The results of the application of a density functional theory method incorporating dispersive corrections in the 2010 crystal structure prediction blind test are reported. The method correctly predicted four out of the six experimental structures. Three of the four correct predictions were found to have the lowest lattice energy of any crystal structure for that molecule. The experimental crystal structures for all six compounds were found during the structure generation phase of the simulations, indicating that the tailor-made force fields used for screening structures were valid and that the structure generation engine, which combines a Monte Carlo parallel tempering algorithm with an efficient lattice energy minimiser, was working effectively. For the three compounds for which the experimental crystal structures did not correspond to the lowest energy structures found, the method for calculating the lattice energy needs to be further refined or there may be other polymorphs that have not yet been found experimentally.

No / A crystal structure prediction (CSP) study of three small, rigid and structurally related organic compounds (differing only in the position and number of methyl groups) is presented. A tailor-made force field (TMFF; a non-transferable force field specific for each molecule) was constructed with the aid of a dispersion-corrected density functional theory method (the hybrid method). Parameters for all energy terms in each TMFF were fitted to reference data generated by the hybrid method. Each force field was then employed during structure generation. The experimentally observed crystal structures of two of the three molecules were found as the most stable crystal packings in the lists of their force-field-optimised structures. A number of the most stable crystal structures were re-optimised with the hybrid method. One experimental crystal structure was still calculated to be the most stable structure, whereas for another compound the experimental structure became the third most stable structure according to the hybrid method. For the third molecule, the experimentally observed polymorph, which was found to be the fourth most stable form using its TMFF, became the second most stable form. Good geometrical agreements were observed between the experimental structures and those calculated by both methods. The average structural deviation achieved by the TMFFs was almost twice that obtained with the hybrid method. The TMFF approach was extended by exploring the accuracy of a more general TMFF (GTMFF), which involved fitting the force-field parameters to the reference data for all three molecules simultaneously. This GTMFF was slightly less accurate than the individual TMFFs but still of sufficient accuracy to be used in CSP. A study of the isostructural relationships between these molecules and their crystal lattices revealed a potential polymorph of one of the compounds that has not been observed experimentally and that may be accessible in a thorough polymorph screen, through seeding, or through the use of a suitable tailor-made additive.

no / A crystal ball? A new method for crystal structure prediction combines a tailor-made force field with a density functional theory method incorporating a van der Waals correction for dispersive interactions. In a blind test, the method predicts the correct crystal structure for all four compounds, one of which is a cocrystal. The picture shows the predicted structure of one of the compounds in green and the experimental structure in blue.

The knowledge of the packing behaviour of small organic compounds in crystal lattices is of great importance for industries dealing with solid state materials. The properties of materials depend on how the molecules arrange themselves in a crystalline environment. Crystal structure prediction provides a theoretical approach through the application of computational strategies to seek possible crystal packing arrangements (or polymorphs) a compound may adopt. Based on the chemical diagrams, this thesis investigates polymorphism of several small organic compounds. Plausible crystal packings of those compounds are generated, and their lattice energies are minimised using molecular mechanics and/or quantum mechanics methods. Most of the work presented here is conducted using two software packages commercially available in this field, Polymorph Predictor of Materials Studio 4.0 and GRACE 1.0. In general, the computational techniques implemented in GRACE are very good at reproducing the geometries of the crystal structures corresponding to the experimental observations of the compounds, in addition to describing their solid state energetics correctly. Complementing the CSP results obtained using GRACE with isostructurality offers a route by which new potential polymorphs of the targeted compounds might be crystallised using the existing experimental data. Based on all calculations in this thesis, four new potential polymorphs for four different compounds, which have not yet been determined experimentally, are predicted to exist and may be obtained under the right crystallisation conditions. One polymorph is expected to crystallise under pressure. The remaining three polymorphs might be obtained by using a seeding technique or the utilisation of suitable tailor made additives. / University of Bradford

No description available.

We use molecular mechanics (MM) simulations with the tight-binding (TB) potential to study local and global instabilities in initially defect-free finite specimens of gold crystals deformed in shear, simple shear, tension/compression, simple tension/compression, and triaxial tension/compression. The criteria used to delineate local instabilities in a system include the following: (i) a second order spatial derivative of the displacement field having large values relative to its average value in the body, (ii) the minimum eigenvalue of the Hessian of the potential energy of an atom becoming nonpositive, (iii) and structural changes represented by a high value of the common neighborhood parameter. A specimen becomes globally unstable when its potential energy decreases significantly with a small increase in its deformations. It is found that the three criteria for local instability are satisfied essentially simultaneously at the same atomic position. Deformations of a specimen are quite different when it is deformed with some bounding surfaces free from external forces as opposed to essential boundary conditions prescribed on all bounding surfaces. It is found that the initial unloaded configuration (or the reference configuration) of the minimum potential energy has significant in-plane stresses on the bounding surfaces and nonzero normal stresses at interior points. In tensile/compressive deformations of a rectangular prismatic nanobar the yield stress defined as the average axial stress when the average axial stress vs. the average axial strain curve exhibits a sharp discontinuity depends upon the specimen size; a similar result holds for simulations of shear deformations. Specimens deformed with essential boundary conditions on all bounding surfaces experience instabilities at a higher value of the average strain than identical specimens deformed similarly but with one or more pairs of opposite bounding surfaces traction free. For the former set of deformations, the response of a specimen prior to the onset of instability is the same as that of a hyperelastic body with the strain energy derived from the TB potential and deformations obeying the Cauchy-Born rule. Specimens with some traction free bounding surfaces experience local instabilities prior to the onset of a global instability but the two instabilities occur simultaneously in specimens with essential boundary conditions prescribed on all bounding surfaces. It is believed that because of residual stresses in the reference configuration, the average axial stress at yield in compression is nearly one-half of that in tension. / Ph. D.

The knowledge of the packing behaviour of small organic compounds in crystal lattices is of great importance for industries dealing with solid state materials. The properties of materials depend on how the molecules arrange themselves in a crystalline environment. Crystal structure prediction provides a theoretical approach through the application of computational strategies to seek possible crystal packing arrangements (or polymorphs) a compound may adopt. Based on the chemical diagrams, this thesis investigates polymorphism of several small organic compounds. Plausible crystal packings of those compounds are generated, and their lattice energies are minimised using molecular mechanics and/or quantum mechanics methods. Most of the work presented here is conducted using two software packages commercially available in this field, Polymorph Predictor of Materials Studio 4.0 and GRACE 1.0. In general, the computational techniques implemented in GRACE are very good at reproducing the geometries of the crystal structures corresponding to the experimental observations of the compounds, in addition to describing their solid state energetics correctly. Complementing the CSP results obtained using GRACE with isostructurality offers a route by which new potential polymorphs of the targeted compounds might be crystallised using the existing experimental data. Based on all calculations in this thesis, four new potential polymorphs for four different compounds, which have not yet been determined experimentally, are predicted to exist and may be obtained under the right crystallisation conditions. One polymorph is expected to crystallise under pressure. The remaining three polymorphs might be obtained by using a seeding technique or the utilisation of suitable tailor made additives.

Numerous enzymatic reactions are controlled by the chemistry of metallic ions. This dissertation investigates the electronic properties of three transition metal (copper, chromium, and nickel) complexes and describes modeling studies performed on glutathione synthetase. (1) Copper nitrene complexes were computationally characterized, as these complexes have yet to be experimentally isolated. (2) Multireference calculations were carried out on a symmetric C2v chromium dimer derived from the crystal structure of the [(tBu3SiO)Cr(µ-OSitBu3)]2 complex. (3) The T-shaped geometry of a three-coordinate β-diketiminate nickel(I) complex with a CO ligand was compared and contrasted with isoelectronic and isosteric copper(II) complexes. (4) Glutathione synthetase (GS), an enzyme that belongs to the ATP-grasp superfamily, catalyzes the (Mg, ATP)-dependent biosynthesis of glutathione (GSH) from γ-glutamylcysteine and glycine. The free and reactant forms of human GS (wild-type and glycine mutants) were modeled computationally by employing molecular dynamics simulations, as these currently have not been structurally characterized.

Com o avanço do poder computacional nas últimas décadas, a modelagem molecular de problemas em diversas áreas se tornou mais acessível, sendo hoje uma ferramenta fundamental para o entendimento de diversos processos. Em especial, simulações moleculares com campos de força clássicos vem sendo importante para a amostragem de propriedades termodinâmicas, para a determinação de estruturas e população de confôrmeros, e seleção de configurações para utilização com métodos que combinam mecânica quântica com mecânica molecular. Os principais métodos de simulação atualmente utilizados são a dinâmica molecular (MD, do inglês molecular dynamics) e o Monte Carlo (MC). Ambos os métodos são a princípio equivalentes quando o objetivo é a amostragem configuracional, tendo a MD a vantagem de permitir a análise da dinâmica e evolução temporal, e o MC a vantagem de poder gerar configurações de forma probabilística, sem a necessidade de seguir um caminho sobre a superfície de energia potencial, o que pode resultar em uma amostragem mais eficiente. Contudo, não há ainda uma metodologia de MC que possa ser considerada eficiente e bem estabelecida para a amostragem dos graus de liberdade internos de moléculas com complexidade arbitrária. Visando avançar no desenvolvimento de métodos que trabalham nesse sentido, neste trabalho o método apresentado por Shah e Maginn [1] foi implementado e aprimorado. No método, a molécula é fragmentada em partes menores, formadas de graus de liberdade rígidos, que não variam drasticamente durante a simulação. Esses fragmentos por sua vez são conectadas por graus de liberdade maleáveis, os diedros e termos não ligados da energia. Durante a simulação a molécula tem fragmentos apagados, e então é reconstruída utilizando um esquema de Configurational Bias Monte Carlo (CBMC). A contribuição deste trabalho para a metodologia consiste em generalizar os tipos de fragmentos possíveis dentro do método, a simplificação do critério de aceitação e extensões com vieses adicionais, como é o caso do viés no potencial eletrostático e no critério de aceitação da amostragem preferencial com o CBMC. A validade da implementação do método foi avaliada através de simulações em dois sistemas simples: o octano e o 1,2-dicloroetano. Comparando a amostragem e os resultados obtidos para as populações de confôrmeros com resultados de MD e experimentais ou obtidos com outros métodos de MC da literatura foi possível verificar que a implementação reproduz os resultados esperados. Além disso, o equilíbrio conformacional da molécula de óxido mesityl (MOx) que possui duas conformações: syn e anti, foi estudado. Graças a barreira de potencial entre as duas conformações de cerca de 10 kcal/mol, a MD não é capaz de realizar uma amostragem ergódica, enquanto o CBMC realiza a amostragem sem problemas. Na simulação CBMC, a inversão da população dominante em fase gasosa e em água foi observada. Simulações do MOx em acetonitrila e metanol mostraram que a população de confôrmeros anti de fato aumenta conforme a polaridade do solvente. Entretanto, devido ao estiramento da ligação C = O do MOx em metanol devido as ligações de hidrogênio, a contribuição conformacional à posição do máximo da banda de absorção não segue a tendência da polaridade, tendo um deslocamento para o azul maior na acetonitrila do que em metanol. O estiramento da ligação C = O só pode ser observado graças a introdução da amostragem de fragmentos com deslocamentos Cartesianos e algoritmo de Metropolis ao método CBMC original. Esse efeito devido ao estiramento é compensado pelo efeito solvente, de modo que a contribuição total à energia de transição segue a polaridade do solvente. De uma maneira geral, concluímos que o desempenho do método CBMC utilizado é excelente para os casos estudados, e é inclusive superior ao da MD em alguns casos. A implementação no software DICE deixa um legado importante para diversos grupos de pesquisa, não somente por introduzir o CBMC, mas também por melhorias gerais como paralelização, lista de vizinhos e modernização do código, que foram introduzidas ao decorrer do projeto. / With the increase of computational power in the last decades, the molecular modeling of problems in several areas has become more accessible, being today a fundamental tool used to understand several processes. In particular, molecular simulations with classical force fields have been important for the sampling of thermodynamic properties, for the determination of structures and population of conformers, and for the selection of configurations to be used with methods that combine quantum mechanics with molecular mechanics. The most common simulation methods used nowadays are molecular dynamics (MD) and Monte Carlo (MC). Both methods are in principle equivalent when the goal is configurational sampling, with MD having the advantage of allowing the analysis of the dynamics and temporal evolution, while MC has the advantage of generating the configurations in a probabilistic manner, not necessarily following a path in the potential energy surface, possibly resulting in a more efficient sampling. However, there is no MC methodology that can be considered efficient and established to sample the internal degrees of freedom of molecules with arbitrary complexity. In order to advance in the development of methods that want to achieve this goal, in this work the method presented by Shah e Maginn [1] has been implemented and improved. In the method, the molecule is fragmented into smaller parts, each one composed by the hard degrees of freedom, which do not vary dramatically during the simulation. Those fragments are then connected by soft degrees of freedom, the dihedral and non-bonded terms of the energy. During the simulation the molecule has some of its fragments deleted, and is reconstructed using a Configurational Bias Monte Carlo (CBMC) approach. The contribution of this work to the methodology is generalizing the fragment types within the method, the simplification of the acceptance criteria and some extensions with additional biases, such as electrostatic potential bias and the acceptance criterion of the preferential sampling with the CBMC. The implementation was evaluated through simulations in two simple systems: octane and 1,2-dichloroethane. Comparing the sampling and results obtained for the populations of conformers with MD results, experimental data or values obtained with different MC methods present in the literature, we verified that the implementation reproduces the expected results. Beyond that, the conformational equilibrium of the mesityl oxide (MOx) molecule which has two conformers: syn and anti, was investigated. Due to the potential energy barrier between the two conformers of about 10 kcal/mol, the MD does not perform an ergodic simulation, while the CBMC does the same sampling accordingly. In the CBMC simulation, the inversion of the dominant conformer in gas phase and water was observed. The MOx simulation in acetonitrile and methanol showed that the frequency of the anti conformer indeed increases with the solvent polarity. Nonetheless, due to the stretch of the C = O bond of MOx in methanol, attributed to the hydrogen bonds formed with the solvent, the conformational contribution to the maximum of the absorption band does not follow the polarity tendency, having a larger blue shift in acetonitrile than in methanol. The C = O bond stretch can only be seen because the Cartesian displacement sampling with the Metropolis method was introduced to the original CBMC method. This effect attributed to the stretch is compensated by the solvent, in a way that the total contribution to the transition energy follows the solvent polarity. In general, we conclude that the performance of the developed CBMC method is excellent to the studied cases, being even superior to MD in some cases. The implementation in DICE leaves an important legacy to several research groups, not only for introducing the CBMC method, but also due to general improvements such as parallelization, neighbor list and code modernization, which were introduced during the project.

Com o avanço do poder computacional nas últimas décadas, a modelagem molecular de problemas em diversas áreas se tornou mais acessível, sendo hoje uma ferramenta fundamental para o entendimento de diversos processos. Em especial, simulações moleculares com campos de força clássicos vem sendo importante para a amostragem de propriedades termodinâmicas, para a determinação de estruturas e população de confôrmeros, e seleção de configurações para utilização com métodos que combinam mecânica quântica com mecânica molecular. Os principais métodos de simulação atualmente utilizados são a dinâmica molecular (MD, do inglês molecular dynamics) e o Monte Carlo (MC). Ambos os métodos são a princípio equivalentes quando o objetivo é a amostragem configuracional, tendo a MD a vantagem de permitir a análise da dinâmica e evolução temporal, e o MC a vantagem de poder gerar configurações de forma probabilística, sem a necessidade de seguir um caminho sobre a superfície de energia potencial, o que pode resultar em uma amostragem mais eficiente. Contudo, não há ainda uma metodologia de MC que possa ser considerada eficiente e bem estabelecida para a amostragem dos graus de liberdade internos de moléculas com complexidade arbitrária. Visando avançar no desenvolvimento de métodos que trabalham nesse sentido, neste trabalho o método apresentado por Shah e Maginn [1] foi implementado e aprimorado. No método, a molécula é fragmentada em partes menores, formadas de graus de liberdade rígidos, que não variam drasticamente durante a simulação. Esses fragmentos por sua vez são conectadas por graus de liberdade maleáveis, os diedros e termos não ligados da energia. Durante a simulação a molécula tem fragmentos apagados, e então é reconstruída utilizando um esquema de Configurational Bias Monte Carlo (CBMC). A contribuição deste trabalho para a metodologia consiste em generalizar os tipos de fragmentos possíveis dentro do método, a simplificação do critério de aceitação e extensões com vieses adicionais, como é o caso do viés no potencial eletrostático e no critério de aceitação da amostragem preferencial com o CBMC. A validade da implementação do método foi avaliada através de simulações em dois sistemas simples: o octano e o 1,2-dicloroetano. Comparando a amostragem e os resultados obtidos para as populações de confôrmeros com resultados de MD e experimentais ou obtidos com outros métodos de MC da literatura foi possível verificar que a implementação reproduz os resultados esperados. Além disso, o equilíbrio conformacional da molécula de óxido mesityl (MOx) que possui duas conformações: syn e anti, foi estudado. Graças a barreira de potencial entre as duas conformações de cerca de 10 kcal/mol, a MD não é capaz de realizar uma amostragem ergódica, enquanto o CBMC realiza a amostragem sem problemas. Na simulação CBMC, a inversão da população dominante em fase gasosa e em água foi observada. Simulações do MOx em acetonitrila e metanol mostraram que a população de confôrmeros anti de fato aumenta conforme a polaridade do solvente. Entretanto, devido ao estiramento da ligação C = O do MOx em metanol devido as ligações de hidrogênio, a contribuição conformacional à posição do máximo da banda de absorção não segue a tendência da polaridade, tendo um deslocamento para o azul maior na acetonitrila do que em metanol. O estiramento da ligação C = O só pode ser observado graças a introdução da amostragem de fragmentos com deslocamentos Cartesianos e algoritmo de Metropolis ao método CBMC original. Esse efeito devido ao estiramento é compensado pelo efeito solvente, de modo que a contribuição total à energia de transição segue a polaridade do solvente. De uma maneira geral, concluímos que o desempenho do método CBMC utilizado é excelente para os casos estudados, e é inclusive superior ao da MD em alguns casos. A implementação no software DICE deixa um legado importante para diversos grupos de pesquisa, não somente por introduzir o CBMC, mas também por melhorias gerais como paralelização, lista de vizinhos e modernização do código, que foram introduzidas ao decorrer do projeto. / With the increase of computational power in the last decades, the molecular modeling of problems in several areas has become more accessible, being today a fundamental tool used to understand several processes. In particular, molecular simulations with classical force fields have been important for the sampling of thermodynamic properties, for the determination of structures and population of conformers, and for the selection of configurations to be used with methods that combine quantum mechanics with molecular mechanics. The most common simulation methods used nowadays are molecular dynamics (MD) and Monte Carlo (MC). Both methods are in principle equivalent when the goal is configurational sampling, with MD having the advantage of allowing the analysis of the dynamics and temporal evolution, while MC has the advantage of generating the configurations in a probabilistic manner, not necessarily following a path in the potential energy surface, possibly resulting in a more efficient sampling. However, there is no MC methodology that can be considered efficient and established to sample the internal degrees of freedom of molecules with arbitrary complexity. In order to advance in the development of methods that want to achieve this goal, in this work the method presented by Shah e Maginn [1] has been implemented and improved. In the method, the molecule is fragmented into smaller parts, each one composed by the hard degrees of freedom, which do not vary dramatically during the simulation. Those fragments are then connected by soft degrees of freedom, the dihedral and non-bonded terms of the energy. During the simulation the molecule has some of its fragments deleted, and is reconstructed using a Configurational Bias Monte Carlo (CBMC) approach. The contribution of this work to the methodology is generalizing the fragment types within the method, the simplification of the acceptance criteria and some extensions with additional biases, such as electrostatic potential bias and the acceptance criterion of the preferential sampling with the CBMC. The implementation was evaluated through simulations in two simple systems: octane and 1,2-dichloroethane. Comparing the sampling and results obtained for the populations of conformers with MD results, experimental data or values obtained with different MC methods present in the literature, we verified that the implementation reproduces the expected results. Beyond that, the conformational equilibrium of the mesityl oxide (MOx) molecule which has two conformers: syn and anti, was investigated. Due to the potential energy barrier between the two conformers of about 10 kcal/mol, the MD does not perform an ergodic simulation, while the CBMC does the same sampling accordingly. In the CBMC simulation, the inversion of the dominant conformer in gas phase and water was observed. The MOx simulation in acetonitrile and methanol showed that the frequency of the anti conformer indeed increases with the solvent polarity. Nonetheless, due to the stretch of the C = O bond of MOx in methanol, attributed to the hydrogen bonds formed with the solvent, the conformational contribution to the maximum of the absorption band does not follow the polarity tendency, having a larger blue shift in acetonitrile than in methanol. The C = O bond stretch can only be seen because the Cartesian displacement sampling with the Metropolis method was introduced to the original CBMC method. This effect attributed to the stretch is compensated by the solvent, in a way that the total contribution to the transition energy follows the solvent polarity. In general, we conclude that the performance of the developed CBMC method is excellent to the studied cases, being even superior to MD in some cases. The implementation in DICE leaves an important legacy to several research groups, not only for introducing the CBMC method, but also due to general improvements such as parallelization, neighbor list and code modernization, which were introduced during the project.