Several studies were done to illustrate the versatillity of the Abraham model in mathematically describing the various solute-solvent interactions found in a wide range of different chemical and biological systems. The first study focused on using the solvation model to construct mathematical correlations describing the minimum inhibitory concentration of organic compounds for growth inhibition towards the three bacterial strains Porphyromonas gingivalis, Selenomonas artemidis, and Streptococcus sobrinus. The next several studies expand the practicallity of the Abraham model by predicting free energies of partition in chemical systems. The free energy studies expand the use of the Abraham model to other temperatures and properties by developing correlations for the enthalpies of solvation of gaseous solutes of various compounds dissolved in water, 1-octanol, hexane, heptane, hexadecane, cyclohexane, benzene, toluene, carbon tetrachloride, chloroform, methanol, ethanol, 1-butanol, propylene carbonate, dimethyl sulfoxide, 1,2-dichloroethane, N,N-dimethylformamide, tert-butanol, dibutyl ether, ethyl acetate, acetonitrile, and acetone. Also, a generic equation for linear alkanes is created for use when individual datasets are small. The prediction of enthalpies of solvation is furthered by modifying the Abraham model so that experimental data measured at different temperatures can be included into a single correlation expression. The temperature dependence is directly included in the model by separating each coefficient into an enthalpic and entropic component. Specifically, the final study describes the effects of temperature on the sorption coefficients of organic gases onto humic acid. The derived predicted values for each research study show a good correlation with experimental values.

In this experiment, more than one hundred volatile organic compounds were analyzed with the gas chromatograph. Six capillary columns ZB wax plus, ZB 35, TR1MS, TR5, TG5MS and TG1301MS with different polarities have been used for separation of compounds and illicit drugs. The Abraham solvation model has five solute descriptors. The solute descriptors are E, S, A, B, L (or V). Based on the six stationary phases, six equations were constructed as a training set for each of the six columns. The six equations served to calculate the solute descriptors for a set of illicit drugs. Drugs studied are nicotine (S= 0.870, A= 0.000, B= 1.073), oxycodone(S= 2.564. A= 0.286, B= 1.706), methamphetamine (S= 0.297, A= 1.570, B= 1.009), heroin (S=2.224, A= 0.000, B= 2.136) and ketamine (S= 1.005, A= 0.000, B= 1.126). The solute property of Abraham solvation model is represented as a logarithm of retention time, thus the logarithm of experimental and calculated retention times is compared.

"The accurate, fast and low cost computational tools are indispensable for studying the structure and dynamics of biological macromolecules in aqueous solution. The goal of this thesis is development and validation of continuum Fuzzy-Border (FB) solvation model to work with the Polarizable Simulations Second-order Interaction Model (POSSIM) force field for proteins developed by Professor G A Kaminski. The implicit FB model has advantages over the popularly used Poisson Boltzmann (PB) solvation model. The FB continuum model attenuates the noise and convergence issues commonly present in numerical treatments of the PB model by employing fixed position cubic grid to compute interactions. It also uses either second or first-order approximation for the solvent polarization which is similar to the second-order explicit polarization applied in POSSIM force field. The FB model was first developed and parameterized with nonpolarizable OPLS-AA force field for small molecules which are not only important in themselves but also building blocks of proteins and peptide side chains. The hydration parameters are fitted to reproduce the experimental or quantum mechanical hydration energies of the molecules with the overall average unsigned error of ca. 0.076kcal/mol. It was further validated by computing the absolute pKa values of 11 substituted phenols with the average unsigned error of 0.41pH units in comparison with the quantum mechanical error of 0.38pH units for this set of molecules. There was a good transferability of hydration parameters and the results were produced only with fitting of the specific atoms to the hydration energy and pKa targets. This clearly demonstrates the numerical and physical basis of the model is good enough and with proper fitting can reproduce the acidity constants for other systems as well. After the successful development of FB model with the fixed charges OPLS-AA force field, it was expanded to permit simulations with Polarizable Simulations Second-order Interaction Model (POSSIM) force field. The hydration parameters of the small molecules representing analogues of protein side chains were fitted to their solvation energies at 298.15K with an average error of ca.0.136kcal/mol. Second, the resulting parameters were used to reproduce the pKa values of the reference systems and the carboxylic (Asp7, Glu10, Glu19, Asp27 and Glu43) and basic residues (Lys13, Lys29, Lys34, His52 and Lys55) of the turkey ovomucoid third domain (OMTKY3) protein. The overall average unsigned error in the pKa values of the acid residues was found to be 0.37pH units and the basic residues was 0.38 pH units compared to 0.58pH units and 0.72 pH units calculated previously using polarizable force field (PFF) and Poisson Boltzmann formalism (PBF) continuum solvation model. These results are produced with fitting of specific atoms of the reference systems and carboxylic and basic residues of the OMTKY3 protein. Since FB model has produced improved pKa shifts of carboxylic residues and basic protein residues in OMTKY3 protein compared to PBF/PFF, it suggests the methodology of first-order FB continuum solvation model works well in such calculations. In this study the importance of explicit treatment of the electrostatic polarization in calculating pKa of both acid and basic protein residues is also emphasized. Moreover, the presented results demonstrate not only the consistently good degree of accuracy of protein pKa calculations with the second-degree POSSIM approximation of the polarizable calculations and the first-order approximation used in the Fuzzy-Border model for the continuum solvation energy, but also a high degree of transferability of both the POSSIM and continuum solvent Fuzzy Border parameters. Therefore, the FB model of solvation combined with the POSSIM force field can be successfully applied to study the protein and protein-ligand systems in water. "

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.

<p>The copper-binding ability of the prion protein may be closely connected to its function. Identifying the exact function of the prion protein can clarify the underlying mechanism in prion diseases. In this work, the copper-binding octapeptide region in the human prion protein has been studied. The structural characteristics of the binding site are examined by quantum chemical structural optimization. The calculations aim at identifying a substitute for copper(II) to be used in NMR-spectroscopic studies of the copper-binding region. The dynamical and structural features of the peptide region are investigated in molecular dynamics simulations. Aspects of importance in the development of model systems in molecular dynamics simulation are addressed.</p>

Experimental mole fraction solubilities of several carboxylic acids (2-methoxybenzoic acid, 4-methoxybenzoic acid, 4-nitrobenzoic acid, 4-chloro-3-nitrobenzoic acid, 2-chloro-5-nitrobenzoic acid,2-methylbenzoic acid and ibuprofen) and 9-fluorenone, thianthrene and xanthene were measured in a wide range of solvents of varying polarity and hydrogen-bonding characteristics. Results of these measurements were used to calculate gas-to-organic solvent and water-to-organic solvent solubility ratios, which were then substituted into known Abraham process partitioning correlations. The molecular solute descriptors that were obtained as the result of these computations described the measured solubility data to within an average absolute deviation of 0.2 log units. The calculated solute descriptors also enable one to estimate many chemically, biologically and pharmaceutically important properties for the ten solutes studied using published mathematical correlations.

The copper-binding ability of the prion protein may be closely connected to its function. Identifying the exact function of the prion protein can clarify the underlying mechanism in prion diseases. In this work, the copper-binding octapeptide region in the human prion protein has been studied. The structural characteristics of the binding site are examined by quantum chemical structural optimization. The calculations aim at identifying a substitute for copper(II) to be used in NMR-spectroscopic studies of the copper-binding region. The dynamical and structural features of the peptide region are investigated in molecular dynamics simulations. Aspects of importance in the development of model systems in molecular dynamics simulation are addressed. / QC 20101220

The Abraham solvation model (ABSM) is an experimentally derived predictive model used to help predict various solute properties. This work covers various uses for the ABSM including predicting molar enthalpies of vaporization, predicting solvent coefficients for two new solvents (2,2,5,5-tetramethyloxolane and diethyl carbonate), predicting values for multiple new ionic liquids (ILs). This work also introduces a novel method for updating IL ABSM parameters by updating cation- and anion-specific values using linear algebra and binary matrices.

Neste trabalho, sondas solvatocrômicas foram empregadas no estudo de solventes puros, misturas aquosas de solventes próticos e apróticos, líquidos iônicos e suas misturas aquosas. As sondas estudadas foram agrupadas em duas séries, cujas mudanças relevantes foram: (i) série RPMBr2: R de metila a 1-octila permitiu a variação da hidrofobicidade da sonda enquanto o pKa se manteve constante; (ii) série de merocianinas derivadas de piridina, quinolina e acridina. Isso resultou em sondas de hidrofobicidades diferentes com valores parecidos de pKa. Desta forma foi possível isolar os efeitos sobre solvatação provocados pela hidrofobicidade das sondas. As duas séries de sondas mostraram comportamentos solvatocrômicos diferentes. Uma equação modificada de Taft-Kamlet-Abboud permitiu as quantificações individuais de cada propriedade do solvente, tais como acidez, dipolaridade/polarizabilidade e hidrofobicidade para a resposta de cada sonda. O modelo de solvatação preferencial que considera explicitamente a presença de três espécies na mistura binária de solvente foi aplicado, este considera que a água, o solvente orgânico e a espécie solvente orgânico-água competem pela camada de solvatação da sonda. Os resultados deste tratamento ajudaram no entendimento das forças atuantes na solvatação, especialmente com relação aos efeitos das propriedades de ambos a sonda e o solvente, e do aumento da temperatura. Estudos preliminares de misturas aquosas de líquidos iônicos mostraram as semelhanças e as diferenças entre a solvatação por estas misturas \"verdes\" e a por misturas aquosas de álcoois. Uma aplicação do solvatocromismo para o entendimento de un fenômeno físco-químico foi apresentada: os resultados da aplicação do modelo de solvatação preferencial de sondas em misturas aquosas de tetrametiluréia foram usados para explicar o fenômeno de gelificação de proteína neste mesmo sistema de solventes. / In the present work, solvatochromic probes were employed in the study of pure solvents, binary mixtures of water with protic and aprotic solvents, ionic liquids and their aqueous binary mixtures The probes studied are classified in two series: (i) RPMBr2; where R = methyl to 1-octyl allowed increasing the hydrophobicity while maintaining the pKa constant. (ii) The second series involved derivatives of pyridine, quinoline and acridine, this allowed increasing probe hydrophobicity, while maintaining similar pKa. The two series of probes showed different solvatochromic behaviors both in pure solvents and binary solvent mixtures. A modified equation of Taft-Kamlet-Abboud allowed quantification of each solvent property, including acidity, dipolarity/polarizability and hydrophobicity to the response of each probe. The preferential solvation model which explicitly considers the presence of three species was employed; it considers the competition of water, organic solvent and the complex water-organic solvent in the probe solvation shell. The results shed light on the interactions that affect solvation, including temperature-induced desolvation. Preliminary results on aqueous ionic liquids showed the similarities and difference between solvation by these \"green\" mixtures and those of aqueous alcohols. An application of solvatochromism for understanding a physical-chemical phenomenon was presented: the results of application of preferential solvation model of probes in aqueous tetramethylurea mixtures was used to explain the gelation of the protein lysozyme in this same solvent system.

Neste trabalho, sondas solvatocrômicas foram empregadas no estudo de solventes puros, misturas aquosas de solventes próticos e apróticos, líquidos iônicos e suas misturas aquosas. As sondas estudadas foram agrupadas em duas séries, cujas mudanças relevantes foram: (i) série RPMBr2: R de metila a 1-octila permitiu a variação da hidrofobicidade da sonda enquanto o pKa se manteve constante; (ii) série de merocianinas derivadas de piridina, quinolina e acridina. Isso resultou em sondas de hidrofobicidades diferentes com valores parecidos de pKa. Desta forma foi possível isolar os efeitos sobre solvatação provocados pela hidrofobicidade das sondas. As duas séries de sondas mostraram comportamentos solvatocrômicos diferentes. Uma equação modificada de Taft-Kamlet-Abboud permitiu as quantificações individuais de cada propriedade do solvente, tais como acidez, dipolaridade/polarizabilidade e hidrofobicidade para a resposta de cada sonda. O modelo de solvatação preferencial que considera explicitamente a presença de três espécies na mistura binária de solvente foi aplicado, este considera que a água, o solvente orgânico e a espécie solvente orgânico-água competem pela camada de solvatação da sonda. Os resultados deste tratamento ajudaram no entendimento das forças atuantes na solvatação, especialmente com relação aos efeitos das propriedades de ambos a sonda e o solvente, e do aumento da temperatura. Estudos preliminares de misturas aquosas de líquidos iônicos mostraram as semelhanças e as diferenças entre a solvatação por estas misturas \"verdes\" e a por misturas aquosas de álcoois. Uma aplicação do solvatocromismo para o entendimento de un fenômeno físco-químico foi apresentada: os resultados da aplicação do modelo de solvatação preferencial de sondas em misturas aquosas de tetrametiluréia foram usados para explicar o fenômeno de gelificação de proteína neste mesmo sistema de solventes. / In the present work, solvatochromic probes were employed in the study of pure solvents, binary mixtures of water with protic and aprotic solvents, ionic liquids and their aqueous binary mixtures The probes studied are classified in two series: (i) RPMBr2; where R = methyl to 1-octyl allowed increasing the hydrophobicity while maintaining the pKa constant. (ii) The second series involved derivatives of pyridine, quinoline and acridine, this allowed increasing probe hydrophobicity, while maintaining similar pKa. The two series of probes showed different solvatochromic behaviors both in pure solvents and binary solvent mixtures. A modified equation of Taft-Kamlet-Abboud allowed quantification of each solvent property, including acidity, dipolarity/polarizability and hydrophobicity to the response of each probe. The preferential solvation model which explicitly considers the presence of three species was employed; it considers the competition of water, organic solvent and the complex water-organic solvent in the probe solvation shell. The results shed light on the interactions that affect solvation, including temperature-induced desolvation. Preliminary results on aqueous ionic liquids showed the similarities and difference between solvation by these \"green\" mixtures and those of aqueous alcohols. An application of solvatochromism for understanding a physical-chemical phenomenon was presented: the results of application of preferential solvation model of probes in aqueous tetramethylurea mixtures was used to explain the gelation of the protein lysozyme in this same solvent system.