Low level nuclear waste arising from UK nuclear sites, research establishments, hospitals and industry is currently disposed of at the Drigg Disposal Facility in Cumbria. Waste is packed into steel canisters before being compacted and grouted into larger steel storage containers. The aqueous chemistry of wastes, especially radionuclides, in the presence of grout material is of major interest. The gout used at the Drigg site is a mixture of Ordinary Portland Cement and Pulverised Fly Ash additive, from which ingressing water will leach high levels of calcium, sodium and potassium and produce waters of a high pH. Aerobic environments are expected to dominate over the early period of the vault life, after which the combined effect of canister corrosion and microbial activity will lead to anaerobic conditions. After a much longer period (100,000 years) anaerobic conditions may cease and yield once again an aerobic environment where migration of radionuclides may be sorption-controlled rather than on hydroxide precipitation at high pH. Work has been performed under both aerobic and anaerobic conditions to study uranium solubility in the presence of complexing ligands that may be present in the waters of the nearfield of a low-level waste disposal vault. Eleven ligands have been investigated: carbonate, phosphate, chloride, sulphate, acetate, citrate, EDTA, NTA and organic matter- humic acid, fulvic acid and iso-sacchannic acid. Anaerobic conditions were achieved by two different procedures; the first used ferrous ions in hydroxide solution and the second used dithionite in hydroxide solution. Both methods produce reducing electrode potentials and high pH. Computer software has been used to model experimental results, thereby predicting uranium solubilities and speciation, and to propose new formation constants to fit the experimental results more closely. Studies have also been perforined to measure uranium sorption by grout material at high pH in the presence of the above ligands. This work makes a significant contribution to the understanding of uranium solubility and speciation in waters. at high pH and under conditions relevant to low level nuclear waste disposal.

The solubility of cellobiose in 18 organic liquids and water was measured at 20°C. Hydrogen bond acceptors were the most effective solvents. Three models were analyzed to evaluate their accuracy and to understand factors that affect cellobiose solubility: Hansen solubility parameters (HSP), linear free energy relationship (LFER), and UNIQUAC functional-group activity coefficients (UNIFAC). The HSP of cellobiose were determined and the model was able to distinguish between most good and poor solvents, however, proved to be occasionally unreliable due to a false negative. The LFER model produced an empirical equation involving contributions from solvent molar refraction, polarizability, acidity, basicity, and molar volume, which predicted cellobiose solubilities to within ±2 log units. LFER indicated that good solvents were highly polarizable and had low molar volume, which was consistent with the good solvents found for cellobiose. A modified version of UNIFAC that includes an association term (A-UNIFAC) predicted the solubility of cellobiose in water and alcohols to within ±0.6 log units, indicating that A-UNIFAC can be used to predict the solubility of cellobiose and other carbohydrates provided additional data to extend the model to solvents other than water and alcohols.

The Abraham Solvation Parameter Model (ASPM) is a linear, free-energy relationship that can be used to predict various solute properties based on solute-solvent interactions. The ASPM has been used to predict log (K or Cs,organic/Cs,gas) values, as well as log (P or Cs,organic/Cs,water) values for solute transfer into the following organic solvents: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, 2-isopropoxyethanol and 2-butoxyethanol. The derived log (K or Cs,organic/Cs,gas) correlations describe the experimental data to within 0.14 log units (or less). The derived log (P or Cs,organic/Cs,water) correlations describe the experimental data to within 0.16 log units (or less). The ASPM has also been used to predict the enthalpies of solvation of organic solutes dissolved in the following solvents: acetic acid, dimethyl carbonate, diethyl carbonate, 1-butanol, 1-pentanol, 1-hexanol. The derived enthalpy of solvation correlations, using the L solute descriptor, describe the experimental data to within 2.50 log units (or less). The derived enthalpy of solvation correlations, using the V solute descriptor, describe the experimental data to within 3.10 log units (or less). Validation analyses have been performed on several of the correlations; and, as long as the solute descriptors fall within the given ranges as reported, the original correlations show good predictive ability for determining 1) solute transfer into, and 2) enthalpy of solvation for the aforementioned solvents.

The purpose of this dissertation is to investigate the thermochemical properties of nonelectrolyte solutes dissolved in ternary solvent mixtures, and to develop mathematical expressions for predicting and describing behavior in the solvent mixtures. Forty-five ternary solvent systems were studied containing an ether (Methyl tert-butyl ether, Dibutyl ether, or 1,4-Dioxane), an alcohol (1-Propanol, 2-Propanol, 1-Butanol, 2-Butanol, or 2-Methyl-1-propanol), and an alkane (Cyclohexane, Heptane, or 2,2,4-Trimethylpentane) cosolvents. The Combined NIBS (Nearly Ideal Binary Solvent)/Redlich-Kister equation was used to assess the experimental data. The average percent deviation between predicted and observed values was less than ± 2 per cent error, documenting that this model provides a fairly accurate description of the observed solubility behavior. In addition, Mobile Order theory, the Kretschmer-Wiebe model, and the Mecke-Kempter model were extended to ternary solvent mixtures containing an alcohol (or an alkoxyalcohol) and alkane cosolvents. Expressions derived from Mobile Order theory predicted the experimental mole fraction solubility of anthracene in ternary alcohol + alkane + alkane mixtures to within ± 5.8%, in ternary alcohol + alcohol + alkane mixtures to within ± 4.0%, and in ternary alcohol + alcohol + alcohol mixtures to within ± 3.6%. In comparison, expressions derived from the Kretschmer-Wiebe model and the Mecke-Kempter model predicted the anthracene solubility in ternary alcohol + alkane + alkane mixtures to within ± 8.2% and ± 8.8%, respectively. The Kretschmer-Wiebe model and the Mecke-Kempter model could not be extended easily to systems containing two or more alcohol cosolvents.

No / The increasing prevalence of poorly soluble drugs in development provides notable risk of new products demonstrating low and erratic bioavailabilty with consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Although numerous strategies exist for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet able to be guaranteed and is greatly dependent on the physical and chemical nature of the molecules being developed. Crystal engineering offers a number of routes to improved solubility and dissolution rate, which can be adopted through an in-depth knowledge of crystallisation processes and the molecular properties of active pharmaceutical ingredients. This article covers the concept and theory of crystal engineering and discusses the potential benefits, disadvantages and methods of preparation of co-crystals, metastable polymorphs, high-energy amorphous forms and ultrafine particles. Also considered within this review is the influence of crystallisation conditions on crystal habit and particle morphology with potential implications for dissolution and oral absorption.

<p>Aqueous solubility is a key parameter influencing the bioavailability of drugs and drug candidates. In this thesis computational models for the prediction of aqueous drug solubility were explored. High quality experimental solubility data for drugs were generated using a standardised protocol and models were developed using multivariate data analysis tools and calculated molecular descriptors. In addition, structural features associated with either solid-state limited or solvation limited solubility of drugs were identified.</p><p>Solvation, as represented by the octanol-water partition coefficient (log<i>P</i>), was found to be the dominant factor limiting the solubility of drugs, with solid-state properties being the second most important limiting factor.</p><p>The relationship between the chemical structure of drugs and the strength of their crystal lattice was studied for a dataset displaying log<i>P</i>-independent solubility. Large, rigid and flat molecules with an extended ring-structure and a large number of conjugated π-bonds were found to be more likely to have their solubility limited by a strong crystal lattice than were small, spherically shaped molecules with flexible side-chains.</p><p>Finally, the relationship between chemical structure and drug solvation was studied using computer simulated values of the free energy of hydration. Drugs exhibiting poor hydration were found to be large and flexible, to have low polarisability and few hydrogen bond acceptors and donors.</p><p>The relationship between the structural features of drugs and their aqueous solubility discussed in this thesis provide new rules-of-thumb that could guide decision-making in early drug discovery.</p>

Aqueous solubility is a key parameter influencing the bioavailability of drugs and drug candidates. In this thesis computational models for the prediction of aqueous drug solubility were explored. High quality experimental solubility data for drugs were generated using a standardised protocol and models were developed using multivariate data analysis tools and calculated molecular descriptors. In addition, structural features associated with either solid-state limited or solvation limited solubility of drugs were identified. Solvation, as represented by the octanol-water partition coefficient (logP), was found to be the dominant factor limiting the solubility of drugs, with solid-state properties being the second most important limiting factor. The relationship between the chemical structure of drugs and the strength of their crystal lattice was studied for a dataset displaying logP-independent solubility. Large, rigid and flat molecules with an extended ring-structure and a large number of conjugated π-bonds were found to be more likely to have their solubility limited by a strong crystal lattice than were small, spherically shaped molecules with flexible side-chains. Finally, the relationship between chemical structure and drug solvation was studied using computer simulated values of the free energy of hydration. Drugs exhibiting poor hydration were found to be large and flexible, to have low polarisability and few hydrogen bond acceptors and donors. The relationship between the structural features of drugs and their aqueous solubility discussed in this thesis provide new rules-of-thumb that could guide decision-making in early drug discovery.

Experimental data were obtained for the computation of mole fraction solubilities of three dichloronitrobenzenes in organic solvents at 25oC, and solubility ratios were obtained from this data. Abraham model equations were developed for solutes in tributyl phosphate that describe experimental values to within 0.15 log units, and correlations were made to describe solute partitioning in systems that contain either "wet" or "dry" tributyl phosphate. Abraham model correlations have also been developed for solute transfer into anhydrous diisopropyl ether, and these correlations fit in well with those for other ethers. Abraham correlations for the solvation of enthalpy have been derived from experimental and literature data for mesitylene, p-xylene, chlorobenzene, and 1,2-dichlorobenzene at 298.15 K. In addition, the enthalpy contribution of hydrogen bonding between these solutes and acidic solvents were predicted by these correlations and were in agreement with an established method. Residual plots corresponding to Abraham models developed in all of these studies were analyzed for trends in error between experimental and calculated values.

Dissolution rates of hornblende and tremolite were studied in constant pH batch experiments over the pH range 4-6, in order to understand the acid neutralizing role of hornblende in watersheds with low alkalinity. Hornblende and tremolite exhibit linear dissolution kinetics within one or two days after the onset of weathering. During the first 80-100 hours of weathering, base cations are released preferentially to silica in both minerals. During this period a leached surface layer similar in structure to the original material, but altered in composition is believed to be formed. Release rates of Si, Ca, Na, and Mg from hornblende exhibit weak fractional dependence on pH: d[Mg] /dt = k₁[H⁺] 0.13, d[Ca] /dt = k₁[H⁺] 0.065, d[Na] /dt = k₁[H⁺] 0.17, and d[Si] /dt = k₁[H⁺] 0.045. As a result, it is believed that, for large and transient influxes of acidified water, hornblende is not an important pH buffer. Because of rapid dissolution rates, however, hornblende could be an important source of acid neutralizing capacity.

Determinations of design parameters and investigation on operation performance of a tar removal system for gas cleaning of biomass producer gas have been undertaken. The presence of the tars in the producer gas has been the major hindrance for the commercialisation of the biomass gasification technology for power generation, hydrogen production, Fischer Tropsch (FT) synthesis, chemical synthesis and synthetic natural gas (SNG) synthesis. The characteristic of the tars to condense at reduced temperatures cause problems in the downstream processing as the tars can block and foul the downstream process equipment such as gas engines reactor channels, fuel cells, etc. Considerable efforts have been directed at the removal of tars from the producer gas where the tars can be either chemically converted into lighter molecular weight molecules or physically transferred from gas phase to liquid or solid phase. In the former, the tars have been removed in a scrubber by transferring them from the producer gas to a scrubbing liquid and then removed from the liquid to air in a stripper and finally recycled them into air to a gasifier to recover their energy. A tar removal test system involving a scrubber and stripper has been designed based on the predicted tar solubility in canola methyl ester (CME) as the scrubbing liquid and its measured properties (CME is a type of methyl ester biodiesel). The tar solubility has been predicted to decrease with increasing temperatures and thus its value increases at lower temperatures. In designing the test system, the design parameters are needed including equilibrium coefficients of the gas-liquid system, molar transfer coefficient and the optimum liquid to gas flow rate ratio. The equilibrium coefficients have been predicted based on thermodynamic theories where the required data are determined from CME composition and known properties of each component of the CME as well as the properties of the model tar (naphthalene). The molar transfer coefficients are then experimentally determined and the correlations as a function of liquid and gas flow rates are proposed which are consistent with literature. The optimum liquid to gas flow rate ratios have been found to be 21.4±0.1 for the scrubber and 5.7±0.1 for the stripper. Using these optimum ratios, the tar removal efficiencies in the scrubber and the stripper are 77 and 74%, respectively. The analysis of the system performance has been achieved after an innovative method of determining tar concentrations in both the liquid and gas phase had been developed based on the concept of the density of liquid mixtures. However, these tar removal efficiencies are low due to the fact that the targeted tar concentration in the scrubber’s off-gas was large. As a result the system has been redesigned based on the determined design parameters and its operation performance retested. In the redesigned system, the tar removal efficiency in the scrubber and stripper is 99%. The redesigned system would be integrated with the UC gasifier for downstream gas cleaning. Since 1% of tars are not removed, a makeup tar free CME of 0.0375 litres per hour for the 100kW UC gasifier has been introduced in the recycle stream between the scrubber and stripper to avoid tar accumulation in the system.