Investigation of Chelating Agents for the Removal of Thorium from Human Teeth upon Nuclear Contamination.

Thorium-232 (232Th) is a radioactive heavy metal that is of increasing interest as a source of nuclear energy. However, upon nuclear incidents, the ingestion or inhalation of Th in major quantities can contribute to chemical and radiological health problems, including accumulation in the bone tissue and an increased risk of developing pancreatic, lung, and hematopoietic cancers. The major mineral component of the bone is hydroxyapatite (HAP)─also the major mineral component of the teeth. As such, the teeth are the first site of exposure upon oral ingestion of Th-contaminated materials, and Th can pose a potential risk to teeth development. In essence, in the case of human contamination, it is critical to identify effective chelating agents capable of removing Th. Using a batch study methodology, this present work investigates the uptake and the removal of Th from synthetic HAP and from teeth samples by diethylenetriamine pentaacetate (DTPA), ethylenediaminetetraacetic acid (EDTA), and other promising chelating agents. Th uptake over synthetic HAP exceeds 98% at physiological pH with <1 min of contact time and uptake exceeds 90% across the entire pH range. Regarding teeth, over 1 mg Th uptaken per gram of tooth is observed after 24 h. The overall effectiveness of chelating agents for the removal of Th from is as follows: DTPA > EDTA > NaF/mouthwash/3,4,3-LI(1,2-HOPO); this trend was observed both in synthetic HAP and Th-impregnated teeth samples.

Kinetics of hypochlorous acid reactions with organic and chloride-containing tropospheric aerosol.

Chlorine plays an important role in tropospheric oxidation processes, in both marine and continental environments. Although modeling studies have explored the importance of halogen chemistry, uncertainty remains in associated chemical mechanisms and fundamental kinetics parameters. Prior kinetics measurements of multiphase halogen recycling reactions have been largely performed with dilute, bulk solutions, leaving unexplored more realistic chemical systems which have high solute concentrations and are internally mixed with both halide and organic components. Here, we address the multiphase kinetics of gaseous HOCl using an aerosol flow tube and aerosol mass spectrometer to study its reactions with particulate chloride, using atmospherically relevant particle acidity, solute concentrations, and ionic strength. We also investigate the chemistry that results when biomass burning (BB) aerosol components and chloride are internally mixed. Using pH-buffered deliquesced particles, we show that the rate constant for reaction of dissolved HOCl with H+ and Cl- at high relative humidity (RH) (80-85%) is within a factor of two of the literature value for bulk phase conditions. However, at lower RH values (60-70%) where the particles are considerably more concentrated, the rate constant for chloride loss from the particles is an order of magnitude higher. For pure organic compounds commonly found in biomass burning (BB) aerosol, such as coniferaldehyde, salicylic acid and furfural, an increase in the aerosol chlorine content occurs with HOCl exposure, indicating the formation of organochlorine species. Together, these independent findings explain results for internally mixed aerosol particles with both chloride and BB components present where we observed behavior consistent with both chloride loss and organochlorine formation occurring simultaneously upon HOCl exposure. Our results indicate that chlorine recycling via HOCl uptake by chloride-containing particles will occur in the atmosphere efficiently over a wide range of RH conditions, even when reactive organic compounds are present in the same particles as chloride. Simultaneously, formation of organochlorine compounds, which are commonly toxic, is likely occurring when reactive organic components are present.

Reaction of HOCl with Wood Smoke Aerosol: Impacts on Indoor Air Quality and Outdoor Reactive Chlorine.

High loadings of biomass burning (BB) aerosol particles from wildfire or residential heating sources can be present in both outdoor and indoor environments, where they deposit onto surfaces such as walls and furniture. These pollutants can interact with oxidants in both the aerosol and deposited forms. Hypochlorous acid (HOCl), a strong oxidant emitted during cleaning with chlorine-cleaning agents such as bleach, can attain mixing ratios of hundreds of ppbv indoors; moreover, lower mixing ratios are naturally present outdoors. Here, we report the heterogeneous reactivity of HOCl with wood smoke aerosol particles. After exposure to gas-phase HOCl, the particle chlorine content increased reaching chlorine-to-organic mass ratios of 0.07 with the chlorine covalently bound as organochlorine species, many of which are aromatic. Investigating individual potential BB components, we observed that unsaturated species such as coniferaldehyde and furfural react efficiently with HOCl. These observations indicate that organochlorine pollutants will form indoors when bleach cleaning a wildfire impacted space. The chlorine component of particles internally mixed with BB material and chloride initially increased, upon HOCl exposure, indicating that active chlorine recycling in the outdoor environment will be suppressed in the presence of BB emissions.

Uptake and Removal of Uranium by and from Human Teeth.

Uranium-238 (238U), a long-lived radiometal, is widespread in the environment because of both naturally occurring processes and anthropogenic processes. The ingestion or inhalation of large amounts of U is a major threat to humans, and its toxicity is considered mostly chemical rather than radiological. Therefore, a way to remove uranium ingested by humans from uranium-contaminated water or from the air is critically needed. This study investigated the uranium uptake by hydroxyapatite (HAP), a compound found in human bone and teeth. The uptake of U by teeth is a result of U transport as dissolved uranyl (UO22+) in contaminated water, and U adsorption has been linked to delays in both tooth eruption and development. In this present work, the influence of pH, contact time, initial U concentration, and buffer solution on the uptake and removal of U in synthetic HAP was investigated and modeled. The influence of pH (pH of human saliva, 6.7-7.4) on the uptake of uranyl was negligible. Furthermore, the kinetics were extremely fast; in one second of exposure, 98% of uranyl was uptaken by HAP. The uptake followed pseudo-second-order kinetics and a Freundlich isotherm model. A 0.2 M sodium carbonate solution removed all the uranyl from HAP after 1 h. Another series of in vitro tests were performed with real teeth as targets. We found that, for a 50 mg/L U in PBS solution adjusted to physiological pH, ∼35% of the uranyl was uptaken by the tooth after 1 h, following pseudo-first-order kinetics. Among several washing solutions tested, a commercially available carbonate, as well as a commercially available fluoride solution, enabled removal of all the uranyl taken up by the teeth.

Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart.

BACKGROUND: Oshikhandass is a rural village in northern Pakistan where a 1989-1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. METHODS: Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. RESULTS: Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. CONCLUSIONS: We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. TRIAL REGISTRATION: Not Applicable.

Measurement of Formation Rates of Secondary Aerosol in the Ambient Urban Atmosphere Using a Dual Smog Chamber System.

A dual smog chamber system was used to quantify the formation rates of secondary organic and inorganic aerosol in an urban environment (Pittsburgh, US). Ambient air was introduced in both chambers, and HONO photolysis was used to produce hydroxyl radicals (OH) in the perturbed chamber. The second chamber was used as a reference. The production rate of secondary organic aerosol (SOA) under typical noon-time OH concentrations ranged from 0.2 to 0.8 µg m-3 h-1. The production rate of sulfate was approximately five times less than that of the SOA. Nucleation and growth of new particles were observed in the perturbation chamber. The produced SOA had a similar composition with the preexisting oxygenated ambient OA. The reacted amounts of the measured VOCs were able to explain 5-50% of the formed SOA in the perturbed chamber. Intermediate volatility organic compounds could be responsible for the rest. The oxygen to carbon ratio (O:C) in the perturbed chamber remained approximately the same during SOA production, while an increase was observed in the control chamber. A possible explanation could be the loss of less oxidized species to the chamber walls. After 2 h, the OA increased by 70% on average and the sulfate by 40%.

IGF and IGFBP as an index for discrimination between vitamin D supplementation responders and nonresponders in overweight Saudi subjects.

Vitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25(OH)D level <50 nmol/L), aged 40.4 ±â€Š11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population.

Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation.

Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell cancer exhibiting a wide spectrum of disease courses and treatment responses. Molecular characterization of RNA and DNA from CLL cases has led to the identification of important driver mutations and disease subtypes, but the precise mechanisms of disease progression remain elusive. To further our understanding of CLL biology we performed isobaric labeling and mass spectrometry proteomics on 14 CLL samples, comparing them with B-cells from healthy donors (HDB). Of 8694 identified proteins, ∼6000 were relatively quantitated between all samples (q<0.01). A clear CLL signature, independent of subtype, of 544 significantly overexpressed proteins relative to HDB was identified, highlighting established hallmarks of CLL (e.g. CD5, BCL2, ROR1 and CD23 overexpression). Previously unrecognized surface markers demonstrated overexpression (e.g. CKAP4, PIGR, TMCC3 and CD75) and three of these (LAX1, CLEC17A and ATP2B4) were implicated in B-cell receptor signaling, which plays an important role in CLL pathogenesis. Several other proteins (e.g. Wee1, HMOX1/2, HDAC7 and INPP5F) were identified with significant overexpression that also represent potential targets. Western blotting confirmed overexpression of a selection of these proteins in an independent cohort. mRNA processing machinery were broadly upregulated across the CLL samples. Spliceosome components demonstrated consistent overexpression (p = 1.3 × 10-21) suggesting dysregulation in CLL, independent of SF3B1 mutations. This study highlights the potential of proteomics in the identification of putative CLL therapeutic targets and reveals a subtype-independent protein expression signature in CLL.

Sex-specific expression of apolipoprotein levels following replenishment of vitamin D.

Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency [25(OH)D < 50nmol/l] were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ±â€¯16.5nmol/l at end of study vs. 32.5 ±â€¯10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.

The Effect of Hydrogen Bonding in Enhancing the Ionic Affinities of Immobilized Monoprotic Phosphate Ligands.

Environmental remediation requires ion-selective polymers that operate under a wide range of solution conditions. In one example, removal of trivalent and divalent metal ions from waste streams resulting from mining operations before they enter the environment requires treatment at acidic pH. The monoethyl ester phosphate ligands developed in this report operate from acidic solutions. They have been prepared on polystyrene-bound ethylene glycol, glycerol, and pentaerythritol, and it is found that intra-ligand hydrogen bonding affects their metal ion affinities. The affinity for a set of trivalent (Fe(III), Al(III), La(III), and Lu(III)) and divalent (Pb(II), Cd(II), Cu(II), and Zn(II)) ions is greater than that of corresponding neutral diethyl esters and phosphonic acid. In an earlier study, hydrogen bonding was found important in determining the metal ion affinities of immobilized phosphorylated polyol diethyl ester coordinating ligands; their Fourier transform infrared (FTIR) band shifts indicated that the basicity of the phosphoryl oxygen increased by hydrogen bonding to auxiliary -OH groups on the neighboring polyol. The same mechanism is operative with the monoprotic resins along with hydrogen bonding to the P-OH acid site. This is reflected in the FTIR spectra: the neutral phosphate diethyl ester resins have the P=O band at 1265 cm-1 while the monoethyl ester resins have the band shifted to 1230 cm-1; hydrogen bonding is further indicated by the broadness of this region down to 900 cm-1. The monoprotic pentaerythritol has the highest metal ion affinities of the polymers studied.

Modification of Hydroxyapatite with Ion-Selective Complexants: 1-Hydroxyethane-1,1-diphosphonic Acid.

Hydroxyapatite (HAP) was modified with 1-hydroxyethane-1,1-diphosphonic acid (HEDP), and its effect on divalent metal ion binding was determined. HAP was synthesized from calcium hydroxide and phosphoric acid. After calcination, it was modified with HEDP, and the influence of time and temperature on the modification was investigated. HEDP incorporation increased as its initial solution concentration increased from 0.01 to 0.50 M. Unmodified and modified HAP were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, and specific surface area analysis. Ca/P ratios, acid capacities, and phosphorus elemental analyses gave the effect of modification on composition and surface characteristics. A high reaction temperature produced new phosphonate bands at 993, 1082, and 1144 cm-1 that indicated the presence of HEDP. HAP modification at a high temperature-long reaction time had the highest HEDP loading and gave the sharpest XRD peaks. The emergence of new HAP-HEDP strands was observed in SEM images for treated samples while EDS showed high phosphorus contents in these strands. Modified HAP had a high acid capacity from the additional P-OH groups in HEDP. The P(O)OH groups maintain their ability to bind metal ions within the HAP matrix: contacting the modified HAP with 10-4 N nitrate solutions of five transition metal ions gives an affinity sequence of Pb(II) > Cd(II) > Zn(II) > Ni(II) > Cu(II). This result is comparable to that of commercially available di(2-ethylhexyl)phosphoric acid, a common solvent extractant, and the trend is consistent with the Misono softness parameter of metal ion polarizabilities.

Distinguishing between organic and inorganic phosphorus in hydroxyapatite by elemental analysis.

A method is developed to determine the amount of organic and inorganic phosphorus in an inorganic polymer (hydroxyapatite (HAP)) modified with an organic phosphorus - containing complexant. The simplicity and precision of the vanadate method has made it useful for measuring the total phosphorus content in phosphorus - containing organic polymers that are first digested in concentrated sulfuric acid. However, it can be important to quantify the organic and inorganic phosphorus capacities in modified (hybrid) polymers and this method does not distinguish between the two. In the current report, HAP was modified with 1-hydroxyethane-1,1-diphosphonic acid (HEDP) and a method developed to give the respective phosphorus capacities. HAP was contacted with HEDP for 17 h, 28 h, 56 h, 84 h, 112 h, and 140 h. By combining results from the sulfuric acid digestion of the modified polymer with those from a separate digestion in HCl, it was determined that there was a monotonic increase in the organic phosphorus capacity from 0.04 to 2.44 mmol / g, and a decrease in the inorganic phosphorus capacity from 4.68 to 2.54 mmol / g.

Survey of influenza A viruses circulating in wild birds in Canada 2005 to 2007.

A multi-agency, Canada-wide survey of influenza A viruses circulating in wild birds, coordinated by the Canadian Cooperative Wildlife Health Centre, was begun in the summer of 2005. Cloacal swab specimens collected from young-of-year ducks were screened for the presence of influenza A nucleic acids by quantitative, real-time reverse transcription-polymerase chain reaction (RRT-PCR). Specimens that produced positive results underwent further testing for H5 and H7 gene sequences and virus isolation. In addition to live bird sampling, dead bird surveillance based on RRT-PCR was also carried out in 2006 and 2007. The prevalence of influenza A viruses varied depending on species, region of the country, and the year of sampling, but generally ranged from 20% to 50%. All HA subtypes, with the exception of H14 and H15, and all NA subtypes were identified. The three most common HA subtypes were H3, H4, and H5, while N2, N6, and N8 were the three most common NA subtypes. H4N6, H3N2, and H3N8 were the three most common HA-NA combinations. The prevalence of H5 and H7 subtype viruses appears to have a cyclical nature.

Mechanism of ionic recognition by polymer-supported reagents: immobilized tetramethylmalonamide and the complexation of lanthanide ions.

The mechanism of ionic recognition by polymer-supported reagents is probed with cross-linked polystyrene modified with tetramethylmalonamide (TMMA) ligands. The substrates are lanthanide ions in 0.001-8 M HCl and HNO(3) solutions. The results fall into three regions of acid concentration: low, mid, and high. In HCl, distribution coefficients are low in 0.001 to 2 M, increase in 4 and 6 M, and then decrease in 8 M HCl. In the low-acid region, the metal ion remains with its waters of hydration and does not coordinate to the carbonyl oxygens. As the acid concentration exceeds 2 M, protonation of the amide occurs to form an iminium moiety, electrostatically attracting the anionic lanthanide complex through ion-exchange and releasing waters of hydration. At high acid concentration, the apparent affinity decreases due to competition by the large excess of chloride ions for the ion-exchange sites. The affinity sequence in 6 M HCl is Tb > Dy > Eu > Gd > Ho > Sm > Er > Tm > Yb > Lu > Nd > Ce > La. The TMMA-Ln interaction is due to recognition since there is a point of maximum affinity across the series rather than a monotonic trend. The trends are comparable in HNO(3). A comparison of the distribution coefficients at the maxima (6 M HCl and 4 M HNO(3)) shows nitrate to have greater values than chloride due to a hydration effect, as also indicated by results from H(2)SO(4).

Polyols as scaffolds in the development of ion-selective polymer-supported reagents: the effect of auxiliary groups on the mechanism of metal ion complexation.

In developing ion-selective polymer-supported reagents, the inherent affinity of a given ligand for a targeted metal ion is found to be affected by auxiliary groups on a scaffold. A series of polyols (ethylene glycol, glycerol, tris(hydroxymethyl)ethane, pentaerythritol, and pentaerythritol triethoxylate) are immobilized onto cross-linked poly(vinylbenzyl chloride), then monophosphorylated. The pentaerythritol, glycerol, and pentaerythritol triethoxylate polymers have the highest affinities for both trivalent and divalent ions. The distribution coefficients of divalent ions (Pb(II), Cd(II), Cu(II), Ni(II), and Zn(II)) correlate with the Misono softness parameter, reflecting a single-site interaction between the metal ion and the phosphoryl oxygen. The distribution coefficients for trivalent ions are in the order Fe(III) < Al(III) < Y(III) less, approximately < La(III) approximately Eu(III) approximately Lu(III). For example, the phosphorylated pentaerythritol polymer has distribution coefficients (also reported as percent complexed) for Fe of 68.4 (75.3%); for Al of 182 (88.5%); and for the rare earth ions Y, Lu, Eu, and La of 374 (94.4%), 1390 (98.4%), 1690 (98.4%), and 708 (96.9%), respectively, from solutions at pH 2.0. The opposite trend (i.e., Fe(III) > Al(III) > (rare earths)) correlates with their hardness, acidity, electron affinity, electronegativity, and formation constants with soluble complexants, including tributyl phosphate. A binding mechanism is proposed wherein the polymer initially has the auxiliary -OH groups hydrogen-bonded to the phosphate ligand; then, binding to the polarizable phosphoryl oxygen with the divalent ions dominates, while the trivalent ions are drawn closer to the phosphoryl oxygen because of their greater charge and, once closer, bind in a multisite interaction with both the phosphate and -OH groups.

Immobilized tris(hydroxymethyl)aminomethane as a scaffold for ion-selective ligands: the auxiliary group effect on metal ion binding at the phosphate ligand.

The metal ion affinities of a ligand in a polymer-supported reagent can be enhanced by the presence of a proximate group capable of hydrogen bonding. A new polymer-supported reagent has been synthesized by immobilizing tris(hydroxymethyl)aminomethane (Tris) onto cross-linked poly(vinylbenzyl chloride) and then phosphorylating the -OH moieties. The -NH- acts as the auxiliary group to increase the extent of complexation by the phosphate ligand. Additionally, Tris acts as a scaffold, wherein the phosphate ligands are in a known stereochemical arrangement. The Tris resin is mono-, di-, and triphosphorylated, depending on the concentration of the phosphorylating agent. The highest metal ion affinities are found with the resin having a phosphorus-to-nitrogen ratio of 2.36, consistent with one-third of the ligands being triphosphorylated and the remainder being diphosphorylated. The unphosphorylated Tris and phosphonate diester resins have no ionic affinities under the same conditions. Trivalent ions (Fe(III), Al(III), La(III), Eu(III), Lu(III)) are preferred over divalent ions (Pb(II), Cd(II), Cu(II), Zn(II)) from solutions at pH 2. The distribution coefficients of the divalent ions correlate with the Misono softness parameters, indicating that the polarizability of the phosphoryl oxygen is important to binding of the metal ions. The mechanism of complexation is probed with Fe(III) in 0.01-5 M HNO3 and HCl. The high affinities are ascribed to activation of the P=O ligand toward metal ion binding by the N-H moieties acting as auxiliary groups, coupled with intraligand cooperation among the phosphate moieties at a given site. FTIR spectra show that the P=O band at 1261 cm-1 shifts as a function of the extent of hydrogen bonding. Binding at the P=O requires a balance between activation by hydrogen bonding and availability of the lone pair electrons to the metal ions.

New polymer-supported ion-complexing agents: design, preparation and metal ion affinities of immobilized ligands.

Polymer-supported reagents are comprised of crosslinked polymer networks that have been modified with ligands capable of selective metal ion complexation. Applications of these polymers are in environmental remediation, ion chromatography, sensor technology, and hydrometallurgy. Bifunctional polymers with diphosphonate/sulfonate ligands have a high selectivity for actinide ions. The distribution coefficient for the uranyl ion from 1 M nitric acid is 70,000, compared to 900 for the monophosphonate/sulfonate polymer and 200 for the sulfonic acid ion-exchange resin. A bifunctional trihexyl/triethylammonium polymer has a high affinity and selectivity for pertechnetate and perchlorate anions from groundwater. In one example, its distribution coefficient for perchlorate ions in the presence of competing anions is 3,300,000, compared to 203,180 for a commercially available anion-exchange resin. Polystyrene modified with N-methyl-D-glucamine ligands is capable of selectively complexing arsenate from groundwater. It complexes 99% of the arsenate present in a solution of 100 mg/L arsenate with 560 mg/L sulfate ions. Its selectivity is retained even in the presence of 400 mg/L phosphate. There is no affinity for arsenate above pH 9, allowing for the polymer to be regenerated with moderate alkali solution. In studies aimed at developing a Hg(II)-selective resin, simple amine resins were found to have a high Hg(II) affinity and that affinity is dependent upon the solution pH and the counterion.

Immobilized N-methyl-D-glucamine as an arsenate-selective resin.

Immobilization of N-methyl-D-glucamine (NMDG) on poly(vinylbenzyl chloride) beads yields an effective and highly selective sorbent for arsenate ions. Three important parameters in the resin's high As(V) affinity and selectivity are the structure of the ligand, its ionic form, and the crosslink density of the polymer. The NMDG resin crosslinked with 2 wt % divinylbenzene is far more selective than commercially available analogues, especially when sulfate and chloride ions are present in solution at high concentrations. Selectivity studies at neutral pH indicate that the protonated tertiary amine moiety is an important component of the complexation mechanism. The NMDG resin also has a high affinity for the un-ionized As(V) species at pH 1.

Studies on the inhibition of endosome fusion by GTPgammaS-bound ARF.

Using a cell free assay, we have previously shown that ARF is not required for endosome fusion but that inhibition of fusion by GTPgammaS is dependent on a cytosolic pool of ARFs. Since ARF is proposed to function in intracellular membrane traffic by promoting vesicle biogenesis, and components of clathrin- and COP-coated vesicles have been localized on endosomal structures, we investigated whether ARF-mediated inhibition of early endosome fusion involves the recruitment or irreversible association of these proteins onto endosomal membranes. We now report that depletion of components of clathrin coated vesicles (clathrin, AP-1 and AP-2) or COPI vesicles (beta COP) does not affect the capacity of GTPgammaS-activated ARF to inhibit endosome fusion. Inhibition of fusion by activated ARF is also independent of endosomal acidification since assays performed in the presence of the vacuolar ATPase inhibitor bafilomycin A1 are equally sensitive to GTPgammaS-bound ARF. Finally, in contrast to reported effects on lysosomes, we demonstrate that ARF-GTPgammaS does not induce endosomal lysis. These combined data argue that sequestration of known coat proteins to membranes by activated ARF is not involved in the inhibition of early endosome fusion and that its capacity to inhibit fusion involves other specific interactions with the endosome surface. These results contrast with the mechanistic action of ARF on intra-Golgi transport and nuclear envelope assembly.