Abraham Warshawsky

Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition

Iron‐dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)‐B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinsons disease, Alzheimers disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO‐B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO‐B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO‐B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron‐dependent lipid peroxidation in rat brain homogenates with IC50 values (12–16 µm), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 µm were able to attenuate cell death induced by serum deprivation and by 6‐hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti‐Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non‐selective MAO‐A and MAO‐B inhibitor (IC50 < 0.1 µm). However, HLA20 was more selective for MAO‐B but had poor MAO inhibition, with an IC50 value of 64.2 µm. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.

The Separation of Platinum Group Metals (PGM) in Chloride Media by Isothiouronium Resins

Abstract Styrene-divinylbenzene copolymers incorporating isothiourea functional groups show a remarkable affinity for platinum-group-metal (PGM) ions in chloride media, The mode of ion binding to the resin depends on the equilibria between isothiourea (free base) form and isothiouronium (conjugated acid) form, This in return is related to matrix structure, A. resin, Monivex, which shows high binding capacities for PGM ions in high acidities (2–6M HC1) is described. Equilibrium, rate and selectivity data, as well as process application data is presented and discussed, Electron microprobe studies are used to follow chemical changes in resin beads and ion regeneration patterns.

Kinetics of goldcyanide extraction using ion-exchange resins containing piperazine functionality

Abstract The search for suitable resins for goldcyanide recovery from cyanide solutions prompted the synthesis of resins incorporating new functionalities that solve many of the existing problems. A new type of ion-exchange resin (PS-PIP) incorporating a piperazine group, linked onto a styrene–divinylbenzene macroporous network, was developed for goldcyanide solutions. Kinetics measurements were made on the extraction of goldcyanide (Au(CN) 2 − ) with the ion-exchange resin (PS-PIP). The extraction process is accompanied by fast ion-exchange reaction and is characterised by a sharp moving boundary between the reacted shell and the shrinking unreacted core within the resin. Analyses of the respective rate data in accordance with two theoretical models used to explain the metal extraction kinetics showed that the process is controlled by the rate of diffusion of the ions penetrating the reacted layer at goldcyanide concentrations in the range 10–40 mg l −1 and controlled by the rate of diffusion of the ions across the liquid film surrounding the resin particle at goldcyanide concentrations lower than −1 . Particle diffusion coefficients and mass transfer constants across the liquid film were determined from the graphical representation of the proposed models.

Polymers with pendent functional groups. V. Thermooxidative and thermal behavior of chloromethylated polysulfones

Abstract The first step of the thermooxidative and thermal decomposition of some chloromethylated polysulfones (CMPSF) with various degrees of substitution has been studied by thermogravimetry (TG) and thermal volatilization analysis (TVA). A step occurring at lower temperatures 260–370°C is particular for halomethylated polysulfones because the polysulfone (PSF) is thermally stable in this temperature range (its first decomposition step occurs from 400 to 550°C). The higher the degree of substitution, the lower the degradation temperature and a better separation of the processes was found. The thermal decomposition products collected were analyzed by IR spectroscopy and elemental analysis. According to our TG and TVA results and literature data , it can be proposed that –CH2Cl groups react at low temperatures giving cross-linked polymer and gas or liquid products. The thermal characteristics of this process depend on the chlorine content of the sample and explain undesirable cross-linking that could take place during the synthesis of the chloromethylated polysulfones.

Solvent impregnated resins: relation between impregnation process and polymer support morphology I. Di-(2-ethylhexyl)dithiophosphoric acid

Abstract The relationship between polymer support morphology and adsorption of di-(2-ethylhexyl)dithiophosphoric acid (DEHTPA) from alcoholic solution has been studied. As polymer supports investigated are the conventional commercial polymer adsorbents Amberlite XAD-2 and XAD-4 and two microporous polymer adsorbents prepared by post-polymerization crosslinking of swollen chloromethylated gel-type and macroreticular copolymers of styrene and divinylbenzene. Their morphology has been studied by nitrogen adsorption/desorption method. It was found that in the adsorption process DEHTPA fills the pore space gradually from the smallest pores up to pores with a diameter of approximately 10 nm.

Ion exchange resins for gold cyanide extraction containing a piperazine functionality, 1. Synthesis and physico-chemical properties

The synthesis of two types of metal-chelating resins incorporating gold-specific piperazine groups is described. PS-PIP is a styrene-divinylbenzene macroporous network. MC-PIP is a (glycidyl methacrylate)-co-(ethylene dimethacrylate) network. The nominal functional group concentrations are 1.84 mmol/g for PS-PIP and 1.14 mmol/g for MC-PIP. The proton exchange capacity is 1.95 mmol/g for PS-PIP and 0.91 mmol/g for MC-PIP. Acuurate titration curves were used to determine pK, values (PK H = 7.05 ± 0.12). XPS analyses of PS-PIP resin were followed as a function of pH (cf. Fig. 8) demonstrating that the protonation of the amine is observable by a shift in binding energy of the N(1s) peak (±1.6 eV) moving from tertiary amine form (N(1s) 399.7 eV) to the protonated tertiary amine form (N(1s) 401.3 eV). Additionnally, the presence of quaternary ammonium groups was detected at a N(1s) peak at 402.3 eV (cf. Fig.9). Metal extraction from cyanide solutions, including Brazilian mine leach solution, showed considerable preference for gold (cf. Fig. 11-12). The piperazine resins extract gold via two mechanisms: (a) ligand substitution reactions at pH>7.05 (pK H(a) ) or (b) anion exchange reactions via the quaternary ammonium groups at high pH values. Extraction profiles were S-shaped (cf. Fig. 10) with 50% extraction ability at pH values. Extraction profiles were S-shaped (cf. Fig. 10) with 50% extraction ability at pH 8.0. Cyclic experiments involving extraction, elution, regeneration and recomplexation (cf. Tab. 6 and 7) showed the ability of MC-PIP to perform consistently at high extraction efficiencies from pH 8.6.

Membrane extraction of silver by di(2-ethylhexyl) dithiophosphoric acid

A membrane-based process for silver recovery from waste solutions was derived. Silver diffused from the feed solution through the supported liquid membrane containing di(2-ethylhexyl)dithiophosphoric acid (DTPA) as a carrier into the receiver solution, which contain thiourea at a low pH. Silver transfer rate and diffusion coefficient in the membrane were found to be up to 1.5 × 10-9 mol/cm2-sec and 2 × 10-6 cm2/sec, respectively. The membranes used demonstrated an ability to work in contact with waste solutions from silver reclamation eluants until silver had been transferred even against a very high concentration gradient. The dependencies of silver transfer rate on such factors as pH in the receiver and feed phases, DTPA and thiourea concentrations, were investigated.

Solid-liquid distribution studies of divalent metals from nitrate media using impregnated resins containing a bifunctional organophosphorous extractant (O-methyl-dihexyl-phosphine-oxide O′-hexyl-2-ethyl phosphoric acid)

Abstract The present paper presents the results of the extraction of Zn(II), Cu(II) and Cd(II) from 0.1 M NaN0 3 at 25°C by impregnated resins containing a bifunctional extractant, incorporating phosphine oxide and phosphoric acid diester funcionalities, O -methyl-dihexyI-phosphine-oxide O′ -hexyl-2-ethyl phosphoric acid (HL). Solvent impregnated resins have been prepared by direct adsorption of HL into the styrene/divinylbenzene macroporous support, Amberlite XAD2, by using the dry impregnation method. The adsorption of HL, on the styrene/divinylbenzene macroporous support is shown by FTIR spectroscopy to be the result of only weak extractant-support interactions. The distribution coefficient of Zn(II), Cu(II) and Cd(II) was determined as a function of pH and extractant (HL) concentration in the resin phase and the data were analyzed graphically using the slope analysis method and numerically using the program LETAGROP-DISTR. The composition of the extracted species in the resin phase has been determined. Analysis of the results showed that the extraction of these metal ions can be explained assuming the formation of metal complexes in the resin phase with a general composition ML, (N0 3 ) t (HL) q where p, t, q take different values depending on the metal. An extraction reaction is proposed and the extraction constants of these species are given.

Polysulfone-based interpolymer anion exchange membrane☆

Abstract Polysulfone derivatives are a priori good candidates for the preparation of charged membranes. A simple and safer bromomethylating reaction makes the polybase readily available. The bromomethylated polymer is compatible with unmodified polysulfone. Anion exchange membranes were prepared. The influence of various aminating procedures was shown.

Membrane extraction of mercury (II) and silver (I) by bis(di(2-ethylhexyloxy) thiophosphoryl) disulfide

Abstract A supported liquid membrane containing bis(di(2-ethylhexyloxy)thiophosphoryl)disulfide (BTPD) as a novel membrane carrier was prepared and tested. Metal ion transfer was shown to be accelerated by the presence of thiourea or thiosulfate in the receiver stripping solutions. Under varying conditions, mercury and silver transfer rates of up to 7 and 3 μmol/m2s, were measured. Mercury transport mechanism was demonstrated to be dependent on the nature of the anion. Mercury nitrate transport appears to be mainly due to a coupled Hg2+H+ facilitated diffusion mechanism, according to the ion-exchange stoichiometry. Mercury halides were transported mainly as neutral complexed species due to carrier-facilitated diffusion. Selectivity of the membrane for mercury and silver over zinc, nickel, cadmium and copper has been found to be of the order of 103.