Inhibition, by an amphiphilic substance, niflumic acid, of the inward rectification of the crustacean muscle fiber

Agents such as TEA+ or CS+ ions, these last ions instead of K+ ions in poor K extracellular solution, known to reduce or abolish the inwardly rectifying channel in many preparations produced no effect in crayfish muscle membrane By contrast, poor Cl extracellular solution (Cl- ions were replaced by CH3OSO3- ions) blocked the inward current activated by hyperpolarizing pulses and produced an increase of the resting potential. Niflumic acid is a agent which inhibited the inward going rectification of the crayfish muscle membrane. Apparent dissociation constant of niflumic acid with membrane sites was equal to about 6 X 10(-8) M; this value corresponds to that given by Cousin & Motais (1979) concerning translocation of Cl- ions in the membrane of red cells. Activation of the inward going rectification in the crayfish membrane is responsible of an inward current carried by Cl- ions.     

Effects of iron,copper, and chromate ions on the oxidative degradation of cellulose model compounds

Iron(II) and iron(III) ions promote the degradation of the cellulose model 1,5-anhydrocellobiitol by oxygen or hydrogen peroxide; copper and chromate ions have marked and different effects on the iron catalysis. With starch, iron promotes the hydrogen peroxide-induced reaction and copper and chromate ions further enhance the reaction rate. The tensile strength of paper board is reduced by the action of hydrogen peroxide and iron(II) salts, and mixtures of copper, chromate, and arsenate salts (CCA, a timber preservative) also promote degradation in the presence or absence of iron ions. The oxidation of 1,5-anhydrocellobiitol by oxygen in the presence of iron ions is strongly inhibited by CCA and by cetyltrimethylammonium chloride, and is accelerated by phenols and related compounds.     

Macromolecular interactions with cadmium and the effects of zinc,copper, lead,and mercury ions

Interactions of cadmium (Cd) ions with bovine serum albumin (BSA), bovine hepatic metallothionein (MT), calf thymus histone and deoxyribonucleic acid (DNA), and bovine hepatic chromatins were studied in the presence and absence of divalent zinc (Zn), copper (Cu), mercury (Hg), or lead (Pb) ions, using equilibrium dialysis at pH 7 and at 37°C. The BSA had 3.5 Cd-binding sites with an apparent affinity constant of 1×10⁵. The other metal ions inhibited the binding by reducing the affinity constant and the number of Cd-binding sites in BSA. There were 6 high affinity and 13 low affinity Cd-binding sites in the MT. Zinc ions had poor efficacy in reducing the binding of Cd to the MT. However, the Cu²⁺ and Hg²⁺ ions inhibited the Cd binding to a considerable extent, the former ions being more potent in this respect. Histone did not bind Cd. There were two kinds of Cd-binding sites in DNA: One mole of Cd per four moles DNA-phosphorus at low affinity sites, and one mole of Cd per 6.7 moles DNA-phosphorus at high affinity sites. Their apparent association constants were 8.3×10⁵ and 4.4×10⁶ M, respectively. The other metal ions had inhibitory effects on the binding of Cd to DNA. Histone reduced the Cd-DNA interactions to only a minor extent. The other metal ions reduced the binding of Cd to DNA-histone complex to a small extent. Cadmium binds to the euchromatin (Euch), heterochromatin (Het), and Euch-Het mixture almost equally. The other metal ions reduced the binding maximally in Euch-Het followed next in order by Het and Euch. Cupric ions were the most potent inhibitors of the interactions of Cd with the nuclear materials.     

Monoamine metabolites,iron induced seizures,and the anticonvulsant effect of tannins

Intracortical injections of iron ions have been shown to induce recurrent seizures and epileptic discharges in the EEG. (–)-Epigallocatechin (EGC) and (–)-epigallocatecatechin-3-O-gallate (EGCG), isolated from green tea leaves, have been reported to prevent or diminish the occurrence of epileptic discharges induced by iron ions, and to inhibit catechol-O-methyltransferase. Iron ions significantly increased DOPAC and HVA levels in the intrastriatal perfusate 140 and 180 minutes, respectively, after injection. EGC and EGCG inhibited the increases induced by iron ions. Furthermore, EGCG decreased the HVA level in the perfusate 200 minutes after injection whether or not iron ions were injected. Iron ions had no effect on the 5-HIAA level, and EGC and EGCG raised it. These results suggest that formation of an epileptic focus induced by iron ions might be accompanied by activation of dopaminergic neurons, and that EGC and EGCG inhibit that hyperactivity.     

Proton, calcium, and magnesium binding by peptides containing gamma-carboxyglutamic acid.

gamma-Carboxyglutamic acid (Gla) is believed to bind Ca [II] ions and Mg [II] ions in prothrombin and other coagulation proteins. Binding constants for H+, Ca [II] ions, and Mg [II] ions to Gla-containing peptides are determined using pH and ion selective electrode titrations. The binding constants for peptides containing a single Gla residue are similar to the constants for malonic acid. Peptides containing two Gla residues in sequence (di-Gla peptides) bind Ca [II] ions and Mg [II] ions more strongly. KMgL for the di-Gla peptides is similar to the site-binding constant for Ca [II] ions in denatured BF1. These di-Gla peptides may be useful analogs for metal binding by the disordered Gla domain in BF1.     

Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation

In vivo, cysteine in proteins or glutathione is the major amino acid involved in sulfhydryl oxidation-reduction reactions. An in vitro model of cysteine oxidation accelerated by selenium compounds was used to study the interaction of selenocystine and sodium selenite with metal ions. The interaction of metal ions with selenium compounds inhibited cysteine oxidation. The ionic forms of three toxic soft-acid metals, mercury, silver, and gold, were the most effective inhibitors. The antiarthritic gold drugs, aurothiomalate and aurothioglucose, were of particular interest as they inhibit the activity of selenium-glutathione peroxidase. The effect of gold ligands on gold(I) inhibition of selenocystine-accelerated cysteine oxidation was tested. Sodium cyanide partially reversed inhibition and potassium iodide had no effect. Inhibition of selenium-accelerated oxidation-reduction reactions by soft-acid metal ions may be of biological relevance during toxicities or during antiarthritic gold therapy.     

Distributions of the ion temperature,ion pressure,and electron density over the current sheet surface

The distributions of the ion temperature, ion pressure, and electron density over the width (the major transverse dimension) of the current sheet have been studied for the first time. The current sheets were formed in discharges in argon and helium in 2D and 3D magnetic configurations. It is found that the temperature of argon ions in both 2D and 3D magnetic configurations is almost uniform over the sheet width and that argon ions are accelerated by the Ampère force. In contrast, the distributions of the electron density and the temperature of helium ions are found to be substantially nonuniform. As a result, in the 2D magnetic configuration, the ion pressure gradient across the sheet width makes a significant contribution (comparable with the Ampère force) to the acceleration of helium ions, whereas in the 3D magnetic configuration, the Ampère force is counterbalanced by the pressure gradient.     

Heavy meromyosin and subfragment-1 from squid mantle myosin, and Ca-sensitivity of their Mg-ATPases

Heavy meromyosin (HMM) and subfragment-1 (S1) were obtained from squid mantle myosin by tryptic digestion and chymotryptic digestion, respectively. Squid HMM(T) and S1(CT) preparations contained stoichiometric amounts of the two types of light chain subunit; regulatory light chain, LC-2, and essential light chain, LC-1. No difference was detected in the chymotryptic digestibilities of squid mantle myosin in Ca-medium and in EDTA-medium. This is in contrast to the digestibility of scallop adductor myosin. The Mg-ATPase activity of HMM(T) alone and that of acto-HMM(T) were both sensitive to calcium ions. In contrast, the activity of S1(CT) alone and that of acto-S1(CT) were both insensitive to calcium ions. The affinity of HMM(T) for actin was not affected by calcium ions, but the amount of HMM(T) bound to actin was increased by calcium ions from 20% to 60% of the total amount of HMM(T). On the other hand, the actin affinity of S1(CT) and the amount of S1(CT) bound to actin were both unaffected by calcium ions. The role of calcium ions in the regulation of contraction in molluscan muscles is discussed.     

Calcium sensitivity of abalone, Haliotis discus, myosin.

Superprecipitation was observed with abalone myosin and purified rabbit actin in the presence of calcium ions, but was not observed in the absence of calcium. The Mg-ATPase [EC 3.6.1.3] activity of abalone myosin and rabbit actin in the absence of calcium ions (EGTA present) showed about 60% inhibition as compared with values in the presence of calcium ions. The calcium sensitivity may be attributable to abalone myosin, as in the case of scallop myosin.     

Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH.

Evidence is given for a high density of negative surface charge near the sodium channel of myelinated nerve fibres. The voltage dependence of peak sodium permeability is measured in a voltage clamp. The object is to measure voltage shifts in sodium activation as the following external variables are varied: divalent cation concentration and type, monovalent concentration, and pH. With equimolar substitution of divalent ions the order of effectiveness for giving a positive shift is: Ba equals Sr less than Mg less than Ca less than Co approximately equal to Mn less than Ni less than Zn. A tenfold increase of concentration of any of these ions gives a shift of +20 to +25 mV. At low pH, the shift with a tenfold increase in Ca-2+ is much less than at normal pH, and conversely for high pH. Soulutions with no added divalent ions give a shift of minus 18 mV relative to 2 mM Ca-2+. Removal of 7/8 of the cations from the calcium-free solution gives a further shift of minue 35 mV. All shifts are explained quantitatively by assuming that changes in an external surface potential set up by fixed charges near the sodium channel produce the shifts. The model involves a diffuse double layer of counterions at the nerve surface and some binding of H+ions and divalent ions to the fixed charges. Three types of surface groups are postulated: (1) an acid pKa equals 2.88 charge density minus 0.9 nm- minus 2; (i) an acid pKa equals 4.58, charge density minus 0.58 nm- minus 2; (3) a base pKa equals 6.28, charge density +0.33 nm- minus 2. The two acid groups also bind Ca-2+ ions with a dissociation constant K equals 28 M. Reasonable agreement can also be obtained with a lower net surface charge density and stronger binding of divalent ions and H+ ions.     

A scale of metal ion binding strengths correlating with ionic charge, Pauling electronegativity, toxicity, and other physiological effects

Equilibrium constants for binding to plant plasma membranes have been reported for several metal ions, based upon adsorption studies and zeta-potential measurements. LogK values for the ions are these: Al(3+), 4.30; La(3+), 3.34; Cu(2+), 2.60; Ca(2+) and Mg(2+), 1.48; Na(+) and K(+), 0 M(-1). These values correlate well with logK values for ion binding to many organic and inorganic ligands. LogK values for metal ion binding to 12 ligands were normalized and averaged to produce a scale for the binding of 49 ions. The scale correlates well with the values presented above (R(2)=0.998) and with ion binding to cell walls and other biomass. The scale is closely related to the charge (Z) and Pauling electronegativity (PE) of 48 ions (all but Hg(2+)); R(2)=0.969 for the equation (Scale values)=-1.68+Z(1.22+0.444PE). Minimum rhizotoxicity of metal ions appears to be determined by binding strengths: log a(PM,M)=1.60-2.41exp[0.238(Scale values)] determines the value of ion activities at the plasma membrane surface (a(PM,M)) that will ensure inhibition of root elongation. Additional toxicity appears to be related to softness, accounting for the great toxicity of Ag(+), for example. These binding-strength values correlate with additional physiological effects and are suitable for the computation of cell-surface electrical potentials.     

Kinetics of sulfate transport by Penicillium notatum. Interactions of sulfate, protons, and calcium.

The active transport of inorganic sulfate by an ATP sulfurylase-negative strain of Penicillium notatum is promoted by H+ ions and metal ions (divalent metal ions being more effective than monovalent metal ions). Initial velocity studies suggest that H+ and SO4(2-) add to the carrier in an ordered sequence (H+ before SO4(2-)), with H+ at equilibrium with free carrier and carrier-H+ complex. The linear reciprocal plots and replots suggest a 1:1 stoichiometry between H+ and SO4(2-). Ca2+ and other divalent metal ions stimulate sulfate transport markedly in buffered suspensions of low ionic strength. The kinetics of the Ca2+/SO4(2-) interaction suggest that Ca2+ (like H+) adds to the carrier before SO4(2-) and is at equilibrium with free carrier and carrier-Ca2+ complex. The linear reciprocal plots and replots indicate a 1:1 stoichiometry between Ca2+ and SO4(2-). Thus the fully loaded carrier-SO4(2-) -Ca2+ -H+ complex has a net positive charge relative to that of the free carrier, a fact consistent with the chemiosmotic hypothesis of membrane transport. The kinetics of the H+/Ca2+ interaction point to a random A-B (rapid equilibrium), ordered C sequence with A = H+, B = Ca2+, and C = SO4(2-). Selenate (an alternate substrate competitive with sulfate) is an uncompetitive inhibitor with respect to Ca2+, in agreement with the suggested mechanism. Internal charge balance is not accomplished by a stoichiometric coaccumulation of Ca2+ and SO4(2-). Sulfate transport does, however, promote 45Ca2+ uptake. A significant fraction of the added Ca2+ is bound by the mycelial surface. Binding is extremely rapid, but reversible.     

Effect of Various Ions, pH, and Osmotic Pressure on Oxidation of Elemental Sulfur by Thiobacillus thiooxidans

The oxidation of elemental sulfur by Thiobacillus thiooxidans was studied at pH 2.3, 4.5, and 7.0 in the presence of different concentrations of various anions (sulfate, phosphate, chloride, nitrate, and fluoride) and cations (potassium, sodium, lithium, rubidium, and cesium). The results agree with the expected response of this acidophilic bacterium to charge neutralization of colloids by ions, pH-dependent membrane permeability of ions, and osmotic pressure.     

Physicochemical characterization, and relaxometry studies of micro-graphite oxide, graphene nanoplatelets, and nanoribbons

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn(2+) ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.     

Selective Electrodiffusion of Zinc Ions in a Zrt-, Irt-like Protein,ZIPB

All living cells need zinc ions to support cell growth. Zrt-, Irt-like proteins (ZIPs) represent a major route for entry of zinc ions into cells, but how ZIPs promote zinc uptake has been unclear. Here we report the molecular characterization of ZIPB from Bordetella bronchiseptica, the first ZIP homolog to be purified and functionally reconstituted into proteoliposomes. Zinc flux through ZIPB was found to be nonsaturable and electrogenic, yielding membrane potentials as predicted by the Nernst equation. Conversely, membrane potentials drove zinc fluxes with a linear voltage-flux relationship. Direct measurements of metal uptake by inductively coupled plasma mass spectroscopy demonstrated that ZIPB is selective for two group 12 transition metal ions, Zn²⁺ and Cd²⁺, whereas rejecting transition metal ions in groups 7 through 11. Our results provide the molecular basis for cellular zinc acquisition by a zinc-selective channel that exploits in vivo zinc concentration gradients to move zinc ions into the cytoplasm.     

Site-specific interactions of copper(II) ions with heparin revealed with complementary (SRCD, NMR, FTIR and EPR) spectroscopic techniques

The interactions between Cu(II) ions and heparin were investigated using several complementary spectroscopic techniques. NMR indicated an initial binding phase involving specific coordination to four points in the structure that recur in slightly different environments throughout the heparin chain; the carboxylic acid group and the ring oxygen of iduronate-2-O-sulfate, the glycosidic oxygen between this residue and the adjacent (towards the reducing end) glucosamine and the 6-O-sulfate group. In contrast, the later binding phase showed little structural specificity. One- and two-dimensional correlated FTIR revealed that complex out of phase (asynchronous) conformational changes also occurred during the titration of Cu(II) ions into heparin, involving the CO and N-H stretches. EPR demonstrated that the environments of the Cu(II) ions in the initial binding phase were tetragonal (with slightly varied geometry), while the later non-specific phases exhibited conventional coordination. Visible spectroscopy confirmed a shift of the absorbance maximum. Titration of Cu(II) ions into a solution of heparin indicated (both by analysis of FTIR and EPR spectra) that the initial binding phase was complete by 15-20 Cu(II) ions per chain; thereafter the ions bound in the non-specific mode. Hetero-correlation spectroscopy (FTIR-CD) improved resolution and assisted assignment of the broad CD features from the FTIR spectra and indicated both in-phase and more complex out of phase (synchronous and asynchronous, respectively) changes in interactions within the heparin molecule during the titration of Cu(II) ions.     

Synthesis, DNA cleavage, and cytotoxicity of a series of bis(propargylic) sulfone crown ethers

Compounds that couple molecular recognition of specific alkali metal ions with DNA damage may display selective cleavage of DNA under conditions of elevated alkali metal ion levels reported to exist in certain cancer cells. We have prepared a homologous series of compounds in which a DNA reactive moiety, a bis(propargylic) sulfone, is incorporated into an alkali metal ion binding crown ether ring. Using the alkali metal ion pricrate extraction assay, the ability of these crown ethers to bind Li(+), Na(+), and K(+) ions was determined. For the series of crown ethers, the association constants for Li(+) ions are generally low (< 2 x 10(4)M(-1)). Only two of the bis(propargylic) sulfone crown ethers associate with Na(+) or K(+) ions (K(a) 4-8 x 10(4)M(-1)), with little discrimination between Na(+) or K(+) ions. The ability of these compounds to cleave supercoiled DNA at pH 7.4 in the presence of Li(+), Na(+), and K(+) ions was determined. The two crown ethers that bind Na(+) and K(+) display a modest increase in DNA cleavage efficiency in the presence of Na(+) or K(+) ions as compared to Li(+) ions. These two bis(propargylic) sulfone crown ethers are also more cytotoxic against a panel of human cancer cell lines when compared to a non-crown ether macrocyclic bis(propargylic) sulfone.     

Active transport,ion movements,and pH changes

The transport of substances across cell membranes may be the most fundamental activity of living things. When the substance transported is any ion there can be a change in the concentration of hydrogen ions on the two sides of the membrane. These hydrogen ion concentration changes are not caused by fluxes of hydrogen ions although fluxes of hydrogen ions may sometimes be involved. The reason for the apparent contradiction is quite simple. All aqueous systems are subject to two constraints: (1) to maintain the charge balance, the sum of the cationic charges must equal the sum of the anionic charges and (2) the product of the molar concentration of H⁺ and the molar concentration of OH⁻, established and maintained by the association and the dissociation of water, remains always at 10⁻¹⁴. As a consequence the concentrations of H⁺ and OH⁻ are determined uniquely by differences between the concentrations of the other cations and anions, with [H⁺] and [OH⁻] being dependent variables. Hydrogen ions and hydroxyl ions can be produced or consumed in local reactions whereas any strong ions such as Cl⁻, Mg²⁺, or K⁺ can be neither produced nor consumed in biological reactions. Further consequences of these truisms are outlined here in terms of the chemistry of the kinds of reactions which can lead to pH changes.     

Synthesis, characterization, crystal structure and biological activity of a novel heterotetranuclear complex: [NiLPb(SCN)2(DMF)(H2O)]2, bis-{[mu-N,N'-bis(salicylidene)-1,3-propanediaminato-aqua-nickel(II)](thiocyanato)(mu-thiocyanato)(mu-N,N'-dimethylformamide)lead(II)}

The mononuclear nickel complex NiL (LH2 = N,N'-bis(salicylidene)-1,3-diaminopropane) can be transformed into the tetranuclear complex [NiL(H2O)Pb(SCN)2(DMF)]2 in the aid of SCN-, DMF (dimethylformamide) and Pb(II) ions. The complex was characterized by elemental analysis and FTIR investigation. The crystal structure reveals it is a nonlinear Ni(II)-Pb(II)-Pb(II)i-Ni(II)i (i: 1-x, 1-y, 1-z) heterotetranuclear complex and crystallizes in the triclinic space group P1. The Ni(II) and Pb(II) ions have a distorted octahedral coordination geometry. There are three kinds of mu-bridge in the molecule between the metal ions. Each pair of Ni and Pb ions in the asymmetric unit is equatorially linked by two phenolic oxygen bridging atoms of N,N'-bis(salicylidene)-1,3-propanediaminato (salpd(2-), C17H16N2O2(2-)) ligand. The dinuclear centres from tetranuclear clusters Ni-Pb(i) and Ni(i)-Pb pairs are bridged by two mu-1,3-SCN groups. Pb(II) and Pb(II)i ions are also bridged by the oxygen atoms of DMF molecules. The tetranuclear units are hydrogen bonded by two O-H...N intermolecular interactions along the c-axis. The complex was screened for antibacterial and antifungal activities by the disc diffusion and microtiter plate techniques using DMF as solvent. The minimum inhibitory concentration values were calculated. It has been found that antimicrobial activities of the complexes are higher than the free ligand.     

Structural studies of gangliosides by fast atom bombardment ionization, low-energy collision-activated dissociation, and tandem mass spectrometry

Negative ion fast atom bombardment, low-energy collision-activated dissociation, and tandem mass spectrometry techniques were applied for the structural elucidation of gangliosides. The mass spectra were simplified by selecting a single molecular ion or fragment ion in the analysis of mixtures, and interference by background signals from the liquid matrix could be avoided. Introduction of collision-activated dissociation produced abundant fragment ions convenient for structural analysis. In the daughter scan mode, ions were produced by cleavage of the glycosidic bonds, and not by cleavage at the sugar ring. These ions all contain ceramide moieties, except the sialic acid fragment ion. In the parent scan mode, product ions resulting from cleavage at the sugar ring were detected beside the ions resulting from cleavage at the glycosidic bonds, and ions of oligosaccharide fragments were also detected. In parent scan mode spectra of gangliosides based on the sialic acid ion, all ions contained a sialic acid residue, and the observed ions were similar to those obtained in the high-energy collision-activated dissociation daughter scan mode. These results indicate the usefulness of low-energy collision-activated dissociation tandem mass spectrometry in the daughter and parent scan modes for the analysis of ganglioside structure, in combination with fast atom bombardment mass spectrometry and high-energy collision-activated dissociation mass spectrometry.