Ca++ greater than Ba++ greater than Sr++. The transition metal ions Mn++, Co++, Ni++, Zn++, and Cd++ are also permeant. Permeability ratios for divalent ions decreased as the concentration of divalent ion was increased in a manner consistent with the negative surface potential theory of Lewis (1979 J. Physiol. (Lond.). 286: 417--445). With 20 mM XCl2 and 85.5 mM glucosamine.HCl in the external solution, the apparent permeability ratios for the alkaline earth cations (X++) are in the range 0.18--0.25. Alkali metal ions see the endplate channel as a water-filled, neutral pore without high-field-strength sites inside. Their permeability sequence is the same as their aqueous mobility sequence. Divalent ions, however, have a permeability sequence almost opposite from their mobility sequence and must experience some interaction with groups in the channel. In addition, the concentrations of monovalent and divalent ions are increased near the channel mouth by a weak negative surface potential. PMID:6247423

Regulation by divalent cations of /sup 3/H-baclofen binding to GABA/sub B/ sites in rat cerebellar membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, K.; Goto, M.; Fukuda, H.

1983-02-21

When investigating the effects of divalent cations (Mg/sup 2 +/, Ca/sup 2 +/, Sr/sup 2 +/, Ba/sup 2 +/, Mn/sup 2 +/ and Ni/sup 2 +/) on /sup 3/H-baclofen binding to rat cerebellar synaptic membranes, we found that the specific binding of /sup 3/H-baclofen was not only dependent on divalent cations, but was increased dose-dependently in the presence of these cations. The effects were in the following order of potency: Mn/sup 2 +/ approx. = Ni/sup 2 +/ > Mg/sup 2 +/ > Ca/sup 2 +/ > Sr/sup 2 +/ > Ba/sup 2 +/. Scatchard analysis of the binding datamore » revealed a single component of the binding sites in the presence of 2.5 mM MgCl/sub 2/, 2.5 mM CaCl/sub 2/ or 0.3 mM MnCl/sub 2/ whereas two components appeared in the presence of 2.5 mM MnCl/sub 2/ or 1 mM NiCl/sub 2/. In the former, divalent cations altered the apparent affinity (K/sub d/) without affecting density of the binding sites (B/sub max/). In the latter, the high-affinity sites showed a higher affinity and lower density of the binding sites than did the single component of the former. As the maximal effects of four cations (Mg/sup 2 +/, Ca/sup 2 +/, Mn/sup 2 +/, and Ni/sup 2 +/) were not additive, there are probably common sites of action of these divalent cations. Among the ligands for GABA/sub B/ sites, the affinity for (-), (+) and (+/-)baclofen, GABA and ..beta..-phenyl GABA increased 2 - 6 fold in the presence of 2.5 mM MnCl/sub 2/, in comparison with that in HEPES-buffered Krebs solution (containing 2.5 mM CaCl/sub 2/ and 1.2 mM MgSO/sub 4/), whereas that for muscimol was decreased to one-fifth. Thus, the affinity of GABA/sub B/ sites for its ligands is probably regulated by divalent cations, through common sites of action.« less

Induction of divalent cation permeability by heterologous expression of a voltage sensor domain.

PubMed

Arima, Hiroki; Tsutsui, Hidekazu; Sakamoto, Ayako; Yoshida, Manabu; Okamura, Yasushi

2018-01-06

The voltage sensor domain (VSD) is a protein domain that confers sensitivity to membrane potential in voltage-gated ion channels as well as the voltage-sensing phosphatase. Although VSDs have long been considered to function as regulatory units acting on adjacent effectors, recent studies have revealed the existence of direct ion permeation paths in some mutated VSDs and in the voltage-gated proton channel. In this study, we show that calcium currents are evoked upon membrane hyperpolarization in cells expressing a VSD derived from an ascidian voltage-gated ion channel superfamily. Unlike the previously reported omega-pore in the Shaker K + channel and rNav1.4, mutations are not required. From electrophysiological experiments in heterologous expression systems, we found that the conductance is directly mediated by the VSD itself and is carried by both monovalent and divalent cations. This is the first report of divalent cation permeation through a VSD-like structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Opposing effects of cationic antimicrobial peptides and divalent cations on bacterial lipopolysaccharides

NASA Astrophysics Data System (ADS)

Smart, Matthew; Rajagopal, Aruna; Liu, Wing-Ki; Ha, Bae-Yeun

2017-10-01

The permeability of the bacterial outer membrane, enclosing Gram-negative bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS) layer, with surrounding ions and molecules. We present a coarse-grained model for describing how cationic amphiphilic molecules (e.g., antimicrobial peptides) interact with and perturb the LPS layer in a biologically relevant medium, containing monovalent and divalent salt ions (e.g., Mg2+). In our approach, peptide binding is driven by electrostatic and hydrophobic interactions and is assumed to expand the LPS layer, eventually priming it for disruption. Our results suggest that in parameter ranges of biological relevance (e.g., at micromolar concentrations) the antimicrobial peptide magainin 2 effectively disrupts the LPS layer, even though it has to compete with Mg2+ for the layer. They also show how the integrity of LPS is restored with an increasing concentration of Mg2+. Using the approach, we make a number of predictions relevant for optimizing peptide parameters against Gram-negative bacteria and for understanding bacterial strategies to develop resistance against cationic peptides.

In Vitro Inhibition of Leishmania Attachment to Sandfly Midguts and LL-5 Cells by Divalent Metal Chelators, Anti-gp63 and Phosphoglycans.

PubMed

Soares, Rodrigo Pedro; Altoé, Ellen Cristina Félix; Ennes-Vidal, Vítor; da Costa, Simone M; Rangel, Elizabeth Ferreira; de Souza, Nataly Araújo; da Silva, Vanderlei Campos; Volf, Petr; d'Avila-Levy, Claudia Masini

2017-07-01

Leishmania braziliensis and Leishmania infantum are the causative agents of cutaneous and visceral leishmaniasis, respectively. Several aspects of the vector-parasite interaction involving gp63 and phosphoglycans have been individually assayed in different studies. However, their role under the same experimental conditions was not studied yet. Here, the roles of divalent metal chelators, anti-gp63 antibodies and purified type I phosphoglycans (PGs) were evaluated during in vitro parasite attachment to the midgut of the vector. Parasites were treated with divalent metal chelators or anti-gp63 antibodies prior to the interaction with Lutzomyia longipalpis/Lutzomyia intermedia midguts or sand fly LL-5 cells. In vitro binding system was used to examine the role of PG and gp63 in parallel. Treatment with divalent metal chelators reduced Le. infantum adhesion to the Lu. longipalpis midguts. The most effective compound (Phen) inhibited the binding in both vectors. Similar results were observed in the interaction between both Leishmania species and the cell line LL-5. Finally, parallel experiments using anti-gp63-treated parasites and PG-incubated midguts demonstrated that both approaches substantially inhibited attachment in the natural parasite-vector pairs Le. infantum/Lu. longipalpis and Le. braziliensis/Lu. intermedia. Our results suggest that gp63 and/or PG are involved in parasite attachment to the midgut of these important vectors. Copyright © 2017 Elsevier GmbH. All rights reserved.

Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold

PubMed Central

Cao, Xu; Ma, Linlin; Yang, Fan

2014-01-01

Transient receptor potential vanilloid type 1 (TRPV1) channel responds to a wide spectrum of physical and chemical stimuli. In doing so, it serves as a polymodal cellular sensor for temperature change and pain. Many chemicals are known to strongly potentiate TRPV1 activation, though how this is achieved remains unclear. In this study we investigated the molecular mechanism underlying the gating effects of divalent cations Mg2+ and Ba2+. Using a combination of fluorescence imaging and patch-clamp analysis, we found that these cations potentiate TRPV1 gating by most likely promoting the heat activation process. Mg2+ substantially lowers the activation threshold temperature; as a result, a significant fraction of channels are heat-activated at room temperature. Although Mg2+ also potentiates capsaicin- and voltage-dependent activation, these processes were found either to be not required (in the case of capsaicin) or insufficient (in the case of voltage) to mediate the activating effect. In support of a selective effect on heat activation, Mg2+ and Ba2+ cause a Ca2+-independent desensitization that specifically prevents heat-induced channel activation but does not prevent capsaicin-induced activation. These results can be satisfactorily explained within an allosteric gating framework in which divalent cations strongly promote the heat-dependent conformational change or its coupling to channel activation, which is further coupled to the voltage- and capsaicin-dependent processes. PMID:24344247

Dynamics of Pseudomonas aeruginosa association with anionic hydrogel surfaces in the presence of aqueous divalent-cation salts

PubMed Central

Tran, Victoria B.; Sung, Ye Suel; Fleiszig, Suzanne M.J.; Evans, David J.; Radke, C.J.

2013-01-01

Binding of bacteria to solid surfaces is complex with many aspects incompletely understood. We investigate Pseudomonas aeruginosa uptake kinetics onto hydrogel surfaces representative of soft-contact lenses made of nonionic poly(2-hydroxyethylmethacrylate) (p-HEMA), anionic poly(methacrylic acid) (p-MAA), and anionic poly(acrylic acid) (p-AA). Using a parallel-plate flow cell under phase-contrast microscopy, we document a kinetic “burst” at the anionic hydrogel surface: dilute aqueous P. aeruginosa first rapidly accumulates and then rapidly depletes. Upon continuing flow, divalent cations in the suspending solution sorb into the hydrogel network causing the previously surface-accumulated bacteria to desorb. The number of bacteria eventually bound to the surface is low compared to the nonionic p-HEMA hydrogel. We propose that the kinetic burst is due to reversible divalent-cation bridging between the anionic bacteria and the negatively charged hydrogel surface. The number of surface bridging sites diminishes as divalent cations impregnate into and collapse the gel. P. aeruginosa association with the surface then falls. Low eventual binding of P. aeruginosa to the anionic hydrogel is ascribed to increased surface hydrophilicity compared to the counterpart nonionic p-HEMA hydrogel. PMID:21723562

Divalent cation and ionic strength effects on Vinca alkaloid-induced tubulin self-association.

PubMed

Lobert, S; Boyd, C A; Correia, J J

1997-01-01

We present here a systematic study of ionic strength and divalent cation effects on Vinca alkaloid-induced tubulin spiral formation. We used sedimentation velocity experiments and quantitative fitting of weight-average sedimentation coefficients versus free drug concentrations to obtain thermodynamic parameters under various solution conditions. The addition of 50-150 mM NaCl to our standard buffer (10 mM piperazine-N,N'-bis(2-ethanesulfonic acid), 1 mM Mg, 50 microM GDP or GTP, pH 6.9) enhances overall vinblastine- or vincristine-induced tubulin self-association. As demonstrated in previous studies, GDP enhances overall self-association more than GTP, although in the presence of salt, GDP enhancement is reduced. For example, in 150 mM NaCl, GDP enhancement is 0.24 kcal/mol for vinblastine and 0.36 kcal/mol for vincristine versus an average enhancement of 0.87 (+/- 0.34) kcal/mol for the same drugs in the absence of salt. Wyman linkage analysis of experiments with vinblastine or vincristine over a range of NaCl concentrations showed a twofold increase in the change in NaCl bound to drug-induced spirals in the presence of GTP compared to GDP. These data indicate that GDP enhancement of Vinca alkaloid-induced tubulin self-association is due in part to electrostatic inhibition in the GTP state. In the absence of NaCl, we found that vinblastine and 1 mM Mn2+ or Ca2+ causes immediate condensation of tubulin. The predominant aggregates observed by electron microscopy are large sheets. This effect was not found with 1 mM Mg2+. At 100 microM cation concentrations (Mn2+, Mg2+, or Ca2+), GDP enhances vinblastine-induced spiral formation by 0.55 (+/- 0.26) kcal/mol. This effect is found only in K2, the association of liganded heterodimers at the ends of growing spirals. There is no GDP enhancement of K1, the binding of drug to heterodimer, although K1 is dependent upon the divalent cation concentration. NaCl diminishes tubulin condensation, probably by inhibiting lateral

Cluster-Continuum Calculations of Hydration Free Energies of Anions and Group 12 Divalent Cations.

PubMed

Riccardi, Demian; Guo, Hao-Bo; Parks, Jerry M; Gu, Baohua; Liang, Liyuan; Smith, Jeremy C

2013-01-08

Understanding aqueous phase processes involving group 12 metal cations is relevant to both environmental and biological sciences. Here, quantum chemical methods and polarizable continuum models are used to compute the hydration free energies of a series of divalent group 12 metal cations (Zn(2+), Cd(2+), and Hg(2+)) together with Cu(2+) and the anions OH(-), SH(-), Cl(-), and F(-). A cluster-continuum method is employed, in which gas-phase clusters of the ion and explicit solvent molecules are immersed in a dielectric continuum. Two approaches to define the size of the solute-water cluster are compared, in which the number of explicit waters used is either held constant or determined variationally as that of the most favorable hydration free energy. Results obtained with various polarizable continuum models are also presented. Each leg of the relevant thermodynamic cycle is analyzed in detail to determine how different terms contribute to the observed mean signed error (MSE) and the standard deviation of the error (STDEV) between theory and experiment. The use of a constant number of water molecules for each set of ions is found to lead to predicted relative trends that benefit from error cancellation. Overall, the best results are obtained with MP2 and the Solvent Model D polarizable continuum model (SMD), with eight explicit water molecules for anions and 10 for the metal cations, yielding a STDEV of 2.3 kcal mol(-1) and MSE of 0.9 kcal mol(-1) between theoretical and experimental hydration free energies, which range from -72.4 kcal mol(-1) for SH(-) to -505.9 kcal mol(-1) for Cu(2+). Using B3PW91 with DFT-D3 dispersion corrections (B3PW91-D) and SMD yields a STDEV of 3.3 kcal mol(-1) and MSE of 1.6 kcal mol(-1), to which adding MP2 corrections from smaller divalent metal cation water molecule clusters yields very good agreement with the full MP2 results. Using B3PW91-D and SMD, with two explicit water molecules for anions and six for divalent metal cations, also

Binding symmetry of extracellular divalent cations to conduction pore studied using tandem dimers of a CNG channel.

PubMed

Kwon, Ryuk-Jun; Ha, Tal Soo; Kim, Wonjae; Park, Chul-Seung

2002-11-08

Cyclic nucleotide-gated (CNG) channels are composed of the tetramer of alpha-subunit alone or alpha- and beta-subunits. The alpha-subunits of these channels have a conserved glutamate (Glu) residue within the pore-forming region and the residue determines the selectivity as well as the affinity for the extracellular divalent cations. Using the high-affinity mutant (E363D) of bovine retinal CNG channel in which the Glu at position 363 was replaced to Asp, we constructed tandem dimers and investigated the binding characteristics of divalent cations to the site. The gating and permeation characteristics of individual homomeric tandem dimers are indistinguishable to those of homo-tetramers formed by parental monomers. The heteromeric tandem dimers showed the binding affinity for Sr(2+) identical to the geometric mean of the affinities for two parent channels, indicating the energy additive and thus the simultaneous interaction. On the other hand, the binding affinity for Mg(2+) followed the harmonic mean of those parent channels indicating that Mg(2+) interacts more strongly with the subunit bearing Asp residue at the position. Thus the results strongly suggest that the Glu363 residues in the CNG channel pore be flexible enough to adapt different binding symmetries for different divalent cations. Moreover, the simultaneous interaction between the four Glu residues and Sr(2+) provides an important structural constraint to the CNG channel outer vestibule of unknown structure.

Reversible changes of canavalin solubility controlled by divalent cation concentration in crude sword bean extract.

PubMed

Nishizawa, Kaho; Arii, Yasuhiro

2016-12-01

Canavalin is a vicilin-class (7S) storage protein found in sword bean (Canavalia gladiata). Our previous report indicated that canavalin is precipitated by the addition of 20 mM MgCl 2 to crude sword bean extract. Here, we examined the solubility changes induced by the addition of Mg 2+ and Ca 2+ at various concentrations. Canavalin tended to be insolubilized at relatively low concentrations of MgCl 2 (< 20 mM) and solubilized at relatively high concentrations (> 20 mM). In addition, canavalin was slightly insolubilized in the presence of NaCl. Overall, the results revealed that solubility changes are reversible and depend on the concentration of divalent cations. Therefore, we suggested a reaction scheme that describes the effects of divalent cations on the solubility of canavalin, which would facilitate the study of its physiological function and the application of canavalin in the food processing industry.

PRE- AND POST-SYNAPTIC EFFECTS OF MANIPULATING SURFACE CHARGE WITH DIVALENT CATIONS AT THE PHOTORECEPTOR SYNAPSE

PubMed Central

CADETTI, L.; THORESON, W. B.; PICCOLINO, M.

2006-01-01

Persistence of horizontal cell (HC) light responses in extracellular solutions containing low Ca2+ plus divalent cations to block Ca2+ currents (ICa) has been attributed to Ca2+-independent neurotransmission. Using a retinal slice preparation to record both ICa and light responses, we demonstrate that persistence of HC responses in low [Ca2+]o can instead be explained by a paradoxical increase of Ca2+ influx into photoreceptor terminals arising from surface charge-mediated shifts in ICa activation. Consistent with this explanation, application of Zn2+ or Ni2+ caused a hyperpolarizing block of HC light responses that was relieved by lowering [Ca2+]o. The same concentrations of Zn2+ and Ni2+ reduced the amplitude of ICa at the rod dark potential and this reduction was relieved by a hyperpolarizing shift in voltage dependence induced by lowering [Ca2+]o. Block of ICa by Mg2+, which has weak surface charge effects, was not relieved by low [Ca2+]o. Recovery of HC responses in low [Ca2+]o was assisted by enhancement of rod light responses. To bypass light stimulation, OFF bipolar cells were stimulated by steps to −40 mV applied to presynaptic rods during simultaneous paired recordings. Consistent with surface charge theory, the post-synaptic current was inhibited by Zn2+ and this inhibition was relieved by lowering [Ca2+]o. Nominally divalent-free media produced inversion of HC light responses even though rod light responses remained hyperpolarizing; HC response inversion can be explained by surface charge-mediated shifts in ICa. In summary, HC light responses modifications induced by low divalent cation solutions can be explained by effects on photoreceptor light responses and membrane surface charge without necessitating Ca2+-independent neurotransmission. Furthermore, these results suggest that surface charge effects accompanying physiological changing divalent cation levels in the synaptic cleft may provide a means for modulating synaptic output from photoreceptors

Fluoride ion recognition by chelating and cationic boranes.

PubMed

Hudnall, Todd W; Chiu, Ching-Wen; Gabbaï, François P

2009-02-17

Because of the ubiquity of fluoride ions and their potential toxicity at high doses, researchers would like to design receptors that selectively detect this anion. Fluoride is found in drinking water, toothpaste, and osteoporosis drugs. In addition, fluoride ions also can be detected as an indicator of uranium enrichment (via hydrolysis of UF(6)) or of the chemical warfare agent sarin, which releases the ion upon hydrolysis. However, because of its high hydration enthalpy, the fluoride anion is one of the most challenging targets for anion recognition. Among the various recognition strategies that are available, researchers have focused a great deal of attention on Lewis acidic boron compounds. These molecules typically interact with fluoride anions to form the corresponding fluoroborate species. In the case of simple triarylboranes, the fluoroborates are formed in organic solvents but not in water. To overcome this limitation, this Account examines various methods we have pursued to increase the fluoride-binding properties of boron-based receptors. We first considered the use of bifunctional boranes, which chelate the fluoride anion, such as 1,8-diborylnaphthalenes or heteronuclear 1-boryl-8-mercurio-naphthalenes. In these molecules, the neighboring Lewis acidic atoms can cooperatively interact with the anionic guest. Although the fluoride binding constants of the bifunctional compounds exceed those of neutral monofunctional boranes by several orders of magnitude, the incompatibility of these systems with aqueous media limits their utility. More recently, we have examined simple triarylboranes whose ligands are decorated by cationic ammonium or phosphonium groups. These cationic groups increase the electrophilic character of these boranes, and unlike their neutral analogs, they are able to complex fluoride in aqueous media. We have also considered cationic boranes, which form chelate complexes with fluoride anions. Our work demonstrates that Coulombic and chelate

Salinity-Dependent Contact Angle Alteration in Oil/Brine/Silicate Systems: the Critical Role of Divalent Cations

PubMed Central

2017-01-01

The effectiveness of water flooding oil recovery depends to an important extent on the competitive wetting of oil and water on the solid rock matrix. Here, we use macroscopic contact angle goniometry in highly idealized model systems to evaluate how brine salinity affects the balance of wetting forces and to infer the microscopic origin of the resultant contact angle alteration. We focus, in particular, on two competing mechanisms debated in the literature, namely, double-layer expansion and divalent cation bridging. Our experiments involve aqueous droplets with a variable content of chloride salts of Na+, K+, Ca2+, and Mg2+, wetting surfaces of muscovite and amorphous silica, and an environment of ambient decane containing small amounts of fatty acids to represent polar oil components. By diluting the salt content in various manners, we demonstrate that the water contact angle on muscovite, not on silica, decreases by up to 25° as the divalent cation concentration is reduced from typical concentrations in seawater to zero. Decreasing the ionic strength at a constant divalent ion concentration, however, has a negligible effect on the contact angle. We discuss the consequences for the interpretation of core flooding experiments and the identification of a microscopic mechanism of low salinity water flooding, an increasingly popular, inexpensive, and environment-friendly technique for enhanced oil recovery. PMID:28332396

Salinity-Dependent Contact Angle Alteration in Oil/Brine/Silicate Systems: the Critical Role of Divalent Cations.

PubMed

Haagh, M E J; Siretanu, I; Duits, M H G; Mugele, F

2017-04-11

The effectiveness of water flooding oil recovery depends to an important extent on the competitive wetting of oil and water on the solid rock matrix. Here, we use macroscopic contact angle goniometry in highly idealized model systems to evaluate how brine salinity affects the balance of wetting forces and to infer the microscopic origin of the resultant contact angle alteration. We focus, in particular, on two competing mechanisms debated in the literature, namely, double-layer expansion and divalent cation bridging. Our experiments involve aqueous droplets with a variable content of chloride salts of Na + , K + , Ca 2+ , and Mg 2+ , wetting surfaces of muscovite and amorphous silica, and an environment of ambient decane containing small amounts of fatty acids to represent polar oil components. By diluting the salt content in various manners, we demonstrate that the water contact angle on muscovite, not on silica, decreases by up to 25° as the divalent cation concentration is reduced from typical concentrations in seawater to zero. Decreasing the ionic strength at a constant divalent ion concentration, however, has a negligible effect on the contact angle. We discuss the consequences for the interpretation of core flooding experiments and the identification of a microscopic mechanism of low salinity water flooding, an increasingly popular, inexpensive, and environment-friendly technique for enhanced oil recovery.

Large divalent cations and electrostatic potentials adjacent to membranes. Experimental results with hexamethonium.

PubMed Central

Alvarez, O; Brodwick, M; Latorre, R; McLaughlin, A; McLaughlin, S; Szabo, G

1983-01-01

A simple extension of the Gouy-Chapman theory predicts that the ability of a divalent cation to screen charges at a membrane-solution interface decreases significantly if the distance between the charges on the cation is comparable with the Debye length. We tested this prediction by investigating the effect of hexamethonium on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes. The distance between the two charges of an extended hexamethonium molecule is approximately 1 nm, which is the Debye length in the 0.1 M monovalent salt solutions used in these experiments. Six different experimental approaches were utilized. We measured the electrophoretic mobility of multilamellar vesicles to determine the zeta potential, the line width of the 31P nuclear magnetic resonance (NMR) signal from sonicated vesicles to calculate the change in potential at the phosphodiester moiety of the lipid, and the conductance of planar bilayer membranes exposed to either carriers (nonactin) or pore formers (gramicidin) to estimate the change in potential within the membrane. We also measured directly the effect of hexamethonium on the potential above a monolayer formed from negative lipids, and attempted to calculate the change in the surface potential of a bilayer membrane from capacitance measurements. With the exception of the capacitance calculations, each of the techniques gave comparable results: hexamethonium exerts a smaller effect on the potential than that predicted by the classic screening theory. The results are consistent with the predictions of the extended Gouy-Chapman theory and are relevant to the interpretation of physiological and pharmacological experiments that utilize hexamethonium and other large divalent cations. PMID:6198001

Insights into gelation kinetics and gel front migration in cation-induced polysaccharide hydrogels by viscoelastic and turbidity measurements: Effect of the nature of divalent cations.

PubMed

Huynh, Uyen T D; Chambin, Odile; du Poset, Aline Maire; Assifaoui, Ali

2018-06-15

Polysaccharide-based hydrogels were prepared by the diffusion of various divalent cations (X 2+ ) into the polygalacturonate (polyGal) solution through a dialysis membrane. The diffusion of various divalent cations (Mg 2+ , Ca 2+ , Zn 2+ and Ba 2+ ) was investigated. The polyGal gel growth was studied as a function of the initial cation concentration by both viscoelastic and turbidity measurements. We have demonstrated for the first time that the determination of the spatiotemporal variation of turbidity during the gelation process allowed to study the gel front migration. For Ca-polyGal, Zn-polyGal and Ba-polyGal, the gel front migration was characterized by the presence of a peak at the sol/gel interface. This peak was not observed in the case of Mg-polyGal where the gel was not formed. The apparent diffusion coefficient of the gel front (D app ) which was calculated from the evolution of this peak increased when the initial cation concentration was increased. Moreover, we have suggested a gelation mechanism based on the presence of a threshold molar ratio R* (=[X 2+ ]/[Galacturonic unit]) in which some point-like crosslinks are precursors of the formation of dimers and multimers inducing the contraction of the gel and thus the formation of the gel front. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation of cation exchanger from lemon and sorption of divalent heavy metals.

PubMed

Arslanoglu, Hasan; Soner Altundogan, H; Tumen, Fikret

2008-05-01

A cation exchanging material was developed from lemon by modifying the pectic-cellulosic substances in the lemon peel by lemon juice having citric acid. For this purpose, chopped lemon removed from seeds and yellow skin was heated in two stages, firstly at 50 degrees C for 24h and subsequently at 120 degrees C for 2h. The material obtained was ground, repeatedly washed with water and dried. Lemon peel and lemon resin obtained were characterized through physicochemical analyses and FTIR spectroscopy. Heavy metal binding performance of this material was determined by removal tests conducted by using 10mM solutions of divalent metals. Experimental results show that the resin prepared from lemon is effective especially for Pb and Cu removals. For a lemon resin dosage of 10 g l(-1), sorption affinity of divalent metal ions is found to be in an order of Pb>Cu>Ni>Fe>Cd>Zn>Co>Mn. Typically, sorption capacities are about 0.87 and 0.43 mmol g(-1) for Pb and Mn, respectively.

Membrane Order Is a Key Regulator of Divalent Cation-Induced Clustering of PI(3,5)P2 and PI(4,5)P2.

PubMed

Sarmento, Maria J; Coutinho, Ana; Fedorov, Aleksander; Prieto, Manuel; Fernandes, Fábio

2017-10-31

Although the evidence for the presence of functionally important nanosized phosphorylated phosphoinositide (PIP)-rich domains within cellular membranes has accumulated, very limited information is available regarding the structural determinants for compartmentalization of these phospholipids. Here, we used a combination of fluorescence spectroscopy and microscopy techniques to characterize differences in divalent cation-induced clustering of PI(4,5)P 2 and PI(3,5)P 2 . Through these methodologies we were able to detect differences in divalent cation-induced clustering efficiency and cluster size. Ca 2+ -induced PI(4,5)P 2 clusters are shown to be significantly larger than the ones observed for PI(3,5)P 2 . Clustering of PI(4,5)P 2 is also detected at physiological concentrations of Mg 2+ , suggesting that in cellular membranes, these molecules are constitutively driven to clustering by the high intracellular concentration of divalent cations. Importantly, it is shown that lipid membrane order is a key factor in the regulation of clustering for both PIP isoforms, with a major impact on cluster sizes. Clustered PI(4,5)P 2 and PI(3,5)P 2 are observed to present considerably higher affinity for more ordered lipid phases than the monomeric species or than PI(4)P, possibly reflecting a more general tendency of clustered lipids for insertion into ordered domains. These results support a model for the description of the lateral organization of PIPs in cellular membranes, where both divalent cation interaction and membrane order are key modulators defining the lateral organization of these lipids.

Modulating macrophage polarization with divalent cations in nanostructured titanium implant surfaces

NASA Astrophysics Data System (ADS)

Lee, Chung-Ho; Kim, Youn-Jeong; Jang, Je-Hee; Park, Jin-Woo

2016-02-01

Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function.

Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis

PubMed Central

Rivera, Alicia; Kam, Siok Yuen; Ho, Mengfatt; Romero, Jose R.; Lee, Soohee

2012-01-01

XK is a putative transporter of unknown function that is ubiquitously expressed and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)-converting enzyme. We generated three knockout (KO) mice that lacked either Xk, Kell or both proteins and characterized erythrocyte cation levels, transport and hematological parameters. Absence of Xk or Kell was accompanied by changes in erythrocyte K+, Mg2+, Na+ and Ca2+ transport that were associated with changes in mean cellular volume and corpuscular hemoglobin concentration mean. Baseline Ca2+-ATPase activity was undetected in erythrocytes from all three mouse types but was restored upon pre-incubation with ET-3. Consistent with these alterations in Ca2+ handling, we observed increased Gardos channel activity in Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg2+ permeability while Xk deletion blocked Na/Mg exchanger activity. Our results provide evidence that cellular divalent cation regulation is functionally coupled to the Kell/XK system in erythrocytes and loss of this complex may contribute to acanthocytosis formation in McLeod syndrome. PMID:23122227

Interactions of divalent cations with calcium binding sites of BK channels reveal independent motions within the gating ring.

PubMed

Miranda, Pablo; Giraldez, Teresa; Holmgren, Miguel

2016-12-06

Large-conductance voltage- and calcium-activated K + (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca 2+ and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. In contrast to Ca 2+ that binds to both RCK domains, Mg 2+ , Cd 2+ , or Ba 2+ interact preferentially with either one or the other. Interaction of cations with their binding sites causes molecular rearrangements of the gating ring, but how these motions occur remains elusive. We have assessed the separate contributions of each RCK domain to the cation-induced gating-ring structural rearrangements, using patch-clamp fluorometry. Here we show that Mg 2+ and Ba 2+ selectively induce structural movement of the RCK2 domain, whereas Cd 2+ causes motions of RCK1, in all cases substantially smaller than those elicited by Ca 2+ By combining divalent species interacting with unique sites, we demonstrate that RCK1 and RCK2 domains move independently when their specific binding sites are occupied. Moreover, binding of chemically distinct cations to both RCK domains is additive, emulating the effect of fully occupied Ca 2+ binding sites.

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

PubMed

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Divalent Cations on the Structure of the Antibiotic Daptomycin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Steven W.; Jung, David; Calhoun, Jennifer R.

Abstract Daptomycin, a cyclic anionic lipopeptide antibiotic, whose three-dimensional structure was recently solved using solution state NMR (Ball et al. 2004; Jung et al. 2004; Rotondi and Gierasch 2005), requires calcium for function. To date, the exact nature of the interaction between divalent cations, such as Ca2+ or Mg2+, has not been fully characterized. It has, however, been suggested that addition of Ca2+ to daptomycin in a 1:1 molar ratio induces aggregation. Moreover, it has been suggested that certain residues, e.g. Asp3 and Asp7, which are essential for activity (Grunewald et al. 2004; Kopp et al. 2006), may also bemore » important for Ca2+ binding (Jung et al. 2004).« less

Antibacterial Activity of Probiotic Lactobacillus plantarum HK01: Effect of Divalent Metal Cations and Food Additives on Production Efficiency of Antibacterial Compounds.

PubMed

Sharafi, Hakimeh; Alidost, Leila; Lababpour, Abdolmajid; Shahbani Zahiri, Hossein; Abbasi, Habib; Vali, Hojatollah; Akbari Noghabi, Kambiz

2013-06-01

One hundred and sixty lactic acid bacteria, isolated from Iranian traditional dairy products, were screened for antibacterial potential. Among them, an isolate showing remarkable antibacterial activity against both Staphylococcus aureus (PTCC 1112) and Escherichia coli (PTCC 1338) was selected based on minimum inhibitory concentration (AU/mL). The morphological and biochemical characteristics of the isolate matched the literature description about genus Lactobacillus. Partial sequencing of 16S rRNA gene and its alignment with other Lactobacillus strains revealed that the isolate was closely related to the Lactobacillus plantarum. The isolate also exhibited the highest similarity (>99 %) to L. plantarum. We thus tentatively classified the bacterial isolate as L. plantarum HK01. The antibacterial active compound from HK01 strain remained stable for 45 min at 121 °C, and it reached a maximum activity at the end of log phase and the early part of stationary phase. The antibacterial activity of the test isolate, its probiotic properties and production efficacy through addition of some divalent metal cations and food additives were studied as well. The study of bile salt hydrolase (BSH) activity as a function of growth revealed that HK01 strain hydrolysing up to 5 % of sodium salt of glycodeoxycholic acid, correlated with the presence of bsh gene in the isolate. HK01 strain showed high resistance to lysozyme, good adaptation to simulated gastric juice and a moderate bile tolerance. Results obtained from simulated gastric juice conditions showed no significant difference occured during the 70 min. HK01 strain was classified as a strain with low hydrophobicity (34.2 %). Addition of trisodium citrate dehydrates as a food-grade chelator of divalent cations restored antibacterial compound production in MRS broth. Antibacterial compounds of L. plantarum HK01 endured treatment with 10 g/L of SDS, Tween 20, Tween 80 and urea. Concerning food additives, the results

Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis.

PubMed

Rivera, Alicia; Kam, Siok Yuen; Ho, Mengfatt; Romero, Jose R; Lee, Soohee

2013-02-01

XK is a putative transporter of unknown function that is ubiquitously expressed and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)-converting enzyme. We generated three knockout (KO) mice that lacked either Xk, Kell or both proteins and characterized erythrocyte cation levels, transport and hematological parameters. Absence of Xk or Kell was accompanied by changes in erythrocyte K(+), Mg(2+), Na(+) and Ca(2+) transport that were associated with changes in mean cellular volume and corpuscular hemoglobin concentration mean. Baseline Ca(2+)-ATPase activity was undetected in erythrocytes from all three mouse types but was restored upon pre-incubation with ET-3. Consistent with these alterations in Ca(2+) handling, we observed increased Gardos channel activity in Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg(2+) permeability while Xk deletion blocked Na/Mg exchanger activity. Our results provide evidence that cellular divalent cation regulation is functionally coupled to the Kell/XK system in erythrocytes and loss of this complex may contribute to acanthocytosis formation in McLeod syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

Divalent Metal Cations Potentiate the Predatory Capacity of Amoeba for Cryptococcus neoformans.

PubMed

Fu, Man Shun; Casadevall, Arturo

2018-02-01

Among the best-studied interactions between soil phagocytic predators and a human-pathogenic fungus is that of Acanthamoeba castellanii and Cryptococcus neoformans The experimental conditions used in amoeba-fungus confrontation assays can have major effects on whether the fungus or the protozoan is ascendant in the interaction. In the presence of Mg 2+ and Ca 2+ in phosphate-buffered saline (PBS), C. neoformans was consistently killed when incubated with A. castellanii A. castellanii survived better in the presence of Mg 2+ and Ca 2+ , even when incubated with C. neoformans In the absence of Mg 2+ and Ca 2+ , C. neoformans survived when incubated with A. castellanii , and the percentage of dead amoebae was higher than when incubated without yeast cells. These results show that the presence of Mg 2+ and Ca 2+ can make a decisive contribution toward tilting the outcome of the interaction in favor of the amoeba. Of the two metals, Mg 2+ had a stronger effect than Ca 2+ The cations enhanced A. castellanii activity against C. neoformans via enhanced phagocytosis, which is the major mechanism by which amoebae kill fungal cells. We found no evidence that amoebae use extracellular killing mechanisms in their interactions with C. neoformans In summary, the presence of Mg 2+ and Ca 2+ enhanced the cell adhesion on the surfaces and the motility of the amoeba, thus increasing the chance for contact with C. neoformans and the frequency of phagocytosis. Our findings imply that the divalent cation concentration in soils could be an important variable for whether amoebae can control C. neoformans in the environment. IMPORTANCE The grazing of soil organisms by phagocytic predators such as amoebae is thought to select for traits that enable some of them to acquire the capacity for virulence in animals. Consequently, knowledge about the interactions between amoebae and soil microbes, such as pathogenic fungi, is important for understanding how virulence can emerge. We show that the

Compositional and Ionic-Size Controls on the Diffusion of Divalent Cations in Garnet: Insights from Atomistic Simulations

NASA Astrophysics Data System (ADS)

Carlson, W. D.

2012-12-01

Divalent cations in garnet (Mg, Fe, Mn, Ca) diffuse at rates that depend strongly on the host-crystal composition and on the ionic radius of the diffusant. Understanding of the nanoscale basis for these behaviors comes from atomistic simulations that calculate energies in the static limit for the defects and transition-state configurations associated with each diffusive step. Diffusion of divalent cations requires (a) creation of a cation-vacancy defect in a dodecahedral site and of a charge-compensating oxygen-vacancy defect that may or may not be in close spatial association; (b) except in the case of self-diffusion, creation of an impurity defect in which a foreign atom replaces the normal atom in a dodecahedral site adjacent to the vacancy; and (c) during the diffusive process, motion of the diffusing atom to a 'saddlepoint' position that represents the transition-state configuration. Comparisons of the system's energy in these various states, in structures of different composition and for ions of different ionic size, allows assessment of the nanoscale controls on diffusion kinetics. Molecular-statics calculations quantify defect energies and identify the transition-state configuration: the maximum energy along the diffusion path between two adjacent dodecahedral sites results when the diffusing ion is surrounded symmetrically by the six oxygen atoms that lie between the two sites. Across the range of end-member compositions, self-diffusion coefficients measured at identical conditions, and the tracer diffusivity of a single ion measured at identical conditions, can each vary by five orders of magnitude or more. Measured activation energies for these motions, however, are all equivalent to within ±6%. Calculated activation energies are in agreement with observations, in that they vary by only ±10%. Calculated vacancy-formation energies, on the other hand, are significantly larger in expanded structures; for example, that energy is greater for Prp than for

The bio-physics of condensation of divalent cations into the bacterial wall has implications for growth of Gram-positive bacteria.

PubMed

Rauch, Cyril; Cherkaoui, Mohammed; Egan, Sharon; Leigh, James

2017-02-01

The anionic-polyelectrolyte nature of the wall of Gram-positive bacteria has long been suspected to be involved in homeostasis of essential cations and bacterial growth. A better understanding of the coupling between the biophysics and the biology of the wall is essential to understand some key features at play in ion-homeostasis in this living system. We consider the wall as a polyelectrolyte gel and balance the long-range electrostatic repulsion within this structure against the penalty entropy required to condense cations around wall polyelectrolytes. The resulting equations define how cations interact physically with the wall and the characteristic time required for a cation to leave the wall and enter into the bacterium to enable its usage for bacterial metabolism and growth. The model was challenged against experimental data regarding growth of Gram-positive bacteria in the presence of varying concentration of divalent ions. The model explains qualitatively and quantitatively how divalent cations interact with the wall as well as how the biophysical properties of the wall impact on bacterial growth (in particular the initiation of bacterial growth). The interplay between polymer biophysics and the biology of Gram positive bacteria is defined for the first time as a new set of variables that contribute to the kinetics of bacterial growth. Providing an understanding of how bacteria capture essential metal cations in way that does not follow usual binding laws has implications when considering the control of such organisms and their ability to survive and grow in extreme environments. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Role of cations as components of jelly coats in Bufo arenarum fertilization.

PubMed

Medina, Marcela Fátima; Crespo, Claudia Alejandra; Ramos, Inés; Fernández, Silvia Nélida

2010-02-01

The role of monovalent (Na+, K+) and divalent (Ca2+, Mg2+) cations in Bufo arenarum fertilization was analysed. Our results showed that the highest fertilization percentages were obtained when strings of uterine oocytes (UO) were inseminated. Under these conditions, full jelly (FJ), which represents the jelly coats surrounding the oocytes at the time of deposition, contained 68.5 +/- 7.0 mM Na+, 27.4 +/- 2.4 mM K+, 6.3 +/- 0.9 mM Ca2+ and 6.9 +/- 0.9 mM Mg2+. When the strings of oocytes were washed in deionized water, these cations diffused into the liquid medium surrounding them. There was a marked similarity between the loss of Ca2+ in the jelly and the decrease in the fertilizability of the UO. Furthermore, the use of chelating agents of divalent cations showed the importance of the Ca2+ contained in the jelly. When Ca2+ was sequestered from the jelly coats by the addition of the chelating agents to the insemination medium as well as by pretreatment of the UO strings, a decrease in fertilization percentages occurred, this effect being dose dependent and more marked with EGTA. These results demonstrate that the Ca2+ in the jelly plays a role in fertilization. Nevertheless, taking into account that during the washing of the jelly other jelly coat components were diffused and considering that the addition of Ca2+ to the insemination medium reverted significantly, but only partially, the loss of fertilizability of jellied UO (washed), the participation of other components in the fertilization mechanism is suggested.

The Compact and Biologically Relevant Structure of Inter-α-inhibitor Is Maintained by the Chondroitin Sulfate Chain and Divalent Cations.

PubMed

Scavenius, Carsten; Nikolajsen, Camilla Lund; Stenvang, Marcel; Thøgersen, Ida B; Wyrożemski, Łukasz; Wisniewski, Hans-Georg; Otzen, Daniel E; Sanggaard, Kristian W; Enghild, Jan J

2016-02-26

Inter-α-inhibitor is a proteoglycan of unique structure. The protein consists of three subunits, heavy chain 1, heavy chain 2, and bikunin covalently joined by a chondroitin sulfate chain originating at Ser-10 of bikunin. Inter-α-inhibitor interacts with an inflammation-associated protein, tumor necrosis factor-inducible gene 6 protein, in the extracellular matrix. This interaction leads to transfer of the heavy chains from the chondroitin sulfate of inter-α-inhibitor to hyaluronan and consequently to matrix stabilization. Divalent cations and heavy chain 2 are essential co-factors in this transfer reaction. In the present study, we have investigated how divalent cations in concert with the chondroitin sulfate chain influence the structure and stability of inter-α-inhibitor. The results showed that Mg(2+) or Mn(2+), but not Ca(2+), induced a conformational change in inter-α-inhibitor as evidenced by a decrease in the Stokes radius and a bikunin chondroitin sulfate-dependent increase of the thermodynamic stability. This structure was shown to be essential for the ability of inter-α-inhibitor to participate in extracellular matrix stabilization. In addition, the data revealed that bikunin was positioned adjacent to both heavy chains and that the two heavy chains also were in close proximity. The chondroitin sulfate chain interacted with all protein components and inter-α-inhibitor dissociated when it was degraded. Conventional purification protocols result in the removal of the Mg(2+) found in plasma and because divalent cations influence the conformation and affect function it is important to consider this when characterizing the biological activity of inter-α-inhibitor. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Highly conducting divalent Mg{sup 2+} cation solid electrolytes with well-ordered three-dimensional network structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamura, Shinji; Yamane, Megumi; Hoshino, Yasunori

2016-03-15

A three-dimensionally well-ordered NASICON-type Mg{sup 2+} cation conductor, (Mg{sub x}Hf{sub 1−x}){sub 4/(4−2x)}Nb(PO{sub 4}){sub 3}, was firstly developed by partial substitution of lower valent Mg{sup 2+} cation onto the Hf{sup 4+} sites in a HfNb(PO{sub 4}){sub 3} solid to realize high Mg{sup 2+} cation conductivity even at moderate temperatures. Due to the formation of well-ordered NASICON-type structure, both the high Mg{sup 2+} cation conductivity below 450 °C and the low activation energy for Mg{sup 2+} cation migration was successfully realized for the (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{sub 4}){sub 3} solid. Pure Mg{sup 2+} cation conduction in the NASICON-type (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{submore » 4}){sub 3} solid was directly and quantitatively demonstrated by means of two kinds of dc electrolysis. - Graphical abstract: Image of the Mg{sup 2+} cation conduction in NASICON-type (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{sub 4}){sub 3} and its Mg{sup 2+} conductivity. - Highlights: • We develop a three-dimensionally well-ordered NASICON-type Mg{sup 2+} cation conductor. • A high magnesium cation conductivity is realized even at moderate temperatures. • Divalent magnesium cation conduction is demonstrated directly and quantitatively.« less

Role of Reverse Divalent Cation Diffusion in Forward Osmosis Biofouling.

PubMed

Xie, Ming; Bar-Zeev, Edo; Hashmi, Sara M; Nghiem, Long D; Elimelech, Menachem

2015-11-17

We investigated the role of reverse divalent cation diffusion in forward osmosis (FO) biofouling. FO biofouling by Pseudomonas aeruginosa was simulated using pristine and chlorine-treated thin-film composite polyamide membranes with either MgCl2 or CaCl2 draw solution. We related FO biofouling behavior-water flux decline, biofilm architecture, and biofilm composition-to reverse cation diffusion. Experimental results demonstrated that reverse calcium diffusion led to significantly more severe water flux decline in comparison with reverse magnesium permeation. Unlike magnesium, reverse calcium permeation dramatically altered the biofilm architecture and composition, where extracellular polymeric substances (EPS) formed a thicker, denser, and more stable biofilm. We propose that FO biofouling was enhanced by complexation of calcium ions to bacterial EPS. This hypothesis was confirmed by dynamic and static light scattering measurements using extracted bacterial EPS with the addition of either MgCl2 or CaCl2 solution. We observed a dramatic increase in the hydrodynamic radius of bacterial EPS with the addition of CaCl2, but no change was observed after addition of MgCl2. Static light scattering revealed that the radius of gyration of bacterial EPS with addition of CaCl2 was 20 times larger than that with the addition of MgCl2. These observations were further confirmed by transmission electron microscopy imaging, where bacterial EPS in the presence of calcium ions was globular, while that with magnesium ions was rod-shaped.

Chelating agents.

PubMed

Bergan, T; Klaveness, J; Aasen, A J

2001-01-01

The antibacterial activity of metal ions, metal chelates, and molecules with chelating ability for polyvalent cations have been evaluated. The chelator N, N'-ethylenebis[2-(2-hydroxyphenyl)-glycine] (EHPG) exerted moderate-to-good activity against isolates of pathogenic bacteria and fungi. Other chelating agents such as ethylenediamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) revealed weak-to-moderate activity. Metal chelation of ligands reduced the activity of EDTA and DTPA. Copyright 2001 S. Karger AG, Basel

Solid-state NMR study of various mono- and divalent cation forms of the natural zeolite natrolite.

PubMed

Park, Min Bum; Vicente, Aurélie; Fernandez, Christian; Hong, Suk Bong

2013-05-28

Here we present the one-dimensional (29)Si and (27)Al MAS NMR and two-dimensional (27)Al MQMAS and DQF-STMAS NMR spectra of the monovalent (Na(+), K(+), Rb(+), Cs(+) and NH4(+)) and divalent (Ca(2+), Sr(2+) and Ba(2+)) cation forms of the natural zeolite natrolite (framework type NAT) with complete Si-Al ordering over the crystallographically distinct tetrahedral sites and with the same hydration state (hydrated, partially dehydrated or fully dehydrated). In the case of monovalent cation-exchanged natrolites, the differences in their crystal symmetry evidenced by (29)Si MAS NMR were found to be in good agreement with those determined by crystallographic analyses. However, (27)Al DQF-STMAS NMR spectroscopy shows the presence of two distinct Al sites in dehydrated K-NAT, Rb-NAT and NH4-NAT, suggesting that their actual crystal symmetry is lower than the reported one (i.e., orthorhombic Fdd2). The MAS NMR results also show that the space group of hydrated Ca-NAT is lower than that (monoclinic F1d1) of hydrated scolecite, the natural calcium counterpart of natrolite, which is also the case with hydrated Sr-NAT and Ba-NAT. We believe that the unexpected diversity in the crystal symmetry of natrolite caused by exchange of various mono- and divalent ions, as well as by dehydration, may be inherently due to the high framework flexibility of this natural zeolite.

Identification of a divalent metal cation binding site in herpes simplex virus 1 (HSV-1) ICP8 required for HSV replication.

PubMed

Bryant, Kevin F; Yan, Zhipeng; Dreyfus, David H; Knipe, David M

2012-06-01

Herpes simplex virus 1 (HSV-1) ICP8 is a single-stranded DNA-binding protein that is necessary for viral DNA replication and exhibits recombinase activity in vitro. Alignment of the HSV-1 ICP8 amino acid sequence with ICP8 homologs from other herpesviruses revealed conserved aspartic acid (D) and glutamic acid (E) residues. Amino acid residue D1087 was conserved in every ICP8 homolog analyzed, indicating that it is likely critical for ICP8 function. We took a genetic approach to investigate the functions of the conserved ICP8 D and E residues in HSV-1 replication. The E1086A D1087A mutant form of ICP8 failed to support the replication of an ICP8 mutant virus in a complementation assay. E1086A D1087A mutant ICP8 bound DNA, albeit with reduced affinity, demonstrating that the protein is not globally misfolded. This mutant form of ICP8 was also recognized by a conformation-specific antibody, further indicating that its overall structure was intact. A recombinant virus expressing E1086A D1087A mutant ICP8 was defective in viral replication, viral DNA synthesis, and late gene expression in Vero cells. A class of enzymes called DDE recombinases utilize conserved D and E residues to coordinate divalent metal cations in their active sites. We investigated whether the conserved D and E residues in ICP8 were also required for binding metal cations and found that the E1086A D1087A mutant form of ICP8 exhibited altered divalent metal binding in an in vitro iron-induced cleavage assay. These results identify a novel divalent metal cation-binding site in ICP8 that is required for ICP8 functions during viral replication.

Synergistic effect of divalent cations in improving technological properties of cross-linked alginate beads.

PubMed

Cerciello, Andrea; Del Gaudio, Pasquale; Granata, Veronica; Sala, Marina; Aquino, Rita P; Russo, Paola

2017-08-01

Gelling solution parameters are some of the most important variables in ionotropic gelation and consequently influence the technological characteristics of the product. To date, only a few studies have focused on the simultaneous use of multiple cations as gelling agents. With the aim to deeply explore this possibility, in this research we investigated the effect of two divalent cations (Ca 2+ and Zn 2+ ) on alginate beads formation and properties. Alginate beads containing prednisolone (P) as model drug were prepared by prilling technique. The main critical variables of the ionotropic gelation process i.e. composition of the aqueous feed solutions (sodium alginate and prednisolone concentration) and cross-linking conditions (Ca 2+ , Zn 2+ or Ca 2+ +Zn 2+ ), were studied. The obtained beads were characterized and their in vitro release performances were assessed in conditions simulating the gastrointestinal environment. Results evidenced a synergistic effect of the two cations, affecting positively both the encapsulation efficiency and the ability of the alginate polymeric matrix to control the drug release. A Ca 2+ /Zn 2+ ratio of 4:1, in fact, exploited the Ca 2+ ability of establish quicker electrostatic interactions with guluronic groups of alginate and the Zn 2+ ability to establish covalent-like bonds with carboxylate groups of both guluronic and mannuronic moieties of alginate. Copyright © 2017 Elsevier B.V. All rights reserved.

Headgroup interactions and ion flotation efficiency in mixtures of a chelating surfactant, different foaming agents, and divalent metal ions.

PubMed

Svanedal, Ida; Boija, Susanne; Norgren, Magnus; Edlund, Håkan

2014-06-10

The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

Bacteriophages BCP1-1 and BCP8-2 require divalent cations for efficient control of Bacillus cereus in fermented foods.

PubMed

Bandara, Nadeeka; Jo, Junhee; Ryu, Sangryeol; Kim, Kwang-Pyo

2012-08-01

Bacillus cereus is a foodborne bacterial pathogen that causes diarrhea and vomiting. In this study, the usefulness of bacteriophages to eradicate B. cereus from fermented foods was investigated. A total of 13 phages were isolated from Korean fermented food products, and 2 (BCP1-1 and BCP8-2) were further characterized. Transmission electron microscopy (TEM), restriction enzyme digestion pattern analysis, and SDS-PAGE of the structural proteins suggest that both phages belong to the family Myoviridae, containing approximately 150 kbp-long genomes. The host ranges of both phages were limited to B. cereus group species (12/13), as they were not able to lyse other Gram-positive or negative strains including Bacillus subtilis. Purified phages were used to inhibit B. cereus growth in a model fermented food system, cheonggukjang, a fast-fermented soybean paste product. BCP1-1 and BCP8-2 were able to effectively eradicate B. cereus from the food only if divalent cations (Ca²⁺, Mg²⁺, or Mn²⁺) were added to the medium. Further studies reveal that divalent cations are essential for phage adsorption, while a monovalent cation (Na⁺) is required for the post-adsorption phase of phage infection. Taken together, our findings imply that a phage could be an ideal anti-bacterial agent for use in fermented food products that require the presence of beneficial microflora and, during phage application, optimization of phage reaction conditions is critical for the successful utilization of phage biocontrol. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cold-set hydrogels made of whey protein nanofibrils with different divalent cations.

PubMed

Mohammadian, Mehdi; Madadlou, Ashkan

2016-08-01

Whey protein nanofibrils are gaining interest to fabricate cold-set hydrogels due to their ability to gel at lower concentrations than parent proteins. In the present research, fibrillated protein solution was gelled with three different divalent cation salts including CaCl2, MnCl2 and ZnCl2 and the textural and functional characteristics of the resulting hydrogel samples were studied. Atomic force microscopy indicated that the flexible micron-scaled fibrils with nanometric thickness (up to 8.0nm) that formed at pH 2.0 underwent breaking in length upon post-formation pH rise to 7.5. Whilst heat-denatured protein solution failed to form self-supporting gel at pH 7.5, fibrillated protein solution gelled by all three types of cations. Fibrillation increased the protein solution consistency coefficient (K) much more than heat denaturation. It was suggested based on Fourier-transform infra-red (FT-IR) spectra that some hydrogen bonds were disrupted by fibrillation. Zn(2+)-induced gel was firmer, had a higher water holding capacity and a more compact microstructure, as well, required a higher compressive stress to fracture than its counterparts. Nonetheless, the Mn(2+)- and Ca(2+)-induced gels disintegrated to a much lesser extent in both pepsin-free and pepsin-present simulated gastric juice than Zn(2+)-induced sample. Chitosan coating approximately halved the simulated degradability of all gel samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The multiple nucleotide-divalent cation binding modes of Saccharomyces cerevisiae CK2α indicate a possible co-substrate hydrolysis product (ADP/GDP) release pathway.

PubMed

Liu, Huihui; Wang, Hong; Teng, Maikun; Li, Xu

2014-02-01

CK2 is a ubiquitous and conserved protein kinase in eukaryotic organisms and is important in many biological processes. It is unique in maintaining constitutive activity and in using both ATP and GTP as phosphor donors. In this study, crystal structures of recombinant Saccharomyces cerevisiae CK2α (scCK2α) complexed with GMPPNP, ATP and AMPPN with either Mg2+ or Mn2+ as the coordinated divalent cation are presented. The overall structure of scCK2α shows high similarity to its homologous proteins by consisting of two domains with the co-substrate lying in the cleft between them. However, three characteristic features distinguish scCK2α from its homologues. Firstly, the Lys45-Glu53 and Arg48-Glu53 interactions in scCK2α lead Lys50 to adopt a unique conformation that is able to stabilize the γ-phosphate of the co-substrate, which makes the existence of the `essential divalent cation' not so essential. The multiple nucleotide-divalent cation binding modes of the active site of scCK2α are apparently different from the two-divalent-cation-occupied active site of Zea mays CK2α and human CK2α. Secondly, conformational change of Glu53 in scCK2α-AMPPN breaks its interaction with Lys45 and Arg48; as a result, the co-substrate binding pocket becomes more open. This may suggest a clue to a possible ADP/GDP-release pathway, because the NE1 atom of the Trp in the `DWG motif' of CK2α forms a hydrogen bond to the O atom of Leu212, which seems to make ADP release by means of the `DFG-in flip to DFG-out' model found in most eukaryotic protein kinases impossible. Coincidentally, two sulfate ions which may mimic two phosphate groups were captured by Arg161 and Lys197 around the pocket. Mutagenesis and biochemical experiments on R161A and K197A mutants support the above proposal. Finally, scCK2α is unique in containing an insertion region whose function had not been identified in previous research. It is found that the insertion region contributes to maintaining the

Metallomics for Alzheimer's disease treatment: Use of new generation of chelators combining metal-cation binding and transport properties.

PubMed

D'Acunto, Cosimo Walter; Kaplánek, Robert; Gbelcová, Helena; Kejík, Zdeněk; Bříza, Tomáš; Vasina, Liudmila; Havlík, Martin; Ruml, Tomáš; Král, Vladimír

2018-04-25

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting tens of million people. Currently marketed drugs have limited therapeutic efficacy and only slowing down the neurodegenerative process. Interestingly, it has been suggested that biometal cations in the amyloid beta (Aβ) aggregate deposits contribute to neurotoxicity and degenerative changes in AD. Thus, chelation therapy could represent novel mode of therapeutic intervention. Here we describe the features of chelators with therapeutically relevant mechanism of action. We have found that the tested compounds effectively reduce the toxicity of exogenous Aβ and suppress its endogenous production as well as decrease oxidative stress. Cholyl hydrazones were found to be the most active compounds. In summary, our data show that cation complexation, together with improving transport efficacy may represent basis for eventual treatment strategy in AD. Copyright © 2018. Published by Elsevier Masson SAS.

Enhanced desorption of cesium from collapsed interlayer regions in vermiculite by hydrothermal treatment with divalent cations.

PubMed

Yin, Xiangbiao; Wang, Xinpeng; Wu, Hao; Ohnuki, Toshihiko; Takeshita, Kenji

2017-03-15

Adsorption of cesium (Cs) on phyllosilicates has been intensively investigated because natural soils have strong ability of immobilizing Cs within clay minerals resulting in difficulty of decontamination. The objectives of present study are to clarify how Cs fixation on vermiculite is influenced by structure change caused by Cs sorption at different loading levels and how Cs desorption is affected by various replacing cations induced at different treating temperature. As a result, more than 80% of Cs was readily desorbed from vermiculite with loading amount of 2% saturated Cs (5.49×10 -3 mmolg -1 ) after four cycles of treatment of 0.01M Mg 2+ /Ca 2+ at room temperature, but less than 20% of Cs was desorbed from saturated vermiculite. These distinct desorption patterns were attributed to inhibition of Cs desorption by interlayer collapse of vermiculite, especially at high Cs loadings. In contrast, elevated temperature significantly facilitated divalent cations to efficiently desorb Cs from collapsed regions. After five cycles of treatment at 250°C with 0.01M Mg 2+ , ∼100% removal of saturated Cs was achieved. X-ray diffraction analysis results suggested that Cs desorption was completed through enhanced diffusion of Mg 2+ cations into collapsed interlayer space under hydrothermal condition resulting in subsequent interlayer decollapse and readily release of Cs + . Copyright © 2016 Elsevier B.V. All rights reserved.

The bovine immune response to Brucella abortus. II. Elimination of some sporadic serological reactions by chelation of divalent cations.

PubMed Central

Nielsen, K; Samagh, B S; Speckmann, G; Stemshorn, B

1979-01-01

The standard agglutination tests for detecting antibody to Brucella abortus were modified by addition of chelating agents (EDTA and EGTA) to the antigens. Approximately 80% of "singleton" agglutination test reactions, negative on the diagnostic complement fixation test, obtained with cattle sera were eliminated while no decrease in titer was apparent when sera from B. abortus infected or vaccinated cattle were tested. PMID:121242

Hydration of cations: a key to understanding of specific cation effects on aggregation behaviors of PEO-PPO-PEO triblock copolymers.

PubMed

Lutter, Jacob C; Wu, Tsung-yu; Zhang, Yanjie

2013-09-05

This work reports results from the interactions of a series of monovalent and divalent cations with a triblock copolymer, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO). Phase transition temperatures of the polymer in the presence of chloride salts with six monovalent and eight divalent cations were measured using an automated melting point apparatus. The polymer undergoes a two-step phase transition, consisting of micellization of the polymer followed by aggregation of the micelles, in the presence of all the salts studied herein. The results suggest that hydration of cations plays a key role in determining the interactions between the cations and the polymer. The modulation of the phase transition temperature of the polymer by cations can be explained as a balance between three interactions: direct binding of cations to the oxygen in the polymer chains, cations sharing one water molecule with the polymer in their hydration layer, and cations interacting with the polymer via two water molecules. Monovalent cations Na(+), K(+), Rb(+), and Cs(+) do not bind to the polymer, while Li(+) and NH4(+) and all the divalent cations investigated including Mg(2+), Ca(2+), Sr(2+), Ba(2+), Co(2+), Ni(2+), Cu(2+), and Cd(2+) bind to the polymer. The effects of the cations correlate well with their hydration thermodynamic properties. Mechanisms for cation-polymer interactions are discussed.

The Rubella Virus Nonstructural Protease Requires Divalent Cations for Activity and Functions in trans

PubMed Central

Liu, Xin; Ropp, Susan L.; Jackson, Richard J.; Frey, Teryl K.

1998-01-01

The rubella virus (RUB) nonstructural (NS) protease is a papain-like cysteine protease (PCP) located in the NS-protein open reading frame (NSP-ORF) that cleaves the NSP-ORF translation product at a single site to produce two products, P150 (the N-terminal product) and P90 (the C-terminal product). The RUB NS protease was found not to function following translation in vitro in a standard rabbit reticulocyte lysate system, although all of the other viral PCPs do so. However, in the presence of divalent cations such as Zn2+, Cd2+, and Co2+, the RUB NS protease functioned efficiently, indicating that these cations are required either as direct cofactors in catalytic activity or for correct acquisition of three-dimensional conformation of the protease. Since other viral and cell PCPs do not require cations for activity and the RUB NS protease contains a putative zinc binding motif, the latter possibility is more likely. Previous in vivo expression studies of the RUB NS protease failed to demonstrate trans cleavage activity (J.-P. Chen et al., J. Virol. 70:4707–4713, 1996). To study whether trans cleavage could be detected in vitro, a protease catalytic site mutant and a mutant in which the C-terminal 31 amino acids of P90 were deleted were independently introduced into plasmid constructs that express the complete NSP-ORF. Cotranslation of these mutants in vitro yielded both the native and the mutated forms of P90, indicating that the protease present in the mutated construct cleaved the catalytic-site mutant precursor. Thus, RUB NS protease can function in trans. PMID:9557742

Molecular cloning of a putative divalent-cation transporter gene as a new genetic marker for the identification of Lactobacillus brevis strains capable of growing in beer.

PubMed

Hayashi, N; Ito, M; Horiike, S; Taguchi, H

2001-05-01

Random amplified polymorphic DNA (RAPD) PCR analysis of Lactobacillus brevis isolates from breweries revealed that one of the random primers could distinguish beer-spoilage strains of L. brevis from nonspoilage strains. The 1.1-kb DNA fragment amplified from all beer-spoilers included one open reading frame, termed hitA (hop-inducible cation transporter), which encodes an integral membrane protein with 11 putative trans-membrane domains and a binding protein-dependent transport signature of a non-ATP binding membrane transporter common to several prokaryotic and eukaryotic transporters. The hitA polypeptide is homologous to the natural resistance-associated macrophage protein (Nramp) family characterized as divalent-cation transport proteins in many prokaryotic and eukaryotic organisms. Northern blot analysis indicated that the hitA transcripts are expressed in cells cultivated in MRS broth supplemented with hop bitter compounds, which act as mobile-carrier ionophores, dissipating the trans-membrane pH gradient in bacteria sensitive to the hop bitter compounds by exchanging H+ for cellular divalent cations such as Mn2+. This suggests that the hitA gene products may play an important role in making the bacteria resistant to hop bitter compounds in beer by transporting metal ions such as Mn2+ into cells that no longer maintain the proton gradient.

Hydroxypyridonate chelating agents and synthesis thereof

DOEpatents

Raymond, K.N.; Scarrow, R.C.; White, D.L.

1985-11-12

Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

Monovalent and divalent cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic ganglia

PubMed Central

1995-01-01

Acetylcholine-evoked currents mediated by activation of nicotinic receptors in rat parasympathetic neurons were examined using whole-cell voltage clamp. The relative permeability of the neuronal nicotinic acetylcholine (nACh) receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements. The channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Cs+ > K+ > Rb+ > Na+ > Li+, and permeability ratios relative to Na+ (Px/PNa) ranging from 1.27 to 0.75. The selectivity of the alkaline earths was also weak, with the sequence of Mg2+ > Sr2+ > Ba2+ > Ca2+, and relative permeabilities of 1.10 to 0.65. The relative Ca2+ permeability (PCa/PNa) of the neuronal nACh receptor channel is approximately fivefold higher than that of the motor endplate channel (Adams, D. J., T. M. Dwyer, and B. Hille. 1980. Journal of General Physiology. 75:493-510). The transition metal cation, Mn2+ was permeant (Px/PNa = 0.67), whereas Ni2+, Zn2+, and Cd2+ blocked ACh-evoked currents with half-maximal inhibition (IC50) occurring at approximately 500 microM, 5 microM and 1 mM, respectively. In contrast to the muscle endplate AChR channel, that at least 56 organic cations which are permeable to (Dwyer et al., 1980), the majority of organic cations tested were found to completely inhibit ACh- evoked currents in rat parasympathetic neurons. Concentration-response curves for guanidinium, ethylammonium, diethanolammonium and arginine inhibition of ACh-evoked currents yielded IC50's of approximately 2.5- 6.0 mM. The organic cations, hydrazinium, methylammonium, ethanolammonium and Tris, were measureably permeant, and permeability ratios varied inversely with the molecular size of the cation. Modeling suggests that the pore has a minimum diameter of 7.6 A. Thus, there are substantial differences in ion permeation and block between the nACh receptor channels of mammalian parasympathetic neurons and amphibian

Layered inorganic/organic mercaptopropyl pendant chain hybrid for chelating heavy cations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macedo, Thais R.; Petrucelli, Giovanni C.; Pinto, Alane A.

2011-12-15

Graphical abstract: Crystalline lamellar silicate RUB-18 was immobilized with mercaptopropyl groups at the surface and then used as support for cadmium and lead removal from aqueous solutions. Highlights: Black-Right-Pointing-Pointer Synthetic methodology requires intercalation. Black-Right-Pointing-Pointer Organofunctionalized ilerite compound as sorbent. Black-Right-Pointing-Pointer Active mercaptopropyl groups remove cations. Black-Right-Pointing-Pointer High maximum sorption capacity for cadmium. -- Abstract: Heavy metal sorbents with uptake capacities for divalent cadmium and lead cation removal from aqueous solutions have been synthesized by grafting mercaptopropyltrimethoxysilane onto the surface of two different precursors obtained from lamellar ilerite, its acidic and the cetyltrimethylammonium exchanged forms. The organofunctionalization was carried out bymore » two different procedures: reflux and solvent evaporation methodologies. Elemental analysis data based on carbon content gave 1.37 and 3.53 mmol of organic pendant groups per gram of hybrid by the reflux method, when starting from acidic ilerite and the surfactant form. X-ray diffraction corroborated the maintenance of the original crystallinity. Infrared spectroscopy and nuclear magnetic resonance for {sup 29}Si and {sup 13}C nuclei are in agreement with the success of the proposed method. The sulfur basic centers attached to the lamellar structure are used to coordinate both cations at the solid/liquid interface. The isotherms were obtained through the batchwise process and the experimental data were adjusted to the Freundlich model. The maximum sorption capacities of 5.55 and 5.12 mmol g{sup -1} for lead and 6.10 and 7.10 mmol g{sup -1} for cadmium were obtained for organofunctionalized ilerite and its surfactant form, synthesized by reflux methodology. This behavior suggested that these hybrids could be employed as promising sorbents with a polluted system.« less

Partitioning of dopant cations between β-tricalcium phosphate and fluorapatite

NASA Astrophysics Data System (ADS)

Jay, E. E.; Mallinson, P. M.; Fong, S. K.; Metcalfe, B. L.; Grimes, R. W.

2011-07-01

Mixed crystalline phase composite ceramics offer the possibility of partitioning defect species between the phases as well as occupancy of specific sites within a given phase. Here we use atomic scale simulations to study the site preference of an extensive range of divalent and trivalent substitutional ions across the five cation sites in β-tricalcium phosphate ( β-TCP) and the two cations sites in fluorapatite (FAp). This study indicates that in β-TCP small dopant species occupy the smaller of the five cation sites and vice versa. Conversely, in FAp, small divalent species occupy the nominally larger Ca(1) site while larger cations occupy the Ca(2) site. Partition energies between the two phases indicate that divalent species strongly segregate to β-TCP as do Al 3+ and Ga 3+, whereas all other (larger) trivalent ions exhibit little preference.

Prediction of Intrinsic Cesium Desorption from Na-Smectite in Mixed Cation Solutions.

PubMed

Fukushi, Keisuke; Fukiage, Tomo

2015-09-01

Quantitative understanding of the stability of sorbed radionuclides in smectite is necessary to assess the performance of engineering barriers used for nuclear waste disposal. Our previous study demonstrated that the spatial organization of the smectite platelets triggered by the divalent cations led to the apparent fixation of intrinsic Cs in smectite, because some Cs is retained inside the formed tactoids. Natural water is usually a mixture of Na(+) and divalent cations (Ca(2+) and Mg(2+)). This study therefore investigated the desorption behavior of intrinsic Cs in Na-smecite in mixed Na(+)-divalent cation solutions under widely various cation concentrations using batch experiments, grain size measurements, and cation exchange modeling (CEM). Results show that increased Na(+) concentrations facilitate Cs desorption because Na(+) serves as the dispersion agent. A linear relation was obtained between the logarithm of the Na(+) fraction and the accessible Cs fraction in smectite. That relation enables the prediction of accessible Cs fraction as a function of solution cationic compositions. The corrected CEM considering the effects of the spatial organization suggests that the stability of intrinsic Cs in the smectite is governed by the Na(+) concentration, and suggests that it is almost independent of the concentrations of divalent cations in natural water.

Response of a benzoxainone derivative linked to monoaza-15-crown-5 with divalent heavy metals.

PubMed

Addleman, R S; Bennett, J; Tweedy, S H; Elshani, S; Wai, C M

1998-08-01

The response of a monoaza-15-crown-5 with an optically active aminobenzoxazinone moiety to divalent cations was investigated. The crown ether was found to undergo a strong emission shift to the blue when complexed with specific divalent metals that have ionic diameters between 1.9-2.4 A. Consequently the photoactive macrocycle is responsive to Mg(2+), Ca(2+), Ba(2+), Sr(2+), Cd(2+), and particularly responsive to Hg(2+)and Pb(2+). Macrocycle emission spectra are shown to be a function of cation concentration. Alkaline metal cations and smaller transition metals ions such as Ni(2+), Co(2+)and Zn(2+)do not cause significant changes in the macrocycle emission spectra. Emission, absorption, and complex stability constants are determined. Mechanisms of cation selectivity and spectral emission shifts are discussed. Challenges involving immobilization of the macrocycle while preserving its spectral response to cations are explored.

Metal cation detection in positive ion mode electrospray ionization mass spectrometry using a tetracationic salt as a gas-phase ion-pairing agent: evaluation of the effect of chelating agents on detection sensitivity.

PubMed

Xu, Chengdong; Dodbiba, Edra; Padivitage, Nilusha L T; Breitbach, Zachary S; Armstrong, Daniel W

2012-12-30

The detection of metal cations continues to be essential in many scientific and industrial areas of interest. The most common electrospray ionization mass spectrometry (ESI-MS) approach involves chelating the metal ions and detecting the organometallic complex in the negative ion mode. However, it is well known that negative ion mode ESI-MS is generally less sensitive than the positive ion mode. To achieve greater sensitivity, it is necessary to examine the feasibility of detecting the chelated metal cations in positive ion mode ESI-MS. Since highly solvated native metal cations have relatively low ionization efficiency in ESI-MS, and can be difficult to detect in the positive ion mode, a tetracationic ion-pairing agent was added to form a complex with the negatively charged metal chelate. The use of the ion-pairing agent leads to the generation of an overall positively charged complex, which can be detected at higher m/z values in the positive ion mode by electrospray ionization linear quadrupole ion trap mass spectrometry. Thirteen chelating agents with diverse structures were evaluated in this study. The nature of the chelating agent played as important a role as was previously determined for cationic pairing agents. The detection limits of six metal cations reached sub-picogram levels and significant improvements were observed when compared to negative ion mode detection where the metal-chelates were monitored without adding the ion-pairing reagent (IPR). Also, selective reaction monitoring (SRM) analyses were performed on the ternary complexes, which improved detection limits by one to three orders of magnitude. With this method it was possible to analyze the metal cations in the positive ion mode ESI-MS with the advantage of speed, sensitivity and selectivity. The optimum solution pH for this type of analysis is 5-7. Tandem mass spectrometry (MS/MS) further increases the sensitivity. Speciation is straightforward making this a broadly useful approach for the

Selective digestion of Ba2+/Ca2+ alginate gel microdroplets for single-cell handling

NASA Astrophysics Data System (ADS)

Odaka, Masao; Hattori, Akihiro; Matsuura, Kenji; Yasuda, Kenji

2018-06-01

Cells encapsuled by polymer microdroplets are an effective platform for the identification and separation of individual cells for single-cell-based analysis. However, a key challenge is to maintain and release the captured cells in the microdroplets selectively, nondestructively, and noninvasively. We developed a simple method of encapsulating cells in alginate microdroplets having different digestion characteristics. Cells were diluted with an alginate polymer of sol state and encapsulated into microdroplets with Ba2+ and Ca2+ by a spray method. When a chelating buffer was applied, alginate gel microdroplets were digested according to the difference in chelating efficiency of linkage-divalent cations; hence, two types of alginate microdroplets were formed. Moreover, we examined the capability of the alginate gel to exchange linkage-divalent cations and found that both Ca2+ exchange in Ba-alginate microdroplets and Ba2+ exchange in Ca-alginate microdroplets occurred. These results indicate that the potential applications of a mixture of alginate microdroplets with different divalent cations control the selective digestion of microdroplets to improve the high-throughput, high-content microdroplet-based separation, analysis, or storage of single cells.

Adsorptive behaviour of mercury on algal biomass: competition with divalent cations and organic compounds.

PubMed

Carro, Leticia; Barriada, José L; Herrero, Roberto; Sastre de Vicente, Manuel E

2011-08-15

Biosorption processes constitute an effective technique for mercury elimination. Sorption properties of native and acid-treated Sargassum muticum have been studied. Effect of pH, initial mercury concentration and contact time studies provided fundamental information about the sorption process. This information was used as the reference values to analyse mercury sorption under competition conditions. Saline effect has shown little influence in sorption, when only electrostatic modifications took place upon salt addition. On the contrary, if mercury speciation dramatically changed owing to the addition of an electrolyte, such as in the case of chloride salt, very large modifications in mercury sorption were observed. Competition with other divalent cations or organic compounds has shown little or none effect on mercury, indicating that a different mechanism is taking place during the removal of these pollutants. Finally, continuous flow experiments have clearly shown that a reduction process is also taking place during mercury removal. This fact is not obvious to elucidate under batch sorption experiments. Scanning Electron Microscopy analysis of the surface of the materials show deposits of mercury(I) and metallic mercury which is indicative of the reduction process proposed. Copyright © 2011 Elsevier B.V. All rights reserved.

Shewanella frigidimarina microbial fuel cells and the influence of divalent cations on current output.

PubMed

Fitzgerald, Lisa A; Petersen, Emily R; Leary, Dagmar H; Nadeau, Lloyd J; Soto, Carissa M; Ray, Richard I; Little, Brenda J; Ringeisen, Bradley R; Johnson, Glenn R; Vora, Gary J; Biffinger, Justin C

2013-02-15

The genes involved in the proposed pathway for Shewanella extracellular electron transfer (EET) are highly conserved. While extensive studies involving EET from a fresh water Shewanella microbe (S. oneidensis MR-1) to soluble and insoluble electron acceptors have been published, only a few reports have examined EET from marine strains of Shewanella. Thus, Shewanella frigidimarina (an isolate from Antarctic Sea ice) was used within miniature microbial fuel cells (mini-MFC) to evaluate potential power output. During the course of this study several distinct differences were observed between S. oneidensis MR-1 and S. frigidimarina under comparable conditions. The maximum power density with S. frigidimarina was observed when the anolyte was half-strength marine broth (1/2 MB) (0.28 μW/cm(2)) compared to Luria-Bertani (LB) (0.07 μW/cm(2)) or a defined growth minimal medium (MM) (0.02 μW/cm(2)). The systematic modification of S. frigidimarina cultured in 1/2 MB and LB with divalent cations shows that a maximum current output can be generated independent of internal ionic ohmic losses and the presence of external mediators. Published by Elsevier B.V.

X-ray crystal structure of divalent metal-activated ß-xyloisdase, RS223BX

USDA-ARS?s Scientific Manuscript database

We report the first X-ray structure of a glycoside hydrolase family 43 ß-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 Å structure reveals that the Ca2+ cation is located at the back of the active site pocket. The Ca2+ coordinates to H274 to sta...

The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin

PubMed Central

Cavaliere, Rosalia; Ball, Jessica L; Turnbull, Lynne; Whitchurch, Cynthia B

2014-01-01

Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections. PMID:25044339

Negative effects of divalent mineral cations on the bioaccessibility of carotenoids from plant food matrices and related physical properties of gastro-intestinal fluids.

PubMed

Corte-Real, Joana; Bertucci, Marie; Soukoulis, Christos; Desmarchelier, Charles; Borel, Patrick; Richling, Elke; Hoffmann, Lucien; Bohn, Torsten

2017-03-22

Carotenoid intake and tissue levels have been frequently associated with reduced risk of chronic diseases. However, their bioavailability is low and influenced by many dietary related parameters. Divalent mineral cations have been suggested to interfere with carotenoid digestion and to hamper micellarization, a prerequisite for their uptake, via complexation of bile salts and precipitation of fatty acids. In the present investigation, we have evaluated the effects of increasing concentrations of magnesium (0-300 mg L -1 ), calcium (0-1500 mg L -1 ), zinc (0-200 mg L -1 ), and sodium (0-1500 mg L -1 ; control monovalent cation), on carotenoid bioaccessibility from frequently consumed food items rich in carotenoids (tomato juice, carrot juice, apricot nectar, spinach and field salad), following simulated gastro-intestinal digestion. In addition, physicochemical parameters of digesta (macroviscosity, surface tension), micelle size, and zeta-potential were evaluated. All divalent minerals (DM) reduced bioaccessibility of total carotenoids (P < 0.01), as well as of individual carotenoids. Calcium and magnesium led to reductions of up to 100% at the 2 highest concentrations. Curiously, sodium increased (P < 0.01) carotenoid bioaccessiblity of most investigated matrices. The absolute value of the zeta-potential decreased with increasing concentrations of DM, suggesting a decreased stability of the colloidal digesta dispersion. Viscosity decreased, except for apricot nectar samples, while surface tension increased with DM concentration (P < 0.05). Thus, at physiological ranges, calcium and magnesium could negatively impact carotenoid bioavailability, while for zinc, negative effects were only seen at supplemental concentrations. The potential negative effects of DM on carotenoid bioavailability should be further studied in vivo.

Effects of targeting moiety, linker, bifunctional chelator, and molecular charge on biological properties of 64Cu-labeled triphenylphosphonium cations.

PubMed

Kim, Young-Seung; Yang, Chang-Tong; Wang, Jianjun; Wang, Lijun; Li, Zi-Bo; Chen, Xiaoyuan; Liu, Shuang

2008-05-22

In this report, we present the synthesis and evaluation of six new 64Cu-labeled triphenylphosphonium (TPP) cations. Biodistribution studies were performed using the athymic nude mice bearing U87MG human glioma xenografts to explore the impact of TPP moieties, linkers, bifunctional chelators (BFCs), and molecular charge on biological properties of 64Cu radiotracers. On the basis of the results from this study, it is concluded that (1) mTPP (tris(4-methoxyphenyl)phosphonium) is a better mitochondrion-targeting molecule than TPP and 3mTPP (tris(2,4,6-trimethoxyphenyl)phosphonium); (2) DO3A (1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid) and DO2A (1,4,7,10-tetraazacyclododecane-4,7-diacetic acid) are suitable BFCs for the 64Cu-labeling of TPP cations; (3) NOTA-Bn ( S-2-(4-thioureidobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) has a significant adverse effect on the radiotracer tumor uptake and tumor-to-background ratios; and (4) monoanionic BFCs should be avoided to ensure that 64Cu chelate has a neutral or negative charge. Considering the tumor uptake and tumor/liver ratios, 64Cu(DO2A-xy-TPP)+ is the best candidate for more extensive evaluations in different tumor-bearing animal models.

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Spectrophotometric Study of the Complex Formation of Anionic Chelates of Cobalt(II) with Monotetrazolium Cations

NASA Astrophysics Data System (ADS)

Divarova, V. V.; Stojnova, K. T.; Racheva, P. V.; Lekova, V. D.

2017-05-01

The complex formation and extraction of anionic chelates of Co(II)-4-(2-thiazolylazo)resorcinol (TAR) with cations of monotetrazolium salts (TS) — (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and 3-(2-naphthyl)-2,5-diphenyl-2H-tetrazolium chloride (TV) — in the liquid-liquid extraction system Co(II)-TAR-TS-H2O-CHCl3 were studied by spectrophotometric methods. The optimum conditions for the extraction of Co(II) were found. The molar ratio of the components and the form of the anionic chelates of Co(II) in the extracted compounds were determined by independent methods. The association process in the aqueous phase and the extraction process were investigated and quantitatively characterized. The following key constants were calculated: association constant, distribution constant, extraction constant, and recovery factor. The validity of the Beer's law was checked, and some analytical characteristics were calculated. Based on the obtained results and the lower price of the monotetrazolium salt MTT compared with that of TV, the ion-associated complex of Co(II)-TAR-MTT can be implemented for determination of cobalt(II) traces in alloys and biological, medical, and pharmaceutical samples.

Influence of ionic strength, anions, cations, and natural organic matter on the adsorption of pharmaceuticals to silica.

PubMed

Bui, Tung Xuan; Choi, Heechul

2010-08-01

The adsorption of four wide-use pharmaceuticals (carbamazepine, diclofenac, ibuprofen, and ketoprofen) onto a porous silica was investigated under varied ionic strengths, different anions, divalent cations (Ca(2+) and Mg(2+)), trivalent cations (Al(3+) and Fe(3+)), and natural organic matter (NOM). The experiments demonstrated that at a given pH the adsorption was most affected by ionic strength, trivalent cations, and properties of pharmaceuticals. The increase of ionic strength resulted in an increase in the adsorption of ketoprofen, but a decrease in the adsorption of carbamazepine. Trivalent metal cations made intense increases in the adsorption of three acidic pharmaceuticals, which could be due to the formation of inner-sphere complex of the cations on the surface and/or complexation of the pharmaceuticals with both surface and aqueous metal species. It was found that the adsorption of carbamazepine was not affected by divalent and trivalent cations, whereas the adsorption of diclofenac was solely impacted by the presence of Al(3+). Moreover, divalent cations at low concentration could slightly enhance the adsorption of ibuprofen and ketoprofen, whereas NOM caused a reduction in the adsorption of the tested pharmaceuticals except for diclofenac. These results suggest that ionic strength, divalent cations, trivalent cations, and NOM are notable factors affecting the adsorption of pharmaceuticals and thus the ultimate fate of pharmaceuticals in the aqueous environment. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of divalent cations, EDTA and chitosan on the uptake and photoinactivation of Escherichia coli mediated by cationic and anionic porphyrins.

PubMed

Gsponer, Natalia S; Spesia, Mariana B; Durantini, Edgardo N

2015-03-01

The effect of divalent cations, EDTA and chitosan (CS) on the uptake and photoinactivation of Escherichia coli produced by 5,10,15,20-tetrakis(4-N,N,N-trimethylammoniumphenyl)porphyrin (TMAP(4+)), 5,10-di(4-methylphenyl)-15,20-di(4-N,N,N-trimethylammoniumphenyl)porphyrin (MPAP(2+)) and 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS(4-)) were examined under different conditions. These porphyrins were rapidly bound to E. coli cells (<2.5min) and the uptake of photosensitizers was not dependent on incubation temperature, reaching values of 0.61, 0.18 and 0.08nmol/10(8) cells for TMAP(4+), MPAP(2+) and TPPS(4-), respectively. The addition of Ca(2+) or Mg(2+) to the cultures enhanced the uptake of MPAP(2+) and TPPS(4-) by cells. In contrast, the amount of TMAP(4+) bound to cells was decreased. The presence of EDTA produced an increase in the uptake of porphyrins by cells, while CS mainly enhanced the amount of TPPS(4-) bound to E. coli. The photoinactivation of E. coli cells mediated by TMAP(4+) was highly effective even at low concentration (1μM) and short irradiation period (5min). However, a reduction in the phototoxicity was found for TMAP(4+) in presence of Ca(2+) and Mg(2+). In contrast, the phototoxic activity mediated by MPAP(2+) and TPPS(4-) was increased. Addition of EDTA did not show effect on the photoinactivation induced by cationic porphyrins, while a small enhance was found for TPPS(4-). Moreover, inactivation of E. coli cells was achieved in the presence CS. This cationic polymer was antimicrobial by itself in the dark. Using a slightly toxic CS concentration, the phototoxic activity induced by TMAP(4+) was diminished. This effect was mainly observed at lower concentration of TMAP(4+) (0.5-1μM). In contrast, an increase in E. coli photoinactivation was obtained for MPAP(2+) and TPPS(4-) in presence of CS. Thus, this natural polymeric destabilizer agent mainly benefited the photoinactivation mediated by TPPS(4-). Copyright © 2014 Elsevier B.V. All

Cation Effects on the Electron-Acceptor Side of Photosystem II.

PubMed

Khan, Sahr; Sun, Jennifer S; Brudvig, Gary W

2015-06-18

The normal pathway of electron transfer on the electron-acceptor side of photosystem II (PSII) involves electron transfer from quinone A, QA, to quinone B, QB. It is possible to redirect electrons from QA(-) to water-soluble Co(III) complexes, which opens a new avenue for harvesting electrons from water oxidation by immobilization of PSII on electrode surfaces. Herein, the kinetics of electron transfer from QA(-) to [Co(III)(terpy)2](3+) (terpy = 2,2';6',2″-terpyridine) are investigated with a spectrophotometric assay revealing that the reaction follows Michaelis-Menten saturation kinetics, is inhibited by cations, and is not affected by variation of the QA reduction potential. A negatively charged site on the stromal surface of the PSII protein complex, composed of glutamic acid residues near QA, is hypothesized to bind cations, especially divalent cations. The cations are proposed to tune the redox properties of QA through electrostatic interactions. These observations may thus explain the molecular basis of the effect of divalent cations like Ca(2+), Sr(2+), Mg(2+), and Zn(2+) on the redox properties of the quinones in PSII, which has previously been attributed to long-range conformational changes propagated from divalent cations binding to the Ca(II)-binding site in the oxygen-evolving complex on the lumenal side of the PSII complex.

Mesoporous silica originating from a gaseous ammonia epoxide ring opening and the thermodynamic data on some divalent cation adsorptions.

PubMed

Sales, José A A; Petrucelli, Giovanni C; Oliveira, Fernando J V E; Airoldi, Claudio

2007-11-15

An organofunctionalized mesoporous HMS-like compound has been synthesized by reacting the silylating agent 3-glycidoxypropyltrimethoxysilane with gaseous ammonia. The reaction path leads to the opening of the three membered epoxide ring to incorporate ammonia to give the modified silylating agent. This new silylating agent was used to synthesize a mesostructure inorganic-organic hybrid through the neutral template directing agent, dodecylamine, using a co-condensation process, and exploring the ability of the silicon source tetraethoxysilane. The final solid named HMS-NH has been characterized through elemental analysis, X-ray powder diffraction, nitrogen gas adsorption, infrared spectroscopy and solid state NMR for the 29Si nucleus. An amount of 1.06+/-0.10 mmol of pendant groups is covalently bonded to the inorganic backbone. The attached basic centers adsorbed divalent cations to give the maxima adsorption capacity of 0.74+/-0.03, 0.55+/-0.06, 0.53+/-0.05 and 0.51+/-0.06 mmolg(-1) for copper, nickel, zinc and cobalt, respectively. From calorimetric determinations the quantitative thermal effects for all these cation/basic center interactions gave exothermic enthalpy, negative Gibbs free energy and positive entropy. These thermodynamic data confirmed the energetically favorable condition of such interactions at the solid/liquid interface for all systems.

The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin.

PubMed

Cavaliere, Rosalia; Ball, Jessica L; Turnbull, Lynne; Whitchurch, Cynthia B

2014-08-01

Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Raman spectroscopy of DNA-metal complexes. I. Interactions and conformational effects of the divalent cations: Mg, Ca, Sr, Ba, Mn, Co, Ni, Cu, Pd, and Cd.

PubMed

Duguid, J; Bloomfield, V A; Benevides, J; Thomas, G J

1993-11-01

Interactions of divalent metal cations (Mg2+, Ca2+, Ba2+, Sr2+, Mn2+, Co2+, Ni2+, Cu2+, Pd2+, and Cd2+) with DNA have been investigated by laser Raman spectroscopy. Both genomic calf-thymus DNA (> 23 kilobase pairs) and mononucleosomal fragments (160 base pairs) were employed as targets of metal interaction in solutions containing 5 weight-% DNA and metal:phosphate molar ratios of 0.6:1. Raman difference spectra reveal that transition metal cations (Mn2+, Co2+, Ni2+, Cu2+, Pd2+, and Cd2+) induce the greatest structural changes in B-DNA. The Raman (vibrational) band differences are extensive and indicate partial disordering of the B-form backbone, reduction in base stacking, reduction in base pairing, and specific metal interaction with acceptor sites on the purine (N7) and pyrimidine (N3) rings. Many of the observed spectral changes parallel those accompanying thermal denaturation of B-DNA and suggest that the metals link the bases of denatured DNA. While exocyclic carbonyls of dT, dG, and dC may stabilize metal ligation, correlation plots show that perturbations of the carbonyls are mainly a consequence of metal-induced denaturation of the double helix. Transition metal interactions with the DNA phosphates are weak in comparison to interactions with the bases, except in the case of Cu2+, which strongly perturbs both base and phosphate group vibrations. On the other hand, the Raman signature of B-DNA is largely unperturbed by Mg2+, Ca2+, Sr2+, and Ba2+, suggesting much weaker interactions of the alkaline earth metals with both base and phosphate sites. A notable exception is a moderate perturbation by alkaline earths of purine N7 sites in 160-base pair DNA, with Ca2+ causing the greatest effect. Correlation plots demonstrate a strong interrelationship between perturbations of Raman bands assigned to ring vibrations of the bases and those of bands assigned to exocyclic carbonyls and backbone phosphodiester groups. However, strong correlations do not occur between

Multisite occupation of divalent dopants in barium and strontium titanates

NASA Astrophysics Data System (ADS)

Zulueta, Yohandys A.; Nguyen, Minh Tho

2018-10-01

Based on recent experimental and theoretical proofs of calcium multisite occupation in barium titanate, we investigated a mixed incorporation mechanism for divalent dopants in barium and strontium titanates (BaTiO3 and SrTiO3). Our present theoretical results demonstrated the multisite occupation of divalent dopants in both perovskite structures. We determined the dependences of the solution, binding energies, and final solution energies with respect to the ionic radii of the dopants. Calculated results obtained based on classical simulations showed that the divalent dopants can occupy both A- and Ti- cation sites in ATiO3 perovskite structures. Such a multisite occupation has direct implications for other experimental findings regarding BaTiO3, such as non-stabilization of the tetragonal phase, shifts in the Curie temperature, intensification of the diffuse phase transition, and shifts in the absorption of ultraviolet light to the visible range in photocatalytic applications related to solar cells for producing energy.

Mechanistic insights into allosteric regulation of the A 2A adenosine G protein-coupled receptor by physiological cations

DOE PAGES

Ye, Libin; Neale, Chris Andrew; Sljoka, Adnan; ...

2018-04-10

Cations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here, 19F NMR is used to delineate the effects of cations on functional states of the adenosine A 2A GPCR. While Na + reinforces an inactive ensemble and a partial-agonist stabilized state, Ca 2+ and Mg 2+ shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridgemore » specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. Lastly, an understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu.« less

Mechanistic insights into allosteric regulation of the A 2A adenosine G protein-coupled receptor by physiological cations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Libin; Neale, Chris Andrew; Sljoka, Adnan

Cations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here, 19F NMR is used to delineate the effects of cations on functional states of the adenosine A 2A GPCR. While Na + reinforces an inactive ensemble and a partial-agonist stabilized state, Ca 2+ and Mg 2+ shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridgemore » specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. Lastly, an understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu.« less

Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C

PubMed Central

Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

2015-01-01

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically. PMID:26658739

Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C.

PubMed

Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

2015-01-01

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically.

Drawbacks of Dialysis Procedures for Removal of EDTA

PubMed Central

Mónico, Andreia; Martínez-Senra, Eva; Cañada, F. Javier; Zorrilla, Silvia

2017-01-01

Ethylenediaminetetraacetic acid (EDTA) is a chelating agent commonly used in protein purification, both to eliminate contaminating divalent cations and to inhibit protease activity. For a number of subsequent applications EDTA needs to be exhaustively removed. Most purification methods rely in extensive dialysis and/or gel filtration in order to exchange or remove protein buffer components, including metal chelators. We report here that dialysis protocols, even as extensive as those typically employed for protein refolding, may not effectively remove EDTA, which is reduced only by approximately two-fold and it also persists after spin-column gel filtration, as determined by NMR and by colorimetric methods. Remarkably, the most efficient removal was achieved by ultrafiltration, after which EDTA became virtually undetectable. These results highlight a potentially widespread source of experimental variability affecting free divalent cation concentrations in protein applications. PMID:28099451

Heavy metal cations permeate the TRPV6 epithelial cation channel.

PubMed

Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A

2011-01-01

TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

Reusable chelating resins concentrate metal ions from highly dilute solutions

NASA Technical Reports Server (NTRS)

Bauman, A. J.; Weetal, H. H.; Weliky, N.

1966-01-01

Column chromatographic method uses new metal chelating resins for recovering heavy-metal ions from highly dilute solutions. The absorbed heavy-metal cations may be removed from the chelating resins by acid or base washes. The resins are reusable after the washes are completed.

Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant co factors Cu, Se, Fe, Zn. Does a foreign cation substitution at prion protein's Cu domain initiate TSE?

PubMed

Purdey, M

2000-02-01

Analyses of food chains supporting isolated clusters of sporadic TSEs (CWD in N Colorado, scrapie in Iceland, CJD in Slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cation, manganese (Mn), in relation to normal levels recorded in adjoining TSE-free localities. Deficiencies of the antioxidant co factors Cu/Se/Zn/Fe and Mg, P and Na were also consistently recorded in TSE foodchains. Similarities between the clinical/pathological profile of TSEs and Mn delayed psycho-neurotoxicity in miners are cited, and a novel theory generated which suggests that sporadic TSE results from early life dependence of TSE susceptible genotypes on ecosystems characterised by this specific pattern of mineral imbalance. Low Cu/Fe induces an excessive absorption of Mn in ruminants and an increased oxidation of Mn2+ into its pro oxidant species, Mn3+, which accumulates in mitochondria of CNS astrocytes in Mn SOD deficient genotypes. Deficiencies of scavenger co factors Cu/Zn/Se/Fe in the CNS permits Mn3+ initiated chain reactions of auto-oxidant mediated neuronal degeneration to proliferate, which, in turn, up-regulates the expression of the Cu-metalloprotein, prion protein (PrP). Once the rate of PrP turnover and its demand for Cu exceeds the already depleted supply of Cu within the CNS, PrP can no longer bind sufficient Cu to maintain its conformation. Mn3+ substitutes at the vacated Cu domain on PrP, thus priming up a latent capacity for lethal auto-oxidative activity to be carried along with PrP like a 'trojan horse'; where Mn 3+ serves as the integral 'infectious' transmissible component of the misfolded PrP-cation complex. The Mn overactivation of concanavalin A binding to glycoprotein and Mn-initiated autoxidation results in a diverse pathological profile involving receptor capping, aggregation/modification of CNS membrane/cytoskeletal proteins. TSE ensues. The BSE/nv CJD strain entails a 'synthetic' induction of the same CNS mineral

Generation of an unusual depolarizing response in rabbit primary afferent neurones in the absence of divalent cations.

PubMed

Stansfeld, C E; Wallis, D I

1984-07-01

The effects of divalent cations on responses to 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were investigated using a sucrose-gap method to record population responses. In Ca-free medium responses to 5-HT were enhanced, those to DMPP depressed and those to GABA unchanged. In Mg-free medium responses to 5-HT were unchanged, while those to DMPP and GABA were depressed. Removal of both Ca and Mg from the superfusion medium caused a small reduction of GABA responses and a large reduction of DMPP responses. Responses to 5-HT were not only greatly potentiated but were changed in character; the depolarizing phase became sigmoid and the dose dependence between quantity of 5-HT and response magnitude was lost as if 5-HT were triggering an all-or-nothing phenomenon. Dose--response relationships for GABA were normal in the large majority of preparations. In about 10% of preparations, supramaximal amounts of GABA or DMPP evoked large responses of a similar character to those evoked by 5-HT. The large responses, generated by an unknown mechanism, were termed X responses. Further reduction in tissue divalent cations by EGTA (1 mM) caused X responses to be generated spontaneously. Ca, Mg, Mn or Co (1 mM) could suppress X responses. DMPP responses, reduced in Ca/Mg-free medium, were largely restored by 1 mM-Ca. Depression of GABA responses in Ca/Mg-free medium could be entirely attributed to the absence of Mg, Mn being able to substitute for Mg. X responses were generated only after equilibration for 1 h with Ca/Mg-free medium. Attempts to manipulate [Ca]i with dinitrophenol or caffeine did not produce the conditions under which X responses were generated. Intracellular records of responses to 5-HT, GABA or DMPP showed that cells with A fibres responded to GABA but not to 5-HT or DMPP. Fifty-four out of sixty-seven cells with C fibre axons (80%) were depolarized by 5-HT, thirty-seven out of forty-nine (76%) by DMPP and

Uptake of photosensitizers by bacteria is influenced by the presence of cations

NASA Astrophysics Data System (ADS)

Kishen, A.; George, S.

2007-05-01

This investigation studies the influence of cations on photosensitizer uptake by Enterococcus faecalis (gram positive) and Actinobacillus actinomycetemcomitans (gram negative). Methods- The uptake of Methylene blue (MB) and Indocyanine Green (ICG), by bacteria were studied under the influence of divalent cations (CaCl II & MgCl II) and EDTA. Further, E. faecalis cells subjected to trypsinisation and calcium channel blocker (verapamil) were also analysed for MB and ICG uptake inorder to understand the mechanism of photosensitizer uptake. Results- Uptake of ICG was enhanced in the presence of divalent cations in E. faecalis and A. actinomycetemcomitans. Treating cells with EDTA had no significant effect on the photosensitizer uptake, although the highest concentration tested showed an enhancement of uptake. In contrast to ICG, MB showed a decreased uptake by bacterial cells on subjecting them to divalent cations and EDTA. Calcium channel blocker had no significant inhibitory effect on photosensitizers uptake. However, trypsin treatment resulted in significant reduction of ICG uptake. The result suggested that ICG uptake by bacteria is mediated through specific transporter protein while MB is associated with the outer surface structures of bacterial cells.

Cation-containing lipid membranes – experiment and md simulations

DOE PAGES

Kučerka, Norbert; Dushanov, Ermuhammas; Kholmurodov, Kholmirzo T.; ...

2017-11-27

Here, using small angle neutron diffraction and molecular dynamics simulations we studied the interactions between calcium (Ca 2+) or zinc (Zn 2+) cations, and oriented gel phase dipalmitoyl-phosphatidylcholine (DPPC) bilayers. For both cations studied at ~1:7 divalent metal ion to lipid molar ratio (Me2+:DPPC), bilayer thickness increased. Simulation results helped reveal subtle differences in the effects of the two cations on gel phase membranes.

Lipid domains in zwitterionic-anionic lipid mixtures induced by combined effect of monovalent and divalent ions

NASA Astrophysics Data System (ADS)

Xu, Hongcheng; Ganesan, Sai; Matysiak, Silvina

Lipid domain formation is an important process for many cellular processes. In experiment, the effects of Ba2+, Sr2+, Ca2+ and Mg2+ in inducing lateral phase separation in the binary phosphatidylcholine-phosphatidylserine (PC-PS) bilayer are quite different, of which the molecular mechanism remains to be understood. We have explored the effect of monovalent (MI) and divalent (MII) cationic radii on lipid domain formation in mixed zwitterionic-anionic lipid bilayers. We propose a mechanism for the formation of divalent-cation-induced lipid domains based on MD simulations with our Water-Explicit Polarizable MEMbrane (WEPMEM) coarse-grained model, which uses PC as the model for zwitterionic and PS for anionic lipids. Lipid aggregation only occurs with limited range of monovalent and divalent ion sizes in agreement with experimental observations. More ordering and closer packing of the lipids are noted within the domains, which correlate with bilayer thickness, curvature and lipid asymmetry. The results of the simulations reveal that the lipid domain consists of MII-mediated anionic lipid dimer/trimer complexes bridged by monovalent ions MI and provide a stereochemical insight in understanding the experimentally observed calcium-induced phase separation.

Divalent counterion-induced condensation of triple-strand DNA.

PubMed

Qiu, Xiangyun; Parsegian, V Adrian; Rau, Donald C

2010-12-14

Understanding and manipulation of the forces assembling DNA/RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence ≥ 3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triple-strand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg(2+), Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.

Treatment of drinking water residuals: comparing sedimentation and dissolved air flotation performance with optimal cation ratios.

PubMed

Bourgeois, J C; Walsh, M E; Gagnon, G A

2004-03-01

Spent filter backwash water (SFBW) and clarifier sludge generally comprise the majority of the waste residual volume generated and in relative terms, these can be collectively referred to as combined filter backwash water (CFBW). CFBW is essentially a low-solids wastewater with metal hydroxide flocs that are typically light and slow to settle. This study evaluates the impact of adding calcium and magnesium carbonates to CFBW in terms of assessing the impacts on the sedimentation and DAF separation processes. Representative CFBW samples were collected from two surface water treatment plants (WTP): Lake Major WTP (Dartmouth, Nova Scotia, Canada) and Victoria Park WTP (Truro, Nova Scotia, Canada). Bench-scale results indicated that improvements in the CFBW settled water quality could be achieved through the addition of the divalent cations, thereby adjusting the monovalent to divalent (M:D) ratios of the wastewater. In general, the DAF process required slightly higher M:D ratios than the sedimentation process. The optimum M:D ratios for DAF and sedimentation were determined to be 1:1 and 0.33:1, respectively. It was concluded that the optimisation of the cation balance between monovalent cations (e.g., Na(+), K(+)) and added divalent cations (i.e., Ca(2+), Mg(2+)) aided in the settling mechanism through charge neutralisation-precipitation. The increase in divalent cation concentrations within the waste residual stream promoted destabilisation of the negatively charged colour molecules within the CFBW, thereby causing the colloidal content to become more hydrophobic.

RENAL TUBULAR TRANSPORT OF INORGANIC DIVALENT IONS BY THE AGLOMERULAR MARINE TELEOST, LOPHIUS AMERICANUS

PubMed Central

Berglund, Fredrik; Forster, Roy P.

1958-01-01

A characterization was attempted of the mechanisms involved in the tubular transport of inorganic divalent ions by the aglomerular kidney of Lophius, attention being paid particularly to the possible existence of transport maxima (Tm) and to competition for transport among related substances undergoing tubular excretion. Excretory rates of divalent ions in non-treated fish during standard laboratory conditions paralleled spontaneous changes in urine flow. Tm rates of excretion were reached for magnesium, sulfate, and thiosulfate with corresponding plasma levels of 2 to 5, 5 to 17, and 4 to 12 µM/ml. respectively. Elevation of magnesium chloride levels in plasma markedly depressed calcium excretion; sodium thiosulfate similarly depressed sulfate excretion. Experimental observations suggest the existence of a transport system for divalent cations separate from another for divalent anions. Within each transport system the ion with the higher excretion rate depressed competitively transfer of the other ion. Neither system was influenced by probenecid (benemid) in doses which markedly depressed the simultaneous excretion rate of p-aminohippuric acid. PMID:13491814

Metal-Chelate Immobilization of Lipase onto Polyethylenimine Coated MCM-41 for Apple Flavor Synthesis.

PubMed

Sadighi, Armin; Motevalizadeh, Seyed Farshad; Hosseini, Morteza; Ramazani, Ali; Gorgannezhad, Lena; Nadri, Hamid; Deiham, Behnaz; Ganjali, Mohammad Reza; Shafiee, Abbas; Faramarzi, Mohammad Ali; Khoobi, Mehdi

2017-08-01

An enzyme immobilized on a mesoporous silica nanoparticle can serve as a multiple catalyst for the synthesis of industrially useful chemicals. In this work, MCM-41 nanoparticles were coated with polyethylenimine (MCM-41@PEI) and further modified by chelation of divalent metal ions (M = Co 2+ , Cu 2+ , or Pd 2+ ) to produce metal-chelated silica nanoparticles (MCM-41@PEI-M). Thermomyces lanuginosa lipase (TLL) was immobilized onto MCM-41, MCM-41@PEI, and MCM-41@PEI-M by physical adsorption. Maximum immobilization yield and efficiency of 75 ± 3.5 and 65 ± 2.7% were obtained for MCM@PEI-Co, respectively. The highest biocatalytic activity at extremely acidic and basic pH (pH = 3 and 10) values were achieved for MCM-PEI-Co and MCM-PEI-Cu, respectively. Optimum enzymatic activity was observed for MCM-41@PEI-Co at 75 °C, while immobilized lipase on the Co-chelated support retained 70% of its initial activity after 14 days of storage at room temperature. Due to its efficient catalytic performance, MCM-41@PEI-Co was selected for the synthesis of ethyl valerate in the presence of valeric acid and ethanol. The enzymatic esterification yield for immobilized lipase onto MCM-41@PEI-Co was 60 and 53%, respectively, after 24 h of incubation in n-hexane and dimethyl sulfoxide media. Graphical Abstract Divalent metal chelated polyethylenimine coated MCM-41 (MCM-41@PEI-M) was used for immobilization of Thermomyces lanuginosa lipase catalyzing green apple flavor preparation.

Cation exchange in a glacial till drumlin at a road salt storage facility

NASA Astrophysics Data System (ADS)

Ostendorf, David W.; Xing, Baoshan; Kallergis, Niki

2009-05-01

We use laboratory and field data to calibrate existing geochemical and transport models of cation exchange induced by contamination of an unconfined aquifer at a road salt storage facility built upon a glacial till drumlin in eastern Massachusetts. A Gaines and Thomas selectivity coefficient K models the equilibrium sodium and divalent cation distribution in the groundwater and solid matrix, while an existing method of characteristics model describes the advective transport of total dissolved cations and sorbed sodium. Laboratory isotherms of split spoon soil samples from the drumlin calibrate K with an average value of 0.0048 (L/g) 1/2 for a measured cation exchange capacity of 0.057 meq/g dry soil. Ten years of monitoring well data document groundwater flow and the advection of conservative chloride due to outdoor storage and handling of road salt at the site. The monitoring well cation data and retarded transport model offer an independent K calibration of 0.0040 to 0.0047 (L/g) 1/2: the consistency of the field and laboratory selectivity coefficient calibrations endorse this application of the Gaines and Thomas and method of characteristics models. The advancing deicing agent plume releases divalent cations from the till into the groundwater, so that monitoring well samples do not reflect the chemical composition of the road salt. In this regard, dissolved divalent cation milliequivalent concentrations are as high as 80% of the total dissolved cationic concentrations in the salt contaminated monitoring well samples, far greater than their 2.5% level in the road salt stored at the site. Cation exchange can thus obscure attempts to hindcast stored road salt sodium water table concentration from monitoring well sample stoichiometry, or to predict sodium impacts on groundwater or receiving stream quality downgradient of the well.

Cation exchange in a glacial till drumlin at a road salt storage facility.

PubMed

Ostendorf, David W; Xing, Baoshan; Kallergis, Niki

2009-05-12

We use laboratory and field data to calibrate existing geochemical and transport models of cation exchange induced by contamination of an unconfined aquifer at a road salt storage facility built upon a glacial till drumlin in eastern Massachusetts. A Gaines and Thomas selectivity coefficient K models the equilibrium sodium and divalent cation distribution in the groundwater and solid matrix, while an existing method of characteristics model describes the advective transport of total dissolved cations and sorbed sodium. Laboratory isotherms of split spoon soil samples from the drumlin calibrate K with an average value of 0.0048 (L/g)(1/2) for a measured cation exchange capacity of 0.057 meq/g dry soil. Ten years of monitoring well data document groundwater flow and the advection of conservative chloride due to outdoor storage and handling of road salt at the site. The monitoring well cation data and retarded transport model offer an independent K calibration of 0.0040 to 0.0047 (L/g)(1/2): the consistency of the field and laboratory selectivity coefficient calibrations endorse this application of the Gaines and Thomas and method of characteristics models. The advancing deicing agent plume releases divalent cations from the till into the groundwater, so that monitoring well samples do not reflect the chemical composition of the road salt. In this regard, dissolved divalent cation milliequivalent concentrations are as high as 80% of the total dissolved cationic concentrations in the salt contaminated monitoring well samples, far greater than their 2.5% level in the road salt stored at the site. Cation exchange can thus obscure attempts to hindcast stored road salt sodium water table concentration from monitoring well sample stoichiometry, or to predict sodium impacts on groundwater or receiving stream quality downgradient of the well.

The Drosophila divalent metal ion transporter Malvolio is required in dopaminergic neurons for feeding decisions

PubMed Central

Søvik, Eirik; LaMora, Angela; Seehra, Gurpreet; Barron, Andrew B.; Duncan, Jennifer G.; Ben-Shahar, Yehuda

2017-01-01

Members of the Natural resistance-associated macrophage protein (NRAMP) family are evolutionarily-conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive. Here we demonstrate that normal food choice requires Mvl function specifically in the dopaminergic system, and can be rescued by supplementing food with manganese. Collectively, our data indicate that the action of the Mvl transporter affects food choice behavior via the regulation of dopaminergic innervation of the mushroom bodies, a principle brain region associated with decision making in insects. Our studies suggest that the homeostatic regulation of the intra-neuronal levels of divalent cations plays an important role in the development and function of the dopaminergic system and associated behaviors. PMID:28220999

Interaction of divalent cations with basal planes and edge surfaces of phyllosilicate minerals: muscovite and talc.

PubMed

Yan, Lujie; Masliyah, Jacob H; Xu, Zhenghe

2013-08-15

Smooth basal plane and edge surfaces of two platy phyllosilicate minerals (muscovite and talc) were prepared successfully to allow accurate colloidal force measurement using an atomic force microscope (AFM), which allowed us to probe independently interactions of divalent cations with phyllosilicate basal planes and edge surfaces. The Stern potential of basal planes and edge surfaces was obtained by fitting the measured force profiles with the classical DLVO theory. The fitted Stern potential of the muscovite basal plane became less negative with increasing Ca(2+) or Mg(2+) concentration but did not reverse its sign even at Ca(2+) or Mg(2+) concentrations up to 5 mM. In contrast, the Stern potential of the muscovite edge surface reversed at Ca(2+) or Mg(2+) concentrations as low as 0.1 mM. The Stern potential of the talc basal plane became less negative with 0.1 mM Ca(2+) addition and nearly zero with 1 mM Ca(2+) addition. The Stern potential of talc edge surface became reversed with 0.1 mM Ca(2+) or 1 mM Mg(2+) addition, showing not only a different binding mechanism of talc basal planes and edge surfaces with Ca(2+) and Mg(2+), but also different binding mechanism between Ca(2+) and Mg(2+) ions with basal planes and edge surfaces. Copyright © 2013 Elsevier Inc. All rights reserved.

Drosophila divalent metal ion transporter Malvolio is required in dopaminergic neurons for feeding decisions.

PubMed

Søvik, E; LaMora, A; Seehra, G; Barron, A B; Duncan, J G; Ben-Shahar, Y

2017-06-01

Members of the natural resistance-associated macrophage protein (NRAMP) family are evolutionarily conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive. Here, we show that normal food choice requires Mvl function specifically in the dopaminergic system, and can be rescued by supplementing food with manganese. Collectively, our data indicate that the action of the Mvl transporter affects food choice behavior via the regulation of dopaminergic innervation of the mushroom bodies, a principle brain region associated with decision-making in insects. Our studies suggest that the homeostatic regulation of the intraneuronal levels of divalent cations plays an important role in the development and function of the dopaminergic system and associated behaviors. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Energy-resolved collision-induced dissociation studies of 1,10-phenanthroline complexes of the late first-row divalent transition metal cations: determination of the third sequential binding energies.

PubMed

Nose, Holliness; Chen, Yu; Rodgers, M T

2013-05-23

The third sequential binding energies of the late first-row divalent transition metal cations to 1,10-phenanthroline (Phen) are determined by energy-resolved collision-induced dissociation (CID) techniques using a guided ion beam tandem mass spectrometer. Five late first-row transition metal cations in their +2 oxidation states are examined including: Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+). The kinetic energy dependent CID cross sections for loss of an intact Phen ligand from the M(2+)(Phen)3 complexes are modeled to obtain 0 and 298 K bond dissociation energies (BDEs) after accounting for the effects of the internal energy of the complexes, multiple ion-neutral collisions, and unimolecular decay rates. Electronic structure theory calculations at the B3LYP, BHandHLYP, and M06 levels of theory are employed to determine the structures and theoretical estimates for the first, second, and third sequential BDEs of the M(2+)(Phen)x complexes. B3LYP was found to deliver results that are most consistent with the measured values. Periodic trends in the binding of these complexes are examined and compared to the analogous complexes to the late first-row monovalent transition metal cations, Co(+), Ni(+), Cu(+), and Zn(+), previously investigated.

Interaction studies of human prion protein (HuPrP109-111: methionine-lysine-histidine) tripeptide model with transition metal cations.

PubMed

Pitchumani Violet Mary, C; Shankar, R; Vijayakumar, S; Kolandaivel, P

2016-09-01

In the present study, the coordination bonds between the Methionine-Lysine-Histidine (Ac-MKH-NHMe) tripeptide model associated with the fifth metal binding site, which triggers the β-sheet formation of human prion protein and the divalent metal cations such as Mn(2+), Cu(2+) and Zn(2+) were studied using B3LYP and M052X levels of theory with LANL2DZ basis set. For each transition divalent metal cation, three different coordination modes (4N, 3NO, and 2NSO) were analyzed. The present result reveals that overall structural parameters of MKH model tripeptide are altered due to the interaction of divalent metal cations. Among these three coordination modes, the 4N-M(2)(+) and 4N2O-Mn(2+) complexes are found to have the larger interaction energy, MIA and deformation energies. The triply deprotonated coordination mode of the Ac-MKH-NHMe tripeptide transfers more amount of charge to the divalent metal cations than the dually and singly deprotonated complexes. Furthermore, the atoms in molecules (AIM) topological analysis confirm that, the interaction between the metal cations Mn(2+), Cu(2+) and Zn(2+) and Ac-MKH-NHMe tripeptide are electrostatic dominant and the coordination modes with triply deprotonation states possess larger electron density at their BCP corresponding to their coordination bonds. The electrostatic potential difference maps of the most stable 4N-M(2+) (M(2+)=Cu(2+) and Zn(2+)) and 4N2O-Mn(2+) reveals that, as the ionic radii of the metal ion increases, the delocalization charges localized on the metal cations are found to be decreased. The Infra-red stretching frequencies of NH, CH, and CH2 groups of each coordination complexes are observed with shift in their stretching frequencies. From these observations we conclude that, the transition divalent metal cations binding in 4N coordination mode will induce more conformational changes of the Prion protein. Copyright © 2016 Elsevier Inc. All rights reserved.

Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.

PubMed

Anderson, Michael; Schultz, Eric P; Martick, Monika; Scott, William G

2013-10-23

We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na(+) ion binding in the ribozyme's active site. At least two such Na(+) ions are observed. The first Na(+) ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na(+) ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na(+), but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na(+) directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fast kinetics of magnesium monochloride cations in interlayer-expanded titanium disulfide for magnesium rechargeable batteries

DOE PAGES

Yoo, Hyun Deog; Liang, Yanliang; Dong, Hui; ...

2017-08-24

Magnesium rechargeable batteries potentially offer high-energy density, safety, and low cost due to the ability to employ divalent, dendrite-free, and earth-abundant magnesium metal anode. Despite recent progress, further development remains stagnated mainly due to the sluggish scission of magnesium-chloride bond and slow diffusion of divalent magnesium cations in cathodes. Here in this paper we report a battery chemistry that utilizes magnesium monochloride cations in expanded titanium disulfide. Combined theoretical modeling, spectroscopic analysis, and electrochemical study reveal fast diffusion kinetics of magnesium monochloride cations without scission of magnesium-chloride bond. The battery demonstrates the reversible intercalation of 1 and 1.7 magnesium monochloridemore » cations per titanium at 25 and 60 °C, respectively, corresponding to up to 400 mAh g -1 capacity based on the mass of titanium disulfide. The large capacity accompanies with excellent rate and cycling performances even at room temperature, opening up possibilities for a variety of effective intercalation hosts for multivalent-ion batteries.« less

Distinct reaction pathway promoted by non-divalent-metal cations in a tertiary stabilized hammerhead ribozyme

PubMed Central

Roychowdhury-Saha, Manami; Burke, Donald H.

2007-01-01

Divalent ion sensitivity of hammerhead ribozymes is significantly reduced when the RNA structure includes appropriate tertiary stabilization. Therefore, we investigated the activity of the tertiary stabilized “RzB” hammerhead ribozyme in several nondivalent ions. Ribozyme RzB is active in spermidine and Na+ alone, although the cleavage rates are reduced by more than 1,000-fold relative to the rates observed in Mg2+ and in transition metal ions. The trivalent cobalt hexammine (CoHex) ion is often used as an exchange-inert analog of hydrated magnesium ion. Trans-cleavage rates exceeded 8 min−1 in 20 mM CoHex, which promoted cleavage through outersphere interactions. The stimulation of catalysis afforded by the tertiary structural interactions within RzB does not require Mg2+, unlike other extended hammerhead ribozymes. Site-specific interaction with at least one Mg2+ ion is suggested by CoHex competition experiments. In the presence of a constant, low concentration of Mg2+, low concentrations of CoHex decreased the rate by two to three orders of magnitude relative to the rate in Mg2+ alone. Cleavage rates increased as CoHex concentrations were raised further, but the final fraction cleaved was lower than what was observed in CoHex or Mg2+ alone. These observations suggest that Mg2+ and CoHex compete for binding and that they cause misfolded structures when they are together. The results of this study support the existence of an alternate catalytic mechanism used by nondivalent ions (especially CoHex) that is distinct from the one promoted by divalent metal ions, and they imply that divalent metals influence catalysis through a specific nonstructural role. PMID:17456566

Case study II: application of the divalent cation bridging theory to improve biofloc properties and industrial activated sludge system performance-using alternatives to sodium-based chemicals.

PubMed

Higgins, Matthew J; Sobeck, David C; Owens, Steven J; Szabo, Lynn M

2004-01-01

The objective of this study was to investigate the application of the divalent cation bridging theory (DCBT) as a tool in the chemical selection process at an activated sludge plant to improve settling, dewatering, and effluent quality. According to the DCBT, to achieve improvements, the goal of chemical selection should be to reduce the ratio of monovalent-to-divalent (M/D) cations. A study was conducted to determine the effect of using magnesium hydroxide [Mg(OH)2] as an alternative to sodium hydroxide (NaOH) at a full-scale industrial wastewater treatment plant. Floc properties and treatment plant performance were measured for approximately one year during two periods of NaOH addition and Mg(OH)2 addition. A cost analysis of plant operation during NaOH and Mg(OH)2 use was also performed. During NaOH addition, the M/D ratio was 48, while, during Mg(OH)2 addition, this ratio was reduced to an average of approximately 0.1. During the Mg(OH)2 addition period, the sludge volume index, effluent total suspended solids, and effluent chemical oxygen demand were reduced by approximately 63, 31, and 50%, respectively, compared to the NaOH addition period. The alum and polymer dose used for clarification was reduced by approximately 50 and 60%, respectively, during Mg(OH)2 addition. The dewatering properties of the activated sludge improved dewatering as measured by decreased capillary suction time and specific resistance to filtration (SRF), along with an increase in cake solids from the SRF test. This corresponded to a reduction in the volume of solids thickened by centrifuges at the treatment plant, which reduced the disposal costs of solids. Considering the costs for chemicals and solids disposal, the annual cost of using Mg(OH)2 was approximately 30,000 dollars to 115,000 dollars less than using NaOH, depending on the pricing of NaOH. The results of this study confirm that the DCBT is a useful tool for assessing chemical-addition strategies and their potential effect

Adsorption of DNA to mica mediated by divalent counterions: a theoretical and experimental study.

PubMed

Pastré, David; Piétrement, Olivier; Fusil, Stéphane; Landousy, Fabrice; Jeusset, Josette; David, Marie-Odile; Hamon, Loïc; Le Cam, Eric; Zozime, Alain

2003-10-01

The adsorption of DNA molecules onto a flat mica surface is a necessary step to perform atomic force microscopy studies of DNA conformation and observe DNA-protein interactions in physiological environment. However, the phenomenon that pulls DNA molecules onto the surface is still not understood. This is a crucial issue because the DNA/surface interactions could affect the DNA biological functions. In this paper we develop a model that can explain the mechanism of the DNA adsorption onto mica. This model suggests that DNA attraction is due to the sharing of the DNA and mica counterions. The correlations between divalent counterions on both the negatively charged DNA and the mica surface can generate a net attraction force whereas the correlations between monovalent counterions are ineffective in the DNA attraction. DNA binding is then dependent on the fractional surface densities of the divalent and monovalent cations, which can compete for the mica surface and DNA neutralizations. In addition, the attraction can be enhanced when the mica has been pretreated by transition metal cations (Ni(2+), Zn(2+)). Mica pretreatment simultaneously enhances the DNA attraction and reduces the repulsive contribution due to the electrical double-layer force. We also perform end-to-end distance measurement of DNA chains to study the binding strength. The DNA binding strength appears to be constant for a fixed fractional surface density of the divalent cations at low ionic strength (I < 0.1 M) as predicted by the model. However, at higher ionic strength, the binding is weakened by the screening effect of the ions. Then, some equations were derived to describe the binding of a polyelectrolyte onto a charged surface. The electrostatic attraction due to the sharing of counterions is particularly effective if the polyelectrolyte and the surface have nearly the same surface charge density. This characteristic of the attraction force can explain the success of mica for performing single

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

NASA Technical Reports Server (NTRS)

Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

1999-01-01

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

Whole-cell and single channel monovalent cation currents through the novel rabbit epithelial Ca2+ channel ECaC

PubMed Central

Nilius, Bernd; Vennekens, Rudi; Prenen, Jean; Hoenderop, Joost G J; Bindels, René J M; Droogmans, Guy

2000-01-01

This study describes properties of monovalent cation currents through ECaC, a recently cloned epithelial Ca2+-permeable channel from rabbit. The kinetics of currents through ECaC was strongly modulated by divalent cations. Currents were inhibited in the presence of extracellular Ca2+. They showed an initial voltage-dependent decay in the presence of 1 mm Mg2+ at hyperpolarizing steps in Ca2+-free solutions, which represents a voltage-dependent Mg2+ block through binding of Mg2+ to a site localized in the electrical field of the membrane (δ = 0.31) and a voltage-dependent binding constant (at 0 mV 3.1 mm Ca2+, obtained from a Woodhull type analysis). Currents were only stable in the absence of divalent cations and showed under these conditions a small time- and voltage-dependent component of activation. Single channel currents in cell-attached and inside-out patches had a conductance of 77.5 ± 4.9 pS (n = 11) and reversed at +14.8 ± 1.6 mV (n = 9) in the absence of divalent cations. The permeation sequence for monovalent cations through ECaC was Na+ > Li+ > K+ > Cs+ > NMDG+ which is identical to the Eisenmann sequence X for a strong field-strength binding site. It is concluded that the permeation profile of ECaC for monovalent cations suggests a strong field-strength binding site that may be involved in Ca2+ permeation and Mg2+ block. PMID:10970426

Molecular dynamics simulations of the structure and single-particle dynamics of mixtures of divalent salts and ionic liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gómez-González, Víctor; Docampo-Álvarez, Borja; Gallego, Luis J.

2015-09-28

We report a molecular dynamics study of the structure and single-particle dynamics of mixtures of a protic (ethylammonium nitrate) and an aprotic (1-butyl-3-methylimidazolium hexaflurophosphate [BMIM][PF{sub 6}]) room-temperature ionic liquids doped with magnesium and calcium salts with a common anion at 298.15 K and 1 atm. The solvation of these divalent cations in dense ionic environments is analyzed by means of apparent molar volumes of the mixtures, radial distribution functions, and coordination numbers. For the protic mixtures, the effect of salt concentration on the network of hydrogen bonds is also considered. Moreover, single-particle dynamics of the salt cations is studied by means ofmore » their velocity autocorrelation functions and vibrational densities of states, explicitly analyzing the influence of salt concentration, and cation charge and mass on these magnitudes. The effect of the valency of the salt cation on these properties is considered comparing the results with those for the corresponding mixtures with lithium salts. We found that the main structural and dynamic features of the local solvation of divalent cations in ionic liquids are similar to those of monovalent salts, with cations being localized in the polar nanoregions of the bulk mixture coordinated in monodentate and bidentate coordination modes by the [NO{sub 3}]{sup −} and [PF{sub 6}]{sup −} anions. However, stronger electrostatic correlations of these polar nanoregions than in mixtures with salts with monovalent cations are found. The vibrational modes of the ionic liquid (IL) are seen to be scarcely affected by the addition of the salt, and the effect of mass and charge on the vibrational densities of states of the dissolved cations is reported. Cation mass is seen to exert a deeper influence than charge on the low-frequency vibrational spectra, giving a red shift of the vibrational modes and a virtual suppression of the higher energy vibrational modes for the heavier Ca

A comparative study of chelating and cationic ion exchange resins for the removal of palladium(II) complexes from acidic chloride media.

PubMed

Hubicki, Zbigniew; Wołowicz, Anna

2009-05-30

The increasing demand for palladium for technological application requires the development of ion exchange chromatography. Recently ion exchange chromatography has developed largely as a result of new types of ion exchangers available on the market of which two types are widely applied. One of them are selective (chelating) and modified ion exchangers and the other one are liquid exchangers. Two types of ion exchange resins such as chelating (Lewatit TP 214, Purolite S 920) and cationic (Chelite S, Duolite GT 73) ion exchangers are used for the recovery of palladium(II) complexes from chloride media (0.1-2.0M HCl-1.0M NaCl-0.0011 M Pd(II); 0.1-2.0M HCl-2.0M NaCl-0.0011M Pd(II)). The influence of concentration of hydrochloric acid, sodium chloride as well as the phase contact time on the degree of recovery of palladium(II) complexes was studied. Moreover, the amount of palladium(II) chlorocomplexes sorbed onto ion exchangers, the working ion exchange capacities and the weight and bed distribution coefficients were calculated in order to judge which of two types of resins possesses the best performance towards palladium(II) complexes.

Structural classification of RAO3( MO) n compounds ( R =Sc, In, Y, or lanthanides; A =Fe(III), Ga, Cr, or Al; M =divalent cation; n = 1-11)

NASA Astrophysics Data System (ADS)

Kimizuka, Noboru; Mohri, Takahiko

1989-01-01

A series of new compounds RAO3( MO) n ( n = 1-11) having spinel, YbFe 2O 4, or InFeO 3(ZnO) n types of structures were newly synthesized ( R =Sc, In, Y, Lu, Yb, Tm, or Er; A =Fe(III), Ga, Cr, or Al; M =Mg, Mn, Fe(II), Co, Ni, Zn, or Cd) at elevated temperatures. The conditions of synthesis and the lattice constants for these compounds are reported. The stacking sequences of the InO 1.5, (FeZn)O 2.5, and ZnO layers for InFeO 3(ZnO) 10 and the TmO 1.5, (AlZn)O 2.5, and ZnO layers for TmAlO 3(ZnO) 11 are presented, respectively. The crystal structures of the( RAO3) m( MO) n phases ( R =Sc, In, Y, or lanthanide elements; A =Fe(III), Ga, Cr, or Al; M =divalent cation elements; m and n =integer) are classified into four crystal structure types (K 2NiF 4, CaFe 2O 4, YbFe 2O 4, and spinel), based upon the constituent cations R, A, and M

Cations Form Sequence Selective Motifs within DNA Grooves via a Combination of Cation-Pi and Ion-Dipole/Hydrogen Bond Interactions

PubMed Central

Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

2013-01-01

The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl+) and the polarized first hydration shell waters of divalent cations (Mg2+, Ca2+) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves. PMID:23940752

Cations form sequence selective motifs within DNA grooves via a combination of cation-pi and ion-dipole/hydrogen bond interactions.

PubMed

Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

2013-01-01

The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl⁺) and the polarized first hydration shell waters of divalent cations (Mg²⁺, Ca²⁺) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves.

Effect of cation size and charge on the interaction between silica surfaces in 1:1, 2:1, and 3:1 aqueous electrolytes.

PubMed

Dishon, Matan; Zohar, Ohad; Sivan, Uri

2011-11-01

Application of two complementary AFM measurements, force vs separation and adhesion force, reveals the combined effects of cation size and charge (valency) on the interaction between silica surfaces in three 1:1, three 2:1, and three 3:1 metal chloride aqueous solutions of different concentrations. The interaction between the silica surfaces in 1:1 and 2:1 salt solutions is fully accounted for by ion-independent van der Waals (vdW) attraction and electric double-layer repulsion modified by cation specific adsorption to the silica surfaces. The deduced ranking of mono- and divalent cation adsorption capacity (adsorbability) to silica, Mg(2+) < Ca(2+) < Na(+) < Sr(2+) < K(+) < Cs(+), follows cation bare size as well as cation solvation energy but does not correlate with hydrated ionic radius or with volume or surface ionic charge density. In the presence of 3:1 salts, the coarse phenomenology of the force between the silica surfaces as a function of salt concentration resembles that in 1:1 and 2:1 electrolytes. Nevertheless, two fundamental differences should be noticed. First, the attraction between the silica surfaces is too large to be attributed solely to vdW force, hence implying an additional attraction mechanism or gross modification of the conventional vdW attraction. Second, neutralization of the silica surfaces occurs at trivalent cation concentrations that are 3 orders of magnitude smaller than those characterizing surface neutralization by mono- and divalent cations. Consequently, when trivalent cations are added to our cation adsorbability series the correlation with bare ion size breaks down abruptly. The strong adsorbability of trivalent cations to silica contrasts straightforward expectations based on ranking of the cationic solvation energies, thus suggesting a different adsorption mechanism which is inoperative or weak for mono- and divalent cations.

Specificity in cationic interaction with poly(N-isopropylacrylamide).

PubMed

Du, Hongbo; Wickramasinghe, Sumith Ranil; Qian, Xianghong

2013-05-02

Classical molecular dynamics (MD) simulations were conducted for PNIPAM in 1 M monovalent alkali chloride salt solutions as well as in 0.5 M divalent Mg(2+) and Ca(2+) chloride salt solutions. It was found that the strength for the direct alkali ion-amide O binding is strongly correlated with the size of the ionic radius. The smallest Li(+) ion binds strongest to amide O, and the largest Cs(+) ion has the weakest interaction with the amide bond. For the divalent Mg(2+) and Ca(2+) ions, their interactions with the amide bond are weak and appear to be mediated by the water molecules, particularly in the case of Mg(2+), resulting from their strong hydration. The direct binding between the cations and amide O requires partial desovlation of the ions that is energetically unfavorable for Mg(2+) and also to a great extent for Ca(2+). The higher cation charge makes the electrostatic interaction more favorable but the dehydration process less favorable. This competition between electrostatic interaction and the dehydration process largely dictates whether the direct binding between the cation and amide O is energetically preferred or not. For monovalent alkali ions, it is energetically preferred to bind directly with the amide O. Moreover, Li(+) ion is also found to associate strongly with the hydrophobic residues on PNIPAM.

Divalent fluoride doped cerium fluoride scintillator

DOEpatents

Anderson, David F.; Sparrow, Robert W.

1991-01-01

The use of divalent fluoride dopants in scintillator materials comprising cerium fluoride is disclosed. The preferred divalent fluoride dopants are calcium fluoride, strontium fluoride, and barium fluoride. The preferred amount of divalent fluoride dopant is less than about two percent by weight of the total scintillator. Cerium fluoride scintillator crystals grown with the addition of a divalent fluoride have exhibited better transmissions and higher light outputs than crystals grown without the addition of such dopants. These scintillators are useful in radiation detection and monitoring applications, and are particularly well suited for high-rate applications such as positron emission tomography (PET).

Chelating ionic liquids for reversible zinc electrochemistry.

PubMed

Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

2013-05-21

Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions.

Interfacial binding of divalent cations to calixarene-based Langmuir monolayers

DOE PAGES

Tulli, Ludovico G.; Wang, Wenjie; Lindemann, William R.; ...

2015-02-20

The interactions of Langmuir monolayers produced through the self-assembly of an amphiphilic p-carboxycalix[4]arene with a series of divalent, fourth-period transition metals, at the air-water interface, were investigated. Changes in the interfacial behavior of 1 in response to the presence of CuCl 2, CoCl 2, MnCl 2, and NiCl 2 were studied by means of Langmuir compression isotherms and Brewster angle microscopy (BAM). The measurements revealed that the self-assembly properties of 1 are significantly affected by Cu 2+ ions. The interactions of 1-based monolayers with Co 2+ and Cu 2+ ions were further investigated by means of synchrotron radiation-based X-ray reflectivitymore » (XRR), X-ray near-total-reflection fluorescence (XNTRF), and grazing incidence X-ray diffraction (GIXD). XNTRF and XRR analyses revealed that the monolayer of 1 binds more strongly to Cu 2+ than Co 2+ ions. In the presence of relatively high concentrations of Cu 2+ ions in the subphase (1.4 × 10 -3 M), XNTRF exhibited anomalous depth profile behavior and GIXD measurements showed considerably strong diffuse scattering. Furthermore, both measurements suggest the formation of Cu 2+ clusters contiguous to the monolayer of 1.« less

Interactions of chlorphenesin and divalent metal ions with phosphodiesterase.

PubMed

Edelson, J; McMullen, J P

1976-09-01

Chlorphenesin inhibition of the hydrolysis of cyclic AMP by guinea-pig lung phosphodiesterase was reversed by the addition of exogenous magnesium ions. Chlorphenesin and theophylline inhibition of this enzyme was shown to be noncompetitive when the substrate concentration was low. Kinetic studies of the inhibition of beef heart phosphodiesterase by chlorphenesin and theophylline indicated that the substrate concentration was a factor in determining whether inhibition was competitive or noncompetitive. Calcium, cobalt and copper ions were inhibitory to guinea-pig lung phosphodiesterase. The inhibition due to chlorphenesin was partially reversed by low (40 mM or less) concentrations of barium ions; high concentrations of barium ions, or manganese ions, were inhibitory. The concentration of the divalent cation did not affect the type of inhibition that was observed.

Energy levels scheme simulation of divalent cobalt doped bismuth germanate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreici, Emiliana-Laura, E-mail: andreicilaura@yahoo.com; Petkova, Petya; Avram, Nicolae M.

The aim of this paper is to simulate the energy levels scheme for Bismuth Germanate (BGO) doped with divalent cobalt, in order to give a reliable explanation for spectral experimental data. In the semiempirical crystal field theory we first modeled the Crystal Field Parameters (CFPs) of BGO:Cr{sup 2+} system, in the frame of Exchange Charge Model (ECM), with actually site symmetry of the impurity ions after doping. The values of CFPs depend on the geometry of doped host matrix and by parameter G of ECM. First, we optimized the geometry of undoped BGO host matrix and afterwards, that of dopedmore » BGO with divalent cobalt. The charges effect of ligands and covalence bonding between cobalt cations and oxygen anions, in the cluster approach, also were taken into account. With the obtained values of the CFPs we simulate the energy levels scheme of cobalt ions, by diagonalizing the matrix of the doped crystal Hamiltonian. Obviously, energy levels and estimated Racah parameters B and C were compared with the experimental spectroscopic data and discussed. Comparison of obtained results with experimental data shows quite satisfactory, which justify the model and simulation schemes used for the title system.« less

Effect of soil parameters on the kinetics of the displacement of Fe from FeEDDHA chelates by Cu.

PubMed

Schenkeveld, Walter D C; Reichwein, Arjen M; Temminghoff, Erwin J M; van Riemsdijk, Willem H

2012-06-28

In soil application, o,o-FeEDDHA (iron (3+) ethylene diamine-N,N'-bis(2-hydroxy phenyl acetic acid) complex) is the active ingredient of FeEDDHA chelate-based Fe fertilizers. The effectiveness of o,o-FeEDDHA is potentially compromised by the displacement of Fe from FeEDDHA by Cu. The actual impact of Cu competition is codetermined by the kinetics of the displacement reaction. In this study, the influence of soil parameters on the displacement kinetics has been examined in goethite suspensions. The displacement reaction predominantly takes place on the reactive surface rather than in solution. The rate at which the o,o-FeEDDHA concentration declined depended on the available reactive surface area, the Cu loading, and the FeEDDHA loading. Soil factors reducing FeEDDHA adsorption (high ionic strength, humic acid adsorption onto the goethite surface, and monovalent instead of divalent cations in the electrolyte) decreased the displacement rate. For meso o,o-FeEDDHA, the displacement rate equation was derived, which is first order in FeEDDHA loading and half order in Cu loading. For soil conditions, the equation can be simplified to an exponential decay function in meso o,o-FeEDDHA solution concentration.

Selective Metal Cation Capture by Soft Anionic Metal-Organic Frameworks via Drastic Single-Crystal-to-Single-Crystal Transformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Jian; Saraf, Laxmikant V.; Schwenzer, Birgit

2012-05-25

Flexible anionic metal-organic frameworks transform to neutral heterobimetallic systems via single-crystal-to-single-crystal processes invoked by cation insertion. These transformations are directed by cooperative bond breakage and formation, resulting in expansion or contraction of the 3D framework by up to 33% due to the flexible nature of the organic linker. These MOFs displays highly selective uptake of divalent transition metal cations (Co2+ and Ni2+ for example) over alkali metal cations (Li+ and Na+).

EFFECT OF INORGANIC CATIONS ON BACTERICIDAL ACTIVITY OF ANIONIC SURFACTANTS

PubMed Central

Voss, J. G.

1963-01-01

Voss, J. G. (Procter & Gamble Co., Cincinnati, Ohio). Effect of inorganic cations on bactericidal activity of anionic surfactants. J. Bacteriol. 86:207–211. 1963.—The bactericidal effectiveness of two alkyl benzene sulfonates and of three other types of anionic surfactants against Staphylococcus aureus is increased in the presence of low concentrations of divalent cations, especially alkaline earths and metals of group IIB of the periodic table. The cations may act by decreasing the negative charge at the cell surface and increasing adsorption of the surfactant anions, leading to damage to the cytoplasmic membrane and death of the cell. Increased adsorption of surfactant is also found with Escherichia coli, but does not lead to death of the cell. PMID:14058942

High voltage electron microscopy studies of axoplasmic transport in neurons: a possible regulatory role for divalent cations

PubMed Central

1982-01-01

Light and high voltage electron microscopy (HVEM) procedures have been employed to examine the processes regulating saltatory motion in neurons. Light microscope studies demonstrate that organelle transport occurs by rapid bidirectional saltations along linear pathways in cultured neuroblastoma cells. HVEM stereo images of axons reveal that microtubules (Mts) and organelles are suspended in a continuous latticework of fine microtrabecular filaments and that the Mts and lattice constitute a basic cytoskeletal structure mediating the motion of particles along axons. We propose that particle transport depends on dynamic properties of nonstatic microtrabecular lattice components. EXperiments were initiated to determine the effects of changes in divalent cation concentrations (Ca2+ and Mg2+) on: (a)the continuation of transport and (b) the corresponding structural properties of the microtrabecular lattice. We discovered that transport continues or is stimulated to a limited extent in cells exposed to small amounts of exogenously supplied Ca2+ and Mg2+ ions (less than 0.1 mM). Exposure of neurons to increased dosages of Ca2+ and Mg2+ (0.2-1.0 mM) stimulates transport for 2-4 min at 37 degrees C, but after a 5- to 20-min exposure the saltatory movements of organelles are observed gradually to become shorter in duration and rate particle motion ceases to occur. HVEM observations demonstrated that Ca2+ - and with the cessation of motion. Ca2+-containing solutions produced contractions of the microtrabecular filaments, whereas Mg2+-containing solutions had the opposing effect of stimulating an elongation and assembly (expansion) of microtrabeculae. On the basis of these observations we hypothesize that cycles of Ca2+/Mg2+-coupled contractions and expansions of the microtrabecular lattice probably regulate organelle motion in nerve cells. PMID:6177704

Multisite Ion Model in Concentrated Solutions of Divalent Cations (MgCl2 and CaCl2): Osmotic Pressure Calculations

PubMed Central

2015-01-01

Accurate force field parameters for ions are essential for meaningful simulation studies of proteins and nucleic acids. Currently accepted models of ions, especially for divalent ions, do not necessarily reproduce the right physiological behavior of Ca2+ and Mg2+ ions. Saxena and Sept (J. Chem. Theor. Comput.2013, 9, 3538–3542) described a model, called the multisite-ion model, where instead of treating the ions as an isolated sphere, the charge was split into multiple sites with partial charge. This model provided accurate inner shell coordination of the ion with biomolecules and predicted better free energies for proteins and nucleic acids. Here, we expand and refine the multisite model to describe the behavior of divalent ions in concentrated MgCl2 and CaCl2 electrolyte solutions, eliminating the unusual ion–ion pairing and clustering of ions which occurred in the original model. We calibrate and improve the parameters of the multisite model by matching the osmotic pressure of concentrated solutions of MgCl2 to the experimental values and then use these parameters to test the behavior of CaCl2 solutions. We find that the concentrated solutions of both divalent ions exhibit the experimentally observed behavior with correct osmotic pressure, the presence of solvent separated ion pairs instead of direct ion pairs, and no aggregation of ions. The improved multisite model for (Mg2+ and Ca2+) can be used in classical simulations of biomolecules at physiologically relevant salt concentrations. PMID:25482831

Metal-organic complexes in geochemical processes: temperature dependence of the standard thermodynamic properties of aqueous complexes between metal cations and dicarboxylate ligands

NASA Astrophysics Data System (ADS)

Prapaipong, Panjai; Shock, Everett L.; Koretsky, Carla M.

1999-10-01

By combining results from regression and correlation methods, standard state thermodynamic properties for aqueous complexes between metal cations and divalent organic acid ligands (oxalate, malonate, succinate, glutarate, and adipate) are evaluated and applied to geochemical processes. Regression of experimental standard-state equilibrium constants with the revised Helgeson-Kirkham-Flowers (HKF) equation of state yields standard partial molal entropies (S¯°) of aqueous metal-organic complexes, which allow determination of thermodynamic properties of the complexes at elevated temperatures. In cases where S¯° is not available from either regression or calorimetric measurement, the values of S¯° can be estimated from a linear correlation between standard partial molal entropies of association (ΔS¯°r) and standard partial molal entropies of aqueous cations (S¯°M). The correlation is independent of cation charge, which makes it possible to predict S¯° for complexes between divalent organic acids and numerous metal cations. Similarly, correlations between standard Gibbs free energies of association of metal-organic complexes (ΔḠ°r) and Gibbs free energies of formation (ΔḠ°f) for divalent metal cations allow estimates of standard-state equilibrium constants where experimental data are not available. These correlations are found to be a function of ligand structure and cation charge. Predicted equilibrium constants for dicarboxylate complexes of numerous cations were included with those for inorganic and other organic complexes to study the effects of dicarboxylate complexes on the speciation of metals and organic acids in oil-field brines. Relatively low concentrations of oxalic and malonic acids affect the speciation of cations more than similar concentrations of succinic, glutaric, and adipic acids. However, the extent to which metal-dicarboxylate complexes contribute to the speciation of dissolved metals depends on the type of dicarboxylic acid

Tissue-Specific Induction of Mouse ZIP8 and ZIP14 Divalent Cation/Bicarbonate Symporters by, and Cytokine Response to, Inflammatory Signals

PubMed Central

Gálvez-Peralta, Marina; Wang, Zhifang; Bao, Shengying; Knoell, Daren L; Nebert, Daniel W

2014-01-01

Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3−)2 symporters responsible for uptake of Zn2+, Fe2+ and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has two exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell-type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with ZIP8 and ZIP14 up-regulation, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein we show that C57BL/6J male mice—treated intraperitoneally with lipopolysaccharide (LPS), or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6)—exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and down-regulation of ZIP8, ZIP14A and ZIP14B mRNA levels in twelve tissues. Magnitude of the inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6 and interleukin-1β (IL1B) mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A and/or ZIP14B) for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels, due to Zn2+ redistribution not just in liver, but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney and lung should also be considered. PMID:24728862

Effects of inorganic acids and divalent hydrated metal cations (Mg(2+), Ca(2+), Co(2+), Ni(2+)) on γ-AlOOH sol-gel process.

PubMed

Zhang, Jian; Xia, Yuguo; Zhang, Li; Chen, Dairong; Jiao, Xiuling

2015-11-07

In-depth understanding of the sol-gel process plays an essential role in guiding the preparation of new materials. Herein, the effects of different inorganic acids (HCl, HNO3 and H2SO4) and divalent hydrated metal cations (Mg(2+), Ca(2+), Co(2+), Ni(2+)) on γ-AlOOH sol-gel process were studied based on experiments and density functional theory (DFT) calculations. In these experiments, the sol originating from the γ-AlOOH suspension was formed only with the addition of HCl and HNO3, but not with H2SO4. Furthermore, the DFT calculations showed that the strong adsorption of HSO4(-) on the surface of the γ-AlOOH particles, and the hydrogen in HSO4(-) pointing towards the solvent lead to an unstable configuration of electric double layer (EDL). In the experiment, the gelation time sequence of γ-AlOOH sol obtained by adding metal ions changed when the ionic strength was equal to or greater than 0.198 mol kg(-1). The DFT calculations demonstrated that the adsorption energy of hydrated metal ions on the γ-AlOOH surface can actually make a difference in the sol-gel process.

Influence of cations on noncovalent interactions between 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and dissolved fulvic and humic acids.

PubMed

Gadad, Praveen; Nanny, Mark A

2008-12-01

The influence of cations (Na(+), Ca(2+) and Mg(2+)) on noncovalent interactions between 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and dissolved fulvic acids (FAs) (Norman landfill leachate fulvic acid (NLFA) and Suwannee River fulvic acid (SRFA)) and dissolved humic acids (HAs) (Suwannee River humic acid (SRHA) and Leonardite humic acid (LHA)) was examined using steady-state fluorescence spectroscopy at pH 4, 7 and 10 as a function of cation concentration (up to 25-100mM). Regardless of pH and cation concentration, PRODAN quenching by FA was unaffected by cations. However, interactions between PRODAN and HA decreased in the presence of cations at pH 7 and 10. Cation concentrations below the HA charge density resulted in the greatest decrease of PRODAN quenching, while very little additional decrease in PRODAN quenching occurred at cation concentrations above the HA charge density. This suggests that as the HA carboxylic acid functional groups form inner sphere complexes with divalent cations, intramolecular interactions result in a contraction of the HA molecular structure, thereby preventing PRODAN from associating with the condensed aromatic, electron accepting moieties inherent within HA molecules and responsible for PRODAN quenching. However, once the HA carboxylic acid functional groups are fully titrated with divalent cations, PRODAN quenching is no longer significantly influenced by the further addition of cations, even though these additional cations facilitate intermolecular interactions between the HA molecules to form supramolecular HA aggregates that can continue to increase in size. Regardless of FA and HA type, pH, cation type and concentration, the lack of blue-shifted fluorescence emission spectra indicated that micelle-like hydrophobic regions, amenable to PRODAN partitioning, were not formed by intra- and intermolecular interactions of FA and HA.

Structural classification of RAO/sub 3/(MO)/sub n/ compounds (R = Sc, In, Y, or lanthanides; A = Fe(III), Ga, Cr, or Al; M = divalent cation; n = 1-11)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimizuka, N.; Mohri, T.

A series of new compounds (RAO/sub 3/MO)/sub n/ (n = 1-11) having spinel, YbFe/sub 2/O/sub 4/, or InFeO/sub 3/(ZnO)/sub n/ types of structures were newly synthesized (R = Sc, In, Y, Lu, Yb, Tm, or Er; A = Fe(III), Ga, Cr, or Al; M = Mg, Mn, Fe(II), Co, Ni, Zn, or Cd) at elevated temperatures. The conditions of synthesis and the lattice constants for these compounds are reported. The stacking sequences of the InO/sub 1.5/, (FeZn)O/sub 2.5/, and ZnO layers for InFeO/sub 3/(ZnO)/sub 10/ and the TmO/sub 1.5/, (AlZn)O/sub 2.5/, and ZnO layers for TmAlO/sub 3/(ZnO)/sub 11/ are presented,more » respectively. The crystal structures of the (RAO/sub 3/)/sub m/(MO)/sub n/ phases R = Sc, In, Y, or lanthanide elements; A = Fe(III), Ga, Cr, or Al; M = divalent cation elements; m and n = integer are classified into four crystal structure types (K/sub 2/NiF/sub 4/, CaFe/sub 2/O/sub 4/, YbFe/sub 2/O/sub 4/, and spinel), based upon the constituent cations R, A, and M.« less

Sorption of the organic cation metoprolol on silica gel from its aqueous solution considering the competition of inorganic cations.

PubMed

Kutzner, Susann; Schaffer, Mario; Börnick, Hilmar; Licha, Tobias; Worch, Eckhard

2014-05-01

Systematic batch experiments with the organic monovalent cation metoprolol as sorbate and the synthetic material silica gel as sorbent were conducted with the aim of characterizing the sorption of organic cations onto charged surfaces. Sorption isotherms for metoprolol (>99% protonated in the tested pH of around 6) in competition with mono- and divalent inorganic cations (Na(+), NH4(+), Ca(2+), and Mg(2+)) were determined in order to assess their influence on cation exchange processes and to identify the role of further sorptive interactions. The obtained sorption isotherms could be described well by an exponential function (Freundlich isotherm model) with consistent exponents (about 0.8). In general, a decreasing sorption of metoprolol with increasing concentrations in inorganic cations was observed. Competing ions of the same valence showed similar effects. A significant sorption affinity of metoprolol with ion type dependent Freundlich coefficients KF,0.77 between 234.42 and 426.58 (L/kg)(0.77) could still be observed even at very high concentrations of competing inorganic cations. Additional column experiments confirm this behavior, which suggests the existence of further relevant interactions beside cation exchange. In subsequent batch experiments, the influence of mixtures with more than one competing ion and the effect of a reduced negative surface charge at a pH below the point of zero charge (pHPZC ≈ 2.5) were also investigated. Finally, the study demonstrates that cation exchange is the most relevant but not the sole mechanism for the sorption of metoprolol on silica gel. Copyright © 2014 Elsevier Ltd. All rights reserved.

DESCRIPTIVE ANALYSIS OF DIVALENT SALTS

PubMed Central

YANG, HEIDI HAI-LING; LAWLESS, HARRY T.

2005-01-01

Many divalent salts (e.g., calcium, iron, zinc), have important nutritional value and are used to fortify food or as dietary supplements. Sensory characterization of some divalent salts in aqueous solutions by untrained judges has been reported in the psychophysical literature, but formal sensory evaluation by trained panels is lacking. To provide this information, a trained descriptive panel evaluated the sensory characteristics of 10 divalent salts including ferrous sulfate, chloride and gluconate; calcium chloride, lactate and glycerophosphate; zinc sulfate and chloride; and magnesium sulfate and chloride. Among the compounds tested, iron compounds were highest in metallic taste; zinc compounds had higher astringency and a glutamate-like sensation; and bitterness was pronounced for magnesium and calcium salts. Bitterness was affected by the anion in ferrous and calcium salts. Results from the trained panelists were largely consistent with the psychophysical literature using untrained judges, but provided a more comprehensive set of oral sensory attributes. PMID:16614749

Micronutrient metal speciation is driven by competitive organic chelation in grassland soils.

NASA Astrophysics Data System (ADS)

Boiteau, R.; Shaw, J. B.; Paša-Tolić, L.; Koppenaal, D.; Jansson, J.

2017-12-01

Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or how they interact and compete for metal binding. Identifying these metallo-organic species within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrix. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) from Kansas Prairie soil. Both plant and fungal chelators were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant iron acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamine, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2-57 pmol / g soil). In contrast, the fungal siderophore ferricrocine bound comparatively more trivalent Fe (9pmol / g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population.

Degradation of S-nitrosocysteine in vascular tissue homogenates: role of divalent ions.

PubMed

Kostka, P; Xu, B; Skiles, E H

1999-04-01

The objective of the study was to inquire about the mechanism(s) involved in the catabolism of S-nitrosothiols by vascular tissue under in vitro conditions. Incubations of S-nitrosocysteine (CYSNO) or S-nitrosoglutathione (GSNO) with homogenates isolated from porcine aortic smooth muscle resulted in only a marginal depletion of S-nitrosothiols from the reaction mixtures, which became statistically significant at relatively high concentrations of homogenate (> or =300 microg of protein/ml). Degradation of CYSNO (but not GSNO) was found to be potentiated several-fold by millimolar concentrations of either Mg2+ or Ca2+ ions. Under such conditions, the degradation of CYSNO was significantly suppressed by the removal of proteins by ultrafiltration (>80% inhibition) and eliminated completely by the alkylation of thiol groups with 1 mM N-ethylmaleimide. The potentiating effect of divalent ions on the degradation of CYSNO was insensitive to 0.1 mM neocuproine (selective chelator of Cu+ ions), although it was enhanced in the presence of 0.1 mM o-phenanthroline (selective chelator of Fe2+ ions). It is concluded that the degradation of CYSNO by tissue homogenate involves the interaction with protein-bound sulfhydryl groups, which is stimulated by Mg2+ or Ca2+ ions. The potentiating effect of o-phenanthroline suggests that the liberation of the nitrosonium moiety in such a process may be accompanied by its transfer to sulfur center(s) by transient formation of dinitrosyl-iron complexes.

Solid-state chelation of metal ions by ethylenediaminetetraacetate intercalated in a layered double hydroxide.

PubMed

Tarasov, Konstantin A; O'Hare, Dermot; Isupov, Vitaly P

2003-03-24

The solid-state chelation of transition metal ions (Co(2+), Ni(2+), and Cu(2+)) from aqueous solutions into the lithium aluminum layered double hydroxide ([LiAl(2)(OH)(6)]Cl x 0.5H(2)O or LDH) which has been pre-intercalated with EDTA (ethylenediaminetetraacetate) ligand has been investigated. The intercalated metal cations form [M(edta)](2)(-) complexes between the LDH layers as indicated by elemental analysis, powder X-ray diffraction, and IR and UV-vis spectroscopies. If metal chloride or nitrate salts are used in the reaction with the LDH then co-intercalation of either the Cl(-) or NO(3)(-) anions is observed. In the case of metal acetate salts the cations intercalate without the accompanying anion. This can be explained by the different intercalation selectivity of the anions in relation to the LDH. In the latter case the introduction of the positive charge into LDH structure was compensated for by the release from the solid of the equivalent quantity of lithium and hydrogen cations. Time-resolved in-situ X-ray diffraction measurements have revealed that the chelation/intercalation reactions proceed very quickly. The rate of the reaction found for nickel acetate depends on concentration as approximately k[Ni(Ac)(2)](3).

Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site.

PubMed Central

Liaw, S. H.; Kuo, I.; Eisenberg, D.

1995-01-01

Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to yield glutamine, ADP, and inorganic phosphate in the presence of divalent cations. Bacterial GS is an enzyme of 12 identical subunits, arranged in two rings of 6, with the active site between each pair of subunits in a ring. In earlier work, we have reported the locations within the funnel-shaped active site of the substrates glutamate and ATP and of the two divalent cations, but the site for ammonia (or ammonium) has remained elusive. Here we report the discovery by X-ray crystallography of a binding site on GS for monovalent cations, Tl+ and Cs+, which is probably the binding site for the substrate ammonium ion. Fourier difference maps show the following. (1) Tl+ and Cs+ bind at essentially the same site, with ligands being Glu 212, Tyr 179, Asp 50', Ser 53' of the adjacent subunit, and the substrate glutamate. From its position adjacent to the substrate glutamate and the cofactor ADP, we propose that this monovalent cation site is the substrate ammonium ion binding site. This proposal is supported by enzyme kinetics. Our kinetic measurements show that Tl+, Cs+, and NH4+ are competitive inhibitors to NH2OH in the gamma-glutamyl transfer reaction. (2) GS is a trimetallic enzyme containing two divalent cation sites (n1, n2) and one monovalent cation site per subunit. These three closely spaced ions are all at the active site: the distance between n1 and n2 is 6 A, between n1 and Tl+ is 4 A, and between n2 and Tl+ is 7 A. Glu 212 and the substrate glutamate are bridging ligands for the n1 ion and Tl+. (3) The presence of a monovalent cation in this site may enhance the structural stability of GS, because of its effect of balancing the negative charges of the substrate glutamate and its ligands and because of strengthening the "side-to-side" intersubunit interaction through the cation-protein bonding. (4) The presence of the cofactor ADP increases the Tl+ binding to GS

Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer

PubMed Central

Street, Steven T. G.; Chin, Donovan N.; Hollingworth, Gregory J.; Berry, Monica

2017-01-01

Abstract Selective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. We demonstrate that an imidazolium‐bearing mannoside‐conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine‐bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI‐38. PMID:28257554

Micronutrient metal speciation is controlled by competitive organic chelation in grassland soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boiteau, Rene M.; Shaw, Jared B.; Pasa-Tolic, Ljiljana

Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or howmore » they interact and compete for metal binding. Identifying these metallo-organic species within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrix. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) from Kansas Prairie soil. Both plant and fungal chelators were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant iron acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamine, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2-57 pmol / g soil). In contrast, the fungal siderophore ferricrocine bound comparatively more trivalent Fe (9pmol / g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population. Even small structural

Existence of efficient divalent metal ion-catalyzed and inefficient divalent metal ion-independent channels in reactions catalyzed by a hammerhead ribozyme

PubMed Central

Zhou, Jing-Min; Zhou, De-Min; Takagi, Yasuomi; Kasai, Yasuhiro; Inoue, Atsushi; Baba, Tadashi; Taira, Kazunari

2002-01-01

The hammerhead ribozyme is generally accepted as a well characterized metalloenzyme. However, the precise nature of the interactions of the RNA with metal ions remains to be fully defined. Examination of metal ion-catalyzed hammerhead reactions at limited concentrations of metal ions is useful for evaluation of the role of metal ions, as demonstrated in this study. At concentrations of Mn2+ ions from 0.3 to 3 mM, addition of the ribozyme to the reaction mixture under single-turnover conditions enhances the reaction with the product reaching a fixed maximum level. Further addition of the ribozyme inhibits the reaction, demonstrating that a certain number of divalent metal ions is required for proper folding and also for catalysis. At extremely high concentrations, monovalent ions, such as Na+ ions, can also serve as cofactors in hammerhead ribozyme-catalyzed reactions. However, the catalytic efficiency of monovalent ions is extremely low and, thus, high concentrations are required. Furthermore, addition of monovalent ions to divalent metal ion-catalyzed hammerhead reactions inhibits the divalent metal ion-catalyzed reactions, suggesting that the more desirable divalent metal ion–ribozyme complexes are converted to less desirable monovalent metal ion–ribozyme complexes via removal of divalent metal ions, which serve as a structural support in the ribozyme complex. Even though two channels appear to exist, namely an efficient divalent metal ion-catalyzed channel and an inefficient monovalent metal ion-catalyzed channel, it is clear that, under physiological conditions, hammerhead ribozymes are metalloenzymes that act via the significantly more efficient divalent metal ion-dependent channel. Moreover, the observed kinetic data are consistent with Lilley’s and DeRose’s two-phase folding model that was based on ground state structure analyses. PMID:12034824

Adsorption of reovirus to clay minerals: effects of cation-exchange capacity, cation saturation, and surface area.

PubMed Central

Lipson, S M; Stotzky, G

1983-01-01

The adsorption of reovirus to clay minerals has been reported by several investigators, but the mechanisms defining this association have been studied only minimally. The purpose of this investigation was to elucidate the mechanisms involved with this interaction. More reovirus type 3 was adsorbed, in both distilled and synthetic estuarine water, by low concentrations of montmorillonite than by comparable concentrations of kaolinite containing a mixed complement of cations on the exchange complex. Adsorption to the clays was essentially immediate and was correlated with the cation-exchange capacity of the clays, indicating that adsorption was primarily to negatively charged sites on the clays. Adsorption was greater with low concentrations of clays in estuarine water than in distilled water, as the higher ionic strength of the estuarine water reduced the electrokinetic potential of both clay and virus particles. The addition of cations (as chloride salts) to distilled water enhanced adsorption, with divalent cations being more effective than monovalent cations and 10(-2) M resulting in more adsorption than 10(-3) M. Potassium ions suppressed reovirus adsorption to montmorillonite, probably by collapsing the clay lattices and preventing the expression of the interlayer-derived cation-exchange capacity. More virus was adsorbed by montmorillonite made homoionic to various mono-, di-, and trivalent cations (except by montmorillonite homoionic to potassium) than by comparable concentrations of kaolinite homoionic to the same cations. The sequence of the amount of adsorption to homoionic montmorillonite was Al greater than Ca greater than Mg greater than Na greater than K; the sequence of adsorption to kaolinite was Na greater than Al greater than Ca greater than Mg greater than K. The constant partition-type adsorption isotherms obtained when the clay concentration was maintained constant and the virus concentration was varied indicated that a fixed proportion of the

Cation dependence, pH tolerance, and dosage requirement of a bioflocculant produced by Bacillus spp. UPMB13: flocculation performance optimization through kaolin assays.

PubMed

Zulkeflee, Zufarzaana; Aris, Ahmad Zaharin; Shamsuddin, Zulkifli H; Yusoff, Mohd Kamil

2012-01-01

A bioflocculant-producing bacterial strain with highly mucoid and ropy colony morphological characteristics identified as Bacillus spp. UPMB13 was found to be a potential bioflocculant-producing bacterium. The effect of cation dependency, pH tolerance and dosage requirement on flocculating ability of the strain was determined by flocculation assay with kaolin as the suspended particle. The flocculating activity was measured as optical density and by flocs formation. A synergistic effect was observed with the addition of monovalent and divalent cations, namely, Na⁺, Ca²⁺, and Mg²⁺, while Fe²⁺ and Al³⁺ produced inhibiting effects on flocculating activity. Divalent cations were conclusively demonstrated as the best cation source to enhance flocculation. The bioflocculant works in a wide pH range, from 4.0 to 8.0 with significantly different performances (P < 0.05), respectively. It best performs at pH 5.0 and pH 6.0 with flocculating performance of above 90%. A much lower or higher pH would inhibit flocculation. Low dosage requirements were needed for both the cation and bioflocculant, with only an input of 50 mL/L for 0.1% (w/v) CaCl₂ and 5 mL/L for culture broth, respectively. These results are comparable to other bioflocculants produced by various microorganisms with higher dosage requirements.

Iminodiacetic acid functionalised organopolymer monoliths: application to the separation of metal cations by capillary high-performance chelation ion chromatography.

PubMed

Moyna, Áine; Connolly, Damian; Nesterenko, Ekaterina; Nesterenko, Pavel N; Paull, Brett

2013-03-01

Lauryl methacrylate-co-ethylene dimethacrylate monoliths were polymerised within fused silica capillaries and subsequently photo-grafted with varying amounts of glycidyl methacrylate (GMA). The grafted monoliths were then further modified with iminodiacetic acid (IDA), resulting in a range of chelating ion-exchange monoliths of increasing capacity. The IDA functional groups were attached via ring opening of the epoxy group on the poly(GMA) structure. Increasing the amount of attached poly(GMA), via photo-grafting with increasing concentrations of GMA, from 15 to 35%, resulted in a proportional and controlled increase in the complexation capacity of the chelating monoliths. Scanning capacitively coupled contactless conductivity detection (sC(4)D) was used to characterise and verify homogenous distribution of the chelating ligand along the length of the capillaries non-invasively. Chelation ion chromatographic separations of selected transition and heavy metals were carried out, with retention factor data proportional to the concentration of grafted poly(GMA). Average peak efficiencies of close to 5,000 N/m were achieved, with the isocratic separation of Na, Mg(II), Mn(II), Co(II), Cd(II) and Zn(II) possible on a 250-mm-long monolith. Multiple monolithic columns produced to the same recipes gave RSD data for retention factors of <15% (averaged for several metal ions). The monolithic chelating ion-exchanger was applied to the separation of alkaline earth and transition metal ions spiked in natural and potable waters.

The influence of various cations on the catalytic properties of clays. [polymerization of alanine adenylate

NASA Technical Reports Server (NTRS)

Paecht-Horowitz, M.

1978-01-01

The polymerization of alanine adenylate in the presence of the sodium form of various clays was studied, and hectorite was found to cause more polymerization than nontronite and montmorillonite (in that order) although the differences were not great. The effect on polymerization of presaturating montmorillonite with different cations was determined. Hectorite, with increased basicity of the interspatial planes, allows polymerization of lysine, which montmorillonite does not. The general trend is that, for the same amino acid, higher degrees of polymerization are obtained when the cation in the octahedral lattice of the clay is divalent rather than trivalent. With the exchangeable cations the order is reversed, for a reason that is explained. The main role of clays in the polymerization mechanism of amino acids is concentration and neutralization of charges.

EDTA Inhibits Biofilm Formation, Extracellular Vesicular Secretion, and Shedding of the Capsular Polysaccharide Glucuronoxylomannan by Cryptococcus neoformans

PubMed Central

Robertson, Emma J.; Wolf, Julie M.

2012-01-01

The fungal pathogen Cryptococcus neoformans can grow as a biofilm on a range of synthetic and prosthetic materials. Cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. Biofilms are generally advantageous to pathogens in vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case of C. neoformans. EDTA can inhibit biofilm formation by several microbes and enhances the susceptibility of biofilms to antifungal drugs. In this study, we evaluated the effect of sublethal concentrations of EDTA on the growth of cryptococcal biofilms. EDTA inhibited biofilm growth by C. neoformans, and the inhibition could be reversed by the addition of magnesium or calcium, implying that the inhibitory effect was by divalent cation starvation. EDTA also reduced the amount of the capsular polysaccharide glucuronoxylomannan shed into the biofilm matrix and decreased vesicular secretion from the cell, thus providing a potential mechanism for the inhibitory effect of this cation-chelating compound. Our data imply that the growth of C. neoformans biofilms requires the presence of divalent metals in the growth medium and suggest that cations are required for the export of materials needed for biofilm formation, possibly including extracellular vesicles. PMID:22941091

N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane (Deofix) - a high-affinity, high-specificity chelator for first transition series metal cations with significant deodorant, antimicrobial, and antioxidant activity.

PubMed

Laden, Karl; Zaklad, Haim; Simhon, Elliot D; Klein, Joseph Y; Cyjon, Rosa L; Winchell, Harry S

2003-01-01

Deofix, N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane, is a high-affinity, high-specificity chelator for first transition series cations such as iron, zinc, manganese, and copper. A 1% solution in 50% ethanol was found to be significantly better at reducing underarm malodor than a solution of 0.3% Triclosan in 50% ethanol. Compared to a 50% alcohol control, Deofix was found to produce a significant reduction in malodor for at least 48 hours. Deofix appears to work by reducing the concentration of first transition series metal ions below the levels needed for microbial cell reproduction and by inhibiting oxidative processes by interfering with catalytic formation of free radicals. Deofix has very low levels of toxicity when measured via a number of screening techniques.

Divalent cations and molecular crowding buffers stabilize G-triplex at physiologically relevant temperatures

PubMed Central

Jiang, Hong-Xin; Cui, Yunxi; Zhao, Ting; Fu, Hai-Wei; Koirala, Deepak; Punnoose, Jibin Abraham; Kong, De-Ming; Mao, Hanbin

2015-01-01

G-triplexes are non-canonical DNA structures formed by G-rich sequences with three G-tracts. Putative G-triplex-forming sequences are expected to be more prevalent than putative G-quadruplex-forming sequences. However, the research on G-triplexes is rare. In this work, the effects of molecular crowding and several physiologically important metal ions on the formation and stability of G-triplexes were examined using a combination of circular dichroism, thermodynamics, optical tweezers and calorimetry techniques. We determined that molecular crowding conditions and cations, such as Na+, K+, Mg2+ and Ca2+, promote the formation of G-triplexes and stabilize these structures. Of these four metal cations, Ca2+ has the strongest stabilizing effect, followed by K+, Mg2+, and Na+ in a decreasing order. The binding of K+ to G-triplexes is accompanied by exothermic heats, and the binding of Ca2+ with G-triplexes is characterized by endothermic heats. G-triplexes formed from two G-triad layers are not stable at physiological temperatures; however, G-triplexes formed from three G-triads exhibit melting temperatures higher than 37°C, especially under the molecular crowding conditions and in the presence of K+ or Ca2+. These observations imply that stable G-triplexes may be formed under physiological conditions. PMID:25787838

Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

PubMed

Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

2008-01-01

Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease. Copyright (c) 2007 John Wiley & Sons, Ltd.

Iron Chelation

MedlinePlus

... fortified cereals and eggs. What is Iron Chelation Therapy? Drugs called iron chelators remove extra iron from ... form that must be dissolved in juice or water and taken (by mouth) once a day. Most ...

Studies on the effect of divalent metal ions on exfoliative toxins from Staphylococcus hyicus: indications of ExhA and ExhB being metalloproteins.

PubMed

Andresen, L O

1999-04-01

The exfoliative toxins ExhA and ExhB produced by Staphylococcus hyicus strains NCTC10350 and 1289D-88, respectively, were investigated with regard to the effect of divalent metal ions on toxin production as measured in indirect enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies. Data were obtained as endpoint titer values and used as semiquantitative measures for the amount of exfoliative toxin detected in culture supernatants. It was shown that the endpoint titers of ExhA in supernatants from cultures of strain NCTC10350 grown in the presence of 0.5 mM CaCl2, Cu(NO3)2 or ZnSO4 were higher compared to titers obtained by growth in medium supplemented with a number of other divalent metal salts. The titer of ExhB as determined in the indirect ELISA was increased by addition of 0.5 mM CoCl2, Cu(NO3)2 or CuSO4 to the growth medium. When ExhA or ExhB, prepared without addition of metal salt to the liquid growth medium, was subsequently incubated with 25 mM of Co2+, Cu2+ or Zn2+, the endpoint titers of the toxins were increased. Dialysis of ExhA and ExhB prepared with Zn2+ and Co2+, respectively, against certain metal chelators, resulted in a reduction of the titer determined in ELISA. Other metal chelators had varied effect in the detection of the toxins in ELISA. It was, however, not possible to restore the recognition of toxins by the monoclonal antibodies by incubation of EDDHA-dialyzed toxin preparations with Co2+, Cu2+ or Zn2+. The results of this study suggest that ExhA and ExhB are metalloproteins.

Synthesis of palladium(0) and -(II) complexes with chelating bis(N-heterocyclic carbene) ligands and their application in semihydrogenation.

PubMed

Sluijter, Soraya N; Warsink, Stefan; Lutz, Martin; Elsevier, Cornelis J

2013-05-28

A transmetallation route, using silver(I) precursors, to several zero- and di-valent palladium complexes with chelating bis(N-heterocyclic carbene) ligands bearing various N-substituents has been established. The resulting complexes have been characterized by NMR and mass spectroscopy. In addition, the structure of a representative compound, [Pd(0)(bis-(Mes)NHC)(η(2)-ma)] (3a), was confirmed by X-ray crystal structure determination. In contrast to the transfer semihydrogenation, in which only low activity was observed, complex 3a showed activity (TOF = 49 mol(sub) mol(cat)(-1) h(-1)) and selectivity comparable to its monodentate counterparts in the semihydrogenation of 1-phenyl-1-propyne with molecular hydrogen.

Liposome encapsulation of chelating agents

DOEpatents

Rahman, Yueh Erh

1976-01-13

A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

Transport of K+ and other cations across phospholipid membranes by nonesterified fatty acids.

PubMed

Sharpe, M A; Cooper, C E; Wrigglesworth, J M

1994-07-01

The rate of change of internal pH and transmembrane potential has been monitored in liposomes following the external addition of various cation salts. Oleic acid increases the transmembrane movement of H+ following the imposition of a K+ gradient. An initial fast change in internal pH is seen followed by a slower rate of alkalinization. High concentrations of the fatty acid enhance the rate comparable to that seen in the presence of nigericin in contrast to the effect of FCCP (carbonyl cyanide p-(tri-fluoromethoxy)phenyl hydrazone) which saturates at an intermediate value. The ability of nonesterified fatty acids to catalyze the movement of cations across the liposome membrane increases with the degree of unsaturation and decreases with increasing chain length. Li and Na salts cause a similar initial fast pH change but have less effect on the subsequent slower rate. Similarly, the main effect of divalent cation salts is on the initial fast change. The membrane potential can enhance or inhibit cation transport depending on its polarity with respect to the cation gradient. It is concluded that nonesterified fatty acids have the capability to complex with, and transport, a variety of cations across phospholipid bilayers. However, they do not act simply as proton/cation exchangers analogous to nigericin nor as protonophores analogous to FCCP. The full cycle of ionophoric action involves a combination of both functions.

Micronutrient metal speciation is controlled by competitive organic chelation in grassland soils

DOE PAGES

Boiteau, Rene M.; Shaw, Jared B.; Pasa-Tolic, Ljiljana; ...

2018-03-08

Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or howmore » they interact and compete for metal binding. Identifying these metallophores within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrices. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) of soils from native tallgrass prairies in Kansas and Iowa. Both plant and fungal metallophores were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant Fe acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamines, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2–90 pmol/g soil). In contrast, the fungal siderophore ferricrocin was specific for trivalent Fe (7–32 pmol/g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population. In

Micronutrient metal speciation is controlled by competitive organic chelation in grassland soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boiteau, Rene M.; Shaw, Jared B.; Pasa-Tolic, Ljiljana

Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or howmore » they interact and compete for metal binding. Identifying these metallophores within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrices. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) of soils from native tallgrass prairies in Kansas and Iowa. Both plant and fungal metallophores were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant Fe acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamines, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2–90 pmol/g soil). In contrast, the fungal siderophore ferricrocin was specific for trivalent Fe (7–32 pmol/g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population. In

Regulation of Cation Balance in Saccharomyces cerevisiae

PubMed Central

Cyert, Martha S.; Philpott, Caroline C.

2013-01-01

All living organisms require nutrient minerals for growth and have developed mechanisms to acquire, utilize, and store nutrient minerals effectively. In the aqueous cellular environment, these elements exist as charged ions that, together with protons and hydroxide ions, facilitate biochemical reactions and establish the electrochemical gradients across membranes that drive cellular processes such as transport and ATP synthesis. Metal ions serve as essential enzyme cofactors and perform both structural and signaling roles within cells. However, because these ions can also be toxic, cells have developed sophisticated homeostatic mechanisms to regulate their levels and avoid toxicity. Studies in Saccharomyces cerevisiae have characterized many of the gene products and processes responsible for acquiring, utilizing, storing, and regulating levels of these ions. Findings in this model organism have often allowed the corresponding machinery in humans to be identified and have provided insights into diseases that result from defects in ion homeostasis. This review summarizes our current understanding of how cation balance is achieved and modulated in baker’s yeast. Control of intracellular pH is discussed, as well as uptake, storage, and efflux mechanisms for the alkali metal cations, Na+ and K+, the divalent cations, Ca2+ and Mg2+, and the trace metal ions, Fe2+, Zn2+, Cu2+, and Mn2+. Signal transduction pathways that are regulated by pH and Ca2+ are reviewed, as well as the mechanisms that allow cells to maintain appropriate intracellular cation concentrations when challenged by extreme conditions, i.e., either limited availability or toxic levels in the environment. PMID:23463800

Cation Binding to Xanthorhodopsin: Electron Paramagnetic Resonance and Magnetic Studies.

PubMed

Smolensky Koganov, Elena; Leitus, Gregory; Rozin, Rinat; Weiner, Lev; Friedman, Noga; Sheves, Mordechai

2017-05-04

Xanthorhodopsin (xR) is a member of the retinal protein family and acts as a proton pump in the cell membranes of the extremely halophilic eubacterium Salinibacter ruber. In addition to the retinal chromophore, xR contains a carotenoid, which acts as a light-harvesting antenna as it transfers 40% of the quanta it absorbs to the retinal. Our previous studies have shown that the CD and absorption spectra of xR are dramatically affected due to the protonation of two different residues. It is still unclear whether xR can bind cations. Electron paramagnetic resonance (EPR) spectroscopy used in the present study revealed that xR can bind divalent cations, such as Mn 2+ and Ca 2+ , to deionized xR (DI-xR). We also demonstrate that xR can bind 1 equiv of Mn 2+ to a high-affinity binding site followed by binding of ∼40 equiv in cooperative manner and ∼100 equiv of Mn 2+ that are weakly bound. SQUID magnetic studies suggest that the high cooperative binding of Mn 2+ cations to xR is due to the formation of Mn 2+ clusters. Our data demonstrate that Ca 2+ cations bind to DI-xR with a lower affinity than Mn 2+ , supporting the assumption that binding of Mn 2+ occurs through cluster formation, because Ca 2+ cations cannot form clusters in contrast to Mn 2+ .

Chelation in Metal Intoxication

PubMed Central

Flora, Swaran J.S.; Pachauri, Vidhu

2010-01-01

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications. PMID:20717537

How Cations Can Assist DNase I in DNA Binding and Hydrolysis

PubMed Central

Guéroult, Marc; Picot, Daniel; Abi-Ghanem, Joséphine; Hartmann, Brigitte; Baaden, Marc

2010-01-01

DNase I requires Ca2+ and Mg2+ for hydrolyzing double-stranded DNA. However, the number and the location of DNase I ion-binding sites remain unclear, as well as the role of these counter-ions. Using molecular dynamics simulations, we show that bovine pancreatic (bp) DNase I contains four ion-binding pockets. Two of them strongly bind Ca2+ while the other two sites coordinate Mg2+. These theoretical results are strongly supported by revisiting crystallographic structures that contain bpDNase I. One Ca2+ stabilizes the functional DNase I structure. The presence of Mg2+ in close vicinity to the catalytic pocket of bpDNase I reinforces the idea of a cation-assisted hydrolytic mechanism. Importantly, Poisson-Boltzmann-type electrostatic potential calculations demonstrate that the divalent cations collectively control the electrostatic fit between bpDNase I and DNA. These results improve our understanding of the essential role of cations in the biological function of bpDNase I. The high degree of conservation of the amino acids involved in the identified cation-binding sites across DNase I and DNase I-like proteins from various species suggests that our findings generally apply to all DNase I-DNA interactions. PMID:21124947

Phenolic cation exchange resin material for recovery of cesium and strontium

DOEpatents

Ebra, Martha A.; Wallace, Richard M.

1983-01-01

A phenolic cation exchange resin with a chelating group has been prepared by reacting resorcinol with iminodiacetic acid in the presence of formaldehyde at a molar ratio of about 1:1:6. The material is highly selective for the simultaneous recovery of both cesium and strontium from aqueous alkaline solutions, such as, aqueous alkaline nuclear waste solutions. The organic resins are condensation polymers of resorcinol and formaldehyde with attached chelating groups. The column performance of the resins compares favorably with that of commercially available resins for either cesium or strontium removal. By combining Cs.sup.+ and Sr.sup.2+ removal in the same bed, the resins allow significant reduction of the size and complexity of facilities for processing nuclear waste.

Macrocyclic bifunctional chelating agents

DOEpatents

Meares, Claude F.; DeNardo, Sally J.; Cole, William C.; Mol, Min K.

1987-01-01

A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.

Cation-Inhibited Transport of Graphene Oxide Nanomaterials in Saturated Porous Media: The Hofmeister Effects.

PubMed

Xia, Tianjiao; Qi, Yu; Liu, Jing; Qi, Zhichong; Chen, Wei; Wiesner, Mark R

2017-01-17

Transport of negatively charged nanoparticles in porous media is largely affected by cations. To date, little is known about how cations of the same valence may affect nanoparticle transport differently. We observed that the effects of cations on the transport of graphene oxide (GO) and sulfide-reduced GO (RGO) in saturated quartz sand obeyed the Hofmeister series; that is, transport-inhibition effects of alkali metal ions followed the order of Na + < K + < Cs + , and those of alkaline earth metal ions followed the order of Mg 2+ < Ca 2+ < Ba 2+ . With batch adsorption experiments and microscopic data, we verified that cations having large ionic radii (and thus being weakly hydrated) interacted with quartz sand and GO and RGO more strongly than did cations of small ionic radii. In particular, the monovalent Cs + and divalent Ca 2+ and Ba 2+ , which can form inner-sphere complexes, resulted in very significant deposition of GO and RGO via cation bridging between quartz sand and GO and RGO, and possibly via enhanced straining, due to the enhanced aggregation of GO and RGO from cation bridging. The existence of the Hofmeister effects was further corroborated with the interesting observation that cation bridging was more significant for RGO, which contained greater amounts of carboxyl and phenolic groups (i.e., metal-complexing moieties) than did GO. The findings further demonstrate that transport of nanoparticles is controlled by the complex interplay between nanoparticle surface functionalities and solution chemistry constituents.

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayaaltı, Zeliha, E-mail: kayaalti@ankara.edu.tr; Akyüzlü, Dilek Kaya; Söylemezoğlu, Tülin

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metalmore » trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. �

On the real performance of cation exchange resins in wastewater treatment under conditions of cation competition: the case of heavy metal pollution.

PubMed

Prelot, Benedicte; Ayed, Imen; Marchandeau, Franck; Zajac, Jerzy

2014-01-01

Sorption performance of cation-exchange resins Amberlite® IRN77 and Amberlite™ IRN9652 toward Cs(I) and Sr(II) has been tested in single-component aqueous solutions and simulated waste effluents containing other monovalent (Effluent 1) or divalent (Effluent 2) metal cations, as well as nitrate, borate, or carbonate anions. The individual sorption isotherms of each main component were measured by the solution depletion method. The differential molar enthalpy changes accompanying the ion-exchange between Cs+ or Sr2+ ions and protons at the resin surface from single-component nitrate solutions were measured by isothermal titration calorimetry and they showed a higher specificity of the two resins toward cesium. Compared to the retention limits of both resins under such idealized conditions, an important depression in the maximum adsorption capacity toward each main component was observed in multication systems. The overall effect of ion exchange process appeared to be an unpredictable outcome of the individual sorption capacities of the two resins toward various cations as a function of the cation charge, size, and concentration. The cesium retention capacity of the resins was diminished to about 25% of the "ideal" value in Effluent 1 and 50% in Effluent 2; a further decrease to about 15% was observed upon concomitant strontium addition. The uptake of strontium by the resins was found to be less sensitive to the addition of other metal components: the greatest decrease in the amount adsorbed was 60% of the ideal value in the two effluents for Amberlite® IRN77 and 75% for Amberlite™ IRN9652. It was therefore demonstrated that any performance tests carried out under idealized conditions should be exploited with much caution to predict the real performance of cation exchange resins under conditions of cation competition.

Increasing Mechanical Strength of Gelatin Hydrogels by Divalent Metal Ion Removal

PubMed Central

Xing, Qi; Yates, Keegan; Vogt, Caleb; Qian, Zichen; Frost, Megan C.; Zhao, Feng

2014-01-01

The usage of gelatin hydrogel is limited due to its instability and poor mechanical properties, especially under physiological conditions. Divalent metal ions present in gelatin such as Ca2+ and Fe2+ play important roles in the gelatin molecule interactions. The objective of this study was to determine the impact of divalent ion removal on the stability and mechanical properties of gelatin gels with and without chemical crosslinking. The gelatin solution was purified by Chelex resin to replace divalent metal ions with sodium ions. The gel was then chemically crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Results showed that the removal of divalent metal ions significantly impacted the formation of the gelatin network. The purified gelatin hydrogels had less interactions between gelatin molecules and form larger-pore network which enabled EDC to penetrate and crosslink the gel more efficiently. The crosslinked purified gels showed small swelling ratio, higher crosslinking density and dramatically increased storage and loss moduli. The removal of divalent ions is a simple yet effective method that can significantly improve the stability and strength of gelatin hydrogels. The in vitro cell culture demonstrated that the purified gelatin maintained its ability to support cell attachment and spreading. PMID:24736500

Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

NASA Astrophysics Data System (ADS)

Shi, Sixiang; Fliss, Brianne C.; Gu, Zi; Zhu, Yian; Hong, Hao; Valdovinos, Hector F.; Hernandez, Reinier; Goel, Shreya; Luo, Haiming; Chen, Feng; Barnhart, Todd E.; Nickles, Robert J.; Xu, Zhi Ping; Cai, Weibo

2015-11-01

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

Effects of pH and cation adsorption on colloidal stability of graphene oxide in aquatic environments

NASA Astrophysics Data System (ADS)

Terracciano, Amalia

The presented doctoral research aims to improve the current understanding of the chemistry of Graphene Oxide Nanoparticles (GONPs) in common water systems. The widespread demand and future use of this nanomaterial in a broad range of different applications (i.e. biomedical, electronic, environmental) will certainly lead to its release in the environment with consequent exposure of ecosystems to graphene oxide (GO) toxicity. The described scenario demand a careful investigation and deep understanding of the environmental behavior and fate of GONPs, especially in water systems. Therefore this study focused on the investigation the effects of pH some of the most common water electrolytes (monovalent and divalent) and on GO colloidal stability. The interactions between the selected ions and the GO functional groups was also studied. The mobility of GO in porous media was first studied through filtrations tests that determine influence of ionic strength (IS) and solution composition on GO mobility. The GONPs showed to be completely retained in the porous media in presence of 3.5 mM of CaCl2 and in tap water while no retention was found for 10 mM of NaCl solution. The results indicated significant impact of divalent cations on the mobility of GO. Serial experiments were performed to quantify the adsorption of several cations (Na+, Ca2+ and Ba2+) on GO. The divalent cations showed to be strongly adsorbed on the GO surface with increasing pH and cation concentrations, while no significant sodium adsorption was detected. Raman spectroscopy and XPS analysis also showed strong differences in the typical spectra of GO, before and after adsorption of Ca2+ and Ba2+ which suggest chemical bond formation with the GO functional groups. The aggregation regime and the colloidal stability of the GO suspension in presence of selected electrolytes (Na+, Mg2+, Ca2+ and Ba2+) as function of pH was also extensively studied. The zeta potential, which is index of the stability of a colloidal

Influence of pH and Metal Cations on Aggregative Growth of Non-Slime-forming Strains of Zoogloea ramigera

PubMed Central

Angelbeck, Donald I.; Kirsch, Edwin J.

1969-01-01

Aggregative growth of non-slime-forming strains of Zoogloea ramigera was induced by growing the organisms at a depressed pH. Calcium and magnesium ion was found to reverse aggregative growth of the organisms. Conversely, aggregation was stimulated when the available inorganic cation concentration of the growth medium was lowered by the use of a chelating agent. The aggregative effects of pH depression or cation depletion and the dispersal effects of cation supplementation were observed only during cellular growth. The data suggest that aggregate formation of non-slime-forming strains of Z. ramigera may be related to the calcium or magnesium metabolism of the organisms, or both. Images PMID:4976326

Cations Stiffen Actin Filaments by Adhering a Key Structural Element to Adjacent Subunits

PubMed Central

2016-01-01

Ions regulate the assembly and mechanical properties of actin filaments. Recent work using structural bioinformatics and site-specific mutagenesis favors the existence of two discrete and specific divalent cation binding sites on actin filaments, positioned in the long axis between actin subunits. Cation binding at one site drives polymerization, while the other modulates filament stiffness and plays a role in filament severing by the regulatory protein, cofilin. Existing structural methods have not been able to resolve filament-associated cations, and so in this work we turn to molecular dynamics simulations to suggest a candidate binding pocket geometry for each site and to elucidate the mechanism by which occupancy of the “stiffness site” affects filament mechanical properties. Incorporating a magnesium ion in the “polymerization site” does not seem to require any large-scale change to an actin subunit’s conformation. Binding of a magnesium ion in the “stiffness site” adheres the actin DNase-binding loop (D-loop) to its long-axis neighbor, which increases the filament torsional stiffness and bending persistence length. Our analysis shows that bound D-loops occupy a smaller region of accessible conformational space. Cation occupancy buries key conserved residues of the D-loop, restricting accessibility to regulatory proteins and enzymes that target these amino acids. PMID:27146246

Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative.

PubMed

Roy, Mithun; Chakravarthi, Balabhadrapatruni V S K; Jayabaskaran, Chelliah; Karande, Anjali A; Chakravarty, Akhil R

2011-05-14

A new water soluble cationic imidazopyridine species, viz. (1E)-1-((pyridin-2-yl)methyleneamino)-3-(3-(pyridin-2-yl)imidazo[1,5-a]pyridin-2(3H)-yl)propan-2-ol (1), as a metal chelator is prepared as its PF(6) salt and characterized. Compound 1 shows fluorescence at 438 nm on excitation at 342 nm in Tris-HCl buffer giving a fluorescence quantum yield (φ) of 0.105 and a life-time of 5.4 ns. Compound 1, as an avid DNA minor groove binder, shows pUC19 DNA cleavage activity in UV-A light of 365 nm forming singlet oxygen species in a type-II pathway. The photonuclease potential of 1 gets enhanced in the presence of Fe(2+), Cu(2+) or Zn(2+). Compound 1 itself displays anticancer activity in HeLa, HepG2 and Jurkat cells with an enhancement on addition of the metal ions. Photodynamic effect of 1 at 365 nm also gets enhanced in the presence of Fe(2+) and Zn(2+). Fluorescence-based cell cycle analysis shows a significant dead cell population in the sub-G1 phase of the cell cycle suggesting apoptosis via ROS generation. A significant change in the nuclear morphology is observed from Hoechst 33258 and an acridine orange/ethidium bromide (AO/EB) dual nuclear staining suggesting apoptosis in cells when treated with 1 alone or in the presence of the metal ions. Apoptosis is found to be caspase-dependent. Fluorescence imaging to monitor the distribution of 1 in cells shows that 1 in the presence of metal ions accumulates predominantly in the cytoplasm. Enhanced uptake of 1 into the cells within 12 h is observed in the presence of Fe(2+) and Zn(2+).

Phenolic cation-exchange resin material for recovery of cesium and strontium. [Patent application

DOEpatents

Ebra, M.A.; Wallace, R.M.

1982-05-05

A phenolic cation exchange resin with a chelating group has been prepared by reacting resorcinol with iminodiacetic acid in the presence of formaldehyde at a molar ratio of about 1:1:6. The material is highly selective for the simultaneous recovery of both cesium and strontium from aqueous alkaline solutions, such as, aqueous alkaline nuclear wate solutions. The organic resins are condensation polymers of resorcinol and formaldehyde with attached chelating groups. The column performance of the resins compares favorably with that of commercially available resins for either cesium or strontium removal. By combining Cs/sup +/ and Sr/sup 2 +/ removal in the same bed, the resins allow significant reduction of the size and complexity of facilities for processing nuclear waste.

Cation distribution and optical properties of Cr-doped MgGa2O4 nanocrystals

NASA Astrophysics Data System (ADS)

Duan, Xiulan; Liu, Jian; Wang, Xinqiang; Jiang, Huaidong

2014-11-01

The distribution of cations in the spinel-type MgCr2yGa2-2yO4 (y = 0-0.6) nanocrystals and their optical properties as a function of annealing temperature and chromium content were investigated by using X-ray photoelectron spectroscopy (XPS) in combination with absorption spectroscopy. The cations in MgCr2yGa2-2yO4 nanocrystals are disorderly distributed with mixing of divalent and trivalent cations occupying the tetrahedral and octahedral sites. With the increase of annealing temperature, the inversion parameter (the fraction of Mg2+ ions in octahedral sites) decreases, which has the same varying tendency with the proportion of tetrahedral Ga3+ or Cr3+ ions. The inversion parameter increases with increasing Cr3+ concentration. The absorption spectra indicate that Cr3+ ions are located in the octahedral sites as well as in the tetrahedral sites. The fraction of tetrahedral Cr3+ decreases with Cr-enrichment. The optical absorption properties of Cr-doped MgGa2O4 nanocrystals may be tuned by varying the preparation temperature or Cr concentration.

The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

PubMed Central

Klinger, M.; Hermann, B.; Sachse, S.; Nietzsche, S.; Makarewicz, O.; Keller, P. M.; Pfister, W.; Straube, E.

2012-01-01

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity. PMID:22926564

Interaction of Aluminum with PHFτ in Alzheimer’s Disease Neurofibrillary Degeneration Evidenced by Desferrioxamine-Assisted Chelating Autoclave Method

PubMed Central

Murayama, Harunobu; Shin, Ryong-Woon; Higuchi, Jun; Shibuya, Satoshi; Muramoto, Tamaki; Kitamoto, Tetsuyuki

1999-01-01

To demonstrate that aluminum III (Al) interacts with PHFτ in neurofibrillary degeneration (NFD) of Alzheimer’s disease (AD) brain, we developed a “chelating autoclave method” that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti-τ antibodies, significantly enhanced the PHFτ immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHFτ are partially masked by Al binding. Incubation of AD sections with AlCl3 before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti-τ antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHFτ. Al binding was further documented for electrophoretically-resolved PHFτ on immunoblots, indicating direct Al binding to PHFτ. In vitro aggregation by AlCl3 was observed for PHFτ but was lost on dephosphorylation of PHFτ. Taken together, phosphorylation-dependent and direct PHFτ-Al interaction occurs in the NFD of the AD brain. PMID:10487845

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

PubMed Central

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Natural chelating agents for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1985-06-11

This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

PubMed

Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert

2014-10-01

Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Self-Incompatibility in Papaver rhoeas Activates Nonspecific Cation Conductance Permeable to Ca2+ and K+[W

PubMed Central

Wu, Juyou; Wang, Su; Gu, Yuchun; Zhang, Shaoling; Publicover, Stephen J.; Franklin-Tong, Vernonica E.

2011-01-01

Cellular responses rely on signaling. In plant cells, cytosolic free calcium is a major second messenger, and ion channels play a key role in mediating physiological responses. Self-incompatibility (SI) is an important genetically controlled mechanism to prevent self-fertilization. It uses interaction of matching S-determinants from the pistil and pollen to allow “self” recognition, which triggers rejection of incompatible pollen. In Papaver rhoeas, the S-determinants are PrsS and PrpS. PrsS is a small novel cysteine-rich protein; PrpS is a small novel transmembrane protein. Interaction of PrsS with incompatible pollen stimulates S-specific increases in cytosolic free calcium and alterations in the actin cytoskeleton, resulting in programmed cell death in incompatible but not compatible pollen. Here, we have used whole-cell patch clamping of pollen protoplasts to show that PrsS stimulates SI-specific activation of pollen grain plasma membrane conductance in incompatible but not compatible pollen grain protoplasts. The SI-activated conductance does not require voltage activation, but it is voltage sensitive. It is permeable to divalent cations (Ba2+ ≥ Ca2+ > Mg2+) and the monovalent ions K+ and NH4+ and is enhanced at voltages negative to −100 mV. The Ca2+ conductance is blocked by La3+ but not by verapamil; the K+ currents are tetraethylammonium chloride insensitive and do not require Ca2+. We propose that the SI-stimulated conductance may represent a nonspecific cation channel or possibly two conductances, permeable to monovalent and divalent cations. Our data provide insights into signal-response coupling involving a biologically important response. PrsS provides a rare example of a protein triggering alterations in ion channel activity. PMID:21177472

Influence of liposome charge on the association of liposomes with Kupffer cells in vitro. Effects of divalent cations and competition with latex particles.

PubMed

Dijkstra, J; van Galen, M; Scherphof, G

1985-03-14

We studied the interaction of large unilamellar liposomes carrying different surface charges with rat Kupffer cells in maintenance culture. In addition to 14C-labeled phosphatidylcholine, all liposome preparations contained either 3H-labeled inulin or 125I-labeled bovine serum albumin as a non-degradable or a degradable aqueous space marker, respectively. With vesicles carrying no net charge, intracellular processing of internalized liposomes caused nearly complete release of protein label into the medium in acid-soluble form, while phospholipid label was predominantly retained by the cells, only about one third being released. The presence of the lysosomotropic agent, ammonia, inhibited the release of both labels from the cells. At 4 degrees C, the association and degradation of the vesicles were strongly reduced. These results are very similar to what we reported on negatively charged liposomes (Dijkstra, J., Van Galen, W.J.M., Hulstaert, C.E., Kalicharan, D., Roerdink, F.H. and Scherphof, G.L. (1984) Exp. Cell Res. 150, 161-176). The interaction of both types of vesicles apparently proceeds by adsorption to the cell surface followed by virtually complete internalization by endocytosis. Similar experiments with positively charged vesicles indicated that only about half of the liposomes were taken up by the endocytic route, the other half remaining adsorbed to the cell-surface. Attachment of all types of liposomes to the cells was strongly dependent on the presence of divalent cations; Ca2+ appeared to be required for optimal binding. Neutral liposomes only slightly competed with the uptake of negatively charged vesicles, both at 4 degrees and 37 degrees C, whereas negatively charged small unilamellar vesicles and negatively charged latex beads were found to compete very effectively with the large negatively charged liposomes. Neutral vesicles competed effectively for uptake with positively charged ones. These results suggest that neutral and positively charged

Nanoprobing of the effect of Cu2+ cations on misfolding, interaction and aggregation of amyloid β peptide

PubMed Central

Lv, Zhengjian; Condron, Margaret M.; Teplow, David B.; Lyubchenko, Yuri L.

2012-01-01

Misfolding and aggregation of the amyloid β-protein (Aβ) are hallmarks of Alzheimer’s disease. Both processes are dependent on the environmental conditions, including the presence of divalent cations, such as Cu2+. Cu2+ cations regulate early stages of Aβ aggregation, but the molecular mechanism of Cu2+ regulation is unknown. In this study we applied single molecule AFM force spectroscopy to elucidate the role of Cu2+ cations on interpeptide interactions. By immobilizing one of two interacting Aβ42 molecules on a mica surface and tethering the counterpart molecule onto the tip, we were able to probe the interpeptide interactions in the presence and absence of Cu2+ cations at pH 7.4, 6.8, 6.0, 5.0, and 4.0. The results show that the presence of Cu2+ cations change the pattern of Aβ interactions for pH values between pH 7.4 and pH 5.0. Under these conditions, Cu2+ cations induce Aβ42 peptide structural changes resulting in N–termini interactions within the dimers. Cu2+ cations also stabilize the dimers. No effects of Cu2+ cations on Aβ–Aβ interactions were observed at pH 4.0, suggesting that peptide protonation changes the peptide-cation interaction. The effect of Cu2+ cations on later stages of Aβ aggregation was studied by AFM topographic images. The results demonstrate that substoichiometric Cu2+ cations accelerate the formation of fibrils at pH 7.4 and 5.0, whereas no effect of Cu2+ cations was observed at pH 4.0. Taken together, the combined AFM force spectroscopy and imaging analyses demonstrate that Cu2+ cations promote both the initial and the elongation stages of Aβ aggregation, but protein protonation diminishes the effect of Cu2+. PMID:23143330

Iron chelating active packaging: Influence of competing ions and pH value on effectiveness of soluble and immobilized hydroxamate chelators.

PubMed

Ogiwara, Yoshiko; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2016-04-01

Many packaged foods utilize synthetic chelators (e.g. ethylenediaminetetraacetic acid, EDTA) to inhibit iron-promoted oxidation or microbial growth which would result in quality loss. To address consumer demands for all natural products, we have previously developed a non-migratory iron chelating active packaging material by covalent immobilization of polyhydroxamate and demonstrated its efficacy in delaying lipid oxidation. Herein, we demonstrate the ability of this hydroxamate-functionalized iron chelating active packaging to retain iron chelating capacity; even in the presence of competing ions common in food. Both immobilized and soluble hydroxamate chelators retained iron chelating capacity in the presence of calcium, magnesium, and sodium competing ions, although at pH 5.0 the presence of calcium reduced immobilized hydroxamate iron chelation. A strong correlation was found between colorimetric and mass spectral analysis of iron chelation by the chelating packaging material. Such chelating active packaging may support reducing additive use in product formulations, while retaining quality and shelf life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cleaving Off Uranyl Oxygens through Chelation: A Mechanistic Study in the Gas Phase

DOE PAGES

Abergel, Rebecca J.; de Jong, Wibe A.; Deblonde, Gauthier J. -P.; ...

2017-10-11

Recent efforts to activate the strong uranium-oxygen bonds in the dioxo uranyl cation have been limited to single oxo-group activation through either uranyl reduction and functionalization in solution, or by collision induced dissociation (CID) in the gas-phase, using mass spectrometry (MS). Here, we report and investigate the surprising double activation of uranyl by an organic ligand, 3,4,3-LI(CAM), leading to the formation of a formal U 6+ chelate in the gas-phase. The cleavage of both uranyl oxo bonds was experimentally evidence d by CID, using deuterium and 18O isotopic substitutions, and by infrared multiple photon dissociation (IRMPD) spectroscopy. Density functional theorymore » (DFT) computations predict that the overall reaction requires only 132 kJ/mol, with the first oxygen activation entailing about 107 kJ/mol. Here, combined with analysis of similar, but unreactive ligands, these results shed light on the chelation-driven mechanism of uranyl oxo bond cleavage, demonstrating its dependence on the presence of ligand hydroxyl protons available for direct interactions with the uranyl oxygens.« less

Reversible Calcium-Regulated Stopcocks in Legume Sieve TubesW⃞

PubMed Central

Knoblauch, Michael; Peters, Winfried S.; Ehlers, Katrin; van Bel, Aart J. E.

2001-01-01

Sieve tubes of legumes (Fabaceae) contain characteristic P-protein crystalloids with controversial function. We studied their behavior by conventional light, electron, and confocal laser scanning microscopy. In situ, crystalloids are able to undergo rapid (<1 sec) and reversible conversions from the condensed resting state into a dispersed state, in which they occlude the sieve tubes. Crystalloid dispersal is triggered by plasma membrane leakage induced by mechanical injury or permeabilizing substances. Similarly, abrupt turgor changes imposed by osmotic shock cause crystalloid dispersal. Because chelators generally prevent the response, divalent cations appear to be the decisive factor in crystalloid expansion. Cycling between dispersal and condensation can be induced in opened cells by repetitive exchange of bathing media containing either Ca2+ or chelators. Sr2+ and Ba2+, but not Mg2+, are equally active. In conclusion, the fabacean P-protein crystalloids represent a novel class of mechanically active proteinaceous structures, which provide an efficient mechanism with which to control sieve tube conductivity. PMID:11340193

Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels

PubMed Central

Krzesiak, A.; Lipskaia, L.; Adnot, S.; Hajjar, R.J.; Cognard, C.

2016-01-01

In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca2+ influx due to dysregulation of sarcolemmal channels such as stretch-activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. At rest, our results suggest that activation of TRPV2 channels participates to a constitutive basal cation entry in mdx cardiomyocytes.Using microcarbon fibres technique, an axial stretchwas applied to mimic effects of physiological conditions of ventricular filling and study on cation influx bythe Mn2+-quenching techniquedemonstrated a high stretch-dependentcationic influx in dystrophic cells, partially due to SACs. Involvement of TRPs channels in this excessive Ca2+ influx has been investigated using specific modulators and demonstratedboth sarcolemmal localization and an abnormal activity of TRPV2 channels. In conclusion, TRPV2 channels are demonstrated here to play a key role in cation influx and dysregulation in dystrophin deficient cardiomyocytes, enhanced in stretching conditions. PMID:26803937

Natural chelates for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1983-08-25

This invention relates to the method and resulting chelates of desorbing a radionuclide selected from thorium, uranium, and plutonium containing cultures in a bioavailable form involving pseudomonas or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 1000 to 1000 and also forms chelates with uranium of molecular weight in the area of 100 to 1000 and 1000 to 2000.

Persister cells, the biofilm matrix and tolerance to metal cations in biofilm and planktonic Pseudomonas aeruginosa.

PubMed

Harrison, Joe J; Turner, Raymond J; Ceri, Howard

2005-07-01

In this study, we examined Pseudomonas aeruginosa ATCC 27853 biofilm and planktonic cell susceptibility to metal cations. The minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC) required to eradicate 100% of the planktonic population (MBC 100), and the minimum biofilm eradication concentration (MBEC) were determined using the MBEC trade mark-high throughput assay. Six metals - Co(2+), Ni(2+), Cu(2+), Zn(2+), Al(3+) and Pb(2+)- were each tested at 2, 4, 6, 8, 10 and 27 h of exposure to biofilm and planktonic cultures grown in rich or minimal media. With 2 or 4 h of exposure, biofilms were approximately 2-25 times more tolerant to killing by metal cations than the corresponding planktonic cultures. However, by 27 h of exposure, biofilm and planktonic bacteria were eradicated at approximately the same concentration in every instance. Viable cell counts evaluated at 2 and 27 h of exposure revealed that at high concentrations, most of the metals assayed had killed greater than 99.9% of biofilm and planktonic cell populations. The surviving cells were propogated in vitro and gave rise to biofilm and planktonic cultures with normal sensitivity to metals. Further, retention of copper by the biofilm matrix was investigated using the chelator sodium diethlydithiocarbamate. Formation of visible brown metal-chelates in biofilms treated with Cu(2+) suggests that the biofilm matrix may coordinate and sequester metal cations from the aqueous surroundings. Overall, our data suggest that both metal sequestration in the biofilm matrix and the presence of a small population of 'persister' cells may be contributing factors in the time-dependent tolerance of both planktonic cells and biofilms to high concentrations of metal cations.

Development of a stable cation modified graphene oxide membrane for water treatment

NASA Astrophysics Data System (ADS)

Yu, Wenzheng; (Yet Yu, Tong; Graham, Nigel

2017-12-01

Membranes prepared from layers of graphene oxide (GO) offer substantial advantages over conventional materials for water treatment (e.g. greater flux), but the stability of GO membranes in water has not been achieved until now. In this study the behavior of GO membranes prepared with different quantities and species of cations has been investigated to establish the feasibility of their application in water treatment. A range of cation-modified GO membranes were prepared and exposed to aqueous solutions containing specific chemical constituents. In pure water, unmodified and Na-modified GO membranes were highly unstable, while GO membranes modified with multivalent cations were stable provided there were sufficient quantities of cations present; their relative capability to achieve GO stability was as follows: Al3+  >  Ca2+  >  Mg2+  >  Na+. It is believed that the mechanism of cross-linking, and membrane stability, is via metal-carboxylate chelates and cation-graphite surface interactions (cation-π interaction), and that the latter appears to increase with increasing cation valency. The instability of cation (Ca or Al)-modified GO membranes by NaCl solutions during permeation occurred as Na+ exchanged with the incorporated multivalent cations, but a high content of Al3+ in the GO membrane impeded Al3+/Na+ exchange and thus retained membrane stability. In solutions containing biopolymers representative of surface waters or seawater (protein and polysaccharide solutions), Ca-GO membranes (even with high Ca2+ content) were not stable, while Al-GO membranes were stable if the Al3+ content was sufficiently high; Al-formed membranes also had a greater flux than Ca-GO membranes.

Divalent carbon(0) chemistry, part 1: Parent compounds.

PubMed

Tonner, Ralf; Frenking, Gernot

2008-01-01

Quantum-chemical calculations with DFT (BP86) and ab initio methods [MP2, SCS-MP2, CCSD(T)] have been carried out for the molecules C(PH(3))(2) (1), C(PMe(3))(2) (2), C(PPh(3))(2) (3), C(PPh(3))(CO) (4), C(CO)(2) (5), C(NHC(H))(2) (6), C(NHC(Me))(2) (7) (Me(2)N)(2)C=C=C(NMe(2))(2) (8), and NHC (9), where NHC=N-heterocyclic carbene and NHC(Me)=N-methyl-substituted NHC. The electronic structure in 1-9 was analyzed with charge- and energy-partitioning methods. The results show that the bonding situations in L(2)C compounds 1-8 can be interpreted in terms of donor-acceptor interactions between closed-shell ligands L and a carbon atom which has two lone-pair orbitals L-->C<--L. This holds particularly for the carbodiphosphoranes 1-3 where L=PR(3), which therefore are classified as divalent carbon(0) compounds. The NBO analysis suggests that the best Lewis structures for the carbodicarbenes 6 and 7 where L is a NHC ligand have C==C==C double bonds as in the tetraaminoallene 8. However, the Lewis structures of 6-8, in which two lone-pair orbitals at the central carbon atom are enforced, have only a slightly higher residual density. Visual inspection of the frontier orbitals of the latter species reveals their pronounced lone-pair character, which suggests that even the quasi-linear tetraaminoallene 8 is a "masked" divalent carbon(0) compound. This explains the very shallow bending potential of 8. The same conclusion is drawn for phosphoranylketene 4 and for carbon suboxide (5), which according to the bonding analysis have hidden double-lone-pair character. The AIM analysis and the EDA calculations support the assignment of carbodiphosphoranes as divalent carbon(0) compounds, while NHC 9 is characterized as a divalent carbon(II) compound. The L-->C((1)D) donor-acceptor bonds are roughly twice as strong as the respective L-->BH(3) bond.

Adsorption of myoglobin to metal-chelating lipid monolayers by neutron reflectivity

NASA Astrophysics Data System (ADS)

Kent, Michael; Yim, Hyun; Sasaki, Darryl; Smith, Greg

2002-03-01

In an effort to devise simple and robust systems that can reproduce in synthetic membranes important features of biological targeting and surface assembly, a versatile system for targeting proteins to lipid membranes has been developed.1 This system utilizes metal-chelating iminodiacetate lipids loaded with divalent metal ions (Cu+2 or Ni+2) to target adsorption of specific residues in proteins. In the present work we use neutron reflection to study the adsorption of myoglobin to monolayers containing such lipids at the air-water interface. The metal-chelating lipids were mixed with deuterated DPPC at a composition of 20subphase buffered with MOPS at a pH of 7.5, compressed to a pressure of 35-40 dyn/cm, and the reflectivity was measured. Following this, a solution of CuCl2 or NiCl2 was added to the subphase, and after mixing for 1 hr the reflectivity was again collected. Finally, a solution of myoglobin was added to the subphase, and after mixing the subphase for roughly 1 hr the reflectivity was again collected. The reflectivity revealed a greater adsorbed amount of myoglobin in the case of the Cu+2 ions than for Ni+2. In addition, the conformation of the adsorbed myoglobin was quite different in the two cases, with the adsorbed layer exhibiting a large dimension ( 90 \\x81) in the case of Cu+2 but a much smaller dimension ( 20\\x81) for the case of Ni+2. Corresponding changes in the structure of the lipid layer investigated with X-ray reflectivity and grazing incidence X-ray diffraction will also be presented. 1K. Ng, D. W. Pack, D. Sasaki, F. H. Arnold, Langmuir 1995, 11, 4048. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under contract CE-AC04-94AL85000.

Impact of iron chelators on short-term dissolution of basaltic glass

NASA Astrophysics Data System (ADS)

Perez, Anne; Rossano, Stéphanie; Trcera, Nicolas; Verney-Carron, Aurélie; Huguenot, David; van Hullebusch, Eric D.; Catillon, Gilles; Razafitianamaharavo, Angelina; Guyot, François

2015-08-01

Although microorganisms seem to play an important role in the alteration processes of basaltic glasses in solution, the elementary mechanisms involved remain unclear in particular with regard to the role of organic ligands excreted by the cells. Two glasses, one with Fe and one without Fe were synthesized to model basaltic glass compositions. Fe in the glass was mostly Fe(III) for enhancing interaction with siderophores, yet with small but significant amounts of Fe(II) (between 10% and 30% of iron). The prepared samples were submitted to abiotic alteration experiments in buffered (pH 6.4) diluted solutions of metal-specific ligands, namely oxalic acid (OA, 10 mM), desferrioxamine (DFA, 1 mM) or 2,2‧-bipyridyl (BPI, 1 mM). Element release from the glass into the solution after short term alteration (maximum 1 week) was measured by ICP-OES, and normalized mass losses and relative release ratios (with respect to Si) were evaluated for each element in each experimental condition. The presence of organic ligands had a significant effect on the dissolution of both glasses. Trivalent metals chelators (OA, DFA) impacted on the release of Fe3+ and Al3+, and thus on the global dissolution of both glasses, enhancing all release rates and dissolution stoichiometry (release rates were increased up to 7 times for Al or Fe). As expected, the mostly divalent metal chelator BPI interacted preferentially with Ca2+, Mg2+ and Fe2+. This study thus allows to highlight the central roles of iron and aluminium in interaction with some organic ligands in the alteration processes of basaltic glasses. It thus provides a step toward understanding the biological contribution of this fundamental geological process.

Luminescent lanthanide chelates and methods of use

DOEpatents

Selvin, Paul R.; Hearst, John

1997-01-01

The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

Relative affinities of divalent polyamines and of their N-methylated analogues for helical DNA determined by sup 23 Na NMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Padmanabhan, S.; Brushaber, V.M.; Anderson, C.F.

1991-07-30

Interactions of divalent polyamines with double-helical DNA in aqueous solution are investigated by monitoring the decrease in {sup 23}Na NMR relaxation rates as NaDNA is titrated with H{sub 3}N{sup +}-(CH{sub 2}){sub m}-{sup +}NH{sup 3}, where m = 3, 4, 5, or 6. Analogous measurements are made for the same homologous series of methylated polyamines (methonium ions). The dependence of the {sup 23}Na relaxation rates on the amount of added divalent cation (M{sup 2+}) is analyzes quantitatively in terms of a two-state model. The sodium ions are assumed to be in rapid exchange between a bound state, where they are closemore » enough to DNA so that it affects their relaxation rate, and a free state in bulk solution, where their relaxation rate is the same as in solutions containing no DNA. (1) For polyamines and methonium ions of the same m, D{sub H} exceeds D{sub Me} by factors that are significantly larger for m = 3 and 4 than for m = 5 and 6. (2) D{sub H} for m = 3 and 4 is larger than D{sub H} for m = 5 and 6. (3) D{sub Me} for m = 3 and 4 is smaller than D{sub Me} for m = 5 and 6.« less

The Chelate Effect Redefined.

ERIC Educational Resources Information Center

da Silva, J. J. R. Frausto

1983-01-01

Discusses ambiguities of the accepted definition of the chelate effect, suggesting that it be defined in terms of experimental observation rather than mathematical abstraction. Indicates that the effect depends on free energy change in reaction, ligand basicity, pH of medium, type of chelates formed, and concentration of ligands in solution. (JN)

Chelation for Coronary Heart Disease

MedlinePlus

... also turn to chelation therapy using disodium EDTA (ethylene diamine tetra-acetic acid), a controversial complementary health ... and answers about two trials of an EDTA (ethylene diamine tetra-acetic acid) chelation therapy regimen for ...

Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

PubMed

Corcé, Vincent; Morin, Emmanuelle; Guihéneuf, Solène; Renault, Eric; Renaud, Stéphanie; Cannie, Isabelle; Tripier, Raphaël; Lima, Luís M P; Julienne, Karine; Gouin, Sébastien G; Loréal, Olivier; Deniaud, David; Gaboriau, François

2012-09-19

Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

Metal-chelate dye-controlled organization of Cd32S14(SPh)40(4-) nanoclusters into three-dimensional molecular and covalent open architecture.

PubMed

Zheng, Nanfeng; Lu, Haiwei; Bu, Xianhui; Feng, Pingyun

2006-04-12

Chalcogenide II-VI nanoclusters are usually prepared as isolated clusters and have defied numerous efforts to join them into covalent open-framework architecture with conventional templating methods such as protonated amines or inorganic cations commonly used to direct the formation of porous frameworks. Herein, we report the first templated synthesis of II-VI covalent superlattices from large II-VI tetrahedral clusters (i.e., [Cd32S14(SPh)38]2-). Our method takes advantage of low charge density of metal-chelate dyes that is a unique match with three-dimensional II-VI semiconductor frameworks in charge density, surface hydrophilicity-hydrophobicity, and spatial organization. In addition, metal-chelate dyes also serve to tune the optical properties of resulting dye semiconductor composite materials.

Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by forskolin analogs.

PubMed

Erdorf, Miriam; Mou, Tung-Chung; Seifert, Roland

2011-12-01

Mammalian membranous adenylyl cyclases (mACs) play an important role in transmembrane signalling events in almost every cell and represent an interesting drug target. Forskolin (FS) is an invaluable research tool, activating AC isoforms 1-8. However, there is a paucity of AC isoform-selective FS analogs. Therefore, we examined the effects of FS and six FS derivatives on recombinant ACs 1, 2 and 5, representing members of different mAC families. Correlations of the pharmacological properties of the different AC isoforms revealed pronounced differences between ACs 1, 2 and 5. Additionally, potencies and efficacies of FS derivatives changed for any given AC isoform, depending on the metal ion, Mg(2+) or Mn(2+). The most striking effects of Mg(2+) and Mn(2+) on the diterpene profile were observed for AC2 where the large inhibitory effect of BODIPY-FS in the presence of Mg(2+) was considerably reduced in the presence of Mn(2+). Sequence alignment and docking experiments confirmed an exceptional position of AC2 compared to ACs 1 and 5 with respect to the structural environment of the catalytic core and cation-dependent diterpene effects. In conclusion, mAC isoforms 1, 2 and 5 exhibit a distinct pharmacological diterpene profile, depending on the divalent cation present. mAC crystal structures and modelling/docking studies provided an explanation for the pharmacological differences between the AC isoforms. Our study constitutes an important step towards the development of isoform-specific diterpenes exhibiting stimulatory or inhibitory effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, Chien M.; Smart, Neil G.; Lin, Yuehe

1998-01-01

A method of extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered.

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, N.G.; Wai, C.M.; Lin, Y.; Kwang, Y.H.

1998-11-24

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO{sub 2}, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO{sub 2} and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process. 1 fig.

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

1998-01-01

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

A rice tonoplastic calcium exchanger, OsCCX2 mediates Ca2+/cation transport in yeast

PubMed Central

Yadav, Akhilesh K.; Shankar, Alka; Jha, Saroj K.; Kanwar, Poonam; Pandey, Amita; Pandey, Girdhar K.

2015-01-01

In plant cell, cations gradient in cellular compartments is maintained by synergistic action of various exchangers, pumps and channels. The Arabidopsis exchanger family members (AtCCX3 and AtCCX5) were previously studied and belong to CaCA (calcium cation exchangers) superfamily while none of the rice CCXs has been functionally characterized for their cation transport activities till date. Rice genome encode four CCXs and only OsCCX2 transcript showed differential expression under abiotic stresses and Ca2+ starvation conditions. The OsCCX2 localized to tonoplast and suppresses the Ca2+ sensitivity of K667 (low affinity Ca2+ uptake deficient) yeast mutant under excess CaCl2 conditions. In contrast to AtCCXs, OsCCX2 expressing K667 yeast cells show tolerance towards excess Na+, Li+, Fe2+, Zn2+ and Co2+ and suggest its ability to transport both mono as well as divalent cations in yeast. Additionally, in contrast to previously characterized AtCCXs, OsCCX2 is unable to complement yeast trk1trk2 double mutant suggesting inability to transport K+ in yeast system. These finding suggest that OsCCX2 having distinct metal transport properties than previously characterized plant CCXs. OsCCX2 can be used as potential candidate for enhancing the abiotic stress tolerance in plants as well as for phytoremediation of heavy metal polluted soil. PMID:26607171

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, C.M.; Smart, N.G.; Lin, Y.

1998-08-11

A method is described for extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered. 3 figs.

The cation-controlled and hydrogen bond-mediated shear-thickening behaviour of a tree-fern isolated polysaccharide.

PubMed

Wee, May S M; Matia-Merino, Lara; Goh, Kelvin K T

2015-10-05

The shear-thickening rheological behaviour (between 5 and 20s(-1)) of a 5% (w/w) viscoelastic gum extracted from the fronds of the native New Zealand black tree fern or mamaku in Māori was further explored by manipulating the salt content. The freeze-dried mamaku gum contained a high mineral content and sugars which upon removal via dialysis, resulted in the loss of shear thickening. However, this loss was reversible by the addition of salts to the dialysed dispersion. The mechanism of shear-thickening behaviour was therefore hypothesised to be due to shear-induced transition of intra- to intermolecular hydrogen bonding, promoted by the screening effect of cations. Mono-, di- and trivalent salts, i.e. Na(+), K(+), N(CH3)4(+), Ca(2+), Mg(2+), Al(3+) and La(3+) at concentrations between 0.001 and 1.0M were tested to support the hypothesis as well as to demonstrate the sensitivity of the biopolymer to cation valency and concentrations. The cation valency and concentration were crucial factors in determining: (i) zero-shear viscosity, (ii) critical shear rate, γ˙c (or shear rate at the onset of shear-thickening) and (iii) the extent of shear-thickening of the solution. For mono- and divalent cations these parameters were similar at equivalent ionic strengths and fairly independent of the cation type. Trivalent cations (La(3+)) however caused precipitation of the gum in the concentration range of 0.005-0.05 M but clear dispersions were obtained above 0.05 M. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Divalent Electrolytes on Electroosmotic Flow

NASA Astrophysics Data System (ADS)

Li, Haifeng; Gnanaprakasam, Pradeep

2005-11-01

Electroosmotic flow (EOF) is of importance in micro- and nanofluidic applications. Recent numerical results [Zheng et al. (2003) Electrophoresis 24, 3006] suggest that the addition of even trace amounts of divalent counterions can greatly affect the velocity and electric potential distribution for EOF of a nominally monovalent electrolyte solution, nearly halving the flow rate in 20 nm channels. Scaled experiments were therefore carried out for steady and fully-developed EOF of buffered aqueous mono- and divalent electrolyte mixtures through fused silica microchannels. Nano-particle image velocimetry (nPIV), based upon evanescent-wave illumination of colloidal tracers, was used to obtain velocity data within about 300 nm of the wall. In all cases, the thickness of the electric double layer, defined as the distance from the wall where the velocity and electric potential recover to 99% of their freestream values, is of O(10 nm), or much less than the channel dimension of O(10 μm). The nPIV results are compared with predictions from an asymptotic perturbation analysis.

Effect of divalent versus monovalent cations on the MS2 retention capacity of amino-functionalized ceramic filters.

PubMed

Bartels, J; Hildebrand, N; Nawrocki, M; Kroll, S; Maas, M; Colombi Ciacchi, L; Rezwan, K

2018-04-25

Ceramic capillary membranes conditioned for virus filtration via functionalization with n-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) are analyzed with respect to their virus retention capacity when using feed solutions based on monovalent and divalent salts (NaCl, MgCl2). The log reduction value (LRV) by operating in dead-end mode using the model bacteriophage MS2 with a diameter of 25 nm and an IEP of 3.9 is as high as 9.6 when using feeds containing MgCl2. In contrast, a lesser LRV of 6.4 is observed for feed solutions based on NaCl. The TPDA functionalized surface is simulated at the atomistic scale using explicit-solvent molecular dynamics in the presence of either Na+ or Mg2+ ions. Computational prediction of the binding free energy reveals that the Mg2+ ions remain preferentially adsorbed at the surface, whereas Na+ ions form a weakly bound dissolved ionic layer. The charge shielding between surface and amino groups by the adsorbed Mg2+ ions leads to an upright orientation of the TPDA molecules as opposed to a more tilted orientation in the presence of Na+ ions. The resulting better accessibility of the TPDA molecules is very likely responsible for the enhanced virus retention capacity using a feed solution with Mg2+ ions.

Predicting stability of DNA duplexes in solutions containing magnesium and monovalent cations.

PubMed

Owczarzy, Richard; Moreira, Bernardo G; You, Yong; Behlke, Mark A; Walder, Joseph A

2008-05-13

Accurate predictions of DNA stability in physiological and enzyme buffers are important for the design of many biological and biochemical assays. We therefore investigated the effects of magnesium, potassium, sodium, Tris ions, and deoxynucleoside triphosphates on melting profiles of duplex DNA oligomers and collected large melting data sets. An empirical correction function was developed that predicts melting temperatures, transition enthalpies, entropies, and free energies in buffers containing magnesium and monovalent cations. The new correction function significantly improves the accuracy of predictions and accounts for ion concentration, G-C base pair content, and length of the oligonucleotides. The competitive effects of potassium and magnesium ions were characterized. If the concentration ratio of [Mg (2+)] (0.5)/[Mon (+)] is less than 0.22 M (-1/2), monovalent ions (K (+), Na (+)) are dominant. Effects of magnesium ions dominate and determine duplex stability at higher ratios. Typical reaction conditions for PCR and DNA sequencing (1.5-5 mM magnesium and 20-100 mM monovalent cations) fall within this range. Conditions were identified where monovalent and divalent cations compete and their stability effects are more complex. When duplexes denature, some of the Mg (2+) ions associated with the DNA are released. The number of released magnesium ions per phosphate charge is sequence dependent and decreases surprisingly with increasing oligonucleotide length.

Crystal and electronic structures of magnesium(II), copper(II), and mixed magnesium(II)-copper(II) complexes of the quinoline half of styrylquinoline-type HIV-1 integrase inhibitors.

PubMed

Courcot, B; Firley, D; Fraisse, B; Becker, P; Gillet, J-M; Pattison, P; Chernyshov, D; Sghaier, M; Zouhiri, F; Desmaële, D; d'Angelo, J; Bonhomme, F; Geiger, S; Ghermani, N E

2007-05-31

A new target in AIDS therapy development is HIV-1 integrase (IN). It was proven that HIV-1 IN required divalent metal cations to achieve phosphodiester bond cleavage of DNA. Accordingly, all newly investigated potent IN inhibitors contain chemical fragments possessing a high ability to chelate metal cations. One of the promising leads in the polyhydroxylated styrylquinolines (SQLs) series is (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoline carboxylic acid (1). The present study focuses on the quinoline-based progenitor (2), which is actually the most probable chelating part of SQLs. Conventional and synchrotron low-temperature X-ray crystallographic studies were used to investigate the chelating power of progenitor 2. Mg2+ and Cu2+ cations were selected for this purpose, and three types of metal complexes of 2 were obtained: Mg(II) complex (4), Cu(II) complex (5) and mixed Mg(II)-Cu(II) complexes (6 and 7). The analysis of the crystal structure of complex 4 indicates that two tridentate ligands coordinate two Mg2+ cations, both in octahedral geometry. The Mg-Mg distance was found equal to 3.221(1) A, in agreement with the metal-metal distance of 3.9 A encountered in the crystal structure of Escherichia coli DNA polymerase I. In 5, the complex is formed by two bidentate ligands coordinating one copper ion in tetrahedral geometry. Both mixed Mg(II)-Cu(II) complexes, 6 and 7 exhibit an original arrangement of four ligands linked to a central heterometallic cluster consisting of three octahedrally coordinated magnesium ions and one tetrahedrally coordinated copper ion. Quantum mechanics calculations were also carried out in order to display the electrostatic potential generated by the dianionic ligand 2 and complex 4 and to quantify the binding energy (BE) during the formation of the magnesium complex of progenitor 2. A comparison of the binding energies of two hypothetical monometallic Mg(II) complexes with that found in the bimetallic magnesium

Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase Activating Enzyme.

PubMed

Shisler, Krista A; Hutcheson, Rachel U; Horitani, Masaki; Duschene, Kaitlin S; Crain, Adam V; Byer, Amanda S; Shepard, Eric M; Rasmussen, Ashley; Yang, Jian; Broderick, William E; Vey, Jessica L; Drennan, Catherine L; Hoffman, Brian M; Broderick, Joan B

2017-08-30

Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l-methionine (SAM) enzyme that installs a catalytically essential glycyl radical on pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential monovalent cation at its active site, yet another parallel with B 12 enzymes, and we characterize this cation site by a combination of structural, biochemical, and spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na + as the most likely ion present in the solved structures, and pulsed electron nuclear double resonance (ENDOR) demonstrates that the same cation site is occupied by 23 Na in the solution state of the as-isolated enzyme. A SAM carboxylate-oxygen is an M + ligand, and EPR and circular dichroism spectroscopies reveal that both the site occupancy and the identity of the cation perturb the electronic properties of the SAM-chelated iron-sulfur cluster. ENDOR studies of the PFL-AE/[ 13 C-methyl]-SAM complex show that the target sulfonium positioning varies with the cation, while the observation of an isotropic hyperfine coupling to the cation by ENDOR measurements establishes its intimate, SAM-mediated interaction with the cluster. This monovalent cation site controls enzyme activity: (i) PFL-AE in the absence of any simple monovalent cations has little-no activity; and (ii) among monocations, going down Group 1 of the periodic table from Li + to Cs + , PFL-AE activity sharply maximizes at K + , with NH 4 + closely matching the efficacy of K + . PFL-AE is thus a type I M + -activated enzyme whose M + controls reactivity by interactions with the cosubstrate, SAM, which is bound to the catalytic iron-sulfur cluster.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chunya; Skelton, Adam A.; Chen, Mingjun

Here the binding of a negatively charged residue, aspartic acid (Asp) in tripeptide arginine-glycine-aspartic acid, onto a negatively charged hydroxylated rutile (110) surface in aqueous solution, containing divalent (Mg 2+, Ca 2+, or Sr 2+) or monovalent (Na +, K +, or Rb +) cations, was studied by molecular dynamics (MD) simulations. The results indicate that ionic radii and charges will significantly affect the hydration, adsorption geometry, and distance of cations from the rutile surface, thereby regulating the Asp/rutile binding mode. The adsorption strength of monovalent cations on the rutile surface in the order Na + > K + >more » Rb + shows a “reverse” lyotropic trend, while the divalent cations on the same surface exhibit a “regular” lyotropic behavior with decreasing crystallographic radii (the adsorption strength of divalent cations: Sr 2+ > Ca 2+ > Mg 2+). The Asp side chain in NaCl, KCl, and RbCl solutions remains stably H-bonded to the surface hydroxyls and the inner-sphere adsorbed compensating monovalent cations act as a bridge between the COO – group and the rutile, helping to “trap” the negatively charged Asp side chain on the negatively charged surface. In contrast, the mediating divalent cations actively participate in linking the COO– group to the rutile surface; thus the Asp side chain can remain stably on the rutile (110) surface, even if it is not involved in any hydrogen bonds with the surface hydroxyls. Inner- and outer-sphere geometries are all possible mediation modes for divalent cations in bridging the peptide to the rutile surface.« less

Divalent and trivalent gas-phase coordination complexes of californium: evaluating the stability of Cf(II)

DOE PAGES

Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel; ...

2016-07-07

The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less

Divalent and trivalent gas-phase coordination complexes of californium: evaluating the stability of Cf(II)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel

The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less

Condensation of monovalent and divalent metal ions on a Langmuir monolayer

NASA Astrophysics Data System (ADS)

Bloch, J. Mati; Yun, Wenbing

1990-01-01

A system that consists of a monolayer spread on a solution containing a monovalent and a divalent ion is investigated. The solution of the Poisson-Boltzmann-Stern equation for this system indicates that the metal ions segregating to the surface can be found in two distinct states. Divalent ions are chemically condensed on the monolayer, while monovalent ions are electrically attracted to it. We derive simple expressions for the charge left on the surfactant monolayer and the amount of metal ions condensed on the monolayer. These formulas reproduce very accurately (to within pro milles) the values obtained using the nonlinear Grahame equation and eliminate the need to solve that equation. That permits a simple identification of the state of the surfactant monolayer and we propose a universal condensation chart that characterizes the state of the surfactant. We further derive a chemical equilibrium equation for the surface components that has considerable range of validity. This equation requires a knowledge of the bulk concentrations only, and thus allows in many cases the identification of the state of the monolayer, avoiding the need to solve the full nonlinear Poisson-Boltzmann equation. All existing experimental results on Langmuir systems are in good agreement with the one-dimensional Poisson-Boltzmann-Stern model with no adjustable parameters. Several of these fits are presented in this work and are also mapped on the condensation chart. Our calculations point to some characteristic differences between the monovalent and the divalent ions that explain why it is possible to build Langmuir-Blodgett multilayers from divalent compensated surfactants but not from monovalent ones.

Super-high-affinity binding site for [3H]diazepam in the presence of Co2+, Ni2+, Cu2+, or Zn2+.

PubMed

Mizuno, S; Ogawa, N; Mori, A

1982-12-01

Chloride salts of Li+, Na+, K+, Mg2+, Ca2+, Cr3+, Mn2+, Fe2+, and Fe3+ had no effect on [3H]diazepam binding. Chloride salts of Co2+, Ni2+, Cu2+, and Zn2+ increased [3H]diazepam binding by 34 to 68% in a concentration-dependent fashion. Since these divalent cations potentiated the GABA-enhanced [3H]diazepam binding and the effect of each divalent cation was nearly additive with GABA, these cations probably act at a site different from the GABA recognition site in the benzodiazepine-receptor complex. Scatchard plots of [3H]diazepam binding without an effective divalent cation showed a single class of binding, with a Kd value of 5.3 nM. In the presence of 1 mM Co2+, Ni2+, Cu2+, or Zn2+, two distinct binding sites were evident with apparent Kd values of 1.0 nM and 5.7 nM. The higher-affinity binding was not detected in the absence of an effective divalent cation and is probably a novel, super-high-affinity binding site.

Influence of competing inorganic cations on the ion exchange equilibrium of the monovalent organic cation metoprolol on natural sediment.

PubMed

Niedbala, Anne; Schaffer, Mario; Licha, Tobias; Nödler, Karsten; Börnick, Hilmar; Ruppert, Hans; Worch, Eckhard

2013-02-01

The aim of this study was to systematically investigate the influence of the mono- and divalent inorganic ions Na(+) and Ca(2+) on the sorption behavior of the monovalent organic cation metoprolol on a natural sandy sediment at pH=7. Isotherms for the beta-blocker metoprolol were obtained by sediment-water batch tests over a wide concentration range (1-100000 μg L(-1)). Concentrations of the competing inorganic ions were varied within freshwater relevant ranges. Data fitted well with the Freundlich sorption model and resulted in very similar Freundlich exponents (n=0.9), indicating slightly non-linear behavior. Results show that the influence of Ca(2+) compared to Na(+) is more pronounced. A logarithmic correlation between the Freundlich coefficient K(Fr) and the concentration or activity of the competing inorganic ions was found allowing the prediction of metoprolol sorption on the investigated sediment at different electrolyte concentrations. Additionally, the organic carbon of the sediment was completely removed for investigating the influence of organic matter on the sorption of metoprolol. The comparison between the experiments with and without organic carbon removal revealed no significant contribution of the organic carbon fraction (0.1%) to the sorption of metoprolol on the in this study investigated sediment. Results of this study will contribute to the development of predictive models for the transport of organic cations in the subsurface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Unraveling the Fate and Transport of SrEDTA-2 and Sr+2 in Hanford Sediments

NASA Astrophysics Data System (ADS)

Pace, M. N.; Mayes, M. A.; Jardine, P. M.; Mehlhorn, T. L.; Liu, Q. G.; Yin, X. L.

2004-12-01

Accelerated migration of strontium-90 has been observed in the vadose zone beneath the Hanford tank farm. The goal of this paper is to provide an improved understanding of the hydrogeochemical processes that contribute to strontium transport in the far-field Hanford vadose zone. Laboratory scale batch, saturated packed column experiments, and an unsaturated transport experiment in an undisturbed core were conducted to quantify geochemical and hydrological processes controlling Sr+2 and SrEDTA-2 sorption to Hanford flood deposits. After experimentation, the undisturbed core was disassembled and samples were collected from different bedding units as a function of depth. Sequential extractions were then performed on the samples. It has been suggested that organic chelates such as EDTA may be responsible for the accelerated transport of strontium due to the formation of stable anionic complexes. Duplicate batch and column experiments performed with Sr+2 and SrEDTA-2 suggested that the SrEDTA-2 complex was not stable in the presence of soil and rapid dissociation allowed strontium to be transported as a divalent cation. Batch experiments indicated a decrease in sorption with increasing rock:water ratios, whereas saturated packed column experiments indicated equal retardation in columns of different lengths. This difference between the batch and column experiments is primarily due to the difference between equilibrium conditions where dissolution of cations may compete for sorption sites versus flowing conditions where any dissolved cations are flushed through the system minimizing competition for sorption sites. Unsaturated transport in the undisturbed core resulted in significant Sr+2 retardation despite the presence of physical nonequilibrium. Core disassembly and sequential extractions revealed the mass wetness distribution and reactive mineral phases associated with strontium in the core. Overall, results indicated that strontium will most likely be transported

(3H)WB4101 labels the 5-HT1A serotonin receptor subtype in rat brain. Guanine nucleotide and divalent cation sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norman, A.B.; Battaglia, G.; Creese, I.

1985-12-01

In the presence of a 30 nM prazosin mask, (/sup 3/H)-2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane ((/sup 3/H)WB4101) can selectively label 5-HT1 serotonin receptors. Serotonin exhibits high affinity (Ki = 2.5 nM) and monophasic competition for (/sup 3/H) WB4101 binding in cerebral cortex. We have found a significant correlation (r = 0.96) between the affinities of a number of serotonergic and nonserotonergic compounds at (/sup 3/H)WB4101-binding sites in the presence of 30 nM prazosin and (/sup 3/H) lysergic acid diethylamide ((/sup 3/H)LSD)-labeled 5-HT1 serotonin receptors in homogenates of rat cerebral cortex. Despite similar pharmacological profiles, distribution studies indicate that, in the presence of 5more » mM MgSO4, the Bmax of (/sup 3/H)WB4101 is significantly lower than the Bmax of (/sup 3/H)LSD in various brain regions. WB4101 competition for (/sup 3/H) LSD-labeled 5-HT1 receptors fits best to a computer-derived model assuming two binding sites, with the KH for WB4101 being similar to the KD of (/sup 3/H)WB4101 binding derived from saturation experiments. This suggests that (/sup 3/H)WB4101 labels only one of the subtypes of the 5-HT1 serotonin receptors labeled by (/sup 3/H)LSD. The selective 5-HT1A serotonin receptor antagonist, spiperone, and the selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetraline, exhibit high affinity and monophasic competition for (/sup 3/H)WB4101 but compete for multiple (/sup 3/H)LSD 5-HT1 binding sites. These data indicate that (/sup 3/H)WB4101 selectively labels the 5-HT1A serotonin receptor, whereas (/sup 3/H) LSD appears to label both the 5-HT1A and the 5-HT1B serotonin receptor subtypes. The divalent cations, Mn2+, Mg2+, and Ca2+ were found to markedly increase the affinity and Bmax of (/sup 3/H)WB4101 binding in cerebral cortex. Conversely, the guanine nucleotides guanylylimidodiphosphate and GTP, but not the adenosine nucleotide ATP, markedly reduce the Bmax of (/sup 3/H)WB4101 binding.« less

Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

DOEpatents

Rahman, Yueh Erh

1977-11-10

A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

Selective interactions of trivalent cations Fe³⁺, Al³⁺ and Cr³⁺ turn on fluorescence in a naphthalimide based single molecular probe.

PubMed

Janakipriya, Subramaniyan; Chereddy, Narendra Reddy; Korrapati, Purnasai; Thennarasu, Sathiah; Mandal, Asit Baran

2016-01-15

Synthesis and fluorescence turn-on behavior of a naphthalimide based probe is described. Selective interactions of trivalent cations Fe(3+), Al(3+) or Cr(3+) with probe 1 inhibit the PET operating in the probe, and thereby, permit the detection of these trivalent cations present in aqueous samples and live cells. Failure of other trivalent cations (Eu(3+), Gd(3+) and Nb(3+)) to inhibit the PET process in 1 demonstrates the role of chelating ring size vis-à-vis ionic radius in the selective recognition of specific metal ions. Copyright © 2015 Elsevier B.V. All rights reserved.

Malic enzyme: Tritium isotope effects with alternative dinucleotide substrates and divalent metal ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karsten, W.E.; Harris, B.G.; Cook, P.F.

1992-01-01

The NAD-malic enzyme from Ascaris suum catalyzes the divalent metal ion dependent oxidative decarboxylation of L-malate to yield pyruvate, carbon dioxide and NADH. Multiple isotope effect studies suggest a stepwise chemical mechanism with hydride transfer from L-malate to NAD occurring first to form oxalacetate, followed by decarboxylation. Utilizing L-malate-2-T, tritium V/K isotope effects have been determined for the hydride transfer step using a variety of alternative dinucleotide substrates and divalent metal ions. Combination of these data with deuterium isotope effects data and previously determined [sup 13]C isotope effects has allowed the calculation of intrinsic isotope effects for the malic enzymemore » catalyzed reaction. The identity of both the dinucleotide substrate and divalent metal ion has an effect of the size of the intrinsic isotope effect for hydride transfer.« less

Modeling sorption of divalent metal cations on hydrous manganese oxide using the diffuse double layer model

USGS Publications Warehouse

Tonkin, J.W.; Balistrieri, L.S.; Murray, J.W.

2004-01-01

Manganese oxides are important scavengers of trace metals and other contaminants in the environment. The inclusion of Mn oxides in predictive models, however, has been difficult due to the lack of a comprehensive set of sorption reactions consistent with a given surface complexation model (SCM), and the discrepancies between published sorption data and predictions using the available models. The authors have compiled a set of surface complexation reactions for synthetic hydrous Mn oxide (HMO) using a two surface site model and the diffuse double layer SCM which complements databases developed for hydrous Fe (III) oxide, goethite and crystalline Al oxide. This compilation encompasses a range of data observed in the literature for the complex HMO surface and provides an error envelope for predictions not well defined by fitting parameters for single or limited data sets. Data describing surface characteristics and cation sorption were compiled from the literature for the synthetic HMO phases birnessite, vernadite and ??-MnO2. A specific surface area of 746 m2g-1 and a surface site density of 2.1 mmol g-1 were determined from crystallographic data and considered fixed parameters in the model. Potentiometric titration data sets were adjusted to a pH1EP value of 2.2. Two site types (???XOH and ???YOH) were used. The fraction of total sites attributed to ???XOH (??) and pKa2 were optimized for each of 7 published potentiometric titration data sets using the computer program FITEQL3.2. pKa2 values of 2.35??0.077 (???XOH) and 6.06??0.040 (???YOH) were determined at the 95% confidence level. The calculated average ?? value was 0.64, with high and low values ranging from 1.0 to 0.24, respectively. pKa2 and ?? values and published cation sorption data were used subsequently to determine equilibrium surface complexation constants for Ba2+, Ca2+, Cd 2+, Co2+, Cu2+, Mg2+, Mn 2+, Ni2+, Pb2+, Sr2+ and Zn 2+. In addition, average model parameters were used to predict additional

Method for preparing radionuclide-labeled chelating agent-ligand complexes

DOEpatents

Meares, Claude F.; Li, Min; DeNardo, Sally J.

1999-01-01

Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

Enhancing tonoplast Cd/H antiport activity increases Cd, Zn, and Mn tolerance, and impacts root/shoot Cd partitioning in Nicotiana tabacum L.

USDA-ARS?s Scientific Manuscript database

Sequestration mechanisms that prevent high concentrations of free metal ions from persisting in metabolically active compartments of cells are thought to be central in tolerance of plants to high levels of divalent cation metals. Expression of "AtCAX2" or "AtCAX4", which encode divalent cation/proto...

Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance

PubMed Central

Barber-Zucker, Shiran; Uebe, René; Davidov, Geula; Navon, Yotam; Sherf, Dror; Chill, Jordan H.; Kass, Itamar; Bitton, Ronit; Schüler, Dirk; Zarivach, Raz

2016-01-01

Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins’ proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human. PMID:27550551

Strontium, barium, and manganese metabolism in isolated presynaptic nerve terminals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasgado-Flores, H.; Sanchez-Armass, S.; Blaustein, M.P.

1987-06-01

To gain insight into the mechanisms by which the divalent cations Sr, Ba, and Mn affect neurotransmitter release from presynaptic nerve terminals, the authors examined the sequestration of these cations, ion comparison to Ca, by mitochondrial and nonmitochondrial organelles and the extrusion of these cations from isolated nerve terminals. Sequestration was studied in synaptosomes made leaky to small ions by treatment with saponin; efflux was examined in intact synaptosomes that were preloaded with the divalent cations by incubation in depolarizing (K rich) media. The selectivity sequence for ATP-dependent mitochondrial uptake that they observed was Mn>>Ca>Sr>>Ba, whereas that for the SERmore » was Ca greater than or equal to Mn>Sr>>Ba. When synaptosomes that were preloaded with divalent cations were incubated in Na- and Ca-free media, there was little efflux of /sup 45/Ca, /sup 133/Ba, /sup 85/Sr, or /sup 54/Mn. When the incubation was carried out in media containing Na without Ca, there was substantial stimulation of Ca and Sr efflux, but only slight stimulation of Ba or Mn efflux. In Na-free media, the addition of 1 mM Ca promoted the efflux of all four divalent cations, probably via Ca-divalent cation exchange. In summary, the sequestration and extrusion data suggest that, with equal loads, Mn will be buffered to the greatest extent, whereas Ba will be least well buffered. These results may help to explain why Mn has a very long-lasting effect on transmitter release, while the effect of Sr is much briefer.« less

Chelation in root canal therapy reconsidered.

PubMed

Zehnder, Matthias; Schmidlin, Patrick; Sener, Beatrice; Waltimo, Tuomas

2005-11-01

The aim of this study was to assess interactions of EDTA and citric acid (CA) with sodium hypochlorite (NaOCl), the indispensable endodontic irrigant. Other chelators were simultaneously evaluated as possible alternatives: sodium triphosphate (STP), amino tris methylenephosphonic acid (ATMA), and 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP). Available chlorine was titrated in chelator-NaOCl solutions. All chelators other than HEBP and STP caused an almost complete, immediate loss of available chlorine in solution. Atomic absorbtion spectrometry and SEM evaluation of root canal walls of instrumented teeth indicated that NaOCl had no negative effect on calcium-complexing ability of chelators. STP was too weak a complexing agent to warrant further studies. Finally, CA-, EDTA-, and HEBP-NaOCl mixtures were evaluated for their antimicrobial capacity. Again, EDTA and CA negatively interfered with NaOCl, while HEBP did not.

Highly tunable colloidal perovskite nanoplatelets through variable cation, metal, and halide composition

DOE PAGES

Weidman, Mark C.; Seitz, Michael; Stranks, Samuel D.; ...

2016-07-29

Here, colloidal perovskite nanoplatelets are a promising class of semiconductor nanomaterials-exhibiting bright luminescence, tunable and spectrally narrow absorption and emission features, strongly confined excitonic states, and facile colloidal synthesis. Here, we demonstrate the high degree of spectral tunability achievable through variation of the cation, metal, and halide composition as well as nanoplatelet thickness. We synthesize nanoplatelets of the form L 2[ABX 3] n-1BX 4, where L is an organic ligand (octylammonium, butylammonium), A is a monovalent metal or organic molecular cation (cesium, methylammonium, formamidinium), B is a divalent metal cation (lead, tin), X is a halide anion (chloride, bromide, iodide),more » and n-1 is the number of unit cells in thickness. We show that variation of n, B, and X leads to large changes in the absorption and emission energy, while variation of the A cation leads to only subtle changes but can significantly impact the nanoplatelet stability and photoluminescence quantum yield (with values over 20%). Furthermore, mixed halide nanoplatelets exhibit continuous spectral tunability over a 1.5 eV spectral range, from 2.2 to 3.7 eV. The nanoplatelets have relatively large lateral dimensions (100 nm to 1 μm), which promote self-assembly into stacked superlattice structures-the periodicity of which can be adjusted based on the nanoplatelet surface ligand length. These results demonstrate the versatility of colloidal perovskite nanoplatelets as a material platform, with tunability extending from the deep-UV, across the visible, into the near-IR. In particular, the tin-containing nanoplatelets represent a significant addition to the small but increasingly important family of lead- and cadmium-free colloidal semiconductors.« less

Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

NASA Astrophysics Data System (ADS)

Zhou, Wen; Håkansson, Kristina

2013-11-01

Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

64Cu-Labeled Phosphonium Cations as PET Radiotracers for Tumor Imaging

PubMed Central

Zhou, Yang; Liu, Shuang

2011-01-01

Alteration in mitochondrial transmembrane potential (ΔΨm) is an important characteristic of cancer. The observation that the enhanced negative mitochondrial potential is prevalent in tumor cell phenotype provides a conceptual basis for development of mitochondrion-targeting therapeutic drugs and molecular imaging probes. Since plasma and mitochondrial potentials are negative, many delocalized organic cations, such as rhodamine-123 and 3H-tetraphenylphosphonium, are electrophoretically driven through these membranes, and able to localize in the energized mitochondria of tumor cells. Cationic radiotracers, such as 99mTc-Sestamibi and 99mTc-Tetrofosmin, have been clinically used for diagnosis of cancer by single photon emission computed tomography (SPECT) and noninvasive monitoring of the multidrug resistance (MDR) transport function in tumors of different origin. However, their diagnostic and prognostic values are often limited due to their insufficient tumor localization (low radiotracer tumor uptake) and high radioactivity accumulation in the chest and abdominal regions (low tumor selectivity). In contrast, the 64Cu-labeled phosphonium cations represent a new class of PET (positron emission tomography) radiotracers with good tumor uptake and high tumor selectivity. This review article will focus on our recent experiences in evaluation of 64Cu-labeled phosphonium cations as potential PET radiotracers. The main objective is to illustrate the impact of radiometal chelate on physical, chemical and biological properties of 64Cu radiotracers. It will also discuss some important issues related to their tumor selectivity and possible tumor localization mechanism. PMID:21696200

Binding of Dissolved Strontium by Micrococcus luteus

PubMed Central

Faison, Brendlyn D.; Cancel, Carmen A.; Lewis, Susan N.; Adler, Howard I.

1990-01-01

Resting cells of Micrococcus luteus have been shown to remove strontium (Sr) from dilute aqueous solutions of SrCl2 at pH 7. Loadings of 25 mg of Sr per g of cell dry weight were achieved by cells exposed to a solution containing 50 ppm (mg/liter) of Sr. Sr binding occurred in the absence of nutrients and did not require metabolic activity. Initial binding was quite rapid (<0.5 h), although a slow, spontaneous release of Sr was observed over time. Sr binding was inhibited in the presence of polyvalent cations but not monovalent cations. Ca and Sr were bound preferentially over all other cations tested. Sr-binding activity was localized on the cell envelope and was sensitive to various chemical and physical pretreatments. Bound Sr was displaced by divalent ions or by H+. Other monovalent ions were less effective. Bound Sr was also removed by various chelating agents. It was concluded that Sr binding by M. luteus is a reversible equilibrium process. Both ion exchange mediated by acidic cell surface components and intracellular uptake may be involved in this activity. PMID:16348370

Synthesis, crystal structure, and magnetic properties of two-dimensional divalent metal glutarate/dipyridylamine coordination polymers, with a single crystal-to-single crystal transformation in the copper derivative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montney, Matthew R.; Supkowski, Ronald M.; Staples, Richard J.

Hydrothermal reaction of divalent metal chlorides with glutaric acid and 4,4'-dipyridylamine (dpa) has afforded an isostructural family of coordination polymers with formulation [M(glu)(dpa)]{sub n} (M=Co (1), Ni (2), Cu (3); glu=glutarate). Square pyramidal coordination is seen in 1-3, with semi-ligation of a sixth donor to produce a '5+1' extended coordination sphere. Neighboring metal atoms are linked into 1D [M(glu)]{sub n} neutral chains through chelating/monodentate bridging glutarate moieties with a syn-anti binding mode, and semi-chelation of the pendant carboxylate oxygen. These chains further connect into 2D layers through dipodal dpa ligands. Neighboring layers stack into the pseudo 3D crystal structure ofmore » 1-3 through supramolecular hydrogen bonding between dpa amine units and the semi-chelated glutarate oxygen atoms. The variable temperature magnetic behavior of 1-3 was explored and modeled as infinite 1D Heisenberg chains. Notably, complex 3 undergoes a thermally induced single crystal-to-single crystal transformation between centric and acentric space groups, with a conformationally disordered unilayer structure at 293 K and an ordered bilayer structure at 173 K. All materials were further characterized via infrared spectroscopy and elemental and thermogravimetric analyses. - Graphical abstract: The coordination polymers [M(glu)(dpa)]{sub n} (M=Co (1), Ni (2), Cu (3); glu=glutarate, dpa=4,4'-dipyridylamine) exhibit 2D layer structures based on 1D [M(glu)]{sub n} chains linked through dpa tethers. Antiferromagnetic coupling is observed for 2 and 3, while ferromagnetism is predominant in 1. Compound 3 undergoes a thermally induced single crystal-to-single crystal transformation from an acentric to a centrosymmetric space group.« less

Chelate assisted phytoextraction of heavy metals from soil. Effect, mechanism, toxicity, and fate of chelating agents.

PubMed

Evangelou, Michael W H; Ebel, Mathias; Schaeffer, Andreas

2007-06-01

The low-cost, plant-based phytoextraction technique has often been described as a promising technique to remediate heavy metal contaminated agricultural land. The application of chelating agents has shown positive effects in increasing the solubility of heavy metals in soil and therefore in enhancing phytoextraction. This paper gives an overview of the chelating agents applied in recent studies. Various synthetic aminopolycarboxylic acids, such as ethylene diamine tetraacetic acid, and natural ones such as, ethylene diamine disuccinate and nitrilotriacetic acid, are described. Additionally, results of the application of natural low molecular weight organic acids, such as citric and tartaric acid are given. The effectiveness of these different chelating agents varies according to the plant and the heavy metals used. Furthermore, a focus is laid on the chelating agents fate after application and on its toxicity to plants and soil microorganisms, as well as it degradation. The rate of degradation is of great importance for the future of chelate assisted phytoextraction as it has a direct impact on the leaching probability. An effective prevention of leaching will be crucial for the acceptance and the economic breakthrough of enhanced phytoextraction, but a satisfactory solution to this key issue has so far not been found. Possibly further experiments in the field of enhanced phytoextraction will be able to solve this major problem, but over decades various greenhouse experiments and recently field experiments have resulted in different observations. Therefore, it is questionable if further research in this direction will lead to a promising solution. Phytoextraction has possibly reached a turning point in which it should distance itself from chelate assisted phytoextraction and focus on alternative options.

Effects of cations on Helicobacter pylori urease activity, release, and stability.

PubMed Central

Pérez-Pérez, G I; Gower, C B; Blaser, M J

1994-01-01

The urease of Helicobacter pylori is an important antigen and appears critical for colonization and virulence. Several studies have indicated a superficial localization for the H. pylori urease, and the purpose of this study was to determine the effects of cations on the release and stability of urease activity from H. pylori cells. Incubation of partially purified H. pylori urease in water containing 1, 5, or 10 mM Ca2+, Mg2+, K+, Na+, EDTA, or EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] had little effect on activity. In contrast, 1 mM Fe3+, Cu2+, Co2+, or Zn2+ substantially (> 80%) inhibited activity, and 10 mM Fe2+, Mn2+, and Ni2+ inhibited about 30% of the activity. Addition of Ca2+ or Mg2+ markedly decreased extraction of urease from intact H. pylori cells by water, but 1 mM Na+, K+, EGTA, or EDTA each had minimal effects on release, suggesting that divalent cations have a role in attachment of urease to H. pylori cells. The stability of enzymatic activity at 4 degrees C was enhanced by addition of glycerol or 2-mercaptoethanol; however, even after loss of activity, full antigenicity for human serum was retained. PMID:8262643

Iron chelation and multiple sclerosis

PubMed Central

Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

2014-01-01

Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen. PMID:24397846

[Susceptibility of enterococci to natural and synthetic iron chelators].

PubMed

Lisiecki, Paweł; Mikucki, Jerzy

2002-01-01

A total of 79 strains of enterococci belonging to 10 species were tested for susceptibility to natural and synthetic iron chelators. All strains produced siderophores. These enterococci were susceptible to three synthetic iron chelators only: 8-hydroxyquinoline, disodium versenate (EDTA) and o-phenanthroline. They were resistant to all other synthetic chelators: ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA), nitrilotriacetate, 2,2'-bipiridyl, salicylic acid, 8-hydroxy-5-sulphonic acid and to all natural chelators: ovotransferrine, human apotransferrine, horse apoferritine, desferrioxamine B, ferrichrome and rhodotorulic acid. The relations between susceptibility/resistance, iron assimilation and structure and stability constants of iron chelators were discussed.

Determination of the nitrogen vacancy as a shallow compensating center in GaN doped with divalent metals.

PubMed

Buckeridge, J; Catlow, C R A; Scanlon, D O; Keal, T W; Sherwood, P; Miskufova, M; Walsh, A; Woodley, S M; Sokol, A A

2015-01-09

We report accurate energetics of defects introduced in GaN on doping with divalent metals, focusing on the technologically important case of Mg doping, using a model that takes into consideration both the effect of hole localization and dipolar polarization of the host material, and includes a well-defined reference level. Defect formation and ionization energies show that divalent dopants are counterbalanced in GaN by nitrogen vacancies and not by holes, which explains both the difficulty in achieving p-type conductivity in GaN and the associated major spectroscopic features, including the ubiquitous 3.46 eV photoluminescence line, a characteristic of all lightly divalent-metal-doped GaN materials that has also been shown to occur in pure GaN samples. Our results give a comprehensive explanation for the observed behavior of GaN doped with low concentrations of divalent metals in good agreement with relevant experiment.

Determination of the Nitrogen Vacancy as a Shallow Compensating Center in GaN Doped with Divalent Metals

NASA Astrophysics Data System (ADS)

Buckeridge, J.; Catlow, C. R. A.; Scanlon, D. O.; Keal, T. W.; Sherwood, P.; Miskufova, M.; Walsh, A.; Woodley, S. M.; Sokol, A. A.

2015-01-01

We report accurate energetics of defects introduced in GaN on doping with divalent metals, focusing on the technologically important case of Mg doping, using a model that takes into consideration both the effect of hole localization and dipolar polarization of the host material, and includes a well-defined reference level. Defect formation and ionization energies show that divalent dopants are counterbalanced in GaN by nitrogen vacancies and not by holes, which explains both the difficulty in achieving p -type conductivity in GaN and the associated major spectroscopic features, including the ubiquitous 3.46 eV photoluminescence line, a characteristic of all lightly divalent-metal-doped GaN materials that has also been shown to occur in pure GaN samples. Our results give a comprehensive explanation for the observed behavior of GaN doped with low concentrations of divalent metals in good agreement with relevant experiment.

Oxidation-Induced Degradable Nanogels for Iron Chelation

NASA Astrophysics Data System (ADS)

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-02-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

Oxidation-Induced Degradable Nanogels for Iron Chelation

PubMed Central

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-01-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

Synthetic laser medium

DOEpatents

Stokowski, S.E.

1987-10-20

A laser medium is particularly useful in high average power solid state lasers. The laser medium includes a chromium dopant and preferably neodymium ions as codopant, and is primarily a gadolinium scandium gallium garnet, or an analog thereof. Divalent cations inhibit spiral morphology as large boules from which the laser medium is derived are grown, and a source of ions convertible between a trivalent state and a tetravalent state at a low ionization energy are in the laser medium to reduce an absorption coefficient at about one micron wavelength otherwise caused by the divalent cations. These divalent cations and convertible ions are dispersed in the laser medium. Preferred convertible ions are provided from titanium or cerium sources.

Synthetic laser medium

DOEpatents

Stokowski, Stanley E.

1989-01-01

A laser medium is particularly useful in high average power solid state lasers. The laser medium includes a chormium dopant and preferably neodymium ions as codopant, and is primarily a gadolinium scandium gallium garnet, or an analog thereof. Divalent cations inhibit spiral morphology as large boules from which the laser medium is derived are grown, and a source of ions convertible between a trivalent state and a tetravalent state at a low ionization energy are in the laser medium to reduce an absorption coefficient at about one micron wavelength otherwise caused by the divalent cations. These divalent cations and convertible ions are dispersed in the laser medium. Preferred convertible ions are provided from titanium or cerium sources.

Structural insights into the osteopontin-aptamer complex y molecular dynamics simulations

NASA Astrophysics Data System (ADS)

La Penna, Giovanni; Chelli, Riccardo

2018-01-01

Osteopontin is an intrinsically disordered protein involved in tissue remodeling. As a biomarker for pathological hypertrophy and fibrosis, the protein is targeted by an RNA aptamer. In this work, we model the interactions between osteopontin and its aptamer, including mono- (Na+) and divalent (Mg2+) cations. The molecular dynamics simulations suggest that the presence of divalent cations forces the N-terminus of osteopontin to bind the shell of divalent cations adsorbed over the surface of its RNA aptamer, the latter exposing a high negative charge density. The osteopontin plasticity as a function of the local concentration of Mg is discussed in the frame of the proposed strategies for osteopontin targeting as biomarker and in theranostic.

Multiple regulation by external ATP of nifedipine-insensitive, high voltage-activated Ca(2+) current in guinea-pig mesenteric terminal arteriole.

PubMed

Morita, Hiromitsu; Sharada, Thapaliya; Takewaki, Tadashi; Ito, Yushi; Inoue, Ryuji

2002-03-15

We investigated the receptor-mediated regulation of nifedipine-insensitive, high voltage-activated Ca(2+) currents in guinea-pig terminal mesenteric arterioles (I(mVDCC)) using the whole-cell clamp technique. Screening of various vasoactive substances revealed that ATP, histamine and substance P exert modulatory effects on I(mVDCC). The effects of ATP on I(mVDCC) after complete P2X receptor desensitization exhibited a complex concentration dependence. With 5 mM Ba(2+), ATP potentiated I(mVDCC) at low concentrations (approximately 1-100 microM), but inhibited it at higher concentrations (>100 microM). The potentiating effects of ATP were abolished by suramin (100 microM) and PPADS (10 microM) and by intracellular application of GDPbetaS (500 microM), whereas a substantial part of I(mVDCC) inhibition by milimolar concentrations of ATP remained unaffected; due probably to its divalent cation chelating actions. In divalent cation-free solution, I(mVDCC) was enlarged and underwent biphasic effects by ATPgammaS and ADP, while 2-methylthio ATP (2MeSATP) exerted only inhibition, and pyrimidines such as UTP and UDP were ineffective. ATP-induced I(mVDCC) potentiation was selectively inhibited by anti-Galpha(s) antibodies or protein kinase A (PKA) inhibitory peptides and mimicked by dibutyryl cAMP. In contrast, ATP-induced inhibition was selectively inhibited by Galpha(q/11) antibodies or protein kinase C (PKC) inhibitory peptides and mimicked by PDBu. Pretreatment with pertussis toxin was ineffective. The apparent efficacy for I(mVDCC) potentiation with PKC inhibitors was: ATPgammaS > ATP>/=ADP and for inhibition with PKA inhibitors was: 2MeSATP > ATPgammaS > ATP > ADP. Neither I(mVDCC) potentiation nor inhibition showed voltage dependence. These results suggest that I(mVDCC) is multi-phasically regulated by external ATP via P2Y(11)-resembling receptor/G(s)/PKA pathway, P2Y(1)-like receptor/G(q/11)/PKC pathway, and metal chelation.

Timed non-transferrin bound iron determinations probe the origin of chelatable iron pools during deferiprone regimens and predict chelation response

PubMed Central

Aydinok, Yesim; Evans, Patricia; Manz, Chantal Y.; Porter, John B.

2012-01-01

Background Plasma non-transferrin bound iron refers to heterogeneous plasma iron species, not bound to transferrin, which appear in conditions of iron overload and ineffective erythropoiesis. The clinical utility of non-transferrin bound iron in predicting complications from iron overload, or response to chelation therapy remains unproven. We undertook carefully timed measurements of non-transferrin bound iron to explore the origin of chelatable iron and to predict clinical response to deferiprone. Design and Methods Non-transferrin bound iron levels were determined at baseline and after 1 week of chelation in 32 patients with thalassemia major receiving deferiprone alone, desferrioxamine alone, or a combination of the two chelators. Samples were taken at baseline, following a 2-week washout without chelation, and after 1 week of chelation, this last sample being taken 10 hours after the previous evening dose of deferiprone and, in those receiving desferrioxamine, 24 hours after cessation of the overnight subcutaneous infusion. Absolute or relative non-transferrin bound iron levels were related to transfusional iron loading rates, liver iron concentration, 24-hour urine iron and response to chelation therapy over the subsequent year. Results Changes in non-transferrin bound iron at week 1 were correlated positively with baseline liver iron, and inversely with transfusional iron loading rates, with deferiprone-containing regimens but not with desferrioxamine monotherapy. Changes in week 1 non-transferrin bound iron were also directly proportional to the plasma concentration of deferiprone-iron complexes and correlated significantly with urine iron excretion and with changes in liver iron concentration over the next 12 months. Conclusions The widely used assay chosen for this study detects both endogenous non-transferrin bound iron and the iron complexes of deferiprone. The week 1 increments reflect chelatable iron derived both from liver stores and from red cell

Questions and Answers on Unapproved Chelation Products

MedlinePlus

... OTC) to prevent or treat diseases. Companies are marketing unapproved OTC chelation therapy products to patients with ... 4. Why did FDA take this action? Companies marketing unapproved OTC chelation products with unsubstantiated treatment claims ...

The amino acid sequences of carboxypeptidases I and II from Aspergillus niger and their stability in the presence of divalent cations.

PubMed

Svendsen, I; Dal Degan, F

1998-09-08

The amino acid sequences of serine carboxypeptidase I (CPD-I) and II (CPD-II), respectively, from Aspergillus niger have been determined by conventional Edman degradation of the reduced and vinylpyridinated enzymes and peptides hereof generated by cleavage with cyanogen bromide, iodobenzoic acid, glutamic acid cleaving enzyme, AspN-endoproteinase and EndoLysC proteinase. CPD-I consists of a single peptide chain of 471 amino acid residues, three disulfide bridges and nine N-glycosylated asparaginyl residues, while CPD-II consists of a single peptide chain of 481 amino acid residues, has three disulfide bridges, one free cysteinyl residue and nine glycosylated asparaginyl residues. The enzymes are closely related to carboxypeptidase S3 from Penicillium janthinellum. Both Ca2+ and Mg2+ stabilize CPD-I as well as CPD-II, at basic pH values, Ca2+ being most effective, while the divalent ions have no effect on the activity of the two enzymes.

Thermodynamics of binding interactions between extracellular polymeric substances and heavy metals by isothermal titration microcalorimetry.

PubMed

Yan, Peng; Xia, Jia-Shuai; Chen, You-Peng; Liu, Zhi-Ping; Guo, Jin-Song; Shen, Yu; Zhang, Cheng-Cheng; Wang, Jing

2017-05-01

Extracellular polymeric substances (EPS) play a crucial role in heavy metal bio-adsorption using activated sludge, but the interaction mechanism between heavy metals and EPS remains unclear. Isothermal titration calorimetry was employed to illuminate the mechanism in this study. The results indicate that binding between heavy metals and EPS is spontaneous and driven mainly by enthalpy change. Extracellular proteins in EPS are major participants in the binding process. Environmental conditions have significant impact on the adsorption performance. Divalent and trivalent cations severely impeded the binding of heavy metal ions to EPS. Electrostatic interaction mainly attributed to competition between divalent cations and heavy metal ions; trivalent cations directly competed with heavy metal ions for EPS binding sites. Trivalent cations were more competitive than divalent cations for heavy metal ion binding because they formed complexing bonds. This study facilitates a better understanding about the interaction between heavy metals and EPS in wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms of Divalent Metal Toxicity in Affective Disorders

PubMed Central

Menon, Archita Venugopal; Chang, JuOae; Kim, Jonghan

2016-01-01

Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID:26551072

Effect of divalent ions on the optical emission behavior of protein thin films

NASA Astrophysics Data System (ADS)

Bhowal, Ashim Chandra; Kundu, Sarathi

2016-05-01

Photoluminescence behaviors of proteinthin film, bovine serum albumin (BSA) have been studied in the presence of three divalent ions (Mg2+, Ca2+ and Ba2+) at different temperatures using fluorescence spectroscopy. Film thickness and morphology have been studied using atomic force microscopy. Variation of different physicochemical parameters like temperature, solvent polarity, pH, ionic strength, substrate binding etc. can make conformational changes in the protein structure and hence influences the emission behavior.In thin film conformation of BSA, dynamic quenching behavior has beenidentified in the presence of all the three divalent ions at pH≈ 5.5. Depending upon the charge density of the divalent ions interaction with protein molecules modifies and as a result quenching efficiency varies. Also after heat treatment, conformation of the protein molecules changes and as a result the quenching efficiency enhances than that of the unheated films. Studies on such protein-ion interactions and conformational variation may explore various functions of protein when it will adsorb on soft surfaces like membranes, vesicles, etc.

Luminescent Properties of Eu(III) Chelates on Metal Nanorods

PubMed Central

Zhang, Jian; Fu, Yi; Ray, Krishanu; Wang, Yuan; Lakowicz, Joseph. R.

2013-01-01

In this article, we report the change of optical properties for europium chelates on silver nanorods by near-field interactions. The silver rods were fabricated in a seed-growth method followed by depositing thin layers of silica on the surfaces. The europium chelates were physically absorbed in the silica layers on the silver rods. The silver rods were observed to exhibit two plasmon absorption bands from longitudinal and transverse directions, respectively, centered at 394 and 675 nm, close to absorption and emission bands from the Eu(III) chelates. As a result, the immobilized Eu(III) chelates on the silver rods should have strong interactions with the silver nanorods and lead to greatly improved optical properties. The Eu–Ag rod complexes were observed to have enhanced emission intensity up to 240-fold in comparison with the Eu(III) chelates in the metal-free silica templates. This enhancement is much larger than the value for the Eu(III) chelates on the gold rods or silver spheres indicating the presence of stronger interactions for the Eu(III) chelates with the silver rods. The interactions of Eu(III) chelates with the silver rods were also proven by extremely reduced lifetime. Moreover, the Eu–Ag rod complexes exhibited a polarized emission, which was also due to strong interactions of the Eu(III) chelates with the silver rods. All of these features may promise that the Eu(III)–Ag rod complexes have great potential for use as fluorescence imaging agents in biological assays. PMID:24363816

Spectroscopic properties and Judd-Ofelt theory analysis of erbium chelates.

PubMed

Wang, Huaishan; Qian, Guodong; Wang, Zhiyu; Wang, Minquan

2005-11-01

Erbium chelates including tris(acetylacetonato) erbium(III) monohydrate, tris(acetylacetonato)(1,10-phenanthroline) erbium(III) and tris(trifluoroacetylacetonato)(1,10-phenanthroline) erbium(III) are synthesized. Judd-Ofelt theory is employed on basis of the UV-Vis-NIR absorption spectra of erbium chelates dissolved in methanol. Judd-Ofelt parameters of erbium chelates are determined by a least square fitting and dealt with the chemical structure of erbium chelates. Photoluminescence characteristics of erbium chelates are investigated upon excitation at 488 nm by an Ar(+) laser. The qualitative correlation of Judd-Ofelt parameters with photoluminescence properties for erbium chelates is also discussed. It is found that larger Omega(6) value for erbium chelate is and larger photoluminescence intensity at 1.54 microm is, and Omega(2) value should contribute to the photoluminescence full width at half maximum (FWHM) at 1.54 microm. The changes of Judd-Ofelt parameters result from the introduction of the second ligand phenathroline or the substitution of electron-drawing group CF(3) in beta-diketone for erbium chelates.

Simulation of the influence of EDTA on the sorption of heavy metals by humic acids

NASA Astrophysics Data System (ADS)

Kropacheva, T. N.; Didik, M. V.; Kornev, V. I.

2015-04-01

The results of mathematical simulation of sorption equilibria with the participation of divalent cations of heavy metals (HMs), chelant (EDTA), and insoluble forms of humic acids (HAs) are discussed. It is shown that the formation of chelates of metals with EDTA in solutions results in the decreasing sorption of the metals by humic acids. We also analyzed the effect of the acidity of the medium and the HM: EDTA: HA ratio (in a wide range) on the desorption of metals. The desorbing effect of EDTA on the metals is the highest at pH 3-5 and increases with an increase in the concentration of EDTA and a decrease in the concentration of HAs. With respect to the remobilization of metals under the impact of EDTA, the metal cations can be arranged into the following sequence: Cu(II) > Ni(II) > Pb(II) ≫ Cd(II) > Co(II) > Zn(II). The obtained data have been used to analyze the remobilization / extraction of HMs from soils with a high content of humic substances.

Obligatory reduction of ferric chelates in iron uptake by soybeans.

PubMed

Chaney, R L; Brown, J C; Tiffin, L O

1972-08-01

The contrasting Fe(2+) and Fe(3+) chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe(3+)-chelates. EDDHA binds Fe(3+) strongly, but Fe(2+) weakly; BPDS binds Fe(2+) strongly but Fe(3+) weakly. Addition of an excess of BPDS to nutrient solutions containing Fe(3+)-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)(3)](4-) accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe(3+)-chelates appear to require reduction of Fe(3+)-chelate to Fe(2+)-chelate at the root, with Fe(2+) being the principal form of Fe absorbed by soybean.

Chelators whose affinity for calcium is decreased by illumination

NASA Technical Reports Server (NTRS)

Tsien, Roger Y. (Inventor); Grynkiewicz, Grzegorz (Inventor); Minta, Akwasi (Inventor)

1987-01-01

The present invention discloses a group of calcium chelating compounds which have a descreased affinity for calcium following illumination. These new compounds contain a photolabile nitrobenzyl derivative coupled to a tetracarboxylate Ca.sup.2+ chelating parent compound having the octacoordinate chelating groups characteristic of EGTA or BAPTA. In a first form, the new compounds are comprised of a BAPTA-like chelator coupled to a single 2-nitrobenzyl derivative, which in turn is a photochemical precursor of a 2-nitrosobenzophenone. In a second form, the new compounds are comprised of a BAPTA-like chelator coupled to two 2-nitrobenzyl derivatives, themselves photochemical prcursors of the related 2-nitrosobenzophenones. The present invention also discloses a novel method for preparing 1-hydroxy- or 1-alkoxy-1-(2-nitroaryl)-1-aryl methanes. Methanes of this type are critical to the preparation of, or actually constitute, the photolabile Ca.sup.2+ chelating compounds disclosed and claimed herein.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

Molecular recognition modes between adenine or adeniniun(1+) ion and binary M(II)(pdc) chelates (MCoZn; pdc=pyridine-2,6-dicarboxylate(2-) ion).

PubMed

Del Pilar Brandi-Blanco, María; Choquesillo-Lazarte, Duane; Domínguez-Martín, Alicia; Matilla-Hernández, Antonio; González-Pérez, Josefa María; Castiñeiras, Alfonso; Niclós-Gutiérrez, Juan

2013-10-01

Mixed ligand M(II)-complexes (MCoZn) with pyridine-2,6-dicarboxylate(2-) chelator (pdc) and adenine (Hade) have been synthesized and studied by X-ray diffraction and other spectral and thermal methods: [Cu(pdc)(H(N9)ade)(H2O)] (1), [Cu2(pdc)2(H2O)2(μ2-N3,N7-H(N9)ade)]·3H2O (2), trans-[M(pdc)(H(N9)ade)(H2O)2]·nH2O for MCo (3-L, 3-M, 3-H) or Zn (4-L, 4-H), where n is 0, 1 or 3 for the 'lowest' (L), 'medium' (M) and 'highest' (H) hydrated forms, and the salt trans-[Ni(pdc)(H2(N1,N9)ade)(H2O)2]Cl·2H2O (5). In all the nine compounds, both neutral and cationic adenine exist as their most stable tautomer and the molecular recognition pattern between the metal-pdc chelates and the adenine or adeninium(1+) ligands involves the MN7 bond in cooperation with an intra-molecular N6H⋯O(coordinated carboxylate) interligand interaction. In addition the dinuclear copper(II) compound (2) has the CuN3 bond and the N9H⋯O(coord. carboxylate) interaction. The structures of mononuclear ternary complexes proved that the molecular recognition pattern is the same irrespective of (a) the coordination geometry of the complex molecule, (b) the different hydrated forms of crystals with Co or Zn, and (c) the neutral of cationic form of the adenine ligand. These features are related to the mer-NO2 chelating ligand conformation (imposed by the planar rigidity of pdc) as a driving force for the observed metal binding mode. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of iron chelators for Cooley's anemia. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crosby, W.H.; Green, R.

Iron chelators were screened in an iron-loaded rat model using selective radioiron probes. In all experiments, chelators D and F, in that order, induced significant loss of radioiron compared with controls. However, use of chelator D was associated with side effects, and resulted in the death of some animals. There was some evidence that chelator A also caused iron loss significantly greater than controls. Chelators B, C and E were without apparent enhancing effect on radioiron excretion. This was a blind study and the compounds used were A - 2,3-Dihydroxybenzoic acid; B - N,N1-Dimethyladipohydroxamic acid; C - DL-Phenylalanine hydroxamic acid;more » D - Ethylenediamine-N,N1-bis(2-hydroxphenylacetic acid); E - Propionohydroxamic acid; and F - Deferrioxamine B.« less

Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

PubMed

Sakakihara, Y; Volpe, J J

1985-12-15

The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

Yeast Kch1 and Kch2 membrane proteins play a pleiotropic role in membrane potential establishment and monovalent cation homeostasis regulation.

PubMed

Felcmanova, Kristina; Neveceralova, Petra; Sychrova, Hana; Zimmermannova, Olga

2017-08-01

The Kch1 and Kch2 plasma-membrane proteins were identified in Saccharomyces cerevisiae as being essential for the activation of a high-affinity Ca2+ influx system. We searched for Kch proteins roles in the maintenance of cation homeostasis and tested the effect of kch1 and/or kch2 deletions on various physiological parameters. Compared to wild-type, kch1 kch2 mutant cells were smaller, relatively hyperpolarised, grew better under limited K+ conditions and exhibited altered growth in the presence of monovalent cations. The absence of Kch1 and Kch2 did not change the intracellular pH in cells growing at low potassium or the tolerance of cells to divalent cations, high concentration of sorbitol or extreme external pH. The overexpression of KCH1 only increased the intracellular pH in the presence of elevated K+ in media. None of the phenotypes associated with the deletion of KCH1 and KCH2 in wild type were observed in a strain lacking KCH genes and main K+ uptake systems Trk1 and Trk2. The role of the Kch homologue in cation homeostasis was also tested in Candida albicans cells. Our data demonstrate that Kch proteins significantly contribute to the maintenance of optimal cation homeostasis and membrane potential in S. cerevisiae but not in C. albicans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interaction of divalent minerals with liposoluble nutrients and phytochemicals during digestion and influences on their bioavailability - a review.

PubMed

Corte-Real, Joana; Bohn, Torsten

2018-06-30

Several divalent minerals, including the macroelements calcium and magnesium, are essential nutrients for humans. However, their intake, especially via high-dose supplements, has been suspected to reduce the availability of lipophilic dietary constituents, including lipids, liposoluble vitamins, and several phytochemicals such as carotenoids. These constituents require emulsification in order to be bioavailable, and high divalent mineral concentrations may perturb this process, due to precipitations of free fatty acids or bile salt complexation, both pivotal for mixed micelle formation. Though in part based on in vitro or indirect evidence, it appears likely that high-dose supplements of divalent minerals around or even below their recommended dietary allowance perturb the availability of certain liposoluble miroconstituents, in addition to reducing absorption of dietary lipids/cholesterol. In this review, we investigate possible negative influences of divalent minerals, including trace elements (iron, zinc), on the digestion and intestinal uptake of lipophilic dietary constituents, with a focus on carotenoids. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cation Coordination Alters the Conformation of a Thrombin-Binding G-Quadruplex DNA Aptamer That Affects Inhibition of Thrombin.

PubMed

Zavyalova, Elena; Tagiltsev, Grigory; Reshetnikov, Roman; Arutyunyan, Alexander; Kopylov, Alexey

2016-10-01

Thrombin-binding aptamers are promising anticoagulants. HD1 is a monomolecular antiparallel G-quadruplex with two G-quartets linked by three loops. Aptamer-thrombin interactions are mediated with two TT-loops that bind thrombin exosite I. Several cations were shown to be coordinated inside the G-quadruplex, including K + , Na + , NH 4 + , Ba 2+ , and Sr 2+ ; on the contrary, Mn 2+ was coordinated in the grooves, outside the G-quadruplex. K + or Na + coordination provides aptamer functional activity. The effect of other cations on aptamer functional activity has not yet been described, because of a lack of relevant tests. Interactions between aptamer HD1 and a series of cations were studied. A previously developed enzymatic method was applied to evaluate aptamer inhibitory activity. The structure-function correlation was studied using the characterization of G-quadruplex conformation by circular dichroism spectroscopy. K + coordination provided the well-known high inhibitory activity of the aptamer, whereas Na + coordination supported low activity. Although NH 4 + coordination yielded a typical antiparallel G-quadruplex, no inhibitory activity was shown; a similar effect was observed for Ba 2+ and Sr 2+ coordination. Mn 2+ coordination destabilized the G-quadruplex that drastically diminished aptamer inhibitory activity. Therefore, G-quadruplex existence per se is insufficient for aptamer inhibitory activity. To elicit the nature of these effects, we thoroughly analyzed nuclear magnetic resonance (NMR) and X-ray data on the structure of the HD1 G-quadruplex with various cations. The most reasonable explanation is that cation coordination changes the conformation of TT-loops, affecting thrombin binding and inhibition. HD1 counterparts, aptamers 31-TBA and NU172, behaved similarly with some distinctions. In 31-TBA, an additional duplex module stabilized antiparallel G-quadruplex conformation at high concentrations of divalent cations; whereas in NU172, a different

A Transient Rise in Free Mg2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation.

PubMed

Maeshima, Kazuhiro; Matsuda, Tomoki; Shindo, Yutaka; Imamura, Hiromi; Tamura, Sachiko; Imai, Ryosuke; Kawakami, Syoji; Nagashima, Ryosuke; Soga, Tomoyoshi; Noji, Hiroyuki; Oka, Kotaro; Nagai, Takeharu

2018-02-05

For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1-5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6-17], free divalent cations such as Mg 2+ and Ca 2+ , which condense chromatin or chromosomes in vitro [18-28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like "beads on a string" by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg 2+ , have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg 2+ indicator that monitors free Mg 2+ dynamics throughout the cell cycle. By combining this indicator with Ca 2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg 2+ , but not Ca 2+ , increase during mitosis. The Mg 2+ increase is coupled with a decrease in ATP, which is normally bound to Mg 2+ in the cell [33]. ATP inhibited Mg 2+ -dependent chromatin condensation in vitro. Chelating Mg 2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg 2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg 2+ -ATP balance. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Molecular crowding has no effect on the dilution thermodynamics of the biologically relevant cation mixtures.

PubMed

Głogocka, Daria; Przybyło, Magdalena; Langner, Marek

2017-04-01

The ionic composition of intracellular space is rigorously maintained in the expense of high-energy expenditure. It has been recently postulated that the cytoplasmic ionic composition is optimized so the energy cost of the fluctuations of calcium ion concentration is minimized. Specifically, thermodynamic arguments have been produced to show that the presence of potassium ions at concentrations higher than 100 mM reduce extend of the energy dissipation required for the dilution of calcium cations. No such effect has been measured when sodium ions were present in the solution or when the other divalent cation magnesium was diluted. The experimental observation has been interpreted as the indication of the formation of ionic clusters composed of calcium, chloride and potassium. In order to test the possibility that such clusters may be preserved in biological space, the thermodynamics of ionic mixtures dilution in solutions containing albumins and model lipid bilayers have been measured. Obtained thermograms clearly demonstrate that the energetics of calcium/potassium mixture is qualitatively different from calcium/sodium mixture indicating that the presence of the biologically relevant quantities of proteins and membrane hydrophilic surfaces do not interfere with the properties of the intracellular aqueous phase.

Metal regeneration of iron chelates in nitric oxide scrubbing

DOEpatents

Chang, Shih-Ger; Littlejohn, David; Shi, Yao

1997-08-19

The present invention relates to a process of using metal particles to reduce NO to NH.sub.3. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20.degree. and 90.degree. C. to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution.

Metal regeneration of iron chelates in nitric oxide scrubbing

DOEpatents

Chang, S.G.; Littlejohn, D.; Shi, Y.

1997-08-19

The present invention relates to a process of using metal particles to reduce NO to NH{sub 3}. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: (a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20 and 90 C to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution. 34 figs.

Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

PubMed

Pottosin, Igor; Dobrovinskaya, Oxana

2014-05-15

Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol. Copyright © 2014 Elsevier GmbH. All rights reserved.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

Evolution in vitro of an RNA enzyme with altered metal dependence

NASA Technical Reports Server (NTRS)

Lehman, N.; Joyce, G. F.

1993-01-01

The Tetrahymena group I ribozyme catalyses a sequence-specific phosphodiester cleavage reaction on an external RNA oligonucleotide substrate in the presence of a divalent metal cation cofactor. This reaction proceeds readily with either Mg2+ or Mn2+, but no detectable reaction has been reported when other divalent cations are used as the sole cofactor. Cations such as Ca2+, Sr2+ and Ba2+ can stabilize the correct folded conformation of the ribozyme, thereby partially alleviating the Mg2+ or Mn2+ requirement. But catalysis by the ribozyme involves coordination of either Mg2+ or Mn2+ at the active site, resulting in an overall requirement for one of these two cations. Here we use an in vitro evolution process to obtain variants of the Tetrahymena ribozyme that are capable of cleaving an RNA substrate in reaction mixtures containing Ca2+ as the divalent cation. These findings extend the range of different chemical environments available to RNA enzymes and illustrate the power of in vitro evolution in generating macromolecular catalysts with desired properties.

Chemical evaluation of HBED/Fe(3+) and the novel HJB/Fe(3+) chelates as fertilizers to alleviate iron chlorosis.

PubMed

López-Rayo, Sandra; Hernández, Diana; Lucena, Juan J

2009-09-23

Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenylacetic) acid (o,o-EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soil. A new chelating agent, HJB (N,N'-bis(2-hydroxy-5-methylphenyl)ethylendiamine-N,N'-diacetic acid) may be an alternative to o,o-EDDHA since its synthesis yields a purer product, but its chemical behavior and efficiency as chlorosis corrector should be evaluated. In this research, a known analogous HBED (N,N'-bis(2-hydroxyphenyl)ethylendiamine-N,N'-diacetic acid) has also been considered. First, an ion-pair high performance liquid chromatography (HPLC) method has been tested for the HJB/Fe(3+) and HBED/Fe(3+) determination. The ability of HJB and HBED to maintain Fe in solution has been compared with respect to o,o-EDDHA. Theoretical modelization for HBED and HJB in agronomic conditions has been done after the determination of the protonation and Ca(II), Mg(II), Fe(III), and Cu(II) stability constants for HJB. Also, batch interaction experiments with soils and soil materials have been conducted. According to our results, HJB/Fe(3+) and HBED/Fe(3+) present high stability, even when competing cations (Cu(2+), Ca(2+)) are present, and have low reactivity with soils and soil components. The chelating agent HJB dissolves a higher amount of Fe than o,o-EDDHA, and it seems as effective as o,o-EDDHA in keeping Fe in solution. These results indicate that these chelates may be very efficient products to correct Fe chlorosis, and additional plant experiments should demonstrate plants' ability to assimilate Fe from HJB/Fe(3+) and HBED/Fe(3+).

Novel hexadentate and pentadentate chelators for 64Cu-based targeted PET imaging

PubMed Central

Sin, Inseok; Kang, Chisoo; Bandara, Nilantha; Sun, Xiang; Zhong, Yongliang; Rogers, Buck E.; Chong, Hyun-Soon

2014-01-01

A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of 64Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability with 64Cu. The new chelators instantly bound to 64Cu with high labeling efficiency and maximum specific activity. All 64Cu-radiolabeled complexes in human serum remained intact for 2 days. The 64Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Among the 64Cu-radiolabeled complexes evaluated, 64Cu-complex of the new chelator E was well tolerated with a minimal transfer of 64Cu to EDTA. 64Cu-radiolabeled complex of the new chelator E was further evaluated for biodistribution studies using mice and displayed rapid blood clearance and low organ uptake. 64Cu-chelator E produced a favorable in vitro and in vivo complex stability profiles comparable to 64Cu complex of the known hexadentate NOTA chelator. The in vitro and in vivo data highlight strong potential of the new chelator E for targeted PET imaging application. PMID:24657050

Chelation therapy to prevent diabetes-associated cardiovascular events.

PubMed

Diaz, Denisse; Fonseca, Vivian; Aude, Yamil W; Lamas, Gervasio A

2018-05-24

For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD. This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis. In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients.

Glyphosate, a chelating agent-relevant for ecological risk assessment?

PubMed

Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

2018-02-01

Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

Carboxylate-containing chelating agent interactions with amorphous chromium hydroxide: Adsorption and dissolution

NASA Astrophysics Data System (ADS)

Carbonaro, Richard F.; Gray, Benjamin N.; Whitehead, Charles F.; Stone, Alan T.

2008-07-01

Anthropogenic chelating agents and biological chelating agents produced by indigenous organisms may dissolve Cr III (hydr)oxides in soils and sediments. The resulting dissolved Cr III-chelating agent complexes are more readily transported through porous media, thereby spreading contamination. With this work, we examine chelating agent-assisted dissolution of amorphous chromium hydroxide (ACH) by the (amino)carboxylate chelating agents iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), tricarballylic acid (TCA), citric acid (CIT), ethylenediaminetetraacetic acid (EDTA), trans-1,2-cyclohexanediaminetetraacetic acid (CDTA), and trimethylenediaminetetraacetic acid (TMDTA). The extent of chelating agent adsorption onto ACH increased quickly over the first few hours, and then increased more gradually until a constant extent was attained. The extent of chelating agent adsorption versus pH followed "ligand-like" behavior. All chelating agents with the exception of TCA and IDA effectively dissolved significant amounts of ACH within 10 days from pH 4.0 to 9.4. IDA dissolved ACH below pH 6.5 and above pH 7.5. Rates of ACH dissolution normalized to the extent of chelating agent adsorption were pH dependent. IDA, NTA, CIT, and CDTA exhibited an increase in normalized dissolution rate with decreasing pH. EDTA and TMDTA exhibited a maximum in normalized dissolution rate near pH 8.5. Use of acetic acid as a pH buffer in experiments decreased the extent of chelating agent adsorption for IDA, NTA, and CIT but increased normalized rates of chelating agent-assisted dissolution for all chelating agents except EDTA. The results from this study provide the necessary information to calculate the extents and time scales of ACH dissolution in the presence of (amino)carboxylate chelating agents.

High sensitive detection of copper II ions using D-penicillamine-coated gold nanorods based on localized surface plasmon resonance

NASA Astrophysics Data System (ADS)

Hong, Yoochan; Jo, Seongjae; Park, Joohyung; Park, Jinsung; Yang, Jaemoon

2018-05-01

In this paper, we describe the development of a nanoplasmonic biosensor based on the localized surface plasmon resonance (LSPR) effect that enables a sensitive and selective recognition of copper II ions. First, we fabricated the nanoplasmonics as LSPR substrates using gold nanorods (GNR) and the nano-adsorption method. The LSPR sensitivity of the nanoplasmonics was evaluated using various solvents with different refractive indexes. Subsequently, D-penicillamine (DPA)—a chelating agent of copper II ions—was conjugated to the surface of the GNR. The limit of detection (LOD) for the DPA-conjugated nanoplasmonics was 100 pM. Furthermore, selectivity tests were conducted using various divalent cations, and sensitivity tests were conducted on the nanoplasmonics under blood-like environments. Finally, the developed nanoplasmonic biosensor based on GNR shows great potential for the effective recognition of copper II ions, even in human blood conditions.

High sensitive detection of copper II ions using D-penicillamine-coated gold nanorods based on localized surface plasmon resonance.

PubMed

Hong, Yoochan; Jo, Seongjae; Park, Joohyung; Park, Jinsung; Yang, Jaemoon

2018-05-25

In this paper, we describe the development of a nanoplasmonic biosensor based on the localized surface plasmon resonance (LSPR) effect that enables a sensitive and selective recognition of copper II ions. First, we fabricated the nanoplasmonics as LSPR substrates using gold nanorods (GNR) and the nano-adsorption method. The LSPR sensitivity of the nanoplasmonics was evaluated using various solvents with different refractive indexes. Subsequently, D-penicillamine (DPA)-a chelating agent of copper II ions-was conjugated to the surface of the GNR. The limit of detection (LOD) for the DPA-conjugated nanoplasmonics was 100 pM. Furthermore, selectivity tests were conducted using various divalent cations, and sensitivity tests were conducted on the nanoplasmonics under blood-like environments. Finally, the developed nanoplasmonic biosensor based on GNR shows great potential for the effective recognition of copper II ions, even in human blood conditions.

Strategies for the preparation of bifunctional gadolinium(III) chelators

PubMed Central

Frullano, Luca; Caravan, Peter

2012-01-01

The development of gadolinium chelators that can be easily and readily linked to various substrates is of primary importance for the development high relaxation efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over the last 25 years a large number of bifunctional chelators have been prepared. For the most part, these compounds are based on ligands that are already used in clinically approved contrast agents. More recently, new bifunctional chelators have been reported based on complexes that show a more potent relaxation effect, faster complexation kinetics and in some cases simpler synthetic procedures. This review provides an overview of the synthetic strategies used for the preparation of bifunctional chelators for MRI applications. PMID:22375102

Structure and mode of action of cyclic lipopeptide pseudofactin II with divalent metal ions.

PubMed

Janek, Tomasz; Rodrigues, Lígia R; Gudiña, Eduardo J; Czyżnikowska, Żaneta

2016-10-01

The interaction of natural lipopeptide pseudofactin II with a series of doubly charged metal cations was examined by matrix-assisted laser-desorption ionization-time of flight (MALDI-TOF) mass spectrometry and molecular modelling. The molecular modelling for metal-pseudofactin II provides information on the metal-peptide binding sites. Overall, Mg(2+), Ca(2+) and Zn(2+) favor the association with oxygen atoms spanning the peptide backbone, whereas Cu(2+) is coordinated by three nitrogens. Circular dichroism (CD) results confirmed that Zn(2+) and Cu(2+) can disrupt the secondary structure of pseudofactin II at high concentrations, while Ca(2+) and Mg(2+) did not essentially affect the structure of the lipopeptide. Interestingly, our results showed that the addition of Zn(2+) and Cu(2+) helped smaller micelles to form larger micellar aggregates. Since pseudofactin II binds metals, we tested whether this phenomena was somehow related to its antimicrobial activity against Staphylococcus epidermidis and Proteus mirabilis. We found that the antimicrobial effect of pseudofactin II was increased by supplementation of culture media with all tested divalent metal ions. Finally, by using Gram-positive and Gram-negative bacteria we showed that the higher antimicrobial activity of metal complexes of pseudofactin II is attributed to the disruption of the cytoplasmic membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

The Effect of Different Tea Varieties on Iron Chelation

NASA Astrophysics Data System (ADS)

Truong, S. K.; Karim, R.

2016-12-01

The chief objectives of this experiment are to distinguish which type of tea of four variants, pomegranate blackberry green, green, lemon chamomile (herbal), and earl grey (black), are capable of chelating the most iron (III) chloride (FeCl3) through titration. We hypothesized that if each tea variety chelates differing amounts of iron chloride, and if we conduct an experiment in which four different teas are mixed in the same amount of water, iron chloride, and iron chloride indicator EDTA, then the pomegranate blackberry green tea will bind to the most iron due to its large amount of fruit antioxidants. To summarize our methodology, we prepared three solutions of each tea, dissolved with 1 gram of FeCl3 to test three trials per tea variety. The chelation process took place overnight as teas cooled. Six drops of iron chloride indicator added to each solution began the titration. The necessary amount of 0.1M EDTA (ethylenediaminetetraacetic acid) drops required for each solution to turn to a universal amber color from its original dark tone indicates how many free iron molecules were left unbound by the tea solution. After careful analysis of the data, we discovered that blackberry pomegranate green tea possessed the best chelating abilities with 97.48% of FeCl3 adsorbed. Green tea followed with 96.67%. Herbal tea chelated 94.24% of the iron while earl grey absorbed the least amount at 93.43%. From our conclusion, we drew that since blackberry pomegranate green tea contained the highest amount of polyphenols and antioxidants as well as epigallocatechin gallate (EGCG) found in green teas, it was able to chelate the most amount of iron. The substances mentioned in blackberry pomegranate green tea possess the ability to form strong bonds with multiple heavy metals, such as iron (III) chloride atoms. Overall, each variety of tea contains different organic substances. Each of these substances possesses a unique chelating ability, determining how well the type of tea can

Metal chelate process to remove pollutants from fluids

DOEpatents

Chang, Shih-Ger T.

1994-01-01

The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO.sub.x and optionally SO.sub.2 from a fluid using a metal ion (Fe.sup.2+) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC' is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution.

Metal chelate process to remove pollutants from fluids

DOEpatents

Chang, S.G.T.

1994-12-06

The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO[sub x] and optionally SO[sub 2] from a fluid using a metal ion (Fe[sup 2+]) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution. 26 figures.

Mechanisms for monovalent cation-dependent depletion of intracellular Mg2+:Na(+)-independent Mg2+ pathways in guinea-pig smooth muscle.

PubMed

Nakayama, Shinsuke; Nomura, Hideki; Smith, Lorraine M; Clark, Joseph F; Uetani, Tadayuki; Matsubara, Tatsuaki

2003-09-15

It has been suggested that magnesium deficiency is correlated with many diseases. 31P NMR experiments were carried out in order to investigate the effects of Na+ substitution on Mg2+ depletion in smooth muscle under divalent cation-free conditions. In the taenia of guinea-pig caeci, the intracellular free Mg2+ concentration ([Mg2+]i) was estimated from the chemical shifts of (1) the beta-ATP peak alone and (2) beta- and gamma-ATP peaks. Both estimations indicated that [Mg2+]i decreased only very slowly in Mg(2+)-free, Ca(2+)-free solutions in which Na+ was substituted with large cations such as NMDG (N-methyl-D-glucamine) and choline. Furthermore, the measurements of tension development supported the suggestion of preservation of intracellular Mg2+ with NMDG substitution. Substituting extracellular Na+ with the small cation, Li+, also shifted the beta-ATP peak towards a lower frequency, but the frequency shift was significantly less than that seen upon Na+ substitution with K+. The estimated [Mg2+]i depletion was, however, comparable with that seen after Na+ substitution with K+ using the titration curves of metal-free and Mg(2+)-bound ATP obtained in Li(+)-based model solutions. It was concluded that Mg2+ rapidly decreases only when small cations were the major electrolyte of the extracellular medium. Na+ substitutions with NMDG, choline or Li+ had little effect on intracellular ATP concentration after 100 min treatment.

Devil's staircase of odd-number charge order modulations in divalent β -vanadium bronzes under pressure

NASA Astrophysics Data System (ADS)

Yamauchi, Touru; Ueda, Hiroaki; Ohwada, Kenji; Nakao, Hironori; Ueda, Yutaka

2018-03-01

A common characteristic of quasi-one-dimensional (q1D) conductors β -A0.33V2O5 (A = Li, Na, and Ag) is that the charge ordering (CO), the ground state (GS) at ambient pressure, and the superconducting (SC) phases, the GS under high pressure, are competing with each other. We have explored high-pressure properties of divalent β -vanadium bronzes, β -A0.33V2O5 (A = Ca, Sr, and Pb), which are A -cation stoichiometry finely controlled single-crystal/powder samples, and found the absence of the SC phase. In these observations, however, we observed enormous and novel phase transitions, a kind of "devil's staircase"-type phase transitions in the charge ordering (CO) phases. The most surprising discovery in this devil's staircase, which was found mainly in β -Sr0.33V2O5 , is that all the charge modulation vectors of many kinds of CO phases can be represented as a primitive lattice translation vector along the b axis multiplied by several odd numbers. This discovery surely demonstrates interplay between the charge degree freedom and the crystallographic symmetry. We propose two possible mechanisms to explain this phenomenon: "self-charge transfer (carrier redistribution)" between the two subsystems in these compounds and "sequential symmetry reduction" that was discussed in Landau theory of phase transitions. In β -Ca0.33V2O5 we also found a P -T phase diagram similar in outlook but different in detail. The devil's staircase was also observed but it is an incomplete one. Furthermore, the charge modulation vectors in it are shorter than those in β -Sr0.33V2O5 . In β -Pb0.33V2O5 , which has no CO phase at ambient pressure, the pressure-induced antiferromagnetic ordering was observed at around 50 K above 0.5 GPa. Using these two kinds of mechanisms, we also explain the global high-pressure properties in all the stoichiometric divalent β -vanadium bronzes, which were observed as a wide variety of electromagnetic states. In addition, we also discuss a possible key for

Preferential solvation, ion pairing, and dynamics of concentrated aqueous solutions of divalent metal nitrate salts

NASA Astrophysics Data System (ADS)

Yadav, Sushma; Chandra, Amalendu

2017-12-01

We have investigated the characteristics of preferential solvation of ions, structure of solvation shells, ion pairing, and dynamics of aqueous solutions of divalent alkaline-earth metal nitrate salts at varying concentration by means of molecular dynamics simulations. Hydration shell structures and the extent of preferential solvation of the metal and nitrate ions in the solutions are investigated through calculations of radial distribution functions, tetrahedral ordering, and also spatial distribution functions. The Mg2+ ions are found to form solvent separated ion-pairs while the Ca2+ and Sr2+ ions form contact ion pairs with the nitrate ions. These findings are further corroborated by excess coordination numbers calculated through Kirkwood-Buff G factors for different ion-ion and ion-water pairs. The ion-pairing propensity is found to be in the order of Mg(NO3) 2 < C a (NO3) 2 < S r (NO3) 2, and it follows the trend given by experimental activity coefficients. It is found that proper modeling of these solutions requires the inclusion of electronic polarization of the ions which is achieved in the current study through electronic continuum correction force fields. A detailed analysis of the effects of ion-pairs on the structure and dynamics of water around the hydrated ions is done through classification of water into different subspecies based on their locations around the cations or anions only or bridged between them. We have looked at the diffusion coefficients, relaxation of orientational correlation functions, and also the residence times of different subspecies of water to explore the dynamics of water in different structural environments in the solutions. The current results show that the water molecules are incorporated into fairly well-structured hydration shells of the ions, thus decreasing the single-particle diffusivities and increasing the orientational relaxation times of water with an increase in salt concentration. The different structural

Silver Recovery and Power Generation from Ammonia Chelated Silver Solution in a Bio-Electrochemical Reactor

NASA Astrophysics Data System (ADS)

Ho, N. A. D.; Babel, S.

2017-06-01

Silver has valuable features and limited availability, and thus recovery from wastewater or aqueous solutions plays an important role in environmental protection and economic profits. In this study, silver recovery along with power generation and COD removal were investigated in a bio-electrochemical system (BES). The BES comprised of an anode and a cathode chamber which were separated by a cation exchange membrane to prevent the cross-over of electrolytes. During the biological oxidation of acetate as an electron donor in the anode chamber, the reduction of ammonia chelated silver ions as electron acceptors in the cathode side occurred spontaneously. Results showed that a silver recovery of 99% and COD removal efficiency of 60% were achieved at the initial silver concentration of 1,000 mg/L after 48 hours of operation. The power generation improved 4.66%, from 3,618 to 3,795 mW/m3, by adding NaNO3 of 850 mg/L to the catholyte containing 2,000 mg/L of silver ions. Deposits on the cathode surface were characterized using scanning electron microscope (SEM) and energy dispersive X-ray (EDX). Metallic silver with dendritic structures and high purity were detected. This study demonstrated that BES technology can be employed to recover silver from complex chelating solution, produce electricity, and treat wastewater.

Supercritical Fluid Extraction of Metal Chelate: A Review.

PubMed

Ding, Xin; Liu, Qinli; Hou, Xiongpo; Fang, Tao

2017-03-04

Supercritical fluid extraction (SFE), as a new green extraction technology, has been used in extracting various metal species. The solubilities of chelating agents and corresponding metal chelates are the key factors which influence the efficiency of SFE. Other main properties of them such as stability and selectivity are also reviewed. The extraction mechanisms of mainly used chelating agents are explained by typical examples in this paper. This is the important aspect of SFE of metal ions. Moreover, the extraction efficiencies of metal species also depend on other factors such as temperature, pressure, extraction time and matrix effect. The two main complexation methods namely in-situ and on-line chelating SFE are described in detail. As an efficient chelating agent, tributyl phosphate-nitric acid (TBP-HNO 3 ) complex attracts much attention. The SFE of metal ions, lanthanides and actinides as well as organometallic compounds are also summarized. With the proper selection of ligands, high efficient extraction of metal species can be obtained. As an efficient sample analysis method, supercritical fluid chromatography (SFC) is introduced in this paper. Recently, the extraction method combining ionic liquids (ILs) with supercritical fluid has been becoming a novel technology for treating metal ions. The kinetics related to SFE of metal species is discussed with some specific examples.

Inter-DNA Attraction Mediated by Divalent Counterions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Xiangyun; Andresen, Kurt; Kwok, Lisa W.

2007-07-20

Can nonspecifically bound divalent counterions induce attraction between DNA strands? Here, we present experimental evidence demonstrating attraction between short DNA strands mediated by Mg{sup 2+} ions. Solution small angle x-ray scattering data collected as a function of DNA concentration enable model independent extraction of the second virial coefficient. As the [Mg{sup 2+}] increases, this coefficient turns from positive to negative reflecting the transition from repulsive to attractive inter-DNA interaction. This surprising observation is corroborated by independent light scattering experiments. The dependence of the observed attraction on experimental parameters including DNA length provides valuable clues to its origin.

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

PubMed Central

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

2013-01-01

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling.

PubMed

Tsionou, Maria Iris; Knapp, Caroline E; Foley, Calum A; Munteanu, Catherine R; Cakebread, Andrew; Imberti, Cinzia; Eykyn, Thomas R; Young, Jennifer D; Paterson, Brett M; Blower, Philip J; Ma, Michelle T

2017-10-24

Gallium-68 ( 68 Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68 Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68 Ga 3+ . Ideally, the chelator will rapidly, quantitatively and stably coordinate 68 Ga 3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68 Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68 Ga 3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68 Ga 3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5-50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68 Ga 3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low

Magnetic moment directions and distributions of cations in Cr (Co) substituted spinel ferrites Ni0.7Fe2.3O4

NASA Astrophysics Data System (ADS)

Xue, L. C.; Lang, L. L.; Xu, J.; Li, Z. Z.; Qi, W. H.; Tang, G. D.; Wu, L. Q.

2015-09-01

Powder samples of the spinel ferrites MxNi0.7-xFe2.3O4 (M = Cr, Co and 0.0 ≤ x ≤ 0.3) and CrxNi0.7Fe2.3-xO4 (0.0 ≤ x ≤ 0.3) were synthesized using the chemical co-precipitation method. The XRD spectra confirmed that the samples had a single-phase cubic spinel structure. Magnetic measurements showed that the magnetic moments (μexp) per formula both at 10 K and 300 K increased with Co substitution, while the values of μexp decreased with Cr substitution. Applying the assumption that the magnetic moments of Cr2+ and Cr3+ lie antiparallel to those of the divalent and trivalent Fe, Co, and Ni cations in the same sublattice of spinel ferrites, these interesting behaviors could be easily interpreted. The cation distributions of the three series of samples were estimated successfully by fitting the dependences of μexp, measured at 10 K, on the doping level x, using a quantum-mechanical potential barrier model earlier proposed by our group. The results obtained for the Cr cation distributions at the (A) and [B] sites are very close to those obtained elsewhere using neutron diffraction.

Synthetic and natural iron chelators: therapeutic potential and clinical use

PubMed Central

Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

2013-01-01

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

Efficacy of chelation therapy to remove aluminium intoxication.

PubMed

Fulgenzi, Alessandro; De Giuseppe, Rachele; Bamonti, Fabrizia; Vietti, Daniele; Ferrero, Maria Elena

2015-11-01

There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in μg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

Extraction of metals using supercritical fluid and chelate forming legand

DOEpatents

Wai, Chien M.; Laintz, Kenneth E.

1998-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated .beta.-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated .beta.-diketone and a trialkyl phosphate, or a fluorinated .beta.-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated .beta.-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Extraction of metals using supercritical fluid and chelate forming ligand

DOEpatents

Wai, C.M.; Laintz, K.E.

1998-03-24

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated {beta}-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated {beta}-diketone and a trialkyl phosphate, or a fluorinated {beta}-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated {beta}-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process. 7 figs.

Interactions of protamine with the marine bacterium, Pseudoalteromonas sp. NCIMB 2021.

PubMed

Pustam, A; Smith, C; Deering, C; Grosicki, K M T; Leng, T Y; Lin, S; Yang, J; Pink, D; Gill, T; Graham, L; Derksen, D; Bishop, C; Demont, M E; Wyeth, R C; Smith-Palmer, T

2014-03-01

Pseudoalteromonas sp. NCIMB 2021 (NCIMB 2021) was grown in synthetic seawater (SSW) containing pyruvate, in the presence (SSW(++) ) and absence (SSW(-) ) of divalent cations. Cultures contained single cells. Addition of the cationic antibacterial peptide (CAP), protamine, did not inhibit, but rather increased, the growth of NCIMB 2021 in SSW(++) and caused the bacteria to grow in chains. Bacterial growth was assessed using turbidity, cell counts and the sodium salt of resazurin. In SSW(-) , NCIMB 2021 was no longer resistant to protamine. The minimum inhibitory concentration (MIC) was 5 mg ml(-1) . Protamine is a cationic antimicrobial peptide (CAP), which is active against a variety of bacteria. This is the first in-depth study of the interaction of protamine with a marine bacterium, Pseudoalteromonas sp. NCIMB 2021. Our results show that protamine is only active in seawater in the absence of divalent cations. In the presence of the divalent cations, Mg(2+) and Ca(2+) , protamine enhances the growth of Pseudoalteromonas sp. NCIMB 2021 and produces chains rather than individual cells. These are important considerations when deciding on applications for protamine and in terms of understanding its mechanism of action. © 2013 The Society for Applied Microbiology.

Flocculation of Chlamydomonas reinhardtii with Different Phenotypic Traits by Metal Cations and High pH

PubMed Central

Fan, Jianhua; Zheng, Lvhong; Bai, Yunpeng; Saroussi, Shai; Grossman, Arthur R.

2017-01-01

Concentrating algal cells by flocculation as a prelude to centrifugation could significantly reduce the energy and cost of harvesting the algae. However, how variation in phenotypic traits such as cell surface features, cell size and motility alter the efficiency of metal cation and pH-induced flocculation is not well understood. Our results demonstrate that both wild-type and cell wall-deficient strains of the green unicellular alga Chlamydomonas reinhardtii efficiently flocculate (>90%) at an elevated pH of the medium (pH 11) upon the addition of divalent cations such as calcium and magnesium (>5 mM). The trivalent ferric cation (at 10 mM) proved to be essential for promoting flocculation under weak alkaline conditions (pH ∼8.5), with a maximum efficiency that exceeded 95 and 85% for wild-type CC1690 and the cell wall-deficient sta6 mutant, respectively. Near complete flocculation could be achieved using a combination of 5 mM calcium and a pH >11, while the medium recovered following cell removal could be re-cycled without affecting algal growth rates. Moreover, the absence of starch in the cell had little overall impact on flocculation efficiency. These findings contribute to our understanding of flocculation in different Chlamydomonas strains and have implications with respect to inexpensive methods for harvesting algae with different phenotypic traits. Additional research on the conditions (e.g., pH and metal ions) used for efficient flocculation of diverse algal groups with diverse characteristics, at both small and large scale, will help establish inexpensive procedures for harvesting cell biomass. PMID:29209355

Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

PubMed

da Silva-Souza, Hercules Antônio; Lira, Maria Nathalia de; Costa-Junior, Helio Miranda; da Cruz, Cristiane Monteiro; Vasconcellos, Jorge Silvio Silva; Mendes, Anderson Nogueira; Pimenta-Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Persechini, Pedro Muanis

2014-07-01

We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages. Copyright © 2014 Elsevier B.V. All rights reserved.

Deficiency in the divalent metal transporter 1 augments bleomycin-induced lung injury

EPA Science Inventory

Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate in metal transport ...

Study of the reaction of tungsten carbide in molten alkali metal nitrates. Syntheses of divalent (s and d blocks) metal tungstates

NASA Astrophysics Data System (ADS)

Deloume, Jean-Pierre; Marote, Pedro; Sigala, Catherine; Matei, Cristian

2003-08-01

WC is tested as precursor to synthesize metal tungstates by reaction in molten alkali metal nitrates. This constitutes a complex redox system with two reducing agents, W and C, and an oxidizer having several oxidation states. The mass loss due to the evolution of gases reveals the reaction steps. The infrared analyses of the gas phase show what kind of reaction develops according to the temperature. WC produces a water-soluble alkali metal tungstate. The reaction of a mixture of WC and a divalent metal chloride (Mg, Ca, Ba, Ni, Cu, Zn) leads to water-insoluble metal tungstates. As the reactivity of the cations increases in the order Zn, Ni, Cu, the reaction of WC is modified by their presence. The physico-chemical characterizations of the products show that some of them are contaminated either by WC or by metal oxide. Some others are rather pure products. These differences, in relationship with the other analyses, allow to propose first reaction pathways of the tungsten carbide in molten salts.

Desferrithiocin: A Search for Clinically Effective Iron Chelators

PubMed Central

2015-01-01

The successful search for orally active iron chelators to treat transfusional iron-overload diseases, e.g., thalassemia, is overviewed. The critical role of iron in nature as a redox engine is first described, as well as how primitive life forms and humans manage the metal. The problems that derive when iron homeostasis in humans is disrupted and the mechanism of the ensuing damage, uncontrolled Fenton chemistry, are discussed. The solution to the problem, chelator-mediated iron removal, is clear. Design options for the assembly of ligands that sequester and decorporate iron are reviewed, along with the shortcomings of the currently available therapeutics. The rationale for choosing desferrithiocin, a natural product iron chelator (a siderophore), as a platform for structure–activity relationship studies in the search for an orally active iron chelator is thoroughly developed. The study provides an excellent example of how to systematically reengineer a pharmacophore in order to overcome toxicological problems while maintaining iron clearing efficacy and has led to three ligands being evaluated in human clinical trials. PMID:25207964

Structural and energetic study of cation-π-cation interactions in proteins.

PubMed

Pinheiro, Silvana; Soteras, Ignacio; Gelpí, Josep Lluis; Dehez, François; Chipot, Christophe; Luque, F Javier; Curutchet, Carles

2017-04-12

Cation-π interactions of aromatic rings and positively charged groups are among the most important interactions in structural biology. The role and energetic characteristics of these interactions are well established. However, the occurrence of cation-π-cation interactions is an unexpected motif, which raises intriguing questions about its functional role in proteins. We present a statistical analysis of the occurrence, composition and geometrical preferences of cation-π-cation interactions identified in a set of non-redundant protein structures taken from the Protein Data Bank. Our results demonstrate that this structural motif is observed at a small, albeit non-negligible frequency in proteins, and suggest a preference to establish cation-π-cation motifs with Trp, followed by Tyr and Phe. Furthermore, we have found that cation-π-cation interactions tend to be highly conserved, which supports their structural or functional role. Finally, we have performed an energetic analysis of a representative subset of cation-π-cation complexes combining quantum-chemical and continuum solvation calculations. Our results point out that the protein environment can strongly screen the cation-cation repulsion, leading to an attractive interaction in 64% of the complexes analyzed. Together with the high degree of conservation observed, these results suggest a potential stabilizing role in the protein fold, as demonstrated recently for a miniature protein (Craven et al., J. Am. Chem. Soc. 2016, 138, 1543). From a computational point of view, the significant contribution of non-additive three-body terms challenges the suitability of standard additive force fields for describing cation-π-cation motifs in molecular simulations.

Chelation of heavy group 2 (radio)metals by p-tert-butylcalix[4]arene-1,3-crown-6 and logK determination via NMR

NASA Astrophysics Data System (ADS)

Bauer, David; Gott, Matthew; Steinbach, Jörg; Mamat, Constantin

2018-06-01

A crown-bridged calix[4]arene scaffold was investigated as lead compound for the ligation of heavy alkaline earth metals such as strontium and barium, which appear to be useful for radiopharmaceutical applications in diagnosis as well as in radiotherapy. In particular barium, due to its chemical similarities, could serve as a surrogate for radium, a metal of high radiopharmaceutical interest. The ability of p-tert-butylcalix[4]arene-1,3-crown-6 (1) in particular to chelate cations, such as group 1 and 2 metal ions or ammonium ions is well known. Also, the manifold possibilities of structural modification on the upper- and lower-rim as well as on the crown itself produce properties that may lead to a highly selective and effective chelating agent. In this work, titration experiments of the perchlorate salts of Ba2+, Sr2+ and Pb2+ with ligand 1 were performed to determine their stability constants (logK = 4.7, 4.3, and 3.3, respectively) by 1H NMR measurements in acetonitrile-d3.

The Human Natural Killer Cell Immune Synapse

NASA Astrophysics Data System (ADS)

Davis, Daniel M.; Chiu, Isaac; Fassett, Marlys; Cohen, George B.; Mandelboim, Ofer; Strominger, Jack L.

1999-12-01

Inhibitory killer Ig-like receptors (KIR) at the surface of natural killer (NK) cells induced clustering of HLA-C at the contacting surface of target cells. In this manner, inhibitory immune synapses were formed as human NK cells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distributed into rings around central patches of intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, the opposite orientation to mature murine T cell-activating synapses. This organization of protein was stable for at least 20 min. Cells could support multiple synapses simultaneously, and clusters of HLA-C moved as NK cells crawled over target cells. Clustering required a divalent metal cation, explaining how metal chelators inhibit KIR function. Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine and cytochalsins B and D. Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats.

PubMed

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J S

2009-10-15

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril+DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

Rates of cuticular penetration of chelated Fe(III): role of humidity, concentration, adjuvants, temperature, and type of chelate.

PubMed

Schönherr, Jörg; Fernández, Victoria; Schreiber, Lukas

2005-06-01

Time courses of cuticular penetration of FeCl3 and Fe(III) complexes of citric acid, EDTA, EDDHA (Sequestrene 138Fe), imidodisuccinic acid (IDHA), and ligninsulfonic acid (Natrel) were studied using astomatous cuticular membranes (CMs) isolated from Populus x canescens leaves. At 100% relative humidity, the Fe(III) chelates disappeared exponentially with time from the surface of the CMs; that is, penetration was a first-order process that can be described using rate constants or half-times of penetration (t(1/2)). Half-times ranged from 20 to 30 h. At 90% humidity, penetration rates were insignificant with the exception of Natrel, for which t(1/2) amounted to 58 h. Rate constants were independent of temperature (15, 25, and 35 degrees C). Permeability decreased with increasing Fe chelate concentration (IDHA and EDTA). At 100% humidity, half-times measured with FeIDHA were 11 h (2 mmol L(-1)), 17 h (10 mmol L(-1)) and 36 h (20 mmol L(-1)), respectively. In the presence of FeEDTA, penetration of CaCl2 was slowed greatly. Half-times for penetration of CaCl2, which were 1.9 h in the absence of FeEDTA, rose to 3.12 h in the presence of an equimolar concentration of EDTA and 13.3 h when the FeEDTA concentration was doubled. Hence, Fe chelates reduced permeability of CMs to CaCl2 and to the Fe chelates themselves. It is suggested that Fe chelates reduced the size of aqueous pores. This view is supported by the fact that rate constants for calcium salts were about 5 times higher than for Fe chelates with the same molecular weights. Adding Tween 20 (5 g L(-1)) as a humectant did not increase permeability to FeIDHA at 90% humidity and below, while addition of glycine betaine did. Penetration of FeCl3 applied at 5 g L(-1) (pH 1.5) was not a first order process as rate constants decreased rapidly with time. Only 2% of the dose penetrated during the first 2 h and less than that in the subsequent 8 h. Recovery was only 70%. This was attributed to the formation of insoluble Fe

Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous Model Food Systems.

PubMed

Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2015-09-01

Many packaged food products undergo quality deterioration due to iron promoted oxidative reactions. Recently, we have developed a nonmigratory iron chelating active packaging material that represents a novel approach to inhibit oxidation of foods while addressing consumer demands for "cleanˮ labels. A challenge to the field of nonmigratory active packaging is ensuring that surface-immobilized active agents retain activity in a true food system despite diffusional limitations. Yet, the relationship between food viscosity and nonmigratory active packaging activity retention has never been characterized. The objective of this study was to investigate the influence of food viscosity on iron chelation by a nonmigratory iron chelating active packaging material. Methyl cellulose was added to aqueous buffered iron solutions to yield model systems with viscosities ranging from ∼1 to ∼10(5)  mPa·s, representing viscosities ranging from beverage to mayonnaise. Iron chelation was quantified by material-bound iron content using colorimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES).  Maximum iron chelation was reached in solutions up to viscosity ∼10(2)  mPa·s. In more viscous solutions (up to ∼10(4)  mPa·s), there was a significant decrease in iron chelating capacity (P < 0.05). However, materials still retained at least 76% iron chelating capacity. Additionally, the influence of different food hydrocolloids on the performance of nonmigratory iron chelating active packaging was characterized. Methyl cellulose and carrageenan did not compete with the material for specific iron chelation (P > 0.05). Materials retained 32% to 45% chelating capacity when in contact with competitively chelating hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates the potential application of nonmigratory iron chelating active packaging in liquid and semi-liquid foods to allow for the removal of synthetic chelators, while

Metal-dependent inhibition of HIV-1 integrase by 5CITEP inhibitor: A theoretical QM/MM approach

NASA Astrophysics Data System (ADS)

do Nascimento, Josenaide P.; Araújo Silva, José Rogério; Lameira, Jerônimo; Alves, Cláudio N.

2013-09-01

HIV-1 integrase (IN) is a potential target for developing drugs against AIDS. In this letter, QM/MM approach was used to study the inhibition of IN by 5CITEP inhibitor in presence of divalent cations (Mg2+ or Mn2+). In addition, the main interactions occurring in 5CITEP-IN complex and the influence of divalent cations (Mg2+ or Mn2+) in enzymatic inhibition were investigated using B3LYP/6-31+G(d,p)/MM. The results suggest that the Asp64, Asp116 and four crystal water molecules plays a crucial role in cation (Mg2+ or Mn2+) coordination sphere.

Comparing potential copper chelation mechanisms in Parkinson's disease protein

NASA Astrophysics Data System (ADS)

Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

2011-03-01

We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.

PubMed

Mellado, Laura; Calcagno-Pizarelli, Ana Maria; Lockington, Robin A; Cortese, Marc S; Kelly, Joan M; Arst, Herbert N; Espeso, Eduardo A

2015-09-01

The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to

Characterization of divalent and trivalent species generated in the chemical and electrochemical oxidation of a dimeric pincer complex of nickel.

PubMed

Spasyuk, Denis M; Gorelsky, Serge I; van der Est, Art; Zargarian, Davit

2011-03-21

The electrolytic and chemical oxidation of the dimeric pincer complex [κ(P),κ(C),κ(N),μ(N)-(2,6-(i-Pr(2)POC(6)H(3)CH(2)NBn)Ni](2) (1; Bn = CH(2)Ph) has been investigated by various analytic techniques. Cyclic voltammetry measurements have shown that 1 undergoes a quasi-reversible, one electron, Ni-based redox process (ΔE(0)(1/2) = -0.07 V vs Cp(2)Fe/[Cp(2)Fe](+)), and spectroelectrochemical measurements conducted on the product of the electrolytic oxidation, [1](+•), have shown multiple low-energy electronic transitions in the range of 10,000-15,000 cm(-1). Computational studies using Density Functional Theory (B3LYP) have corroborated the experimentally obtained structure of 1, provided the electronic structure description, and helped interpret the experimentally obtained absorption spectra for 1 and [1](+·). These calculations indicate that the radical cation [1](+·) is a dimeric, mixed-valent species (class III) wherein most of the spin density is delocalized over the two nickel centers (Ni(+2.5)(2)N(2)), but some spin density is also present over the two nitrogen atoms (Ni(2+)(2)N(2)·). Examination of alternative structures for open shell species generated from 1 has shown that the spin density distribution is highly sensitive toward changes in the ligand environment of the Ni ions. NMR, UV-vis, electron paramagnetic resonance (EPR), and single crystal X-ray diffraction analyses have shown that chemical oxidation of 1 with N-Bromosuccinimide (NBS) follows a complex process that gives multiple products, including the monomeric trivalent species κ(P),κ(C),κ(N)-{2,6-(i-Pr(2)PO)(C(6)H(3))(CH═NBn)}NiBr(2) (2). These studies also indicate that oxidation of 1 with 1 equiv of NBS gives an unstable, paramagnetic intermediate that decomposes to a number of divalent species, including succinimide and the monomeric divalent complexes κ(P),κ(C),κ(N)-{2,6-(i-Pr(2)PO)(C(6)H(3))(CH═NBn)}NiBr (3) and κ(P),κ(C),κ(N)-{2,6-(i-Pr(2)PO)(C(6)H(3))(CH(2)N

Development of an iron chelating polyethylene film for active packaging applications.

PubMed

Tian, Fang; Decker, Eric A; Goddard, Julie M

2012-02-29

Metal-promoted oxidation reactions are a major cause of food quality deterioration. Active packaging offers novel approaches to controlling such oxidation for the purpose of extending shelf life. Herein, we report modification of the surface of polyethylene (PE) films to possess metal chelating activity. Metal chelating carboxylic acids were introduced to the film surface using cross-linking agents [polyethylenimine (PEI) or ethylenediamine (ED)] to increase the number of available carboxylic acids. ATR-FTIR, contact angle, dye assay, and iron chelating assay were used to characterize changes in surface chemistry after each functionalization step. The chelator poly(acrylic acid) (PAA) was attached to the surface at a density of 9.12 ± 0.71 nmol carboxyl groups/cm², and exhibited an iron chelating activity. The results indicate that PAA-modified PE films might have a higher affinity to Fe³⁺ than Fe²⁺ with the optimum binding pH at 5.0. Such inexpensive active packaging materials are promising in food industry for the preservation of liquid and semiliquid food products and have application in heavy metal chelation therapy for biomedical materials as well.

Effects of divalent cations and La3+ on contractility and ecto-ATPase activity in the guinea-pig urinary bladder.

PubMed Central

Ziganshin, A U; Ziganshina, L E; Hoyle, C H; Burnstock, G

1995-01-01

1. Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as chloride salts, 1-1000 microM) were tested in the guinea-pig urinary bladder for their ability to: (i) modify contractile responses to electrical field stimulation (EFS), ATP, alpha,beta-methylene ATP (alpha,beta-meATP), carbachol (CCh), and KCl; (ii) affect ecto-ATPase activity. 2. Ba2+ (10-1000 microM) concentration-dependently potentiated contractile responses evoked by EFS (4-16 Hz), ATP (100 microM), alpha,beta-meATP (1 microM), CCh (0.5 microM), and KCl (30 mM). Ni2+ at concentrations of 1-100 microM also potentiated contractility of the urinary bladder, but at concentrations tested its effect was not concentration-dependent. Cu2+ at a concentration of 10 microM and Cd2+ at a concentration of 1 microM potentiated responses to all stimuli, except KCl. Ni2+ at a concentration of 1000 microM and Cd2+ at a concentration of 100 microM inhibited contractions evoked by all stimuli, and at a concentration of 1000 microM Cd2+ abolished any contractions. Responses to ATP and alpha,beta-meATP were selectively inhibited by Cu2+, Zn2+ or La3+, each at a concentration of 1 mM. 3. Cu2+, Ni2+, Zn2+ and La3+ (100-1000 microM) concentration-dependently inhibited ecto-ATPase activity in the urinary bladder smooth muscle preparations, while Ba2+ and Mn2+ were without effect, and Cd2+ and Co2+ caused significant inhibition only at a concentration of 1000 microM. 4. There was no correlation between the extent of ecto-ATPase inhibition and the effect on contractile activity of any of the cations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7735690

IRON UPTAKE AND NRAMP-2/DMTI/DCT IN HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

The capacity of natural resistance-associated macrophage protein-2 [Nramp2; also called divalent metal transporter-1 (DMT1) and divalent cation transporter-1 (DCT1)] to transport iron and its ubiquitous expression make it a likely candidate for transferrin-independent uptake of i...

Simultaneous flow of water and solutes through geological membranes-I. Experimental investigation

USGS Publications Warehouse

Kharaka, Y.K.; Berry, F.A.P.

1973-01-01

The relative retardation by geological membranes of cations and anions generally present in subsurface waters was investigated using a high pressure and high temperature 'filtration cell'. The solutions were forced through different clays and a disaggregated shale subjected to compaction pressures up to 9500 psi and to temperatures from 20 to 70??C. The overall efficiences measured increased with increase of exchange capacity of the material used and with decrease in concentration of the input solution. The efficiency of a given membrane increased with increasing compaction pressure but decreased slightly at higher temperatures for solutions of the same ionic concentration. The results further show that geological membranes are specific for different dissolved species. The retardation sequences varied depending on the material used and on experimental conditions. The sequences for monovalent and divalent cations at laboratory temperatures were generally as follows: Li < Na < NH3 < K < Rb < Cs Mg < Ca < Sr < Ba. The sequences for anions at room temperature were variable, but at 70??C, the sequence was: HCO3 < I < B < SO4 < Cl < Br. Monovalent cations contrary to some field data were generally retarded with respect to divalent cations. The differences in the filtration ratios among the divalent cations were smaller than those between the monovalent cations. The passage rate of B, HCO3, I and NH3 was greatly increased at 70??C. ?? 1973.

Interaction of divalent metal ions with human translocase of inner membrane of mitochondria Tim23.

PubMed

Feng, Wei; Zhang, Yongqiang; Deng, Honghua; Li, Shu Jie

2016-06-17

The preprotein translocase of the inner membrane of mitochondria (TIM23 complex) is the main entry gate for proteins of the matrix and the inner membrane. Tim23p, the core component of TIM23 complex, forms the import pore across the inner membrane and exerts a key function in the protein import. However, the interaction of divalent metal ions with Tim23p and the contribution in the interaction of presequence peptide with Tim23p are still unknown. Herein, we investigated the interaction of divalent metal ions with the intermembrane space domain of Tim23p (Tim23IMS) and the interaction of presequence peptides with Tim23IMS in presence of Ca(2+) ion by fluorescence spectroscopy in vitro. The static fluorescence quenching indicates the existence of strong binding between divalent metal ions and Tim23IMS. The order of the binding strength is Ca(2+), Mg(2+), Cu(2+), Mn(2+), and Co(2+) (from strong to weak). Moreover, the interaction of presequence peptides with Tim23IMS is weakened in presence of Ca(2+) ion, which implicates that Ca(2+) ion may play an important role in the protein import by TIM23 complex. Copyright © 2016 Elsevier Inc. All rights reserved.

Predicting 3D structure and stability of RNA pseudoknots in monovalent and divalent ion solutions.

PubMed

Shi, Ya-Zhou; Jin, Lei; Feng, Chen-Jie; Tan, Ya-Lan; Tan, Zhi-Jie

2018-06-01

RNA pseudoknots are a kind of minimal RNA tertiary structural motifs, and their three-dimensional (3D) structures and stability play essential roles in a variety of biological functions. Therefore, to predict 3D structures and stability of RNA pseudoknots is essential for understanding their functions. In the work, we employed our previously developed coarse-grained model with implicit salt to make extensive predictions and comprehensive analyses on the 3D structures and stability for RNA pseudoknots in monovalent/divalent ion solutions. The comparisons with available experimental data show that our model can successfully predict the 3D structures of RNA pseudoknots from their sequences, and can also make reliable predictions for the stability of RNA pseudoknots with different lengths and sequences over a wide range of monovalent/divalent ion concentrations. Furthermore, we made comprehensive analyses on the unfolding pathway for various RNA pseudoknots in ion solutions. Our analyses for extensive pseudokonts and the wide range of monovalent/divalent ion concentrations verify that the unfolding pathway of RNA pseudoknots is mainly dependent on the relative stability of unfolded intermediate states, and show that the unfolding pathway of RNA pseudoknots can be significantly modulated by their sequences and solution ion conditions.

Metal-chelating active packaging film enhances lysozyme inhibition of Listeria monocytogenes.

PubMed

Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2014-07-01

Several studies have demonstrated that metal chelators enhance the antimicrobial activity of lysozyme. This study examined the effect of metal-chelating active packaging film on the antimicrobial activity of lysozyme against Listeria monocytogenes. Polypropylene films were surface modified by photoinitiated graft polymerization of acrylic acid (PP-g-PAA) from the food contact surface of the films to impart chelating activity based on electrostatic interactions. PP-g-PAA exhibited a carboxylic acid density of 113 ± 5.4 nmol cm(-2) and an iron chelating activity of 53.7 ± 9.8 nmol cm(-2). The antimicrobial interaction of lysozyme and PP-g-PAA depended on growth media composition. PP-g-PAA hindered lysozyme activity at low ionic strength (2.48-log increase at 64.4 mM total ionic strength) and enhanced lysozyme activity at moderate ionic strength (5.22-log reduction at 120 mM total ionic strength). These data support the hypothesis that at neutral pH, synergy between carboxylate metal-chelating films (pKa(bulk) 6.45) and lysozyme (pI 11.35) is optimal in solutions of moderate to high ionic strength to minimize undesirable charge interactions, such as lysozyme absorption onto film. These findings suggest that active packaging, which chelates metal ions based on ligand-specific interactions, in contrast to electrostatic interactions, may improve antimicrobial synergy. This work demonstrates the potential application of metal-chelating active packaging films to enhance the antimicrobial activity of membrane-disrupting antimicrobials, such as lysozyme.

Overcharging below the nanoscale: Multivalent cations reverse the ion selectivity of a biological channel

NASA Astrophysics Data System (ADS)

García-Giménez, Elena; Alcaraz, Antonio; Aguilella, Vicente M.

2010-02-01

We report charge inversion within a nanoscopic biological protein ion channel in salts of multivalent ions. The presence of positive divalent and trivalent counterions reverses the cationic selectivity of the OmpF channel, a general diffusion porin located in the outer membrane of E. coli. We discuss the conditions under which charge inversion can be inferred from the change in sign of the measured quantity, the channel zero current potential. By comparing experimental results in protein channels whose charge has been modified after site-directed mutagenesis, the predictions of current theories of charge inversion are critically examined. It is emphasized that charge inversion does not necessarily increase with the bare surface charge density of the interface and that even this concept of surface charge density may become meaningless in some biological ion channels. Thus, any theory based on electrostatic correlations or chemical binding should explicitly take into account the particular structure of the charged interface.

New tris(dopamine) derivative as an iron chelator. Synthesis, solution thermodynamic stability, and antioxidant research.

PubMed

Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Lei, Shan; Tang, Xingyan; Liang, Hua; Liu, Qiangqiang; Gong, Mei; Peng, Rufang

2017-06-01

A new tris(dopamine) derivative, containing three dopamine chelate moieties which were attached to a trimesic acid molecular scaffold, has been prepared and fully characterized by NMR, FTIR and HRMS. The solution thermodynamic stability of the chelator with Fe(III), Mg(II), Zn(II) and Fe(II) ions was investigated. Results demonstrated that the chelator exhibited effective binding ability and improved selectivity to Fe(III) ion. The chelator possessed affinity similar to that of diethylenetriaminepentaacetic acid chelator for Fe(III) ion. The high affinity could be attributed to the favorable geometric arrangement between the chelator and Fe(III) ion coordination preference. The chelator also exhibited high antioxidant activity and nontoxicity to neuron-like rat pheochromocytoma cells. Hence, the chelator could be used as chelating agent for iron overload situations without depleting essential metal ions, such as Mg(II) and Zn(II) ions. Copyright © 2017. Published by Elsevier Inc.

Heme Regulates Allosteric Activation of the Slo1 BK Channel

PubMed Central

Horrigan, Frank T.; Heinemann, Stefan H.; Hoshi, Toshinori

2005-01-01

Large conductance calcium-dependent (Slo1 BK) channels are allosterically activated by membrane depolarization and divalent cations, and possess a rich modulatory repertoire. Recently, intracellular heme has been identified as a potent regulator of Slo1 BK channels (Tang, X.D., R. Xu, M.F. Reynolds, M.L. Garcia, S.H. Heinemann, and T. Hoshi. 2003. Nature. 425:531–535). Here we investigated the mechanism of the regulatory action of heme on heterologously expressed Slo1 BK channels by separating the influences of voltage and divalent cations. In the absence of divalent cations, heme generally decreased ionic currents by shifting the channel's G–V curve toward more depolarized voltages and by rendering the curve less steep. In contrast, gating currents remained largely unaffected by heme. Simulations suggest that a decrease in the strength of allosteric coupling between the voltage sensor and the activation gate and a concomitant stabilization of the open state account for the essential features of the heme action in the absence of divalent ions. At saturating levels of divalent cations, heme remained similarly effective with its influence on the G–V simulated by weakening the coupling of both Ca2+ binding and voltage sensor activation to channel opening. The results thus show that heme dampens the influence of allosteric activators on the activation gate of the Slo1 BK channel. To account for these effects, we consider the possibility that heme binding alters the structure of the RCK gating ring and thereby disrupts both Ca2+- and voltage-dependent gating as well as intrinsic stability of the open state. PMID:15955873

Characterization of changes in floc morphology, extracellular polymeric substances and heavy metals speciation of anaerobically digested biosolid under treatment with a novel chelated-Fe2+ catalyzed Fenton process.

PubMed

He, Juanjuan; Yang, Peng; Zhang, Weijun; Cao, Bingdi; Xia, Hua; Luo, Xi; Wang, Dongsheng

2017-11-01

A novel chelated-Fe 2+ catalyzed Fenton process (CCFP) was developed to enhance dewatering performance of anaerobically digested biosolid, and changes in floc morphology, extracellular polymeric substances (EPS) and heavy metals speciation were also investigated. The results showed that addition of chelating agents caused EPS solubilization by binding multivalent cations. Like traditional Fenton, CCFP performed well in improving anaerobically digested sludge dewatering property. The highly active radicals (OH, O 2 - ) produced in classical Fenton and CCFP were responsible for sludge flocs destruction and consequently degradation of biopolymers into small molecules. Furthermore, more plentiful pores and channels were presented in cake after Fenton treatment, which was conducive to water drainage under mechanical compression. Additionally, a portion of active heavy metals in the form of oxidizable and reducible states were dissolved under CCFP. Therefore, CCFP could greatly simplify the operating procedure of Fenton conditioning and improve its process adaptability for harmless treatment of biological sludge. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

PubMed

Moniz, T; Leite, A; Silva, T; Gameiro, P; Gomes, M S; de Castro, B; Rangel, M

2017-10-01

We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical analysis of the influence of chelate-ring size and vicinal effects on electronic circular dichroism spectra of cobalt(III) EDDA-type complexes.

PubMed

Wang, Ai; Wang, Yuekui; Jia, Jie; Feng, Lixia; Zhang, Chunxia; Liu, Linlin

2013-06-20

To assess the contributions of configurational and vicinal effects as well as chelate-ring size to rotational strengths, the geometries of a series of cobalt(III) complexes [Co(EDDA-type)(L)](±) with the tetradentate EDDA-type ligands, EDDA (ethylenediamine-N,N'-diacetate), DMEDDA (N,N'-dimethylethylenediamine-N,N'-diacetate), DEEDDA (N,N'-diethylethylenediamine-N,N'-diacetate), and a bidentate ancillary ligand L (L = ethylenediamine, oxalate, carbonate, (S)-alanine, and malonate) in aqueous solution have been optimized at the DFT/B3LYP/6-311++G(2d,p) level of theory. Based on the optimized geometries, the excitation energies and oscillator and rotational strengths have been calculated using the time-dependent density functional theory (TDDFT) method with the same functional and basis set. The calculated circular dichroism (CD) curves are in excellent agreement with the observed ones except for some small red or blue shifts in peak wavelengths. For the influence of chelate-ring size of the bidentate ligands on the CD intensities, a qualitative analysis together with the quantitative TDDFT calculation reveal that it depends on the symmetry of the cobalt-EDDA backbone. For the s-cis-isomers, the influence is negligible due to the perturbation is symmetric. For the uns-cis-isomers, the perturbation is unsymmetric. Since a small ring size means a large perturbation, this leads to the integral CD intensities decreasing with increasing the chelate ring size. The vicinal effects of asymmetric nitrogens incorporate both the substitutent effects and conformational relaxation effects, with the former being dominant. By analyzing the contributions of chiral arrays to rotational strengths, we found that the part of contributions dominated by the S-type chiral nitrogens could be considered as a good measure for the vicinal effects of chiral nitrogens. In addition, we found that the twist form (δ/λ) of the backbone ethylenediamine ring (E-ring) of the coordinated EDDA

Anaerobic Killing of Oral Streptococci by Reduced, Transition Metal Cations

PubMed Central

Dunning, J. C.; Ma, Y.; Marquis, R. E.

1998-01-01

Reduced, transition metal cations commonly enhance oxidative damage to cells caused by hydroperoxides formed as a result of oxygen metabolism or added externally. As expected, the cations Fe2+ and Cu+ enhanced killing of Streptococcus mutans GS-5 by hydroperoxides. However, unexpectedly, they also induced lethal damage under fully anaerobic conditions in a glove box with no exposure to O2 or hydroperoxides from initial treatment with the cations. Sensitivities to anaerobic killing by Fe2+ varied among the organisms tested. The oral streptococci Streptococcus gordonii ATCC 10558, Streptococcus rattus FA-1, and Streptococcus sanguis NCTC 10904 were approximately as sensitive as S. mutans GS-5. Enterococcus hirae ATCC 9790, Actinomyces viscosus OMZ105E, and Actinomyces naeslundii WVU45 had intermediate sensitivity, while Lactobacillus casei ATCC 4646 and Escherichia coli B were insensitive. Killing of S. mutans GS-5 in response to millimolar levels of added Fe2+ occurred over a wide range of temperatures and pH. The organism was able to take up ferrous iron, but ferric reductase activity could not be detected. Chelators, uric acid, and thiocyanate were not effective inhibitors of the lethal damage. Sulfhydryl compounds, ferricyanide, and ferrocyanide were protective if added prior to Fe2+ exposure. Fe2+, but not Fe3+, acted to reduce the acid tolerance of glycolysis by intact cells of S. mutans. The reduction in acid tolerance appeared to be related directly to Fe2+ inhibition of F-ATPase, which could be assayed with permeabilized cells, isolated membranes, or F1 enzyme separated from membranes. Cu+ and Cu2+ also inhibited F-ATPase and sensitized glycolysis by intact cells to acid. All of these damaging actions occurred anaerobically and thus did not appear to involve reactive oxygen species. PMID:9435058

In vitro and in vivo evaluation of potential aluminum chelators.

PubMed

Graff, L; Muller, G; Burnel, D

1995-10-01

The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.

2-Acylpyrroles as mono-anionic O,N-chelating ligands in silicon coordination chemistry.

PubMed

Kämpfe, Alexander; Brendler, Erica; Kroke, Edwin; Wagler, Jörg

2014-07-21

Kryptopyrrole (2,4-dimethyl-3-ethylpyrrole) was acylated with, for example, benzoyl chloride to afford 2-benzoyl-3,5-dimethyl-4-ethylpyrrole (L(1)H). With SiCl4 this ligand reacts under liberation of HCl and formation of the complex L(1)2SiCl2. In related reactions with HSiCl3 or H2SiCl2, the same chlorosilicon complex is formed under liberation of HCl and H2 or liberation of H2, respectively. The chlorine atoms of L(1)2SiCl2 can be replaced by fluoride and triflate using ZnF2 and Me3Si-OTf, respectively. The use of a supporting base (triethylamine) is required for the complexation of phenyltrichlorosilane and diphenyldichlorosilane. The complexes L(1)2SiCl2, L(1)2SiF2, L(1)2Si(OTf)2, L(1)2SiPhCl, and L(1)2SiPh2 exhibit various configurations of the octahedral silicon coordination spheres (i.e. cis or trans configuration of the monodentate substituents, different orientations of the bidentate chelating ligands relative to each other). Furthermore, cationic silicon complexes L(1)3Si(+) and L(1) SiPh(+) were synthesized by chloride abstraction with GaCl3. In contrast, reaction of L(1)2SiCl2 with a third equivalent of L(1)H in the presence of excess triethylamine produced a charge-neutral hexacoordinate Si complex with a new tetradentate chelating ligand which formed by Si-templated C-C coupling of two ligands L(1). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron chelation therapy for transfusional iron overload: a swift evolution.

PubMed

Musallam, Khaled M; Taher, Ali T

2011-01-01

Chronic transfusional iron overload leads to significant morbidity and mortality. While deferoxamine (DFO) is an effective iron chelator with over four decades of experience, it requires tedious subcutaneous infusions that reflect negatively on patient compliance. The novel oral iron chelators deferiprone (L1) and deferasirox (DFRA) opened new horizons for the management of transfusional siderosis. A large body of evidence is now available regarding their efficacy and safety in various populations and settings. Nevertheless, experience with both drugs witnessed some drawbacks, and the search for an ideal and cost-effective iron chelator continues.

Chelate effects in sulfate binding by amide/urea-based ligands.

PubMed

Jia, Chuandong; Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

2015-07-07

The influence of chelate and mini-chelate effects on sulfate binding was explored for six amide-, amide/amine-, urea-, and urea/amine-based ligands. Two of the urea-based hosts were selective for SO4(2-) in water-mixed DMSO-d6 systems. Results indicated that the mini-chelate effect provided by a single urea group with two NH binding sites appears to provide enhanced binding over two amide groups. Furthermore, additional urea binding sites incorporated into the host framework appeared to overcome to some extent competing hydration effects with increasing water content.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia.

PubMed

Chuansumrit, Ampaiwan; Pengpis, Pimprae; Mahachoklertwattana, Pat; Sirachainan, Nongnuch; Poomthavorn, Preamrudee; Sungkarat, Witaya; Kadegasem, Praguywan; Khlairit, Patcharin; Wongwerawattanakoon, Pakawan

2017-01-01

To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003). © 2016 S. Karger AG, Basel.

Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation.

PubMed

Wang, Lu; Yan, WenChao; Chen, JiaChuan; Huang, Feng; Gao, PeiJi

2008-03-01

An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the beta-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.

Copper chelators: chemical properties and bio-medical applications.

PubMed

Tegoni, M; Valensin, D; Toso, L; Remelli, M

2014-01-01

Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

Chelation Treatment for Autism Spectrum Disorders: A Systematic Review

ERIC Educational Resources Information Center

Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin

2013-01-01

Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…

The requirement of ammonium or other cations linked with p-cresol sulfate for cross-reactivity with a peptide of myelin basic protein.

PubMed

Jackson, Patricia L; Cao, Ligong; Blalock, J Edwin; Whitaker, John N

2003-10-15

Urinary myelin basic protein-like material (MBPLM), so designated because of its immunoreactivity with a polyclonal antibody directed against a cryptic epitope located in residues 83-89 of myelin basic protein (MBP), exists in humans normally but increases in concentration in patients with multiple sclerosis who have progressive disease. Given its possible role in reflecting events of neural tissue destruction occurring in multiple sclerosis, urinary MBPLM is a candidate surrogate marker for this phase of the disease. Previously, it has been demonstrated that p-cresol sulfate (PCS) is the dominant component of MBPLM; however, another component(s) was essential in enabling p-cresol sulfate to have molecular mimicry with MBP peptide 83-89 detected by immunoreactivity. In the present investigation, this remaining component(s) was characterized by a combination of high performance size exclusion chromatography followed by nuclear magnetic resonance spectroscopy and shown to be ammonium. The monovalent cation ammonium could be substituted in vitro by several different monovalent and divalent cations, most notably zinc, in restoring to deprotonated p-cresol sulfate its immunoreactivity as MBPLM. These findings indicate the basis for the unexpected molecular mimicry between an epitope of an encephalitogenic protein and a complex containing a small organic molecule, p-cresol sulfate. Furthermore, the reaction of either ammonium or other cations with p-cresol sulfate may represent an in vivo process directly related to damage of axonal membranes.

Ion adsorption-induced wetting transition in oil-water-mineral systems.

PubMed

Mugele, Frieder; Bera, Bijoyendra; Cavalli, Andrea; Siretanu, Igor; Maestro, Armando; Duits, Michel; Cohen-Stuart, Martien; van den Ende, Dirk; Stocker, Isabella; Collins, Ian

2015-05-27

The relative wettability of oil and water on solid surfaces is generally governed by a complex competition of molecular interaction forces acting in such three-phase systems. Herein, we experimentally demonstrate how the adsorption of in nature abundant divalent Ca(2+) cations to solid-liquid interfaces induces a macroscopic wetting transition from finite contact angles (≈ 10°) with to near-zero contact angles without divalent cations. We developed a quantitative model based on DLVO theory to demonstrate that this transition, which is observed on model clay surfaces, mica, but not on silica surfaces nor for monovalent K(+) and Na(+) cations is driven by charge reversal of the solid-liquid interface. Small amounts of a polar hydrocarbon, stearic acid, added to the ambient decane synergistically enhance the effect and lead to water contact angles up to 70° in the presence of Ca(2+). Our results imply that it is the removal of divalent cations that makes reservoir rocks more hydrophilic, suggesting a generalizable strategy to control wettability and an explanation for the success of so-called low salinity water flooding, a recent enhanced oil recovery technology.

A review of pitfalls and progress in chelation treatment of metal poisonings.

PubMed

Andersen, Ole; Aaseth, Jan

2016-12-01

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Polyamine-iron chelator conjugate.

PubMed

Bergeron, Raymond J; McManis, James S; Franklin, April M; Yao, Hua; Weimar, William R

2003-12-04

The current study demonstrates unequivocally that polyamines can serve as vectors for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy-4(1H)-pyridinone is assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III) and to be taken up by the polyamine transporter 1900-fold against a concentration gradient. The K(i) of the conjugate is 3.7 microM vs spermidine for the polyamine transporter. The conjugate is also at least 230 times more active in suppressing the growth of L1210 murine leukemia cells than is the parent ligand, decreases the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N (1)-acetyltransferase. However, the effect on native polyamine pools is a moderate one. These findings are in keeping with the idea that polyamines can also serve as efficient vectors for the intracellular delivery of other iron chelators.

Quality-of-life outcomes with a disodium EDTA chelation regimen for coronary disease: results from the trial to assess chelation therapy randomized trial.

PubMed

Mark, Daniel B; Anstrom, Kevin J; Clapp-Channing, Nancy E; Knight, J David; Boineau, Robin; Goertz, Christine; Rozema, Theodore C; Liu, Diane M; Nahin, Richard L; Rosenberg, Yves; Drisko, Jeanne; Lee, Kerry L; Lamas, Gervasio A

2014-07-01

The National Institutes of Health.funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stablecoronary disease patients aged .50 years who were .6 months post.myocardial infarction (2003.2010) to 40 infusions ofa multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite end point of mortality,recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio, 0.82; 95%confidence interval, 0.69.0.99; P=0.035). In a randomly selected subset of 911 patients, we prospectively collected a battery of quality-of-life(QOL) instruments at baseline and at 6, 12, and 24 months after randomization. The prespecified primary QOL measures were the Duke Activity Status Index (Table I in the Data Supplement) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory-5. All comparisons were by intention to treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and in the 460 patients randomized to placebo. The Duke Activity Status Index improved in both groups during the first 6 months of therapy, but we found no evidence for a treatment-related difference (mean difference [chelation.placebo] during follow-up, 0.9 [95% confidence interval, .0.7 to 2.6; P=0.27]).There was no statistically significant evidence of a treatment-related difference in the Mental Health Inventory-5 during follow-up (mean difference, 1.0; 95% confidence interval, .0.1 to 2.0; P=0.08). None of the secondary QOL measures showed a consistent treatment-related difference. In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction,EDTA chelation therapy did not have a detectable effect on QOL during 2 years of follow-up. URL: http://clinicaltrials.gov. Unique identifier: NCT00044213.

Thermodynamic controls on element partitioning between titanomagnetite and andesitic-dacitic silicate melts

NASA Astrophysics Data System (ADS)

Sievwright, R. H.; Wilkinson, J. J.; O'Neill, H. St. C.; Berry, A. J.

2017-08-01

Titanomagnetite-melt partitioning of Mg, Mn, Al, Ti, Sc, V, Co, Ni, Cu, Zn, Ga, Zr, Nb, Mo, Hf and Ta was investigated experimentally as a function of oxygen fugacity ( fO2) and temperature ( T) in an andesitic-dacitic bulk-chemical compositional range. In these bulk systems, at constant T, there are strong increases in the titanomagnetite-melt partitioning of the divalent cations (Mg2+, Mn2+, Co2+, Ni2+, Zn2+) and Cu2+/Cu+ with increasing fO2 between 0.2 and 3.7 log units above the fayalite-magnetite-quartz buffer. This is attributed to a coupling between magnetite crystallisation and melt composition. Although melt structure has been invoked to explain the patterns of mineral-melt partitioning of divalent cations, a more rigorous justification of magnetite-melt partitioning can be derived from thermodynamic principles, which accounts for much of the supposed influence ascribed to melt structure. The presence of magnetite-rich spinel in equilibrium with melt over a range of fO2 implies a reciprocal relationship between a(Fe2+O) and a(Fe3+O1.5) in the melt. We show that this relationship accounts for the observed dependence of titanomagnetite-melt partitioning of divalent cations with fO2 in magnetite-rich spinel. As a result of this, titanomagnetite-melt partitioning of divalent cations is indirectly sensitive to changes in fO2 in silicic, but less so in mafic bulk systems.

Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated neurones from rat parasympathetic ganglia

PubMed Central

Liu, Dong-Mei; Adams, David J

2001-01-01

The relative permeability of the native P2X receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones dissociated from rat submandibular ganglia using the dialysed whole-cell patch clamp technique. The P2X receptor-channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Na+ > Li+ > Cs+ > Rb+ > K+, and permeability ratios relative to Cs+ (PX/PCs) ranging from 1.11 to 0.86. The selectivity for the divalent alkaline earth cations was also weak with the sequence Ca2+ > Sr2+ > Ba2+ > Mn2+ > Mg2+. ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. The calculated permeability ratios of different ammonium cations are higher than those of the alkali metal cations. The permeability sequence obtained for the saturated organic cations is inversely correlated with the size of the cation. The unsaturated organic cations have a higher permeability than that predicted by molecular size. Acidification to pH 6.2 increased the ATP-induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly reduced current amplitude. Cell dialysis with either anti-P2X2 and/or anti-P2X4 but not anti-P2X1 antibodies attenuated the ATP-evoked current amplitude. Taken together, these data are consistent with homomeric and/or heteromeric P2X2 and P2X4 receptor subtypes expressed in rat submandibular neurones. The permeability ratios for the series of monovalent organic cations, with the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and organic cations tested are similar to those reported previously for cloned rat P2X2 receptors expressed in mammalian cells. PMID:11454961

Rhenium(V) Oxo Complexes of Novel N(2)S(2) Dithiourea (DTU) Chelate Ligands: Synthesis and Structural Characterization.

PubMed

Lipowska, Malgorzata; Hayes, Brittany L.; Hansen, Lory; Taylor, Andrew; Marzilli, Luigi G.

1996-07-03

The compounds RNHC(=S)NH(CH(2))(n)()NHC(=S)NHR were prepared in a search for new, relatively small N(2)S(2) ligands. These dithiourea (DTU) ligands are the first chelates containing two potentially bidentate thiourea moieties. A one-step reaction of 1,3-diaminopropane (1) with aryl or alkyl isothiocyanates or of 1,2-diaminoethane (2) with phenyl isothiocyanate afforded the target ligands in excellent yields (95-98%). The Re(V)=O complexes of RNHC(=S)NH(CH(2))(3)NHC(=S)NHR ligands were obtained through ligand exchange reactions with Re(V) precursors. The chemistry required neither protection of the sulfur atoms for ligand synthesis nor deprotection prior to metal complexation. The structure of (1-phenyl-3-(3-phenylthioureido)propyl]thioureato)oxorhenium(V) (7a), determined by X-ray diffraction methods, revealed the expected pseudo-square-pyramidal geometry with an N(2)S(2) basal and an apical oxo donor set. Both coordinated N's (N(c)) were deprotonated. One uncoordinated N (N(u)) was deprotonated, producing a neutral complex containing an unexpected new type of dianionic, four-membered N,S chelate. In the crystal, the N(u) atoms, N(3)H and N(4), of one complex each formed an H-bond with N(4) and N(3)H, respectively, of a symmetry-related complex. The N(c)-C-S bond angles (106.1(6) and 101.5(6) degrees ) were severely distorted from the 120 degrees expected for an sp(2)-hybridized C. However, these small bite angles and the large N-Re-N bond angle (86.1(3) degrees ) allowed for the formation of two four-membered chelate rings with normal Re-N and Re-S bond distances. Attempts to prepare complexes with the PhNHC(=S)NH(CH(2))(2)NHC(=S)NHPh ligand were unsuccessful. These results suggest that a central five-membered chelate ring is too small to accommodate bidentate coordination of both thiourea moieties. NMR studies in methanol established that the neutral complex with one uncoordinated N deprotonated was the favored form in neutral and basic solutions. However, under

Modeling the surface of Campylobacter fetus: protein surface layer stability and resistance to cationic antimicrobial peptides.

PubMed

Roberts, James M D; Graham, Lori L; Quinn, Bonnie; Pink, David A

2013-03-01

Campylobacter fetus is a Gram negative bacterium recognized for its virulence in animals and humans. This bacterium possesses a paracrystalline array of high molecular weight proteins known as surface-layer proteins covering its cell surface. A mathematical model has been made of the outer membrane of this bacterium, both with its surface-layer proteins (S+) and without (S-). Monte Carlo computer simulation was used to understand the stability of the surface-layer protein structure as a function of ionic concentration. The interactions of an electrically-charged antimicrobial agent, the cationic antimicrobial peptide protamine, with surface-layer proteins and with the lipopolysaccharides of the outer membrane were modeled and analyzed. We found that (1) divalent ions stabilize the surface-layer protein array by reducing the fluctuations perpendicular and parallel to the membrane plane thereby promoting adhesion to the LPS region. This was achieved via (2) divalent ions bridging the negatively-charged LPS Core. The effect of this bridging is to bring individual Core regions closer together so that the O-antigens can (3) increase their attractive van der Waals interactions and "collapse" to form a surface with reduced perpendicular fluctuations. These findings provide support for the proposal of Yang et al. [1]. (4) No evidence for a significant increase in Ca(2+) concentration in the region of the surface-layer protein subunits was observed in S+ simulations compared to S- simulations. (5) We predicted the trends of protamine MIC tests performed on C. fetus and these were in good agreement with our experimental results. Copyright © 2012 Elsevier B.V. All rights reserved.

Interaction of chelating agents with cadmium in mice and rats.

PubMed Central

Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

Involvement of DMT1 +IRE in the transport of lead in an in vitro BBB model.

PubMed

Wang, Qiang; Luo, Wenjing; Zhang, Wenbin; Liu, Mingchao; Song, Haifeng; Chen, Jingyuan

2011-06-01

Homeostasis of the central nervous system (CNS) microenvironment is maintained by the blood-brain barrier (BBB). The BBB is particularly vulnerable to lead (Pb) insults. This study was designed to test the hypothesis that divalent metal transporter 1 (DMT1), which is a divalent cation membrane transporter, was involved in transcellular transport across the BBB. An in vitro BBB model, which was a co-culture system of human umbilical vascular endothelial cells (ECV304) and rat glioma cells (C6), was established. Transendothelial electrical resistance (TEER) and fluoresceinisothiocyanate (FITC)-dextran permeability results showed that Pb exposure at the tested concentrations had no significant effects on intercellular tightness. Pb transport displayed properties that were associated with iron response element (IRE) positive isoform of DMT1. Accordingly, Pb transport was significantly blocked by iron (Fe). Moreover, ECV304 cells that were depleted of Fe with the chelator deferoxamine (DFO) demonstrated increased Pb transport. By transfecting ECV-304 cells with a DMT1 expression vector, overexpression of DMT1 promoted an increase in Pb transport. Treatment of ECV304 cells with DMT1 antisense oligonucleotides (ASONs) MA1 significantly inhibited the transport of Pb. Our results suggest that Pb is transported in the in vitro BBB model by a transporter with biochemical properties similar to those of the DMT1 IRE-positive isoform. Copyright © 2009 Elsevier Ltd. All rights reserved.

Isolation and divalent-metal activation of a ß-xylosidase, RUM630-BX

USDA-ARS?s Scientific Manuscript database

The gene encoding RUM630-BX, a ß-xylosidase/arabinofuranosidase, was identified from activity-based screening of a cow rumen metagenomic library. The recombinant enzyme is activated as much as 14-fold (kcat) by divalent metals Mg2+, Mn2+ and Co2+ but not by Ca2+, Ni2+, and Zn2+. Activation of RUM6...

Magnetic behavior control in niccolite structural metal formate frameworks [NH2(CH3)2][Fe(III)M(II)(HCOO)6] (M = Fe, Mn, and Co) by varying the divalent metal ions.

PubMed

Zhao, Jiong-Peng; Hu, Bo-Wen; Lloret, Francesc; Tao, Jun; Yang, Qian; Zhang, Xiao-Feng; Bu, Xian-He

2010-11-15

By changing template cation but introducing trivalent iron ions in the known niccolite structural metal formate frameworks, three complexes formulated [NH(2)(CH(3))(2)][Fe(III)M(II)(HCOO)(6)] (M = Fe for 1, Mn for 2, and Co for 3) were synthesized and magnetically characterized. The variation in the compositions of the complexes leads to three different complexes: mixed-valent complex 1, heterometallic but with the same spin state complex 2, and heterometallic heterospin complex 3. The magnetic behaviors are closely related to the divalent metal ions used. Complex 1 exhibits negative magnetization assigned as Néel N-Type ferrimagnet, with an asymmetric magnetization reversal in the hysteresis loop, and complex 2 is an antiferromagnet with small spin canting (α(canting) ≈ 0.06° and T(canting) = 35 K), while complex 3 is a ferrimagnet with T(N) = 32 K.

Chelation therapy to treat atherosclerosis, particularly in diabetes: Is it time to reconsider?

PubMed Central

Lamas, Gervasio A; Ergui, Ian

2016-01-01

Summary Reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years. These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. PMID:27149141

Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

PubMed

Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

2016-10-01

Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Won, JaeSeon; Nam, PilWon; Lee, YongChan

2009-04-24

Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G{sub 4}S) between the Fabmore » fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]{sub 2}) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.« less

Succinate, iron chelation, and monovalent cations affect the transformation efficiency of Acinetobacter baylyi ATCC 33305 during growth in complex media.

PubMed

Leong, Colleen G; Boyd, Caroline M; Roush, Kaleb S; Tenente, Ricardo; Lang, Kristine M; Lostroh, C Phoebe

2017-10-01

Natural transformation is the acquisition of new genetic material via the uptake of exogenous DNA by competent bacteria. Acinetobacter baylyi is model for natural transformation. Here we focus on the natural transformation of A. baylyi ATCC 33305 grown in complex media and seek environmental conditions that appreciably affect transformation efficiency. We find that the transformation efficiency for A. baylyi is a resilient characteristic that remains high under most conditions tested. We do find several distinct conditions that alter natural transformation efficiency including addition of succinate, Fe 2+ (ferrous) iron chelation, and substitution of sodium ions with potassium ones. These distinct conditions could be useful to fine tune transformation efficiency for researchers using A. baylyi as a model organism to study natural transformation.

Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

PubMed

Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

2008-02-28

The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renzi, Fabiana; Panetta, Gianna; Vallone, Beatrice

Recombinant His-tagged XendoU, a eukaryotic endoribonuclease, appeared to aggregate in the presence of divalent cations. Monodisperse protein which yielded crystals diffracting to 2.2 Å was obtained by addition of EDTA. XendoU is the first endoribonuclease described in higher eukaryotes as being involved in the endonucleolytic processing of intron-encoded small nucleolar RNAs. It is conserved among eukaryotes and its viral homologue is essential in SARS replication and transcription. The large-scale purification and crystallization of recombinant XendoU are reported. The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potentialmore » drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Purified monodisperse XendoU crystallized in two different space groups: trigonal P3{sub 1}21, diffracting to low resolution, and monoclinic C2, diffracting to higher resolution.« less

Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89

DOE PAGES

Pandya, Darpan N.; Pailloux, Sylvie; Tatum, David; ...

2014-12-18

The development of bifunctional chelators (BFCs) which can stably chelate zirconium-89 ((89)Zr) while being conjugated to targeting molecules is an area of active research. Herein we report the first octadentate terephthalamide ligands, which are easily radiolabeled with (89)Zr and are highly stable in vitro. Lastly, they represent a novel class of chelators, which are worthy of further development as BFCs for (89)Zr.

Enhancement of bismuth antibacterial activity with lipophilic thiol chelators.

PubMed Central

Domenico, P; Salo, R J; Novick, S G; Schoch, P E; Van Horn, K; Cunha, B A

1997-01-01

bacteria. The activity, solubility, and stability of BisBAL were strongly dependent on the pH, temperature, and molar ratio. Chelation of bismuth with certain thiol agents enhanced the solubility and lipophilicity of this cationic heavy metal, thereby significantly enhancing its potency and versatility as an antibacterial agent. PMID:9257744

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

NASA Astrophysics Data System (ADS)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

PubMed

Le Du, Alicia; Sabatié-Gogova, Andrea; Morgenstern, Alfred; Montavon, Gilles

2012-04-01

The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTF) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTF but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules for application in targeted alpha therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

On the Structural Basis for Size-selective Permeation of Organic Cations through the Voltage-gated Sodium Channel

PubMed Central

Sun, Ye-Ming; Favre, Isabelle; Schild, Laurent; Moczydlowski, Edward

1997-01-01

Recent evidence indicates that ionic selectivity in voltage-gated Na+ channels is mediated by a small number of residues in P-region segments that link transmembrane elements S5 and S6 in each of four homologous domains denoted I, II, III, and IV. Important determinants for this function appear to be a set of conserved charged residues in the first three homologous domains, Asp(I), Glu(II), and Lys(III), located in a region of the pore called the DEKA locus. In this study, we examined several Ala-substitution mutations of these residues for alterations in ionic selectivity, inhibition of macroscopic current by external Ca2+ and H+, and molecular sieving behavior using a series of organic cations ranging in size from ammonium to tetraethylammonium. Whole-cell recording of wild-type and mutant channels of the rat muscle μ1 Na+ channel stably expressed in HEK293 cells was used to compare macroscopic current–voltage behavior in the presence of various external cations and an intracellular reference solution containing Cs+ and very low Ca2+. In particular, we tested the hypothesis that the Lys residue in domain III of the DEKA locus is responsible for restricting the permeation of large organic cations. Mutation of Lys(III) to Ala largely eliminated selectivity among the group IA monovalent alkali cations (Li+, Na+, K+, Rb+, Cs+) and permitted inward current of group IIA divalent cations (Mg2+, Ca2+, Sr2+, Ba2+). This same mutation also resulted in the acquisition of permeability to many large organic cations such as methylammonium, tetramethylammonium, and tetraethylammonium, all of which are impermeant in the native channel. The results lead to the conclusion that charged residues of the DEKA locus play an important role in molecular sieving behavior of the Na+ channel pore, a function that has been previously attributed to a hypothetical region of the channel called the “selectivity filter.” A detailed examination of individual contributions of the Asp(I), Glu

Heavy metal displacement in chelate-irrigated soil during phytoremediation

NASA Astrophysics Data System (ADS)

Madrid, F.; Liphadzi, M. S.; Kirkham, M. B.

2003-03-01

Heavy metals in wastewater sewage sludge (biosolids), applied to land, contaminate soils. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with and without roots following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals in biosolids applied to the surface of soil columns (76 cm long; 17 cm diam.) with or without plants (barley; Hordeum vulgare L.). Three weeks after barley was planted, all columns were irrigated with the disodium salt of the chelating agent, EDTA (ethylenediamine tetraacetic acid) (0.5 g/kg soil). Drainage water, soil, and plants were analyzed for heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, Zn). Total concentrations of the heavy metals in all columns at the end of the experiment generally were lower in the top 30 cm of soil with EDTA than without EDTA. The chelate increased concentrations of heavy metals in shoots. With or without plants, the EDTA mobilized Cd, Fe, Mn, Ni, Pb, and Zn, which leached to drainage water. Drainage water from columns without EDTA had concentrations of these heavy metals below detection limits. Only Cu did not leach in the presence of EDTA. Even though roots retarded the movement of Cd, Fe, Mn, Ni, Pb, and Zn through the EDTA-treated soil from 1 d (Cd) to 5 d (Fe), the drainage water from columns with EDTA had concentrations of Cd, Fe, Mn, and Pb that exceeded drinking water standards by 1.3, 500, 620, and 8.6 times, respectively. Because the chelate rendered Cd, Fe, Mn, Ni, Pb, and Zn mobile, it is suggested that the theory for leaching of soluble salts, put forward by Nielsen and associates in 1965, could be applied to control movement of the heavy metals for maximum uptake during chelate-assisted phytoremediation.

Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease.

PubMed

Cooper, Garth J S

2011-07-09

This article reviews recent evidence, much of which has been generated by my group's research programme, which has identified for the first time a previously unknown copper-overload state that is central to the pathogenesis of diabetic organ damage. This state causes tissue damage in the blood vessels, heart, kidneys, retina and nerves through copper-mediated oxidative stress. This author now considers this copper-overload state to provide an important new target for therapeutic intervention, the objective of which is to prevent or reverse the diabetic complications. Triethylenetetramine (TETA) has recently been identified as the first in a new class of anti-diabetic molecules through the original work reviewed here, thus providing a new use for this molecule, which was previously approved by the US FDA in 1985 as a second-line treatment for Wilson's disease. TETA acts as a highly selective divalent copper (Cu(II)) chelator that prevents or reverses diabetic copper overload, thereby suppressing oxidative stress. TETA treatment of diabetic animals and patients has identified and quantified the interlinked defects in copper metabolism that characterize this systemic copper overload state. Copper overload in diabetes mellitus differs from that in Wilson's disease through differences in their respective causative molecular mechanisms, and resulting differences in tissue localization and behaviour of the excess copper. Elevated pathogenetic tissue binding of copper occurs in diabetes. It may well be mediated by advanced-glycation endproduct (AGE) modification of susceptible amino-acid residues in long-lived fibrous proteins, for example, connective tissue collagens in locations such as blood vessel walls. These AGE modifications can act as localized, fixed endogenous chelators that increase the chelatable-copper content of organs such as the heart and kidneys by binding excessive amounts of catalytically active Cu(II) in specific vascular beds, thereby focusing the

Assessment of iron chelates efficiency for photo-Fenton at neutral pH.

PubMed

De Luca, Antonella; Dantas, Renato F; Esplugas, Santiago

2014-09-15

In this study, homogeneous photo-Fenton like at neutral pH was applied to remove sulfamethoxazole from water. The process was performed using different chelating agents in order to solubilize iron in a neutral water solution. The chelating agents tested were: ethylenediaminetetraacetic acid (EDTA); nitrilotriacetic acid (NTA); oxalic acid (OA) and tartaric acid (TA). The iron leaching was monitored over reaction time to evaluate the chelates stability and their resistance to HO· and UV-A radiation. Chelates of EDTA and NTA presented more stability than OA and TA, which also confirmed their higher efficiency. Total Organic Carbon (TOC) analyses were also performed to evaluate the contribution in terms of solution contamination related to the use of chelating agents. The better properties of biodegradability in respect of EDTA combined with better efficiency in terms of microcontaminant removal and the smallest TOC contribution indicate that NTA could represent a useful option to perform photo-Fenton processes at neutral pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

PubMed Central

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-01-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed. PMID:26878770

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil.

PubMed

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-16

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

NASA Astrophysics Data System (ADS)

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

PubMed

Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

2014-08-01

Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of commercial iron chelates and their behavior in an alkaline and calcareous soil.

PubMed

Cantera, Rodrigo G; Zamarreño, Angel M; García-Mina, José M

2002-12-18

Iron deficiency is a common problem for many plants grown in alkaline and calcareous soils. To correct this problem, iron is supplied to plants as chelates. Several iron chelates are sold under diverse trademarks with different characteristics. This work evaluated 18 commercial products containing the most representative chelated iron sources used in agricultural practice in Spain when the study was done, namely the ferric chelates of EDDHA, EDDHMA, EDDCHA, EDDHSA, EDTA, and DTPA. The chelates were comprehensively characterized and quantitated by several techniques, including several chromatographic methods. Iron and chelate dynamics in soil were also studied in a model alkaline and calcareous soil. Results indicate that, in this model soil, among the different iron compounds studied only FeEDDHA and analogues have the capacity to maintain soluble iron in soil solution over time. These results are in agreement with general experience under field conditions. Furthermore, among the different ortho-ortho isomers of FeEDDHA's, FeEDDHSA and FeEDDCHA showed greater capacity than FeEDDHA and FeEDDHMA to maintain the chelated iron in soil solution over time.

Super-Chelators for Advanced Protein Labeling in Living Cells.

PubMed

Gatterdam, Karl; Joest, Eike F; Dietz, Marina S; Heilemann, Mike; Tampé, Robert

2018-05-14

Live-cell labeling, super-resolution microscopy, single-molecule applications, protein localization, or chemically induced assembly are emerging approaches, which require specific and very small interaction pairs. The minimal disturbance of protein function is essential to derive unbiased insights into cellular processes. Herein, we define a new class of hexavalent N-nitrilotriacetic acid (hexaNTA) chelators, displaying the highest affinity and stability of all NTA-based small interaction pairs described so far. Coupled to bright organic fluorophores with fine-tuned photophysical properties, the super-chelator probes were delivered into human cells by chemically gated nanopores. These super-chelators permit kinetic profiling, multiplexed labeling of His 6 - and His 12 -tagged proteins as well as single-molecule-based super-resolution imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlling lipid oxidation via a biomimetic iron chelating active packaging material.

PubMed

Tian, Fang; Decker, Eric A; Goddard, Julie M

2013-12-18

Previously, a siderophore-mimetic metal chelating active packaging film was developed by grafting poly(hydroxamic acid) (PHA) from the surface of polypropylene (PP) films. The objective of the current work was to demonstrate the potential applicability of this PP-g-PHA film to control iron-promoted lipid oxidation in food emulsions. The iron chelating activity of this film was investigated, and the surface chemistry and color intensity of films were also analyzed after iron chelation. In comparison to the iron chelating activity in the free Fe(3+) solution, the PP-g-PHA film retained approximately 50 and 30% of its activity in nitrilotriacetic acid (NTA)/Fe(3+) and citric acid/Fe(3+) solutions, respectively (pH 5.0), indicating a strong chelating strength for iron. The ability of PP-g-PHA films to control lipid oxidation was demonstrated in a model emulsion system (pH 3.0). PP-g-PHA films performed even better than ethylenediaminetetraacetic acid (EDTA) in preventing the formation of volatile oxidation products. The particle size and ζ potential results of emulsions indicated that PP-g-PHA films had no adverse effects on the stability of the emulsion system. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis suggested a non-migratory nature of the PP-g-PHA film surface. These results suggest that such biomimetic, non-migratory metal chelating active packaging films have commercial potential in protecting foods against iron-promoted lipid oxidation.

Extracellular Ca2+ Is Required for Fertilization in the African Clawed Frog, Xenopus laevis

PubMed Central

Duray, Alexis M.; Tembo, Maiwase; Beleny, David O.; Napolitano, Marc A.; Sauer, Monica L.; Wisner, Bennett W.

2017-01-01

Background The necessity of extracellular Ca2+ for fertilization and early embryonic development in the African clawed frog, Xenopus laevis, is controversial. Ca2+ entry into X. laevis sperm is reportedly required for the acrosome reaction, yet fertilization and embryonic development have been documented to occur in high concentrations of the Ca2+ chelator BAPTA. Here we sought to resolve this controversy. Methodology/principal finding Using the appearance of cleavage furrows as an indicator of embryonic development, we found that X. laevis eggs inseminated in a solution lacking added divalent cations developed normally. By contrast, eggs inseminated in millimolar concentrations of BAPTA or EGTA failed to develop. Transferring embryos to varying solutions after sperm addition, we found that extracellular Ca2+ is specifically required for events occurring within the first 30 minutes after sperm addition, but not after. We found that the fluorescently stained sperm were not able to penetrate the envelope of eggs inseminated in high BAPTA, whereas several had penetrated the vitelline envelope of eggs inseminated without a Ca2+ chelator, or with BAPTA and saturating CaCl2. Together these results indicate that fertilization does not occur in high concentrations of Ca2+ chelators. Finally, we found that the jelly coat includes >5 mM of readily diffusible Ca2+. Conclusions/Significance Taken together, these data are consistent with requirement of extracellular Ca2+ for fertilization. Based on our findings, we hypothesize that the jelly coat surrounding the egg acts as a reserve of readily available Ca2+ ions to foster fertilization in changing extracellular milieu. PMID:28114360

Impacts of Cation Type and Clay on Transport of Surface-modified Nanoparticles through Saturated Sand Columns

NASA Astrophysics Data System (ADS)

Torkzaban, S.; Wan, J.; Tokunaga, T. K.

2010-12-01

Transport of three different nanoparticles (NPs) was studied in columns packed with different sands (unwashed Accusand, washed Accusand, and ultrapure quartz) at different ionic strengths (IS) and cation types. The NPs were functionalized (polyacrylic acid) quantum dots (QDs), carboxylic-modified latex, and bare silica. Scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis showed there were regions on the unwashed Accusand grains covered with clay particles. The SEM images of washed Accusand showed that the sand surfaces contained significantly less clay coatings. The breakthrough curves (BTCs) of QDs and latex NPs from unwashed Accusand columns showed minute deposition at 50 and 100 mM Na+. However, significant NP deposition occurred in unwashed Accusand columns at 0.5, 1, and 2 mM Ca2+. The amount of deposition increased as the Ca2+ concentration was increased. These results suggest that, in contrast to monovalent Na+, divalent Ca2+ enhanced deposition of the NPs. The BTCs of QDs and latex NPs in washed Accusand exhibited a similar trend as those of unwashed Accusand, however, much less deposition occurred at any given IS. The BTCs from the ultrapure quartz sand column showed negligible QD deposition at 2 mM Ca2+. Following completion of column experiments, a few Accusand sand grains were analyzed with SEM and the images showed that most of QDs were deposited on the clay surfaces. In contrast with our results from surface-modified NPs, the column experiments using bare silica NPs at 5 mM Ca2+ in unwashed Accusand showed negligible deposition. The enhanced deposition of surface-modified NPs may be attributed to cation bridging in which Ca2+ cations serve as a bridge between the NP, which contain carboxyl group on its surface, and negatively charged clay surfaces at 7. Because Ca2+ is commonly a major cation in groundwater, our results suggest that transport of carboxylic ligand-modified NPs may be very limited in subsurface environments.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

PubMed

Lamas, Gervasio A; Ergui, Ian

2016-08-01

Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

SEPARATION OF PLUTONIUM FROM LANTHANUM BY CHELATION-EXTRACTION

DOEpatents

James, R.A.; Thompson, S.G.

1958-12-01

Plutonium can be separated from a mixture of plutonlum and lanthanum in which the lanthanum to plutonium molal ratio ls at least five by adding the ammonium salt of N-nitrosoarylhydroxylamine to an aqueous solution having a pH between about 3 and 0.2 and containing the plutonium in a valence state of at least +3, to form a plutonium chelate compound of N-nitrosoarylhydroxylamine. The plutonium chelate compound may be recovered from the solution by extracting with an immiscible organic solvent such as chloroform.

Magnetic moment directions and distributions of cations in Cr (Co) substituted spinel ferrites Ni{sub 0.7}Fe{sub 2.3}O{sub 4}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, L. C.; Lang, L. L.; Li, Z. Z.

2015-09-15

Powder samples of the spinel ferrites M{sub x}Ni{sub 0.7−x}Fe{sub 2.3}O{sub 4} (M = Cr, Co and 0.0 ≤ x ≤ 0.3) and Cr{sub x}Ni{sub 0.7}Fe{sub 2.3−x}O{sub 4} (0.0 ≤ x ≤ 0.3) were synthesized using the chemical co-precipitation method. The XRD spectra confirmed that the samples had a single-phase cubic spinel structure. Magnetic measurements showed that the magnetic moments (μ{sub exp}) per formula both at 10 K and 300 K increased with Co substitution, while the values of μ{sub exp} decreased with Cr substitution. Applying the assumption that the magnetic moments of Cr{sup 2+} and Cr{sup 3+} lie antiparallel tomore » those of the divalent and trivalent Fe, Co, and Ni cations in the same sublattice of spinel ferrites, these interesting behaviors could be easily interpreted. The cation distributions of the three series of samples were estimated successfully by fitting the dependences of μ{sub exp}, measured at 10 K, on the doping level x, using a quantum-mechanical potential barrier model earlier proposed by our group. The results obtained for the Cr cation distributions at the (A) and [B] sites are very close to those obtained elsewhere using neutron diffraction.« less

Clioquinol-zinc chelate: a candidate causative agent of subacute myelo-optic neuropathy.

PubMed Central

Arbiser, J. L.; Kraeft, S. K.; van Leeuwen, R.; Hurwitz, S. J.; Selig, M.; Dickersin, G. R.; Flint, A.; Byers, H. R.; Chen, L. B.

1998-01-01

BACKGROUND: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) was used clinically three decades ago as an oral antiparasitic agent and to increase intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc absorption. Use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), characterized by peripheral neuropathy and blindness, which affected 10,000 patients in Japan. Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear. MATERIALS AND METHODS: We tested the effect of clioquinol-metal chelates on neural crest-derived melanoma cells. The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. RESULTS: Of the ions tested, only clioquinol-zinc chelate demonstrated cytotoxicity. The cytotoxicity of clioquinol-zinc chelate was extremely rapid, suggesting that its primary effect was on the mitochondria. Electron microscopic analysis demonstrated that clioquinol-zinc chelate caused mitochondrial damage. This finding was further confirmed by the observation that clioquinol-zinc chelate caused a decrease in mitochondrial membrane potential. CONCLUSIONS: We demonstrate that clioquinol, in the presence of zinc, is converted to a potent mitochondrial toxin. The phenomenon of clioquinol mediated toxicity appears to be specific to zinc and is not seen with other metals tested. Since clioquinol has been shown to cause increased systemic absorption of zinc in humans, it is likely that clioquinol-zinc chelate was present in appreciable levels in patients with SMON and may be the ultimate causative toxin of SMON. Images Fig. 2 Fig. 3 PMID:9848083

Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89

PubMed Central

Xu, Jide; Tatum, David; Magda, Darren

2017-01-01

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation. PMID:28575044

Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

PubMed

Bhatt, Nikunj B; Pandya, Darpan N; Xu, Jide; Tatum, David; Magda, Darren; Wadas, Thaddeus J

2017-01-01

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

Inhibitory activity of chelating agent against bacteria associated with poultry processing

USDA-ARS?s Scientific Manuscript database

Ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N, N’-disuccinic acid (EDDS) are chelating agents that can bind minerals that produce water hardness. By sequestering minerals in hard water, chelators reduce water hardness and increase the ability of cleansers to remove dirt and debris dur...

Reaction of N,N'-dimethylformamide and divalent viologen molecule to generate an organic dopant for molybdenum disulfide

NASA Astrophysics Data System (ADS)

Fukui, A.; Miura, K.; Ichimiya, H.; Tsurusaki, A.; Kariya, K.; Yoshimura, T.; Ashida, A.; Fujimura, N.; Kiriya, D.

2018-05-01

Tuning the carrier concentration is essential for semiconducting materials to apply optoelectronic devices. Molybdenum disulfide (MoS2) is a semiconducting material composed of atomically thin (˜0.7 nm thickness) layers. To dope thin MoS2, instead of using conventional atom/ion injection processes, a surface charge transfer method was successfully applied. In this study, we report a simple preparation method of a molecular dopant applicable to the doping process. The method follows a previous report for producing a molecular dopant, benzyl viologen (BV) which shows electron doping to MoS2. To prepare dopant BV molecules, a reduction process with a commercially available divalent BV by sodium borohydride (NaBH4) is required; however, the reaction requires a large consumption of NaBH4. NaBH4 drastically reacts with the solvent water itself. We found a reaction process of BV in an organic solvent, N,N'-dimethylformamide (DMF), by adding a small amount of water dissolving the divalent BV. The reaction is mild (at room temperature) and is autonomous once DMF comes into contact with the divalent BV aqueous solution. The reaction can be monitored with a UV-Vis spectrometer, and kinetic analysis indicates two reaction steps between divalent/monovalent/neutral viologen isomers. The product was soluble in toluene and did not dissolve in water, indicating it is similar to the reported dopant BV. The synthesized molecule was found to act as a dopant for MoS2 by applying a metal-oxide-semiconductor field-effect-transistor (MOSFET) structure. The process is a general method and applicable to other viologen-related dopants to tune the electronic structure of 2D materials to facilitate generating atomically thin devices.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

PubMed Central

2014-01-01

Background Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. Methods Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. Results Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of

The cation-π interaction.

PubMed

Dougherty, Dennis A

2013-04-16

The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is

Hydroxypyridinone Derivatives: A Fascinating Class of Chelators with Therapeutic Applications - An Update.

PubMed

Chaves, Sílvia; Piemontese, Luca; Hiremathad, Asha; Santos, Maria A

2018-01-01

Hydroxypyridinones (HPs) are a family of N-heterocyclic metal chelators, which have been an attractive target in the development of a variety of new pharmaceutical drugs, due to their high metal chelating efficacy/specificity and easy derivatization to tune the desired biological properties. In fact, along the last decades, hydroxypyridinone derivatives, but mostly 3-hydroxy-4-pyridinone (3,4-HP), have been intensively used in drug design, following either a multitarget approach, in which one chelating unity is extrafunctionalized (hybridized) to enable the interaction with other important specific biological sites, or a polydenticity approach, in which more than one chelating moiety is conveniently attached to one scaffold, to increase the metal chelating efficacy. This review represents an update of the most recent publications (2014-2016) in mono-HP hybrids, namely as potential anti-Alzheimer's drugs, inhibitors of metalloenzymes and anti-microbials, and also polychelating compounds (poly- HP), in view of potential application, such as anti-microbial/biostatic agents, luminescent biosensors or diagnostic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhanced in vitro activity of tigecycline in the presence of chelating agents.

PubMed

Deitchman, Amelia N; Singh, Ravi Shankar Prasad; Rand, Kenneth H; Derendorf, Hartmut

2018-05-01

The lack of availability of novel antibiotic agents and the rise of resistance to existing therapies has led clinicians to utilise combination therapy to adequately treat bacterial infections. Here we examined how chelators may impact the in vitro activity of tigecycline (TIG) against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Minimum inhibitory concentrations (MICs) were determined by broth dilution with and without various combinations of chelators (EDTA and other tetracyclines) and metal ions (i.e. calcium, magnesium). Trimethoprim (TMP) was used as a non-chelating control. Addition of metal ions led to increases in MICs, whilst addition of EDTA led to decreases in MICs. The chelating effects of EDTA were reversed by addition of magnesium and most profoundly calcium. Similar effects of EDTA and calcium were observed for tetracycline (TET) and TMP. When other tetracyclines (TET, oxytetracycline (OXY) and chlortetracycline (CHL)) were used as chelators at concentrations below their MICs, TIG MICs decreased for P. aeruginosa but not for E. coli. Some decreases in TIG MICs were observed for K. pneumoniae when TET and CHL were added. A dose-dependent decrease in TIG MIC was observed for TET and was reversed by the addition of calcium. The presence of effects of EDTA and calcium on TMP MICs indicates that mechanisms outside of TIG chelation likely play a role in enhanced activity. Full characterisation of an unexpected interaction such as TIG-TET with different microorganisms could provide valuable insights into the underlying mechanisms and design of physiologically viable chelators as candidates for future combinations regimens. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Environmentally-relevant concentrations of Al(III) and Fe(III) cations induce aggregation of free DNA by complexation with phosphate group.

PubMed

Qin, Chao; Kang, Fuxing; Zhang, Wei; Shou, Weijun; Hu, Xiaojie; Gao, Yanzheng

2017-10-15

Environmental persistence of free DNA is influenced by its complexation with other chemical species and its aggregation mechanisms. However, it is not well-known how naturally-abundant metal ions, e.g., Al(III) and Fe(III), influence DNA aggregation. This study investigated aggregation behaviors of model DNA from salmon testes as influenced by metal cations, and elucidated the predominant mechanism responsible for DNA aggregation. Compared to monovalent (K + and Na + ) and divalent (Ca 2+ and Mg 2+ ) cations, Al(III) and Fe(III) species in aqueous solution caused rapid DNA aggregations. The maximal DNA aggregation occurred at 0.05 mmol/L Al(III) or 0.075 mmol/L Fe(III), respectively. A combination of atomic force microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy revealed that Al(III) and Fe(III) complexed with negatively charged phosphate groups to neutralize DNA charges, resulting in decreased electrostatic repulsion and subsequent DNA aggregation. Zeta potential measurements and molecular computation further support this mechanism. Furthermore, DNA aggregation was enhanced at higher temperature and near neutral pH. Therefore, DNA aggregation is collectively determined by many environmental factors such as ion species, temperature, and solution pH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

PubMed Central

Huang, Saibo; Lin, Huimin; Deng, Shang-gui

2015-01-01

The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

Synthetic cation-selective nanotube: permeant cations chaperoned by anions.

PubMed

Hilder, Tamsyn A; Gordon, Dan; Chung, Shin-Ho

2011-01-28

The ability to design ion-selective, synthetic nanotubes which mimic biological ion channels may have significant implications for the future treatment of bacteria, diseases, and as ultrasensitive biosensors. We present the design of a synthetic nanotube made from carbon atoms that selectively allows monovalent cations to move across and rejects all anions. The cation-selective nanotube mimics some of the salient properties of biological ion channels. Before practical nanodevices are successfully fabricated it is vital that proof-of-concept computational studies are performed. With this in mind we use molecular and stochastic dynamics simulations to characterize the dynamics of ion permeation across a single-walled (10, 10), 36 Å long, carbon nanotube terminated with carboxylic acid with an effective radius of 5.08 Å. Although cations encounter a high energy barrier of 7 kT, its height is drastically reduced by a chloride ion in the nanotube. The presence of a chloride ion near the pore entrance thus enables a cation to enter the pore and, once in the pore, it is chaperoned by the resident counterion across the narrow pore. The moment the chaperoned cation transits the pore, the counterion moves back to the entrance to ferry another ion. The synthetic nanotube has a high sodium conductance of 124 pS and shows linear current-voltage and current-concentration profiles. The cation-anion selectivity ratio ranges from 8 to 25, depending on the ionic concentrations in the reservoirs.

Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89

DOE PAGES

Bhatt, Nikunj B.; Pandya, Darpan N.; Xu, Jide; ...

2017-06-02

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. We report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. And while both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. The differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimizationmore » is necessary to enhance 89Zr chelation.« less

Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatt, Nikunj B.; Pandya, Darpan N.; Xu, Jide

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. We report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. And while both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. The differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimizationmore » is necessary to enhance 89Zr chelation.« less

The Cation-π Interaction

PubMed Central

DOUGHERTY, DENNIS A.

2014-01-01

CONSPECTUS The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author’s perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forgo aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction – Li+ binds to benzene with 38 kcal/mol of binding energy; NH4+ with 19 kcal/mol– distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2 – 5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) Cδ−–Hδ+ bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li+>Na+>K+>Rb+: as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane

Hydroxypyridonate and hydroxypyrimidinone chelating agents

DOEpatents

Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

2005-01-25

The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

Labeling Biomolecules with Radiorhenium - a Review of the Bifunctional Chelators

PubMed Central

Liu, Guozheng; Hnatowich, Donald J.

2007-01-01

For radiotherapy, biomolecules such as intact antibodies, antibody fragments, peptides, DNAs and other oligomers have all been labeled with radiorhenium (186Re and 188Re). Three different approaches have been employed that may be referred to as direct, indirect and integral labeling. Direct labeling applies to proteins and involves the initial reduction of endogenous disulfide bridges to provide chelation sites. Indirect labeling can apply to most biomolecules and involves the initial attachment of an exogenous chelator. Finally, integral labeling is a special case applying only to small molecules in which the metallic radionuclide serves to link two parts of a biomolecule together in forming the labeled complex. While the number of varieties for the direct and integral radiolabeling approaches is rather limited, a fairly large and diverse number of chelators have been reported in the case of indirect labeling. Our objective herein is to provide an overview of the various chelators that have been used in the indirect labeling of biomolecules with radiorhenium, including details on the labeling procedures, the stability of the radiolabel and, where possible, the influence of the label on biological properties. PMID:17504162

Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes

PubMed Central

Collepardo-Guevara, Rosana; Schlick, Tamar

2012-01-01

Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA–DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH–core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression. PMID:22790986

Improved paramagnetic chelate for molecular imaging with MRI

NASA Astrophysics Data System (ADS)

Winter, Patrick; Athey, Phillip; Kiefer, Garry; Gulyas, Gyongyi; Frank, Keith; Fuhrhop, Ralph; Robertson, David; Wickline, Samuel; Lanza, Gregory

2005-05-01

The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadolinium-diethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent.

Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use

DOEpatents

Srivastava, Suresh C.; Meinken, George E.

2001-01-01

Radiopharmaceutical compositions including .sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like. Methods of making .sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system.

Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of Antioxidant Active Packaging.

PubMed

Lin, Zhuangsheng; Goddard, Julie

2018-02-01

Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA) are widely used as additives to control trace transition metal induced oxidation in consumer products. To enable removal of synthetic chelators in response to increasing consumer demand for clean label products, metal-chelating active food packaging technologies have been developed with demonstrated antioxidant efficacy in simulated food systems. However, prior work in fabrication of metal-chelating materials leveraged batch chemical reactions to tether metal-chelating ligands, a process with limited industrial translatability for large-scale fabrication. To improve the industrial translatability, we have designed a 2-step laminated photo-grafting process to introduce metal chelating functionality onto common polymeric packaging materials. Iminodiacetic acid (IDA) functionalized materials were fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films, followed by a second photo-grafting process to graft-polymerize an IDA functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under atmospheric conditions and was completed in 2 min. The resulting IDA functionalized metal-chelating material was able to chelate iron and copper, and showed antioxidant efficacy against ascorbic acid degradation, supporting its potential to be used synergistically with natural antioxidants for preservation of food and beverage products. The 2-step photo-grafting process improves the throughput of active packaging coatings, enabling potential roll-to-roll fabrication of metal-chelating active packaging materials for antioxidant food packaging applications. To address consumer and retail demands for "clean label" foods and beverages without a corresponding loss in product quality and shelf life, producers are seeking next generation technologies such as active packaging. In this work, we will report the synthesis of metal-chelating active packaging films, which enable removal

Photocatalysts Based on Cobalt-Chelating Conjugated Polymers for Hydrogen Evolution from Water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lianwei; Hadt, Ryan G.; Yao, Shiyu

Developing photocatalytic systems for water splitting to generate oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this work, we report the first example of heterogeneous photocatalysts for hydrogen evolution based on in-chain cobalt-chelating conjugated polymers. Four conjugated polymers chelated with earth abundant cobalt ions were synthesized and found to evolve hydrogen photocatalytically from water. These polymers are designed to combine functions of the conjugated backbone as light-harvesting antenna and electron transfer conduit with the in-chain bipyridyl chelated transition metal centers as catalytic active sites. In addition, these polymers are soluble in organic solvents,more » enabling effective interactions with the substrates as well as detailed characterization. We also found a polymer-dependent optimal cobalt chelating concentration at which the highest photocatalytic hydrogen production (PHP) activity can be achieved.« less

Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease.

PubMed

Marsella, Maria; Borgna-Pignatti, Caterina

2014-08-01

Iron overload is an inevitable consequence of blood transfusions and is often accompanied by increased iron absorption from the gut. Chelation therapy is necessary to prevent the consequences of hemosiderosis. Three chelators, deferoxamine, deferiprone, and deferasirox, are presently available and a fourth is undergoing clinical trials. The efficacy of all 3 available chelators has been demonstrated. Also, many studies have shown the efficacy of the combination of deferoxamine plus deferiprone as an intensive treatment of severe iron overload. Alternating chelators can reduce adverse effects and improve compliance. Adherence to therapy is crucial for good results. Copyright © 2014 Elsevier Inc. All rights reserved.

Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease.

PubMed

Wang, Nan; Jin, Xin; Guo, Dongbo; Tong, Gangsheng; Zhu, Xinyuan

2017-02-13

Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.

Method for separating metal chelates from other materials based on solubilities in supercritical fluids

DOEpatents

Wai, Chien M.; Smart, Neil G.; Phelps, Cindy

2001-01-01

A method for separating a desired metal or metalloi from impurities using a supercritical extraction process based on solubility differences between the components, as well as the ability to vary the solvent power of the supercritical fluid, is described. The use of adduct-forming agents, such as phosphorous-containing ligands, to separate metal or metalloid chelates in such processes is further disclosed. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of .beta.-diketones; phosphine oxides, such as trialkylphosphine oxides, triarylphosphine oxides and alkylarylphosphine oxides; phosphinic acids; carboxylic acids; phosphates, such as trialkylphosphates, triarylphosphates and alkylarylphosphates; crown ethers; dithiocarbamates; phosphine sulfides; phosphorothioic acids; thiophosphinic acids; halogenated analogs of these chelating agents; and mixtures of these chelating agents. In especially preferred embodiments, at least one of the chelating agents is fluorinated.

Use of Iron Chelating Agents in Transfusion Dependent Thalassaemia Major Patients.

PubMed

Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P

2015-10-01

This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.

Targeted Catalytic Inactivation of Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

PubMed Central

Joyner, Jeff C.; Hocharoen, Lalintip; Cowan, J. A.

2012-01-01

A series of compounds that target reactive transition metal chelates to somatic Angiotensin Converting Enzyme (sACE-1) have been synthesized. Half maximal inhibitory concentrations (IC50) and rate constants for both inactivation and cleavage of full length sACE-1 have been determined and evaluated in terms of metal-chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediamine-tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine sidechain of lisinopril by EDC/NHS coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following pre-incubation with metal-chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal-chelate-lisinopril complexes revealed IC50 values ranging from 44 nM to 4,500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal-chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second order rate constants as high as 150,000 M−1min−1 (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primary from sidechain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the metal center was poised near 1000 mV, reflecting the difficulty of protein

Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates.

PubMed

Joyner, Jeff C; Hocharoen, Lalintip; Cowan, J A

2012-02-22

A series of compounds that target reactive transition-metal chelates to somatic angiotensin converting enzyme (sACE-1) have been synthesized. Half-maximal inhibitory concentrations (IC(50)) and rate constants for both inactivation and cleavage of full-length sACE-1 have been determined and evaluated in terms of metal chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine side chain of lisinopril by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride/N-hydroxysuccinimide coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel, and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following preincubation with metal chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal chelate-lisinopril complexes revealed IC(50) values ranging from 44 to 4500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second-order rate constants as high as 150,000 M(-1) min(-1) (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primarily from side chain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the

Catalytic superoxide scavenging by metal complexes of the calcium chelator EGTA and contrast agent EHPG.

PubMed

Fisher, Anna E O; Hague, Theresa A; Clarke, Charlotte L; Naughton, Declan P

2004-10-08

Metal ion chelators widely used in experimental protocols and clinical diagnosis are generally assumed to be inert. We previously reported that the ubiquitous chelator EDTA has high levels of superoxide suppressing activity. Here, we report that the common chelators calcium chelator EGTA and contrast agent EHPG have significant activities in suppressing superoxide levels depending on the nature of metal ion chelated. The most active species is Mn(II)-EGTA which exhibited an IC50 value of 0.19 microM for superoxide destruction. In addition, IC50 values for Mn(II)-EHPG and 2Cu(II)-EGTA were 0.69 and 0.60 microM, respectively. In conclusion, Mn(II) and Cu(II) complexes of the common chelators EGTA and EHPG exhibit considerable superoxide scavenging activities. Caution should be employed in their use in biological systems where superoxide has a key role and they may be useful for the development of catalytic anti-oxidants. Copyright 2004 Elsevier Inc.

Which psychosocial factors are related to chelation adherence in thalassemia? A systematic review.

PubMed

Evangeli, Michael; Mughal, Kulsoom; Porter, John B

2010-06-01

Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.

Kinetics studies with fruit bromelain (Ananas comosus) in the presence of cysteine and divalent ions.

PubMed

Kaur, Tajwinder; Kaur, Amandeep; Grewal, Ravneet K

2015-09-01

The kinetics of cysteine and divalent ion modulation viz. Ca(2+), Cu(2+), Hg(2+) of fruit bromelain (EC 3.4.22.33) have been investigated in the present study. Kinetic studies revealed that at pH 4.5, cysteine induced V-type activation of bromelain catalyzed gelatin hydrolysis. At pH 3.5, Ca(2+) inhibited the enzyme noncompetitively, whereas, both K-and V-type activations of bromelain were observed in the presence of 0.5 mM Ca(2+) at pH 4.5 and 7.5. Bromelain was inhibited competitively at 0.6 mM Cu(2+) ions at pH 3.5, which changed to an uncompetitive inhibition at pH 4.5 and 7.5. An un-competitive inhibition of bromelain catalyzed gelatin hydrolysis was observed in the presence of 0.6 mM Hg(2+) at pH 3.5 and 4.5. These findings suggest that divalent ions modulation of fruit bromelain is pH dependent.

A Radiofluorinated Divalent Cystine Knot Peptide for Tumor PET Imaging

DOE PAGES

Jiang, Lei; Kimura, Richard H.; Ma, Xiaowei; ...

2014-04-09

A divalent knottin containing two separate integrin binding epitopes (RGD) in the adjacent loops, 3-4A, was recently developed and reported in our previous publication. In the current study, 3-4A was radiofluorinated with a 4-nitrophenyl 2- 18F-fluoropropinate ( 18F-NFP) group and the resulting divalent positron emission tomography (PET) probe, 18F-FP–3-4A, was evaluated as a novel imaging probe to detect integrin αvβ3 positive tumors in living animals. Knottin 3-4A was synthesized by solid phase peptide synthesis, folded, and site-specifically conjugated with 18/19F-NFP to produce the fluorinated peptide 18/19F-fluoropropinate-3-4A ( 18/19F-FP–3-4A). The stability of 18F-FP–3-4A was tested in both phosphate buffered saline (PBS)more » buffer and mouse serum. Cell uptake assays of the radiolabeled peptides were performed using U87MG cells. In addition, small animal PET imaging and biodistribution studies of 18F-FP–3-4A were performed in U87MG tumor-bearing mice. The receptor targeting specificity of the radiolabeled peptide was also verified by coinjecting the probe with a blocking peptide cyclo(RGDyK). Our study showed that 18F-FP–3-4A exhibited excellent stability in PBS buffer (pH 7.4) and mouse serum. Small animal PET imaging and biodistribution data revealed that 18F-FP–3-4A exhibited rapid and good tumor uptake (3.76 ± 0.59% ID/g and 2.22 ± 0.62% ID/g at 0.5 and 1 h, respectively). 18F-FP–3-4A was rapidly cleared from the normal tissues, resulting in excellent tumor-to-normal tissue contrasts. For example, liver uptake was only 0.39 ± 0.07% ID/g and the tumor to liver ratio was 5.69 at 1 h p.i. Furthermore, coinjection of cyclo(RGDyK) with 18F-FP–3-4A significantly inhibited tumor uptake (0.41 ± 0.12 vs 1.02 ± 0.19% ID/g at 2.5 h) in U87MG xenograft models, demonstrating specific accumulation of the probe in the tumor. In summary, the divalent probe 18F-FP–3-4A is characterized by rapid and high tumor uptake and excellent tumor

Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005.

PubMed

2006-03-03

Chelating agents bind lead in soft tissues and are used in the treatment of lead poisoning to enhance urinary and biliary excretion of lead, thus decreasing total lead levels in the body. During the past 30 years, environmental and dietary exposures to lead have decreased substantially, resulting in a considerable decrease in population blood lead levels (BLLs) and a corresponding decrease in the number of patients requiring chelation therapy. Chelating agents also increase excretion of other heavy metals and minerals, such as zinc and, in certain cases, calcium. This report describes three deaths associated with chelation-therapy--related hypocalcemia that resulted in cardiac arrest. Several drugs are used in the treatment of lead poisoning, including edetate disodium calcium (CaEDTA), dimercaperol (British anti-Lewisite), D-penicillamine, and meso-2,3-dimercaptosuccinic acid (succimer). Health-care providers who are unfamiliar with chelating agents and are considering this treatment for lead poisoning should consult an expert in the chemotherapy of lead poisoning. Hospital pharmacies should evaluate whether continued stocking of Na2EDTA is necessary, given the established risk for hypocalcemia, the availability of less toxic alternatives, and an ongoing safety review by the Food and Drug Administration (FDA). Health-care providers and pharmacists should ensure that Na2EDTA is not administered to children during chelation therapy.

Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata.

PubMed

Elicharova, Hana; Sychrova, Hana

2014-08-01

Candida glabrata is a salt-tolerant and fluconazole (FLC)-resistant yeast species. Here, we analyse the contribution of plasma-membrane alkali-metal-cation exporters, a cation/proton antiporter and a cation ATPase to cation homeostasis and the maintenance of membrane potential (ΔΨ). Using a series of single and double mutants lacking CNH1 and/or ENA1 genes we show that the inability to export potassium and toxic alkali-metal cations leads to a slight hyperpolarization of the plasma membrane of C. glabrata cells; this hyperpolarization drives more cations into the cells and affects cation homeostasis. Surprisingly, a much higher hyperpolarization of C. glabrata plasma membrane was produced by incubating cells with subinhibitory concentrations of FLC. FLC treatment resulted in a substantially increased sensitivity of cells to various cationic drugs and toxic cations that are driven into the cell by negative-inside plasma-membrane potential. The effect of the combination of FLC plus cationic drug treatment was enhanced by the malfunction of alkali-metal-cation transporters that contribute to the regulation of membrane potential and cation homeostasis. In summary, we show that the combination of subinhibitory concentrations of FLC and cationic drugs strongly affects the growth of C. glabrata cells. © 2014 The Authors.

Lanthanide Oleates: Chelation, Self-assembly, and Exemplification of Ordered Nanostructured Colloidal Contrast Agents for Medical Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guozhen; Conn, Charlotte E.; Drummond, Calum J.

2010-01-12

Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysismore » (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T{sub 1}) and transverse (T{sub 2}) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.« less

Metal transport capabilities of anticancer copper chelators.

PubMed

Gaál, Anikó; Orgován, Gábor; Mihucz, Victor G; Pape, Ian; Ingerle, Dieter; Streli, Christina; Szoboszlai, Norbert

2018-05-01

In the present study, several Cu chelators [2,2'-biquinoline, 8-hydroxiquinoline (oxine), ammonium pyrrolidinedithiocarbamate (APDTC), Dp44mT, dithizone, neocuproine] were used to study Cu uptake, depletion and localization in different cancer cell lines. To better understand the concentration dependent fluctuations in the Cu intracellular metal content and Cu-dependent in vitro antiproliferative data, the conditional stability constants of the Cu complex species of the investigated ligands were calculated. Each investigated chelator increased the intracellular Cu content on HT-29 cells causing Cu accumulation depending on the amount of the free Cu(II). Copper accumulation was 159 times higher for Dp44mT compared to the control. Investigating a number of other transition metals, intracellular accumulation of Cd was observed only for two chelators. Intracellular Zn content slightly decreased (cca. 10%) for MCF-7 cells, while a dramatic decrease was observed on MDA-MB-231 ones (cca. 50%). A similar decrease was observed for HCT-116, while Zn depletion for HT-29 corresponded to cca. 20%. The IC 50 values were registered for the investigated four cell lines at increasing external Cu(II) concentration, namely, MDA-MB-231 cells had the lowest IC 50 values for Dp44mT ranging between 7 and 35 nM. Thus, Zn depletion could be associated with lower IC 50 values. Copper depletion was observed for all ligands being less pronounced for Dp44mT and neocuproine. Copper localization and its colocalization with Zn were determined by μ-XRF imaging. Loose correlation (0.57) was observed for the MCF-7 cells independently of the applied chelator. Similarly, a weak correlation (0.47) was observed for HT-29 cells treated with Cu(II) and oxine. Colocalization of Cu and Zn in the nucleus of HT-29 cells was observed for Dp44mT (correlation coefficient of 0.85). Copyright © 2018 Elsevier GmbH. All rights reserved.

Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

PubMed Central

Kurokawa, Yoshika; Sone, Hideko; Win-Shwe, Tin-Tin; Zeng, Yang; Kimura, Hiroyuki; Koyama, Yosuke; Yagi, Yusuke; Matsui, Yasuto; Yamazaki, Masashi; Hirano, Seishiro

2017-01-01

Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau– Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids. PMID:28579780

Pressure-induced cation-cation bonding in V 2 O 3

DOE PAGES

Bai, Ligang; Li, Quan; Corr, Serena A.; ...

2015-10-09

A pressure-induced phase transition, associated with the formation of cation-cation bonding, occurs in V 2O 3 by combining synchroton x-ray diffraction in a diamond anvil cell and ab initio evolutionary calculations. The high-pressure phase has a monoclinic structure with a C2/c space group, and it is both energetically and dynamically stable at pressures above 47 GPa to at least 105 GPa. this phase transition can be viewed as a two-dimensional Peierls-like distortion, where the cation-cation dimer chains are connected along the c axis of the monoclinic cell. In conclusion, this finding provides insights into the interplay of electron correlation andmore » lattice distortion in V 2O 3, and it may also help to understand novel properties of other early transition-metal oxides.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Hyun Deog; Liang, Yanliang; Dong, Hui

Magnesium rechargeable batteries potentially offer high-energy density, safety, and low cost due to the ability to employ divalent, dendrite-free, and earth-abundant magnesium metal anode. Despite recent progress, further development remains stagnated mainly due to the sluggish scission of magnesium-chloride bond and slow diffusion of divalent magnesium cations in cathodes. Here in this paper we report a battery chemistry that utilizes magnesium monochloride cations in expanded titanium disulfide. Combined theoretical modeling, spectroscopic analysis, and electrochemical study reveal fast diffusion kinetics of magnesium monochloride cations without scission of magnesium-chloride bond. The battery demonstrates the reversible intercalation of 1 and 1.7 magnesium monochloridemore » cations per titanium at 25 and 60 °C, respectively, corresponding to up to 400 mAh g -1 capacity based on the mass of titanium disulfide. The large capacity accompanies with excellent rate and cycling performances even at room temperature, opening up possibilities for a variety of effective intercalation hosts for multivalent-ion batteries.« less

Determination of Mg(2+) Speciation in a TFSI(-)-Based Ionic Liquid With and Without Chelating Ethers Using Raman Spectroscopy.

PubMed

Watkins, Tylan; Buttry, Daniel A

2015-06-11

Raman spectroscopy was employed to assess the complex environment of magnesium salts in the n-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMPyrTFSI) room-temperature ionic liquid (RTIL). At room temperature, Mg(TFSI)2 was miscible with BMPyrTFSI and formulated by [Mg(TFSI)2](x)[BMPyrTFSI](1-x) (x ≤ 0.55). Results suggest that at low concentrations of Mg(TFSI)2, anionic complexes in which Mg(2+) is surrounded by at least four TFSI(-) were formed. Above x = 0.2 an average of three TFSI(-) surround each Mg(2+). Below x = 0.12, there is a greater number of monodentate interactions between TFSI(-) oxygens and Mg(2+) cations, whereas above x = 0.12 bidentate ligands dominate. The fraction of TFSI(-) existing in the cis conformation increased with increasing Mg(2+) concentration. Mg(ClO4)2 was also studied as a Mg(2+) source. At equivalent mole fractions to those of the Mg(TFSI)2 salt, Mg(2+) from Mg(ClO4)2 was surrounded by only two TFSI(-) anions as ClO4(-) appeared to compete with TFSI(-) for coordination with Mg(2+). Similar behavior was also observed for the less soluble halide salts MgX2 (X = Cl, Br, I). Additions of chelating ligands were shown to effectively reduce the average number of TFSI(-) around Mg(2+) in a manner consistent with maintaining a sixfold oxygen coordination number around Mg(2+). Furthermore, an alternative class of ionic liquids, known as "solvate" ionic liquids, were produced. In this case glymes (Gm, m + 1 ether oxygens) were mixed with Mg(TFSI)2 so that glymes chelated Mg(2+), creating Mg(Gm)(y)(2+) complexes. The general formula was given by Mg(Gm)(y)(TFSI)2. These solvate ILs melt between 40 and 80 °C. Raman spectra clearly showed the glyme chelating ability and stronger coordination with Mg(2+) with respect to TFSI(-). Finally, linear sweep voltammograms showed the anodic stability of the glymes to improve due to coordination with Mg(2+).

Ionic configuration of copper ferrimanganites Cu 0.5Mn xFe 2.5- xO 4

NASA Astrophysics Data System (ADS)

Lenglet, M.; Kasperek, J.; Hannoyer, B.; Lopitaux, J.; d'Huysser, A.; Tellier, J. C.

1992-06-01

Mössbauer spectrometry, neutron diffraction, XANES, and XPS have led to the determination of the cation distributions of the system Cu 0.5Mn xFe 2.5- xO 4 (0≤ x≤1.5). The three cations are present in both tetrahedral and octahedral sites, and the relative number of Fe ions on A- and B-sites remains nearly constant in the whole range of x. It appears that for x≤0.5 manganese is divalent and copper is in its two oxidation states. For x>0.5 copper and iron are respectively divalent and trivalent; the manganese is in +2 and +3 oxydation states.

Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction

PubMed Central

Mir, Aamir; Chen, Ji; Robinson, Kyle; Lendy, Emma; Goodman, Jaclyn; Neau, David; Golden, Barbara L.

2016-01-01

The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn2+ specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH–rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction. PMID:26398724

Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.

PubMed

Mir, Aamir; Chen, Ji; Robinson, Kyle; Lendy, Emma; Goodman, Jaclyn; Neau, David; Golden, Barbara L

2015-10-20

The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn(2+) specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH-rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction.

Effects of Physicochemical Factors on the Adhesion to Cellulose Avicel of the Ruminal Bacteria Ruminococcus flavefaciens and Fibrobacter succinogenes subsp. succinogenes.

PubMed

Roger, V; Fonty, G; Komisarczuk-Bony, S; Gouet, P

1990-10-01

Ruminococcus flavefaciens adhered instantly to cellulose, while Fibrobacter succinogenes had the highest percentage of adherent cells after about 25 min of contact between bacteria and cellulose. Adhesion of R. flavefaciens was unaffected by high concentrations of sugars (5%), temperature, pH, oxygen, metabolic inhibitors, and lack of Na. In contrast, the attachment was affected by the removal of divalent cations (Mg and Ca), the presence of cellulose derivatives (methylcellulose and hydroxyethylcellulose), and cystine. Adhesion of F. succinogenes was sensitive to low and high temperatures, high concentrations of glucose and cellobiose (5%), hydroxyethylcellulose (0.1%), redox potential, pH, lack of monovalent cations, and the presence of an inhibitor of membrane ATPases or lasalocid and monensin. Cells of F. succinogenes heated at 100 degrees C no longer were adherent. On the other hand, adhesion was insensitive to the lack of divalent cations (Mg and Ca), the presence of 2,4-dinitrophenol, tetrachlorosalicylanilide, or inhibitors of the electron transfer chains. Adhesion of F. succinogenes seems to be related to the metabolic functions of the cell. External proteins and/or cellulases themselves might play a part in the attachment process. Several mechanisms are probably involved in the adhesion of R. flavefaciens, the main one being the interaction between the large glycocalyx and the divalent cations Ca and Mg. Hydrophobic bonds and enzymes may also be involved.

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fatimah, Soja Siti, E-mail: soja-sf@upi.edu; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor; Bahti, Husein H.

2016-02-08

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, andmore » using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.« less

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

NASA Astrophysics Data System (ADS)

Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

2016-02-01

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, (1H, and 13C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

Development of an upconverting chelate assay

NASA Astrophysics Data System (ADS)

Xiao, Xudong; Haushalter, Jeanne P.; Kotz, Kenneth T.; Faris, Gregory W.

2005-04-01

We report progress on performing a cell-based assay for the detection of EGFR on cell surfaces by using upconverting chelates. An upconversion microscope has been developed for performing assays and testing optical response. A431 cells are labeled with europium DOTA and imaged using this upconverting microscope.

Oxidative degradation stability and hydrogen sulfide removal performance of dual-ligand iron chelate of Fe-EDTA/CA.

PubMed

Miao, Xinmei; Ma, Yiwen; Chen, Zezhi; Gong, Huijuan

2017-09-05

Catalytic oxidation desulfurization using chelated iron catalyst is an effective method to remove H 2 S from various gas streams including biogas. However, the ligand of ethylenediaminetetraacetic acid (EDTA), which is usually adopted to prepare chelated iron catalyst, is liable to be oxidative degraded, and leads to the loss of desulfurization performance. In order to improve the degradation stability of the iron chelate, a series of iron chelates composed of two ligands including citric acid (CA) and EDTA were prepared and the oxidative degradation stability as well as desulfurization performance of these chelated iron catalysts were studied. Results show that the iron chelate of Fe-CA is more stable than Fe-EDTA, while for the desulfurization performance, the situation is converse. For the dual-ligand iron chelates of Fe-EDTA/CA, with the increase of mol ratio of CA to EDTA in the iron chelate solution, the oxidative degradation stability increased while the desulfurization performance decreased. The results of this work showed that Fe-EDTA/CA with a mol ratio of CA:EDTA = 1:1 presents a relative high oxidative degradation stability and an acceptable desulfurization performance with over 90% of H 2 S removal efficiency.

Polycatecholamide chelating agents

DOEpatents

Weitl, F.L.; Raymond, K.N.

1984-04-10

Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula given in patent. Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO[sub 3]H, SO[sub 3]M, NO[sub 2], CO[sub 2]H or CO[sub 2]M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr[sub 3] or BCl[sub 3] in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated. No Drawings

Polycatecholamide chelating agents

DOEpatents

Weitl, Frederick L.; Raymond, Kenneth N.

1984-01-01

Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula ##STR1## Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO.sub.3 H, SO.sub.3 M, NO.sub.2, CO.sub.2 H or CO.sub.2 M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr.sub.3 or BCl.sub.3 in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated.

INFLUENCE OF IRON CHELATION ON R1 AND R2 CALIBRATION CURVES IN GERBIL LIVER AND HEART

PubMed Central

Wood, John C.; Aguilar, Michelle; Otto-Duessel, Maya; Nick, Hanspeter; Nelson, Marvin D.; Moats, Rex

2008-01-01

MRI is gaining increasing importance for the noninvasive quantification of organ iron burden. Since transverse relaxation rates depend on iron distribution as well as iron concentration, physiologic and pharmacologic processes that alter iron distribution could change MRI calibration curves. This paper compares the effect of three iron chelators, deferoxamine, deferiprone, and deferasirox on R1 and R2 calibration curves according to two iron loading and chelation strategies. 33 Mongolian gerbils underwent iron loading (iron dextran 500 mg/kg/wk) for 3 weeks followed by 4 weeks of chelation. An additional 56 animals received less aggressive loading (200 mg/kg/week) for 10 weeks, followed by 12 weeks of chelation. R1 and R2 calibration curves were compared to results from 23 iron-loaded animals that had not received chelation. Acute iron loading and chelation biased R1 and R2 from the unchelated reference calibration curves but chelator-specific changes were not observed, suggesting physiologic rather than pharmacologic differences in iron distribution. Long term chelation deferiprone treatment increased liver R1 50% (p<0.01), while long term deferasirox lowered liver R2 30.9% (p<0.0001). The relationship between R1 and R2 and organ iron concentration may depend upon the acuity of iron loading and unloading as well as the iron chelator administered. PMID:18581418

Reaction of gadolinium chelates with ozone and hydroxyl radicals.

PubMed

Cyris, Maike; Knolle, Wolfgang; Richard, Jessica; Dopp, Elke; von Sonntag, Clemens; Schmidt, Torsten C

2013-09-03

Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.

Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer.

PubMed

Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

2016-12-01

The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. These poly(dendrimer) polymers could store Lewis acids (SnCl 2 ) in their unoccupied orbitals, thus indicating that these poly(dendrimer) polymers consist of a series of nanocontainers.

Monochloro non-bridged half-metallocene-type zirconium complexes containing phosphine oxide-(thio)phenolate chelating ligands as efficient ethylene polymerization catalysts.

PubMed

Tang, Xiao-Yan; Wang, Yong-Xia; Liu, San-Rong; Liu, Jing-Yu; Li, Yue-Sheng

2013-01-14

A series of novel monochloro half-zirconocene complexes containing phosphine oxide-(thio)phenolate chelating ligands of the type, ClCp'Zr[X-2-R(1)-4-R(2)-6-(Ph(2)P=O)C(6)H(2)](2) (Cp' = C(5)H(5), 2a: X = O, R(1) = Ph, R(2) = H; 2b: X = O, R(1) = F, R(2) = H; 2c: X = O, R(1) = (t)Bu, R(2) = H; 2d: X = O, R(1) = R(2) = (t)Bu; 2e: X = O, R(1) = SiMe(3), R(2) = H; 2f: X = S, R(1) = SiMe(3), R(2) = H; Cp' = C(5)Me(5), 2g: X = O, R(1) = SiMe(3), R(2) = H), have been synthesized in high yields. These complexes were identified by (1)H {(13)C} NMR and elemental analyses. Structures for 2b, 2c and 2f were further confirmed by X-ray crystallography. Structural characterization of these complexes reveals crowded environments around the zirconium. Complexes 2b and 2c adopt six-coordinate, distorted octahedral geometry around the zirconium center, in which the equatorial positions are occupied by three oxygen atoms of two chelating phosphine oxide-bridged phenolate ligands and a chlorine atom. The cyclopentadienyl ring and one oxygen atom of the ligand are coordinated on the axial position. Complex 2f also folds a six-coordinate, distorted octahedral geometry around the Zr center, consisting of a Cp-Zr-O (in P=O) axis [177.16°] and a distorted plane of two sulfur atoms and one oxygen atom of two chelating phosphine oxide-bridged thiophenolate ligands as well as a chlorine atom. When activated by modified methylaluminoxane (MMAO), all the complexes exhibited high activities towards ethylene polymerization at high temperature (75 °C), giving high molecular weight polymers with unimodal molecular weight distribution. The formation of 14-electron, cationic metal alkyl species might come from the Zr-O (in phenol ring) bond cleavage based on the DFT calculations study.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract.

PubMed

DeAlba-Montero, I; Guajardo-Pacheco, Jesús; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene; Loredo-Becerra, G M; Martínez-Castañón, Gabriel-Alejandro; Ruiz, Facundo; Compeán Jasso, M E

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli , Staphylococcus aureus , and Enterococcus faecalis . These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis . Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

PubMed Central

DeAlba-Montero, I.; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used. PMID:28286459

Acyclic chelate with ideal properties for (68)Ga PET imaging agent elaboration.

PubMed

Boros, Eszter; Ferreira, Cara L; Cawthray, Jacqueline F; Price, Eric W; Patrick, Brian O; Wester, Dennis W; Adam, Michael J; Orvig, Chris

2010-11-10

We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N(3)O(3)) or DOTA (N(4)O(4)) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N(4)O(2) chelate H(2)dedpa coordinates (67)Ga quantitatively to form [(67)Ga(dedpa)](+) after 10 min at RT. Concentration-dependent coordination to H(2)dedpa of either (68)Ga or (67)Ga showed quantitative conversion to the desired products with ligand concentrations as low as 10(-7) M. With (68)Ga, specific activities as high as 9.8 mCi nmol(-1) were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [(67)Ga(dedpa)](+) showed no decomposition. Two bifunctional versions of H(2)dedpa are also described, and these both coordinate to (67)Ga at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the (67)Ga complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA.

Multi-omic profiling to assess the effect of iron starvation in Streptococcus pneumoniae TIGR4

PubMed Central

Jiménez-Munguía, Irene; Calderón-Santiago, Mónica; Rodríguez-Franco, Antonio; Priego-Capote, Feliciano

2018-01-01

We applied multi-omics approaches (transcriptomics, proteomics and metabolomics) to study the effect of iron starvation on the Gram-positive human pathogen Streptococcus pneumoniae to elucidate global changes in the bacterium in a condition similar to what can be found in the host during an infectious episode. We treated the reference strain TIGR4 with the iron chelator deferoxamine mesylate. DNA microarrays revealed changes in the expression of operons involved in multiple biological processes, with a prevalence of genes coding for ion binding proteins. We also studied the changes in protein abundance by 2-DE followed by MALDI-TOF/TOF analysis of total cell extracts and secretome fractions. The main proteomic changes were found in proteins related to the primary and amino sugar metabolism, especially in enzymes with divalent cations as cofactors. Finally, the metabolomic analysis of intracellular metabolites showed altered levels of amino sugars involved in the cell wall peptidoglycan metabolism. This work shows the utility of multi-perspective studies that can provide complementary results for the comprehension of how a given condition can influence global physiological changes in microorganisms.

Determination of glutathione in human plasma using high-performance liquid chromatography with electrochemical detection with a carbon-epoxy resin composite electrode chemically modified with cobalt phthalocyanine.

PubMed

Wring, S A; Hart, J P; Birch, B J

1989-12-01

High-performance liquid chromatography with electrochemical detection (LCEC), incorporating a novel carbon-epoxy resin working electrode modified with cobalt phthalocyanine, has been employed for preliminary studies directed towards the determination of normal circulating levels of reduced glutathione (GSH) in human plasma. The mobile phase consisted of 0.05 M phosphate buffer (pH 3) containing 0.1% m/m ethylenediaminetetraacetic acid (EDTA); the calibration graph was linear in the range 0.24-30.7 ng of GSH injected. The mean recovery of GSH added to a control serum over the physiological concentration range (0.38-3.07 ng ml-1) was 99%; this was achieved following a simple sample pre-treatment method, prior to LCEC, involving chelation of divalent cations with EDTA and subsequent acidification with orthophosphoric acid. Using the LCEC method, the mean circulating level of GSH in plasma, found in three normal subjects, was 2.69 microM, GSH; this indicates that the method might be applicable to the determination of depressed circulating levels of GSH.

The crystal structure of the calcium-bound con-G[Q6A] peptide reveals a novel metal-dependent helical trimer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cnudde, Sara E.; Prorok, Mary; Jia, Xaofei

2012-02-15

The ability to form and control both secondary structure and oligomerization in short peptides has proven to be challenging owing to the structural instability of such peptides. The conantokin peptides are a family of {gamma}-carboxyglutamic acid containing peptides produced in the venoms of predatory sea snails of the Conus family. They are examples of short peptides that form stable helical structures, especially in the presence of divalent cations. Both monomeric and dimeric conantokin peptides have been identified and represent a new mechanism of helix association, 'the metallozipper motif' that is devoid of a hydrophobic interface between monomers. In the presentmore » study, a parallel/antiparallel three-helix bundle was identified and its crystal structure determined at high resolution. The three helices are almost perfectly parallel and represent a novel helix-helix association. The trimer interface is dominated by metal chelation between the three helices, and contains no interfacial hydrophobic interactions. It is now possible to produce stable monomeric, dimeric, or trimeric metallozippers depending on the peptide sequence and metal ion. Such structures have important applications in protein design.« less

DISTINCT ROLES OF β1 MIDAS, ADMIDAS AND LIMBS CATION-BINDING SITES IN LIGAND RECOGNITION BY INTEGRIN α2β1*

PubMed Central

Valdramidou, Dimitra; Humphries, Martin J.; Mould, A. Paul

2012-01-01

Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as α2β1, ligand recognition takes place exclusively at the α subunit I domain. However, activation of the αI domain depends on its interaction with a structurally similar domain in the β subunit known as the I-like or βI domain. The top face of the βI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS) and LIMBS (ligand-associated metal binding site). The role of these sites in controlling ligand binding to the αI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to α2β1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating mAb TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between αI and βI whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of βI. An activating mutation in the α2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca2+, Mg2+ and Mn2+ on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn2+ stimulates ligand binding, whereas the LIMBS is a stimulatory Ca2+-binding site, occupancy of which increases the affinity of Mg2+ for the MIDAS. PMID:18820259

Effect of diuretics on renal tubular transport of calcium and magnesium.

PubMed