The processes by which anisotropic colloidal and nanoscale particles may come together to form ordered monodisperse structures are not well understood. The canonical example of such a system is provided by the assembly of virus capsids, in which tens to thousands of particles of one or a few types assemble efficiently into ordered, highly symmetrical shells. Other examples include a wide variety of protein oligomers, and there is interest in producing analogous systems of synthetic particles. In this thesis I study the self-assembly of simple model particles, consisting of spheres decorated with attractive patches. I consider in detail the assembly of clusters of particles corresponding to the Platonic solids. For the majority of these structures assembly is found to be efficient over a wide range of parameter space. The optimal conditions represent a compromise between thermodynamic stability and kinetic accessibility. We consider two versions of the model, with and without constraints on the torsion angle of bound particles. In both cases the structures with triangular faces are found to assemble most easily. In the absence of torsional constraints dodecahedra will not assemble under any set of parameters as a result of the preferential formation of disordered aggregates. With torsional constraints included all of the Platonic solids assemble successfully and the behaviour of the model is considerably changed. In particular disordered aggregates become far less favourable. I explore possible methods of assembling larger structures, either via “hierarchical” assembly where small clusters are first assembled and then used as building blocks in another stage of assembly, or by a templating method in which an inner cluster acts as a template for a larger outer cluster. These approaches are studied using the “Virtual Move Monte Carlo” cluster move algorithm, the behaviour of which we examine in some detail.

This thesis is concerned with furthering our understanding of the basis of visible region photocatalytic activity exhibited by doped TiO2-based materials. A range of experimental techniques including high resolution X-ray photoemission spectroscopy and diffuse reflectance spectroscopy are used to investigate electronic structure and an attempt is made to link these results to the observed photocatalytic activity. Both anionic (N) and cationic (Rh and Sn) dopants are investigated. [See pdf file for full abstract].

The behaviour of colloidal particles in two-dimensional (2D) systems is addressed in real space and time using magnetic fields, optical tweezers and optical video microscopy. First, the fluctuations of a grain boundary in a 2D colloidal crystal are analysed. A real space analogue of the capillary fluctuation method is derived and successfully employed to extract the key parameters that characterise the grain boundary. Good agreement is also found with a fluctuation-dissipation based method recently suggested in simulation. Following on from analysis of the interface fluctuations, the properties of the individual grain boundary particles are analysed to investigate the long standing hypothesis that suggests that grain boundary particle dynamics are similar to those in supercooled liquids. The grain boundary particle dynamics display cage breaking at long times, highly heterogeneous particle dynamics and the formation of cooperatively moving regions along the interface, all typical behaviour of a supercooled liquid. Next, the frustration induced by confining colloidal particles inside a pentagonal environment is investigated. The state of the system is adjusted via two separate control parameters: the inter-particle interaction potential and the number density. A gradual crystalline to confined liquid-like transition is observed as the repulsive inter-particle interaction potential is decreased. In contrast, re-entrant orientational ordering and dynamical effects result as the number density of the confined colloidal particles is increased. Finally, the dynamics of colloidal particles distributed amongst a random array of fixed obstacle particles is probed as a function of both the mobile particle and fixed obstacle particle number densities. Increasing the mobile and the obstacle particle number density drives the system towards a glass transition. The dynamics of the free particles are shown to behave in a similar way to the normal glass transition at low obstacle density and more analogous to a localisation glass transition at high obstacle density.

Amperometric gas sensors are widely used for environmental and industrial monitoring. They are sensitive and cheap but suffer from some significant limitations. The aim of the work undertaken in this thesis is the development of ‘intelligent’ gas sensors to overcome some of these limitations. Overall the thesis shows the value of ionic liquids as potential solvents for gas sensors, overcoming issues of solvent volatility and providing a wide potential range for electrochemical measurements. Methods have been developed for sensitive amperometry, the tuning of potentials and especially proof-of-concept (patents Publication numbers: WO2013140140 A3 and WO2014020347 A1) in respect of the intelligent self-monitoring of temperature and humidity by RTIL based sensors. Designs for practical electrodes are also proposed. The specific content is as follows. Chapter 1 outlines the fundamental principles of electrochemistry which are of importance for the reading of this thesis. Chapter 2 reviews the history and modern amperometric gas sensors. Limitations of present electrochemical approaches are critically established. Micro-electrodes and Room Temperature Ionic Liquids (RTILs) are also introduced in this chapter. Chapter 4 is focused on the study of analysing chronoamperometry using the Shoup and Szabo equation to simultaneously determine the values of concentration and diffusion coefficient of dissolved analytes in both non-aqueous and RTIL media. A method to optimise the chronoamperometric conditions is demonstrated. This provides an essential experimental basis for IL based gas sensor. Chapter 5 demonstrates how the oxidation potential of ferrocene can be tuned by changing the anionic component of room temperature ionic liquids. This ability to tune redox potentials has genetic value in gas sensing. Chapters 6 and 7 describe two novel patented approaches to monitor the local environment for amperometric gas detection. In Chapter 6, an in-situ voltammetric ‘thermometer’ is incorporated into an amperometric oxygen sensing system. The local temperature is measured by the formal potential difference of two redox couples. A simultaneous temperature and humidity sensor is reported in Chapter 7. This sensor shows advantageous features where the temperature sensor is humidity independent and vice versa. The Shoup and Szabo analysis (Chapter 4) requires ‘simple’ electron transfer and as such the reduction of oxygen in wet RTILs can be complicated by dissolved water. Chapter 8 proposes a method to stop oxygen reduction at the one electron transfer stage under humid conditions by using phosphonium based RTILs to ‘trap’ the intermediate superoxide ions. Chapters 9 and 10 report the fabrication of low cost disposable electrodes of various geometries and of different materials. The suitability of these electrode for use as working electrodes for electrochemical experiments in aqueous, non-aqueous and RTIL media is demonstrated. Their capability to be used as working probes for amperometric gas sensing systems is discussed.

A química supramolecular de porfirinas e clusters trinucleares de rutênio foi investigada sob o ponto de vista teórico-experimental. Através do desenvolvimento de uma nova metodologia baseada em ferramentas teóricas, as propriedades desses sistemas puderam ser explicadas à luz da mecânica quântica, revelando os mecanismos eletrônicos envolvidos na modificação das propriedades dos anéis porfirínicos pelos compostos de coordenação. As geometrias, a dinâmica e as estruturas eletrônicas desses sistemas foram obtidas através do desenvolvimento de novos parâmetros para campos de força empíricos, e da utilização de métodos semi-empíricos e ab initio. Essas foram utilizadas para interpretar as propriedades físico-químicas dos mesmos, como por exemplo a associação intermolecular em solução e na forma de filmes finos obtidos sobre superfícies não rugosas. O estudo teórico detalhado das estruturas eletrônicas dessas espécies comprovou que a influência supramolecular dos compostos de coordenação se dá através de orbitais de simetria π, representando o principal mecanismo de ativação de anéis porfirínicos por compostos de coordenação. Essa ativação diferenciada pôde ser evidenciada experimentalmente pela aplicação dessas espécies em células fotoeletroquímicas e em sistemas de catálise com atividade citocromo P-450. / The supramolecular chemistry of porphyrins and trinuclear ruthenium clusters has been investigated by a theoretical-experimental approach. Through the development of a new methodology based on theoretical tools, their relevant properties were explained using quantum mechanics, disclosing the electronic mechanisms by which coordination compounds modify the properties of porphyrin rings. Geometries, dynamics and electronic structures of these systems have been obtained by the development of new parameters for empirical force fields, and through semiempirical and ab initio methods. They have been used to explain the physical-chemical properties as, for example, the intermolecular association in solution, and thin film formation over flat surfaces. According to the detailed theoretical study coordination compounds increase the catalytic activity of porphyrin rings via π-orbital coupling, and this is the main mechanism of porphyrin activation. Such enhanced activity has been experimentally observed in photoelectrochemical devices and in the oxidation catalysis of organic substrates, providing synthetic models of cytochrome P-450 systems.

O reconhecimento e interação intermoleculares são cruciais na patogênese de doenças desmielinizantes autoimunes, como a esclerose múltipla (EM). A EM é uma doença que acomete o sistema nervoso central (SNC) e leva à desmielinização e axonopatia. Os alvos da resposta não são claros, mas proteínas da mielina, como a glicoproteína oligodendrocítica da mielina (MOG) e a proteína básica da mielina (MBP), são potenciais candidatas ao reconhecimento por células e autoanticorpos durante o processo autoimune. Assim, métodos de modelagem e simulações de dinâmica molecular (MD) e steered molecular dynamics (SMD) foram empregados para detalhar o reconhecimento e ligação do domínio externo da MOG e do peptídeo imunogênico MBP85-99 por anticorpos específicos. Para a obtenção das estruturas 3D dos anticorpos, particularmente do anti-MBP, um protocolo computacional envolvendo mutações sequenciais da região determinante de complementaridade (CDR) de estruturas-molde foi proposto. Dados obtidos evidenciaram grande contribuição das ligações de hidrogênio na manutenção dos complexos antígeno-anticorpo. Treze resíduos da MOG foram identificados como âncoras da ligação com o anti-MOG, os quais se relacionaram a peptídeos importantes descritos na literatura, principalmente o MOG92-106. No caso da MBP, os resíduos do MBP85-99 com maior interação com o anti-MBP envolveram a Arginina 99, Lisina 93, Asparagina 94 e Histidina 90, corroborando achados na literatura acerca da resposta celular e análises do anti-MBP em casos postmortem. Dados de SMD envolvendo os sistemas moleculares foram confirmados por dados de microscópio de força atômica, sugerindo grande participação do peptídeo MOG92-106 na manutenção da ligação com o anti-MOG. Com relação à MBP, os estudos computacionais indicaram que o ponto de interação da região da Arginina 99 é muito importante para a ligação com o anti-MBP. A consonância entre dados computacionais e dados experimentais resultantes de décadas de pesquisas da MOG e a MBP, bem como com dos experimentos de AFM, ficou evidente. Desta forma, as aproximações teórico-experimentais aplicadas neste trabalho para a caracterização de moléculas ainda não estudadas é uma via em potencial para otimização de passos iniciais e pré-clínicos de investigações de doenças autoimunes, guiando experimentos, reduzindos custos e o uso de modelos animais. / Intermolecular recognition and interaction are crucial in autoimmune demyelinating diseases pathogenesis as multiple sclerosis (MS). MS causes demyelination and axonopathy in the central nervous system (CNS). The targets of immune cells and autoantibodies are not clear, but myelin proteins, such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP), are potential candidates. Thus, methods of molecular modeling, molecular dynamics (MD), and steered molecular dynamics (SMD) simulation were applied to detail the recognition and binding of MOG external domain and the immunogenic MBP85-99 peptide by specific antibodies. A computational protocol based on mutations of complement determinant regions (CDR) in template structures was proposed to obtain antibodies 3D structures, especially the anti-MBP. The obtained data evidenced a significant contribution of hydrogen bonds in the maintenance of antigen-antibody complexes. Thirteen anchor residues were found in the MOG structure. These residues were related to three well-known epitopes recognized by immunologic components, mainly MOG92-106. In the case of MBP, the most interactive residues of the MBP85-99 with the anti-MBP were Arginine 99, Lysine 93, Asparagine 94, and Histidine 90. These data complied with several studies concern cellular recognition of MBP and postmortem cases involving anti-MBP. SMD information of both molecular systems was confirmed by atomic force microscopy and suggested the MOG92-106 acting as an anchor for the complex with the anti-MOG. Regarding MBP, the computational force study evidenced the importance of Arginine 99 interaction region for the antigen-antibody binding. The agreement between the obtained computational data and experimental information resulted of decades of MOG and MBP research was evident. In this context, theoretical and experimental approaches application as described here for characterizing novel molecules in autoimmune disease is a potential pathway to optimize early-stage and pre-clinical steps of investigations, guiding experiments, reducing costs, and animal model usage.

A química supramolecular de porfirinas e clusters trinucleares de rutênio foi investigada sob o ponto de vista teórico-experimental. Através do desenvolvimento de uma nova metodologia baseada em ferramentas teóricas, as propriedades desses sistemas puderam ser explicadas à luz da mecânica quântica, revelando os mecanismos eletrônicos envolvidos na modificação das propriedades dos anéis porfirínicos pelos compostos de coordenação. As geometrias, a dinâmica e as estruturas eletrônicas desses sistemas foram obtidas através do desenvolvimento de novos parâmetros para campos de força empíricos, e da utilização de métodos semi-empíricos e ab initio. Essas foram utilizadas para interpretar as propriedades físico-químicas dos mesmos, como por exemplo a associação intermolecular em solução e na forma de filmes finos obtidos sobre superfícies não rugosas. O estudo teórico detalhado das estruturas eletrônicas dessas espécies comprovou que a influência supramolecular dos compostos de coordenação se dá através de orbitais de simetria π, representando o principal mecanismo de ativação de anéis porfirínicos por compostos de coordenação. Essa ativação diferenciada pôde ser evidenciada experimentalmente pela aplicação dessas espécies em células fotoeletroquímicas e em sistemas de catálise com atividade citocromo P-450. / The supramolecular chemistry of porphyrins and trinuclear ruthenium clusters has been investigated by a theoretical-experimental approach. Through the development of a new methodology based on theoretical tools, their relevant properties were explained using quantum mechanics, disclosing the electronic mechanisms by which coordination compounds modify the properties of porphyrin rings. Geometries, dynamics and electronic structures of these systems have been obtained by the development of new parameters for empirical force fields, and through semiempirical and ab initio methods. They have been used to explain the physical-chemical properties as, for example, the intermolecular association in solution, and thin film formation over flat surfaces. According to the detailed theoretical study coordination compounds increase the catalytic activity of porphyrin rings via π-orbital coupling, and this is the main mechanism of porphyrin activation. Such enhanced activity has been experimentally observed in photoelectrochemical devices and in the oxidation catalysis of organic substrates, providing synthetic models of cytochrome P-450 systems.

This thesis presents a series of electron impact ionization measurements on the gas phase targets of argon and krypton. The (e,2e) coincidence technique has been employed to measure the triple differential cross section (TDCS) using a new coincidence spectrometer designed to operate in the low energy regime (2 to 5 times the ionization energy) and in the coplanar geometry. The spectrometer is a conventional device utilizing a non-energy selected electron gun and two 1800 hemispherical electron analysers fitted with channel electron multipliers for detection of the outgoing electrons. A series of TDCS measurements were performed on the 3s inner-valence and 3p valence orbitals of argon employing coplanar asymmetric kinematics. Measurements for both orbitals were performed at an incident energy of 113.5 eV, ejected energies of 10, 7.5, 5 and 2 eV and a scattering angle of -15°. The energy of the scattered electron in each case was chosen to satis~' energy conservation and is dependent on the ionization energies of the different orbitals. The experimental cross sections are compared to theoretical TDCS calculations using the distorted wave Born approximation (DWBA) and variations of the DWBA in an attempt to investigate the role that post collisional interaction (PCI), polarization and electron exchange play in describing the TDCS in the low energy regime. To further extend this analysis, a series of TDCS measurements were performed on the 3s and 4s. orbitals of argon and krypton, respectively, employing coplanar symmetric kinematics. Measurements were performed for the 3s orbital at outgoing energies of 50, 20, 10 and 4eV and for the 4s orbital at outgoing energies of 85, 50, 20 and 10 eV. The kinematics were chosen to coincide with several of the (e,2e) measurements made in the same geometry on the 3p orbital of argon by Rouvellou et al (1998). The experimental results were again compared to a DWBA calculation and similar variations to those employed for the asymmetric measurements.

This thesis presents and uses the techniques of computational chemistry to explore two different processes induced in human skin by ultraviolet light. The first is the transformation of urocanic acid into a immunosuppressing agent, and the other is the enzymatic action of the 8-oxoguanine glycosylase enzyme. The photochemistry of urocanic acid is investigated by time-dependent density functional theory. Vertical absorption spectra of the molecule in different forms and environments is assigned and candidate states for the photochemistry at different wavelengths are identified. Molecular dynamics simulations of urocanic acid in gas phase and aqueous solution reveals considerable flexibility under experimental conditions, particularly for for the cis isomer where competition between intra- and inter-molecular interactions increases flexibility. A model to explain the observed gas phase photochemistry of urocanic acid is developed and it is shown that a reinterpretation in terms of a mixture between isomers significantly enhances the agreement between theory and experiment , and resolves several peculiarities in the spectrum. A model for the photochemistry in the aqueous phase of urocanic acid is then developed, in which two excited states governs the efficiency of photoisomerization. The point of entrance into a conical intersection seam is shown to explain the wavelength dependence of photoisomerization quantum yield. Finally some mechanistic aspects of the DNA repair enzyme 8-oxoguanine glycosylase is investigated with density functional theory. It is found that the critical amino acid of the active site can provide catalytic power in several different manners, and that a recent proposal involving a SN1 type of mechanism seems the most efficient one.

The reaction mechanisms for the hemoglobin degrading enzymes in the Plasmodium falciparum malaria parasite, plasmepsin II (Plm II) and histo-aspartic protease (HAP), have been analyzed by molecular simulations. The reaction free energy profiles, calculated by the empirical valence bond (EVB) method in combination with molecular dynamics (MD) and free energy perturbation (FEP) simulations are in good agreement with experimental data. Additional computational methods, such as homology modelling and automated substrate docking, were necessary to generate a 3D model and a reactive substrate conformation before the reaction mechanism in HAP could be investigated. HAP is found to be an aspartic protease with a peptide cleaving mechanism similar to plasmepsin II. The major difference between these enzymes is that the negatively charged tetrahedral intermediate is stabilized by the charged histidine in HAP while in Plm II it is a neutral aspartic acid. Also the reaction mechanism for two other aspartic proteases, cathepsin D and HIV-1 protease, was simulated. These enzymes are relevant both for the inhibitor selectivity and for obtaining a general picture of catalysis in aspartic proteases. Another project involves inhibitor design towards plasmepsins. In particular, Plm II directed inhibitors based on the dihydroxyethylene scaffold have been characterized computationally. Molecular dynamics (MD) simulations were used to propagate the investigated system through time and to generate ensembles used for the calculation of free energies. The ligand binding affinities were calculated with the linear interaction energy (LIE) method. The most potent inhibitor had a Ki value of 6 nM and showed 78 % parasite inhibition when tested on red blood cells infected by malaria parasite P. falciparum. Citrate synthase is part of the citric acid cycle and is present in organisms that live in cold sea water as well as hot springs. The temperature adaptation of citrate synthase to cold and heat was investigated in terms of the difference in transition state stabilization between the psychrophilic, mesophilic and hyperthermophilic homologues. The EVB, FEP and MD methods were used to generate reaction free energy profiles. The investigated energetics points toward the electrostatic stabilization during the reaction as the major difference between the different citrate synthase homologues. The electrostatic stabilization of the transition state is most effective in the following order of the citrate synthase homologues: hyperthermophile, mesophile, psycrophile. This could be a general rule for temperature adaptation of enzyme catalysis.