by Wong Yin Kwan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 105-115). / Abstract also in Chinese. / Title page --- p.i / Acknowledgements --- p.ii / Table of contents --- p.iii / Abbreviations --- p.v / Abstract --- p.vi / 摘要 --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Assay Development for Ciprofloxacin / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- HPLC Assay --- p.24 / Chapter 2.3 --- Microbiological Assay --- p.29 / Chapter 2.4 --- Discussion --- p.30 / Chapter Chapter 3 --- The Effects of Oral Ferrous Sulfate on Pharmacokinetics and Pharmacodynamics of Intravenous Ciprofloxacin / Chapter 3.1 --- Introduction --- p.43 / Chapter 3.2 --- Materials and Methods --- p.45 / Chapter 3.3 --- Results --- p.49 / Chapter 3.4 --- Discussion --- p.51 / Chapter Chapter 4 --- The Effects of Oral Ferrous Sulfate on Pharmacokinetics and Pharmacodynamics of Oral Ciprofloxacin / Chapter 4.1 --- Introduction --- p.61 / Chapter 4.2 --- Materials and Methods --- p.62 / Chapter 4.3 --- Results --- p.66 / Chapter 4.4 --- Discussion --- p.68 / Chapter Chapter 5 --- Influence of Mineral Rich Traditional Chinese Medicines on the Pharmacokinetics of Oral Ciprofloxacin / Chapter 5.1 --- Introduction --- p.77 / Chapter 5.2 --- Materials and Methods --- p.81 / Chapter 5.3 --- Results --- p.85 / Chapter 5.4 --- Discussion --- p.86 / Chapter Chapter 6 --- General Conclusion --- p.98 / References --- p.105

Iron precipitation during matrix acidizing treatments is a well-known problem. During matrix acidizing, successful iron control can be critical to the success of the treatment. Extensive literature review highlighted that no systematic study was conducted to determine where this iron precipitates, the factors that affect this precipitation, and the magnitude of the resulting damage. Iron (III) precipitation occurs when acids are spent and the pH rises above 1, which can cause severe formation damage. Chelating agents are used during these treatments to minimize iron precipitation. Disadvantages of currently used chelating agents include limited solubility in strong acids, low thermal stability, and/or poor biodegradability. In this study, different factors affecting iron precipitation in Indiana limestone rocks were examined. Two chelating agents, GLDA and HEDTA, were tested at different conditions to assess their iron control ability. Results show that a significant amount of iron precipitated, producing a minimal or no gain in the final permeability, this indicated severe formation damage. The damage increased with the increase of the amount of iron in solution. When chelating agents were used, the amount of iron recovered depended on both chelate-to-iron mole ratio and the initial permeability of the cores. Calcium is chelated along with iron, which limits the effectiveness of chelating agents to control iron (III) precipitation. Acid solutions should be designed considering this important finding for more successful treatments.

Sandstone acidizing has been carried out with mud acid which combines hydrochloric acid and hydrofluoric acid at various ratios. The application of mud acid in sandstone formations has presented quite a large number of difficulties like corrosion, precipitation of reaction products, matrix deconsolidation, decomposition of clays by HCl, and fast spending of the acids. There has been a recent trend to use chelating agents for stimulation in place of mud acid which are used in oil industry widely for iron control operations. In this study, two chelates, L-glutamic-N, N-diacetic acid (GLDA) and hydroxyethylethylene-diaminetriacetic acid (HEDTA) have been studied as an alternative to mud acid for acidizing. In order to analyze their performance in the application of acidizing, coreflood tests were performed on Berea and Bandera sandstone cores. Another disadvantage of mud acid has been the fast spending at clay mineral surfaces leading to depletion of acid strength, migration of fines, and formation of colloidal silica gel residue. Hence, compatibility of chelates with clay minerals was investigated through the static solubility tests. GLDA and HEDTA were analyzed for their permeability enhancement properties in Berea and Bandera cores. In the coreflood experiments conducted, it was found out that chelating agents can successfully stimulate sandstone formations. The final permeability of the Berea and Bandera cores were enhanced significantly. GLDA performed better than HEDTA in all applications. The substitution of seawater in place of deionized water for mixing purposes also led to an increased conductivity of the core implying GLDA is compatible with seawater. In the static solubility tests, chelates were mixed with HF acid at various concentrations. GLDA fluids kept more amounts of minerals in the solution when compared with HEDTA fluids. Sodium-based chelates when mixed with HF acid showed inhibited performance due to the formation of sodium fluorosilicates precipitates which are insoluble damage creating compounds. The application of ammonium-based chelate with HF acid was able to bring a large amount of aluminosilciates into the solution. The study recommends the use of ammonium-based GLDA in acidizing operations involving HF acid and sodium-based GLDA in the absence of the acid.

Abstract Information about interactions among metals, hydrogen peroxide and chelating agents is needed to develop environmental technology and the operating efficiency of modern elemental chlorine free and total chlorine free bleaching processes. The work presented here focused on the properties of metal chelates and corrosion of titanium in an alkaline hydrogen peroxide solution. A comparative study between three rapid analysis methods, ICP-AES, XRF and ISE, was performed in pulp matrix and error sources of ISE were investigated in detail. Sensitive and selective GC methods for chelating agents ADA and NTA in water matrices were developed. Decomposition of ADA (percentage of residual 71) was observed already at the hydrogen peroxide anion level of 400 mg/l in which DTPA was more persistent (percentage of residual 94). EDTA was stable even in the hydrogen peroxide anion level of 1200 mg/l, in which its percentage of residual was 94. DTPA, EDTA and ADA were more soluble in the presence of iron and manganese than in the absence of these metals. The chelation of iron appeared to be thermodynamically limited in hydrogen peroxide bleaching conditions. Unalloyed (Grade 2) and alloyed (Grade 5) titanium corroded at the hydrogen peroxide anion level of 200 mg/l. The presence of calcium and silica inhibitors and further iron and manganese enhanced the critical hydrogen peroxide anion levels. Grade 5 was inferior to Grade 2. During rapid uniform corrosion, the potential of unalloyed titanium was under 200 mV (SHE) and lower than that of platinum. Over 90% of manganese and many other metals could be leached into aqueous phase for ICP-AES analysis using chelation or acid hydrolysis. An XRF method for manganese, iron and copper in pulp including little or no sample treatment was developed. Measuring temperature differences and atmospheric carbon dioxide were observed to be notable error sources of the ISE technique.

Several new potentially terdentate chelating agents based on the 8-hydroxyquinoline structure have been synthesized and characterized. Protonation constants of these ligands and formation constants of their chelates with selected metal-ions have been determined. Where possible, the chelates have been characterized by elemental analysis and other means. The results show that the ligand 2-(2'-thienyl)-8-hydroxyquinoline acts as a sterically hindering bidentate donor; the unusual relationship found between the formation constants of its bis-chelates (K1 < K2) has been explained on the basis of steric effects. The results of studies involving 4-amino-5-hydroxy-acridine and 4,5-dihydroxyacridine indicate that these ligands act as terdentate and bidentate donors, respectively. The failure of 4,5-dihydroxyacridine to act as a terdentate donor is explained in terms of chelate-ring strain. / Thesis / Doctor of Philosophy (PhD)

Este estudo teve como objetivo avaliar a capacidade de remoção da smear layer das paredes de canais radiculares instrumentados pelas soluções de soro fisiológico, EDTA a 17%, vinagre de maçã e SmearClear®, nos três níveis radiculares, associadas ou não ao ultra-som. Para tal propósito, foram utilizados 70 dentes caninos humanos superiores e inferiores extraídos os quais tiveram suas coroas removidas. O comprimento de trabalho foi determinado pela visualização da ponta de uma lima tipo K com diâmetro 10 no forame apical, subtraindo-se 1 milímetro dessa medida. Para o preparo biomecânico, instrumentou-se os dentes com o sistema rotatório ProTaper®, pela técnica coroa-ápice, até o instrumento F5, irrigando os canais com hipoclorito de sódio a 2,5% a cada troca de instrumento. Os dentes foram divididos aleatoriamente em 6 grupos de 10 dentes e 2 grupos controle de 5 dentes de acordo com o método de irrigação final a serem testados: Grupo 1 (controle) Soro fisiológico por 3 minutos sem ultra-som; Grupo 2 - (controle) Soro fisiológico por 3 minutos, sendo o primeiro minuto ativado pelo ultra-som; Grupo 3 - EDTA a 17% por 3 minutos sem ultra-som; Grupo 4 - EDTA a 17% por 3 minutos, sendo o primeiro minuto ativado pelo ultra-som; Grupo 5 - Vinagre de maçã por 3 minutos sem ultra-som; Grupo 6 - Vinagre de maçã por 3 minutos, sendo o primeiro minuto ativado pelo ultra-som; Grupo 7 - SmearClear® por 1 minuto sem ultra-som; Grupo 8 - SmearClear® por 1 minuto ativado pelo ultra-som. Em seguida, os dentes foram irrigados com hipoclorito de sódio a 2,5% e soro fisiológico e secos com cones de papel absorvente. As raízes foram seccionadas longitudinalmente e preparadas para a microscopia eletrônica de varredura com o aumento de 750 vezes. Fotomicrografias foram obtidas dos terços cervical, médio e apical e analisadas por três examinadores para a atribuição de escores para posterior análise estatística. Concluiu-se que as soluções de EDTA e SmearClear® foram efetivas na remoção da smear layer do canal radicular, com pequena vantagem numérica do EDTA, entretanto, sem diferença estatisticamente significante entre elas. O soro fisiológico apresentou resultado significativamente inferior comparado às demais soluções irrigadoras. O vinagre de maçã se mostrou ligeiramente inferior ao SmearClear® e ao EDTA, apresentando diferença estatisticamente significante ao EDTA no terço cervical. O uso do ultra-som não promoveu uma melhora significante na capacidade de limpeza de todas as soluções irrigadoras testadas. Em todos os grupos, o resultado menos favorável em relação à remoção da camada de smear layer foi observado no terço apical do canal radicular, com diferença estatisticamente significante em relação ao terço cervical. / The aim of this study was to evaluate the smear layer removal from instrumented root canal walls by saline solution, 17% EDTA, apple vinegar and SmearClear®, at three radicular levels, with or without ultrasonics. For that purpose, 70 upper and lower human canines were used, which had their crowns removed. The working length was established by visualizing the tip of a 10 K-type file at the apical foramen, by reducing 1 mm from this measurement. For preparation of root canal, the teeth were instrumented with rotatory files ProTaper®, using the crown-down technique, up to F5 instrument, irrigating with 2,5% sodium hypochlorite between each instrument change. The teeth were randomly divided into 6 groups of 10 teeth each and 2 control groups of 5 teeth according to the final irrigation protocol: Group 1 (control) Saline solution for 3 minutes without ultrasonics; Group 2 (control) Saline solution for 3 minutes, with ultrasonic activation for the first minute; Group 3 17% EDTA for 3 minutes without ultrasonics; Group 4 17% EDTA for 3 minutes, with ultrasonic activation for the first minute; Group 5 Apple vinegar for 3 minutes without ultrasonics; Group 6 Apple vinegar for 3 minutes, with ultrasonic activation for the first minute; Group 7 - SmearClear® for 1 minute without ultrasonics; Group 8 - SmearClear® for 1 minute with ultrasonic activation. Subsequently, the teeth were irrigated with 2,5% sodium hypochlorite and dried with paper points. The teeth were split open longitudinally and prepared for scanning electron microscopy at magnification of 750X. Photomicrographs were taken from coronal, middle and apical thirds and analyzed by three examiners for scores attribution for statistical analysis. It was concluded that EDTA and SmearClear® were efficient for smear layer removal from root canals, with a discrete superiority of EDTA, however, without statistical significance. The saline solution showed significant inferior results compared with the others solutions. Apple vinegar was slightly inferior to SmearClear® and EDTA, with statistical difference observed between apple vinegar and EDTA in coronal third. The ultrasonics did not enhance the cleaning ability of all the irrigating solutions tested. In all cases, the least favorable result regarding smear layer removal was observed in the apical third of the root canal, with statistically significant differences in the coronal third.

Barium sulfate scaling can cause many oilfield problems leading to loss of well productivity and well abandonment. Currently, diethylene triamine pentaacetic acid (DTPA) is used, along with synergist oxalic acid and potassium hydroxide, to remove the scale by dissolution. However, the chemical factors affecting this reaction are not known fully, leading to mixed results in terms of treatment effectiveness. This thesis investigates the effect of these factors, by analyzing the change in barite dissolution due to intrinsic factors like variations in formulation composition and extrinsic factors like presence of competing ions. The dissolution reaction is carried out, by taking the barite powder and chelant solution in a teflon round bottom flask and measuring the barite dissolved periodically, with an ICP-OES. The effect of different factors is studied by varying each factor individually and plotting the changes in solubilities. These lab tests show that solubility of barite (0.01mM in water), ideally, increases with increasing concentrations of chelating agents, even going as high as 239 mM. However experimental or field constraints lead to significant decrease in dissolution, especially at higher chelant concentrations. Thus, field tests to determine most effective chelant concentrations must precede treatment design. Lab tests also show that combination of DTPA with weaker chelating agents like ethylene diamine tetraacetic acid (EDTA), L-glutamic acid, N,N-diacetic acid (GLDA) or methyl glycine diacetic acid (MGDA) reduces barite dissolution and should be avoided during treatment design. Addition of synergists to the formulations, initially improves dissolution performance, especially for moderate chelant concentrations, but proves detrimental and hence must be avoided, over longer treatments. Finally, presence of competing ions in seawater, calcium sulfate and calcium carbonate, can significantly reduce barite dissolution and must be carefully studied for each formation-fluid system before design of treatments. Thus, this project sets a framework to identify the best chelant formulation and estimate its dissolution profile to ensure, a more informed treatment design for barite scale removal.

Patients with acquired iron overload require chelation therapy using either Desferal or Exjade. Iron in excess may promote free radical formation in the Fenton reaction resulting in severe injuries of heart, liver and endocrine organs. Che1ators that bind ferric iron (Fe+3) in a 1:1 complex (Desferal) sequester it more efficiently than those che1ators that form 2:1 (Exjade) complexes. We initiated synthesis of new chelators derived from the tridentate chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogs. The aim of the synthesis was to generate chelators that bind iron in a 1:1 complex, which was confirmed for 8LK02, 10LK02, 11LK02 and 15LK03 by spectrophotometry. All novel chelators mobilized iron more efficiently compared to Desferal and Exjade from murine reticulocytes and human myeloid leukemia cells (K562). Additionally, aforementioned four chelators were also more efficient than PIH and were found to be less or equally toxic as Desferal and Exjade.

The preparation and characterisation of chelating sorbents suitable for the high efficiency separation of trace metals in complex samples, using a single column and isocratic elution, is described. Hydrophobic, neutral polystyrene divinylbenzene resins were either impregnated with chelating dyes or dynamically modified with heterocyclic organic acids, using physical adsorption and chemisorption processes respectively. A hydrophilic silica substrate was covalently bonded with a chelating aminomethylphosphonic acid group, to assess the chelating potential of this molecule. These substrates were characterised in terms of metal retention capability (selectivity coefficients and capacity factors), separation performance, column efficiency and suitability for analytical applications. Chelating molecules with different ligand groups were found to have unique selectivity patterns dependant upon the conditional stability constants of the chelate. Other factors, including mobile phase constituents - complexing agents, ionic strength and pH, column length and column capacity were additionally investigated to examine their effect upon the separation profiles achieved. The promising metal separation abilities illustrated by a number of these chelating columns were exploited for the determination of trace toxic metals in complex sample matrices using High Performance Chelation Ion Chromatography (HPCIC). This included the determination of beryllium in a certified stream sediment, uranium in seawater and a certified stream sediment, and cadmium, lead and copper in a certified rice flour. The results for each analysis fell within the certified limits, and reproducibility was good. The optimisation of post column detection systems using chromogenic ligands additionally gave good detection limits for the metals in each separation system.

The thermal processing of milk changes the composition and surface properties of the colloidal particles present and alters the physical properties of the milk. Whilst some changes such as those used to improve the texture of products such as yoghurt and are desirable, others such as gel formation during the manufacture of Ultra-High Temperature milk are highly undesirable. This work aims to characterize the effects of milk composition and pH on the chemical and physical changes that occur when milk is heated in order to understand and control the effect of thermal processing on the functional properties of the milk. Particularly important are: (i) the changes to the integrity of the casein micelles and the extent to which they are reversible on cooling of the heated milk, (ii) the changes to the speciation of the components of the serum as they re-equilibrate in response to the changed environment during heating and on cooling, (iii) the heat-induced denaturation of the whey proteins, (iv) the interaction between the components of the micelles and those in the milk serum, particularly those interactions that lead to aggregation or other changes that affect the functional properties of the milk on heating. This project includes thermal treatment (90&deg;C/10 min) of control skim milk solutions (9% Milk Solids Non Fat) with or without addition of calcium chelating agents (orthophosphate (Pin) & Ethylenediaminetetraacetic acid (EDTA)) and concentrated skim milk solutions (up to 21% MSNF). The pH range chosen was 6.2 to 7.2. Almost all of the studies on heat stability to date have been carried out by heating the milk and determining the changes that have occurred after the milk is cooled. This project is focussed on the direct measurements in real time of the changes that occur at the exact temperature. The experimental techniques included pH, calcium activity and 31P NMR measurements at high temperatures to investigate the consequences to the change in mineral speciation, Size Exclusion Chromatography in combination with SDS-PAGE analysis for protein speciation during heating and Diffusing Wave Spectroscopy and viscosity measurements to determine the heat stability of milk systems. pH and calcium activity decreased with increase in temperature for all the milk systems studied. These changes were largely reversible as enough time was given for equilibration. pH and calcium activity changes during heating are a function of milk composition. The quantity, size and the composition of the protein aggregates present in the serum phase after mild centrifugation (~33,000g) of heated (90&deg;C/10min) milk solutions were found to be a function of pH and milk composition (including the consequent differences in speciation of the components of milk). DWS and the viscosity measurements showed that pH at the temperature of heating is one of the primary determinants in influencing the aggregation of the proteins, which led to thermal stability of milk systems. Hence, changing the milk composition resulted in differences in pH at the temperature of heating, which led to different behaviours of heat stability of milk systems. Careful control of the composition of milk and thereby the pH at the temperature of heating allows a greater control of thermal stability of milk systems.