Phosphoryl transfers are essential chemical reactions in key life processes, including energy production, signal transduction and protein synthesis. They are known for having extremely low reaction rates in aqueous solution, reaching the scale of millions of years. In order to make life possible, enzymes that catalyse phosphoryl transfer, phosphoryl transferases, have evolved to be tremendously proficient catalysts, increasing reaction rates to the millisecond timescale. Due to the nature of the electronic structure of phosphorus atoms, understanding how hydrolysis of phosphate esters occurs is a complex task. Experimental studies on the hydrolysis of phosphate monoesters with acidic leaving groups suggest a concerted mechanism with a loose, metaphosphate-like transition state. Theoretical studies have suggested two possible concerted pathways, either with loose or tight transition state geometries, plus the possibility of a stepwise mechanism with the formation of a phosphorane intermediate. Different pathways were shown to be energetically preferable depending on the acidity of the leaving group. Here we performed computational studies to revisit how this mechanistic shift occurs along a series of aryl phosphate monoesters, suggesting possible factors leading to such change. The fact that distinct pathways can occur in solution could mean that the same is possible for an enzyme active site. We performed simulations on the catalytic activity of β-phosphoglucomutase, suggesting that it is possible for two mechanisms to occur at the same time for the phosphoryl transfer. Curiously, several phosphoryl transferases were shown to be able to catalyse not only phosphate ester hydrolysis, but also the cleavage of other compounds. We modeled the catalytic mechanism of two highly promiscuous members of the alkaline phosphatase superfamily. Our model reproduces key experimental observables and shows that these enzymes are electrostatically flexible, employing the same set of residues to enhance the rates of different reactions, with different electrostatic contributions per residue.

Yes / We have set out an equation for partition of 87 neutral molecules from water to o-nitrophenyl octyl ether, NPOE, an equation for partition of the 87 neutral molecules and 21 ionic species from water to NPOE, and an equation for partition of 87 neutral molecules from the gas phase to NPOE. Comparison with equations for partition into other solvents shows that, as regards partition of neutral (nonelectrolyte) compounds, NPOE would be a good model for 1,2-dichloroethane and for nitrobenzene. In terms of partition of ions and ionic species, NPOE is quite similar to 1,2-dichloroethane and not far away from other aprotic solvents such as nitrobenzene.

No / The aim of the present work is to evaluate the similarity between PDMS membranes and human skin in vitro in permeation study by linear free energy relationship (LFER) analyses. The values of the permeability coefficient log Kp (cm/s) under reliable experimental conditions were collected from the literature for a set of 94 compounds including both neutral and ionic species, which cover a broad range of structural diversity. The values of log Kp (cm/s) have been correlated with Abraham descriptors to yield an equation with R2 = 0.952 and SD = 0.38 log units. The established LFER model for log Kp (cm/s) across PDMS membranes showed no close analogy with that through human skin in vitro. A further critical analysis of the coefficients of the LFER models confirmed that the PDMS permeation system is a very poor model for human skin permeation.

Yes / We have used literature values for the solubility of vitamin K3 in organic solvents to obtain Abraham descriptorsfor vitamin K3. Although these descriptors themselves are not exceptional in any way, when combined withequations that we have already set out, they lead to the prediction of important properties of vitamin K3.These include the vapor pressure and heat of sublimation (necessary for the analysis of data on the concentrationof vitamin K3 in ambient air), and the partitions air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane, water-skin, as well as permeation from water through skin. Values of the partitions into biologicalphases are all quite large by comparison to those for organic compounds in general.

Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the bilayer barrier domain (hydrocarbon-like) proved to be the major factors to consider in developing LFERs to account for the increased oil/water partition coefficients and enhanced bilayer permeability of small organic molecules. The triglyceride solvent/water partition coefficients of a series of model compounds varying in polarity and H-bond donating/accepting capability were used to establish a correlation between the solvent descriptors and the ester concentration in these solvents using the Abraham LFER approach. The LFER analyses showed that the descriptors representing the polarizability and H-bond basicity of the solvents vary systematically with the ester concentration. A fragment-based LFER to predict membrane permeability or 1,9- decadiene/water partition coefficients of small organic molecules including small peptides was systematically constructed using a total of 47 compounds. Significant nonadditivity was observed in peptides in that the contribution of the peptide backbone amide to the apparent transfer free energy from water into the bilayer barrier domain is considerably smaller than that of a “well-isolated” amide and greatly affected by adjacent polar substituents on the C-termini. In order to explain the phenomenon of nonadditivity, the formation of intramolecular HBs and inductive effects of neighboring polar groups on backbone amide, were investigated using FTIR and MD simulations. Both spectroscopic and computational results provided supportive evidence for the hypothesis that the formation of intramolecular HBs in peptides is the main reason for the observed nonadditivity of Δ(ΔG°)-CONH-. The MD simulation results showed that the inductive effect of neighboring groups is not as important as the effect of intramolecular HBs.

Entre as mais importantes propriedades de soluções aquosas micelares está a capacidade de incorporar substâncias orgânicas com diferentes polaridades e graus de hidrofobicidade. Como demonstrado por Quina et aI. (J Phys. Chem., 1995, 99, 11708-11714), um dos métodos mais promissores para a obtenção de correlações entre e a eficiência de solubilização em micelas e as estruturas do soluto e do detergente é através do uso de relações lineares de energia livre (LSERs). No presente trabalho, investigou-se a incorporação de uma série de solutos neutros em micelas dos detergentes zwitteriônicos dimetil-hexadecilamônio-propano sulfonato (CDAPS; 31 solutos) e o N-óxido de dimetil-dodecilamina (DDAO; 33 solutos), bem como em micelas catiônicas da forma protonada de DDAO (DDAOH+; 33 solutos). As constantes de incorporação dos solutos foram determinadas experimentalmente por meio de técnicas fotofísicas, métodos de solubilização e cromatografia líquida e gasosa. A análise dos resultados foi efetuada através de técnicas de regressão múltipla, obtendo-se as seguintes LSERs: CDAPS: Log Ks = - 0,55 + 0,99 R2 - 0,82 π2 + 0,36 Σα2 - 0,99 Σβ2 + 2,73 Vx DDAOH+: Log Ks = - 0,68 + 1,30 R2 - 0,78 π2 + 0,67 Σα2 - 1,45 Σβ2 + 2,29 Vx DDAO: Log Ks = - 0,46 + 0,89 R2 - 0,61 π2 + 0,82 Σα2 - 1,66 Σβ2 + 2,59 Vx onde Σα2 e Σβ2 representam a \"acidez\" e a \"basicidade\" do soluto, com relação à formação de pontes de hidrogênio, R2 corresponde à refração molar em excesso, π2 representa a dipolaridade e Vx é o volume molar do soluto. As LSERs obtidas indicam que os detergentes zwitteriônicos formam sistemas distintos dos demais estudados até o momento. No entanto, os sistemas DDAO e DDAOH+ apresentam LSERs muito semelhantes entre sí, sugerindo que a incorporação dos solutos não é afetada por uma mudança da estrutura (carga) da cabeça do detergente. / One of the most important properties of aqueous micellar solutions is their capacity to incorporate organic solutes with different degrees of polarity and hydrophobicity. As demonstrated by Quina et aI. (J. Phys. Chem., 1995, 99, 1170811714), one of the most promissing methods for obtaining correlations between solubilization eficiency and the solute and surfactant structure is via the use of linear solvation energy relationships (LSERs). The present work investigates the incorporation of a series of neutral solutes in micelles of the zwitterionic detergents hexadecyldimethylammonium propanesulfonate (CDAPS; 31 solutes) and the N-oxide of dodecyldimethylamine (DDAO; 33 solutes), as well as in the cationic micelles of the protonated form of DDAO (DDAOH+; 33 solutes). The incorporation constants were determined experimentally by photophysical techniques, from solubility measurements and by liquid and gas chromatographic methods. Analysis of the results by multiple regression techniques led to the following LSERs: CDAPS: Log Ks = - 0,55 + 0,99 R2 - 0,82 π2 + 0,36 Σα2 - 0,99 Σβ2 + 2,73 Vx DDAOH+: Log Ks = - 0,68 + 1,30 R2 - 0,78 π2 + 0,67 Σα2 - 1,45 Σβ2 + 2,29 Vx DDAO: Log Ks = - 0,46 + 0,89 R2 - 0,61 π2 + 0,82 Σα2 - 1,66 Σβ2 + 2,59 Vx where Σα2 and Σβ2 are the hydrogen bond acidity and basicity of the solute, R2 is the excess molar refraction, π2 is the dipolarity and Vx corresponds to the molar volume of the solute. The LSERs obtained demonstrate that zwitterionic surfactants are distinct from the other systems investigated previously. However, the similarity of the LSERs of DDAO and DDAOH+ suggests that incorporation of solutes is not affected by changes in the structure (charge) ofthe polar headgroup.

Entre as mais importantes propriedades de soluções aquosas micelares está a capacidade de incorporar substâncias orgânicas com diferentes polaridades e graus de hidrofobicidade. Como demonstrado por Quina et aI. (J Phys. Chem., 1995, 99, 11708-11714), um dos métodos mais promissores para a obtenção de correlações entre e a eficiência de solubilização em micelas e as estruturas do soluto e do detergente é através do uso de relações lineares de energia livre (LSERs). No presente trabalho, investigou-se a incorporação de uma série de solutos neutros em micelas dos detergentes zwitteriônicos dimetil-hexadecilamônio-propano sulfonato (CDAPS; 31 solutos) e o N-óxido de dimetil-dodecilamina (DDAO; 33 solutos), bem como em micelas catiônicas da forma protonada de DDAO (DDAOH+; 33 solutos). As constantes de incorporação dos solutos foram determinadas experimentalmente por meio de técnicas fotofísicas, métodos de solubilização e cromatografia líquida e gasosa. A análise dos resultados foi efetuada através de técnicas de regressão múltipla, obtendo-se as seguintes LSERs: CDAPS: Log Ks = - 0,55 + 0,99 R2 - 0,82 π2 + 0,36 Σα2 - 0,99 Σβ2 + 2,73 Vx DDAOH+: Log Ks = - 0,68 + 1,30 R2 - 0,78 π2 + 0,67 Σα2 - 1,45 Σβ2 + 2,29 Vx DDAO: Log Ks = - 0,46 + 0,89 R2 - 0,61 π2 + 0,82 Σα2 - 1,66 Σβ2 + 2,59 Vx onde Σα2 e Σβ2 representam a \"acidez\" e a \"basicidade\" do soluto, com relação à formação de pontes de hidrogênio, R2 corresponde à refração molar em excesso, π2 representa a dipolaridade e Vx é o volume molar do soluto. As LSERs obtidas indicam que os detergentes zwitteriônicos formam sistemas distintos dos demais estudados até o momento. No entanto, os sistemas DDAO e DDAOH+ apresentam LSERs muito semelhantes entre sí, sugerindo que a incorporação dos solutos não é afetada por uma mudança da estrutura (carga) da cabeça do detergente. / One of the most important properties of aqueous micellar solutions is their capacity to incorporate organic solutes with different degrees of polarity and hydrophobicity. As demonstrated by Quina et aI. (J. Phys. Chem., 1995, 99, 1170811714), one of the most promissing methods for obtaining correlations between solubilization eficiency and the solute and surfactant structure is via the use of linear solvation energy relationships (LSERs). The present work investigates the incorporation of a series of neutral solutes in micelles of the zwitterionic detergents hexadecyldimethylammonium propanesulfonate (CDAPS; 31 solutes) and the N-oxide of dodecyldimethylamine (DDAO; 33 solutes), as well as in the cationic micelles of the protonated form of DDAO (DDAOH+; 33 solutes). The incorporation constants were determined experimentally by photophysical techniques, from solubility measurements and by liquid and gas chromatographic methods. Analysis of the results by multiple regression techniques led to the following LSERs: CDAPS: Log Ks = - 0,55 + 0,99 R2 - 0,82 π2 + 0,36 Σα2 - 0,99 Σβ2 + 2,73 Vx DDAOH+: Log Ks = - 0,68 + 1,30 R2 - 0,78 π2 + 0,67 Σα2 - 1,45 Σβ2 + 2,29 Vx DDAO: Log Ks = - 0,46 + 0,89 R2 - 0,61 π2 + 0,82 Σα2 - 1,66 Σβ2 + 2,59 Vx where Σα2 and Σβ2 are the hydrogen bond acidity and basicity of the solute, R2 is the excess molar refraction, π2 is the dipolarity and Vx corresponds to the molar volume of the solute. The LSERs obtained demonstrate that zwitterionic surfactants are distinct from the other systems investigated previously. However, the similarity of the LSERs of DDAO and DDAOH+ suggests that incorporation of solutes is not affected by changes in the structure (charge) ofthe polar headgroup.

Emerging contaminants are defined as synthetic or naturally occurring chemicals or microorganisms that are not currently regulated but have the potential to enter the environment and cause adverse ecological and/or human health effects. With recent development in analytical techniques, emerging contaminants have been detected in wastewater, source water, and finished drinking water. These environmental occurrence data have raised public concern about the fate and ecological impacts of such compounds. Concerns regarding emerging contaminants and the many chemicals that are in use or production necessitate a task to assess their potential health effects and removal efficiency during water treatment. Advanced oxidation processes (AOPs) are attractive and promising technologies for emerging contaminant control due to its capability of mineralizing organic compound via reactions with highly active hydroxyl radicals. However, the nonselective reactivity of hydroxyl radicals and the radical chain reactions make AOPs mechanistically complex processes. In addition, the diversity and complexity of the structure of a large number of emerging contaminants make it difficult and expensive to study the degradation pathways of each contaminant and the fate of the intermediates and byproducts. The intermediates and byproducts that are produced may pose potential effects to human and aquatic ecosystems. Consequently, there is a need to develop first-principle based mechanistic models that can enumerate reaction pathway, calculate concentrations of the byproducts, and estimate their human effects for both water treatment and reuse practices. This dissertation develops methods to predict reaction rate constants for elementary reactions that are identified by a previously developed computer-based reaction pathway generator. Many intermediates and byproducts that are experimentally identified for HO* induced reactions with emerging contaminants include common lower molecular weight organic compounds on the basis of several carbons. These lower carbon intermediates and byproducts also react with HO* at relatively smaller reaction rate constants (i.e., k < 109 M-1s-1) and may significantly affect overall performance of AOPs. In addition, the structures of emerging contaminants with various functional groups are too complicated to model. As a consequence, the rate constant predictors are established based on the conventional organic compounds as an initial approch. A group contribution method (GCM) predicts the aqueous phase hydroxyl radical reaction rate constants for compounds with a wide range of functional groups. The GCM is a first comprehensive tool to predict aqueous phase hydroxyl radical reaction rate constants for reactions that include hydrogen-atom abstraction from a C-H bond and/or a O-H bond by hydroxyl radical, hydroxyl radical addition to a C=C unsaturated bond in alkenes and aromatic compounds, and hydroxyl radical interaction with sulfur-, nitrogen-, or phosphorus-atom-containing compounds. The GCM shows predictability; factor of difference of 2 from literature-reported experimental values. The GCM successfully predicts the hydroxyl radical reaction rate constants for a limited number of emerging contaminants. Linear free energy relationships (LFERs) bridge a kinetic property with a thermochemical property. The LFERs is a new proof-of-concept approach for Ab initio reaction rate constants predictors. The kinetic property represents literature-reported and our experimentally obtained hydroxyl radical reaction rate constants for neutral and ionized compounds. The thermochemical property represents quantum mechanically calculated aqueous phase free energy of activation. Various Ab initio quantum mechanical methods and solvation models are explored to calculate the aqueous phase free energy of activation of reactantas and transition states. The quantum mechanically calculcated aqueous phase free energies of activation are within the acceptable range when compared to those that are obtained from the experiments. These approaches may be applied to other reaction mechanisms to establish a library of rate constant predictions for the mechanistic modeling of AOPs. The predicted kinetic information enables one to identify important pathways of AOP mechanisms that are initiated by hydroxyl radical, and can be used to calculate concentration profiles of parent compounds, intermediates and byproducts. The mechanistic model guides the design of experiments that are used to examine the reaction mechanisms of important intermediates and byproducts and the application of AOPs to real fields.

L'objectif de cette thèse fut de développer un process pour la production d'acide peroxycarbolique à partir du peroxyde d'hydrogène et d'un acide carboxylique dans un réacteur continu. Dans un premier temps, la stabilité des espèces peroxydées fut étudiée en utilisant une méthode d'analyse en direct (spectromètre de masse). Un effort particulier a été apporté pour trouver un catalyseur hétérogène ne provoquant pas la décomposition des espèces peroxydées et ayant une activité catalytique similaire à l'acide sulfurique. Un réacteur en continu en lit fixe a été construit en utilisant des résines échangeuses de cation. / The purpose of this thesis was to find a way to produce peroxycarboxylic acid from hydrogen peroxide and carboylic acid in a continuous reactor by using heterogeneous catalysts. In the first step the stability of peroxyde species xas studied by using an online analytic method (Mass spectrometer). One of the main challenge was to find a suitable solid acid catalyst, wich does no decompose the peroxyde species and can catalyze the reaction as sulfuric acid. A continuous fixed bed reactor was built by using caion exchange resins as a catalyst.

Priority organic and emerging contaminants are a growing concern for drinking water treatment due to their increasing presence in the environment. This study developed a predictive model for the sorption of anionic organic contaminants from drinking water on three anion exchange resins: a strong polystyrenic (IRA-910), weak polystyrenic (IRA-96), and a strong polacrylic (A860). The model quantifies the individual mechanisms of sorption using poly-parameter linear free energy relationships (pp-LFERs) and the feasibility of phase conversion (e.g., an ideal gas phase as the reference state) for ionic species was examined. To develop the model, a training set of isotherms was obtained using aliphatic and aromatic carboxylates, phenols, anilines, nitrobenzene, and ibuprofen. These compounds were chosen as model organic contaminants in the environment. The training set and 1-3 test compounds (3-methyl-2-nitrobenzoate, phenol, and 4-nitroaniline) were accurately predicted using the created model for each resin. An understanding of the effects of resin structure on sorption interactions was also developed that focused on ionic functional groups, resin matrix, and hydrophilicity (i.e. water content). It was shown that greater sorption efficiency was achieved when electrostatic (ion exchange) and nonelectrostatic (adsorption) interactions were present together to create a synergistic addition. However, sorption on ion exchangers was poor if the pH of the system approached levels lower than the sorbate pKa. Additionally, weak base exchanges lose exchange capacity as pH levels approach resin pKa (IRA-96 pKa = 6.0). Additional contributions to the sorption mechanisms were observed by studying various electron donating/withdrawing functional groups on the contaminants. It was concluded that &#960;-&#960; and H-bonding interactions contributed a greater amount to the nonelectrostatic mechanisms than cavity formation forces and nonspecific forces. A comparison between the three resins showed that IRA-96 (weak base polystyrenic) had a greater removal capacity than IRA-910 (strong base polystyrenic), followed far behind by A860 (strong base polyacrylate). This is due to differences between the resins, such as the hydrophilicity, the density of the ion exchange group, and the presence of aromatic rings within the matrix structure. Although the modeling method accurately predicted the phase change from aqueous to sorbent phases, it was shown that the SPARC calculated aqueous-gas ion transfer energies were poor estimations of the transfer energy to the ideal gas phase and further study is necessary to accurately determine this value. This modeling methodology is believed to be applicable to emerging contaminants such as pharmaceuticals in water systems and helps further new water treatment technologies while developing a mechanistic understanding of electrostatic and nonelectrostatic interactions in general. This can be applied to additional separation processes such as chemical purification and chromatographic separation. / Civil Engineering