The goal of this study was to develop a simple means of estimating the cosolvent/water solubility profile using just the available properties (logKow, dielectric constant etc.) of the solute, cosolvent and water. Ethanol was used as the model cosolvent.One of the most commonly used polarity indicators is the octanol/water partition coefficient (logKow). Numerous programs are used to predict the logKow. The calculated values of logKow from three of the most commonly used programs ClogP®, ACD/logPdb® and KowWin® were compared to experimental values. It was found that all three programs have a user friendly interface but ClogP appears to be more accurate.While the ethanol/water solubility profiles of very polar and very non-polar drugs are monotonic, many semi-polar drugs show a maximum solubility at an ethanol volume fraction (fmax) between zero and one. A new empirical function that describes this deviation from linearity was applied to the experimental data forfifty-one compounds. The proposed model was a more accurate predictor of the co-solvent solubility profile than a general third order polynomial with the samenumber of parameters. The fmax value was also accurately predicted from the first derivative of the model.A sigmoidal relationship was observed between the value of fmax and logKow of the solute. Combining this sigmoidal relationship with the previously reportedlinear relationship between logKow and the initial slope of the plot of log solubility vs. ethanol composition enables the estimation of the totalethanol/water solubility profiles of semi-polar compounds from just logKow.A new bilinear function was also introduced to address the deviation from linearity. This model accounts for both the initial and terminal slopes in theethanol/water solubility profiles of semi-polar solutes. The proposed model is dependent only on logKow and an empirical constant that is cosolvent specific. It is also more accurate than the log-linear model and a general parabolic model.A solubility case study using Antalarmin, a novel stress inhibitor was performed.This study illustrates the use of cosolvents as solubility enhancers as well as pH,surfactants, complexants and lipid based systems.

Os estudos de impacto ambiental em sistemas aquáticos são de grande importância, tanto no âmbito social quanto no econômico. Estes têm que contemplar a avaliação dos danos produzidos pelos mais variados tipos de substâncias, criando a necessidade de conhecer a ação destas ao sistema em questão. O resultado da interação de substâncias com o ambiente pode ser explorado por meio de experimentos envolvendo o coeficiente de partição octanol/água (Kow). A escolha do Kow se deve ao fato deste se relacionar a interação do composto escolhido com o meio, no que diz respeito à absorção e transporte. No caso deste trabalho, uma série de fenóis foi estudada em termos do coeficiente de partição. Cálculos teóricos foram realizados como alternativa para mensuração experimental do coeficiente de partição octanol/água. A elaboração de modelos QSAR (Quantitative Structure Activity Relationship) para a previsão de valores de coeficiente de partição octanol/água foi realizado por meio de cálculos envolvendo física quântica e quimiometria. Os dados das variáveis foram obtidos para o grupo de fenóis em questão utilizando os métodos de cálculos semiempíricos AM1, PM3, PM6 e PM7. A comparação dos modelos QSAR obtidos permitiu a conclusão de que, para os descritores selecionados, o conjunto de valores obtidos com o método PM7 proporcionou a criação dos melhores modelos. Utilizando como variáveis selecionadas energia eletrônica, área molecular, volume molecular, energia de repulsão core-core e massa molecular, obteve-se um modelo que acumulava aproximadamente 99,99% de toda a informação em três componentes, com um coeficiente de correlação externo (referente à calibração) em torno de 0,93, o que indica a força preditiva do modelo. A relação da toxicidade com o Índice de Qualidade das Águas também foi investigado por meio da relação dos valores LogKow obtidos e pH. Com o pKa de cada fenol proveniente de dados teóricos (e fazendo uso da relação de pKa e pH proposta por Henderson-Hasselbach), pode-se concluir que não existe influência intrínseca dos valores de LogKow nos valores de pH, verificado com o baixo coeficiente de correlação entre as variáveis, em torno de 0,15. / The environmental impact on aquatic systems are of great importance, both in the social sphere as the economic. These must include the assessment of the damage caused by all sorts of substances, creating the need to know the action of these to the system in question. The result of the interaction of substances with the environment can be explored through experiments involving octanol / water partition coefficient (Kow). The choice of Kow is due to relate the interaction of the compound with the chosen medium, as regards the absorption and transport. In the case of this work, a number of phenols was studied in terms of the partition coefficient. Theoretical calculations have been performed as an alternative to experimental measurement of octanol / water partition. The use of models QSAR (Quantitative Structure Activity Relationship) for predicting values of octanol / water partition was made by means of calculations involving quantum physics and chemometrics. The data for each variable were obtained for the group concerned phenols using the semi-empirical calculation methods AM1, PM3, PM6 and PM7. A comparison of the obtained QSAR models allowed the conclusion that, for the selected descriptors, a set of values obtained with the method provided PM7 the creation of the best models. Using as selected electronic energy, molecular area, molecular volume, core-core repulsion energy and molecular mass variables, we obtained a model that accumulated approximately 99.99% of all information in three components, with an external correlation coefficient (referring to the calibration) around 0,93, which shows the predictive power of the model. The relationship of toxicity with the Water Quality Index was also investigated by means of the relation of LogKow values obtained and pH. With the pKa of the phenol from each theoretical data (and using the relationship of pKa and pH proposed by Henderson-Hasselbach), it can be concluded that there is no influence of intrinsic values LogKow in pH checked with low coefficient correlation between the variables, around 0,15.

Os estudos de impacto ambiental em sistemas aquáticos são de grande importância, tanto no âmbito social quanto no econômico. Estes têm que contemplar a avaliação dos danos produzidos pelos mais variados tipos de substâncias, criando a necessidade de conhecer a ação destas ao sistema em questão. O resultado da interação de substâncias com o ambiente pode ser explorado por meio de experimentos envolvendo o coeficiente de partição octanol/água (Kow). A escolha do Kow se deve ao fato deste se relacionar a interação do composto escolhido com o meio, no que diz respeito à absorção e transporte. No caso deste trabalho, uma série de fenóis foi estudada em termos do coeficiente de partição. Cálculos teóricos foram realizados como alternativa para mensuração experimental do coeficiente de partição octanol/água. A elaboração de modelos QSAR (Quantitative Structure Activity Relationship) para a previsão de valores de coeficiente de partição octanol/água foi realizado por meio de cálculos envolvendo física quântica e quimiometria. Os dados das variáveis foram obtidos para o grupo de fenóis em questão utilizando os métodos de cálculos semiempíricos AM1, PM3, PM6 e PM7. A comparação dos modelos QSAR obtidos permitiu a conclusão de que, para os descritores selecionados, o conjunto de valores obtidos com o método PM7 proporcionou a criação dos melhores modelos. Utilizando como variáveis selecionadas energia eletrônica, área molecular, volume molecular, energia de repulsão core-core e massa molecular, obteve-se um modelo que acumulava aproximadamente 99,99% de toda a informação em três componentes, com um coeficiente de correlação externo (referente à calibração) em torno de 0,93, o que indica a força preditiva do modelo. A relação da toxicidade com o Índice de Qualidade das Águas também foi investigado por meio da relação dos valores LogKow obtidos e pH. Com o pKa de cada fenol proveniente de dados teóricos (e fazendo uso da relação de pKa e pH proposta por Henderson-Hasselbach), pode-se concluir que não existe influência intrínseca dos valores de LogKow nos valores de pH, verificado com o baixo coeficiente de correlação entre as variáveis, em torno de 0,15. / The environmental impact on aquatic systems are of great importance, both in the social sphere as the economic. These must include the assessment of the damage caused by all sorts of substances, creating the need to know the action of these to the system in question. The result of the interaction of substances with the environment can be explored through experiments involving octanol / water partition coefficient (Kow). The choice of Kow is due to relate the interaction of the compound with the chosen medium, as regards the absorption and transport. In the case of this work, a number of phenols was studied in terms of the partition coefficient. Theoretical calculations have been performed as an alternative to experimental measurement of octanol / water partition. The use of models QSAR (Quantitative Structure Activity Relationship) for predicting values of octanol / water partition was made by means of calculations involving quantum physics and chemometrics. The data for each variable were obtained for the group concerned phenols using the semi-empirical calculation methods AM1, PM3, PM6 and PM7. A comparison of the obtained QSAR models allowed the conclusion that, for the selected descriptors, a set of values obtained with the method provided PM7 the creation of the best models. Using as selected electronic energy, molecular area, molecular volume, core-core repulsion energy and molecular mass variables, we obtained a model that accumulated approximately 99.99% of all information in three components, with an external correlation coefficient (referring to the calibration) around 0,93, which shows the predictive power of the model. The relationship of toxicity with the Water Quality Index was also investigated by means of the relation of LogKow values obtained and pH. With the pKa of the phenol from each theoretical data (and using the relationship of pKa and pH proposed by Henderson-Hasselbach), it can be concluded that there is no influence of intrinsic values LogKow in pH checked with low coefficient correlation between the variables, around 0,15.

Machine learning and artificial intelligence are increasingly becoming mainstream in our daily lives, from smart algorithms that recognize us online to cars that can drive themselves. In this defense, the intersection of machine learning and computational chemistry are applied to the generation of new PFAS molecules that are less toxic than those currently used today without sacrificing the unique properties that make them desirable for industrial use. Additionally, machine learning is used to complete the SAMPL6 logP challenge and to correlate molecules to best DFT functionals for enthalpies of formation.

In this work, we design parallel Monte Carlo algorithms for the Ising spin model on a hierarchical cluster. A hierarchical cluster can be considered as a cluster of homogeneous nodes which are partitioned into multiple supernodes such that communication across homogenous clusters is represented by a supernode topological network. We consider different data layouts and provide equations for choosing the best data layout under such a network paradigm. We show that the data layouts designed for a homogeneous cluster will not yield results as good as layouts designed for a hierarchical cluster. We derive theoretical results on the performance of the algorithms on a modified version of the LogP model that represents such tiered networking, and present simulation results to analyze the utility of the theoretical design and analysis. Furthermore, we consider the 3-D Ising model and design parallel algorithms for sweep spin selection on both homogeneous and hierarchical clusters. We also discuss the simulation of hierarchical clusters on a homogeneous set of machines, and the efficient implementation of the parallel Ising model on such clusters. / Master of Science

The performance of collective communication operations is one of the deciding factors in the overall performance of a MPI application. Open MPI's component architecture offers an easy way to implement new algorithms for collective operations, but current implementations use the point-to-point components to access the InfiniBand network. Therefore it is tried to improve the performance of a collective component by accessing the InfiniBand network directly. This should avoid overhead and make it possible to tune the algorithms to this specific network. The first part of this work gives a short overview of the InfiniBand Architecture and Open MPI. In the next part several models for parallel computation are analyzed. Afterwards various algorithms for the MPI_Scatter, MPI_Gather and MPI_Allgather operations are presented. The theoretical performance of the algorithms is analyzed with the LogfP and LogGP models. Selected algorithms are implemented as part of an Open MPI collective component. Finally the performance of different algorithms and different MPI implementations is compared. The test results show, that the performance of the operations could be improved for several message and communicator size ranges.

The problem of efficient parallelization of 2D Ising spin systems requires realistic algorithmic design and implementation based on an understanding of issues from computer science and statistical physics. In this work, we not only consider fundamental parallel computing issues but also ensure that the major constraints and criteria of 2D Ising spin systems are incorporated into our study. This realism in both parallel computation and statistical physics has rarely been reflected in previous research for this problem. In this thesis,we designed and implemented a variety of parallel algorithms for both sweep spin selection and random spin selection. We analyzed our parallel algorithms on a portable and general parallel machine model, namely the LogP model. We were able to obtain rigorous theoretical run-times on LogP for all the parallel algorithms. Moreover, a guiding equation was derived for choosing data layouts (blocked vs. stripped) for sweep spin selection. In regards to random spin selection, we were able to develop parallel algorithms with efficient communication schemes. We analyzed randomness of our schemes using statistical methods and provided comparisons between the different schemes. Furthermore, algorithms were implemented and performance data gathered and analyzed in order to determine further design issues and validate theoretical analysis. / Master of Science

The MPI_Barrier-collective operation, as a part of the MPI-1.1 standard, is extremely important for all parallel applications using it. The latency of this operation increases the application run time and can not be overlaid. Thus, the whole MPI performance can be decreased by unsatisfactory barrier latency. The main goals of this work are to lower the barrier latency for InfiniBand networks by analyzing well known barrier algorithms with regards to their suitability within InfiniBand networks, to enhance the barrier operation by utilizing standard InfiniBand operations as much as possible, and to design a constant time barrier for InfiniBand with special hardware support. This partition into three main steps is retained throughout the whole thesis. The first part evaluates publicly known models and proposes a new more accurate model (LoP) for InfiniBand. All barrier algorithms are evaluated within the well known LogP and this new model. Two new algorithms which promise a better performance have been developed. A constant time barrier integrated into InfiniBand as well as a cheap separate barrier network is proposed in the hardware section. All results have been implemented inside the Open MPI framework. This work led to three new Open MPI collective modules. The first one implements different barrier algorithms which are dynamically benchmarked and selected during the startup phase to maximize the performance. The second one offers a special barrier implementation for InfiniBand with RDMA and performs up to 40% better than the best solution that has been published so far. The third implementation offers a constant time barrier in a separate network, leveraging commodity components, with a latency of only 2.5 microseconds. All components have their specialty and can be used to enhance the barrier performance significantly.

The performance of collective communication operations is one of the deciding factors in the overall performance of a MPI application. Open MPI's component architecture offers an easy way to implement new algorithms for collective operations, but current implementations use the point-to-point components to access the InfiniBand network. Therefore it is tried to improve the performance of a collective component by accessing the InfiniBand network directly. This should avoid overhead and make it possible to tune the algorithms to this specific network. The first part of this work gives a short overview of the InfiniBand Architecture and Open MPI. In the next part several models for parallel computation are analyzed. Afterwards various algorithms for the MPI_Scatter, MPI_Gather and MPI_Allgather operations are presented. The theoretical performance of the algorithms is analyzed with the LogfP and LogGP models. Selected algorithms are implemented as part of an Open MPI collective component. Finally the performance of different algorithms and different MPI implementations is compared. The test results show, that the performance of the operations could be improved for several message and communicator size ranges.

The MPI_Barrier-collective operation, as a part of the MPI-1.1 standard, is extremely important for all parallel applications using it. The latency of this operation increases the application run time and can not be overlaid. Thus, the whole MPI performance can be decreased by unsatisfactory barrier latency. The main goals of this work are to lower the barrier latency for InfiniBand networks by analyzing well known barrier algorithms with regards to their suitability within InfiniBand networks, to enhance the barrier operation by utilizing standard InfiniBand operations as much as possible, and to design a constant time barrier for InfiniBand with special hardware support. This partition into three main steps is retained throughout the whole thesis. The first part evaluates publicly known models and proposes a new more accurate model (LoP) for InfiniBand. All barrier algorithms are evaluated within the well known LogP and this new model. Two new algorithms which promise a better performance have been developed. A constant time barrier integrated into InfiniBand as well as a cheap separate barrier network is proposed in the hardware section. All results have been implemented inside the Open MPI framework. This work led to three new Open MPI collective modules. The first one implements different barrier algorithms which are dynamically benchmarked and selected during the startup phase to maximize the performance. The second one offers a special barrier implementation for InfiniBand with RDMA and performs up to 40% better than the best solution that has been published so far. The third implementation offers a constant time barrier in a separate network, leveraging commodity components, with a latency of only 2.5 microseconds. All components have their specialty and can be used to enhance the barrier performance significantly.