Applications of surface ligand design to flotation

This thesis involves the design, synthesis and testing of organic hydrophobic ligands. They would act as co-collectors in froth flotation processes to enhance the recovery of sulfidic minerals which have undergone some oxidation on processing and are not efficiently collected by the commercial reagents used in froth flotation. Strong and selective binding to iron(III) oxide/hydroxide surfaces, e.g. goethite, over unwanted silicaceous material was considered essential criteria for such new cocollectors. A general overview of froth flotation processes is given in Chapter 1 as well as a description of the analytical techniques used in this thesis and the features that the ligands must have to act as co-collectors. On the basis of the strong binding to iron(III) surfaces of the organic ligand Irgacor 419®, used commercially as a corrosion inhibitor for iron, this compound was studied as a potential co-collector. Adsorption isotherms were determined by UV-Vis spectroscopy for two carboxylic acids that may also bind strongly to goethite, the results of which are discussed in Chapter 2. Chapter 3 involves the measurement of the strength of binding of one the most widely used type of collectors for sulfide ores, potassium ethyl xanthate. Complications in the analysis of materials in solution by both ICP-OES and UV-Vis spectroscopy arose due to the instability of potassium ethyl xanthate in solution, making determination and interpretation of isotherms difficult. The determination of adsorption isotherms for 2-mercaptobenzothiazole, which showed weak binding to goethite as well as to silica, and the mode of binding of 2-mercaptobenzothiazole on copper(I) surfaces is reported in Chapter 4. A crystal structure was obtained in which four units of 2-mercaptobenzothiazole bridge two nickel atoms through the nitrogen atom and the exocyclic sulfur and is considered as a model for binding to sulfidic minerals. Chapter 5 looks at the strength of binding to goethite and silica of various hydroxamic acids. Benzohydroxamic acid was initially selected for study since hydroxamates are known to act as collectors for oxidized materials. Unpredictably, benzohydroxamic acid showed strong binding to a goethite surface and did not release any iron from the surface into solution, which would have been predicted due to its known strong chelating abilities to iron(III). The X-ray structure determination of the first example of a dinuclear Fe(III) hydroxamate complex showed this to have -oxo bridge formed by the hydroxamate unit and supports multisite attachment between this ligand and the surface, as suggested by adsoption isotherms. Simple models based on this dinucleating motif provide plausible modes of multisite attachment to a goethite surface. Competitive binding studies provided a way of ranking the ability to bind to goethite of acetohydroxamic acid, which was not suitable for analyses by either ICP-OES or UV-Vis spectroscopy. Of the ligands studied in this chapter acetohydroxamic acid was found to bind most strongly to goethite followed by benzohydroxamic acid. In Chapter 6, the attachment to goethite and silica of a series of phosphonic acids is investigated. All show a very high binding strength to goethite. Froth flotation experiments at a laboratory scale are described in Chapter 7. The types of ligand that showed strong binding to goethite in adsorption isotherms experiments were tested as co-collectors in different ores and conditions. There is not a simple correlation between adsorption isotherm data and flotation performance as co-collectors because other factors, besides strength of binding, affect the system. Benzohydroxamic acid was the ligand that increased the grade/recovery of the process in all the cases studied. Irgacor 419® enhances the grade/recovery curve for Palabora ore and phenyl malonic acid for Kennecott ore. These results support the original proposition that it may be possible to increase the recovery of oxidized particles substantially by using a blend of collectors which includes a compound to target the oxidized sites

Surface binding vs. sequestration; the uptake of benzohydroxamic acid at iron(III) oxide surfaces

Benzohydroxamic acid is shown to be an unexpectedly good ligand for iron(III) oxides, favouring surface attachment to the formation of trisbenzohydroxamato complexes, which are known to have very high thermodynamic stability in solution

Proinflammatory effects of bare and PEGylated ORMOSIL-, PLGA- and SUV-NPs on monocytes and PMNs and their modulation by f-MLP

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Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5±0.9h (R(2)=0.995) and 10.6±0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation

Genome-Wide Identification of Alternative Splice Forms Down-Regulated by Nonsense-Mediated mRNA Decay in Drosophila

Alternative mRNA splicing adds a layer of regulation to the expression of thousands of genes in Drosophila melanogaster. Not all alternative splicing results in functional protein; it can also yield mRNA isoforms with premature stop codons that are degraded by the nonsense-mediated mRNA decay (NMD) pathway. This coupling of alternative splicing and NMD provides a mechanism for gene regulation that is highly conserved in mammals. NMD is also active in Drosophila, but its effect on the repertoire of alternative splice forms has been unknown, as has the mechanism by which it recognizes targets. Here, we have employed a custom splicing-sensitive microarray to globally measure the effect of alternative mRNA processing and NMD on Drosophila gene expression. We have developed a new algorithm to infer the expression change of each mRNA isoform of a gene based on the microarray measurements. This method is of general utility for interpreting splicing-sensitive microarrays and high-throughput sequence data. Using this approach, we have identified a high-confidence set of 45 genes where NMD has a differential effect on distinct alternative isoforms, including numerous RNA–binding and ribosomal proteins. Coupled alternative splicing and NMD decrease expression of these genes, which may in turn have a downstream effect on expression of other genes. The NMD–affected genes are enriched for roles in translation and mitosis, perhaps underlying the previously observed role of NMD factors in cell cycle progression. Our results have general implications for understanding the NMD mechanism in fly. Most notably, we found that the NMD–target mRNAs had significantly longer 3′ untranslated regions (UTRs) than the nontarget isoforms of the same genes, supporting a role for 3′ UTR length in the recognition of NMD targets in fly

Nanomaterials as a potential environmental pollutant: Overview of existing risk assessment methodologies

The development and use of engineered nanomaterials is increasing rapidly and there are already a large number of consumer products containing nanomaterials. The possible release of nanomaterials from these products is still uncertain, as is their final fate and effects in the environment. Regulators need to deal with this lack of data when carrying out risk assessment and modify the existing risk assessment approaches to adapt them to the unique features of nanomaterials. Here we give an overview of various risk assessment approaches for nanomaterials developed worldwide in which we describe their strengths and limitations, and have evaluated two of them, the Nano Risk Framework and the Precautionary Matrix for specific cases. Many properties of engineered nanomaterials are unknown and this causes deficiencies in the approaches studied. It is therefore essential to increase the present scarce data on nanomaterials released in the environment and close the gaps in the current methodologies to perform adequate risk assessment for nanomaterialsJRC.I.4-Nanobioscience

Applications of surface ligand design to flotation

This thesis involves the design, synthesis and testing of organic hydrophobic ligands. They would act as co-collectors in froth flotation processes to enhance the recovery of sulfidic minerals which have undergone some oxidation on processing and are not efficiently collected by the commercial reagents used in froth flotation. Strong and selective binding to iron(III) oxide/hydroxide surfaces, e.g. goethite, over unwanted silicaceous material was considered essential criteria for such new cocollectors. A general overview of froth flotation processes is given in Chapter 1 as well as a description of the analytical techniques used in this thesis and the features that the ligands must have to act as co-collectors. On the basis of the strong binding to iron(III) surfaces of the organic ligand Irgacor 419®, used commercially as a corrosion inhibitor for iron, this compound was studied as a potential co-collector. Adsorption isotherms were determined by UV-Vis spectroscopy for two carboxylic acids that may also bind strongly to goethite, the results of which are discussed in Chapter 2. Chapter 3 involves the measurement of the strength of binding of one the most widely used type of collectors for sulfide ores, potassium ethyl xanthate. Complications in the analysis of materials in solution by both ICP-OES and UV-Vis spectroscopy arose due to the instability of potassium ethyl xanthate in solution, making determination and interpretation of isotherms difficult. The determination of adsorption isotherms for 2-mercaptobenzothiazole, which showed weak binding to goethite as well as to silica, and the mode of binding of 2-mercaptobenzothiazole on copper(I) surfaces is reported in Chapter 4. A crystal structure was obtained in which four units of 2-mercaptobenzothiazole bridge two nickel atoms through the nitrogen atom and the exocyclic sulfur and is considered as a model for binding to sulfidic minerals. Chapter 5 looks at the strength of binding to goethite and silica of various hydroxamic acids. Benzohydroxamic acid was initially selected for study since hydroxamates are known to act as collectors for oxidized materials. Unpredictably, benzohydroxamic acid showed strong binding to a goethite surface and did not release any iron from the surface into solution, which would have been predicted due to its known strong chelating abilities to iron(III). The X-ray structure determination of the first example of a dinuclear Fe(III) hydroxamate complex showed this to have -oxo bridge formed by the hydroxamate unit and supports multisite attachment between this ligand and the surface, as suggested by adsoption isotherms. Simple models based on this dinucleating motif provide plausible modes of multisite attachment to a goethite surface. Competitive binding studies provided a way of ranking the ability to bind to goethite of acetohydroxamic acid, which was not suitable for analyses by either ICP-OES or UV-Vis spectroscopy. Of the ligands studied in this chapter acetohydroxamic acid was found to bind most strongly to goethite followed by benzohydroxamic acid. In Chapter 6, the attachment to goethite and silica of a series of phosphonic acids is investigated. All show a very high binding strength to goethite. Froth flotation experiments at a laboratory scale are described in Chapter 7. The types of ligand that showed strong binding to goethite in adsorption isotherms experiments were tested as co-collectors in different ores and conditions. There is not a simple correlation between adsorption isotherm data and flotation performance as co-collectors because other factors, besides strength of binding, affect the system. Benzohydroxamic acid was the ligand that increased the grade/recovery of the process in all the cases studied. Irgacor 419® enhances the grade/recovery curve for Palabora ore and phenyl malonic acid for Kennecott ore. These results support the original proposition that it may be possible to increase the recovery of oxidized particles substantially by using a blend of collectors which includes a compound to target the oxidized sites.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Evaluation of Available Tools for Assessment of Emerging Risks of Nanomaterials

The environmental and health effects of nanomaterials represent significant emerging risks. However, there is at present rather limited knowledge regarding the ways in which nanomaterials might be released from products and enter the environment or how they are transported and accumulate in ecosystems. Additional data is therefore needed to estimate the possible release of nanomaterials at various stages of the life cycle to allow identification of potential pathways into the environment. Available tools for risk assessment of nanomaterials are reviewed with the aim of identifying unknowns and uncertainties and data requirements. To carry out risk assessment it is first necessary to determine where nanomaterials are likely to present hazards that are different from those of conventional chemicals and therefore where the challenges will be greatest. Some of the limitations of current risk assessment methodologies for nanomaterials are examined.JRC.B.6-Digital Econom

Quality of physicochemical data on nanomaterials: an assessment of data completeness and variability

Grouping and read-across has emerged as a reliable approach to generate safety-related data on nanomaterials (NMs). However, its successful implementation relies on the availability of detailed characterisation of NM physicochemical properties, which allows the definition of groups based on read-across similarity. To this end, this study assessed the availability and completeness of existing (meta)data on 11 experimentally determined physicochemical properties and 18 NMs. Data on representative NMs were mainly extracted from existing datasets stored in the eNanoMapper database, now available on the European Observatory on Nanomaterials website, while data on case-study NMs were provided by their industrial manufacturers. The extent of available (meta)data was assessed and data gaps were identified, thereby determining future testing needs. Data completeness was assessed by using the information checklists included in the templates for data logging developed by the EU-funded projects NANoREG and GRACIOUS. A completeness score (CS) between 0 and 1 was calculated for each (meta)data unit, template section, property, technique and NM. The results show a heterogeneous distribution of available (meta)data across materials and properties, with none of the selected NMs fully characterised. The average CS calculated for representative NMs (0.43) was considerably lower than for case-study NMs (0.68). The low CS was largely caused by missing information on sample preparation and standard operating procedures, and was attributed to a lack of harmonised data reporting and entry procedure. This study therefore suggests that a persistent use of well-defined and harmonised reporting schemes for experimental results is a useful tool to increase (meta)data completeness and ensure their integration and reuse.JRC.F.2-Consumer Products Safet

Vial sonication and ultrasonic immersion probe sonication to generate stable dispersions of multiwall carbon nanotubes for physico-chemical characterisation and biological testing

Nanotechnology is considered to be a key enabling technology and in recent years there has been much growth in the use of nanostructured materials in industrial applications and in consumer products. It is therefore important that prior to being commercialised in consumer products, engineered nanomaterials are subjected to a thorough physico-chemical characterization as part of broader risk assessment to evaluate their possible effects on human health and the environment. The proper dispersion of nanomaterials sourced as powders becomes a first crucial step in the characterization process. This paper focuses on the dispersion of multiwall carbon nanotubes -often hydrophobic and tangled- since it may be challenging to re-disperse them effectively in aqueous media prior to characterisation. A comparison has been made of non-contact vial sonication and immersion probe sonication using tannic acid as a dispersant. Transmission electron microscopy and UV-Vis spectroscopy were the techniques used to evaluate the dispersions. We used High Content Imaging and Colony Forming Efficiency to perform in vitro cytotoxicity studies on Human Alveolar Epithelial cells. It was found that both sonication treatments produce equivalent stable dispersions. No cytotoxic effects from MWCNTs were observed although some toxicity was observed and attributed to excess of the tannic acid dispersant.JRC.F.2-Consumer Products Safet