Dissertations / Theses on the topic 'Complete computational structure'

The signal structure is a partial structure representation for dynamic systems. It characterizes the causal relationship between manifest variables and is depicted in a weighted graph, where the weights are dynamic operators. Earlier work has defined signal structure for linear time-invariant systems through dynamical structure function. This thesis focuses on the search for the signal structure of nonlinear systems and proves that the signal structure reduces to the linear definition when the systems are linear. Specifically, this work: (1) Defines the complete computational structure for nonlinear systems. (2) Provides a process to find the complete computational structure given a state space model. (3) Defines the signal structure for dynamic systems in general. (4) Provides a process to find the signal structure for a class of dynamic systems from their complete computational structure.

Proteins are dynamic structural entities that are involved in many biophysical processes through molecular interactions with their ligands. Protein-ligand interactions are of fundamental importance for computer-aided drug discovery. Due to the fast development in computer technologies and theoretical methods, computational studies are by now able to provide atomistic-level description of structures, thermodynamic and dynamic properties of protein-ligand systems, and are becoming indispensable in understanding complicated biomolecular systems. In this dissertation, I have applied molecular dynamic (MD) simulations combined with several state of the art free-energy calculation methodologies, to understand structures and binding properties of several protein-ligand systems. The dissertation consists of six chapters. In the first chapter, I present a brief introduction to classical MD simulations, to recently developed methods for binding free energy calculations, and to enhanced sampling of configuration space of biological systems. The basic features, including the Hamiltonian equations, force fields, integrators, thermostats, and barostats, that contribute to a complete MD simulation are described in chapter 2. In chapter 3, two classes of commonly used algorithms for estimating binding free energies are presented. I highlight enhanced sampling approaches in chapter 4, with a special focus on replica exchange MD simulations and metadynamics, as both of them have been utilized in my work presented in the chapter thereafter. In chapter 5, I outlined the work in the 5 papers included in the thesis. In paper I and II, I applied, respectively, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and alchemical free energy calculation methods to identify the molecular determinant of the affibody protein ZAb3 bound to an amyloid b peptide, and to investigate the binding profile of the positive allosteric modulator NS-1738 with the α7 acetylcholine-binding protein (α7-AChBP protein); in paper III and VI, unbiased MD simulations were integrated with the well-tempered metadynamics approach, with the aim to reveal the mechanism behind the higher selectivity of an antagonist towards corticotropin-releasing factor receptor-1 (CRF1R) than towards CRF2R, and to understand how the allosteric modulation induced by a sodium ion is propagated to the intracellular side of the d-opioid receptor; in the last paper, I proved the structural heterogeneity of the intrinsically disordered AICD peptide, and then employed the bias-exchange metadynamics and kinetic Monte Carlo techniques to understand the coupled folding and binding of AICD to its receptor Fe65-PTB2. I finally proposed that the interactions between AICD and Fe65-PTB2 take place through an induced-fit mechanism. In chapter 6, I made a short conclusion of the work, with an outlook of computational simulations of biomolecular systems.

QC 20170516

This thesis presents electronic structure calculations on problems related to the bonding in inorganic coordination compounds and clusters. A wide range of molecules with the ability to exist in different structural forms or electronic states has been selected and density functional theory is systematically applied in order to gain detailed insight into their characteristics and reactivity at the electronic level. First, we address the question of redox non-innocent behaviour of bipyridine in a series of 1st row transition metal complexes. Complexes of the type [M(2,2'-bipyridine)(mes)₂]⁰ (M = Cr, Mn, Fe, Co, Ni; mes = 2,4,6-Me₃C6H₂) and their one-electron reduced forms have been explored. The results clearly show that the anions are best described as complexes of the monoanionic bipyridine radical (S_bpy = 1/2), giving a rationale for the observed structural changes within the ligand. Likewise, we have identified dianionic bipyridine in both the complexes [Zn2(4,4'-bpy)(mes)₄]²⁻ and [Fe(2,2'-bpy)₂]²⁻. In no case have we found evidence for significant metal-to-ligand backbonding. The subject of redox-noninnocence is further revisited in a comparative study of the two complexes [M(o-Clpap)₃] (M = Cr, Mo; o-Clpap = 2-[(2-chloro-phenyl)azo]-pyridine), and their associated electron transfer series. The results indicate that all electron transfer processes are primarily ligand-based, although in the case of the Mo analogue these are coupled to substantial electron density changes at the metal. The ability of pap to form radical anions finds a contrasting case in the di- nuclear Rh complex [Rh₂(μ-p-Clpap)₂ (cod)Cl₂], where the two ligand bridges act as acceptors of strong dπ∗ backbonding from a formally Rh^–I centre. We then direct our attention to the endohedral Zintl clusters [Fe@Ge₁₀]³⁻ and [Mn@Pb₁₂]³⁻, which reveal peculiar topologies. We have probed the electronic factors that influence their geometric preferences, and propose a model based on the shift of electron density from the endo- hedral metal to the cage to account for the observed geometries. Subsequently, we reassess the electronic structure of the xenophilic clusters Mn₂(thf)₄(Fe(CO)₄)₂ and [Mn(Mn(thf)₂)₃(Mn(CO)₄)₃]^–. We conclude that these are best viewed as exchange coupled Mn^II centres bridged by closed- shell carbonylate fragments. In the closing chapter the reduction of NO₂^– to NO by the complex [Cu(tct)(NO₂)]⁺ (tct = cis,cis-1,3,5-tris(cinnamylideneamino)cyclohexane) is studied, a process that mimics the enzyme-catalysed reaction. Two viable pathways for the reaction have been traced and key inter-mediates identified. Both direct release of NO or via decomposition of a Cu-NO complex are kinetically and thermodynamically feasible.

Dans cette recherche, on construit un modèle simplifié en basses et moyennes fréquences de complexes insonorisants (habillages) de l'industrie automobile à partir d'un élément élastoacoustique stochastique. Le modèle simplifié moyen est issu d'une extension de la théorie des structures floues et dépend de trois paramètres physiques : densité modale, amortissement et masse participante. Le modèle simplifié stochastique qui prend en compte les incertitudes de modèle et de données est construit en utilisant une approche probabiliste non paramétrique et dépend de trois paramètres de dispersion. Le modèle simplifié de l'habillage est implémenté dans un modèle vibroacoustique stochastique industriel d'automobile. Deux problèmes inverses sont résolus à l'aide d'une base de données expérimentales sur véhicules construite en parallèle et permettent d'identifier les paramètres du modèle complet. L'analyse des résultats permet de valider les développements théoriques et la méthodologie proposée

In the last fifty years, computational mechanics has gained the attention of a large number of disciplines, ranging from physics and mathematics to biology, involving all the disciplines that deal with complex systems or processes. With ϵ-machines, computational mechanics provides powerful models that can help characterizing these systems. To date, an increasing number of studies concern the use of such methodologies; nevertheless, an attempt to make this approach more accessible in practice is lacking yet. Starting from this point, this thesis aims at investigating a more practical approach to computational mechanics so as to make it suitable for applications in a wide spectrum of domains. ϵ-machines are analyzed more in the robotics scene, trying to understand if they can be exploited in contexts with typically complex dynamics like swarms. Experiments are conducted with random walk behavior and the aggregation task. Statistical complexity is first studied and tested on the logistical map and then exploited, as a more applicative case, in the analysis of electroencephalograms as a classification parameter, resulting in the discrimination between patients (with different sleep disorders) and healthy subjects. The number of applications that may benefit from the use of such a technique is enormous. Hopefully, this work has broadened the prospect towards a more applicative interest.

We review fold usage on completed genomes in order to explore protein structure evolution and assess the evolutionary relevance of current structural classification systems (SCOP and CATH). We assign folds on a set of 150 completed genomes using fold recognition methods (PSI-BLAST, SUPERFAMILY and Gene3D). The patterns of presence or absence of folds on genomes gives us insights into the relationships between folds and how we have arrived at the set of folds we see today. In particular, we develop a technique to estimate the relative ages of a protein fold based on genomic occurrence patterns in a phylogeny. We find that SCOP's `alpha/beta' class has relatively fewer distinct folds on large genomes, and that folds of this class tend to be older; folds of SCOP's `small protein' class follow opposite trends. Usage patterns show that folds with many copies on a genome are generally old, but that old folds do not necessarily have many copies. In addition, longer domains tend to be older and hydrophobic amino acids have high propensities for older folds whereas, polar - but non-charged - amino acids are associated with younger folds. Generally domains with stabilising features tend to be older. We also show that the reliability of fold recognition methods may be assessed using occurrence patterns. We develop a method, that detects false positives by identifying isolated occurrences in a phylogeny of species, and is able to improve genome wide fold recognition assignment sets. We use a structural fragment library to investigate evolutionary links between protein folds. We show that 'older' folds have relatively more such links than 'younger' folds. This correlation becomes stronger for longer fragment lengths suggesting that such links may reflect evolutionary relatedness.

This thesis describes the synthesis and analysis of organometallic complexes that feature either enyl or ynyl linkages. Chapter 1 introduces a general overview of electron transfer, classification of mixed-valence complexes and the modelling of mixed-valence complexes using density functional theory. The synthesis of a range of trans-RuCl(C≡CC6H4R)(dppe)2 complexes, in which R is either an electron donor (Me, OMe, C5H11) or acceptor (NO2, CO2Me), from the five-coordinate complex [RuCl(dppe)2]OTf is described. This synthetic route represents an alternative to the long-standing methods based on cis-RuCl2(dppe)2. Improved synthetic routes to both [RuCl(dppe)2]OTf and cis-RuCl2(dppe)2 are also given. These compounds were fully characterised spectroscopically and the molecular structures of [RuCl(dppe)2]OTf, trans-RuCl(C≡CC6H4OMe)(dppe)2, trans-RuCl(C≡CC6H4Me)(dppe)2, and trans-RuCl(C≡CC6H4CO2Me)(dppe)2 determined and analysed. The structures conform with literature precedence. The synthesis of ruthenium complexes based on RuCl(dppe)2 and Ru(dppe)Cp* units, featuring 1,3-diethynylbenzene bridging ligands has been achieved. The electronic structures of 1,3-{trans-Cl(dppe)2RuC≡C}c2C6H4, 1,3-{Cp*(dppe)RuC≡C}2C6H4 and 1,3-{Cp*(dppe)RuC≡C}2-5-(HC≡C)C6H3 have been investigated using a combination of UV-vis-NIR and IR spectroscopies and computational studies. In contrast to the case of closely related iron compounds, for the ruthenium complexes 1,3-{trans-Cl(dppe)2RuC≡C}2C6H4, 1,3-{Cp*(dppe)RuC≡C}2C6H4 and 1,3-{Cp*(dppe)RuC≡C}2-5-(HC≡C)C6H3 the bridging aryl moiety is heavily involved in the oxidation process, and consequently descriptions of the electronic structures and electronic transitions in terms of the language developed for mixed-valence systems with clearly identifiable metal oxidation states are not appropriate. The description of the low-energy absorption bands from the mixed-valence complexes are therefore better described as charge transfer transitions rather than IVCT transitions. A range of mono vinyl Ru(CH=CHC6H4R-4)(CO)(PPh3)Tp complexes have been obtained from the reaction of RuHCl(CO)(PPh3)3 with para- substituted ethynylphenylenes, and KTp. (R = NO2, CO2Me, CN, Me and OMe). These complexes have been fully characterised spectroscopically, with molecular structures for Ru(CH=CHC6H4NO2-4)(CO)(PPh3)Tp, Ru(CH=CHC6H4CN-4)(CO)(PPh3)Tp, Ru(CH=CHC6H4CH3)(CO)(PPh3)Tp and Ru(CH=CHC6H4OMe-4)(CO)(PPh3)Tp being determined and analysed. The electronic structures of these mono vinyl complexes have been also investigated using a combination of UV-vis-NIR and IR spectroscopies and computational studies, revealing the redox activity of the styrene-derived ligand. Hydroruthenation of 1,3-, 1,4- diethynylbenzene and 1,3,5-triethynylbenzene affords the di- and trimetalled vinyl complexes, which have been characterised spectroscopically. The bridging ligand is shown to be redox non-innocent. A simple protocol that allows the preparation of either “symmetric” A3 or “asymmetric” AB2 triethynyl methanol derivatives through the reaction of acetylide anions with chloroethylformate, has been explored. This synthetic protocol is not only high yielding, but avoids the harsh conditions used in literature methods. The molecular structures of Me3SiC≡C(COH)(C6H4I)2 and HC≡C(COH)(C6H4I)2 have been determined and analysed, with the packing motifs in the solid state arising from halogen interactions identified. The use of these ligands as branched core ligands has also been investigated, and whilst difficulties have been encountered synthetic work to resolve these has been initiated. A selection of pro-ligands and both mono- and tris-metallated ligand complexes based on a triarylamine core have been prepared. The electronic and structural nature of Me3SiC≡C(C6H4)NTol2, Fe(C≡C(C6H4)NTol2)(dppe)Cp and [{Fe(dppe)Cp}3(μ-(C≡CC6H4)3N)] have been investigated using a combination of UV-vis-NIR and IR spectroscopies and computational studies indicating electronic interactions between the remote metal centres in the case of [{Fe(dppe)Cp}3(μ-(C≡CC6H4)3N)]n+ (n = 1, 2). The molecular structures of Me3SiC≡C(C6H4)NTol2, HC≡C(C6H4)NTol2, Ru(C≡C(C6H4)NTol2)(dppe)Cp* and Fe(C≡C(C6H4)NTol2)(dppe)Cp have been determined and analysed.

This thesis presents the basic concepts of electronic structure theory and the chemical properties of mercury. The theoretical foundation of DFT and the consequences of relativity are also introduced. The electronic structure of Hg(II) ions, [Hg(L)n(H2O)m]q (L = HO-, Cl-, HS-, S2-) has been studied. We show, in this thesis, that the charge transfer (that is calculated from the hard-soft-acid-base principle (Pearson’s principle)), the total NBO charge and the interaction energies are strongly correlated. Our studies indicate the effect of the solvent on the global electrophilicity, the charge transfer and consequently the interaction strength between Hg(II) and ligand L. The formation constants, logK, of Hg2+−complexes are calculated. The procedure that we follow in this thesis to calculate the formation constants, logK’s, are in good agreement with the extrapolated experimental values. We introduce and explain why it is important adding water molecules explicitly during the calculations of the logK. The recommended logK value of HgS is 27.2. We examined two different types of organic compounds as sensors for heavy metal ions: lumazine (Lm) and 6-thienyllumazine (TLm). We found that the simple calculation of pKa values using DFT methods and implicit solvent models failed to reproduce the experimental values. However, calculated orbital energies and gas phase acidities both indicate that the compound TLm is inherently more acidic than the parent species Lm. We demonstrate that: (1) we need to take in our consideration the population of each tautomer and conformer during the calculations of the pKa values, and (2) thienyl group has indirect effect on the acidity of the proton on N1 in the uracil ring. Last but not least, the fluorescence spectrum of the sensors (L) and their [(L)nM(H2O)m]2+ complexes (L = Lumazine (Lm) and 6-thienyllumazine (TLm) and M = Cd2+and Hg2+) are calculated using time dependent DFT (TDDFT). The results show that TDDFT is in good agreement with experimental results. This chapter provides a new concept in the design of fluorescence turn-on/off sensors that has wider applicability for other systems. Finally, we provide a summary of the works compiled in this thesis and an outlook on potential future work.
October 2015

Thesis (Ph. D.)--Biology, Georgia Institute of Technology, 2008.
Committee Chair: Harvey, Stephen C; Committee Member: Hud, Nicholas V; Committee Member: McCarty, Nael A; Committee Member: Wartell, Roger M.

Structure determination of macromolecular protein assemblies remains a challenge for well-established experimental methods. In this thesis, an emerging structural technique, ion mobility-mass spectrometry (IM-MS) is explored. An assessment of collision cross section (CCS) measurement accuracy using travelling-wave IM (TWIMS) instrumentation was carried out (Chapter 3). Through the collation of a protein complex CCS database and the development of a calibration framework for TWIMS, significant improvements to CCS measurement accuracy have been achieved. Next, the advantages and limitations of using IM-MS to generate restraints for structure characterisation were explored. Computational tools designed to exploit IM-MS data for structural modelling were developed and tested on a training set of systems (Chapter 4). These include two heteromeric protein complexes, and an oligomeric intermediate involved in beta-2-microglobulin aggregation. Further structural information can be attained by using gas-phase dissociation techniques, such as collision-induced dissociation (CID). The effects of charge state on CCS and the gas-phase dissociation pathway of complexes were investigated (Chapter 5). This highlighted the possibility of using CID in conjunction with supercharging to manipulate dissociation pathways to achieve more useful structural information. Finally, the gas-phase structures of globular and intrinsically disordered protein complexes were probed by IM-MS and molecular dynamics (MD) simulations (Chapter 6). Experimental observations were recapitulated remarkably closely by simulations, including gas-phase structural collapse and the ejection of monomer subunits when the energy of the system was increased sufficiently. Overall, this research has contributed to the IM-MS field by providing the framework for improved CCS measurements of large protein complexes and the use of restraints from IM-MS for structural modelling. Significantly, IM-MS has been used in combination with charge manipulation, CID and MD simulations to reveal further insights into the gas-phase structures, stabilities and dissociation pathways of multimeric protein complexes.

A series of heterobi- and tri-metallic complexes were prepared by the metallation of the carbanion derived from [M(CO)₄(dppm)] (M = Cr, Mo or W), [ML(dppm)] (L= dithiolene; M = Pd or Pt), or the cationic precursor, [Ru(Cp)(PPh3)(dppm)]PF₆. The complexes were characterized by ¹H and ³¹P NMR, IR and UV/Vis spectroscopies and X-ray crystallography. The presence of electrochemical communication in these complexes was investigated by means of cyclic voltammetry. Correlation studies of electrochemical potentials and 31P NMR data or carbonyl stretching frequencies of the Group 6 mercurated complexes show that the mercury atom does facilitate the flow of electrons through the four-membered chelate ring. However, this effect has been established to be weak. Similar weak electronic effects were found to exist in the case of the Ru, Pd and Pt complexes. Evidence of "through-space" communication was established to be present in the ferrocenyl derivatives. X-ray crystallographic studies show that mercuration of the carbanion neutralizes the residual electron density in the chelate ring for the chromium bi- and tri-metallic complexes. This was also demonstrated for the cationic ruthenium complex. X-ray crystallographic studies were performed on dithizone and its corresponding salt in an attempt to resolve or explain the often debated tautomerism of this molecule in the solid state and in solution. The structure of the parent molecule showed the co-existence of the two tautomeric forms in a single structure, with a 2:1 preference for the symmetrical keto form, compared to the enol form. DFT calculations have been performed and have been shown to be mutually consistent with structural data, showing a negligible energy difference of 3.1 kcal mol⁻¹ between the two forms. Computational calculations were also performed to investigate the solution characteristics of the dithizonate salt. An analysis of the HOMO and Fukui functions show the sulfur atom to be the most nucleophilic and therefore the preferred site for deprotonation with an energy barrier of 17 kJ mol⁻¹ compared to the nitrogen atom. While the 1H NMR spectrum shows evidence of the existence of proton exchange in solution, we were unable to model this. However, DFT solution studies show that the keto form is most stabilized. A series of palladium and platinum dithizonate complexes, with the general formula, [M(PP)(Hdptc)]X or [M(PP)(dptc)] (PP = mono- or bidentate phosphine ligand; M = Pd or Pt; X = PF₆ or BPh₄), was prepared and investigated for their photochromic behaviour. None of these complexes exhibited any photochromism. X-ray crystal structures of [Pt(COD)(dptc)] and [Pt(dppf)(dptc)] were determined. Both complexes contain the dithizone ligand in a doubly deprotonated, or secondary, form. Synthetic routes to the preparation of mixed dithiolene-dithizone complexes of mercury and platinum were developed. The complexes were characterized by ¹H and ¹³C NMR, IR and UV/Vis spectroscopies and X-ray crystallography. Spectroscopic studies show that the mercury complexes are all photochromic, while the platinum complex showed no photochromism in solution. Electrochemical studies show the absence of rich electrochemical activity for the Hg complexes. The [Pt(mnt)(Hdptc)]⁺ complexes, in contrast, showed greater redox activity. X-ray studies on the analogous complexes, Ph₄As[Hg(mnt)(Hdptc)] and Bu₄N[Pt(mnt)(Hdptc)] revealed an absence of any S···S or Metal···S interactions, often associated with planar sulfur rich ligands.

Accurate predictions of binding free energies from computer simulations are an invaluable resource for understanding biochemical processes and drug action. The primary aim of the work described in the thesis was to predict and understand ligand binding to several proteins of major pharmaceutical importance using computational methods. We report a computational strategy to quantitatively predict the effects of alanine scanning and ligand modifications based on molecular dynamics free energy simulations. A smooth stepwise scheme for free energy perturbation calculations is derived and applied to a series of thirteen alanine mutations of the human neuropeptide Y1 G-protein coupled receptor and a series of eight analogous antagonists. The robustness and accuracy of the method enables univocal interpretation of existing mutagenesis and binding data. We show how these calculations can be used to validate structural models and demonstrate their ability to discriminate against suboptimal ones. Site-directed mutagenesis, homology modelling and docking were further used to characterize agonist binding to the human neuropeptide Y2 receptor, which is important in feeding behavior and an obesity drug target.  In a separate project, homology modelling was also used for rationalization of mutagenesis data for an integron integrase involved in antibiotic resistance. Blockade of the hERG potassium channel by various drug-like compounds, potentially causing serious cardiac side effects, is a major problem in drug development. We have used a homology model of hERG to conduct molecular docking experiments with a series of channel blockers, followed by molecular dynamics simulations of the complexes and evaluation of binding free energies with the linear interaction energy method. The calculations are in good agreement with experimental binding affinities and allow for a rationalization of three-dimensional structure-activity relationships with implications for design of new compounds. Docking, scoring, molecular dynamics, and the linear interaction energy method were also used to predict binding modes and affinities for a large set of inhibitors to HIV-1 reverse transcriptase. Good agreement with experiment was found and the work provides a validation of the methodology as a powerful tool in structure-based drug design. It is also easily scalable for higher throughput of compounds.

The ability to accurately predict binding free energies from computer simulations is an invaluable resource in understanding biochemical processes and drug action. Several methods based on microscopic molecular dynamics simulations exist, and in this thesis the validation, application, and development of the linear interaction energy (LIE) method is presented.

For a test case of several hydrophobic ligands binding to P450cam it is found that the LIE parameters do not change when simulations are performed with three different force fields. The nonpolar contribution to binding of these ligands is best reproduced with a constant offset and a previously determined scaling of the van der Waals interactions.

A new methodology for prediction of binding free energies of protein-protein complexes is investigated and found to give excellent agreement with experimental results. In order to reproduce the nonpolar contribution to binding, a different scaling of the van der Waals interactions is neccesary (compared to small ligand binding) and found to be, in part, due to an electrostatic preorganization effect not present when binding small ligands.

A new treatment of the electrostatic contribution to binding is also proposed. In this new scheme, the chemical makeup of the ligand determines the scaling of the electrostatic ligand interaction energies. These scaling factors are calibrated using the electrostatic contribution to hydration free energies and proposed to be applicable to ligand binding.

The issue of codon-anticodon recognition on the ribosome is adressed using LIE. The calculated binding free energies are in excellent agreement with experimental results, and further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with a ribosome loaded with the Phe UUU codon. The simulations also support the previously suggested roles of A1492, A1493, and G530 in the codon-anticodon recognition process.

Computational chemistry has gained interest as a characterization tool to predict photoluminescence, reactivity and structural properties of organic and transition metal complexes. With the rise of methods including relativity, these studies have been expanded to the accurate modeling of luminescence spectra of complexes with considerable spin-orbit splitting due to heavy metal centers as well as the reaction pathways for these complexes to produce natural products such as hydrogen gas. These advances have led to the synthesis and utility of more effective catalysis as well as the development of more effective organic light emitting diodes (OLEDs) through the incorporation of organometallic complexes as emitters instead of typical organic emitters. In terms of significant scientific advancement presented in this work is in relation to the discovery of significant spin-orbit splitting in a gold(I) alkylphosphine complex, where the splitting results in the states that emit in different colors of the visible region of the electromagnetic spectrum. This work also reveals the discovery both computationally and experimentally, of a genuine polar-covalent bond between two-closed shell metals. This work highlights a complex with an incredibly short gold(I) – copper(I) intermetallic distance leading to a vibrational frequency and dissociation energy that is on par with those of other systems with single-bonded metal centers. Lastly, this work outlines a strategy for the production of hydrogen gas through the use of trinuclear cyclic coinage metal complexes as catalysis to split hydrohalic acids.

Numerical analysis of periodic structures in layered media is usually accomplished by using Method of Moments which requires the formation of the impedance matrix of the structure. The construction of this impedance matrix requires the evaluation of the periodic Green&rsquo
s function in layered media which is expressed as an infinite series in terms of the spectral domain Green&rsquo
s function. The slow converging nature of this series make these kinds of analysis computationally expensive. Although some papers have proposed methods to accelerate the computation of these series successfully for a single frequency point, it is still very computation intensive to obtain the frequency response of the structure over a band of frequencies. In this thesis, Discrete Complex Image Method (DCIM) is utilized for the efficient computation of the periodic Green&rsquo
s function. First, the spectral domain Green&rsquo
s function in layered media is approximated by complex exponentials through the use of DCIM. During the application of the DCIM, three-level approximation scheme is employed to improve accuracy. Then, Ewald&rsquo
s transformation is applied to accelerate the computation of the infinite series involved in the periodic Green&rsquo
s functions. The accuracy and the efficiency of the method is demonstrated through numerical examples.

La caractérisation complète d’intermédiaires réactionnels intervenants dans des procédés de catalyse homogène est une tâche ardue en raison de leur réactivité et de leur faible concentration. Ceci est particulièrement vrai pour les espèces radicalaires telles que les complexes organométalliques réduits, qui sont des intermédiaires en photocatalyse ou lorsque ces complexes possèdent des ligands non-innocents. Par conséquent, leur structure électronique est encore mal comprise, sachant que l'électron ajouté peut être situé sur différents sites de la molécule.Dans ce contexte, nous avons développé une méthode d'analyse pour étudier en phase gazeuse des complexes organométalliques radicalaires. Des complexes organométalliques multichargés du zinc et du ruthénium avec des ligands bidentes de type bipyridine ou tridente de type bis(imino)pyridine ont d’abord été obtenus et isolés en phase gazeuse. Ils sont ensuite réduits avec les méthodes d’activation par un électron spécifiques à la spectrométrie de masse, la dissociation par capture ou transfert d’électron (ECD/ETD), permettant de former des espèces métalliques radicalaires monochargées. Celles-ci sont enfin isolés et leur spectre infrarouge est obtenu à l’aide de la spectroscopie d’action basée sur la dissociation induite par l’absorption de plusieurs photons dans l’infrarouge (IRMPD). Les méthodes DFT fournissent un complément pour modéliser la structure électronique et le spectre IR de ces espèces.Les challenges à relever pour développer ce nouvel outil d'analyse étaient de deux ordres. Tout d'abord, nous devions être en mesure d'obtenir les complexes souhaités en phase gazeuse. Ceci nous a conduit à examiner de multiples paramètres, tels que la nature des ligands ou l’énergie interne déposée lors de l’étape de réduction. Le deuxième défi portait sur l'utilisation des méthodes de modélisation. Nous avons montré l’absence de fiabilité des méthodes standards de modélisation pour décrire à la fois la structure électronique et le spectre infrarouge des complexes réduits. Les données expérimentales obtenues durant ce travail ont donc été utilisées comme références pour identifier les fonctionnelles DFT les plus appropriées pour l’étude de ces complexes radicalaires
The complete characterization of reaction intermediates in homogeneous catalytic processes is often a difficult task owing to their reactivity and low concentration. This is particularly true for radical species such as reduced organometallic complexes, which are intermediates in photocatalysis, or when these complexes included non-innocent ligands. Consequently, their electronic structure in the ground state is still poorly understood, knowing that the added electron can be located on different sites of the molecule.In this contect, we developed an analytical method to study radical organometallic complexes in the gas phase. We started with formation of suitable multi-charged zinc organometallic complexes in the gas phase from mixture of zinc metal cation and bipyridine-type bidentate or bis(imino)pyridine tridentate ligands. Multicharged ruthenium complexes with similar ligands have also been studied. Under ideal circumstances these complexes were isolated and reduced in the gas phase to form monocationic metal species. Electron activated methods such as electron capture dissociation (ECD) and electron transferred dissociation (ETD) techniques, available in FT-ICR mass spectrometers, have been used to that end. The resulting Zn and Ru radical cation complexes are then isolated in the gas phase and probed via infrared multi photon dissociation (IRMPD) action spectroscopy. In support, DFT theoretical calculations were performed to model their electronic structure and IR spectra.Two main issues were faced during the development of this new analytical tool. First, we had to be able to obtain the desired complexes in the gas phase. This has lead to monitor various parameters, such as the nature of the ligands or the internal energy provided by the reduction step. The second challenge dealt with the use of modeling methods. We have shown that standard modelling tools lack the accuracy to predict both electronic structure and spectral signatures of reduced complexes. The experimental data gathered in this work have therefore been used as benchmarks for the identification of DFT functionals that are most appropriate for the study of these radical complexes

The question posed in this work is how one would model and predict the rotational spectrum of open-shell open-shell van der Waals complexes. There are two secondary questions that arise: the nature of radical-radical interactions in such systems and the modelling of the large amplitude motion of the constituent molecules. Four different systems were studied in this work, each providing part of the answer to the main question. Starting with the large amplitude motion, there are two theoretical approaches that may be adopted: to either model the whole complex as a semi-rigid molecule, or to perform quantum dynamical calculations. We recorded and analysed the rotational spectrum (using Fourier transform microwave spectroscopy) of the molecule of tertiary butyl acetate (TBAc) which exhibits a high degree of internal rotation; and of the weakly-bound complex between a neon atom and a nitrogen dioxide molecule (Ne-NO2). We used the semi-rigid approach for TBAc and the quantum dynamical approach for Ne-NO2. We also explored the compatibility of these two approaches. Moreover, we were able to predict and analyse the fine and hyperfine structure of the Ne-NO2 spectrum using spherical tensor operator algebra and the results of our dynamics calculations. To explore the nature of the interactions in an radical-radical van der Waals complex we calculated the PESs of the possible states that the complex may be formed in, when an oxygen and a nitrogen monoxide molecule meet on a plane using a number of high level ab initio methods. Finally, our conclusions were tested and applied when we performed the angular quantum dynamics to predict the rotational spectrum of the complex between an oxygen and a nitrogen dioxide molecule, and account for the effect of nuclear spin statistics in that system.

This Thesis describes the synthesis and characterisation of new alkaline earth- and rare earth-transition metal complexes. Experimental and computational studies were performed to investigate the structure and bonding in these complexes. Their reactivity was also studied. Chapter 1 introduces metal-metal bonded complexes and current alkaline earth- and rare earth-transition metal bonded complexes. Chapter 2 describes experimental and computational studies of new alkaline earth- and lanthanide-Fe complexes possessing the [CpFe(CO)2]- anion. Chapter 3 presents experimental studies of the reduction of Fe3(CO)12 with Ca. Chapter 4 describes experimental and computational studies of new alkaline earth- and lanthanide-Co complexes containing the [Co(CO)3(PR3)]- anion. Chapter 5 presents full experimental procedures and characterising data for the new complexes reported. Appendix describes the attempted synthesis of [Ca{CpRu(CO)2}2(THF)x]y and study by DFT of [CaRp2(THF)3]2 CD Appendix contains .cif files for all new crystallographically characterised complexes described.

Les applications industrielles FSI se caractérisent par des géométries et des matériaux complexes. Afin de prédire avec précision leur comportement, des coûts de calcul élevés sont associés, à la fois en temps et en ressources informatiques. Pour améliorer la qualité de la prédiction sans pénaliser le temps de calcul, et pour réduire le temps de calcul sans impacter la précision disponible aujourd'hui, deux axes principaux sont explorés dans ce travail. Le premier est l'étude d'un algorithme asynchrone qui pourrait permettre l'utilisation de modèles structurels complexes. Le second consiste à étudier la méthode des tranches en combinant l'utilisation d'un modèle RANS et d'un modèle FEM non linéaire. D'une part, l'étude de l'asynchronicité dans le domaine FSI a révélé différents aspect d'intérêt qui doivent être approfondis avant que l'approche puisse être utilisée industriellement. Cependant, un premier traitement des points mentionnés ci-dessus a montré des signe d'amélioration qui pourraient conduire à un algorithme prometteur, qui se situe naturellement entre l'algorithme explicite et l'algorithme implicite. D'autre part, il a été montré que la méthode des tranches développée dans ce travail conduit à une réduction significative du temps de calcul sans dégradation de la précision
FSI industrial applications are often described by complex geometries and materials. In order to accurately predict their behavior, high computational costs are associated, both in time and in computational resources. To improve the quality of the prediction without penalizing the computational time, and to reduce the computational time without impacting the accuracy that is available today, two main axes are explored in this work. The first one is the study of an asynchronous algorithm that could allow the use of complex structural models. The second axis consists of the study of the strip method while combining the use of a RANS model and a non-linear FEM model. On the one hand, the study of asynchronicity in the FSI domain revealed different aspects of interest that must be addressed before the approach can be used industrially. However, a first treatment of the limitations found showed signs of an improvement that could lead to a promising algorithm, one that naturally lies between the implicit external algorithm and the implicit internal algorithm. On the other hand, it was shown that the strip method developed in this work achieves a significant reduction in calculation time while maintaining excellent accuracy

Surface plasmon polaritons are non radiative modes which exist at the interface between a dielectric and a metal. They can confine light at sub-wavelength scales. However, their propagation is restricted by the intrinsic losses of the metal which imply a rapid absorption of the mode. The aim of this thesis is the study of the coupling of surface plasmons in metallo-dielectric planar structures. Obtaining the properties of the modes implies the extension of the solutions to the complex plane of propagation constants. The method used consists in determining the poles of the scattering matrix by means of Cauchy's integrals. The first solution to solve the problem of propagation of the surface plasmons consists in coupling these modes to one another. In a symmetric medium, when the thickness of the metallic film becomes thin enough, the coupling between the plasmon modes which exist on each side becomes possible. One of the coupled modes which is created, the so-called long range surface plasmon, has a bigger propagation length than the usual plasmon whereas the other coupled mode, named short range surface plasmon, has a smaller propagation length. We present a configuration which allows the excitation of the long range surface plasmon without the short range mode with a metallic layer deposited on a perfect electric conductor substrate. This excitation can be done in air and allows applications, such as the detection and the characterisation of molecules. Then, we present the coupling between dielectric waveguides, and, in particular, the coupled-mode theory in the case of the transverse magnetic polarisation. We consider also the case of PT symmetric structure. The last part of this work presents the demonstration of the strong coupling regime between a surface plasmon and a guided mode. We demonstrate an increase of the propagation length of the hybrid surface plasmon, which still has the confinement of a surface mode. A linear gain is added in the different layers of the structure. When the gain is added in the layer between both coupled modes allows an enhancement of the propagation lengths of the modes, and more precisely of the hybrid surface plasmon mode, which can propagate at the millimeter scale.

El cerebro está constituido por numerosos elementos que se encuentran interconectados de forma masiva y organizados en módulos que forman redes jerárquicas. Ciertas patologías cerebrales, como la enfermedad de Alzheimer y el trastorno por consumo de alcohol, se consideran el resultado de efectos en cascada que alteran la conectividad cerebral. La presente tesis tiene como objetivo principal la aplicación de las técnicas de análisis de la ciencia de redes para el estudio de las redes estructurales y funcionales en el cerebro, tanto en un estado control como en un estado patológico. Así, en el primer estudio de la presente tesis se examina la relación entre la conectividad estructural y funcional en la corteza cerebral de la rata. Se lleva a cabo un análisis comparativo entre las conexiones estructurales en la corteza cerebral de la rata y los valores de correlación calculados sobre las mismas regiones. La información acerca de la conectividad estructural se ha obtenido a partir de estudios previos, mientras que la conectividad funcional se ha calculado a partir de imágenes de resonancia magnética funcional. Determinadas propiedades topológicas, y extraídas de la conectividad estructural, se relacionan con la organización modular de las redes funcionales en estado de reposo. Los resultados obtenidos en este primer estudio demuestran que la conectividad estructural y funcional cortical están altamente relacionadas entre sí. Estudios recientes sugieren que el origen de la enfermedad de Alzheimer reside en un mecanismo en el cual depósitos de ovillos neurofibrilares y placas de beta-amiloide se acumulan en ciertas regiones cerebrales, y tienen la capacidad de diseminarse por el cerebro actuando como priones. En el segundo estudio de la presente tesis se investiga si las redes estructurales que se generan con la técnica de resonancia magnética ponderada en difusión podrían ser de utilidad para el diagnóstico de la pre-demencia causada por la enfermedad de Alzheimer. Mediante el uso de imágenes procedentes de la base de datos ADNI, se aplican técnicas de aprendizaje máquina con el fin de identificar medidas de centralidad que se encuentran alteradas en la demencia. En la segunda parte del estudio, se utilizan imágenes procedentes de la base de datos NKI para construir un modelo matemático que simule el proceso de envejecimiento normal, así como otro modelo que simule el proceso de desarrollo de la enfermedad. Con este modelado matemático, se pretende estimar la etapa más temprana que está asociada con la demencia. Los resultados obtenidos de las simulaciones sugieren que en etapas tempranas de la enfermedad de Alzheimer se producen alteraciones estructurales relacionados con la demencia. La cuantificación de la relación estadística entre las señales BOLD de diferentes regiones puede informar sobre el estado funcional cerebral característico de enfermedades neurológicas y psiquiátricas. En el tercer estudio de la presente tesis se estudian las alteraciones en la conectividad funcional que tienen lugar en ratas dependientes del consumo de alcohol cuando se encuentran en estado de reposo. Para ello, se ha aplicado el método NBS. El análisis de este modelo de rata revela diferencias estadísticamente significativas en una subred de regiones cerebrales que están implicadas en comportamientos adictivos. Por lo tanto, estas estructuras cerebrales podrían ser el foco de posibles dianas terapéuticas. La tesis aporta tres innovadoras contribuciones para entender la conectividad cerebral bajo la perspectiva de la ciencia de redes, tanto en un estado control como en un estado patológico. Los resultados destacan que los modelos basados en las redes cerebrales permiten esclarecer la relación entre la estructura y la función en el cerebro. Y quizás más importante, esta perspectiva de red tiene aplicaciones que se podrían trasladar a la práctica clínica.
The brain is composed of massively connected elements arranged into modules that form hierarchical networks. Experimental evidence reveals a well-defined connectivity design, characterized by the presence of strategically connected core nodes that critically contribute to resilience and maintain stability in interacting brain networks. Certain brain pathologies, such as Alzheimer's disease and alcohol use disorder, are thought to be a consequence of cascading maladaptive processes that alter normal connectivity. These findings have greatly contributed to the development of network neuroscience to understand the macroscopic organization of the brain. This thesis focuses on the application of network science tools to investigate structural and functional brain networks in health and disease. To accomplish this goal, three specific studies are conducted using human and rodent data recorded with MRI and tracing technologies. In the first study, we examine the relationship between structural and functional connectivity in the rat cortical network. Using a detailed cortical structural matrix obtained from published histological tracing data, we first compare structural connections in the rat cortex with their corresponding spontaneous correlations extracted empirically from fMRI data. We then show the results of this comparison by relating structural properties of brain connectivity to the functional modularity of resting-state networks. Specifically, we study link reciprocity in both intra- and inter-modular connections as well as the structural motif frequency spectrum within functionally defined modules. Overall, our results provide further evidence that structural connectivity is coupled to and shapes functional connectivity in cortical networks. The pathophysiological process of Alzheimer's disease is thought to begin years before clinical decline, with evidence suggesting pahtogenic seeding and subsequent prion-like spreading processes of neurofibrillary tangles and amyloid plaques. In the second study of this thesis, we investigate whether structural brain networks as measured with dMRI could serve as a complementary diagnostic tool in prodromal dementia. Using imaging data from the ADNI database, we first aim to implement machine learning techniques to extract centrality features that are altered in Alzheimer's dementia. We then incorporate data from the NKI database and create dynamical models of normal aging and Alzheimer's disease to estimate the earliest detectable stage associated with dementia in the simulated disease progression. Our model results suggest that changes associated with dementia begin to manifest structurally at early stages. Statistical dependence measures computed between BOLD signals can inform about brain functional states in studies of neurological and psychiatric disorders. Furthermore, its non-invasive nature allows comparable measurements between clinical and animal studies, providing excellent translational capabilities. In the last study, we apply the NBS method to investigate alterations in the resting-state functional connectivity of the rat brain in a PD state, an established animal model of clinical relevant features in alcoholism. The analysis reveal statistically significant differences in a connected subnetwork of structures with known relevance for addictive behaviors, hence suggesting potential targets for therapy. This thesis provides three novel contributions to understand the healthy and pathological brain connectivity under the perspective of network science. The results obtained in this thesis underscore that brain network models offer further insights into the structure-function coupling in the brain. More importantly, this network perspective provides potential applications for the diagnosis and treatment of neurological and psychiatric disorders.
El cervell està constituït per nombrosos elements que es troben interconnectats de forma massiva i organitzats en mòduls que formen xarxes jeràrquiques. Certes patologies cerebrals, com la malaltia d'Alzheimer i el trastorn per consum d'alcohol, es consideren el resultat d'efectes en cascada que alteren la connectivitat cerebral. La present tesi té com a objectiu principal l'aplicació de les tècniques d'anàlisi de la ciència de xarxes per a l'estudi de les xarxes estructurals i funcionals en el cervell, tant en un estat control com en un estat patològic. Així, en el primer estudi de la present tesi s'examina la relació entre la connectivitat estructural i funcional en l'escorça cerebral de la rata. Es du a terme una anàlisi comparativa entre les connexions estructurals en l'escorça cerebral de la rata i els valors de correlació calculats sobre les mateixes regions. La informació sobre la connectivitat estructural s'ha obtingut a partir d'estudis previs, mentre que la connectivitat funcional s'ha calculat a partir d'imatges de ressonància magnètica funcional. Determinades propietats topològiques, i extretes de la connectivitat estructural, es relacionen amb l'organització modular de les xarxes funcionals en estat de repòs. Els resultats obtinguts en este primer estudi demostren que la connectivitat estructural i funcional cortical estan altament relacionades entre si. Estudis recents suggereixen que l'origen de la malaltia d'Alzheimer resideix en un mecanisme en el qual depòsits d'ovulets neurofibrilars i plaques de beta- miloide s'acumulen en certes regions cerebrals, i tenen la capacitat de disseminar-se pel cervell actuant com a prions. En el segon estudi de la present tesi s'investiga si les xarxes estructurals que es generen amb la tècnica de la imatge per ressonància magnètica ponderada en difusió podrien ser d'utilitat per al diagnòstic de la predemència causada per la malaltia d'Alzheimer. Per mitjà de l'ús d'imatges procedents de la base de dades ADNI, s'apliquen tècniques d'aprenentatge màquina a fi d'identificar mesures de centralitat que es troben alterades en la demència. En la segona part de l'estudi, s'utilitzen imatges procedents de la base de dades NKI per a construir un model matemàtic que simule el procés d'envelliment normal, així com un altre model que simule el procés de desenrotllament de la malaltia. Amb este modelatge matemàtic, es pretén estimar l'etapa més primerenca que està associada amb la demència. Els resultats obtinguts de les simulacions suggereixen que en etapes primerenques de la malaltia d'Alzheimer es produeixen alteracions estructurals relacionats amb la demència. La quantificació de la relació estadística entre els senyals BOLD de diferents regions pot informar sobre l'estat funcional cerebral característic de malalties neurològiques i psiquiàtriques. A més, a causa de la seua naturalesa no invasiva, és possible comparar els resultats obtinguts entre estudis clínics i estudis amb animals d'experimentació. En el tercer estudi de la present tesi s'estudien les alteracions en la connectivitat funcional que tenen lloc en rates dependents del consum d'alcohol quan es troben en estat de repòs. Per a realitzar-ho, s'ha aplicat el mètode NBS. L'anàlisi d'aquest model de rata revela diferències estadísticament significatives en una subxarxa de regions cerebrals que estan implicades en comportaments addictius. Per tant, estes estructures cerebrals podrien ser el focus de possibles dianes terapèutiques. La tesi aporta tres innovadores contribucions per a entendre la connectivitat cerebral davall la perspectiva de la ciència de xarxes, tant en un estat control com en un estat patològic. Els resultats destaquen que els models basats en les xarxes cerebrals permeten aclarir la relació entre l'estructura i la funció en el cervell. I potser més important, esta perspectiva de xarxa té aplicacions que es podrien traslladar a la pràcti
Díaz Parra, A. (2018). A network science approach of the macroscopic organization of the brain: analysis of structural and functional brain networks in health and disease [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/106966
TESIS

Nous proposons un cadre statistique pour analyser les anomalies morphologiques et organisationnelles altérant l'anatomie des circuits neuronaux chez les patients atteints du syndrome de Gilles de la Tourette. Les composants de chaque circuit (matière grise et blanche) sont représentés comme des maillages 3D et intégrés dans un seul complexe. Cela permet d'étudier leur organisation et surtout la connectivité structurelle. La méthode proposée est basée sur une approche statistique appelée construction d'atlas qui résulte en un template, capturant les invariants de la population, et en déformations template-vers-sujets, décrivant la variabilité morphologique. Premièrement, nous intégrons la construction d'atlas dans un cadre bayésien qui permet d'estimer automatiquement des paramètres autrement fixés. Deuxièmement, nous réduisons les ressources de calcul nécessaires au traitement de faisceaux de fibres en définissant un schéma d'approximation basée sur un nouveau modèle appelé courants pondérés. Troisièmement, nous décrivons un nouveau modèle de déformation pour la construction d'atlas qui permet de capturer les variations morphologiques et organisationnelles. On montre l'efficacité de la méthode par comparaison de deux groupes de 44 patients et 22 témoins. Les résultats soulignent des anomalies sur la forme des structures de la matière grise et sur la connectivité structurelle
We propose a statistical framework to analyse morphological and organisational anomalies altering the anatomy of neural circuits in patients with Gilles de la Tourette syndrome. The components of each circuit, from both white and grey matter, are represented as 3D meshes and integrated in a single shape complex. This allows to study their organisation and in particular the structural connectivity. The proposed methodology is based on a statistical approach called atlas construction which results in a template complex, capturing the invariants of the population and in template-to-subject deformations, describing the morphological variability. First, we embed the atlas construction in a Bayesian framework which allows to automatically estimate important parameters otherwise fixed by the user. Second, we reduce the important computational resources required to process fiber bundles by defining an approximation scheme based on a new computational model called weighted currents. Third, we describe a new deformation scheme for the atlas construction which permits to model variations in structural connectivity and at the same time to capture global anatomical changes. We show the effectiveness of the proposed method by comparing two groups of 44 patients and 22 controls respectively. Results highlight anomalies about both the shape of grey matter structures and structural connectivity

Au cours des dernières décennies, des progrès remarquables ont été réalisés au niveau de la simulation d’écoulements sanguins dans des modèles anatomiques réalistes construits à partir de données d'imagerie médicale 3D en vue de simulation hémodynamique et physiologique 3D à grande échelle. Alors que les modèles anatomiques précis sont d'une importance primordiale pour simuler le flux sanguin, des conditions aux limites réalistes sont également importantes surtout lorsqu’il s’agit de calculer des champs de vitesse et de pression. La première cible de cette thèse était d'étudier l'analyse de convergence des inconnus pour différents types de conditions aux limites permettant un cadre flexible par rapport au type de données d'entrée (vitesse, pression, débit, ...). Afin de faire face au grand coût informatique associé, nécessitant un calcul haute performance, nous nous sommes intéressés à comparer les performances de deux préconditionneurs par blocs; le preconditionneur LSC (Least-Squared Commutator et le preconditionneur PCD (Pressure Convection Diffusion). Dans le cadre de cette thèse, nous avons implémenté ce dernier dans la bibliothèque Feel++. Dans le but de traiter l'interaction fluide-structure, nous nous sommes focalisés sur l'approximation de la force exercée par le fluide sur la structure, un champ essentiel intervenant dans la condition de continuité pour assurer le couplage du modèle de fluide avec le modèle de structure. Enfin, afin de valider nos choix numériques, deux cas tests ont été réalisés et une comparaison avec les données expérimentales et numériques a été établie et validée (le benchmark FDA et le benchmark Phantom)
Towards a large scale 3D computational model of physiological hemodynamics, remarkable progress has been made in simulating blood flow in realistic anatomical models constructed from three-dimensional medical imaging data in the past few decades. When accurate anatomic models are of primary importance in simulating blood flow, realistic boundary conditions are equally important in computing velocity and pressure fields. Thus, the first target of this thesis was to investigate the convergence analysis of the unknown fields for various types of boundary conditions allowing for a flexible framework with respect to the type of input data (velocity, pressure, flow rate, ...). In order to deal with the associated large computational cost, requiring high performance computing, we were interested in comparing the performance of two block preconditioners; the least-squared commutator preconditioner and the pressure convection diffusion preconditioner. We implemented the latter, in the context of this thesis, in the Feel++ library. With the purpose of handling the fluid-structure interaction, we focused of the approximation of the force exerted by the fluid on the structure, a field that is essential while setting the continuity condition to ensure the coupling of the fluid model with the structure model. Finally, in order to assess our numerical choices, two benchmarks (the FDA benchmark and the Phantom benchmark) were carried out, and a comparison with respect to experimental and numerical data was established and validated

GATA1 and KLF1 are transcription factors that regulate genes which are important for the development of erythroid cells. The GATA1 transcriptional co-factor FOG1 has been shown to be essential in a wide range of GATA1 dependent cellular functions. Here we tried to understand the diverse mechanisms by which GATA1 and KLF1 recognize their binding sites, how the GATA1 recognition mechanisms are affected by complexation with either FOG1 or KLF1 and how the GATA1 recognition mechanisms affect the transcriptional regulation of the erythroid differentiation. We profiled the DNA binding specificities/affinities of a GATA1 fragment (mGATA1NC), that contains only the two DNA binding domains (N-terminal and C-terminal Zn finger), and the DNA binding specificities/affinities of a KLF1 fragment (mKLF1257-358), that contains the three DNA binding domains, using a novel methodology that combines EMSA with high throughput sequencing (EMSA-seq (Wong et al., 2011a)). We also profiled the DNA binding specificities of the C-terminal Zn finger of GATA1 alone (mGATA1C), the wt-mGATA1, the wt-mGATA1/wt-mFOG1 complex and the mGATA1NC/mKLF1257-358 complex. At first, we confirmed that the N-terminal Zn finger of GATA1 has a strong preference for the “GATC” motif, whereas the C-terminal Zn finger of GATA1 has a strong preference for the “GATA” motif. Next, we found that in the mGATA1NC, both DNA binding domains can bind simultaneously a wide range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. The wt-mGATA1 did not show the ability to bind in the same co-occurring motifs implying an effect of the non-DNA binding domains of the protein in the regulation of its DNA binding specificities. On the contrary, complexation of wt-mGATA1 with the wt-mFOG1 partially restored its ability to bind in a now limited range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. Similar observations were made for other pairs of GATA1 N-terminal and C-terminal Zn finger specific motifs. We then projected the GATA1 DNA binding specificities/affinities in vivo and we classified the GATA1 ChIP-seq peaks in low, medium or high affinity based on the number of the GATA1 motifs. We noticed that high affinity GATA1 ChIP-seq peaks tend to appear in regions with low nucleosome occupancy. We also noticed that GATA1 ChIP-seq peaks in the enhancer regions are usually high affinity whereas GATA1 ChIP-seq peaks in the proximal promoter regions are usually low affinity. Additionally, we observed that high affinity GATA1 ChIP-seq peaks are usually found in regions with increased levels of H3K4me2 and are associated with a higher decrease in the H3K4me3 levels on the TSS of the nearby genes. None of these GATA1 related in vivo observations were found for the KLF1 ChIP-seq positions. These findings significantly advance our understanding of the DNA binding properties of GATA1, KLF1 and their complexes and give an insight on the importance of the GATA1 DNA binding affinities in the regulation of the erythroid transcriptional program. Overall the work establishes an experimental and analytical framework to investigate how transcriptional co-factors can change the DNA binding specificities of specific transcription factors and how integration of the transcription factor DNA binding affinities with in vivo data can give novel insights into the transcriptional regulation.

Attention, ce résumé comporte un peu d'ironie et d'humour. Dans ce mémoire, nous défendons l'idée selon laquelle, pour tout modèle de calcul raisonnable, ce n'est plus tant le modèle qui compte pour caractériser les classes de complexité importantes que la complexité de la structure combinatoire sous-jacente et en définitive d'un graphe sous-jacent. Pour prendre l'exemple des circuits booléens ou algébriques comme modèles, tout ce qui importe est la complexité du graphe orienté sous-jacent au circuit. Par modèle de calcul raisonnable, nous entendons, comme il se doit, un modèle qui étudié sur une classe de graphes standard nous donne la classe de complexité standard attendue afin de satisfaire aux règles élémentaires des tautologies. On pourrait aussi choisir comme modèles raisonnables les modèles Turing-complet (ou une autre notion de complétude plus adaptée selon les objets calculés), formalisables dans une logique simple (afin d'éviter les "tricheries" et les modèles conçus spécialement pour faire échouer la belle idée défendue). Néanmoins, cette seconde option n'étant pas sans risque, nous nous contentons de la proposer. La thèse défendue est une version un peu plus formalisée et précise mathématiquement de cette idée aux contours un peu flous et qui est donc nécessairement un peu fausse telle quelle.

Ce travail de thèse de doctorat, effectué au sein de Laboratoire de Simulation et Modélisation Électromagnétique (LSME) du CEA List, s’intègre dans le cadre du projet européen « NDTonAir » financé sous l'action « H2020-MSCA-ITN-2016- GRANT 722134 ». Le principal objectif est le développement d’un outil de simulation rapide et précis dédié au contrôle non destructif par courants de Foucault des matériaux composites homogénéisés. Comme cas d’application, on s’intéresse particulièrement à l’orientation des fibres d’une part, et d’autre part, à des défauts de type délaminage et ondulation des fibres qui se manifestent par une déformation géométrique locale des interfaces. Les méthodes semi-analytiques existantes dans la littérature, basées sur le formalisme des Dyades de Green, sont limitées jusqu’au là à des structures planes multicouches. Pour introduire des variations locales de géométrie aux interfaces, nous proposons une approche innovante basée sur un changement de coordonnées adapté au profil de la pièce et des interfaces. On propose un modèle numérique performant basé sur le formalisme covariant des équations de Maxwell. Ce formalisme unificateur englobe l'anisotropie du spécimen et les déformations locales des interfaces. La méthode de coordonnées curvilignes est usuellement utilisée pour résoudre des problèmes de diffraction sur des surfaces rugueuses dans le domaine des hautes fréquences (diffraction sur des réseaux). Ce travail de thèse s’inspire des méthodes de Fourier modale et propose de nouveaux outils adaptés au domaine des courants de Foucault. L’extension de la méthode des coordonnées curvilignes au domaine du contrôle des composites par courants de Foucault constitue l’innovation de ce travail. Deux modèles numériques ont été développés pour le calcul de l’interaction du champ émis par un capteur à courants de Foucault avec un matériau composite multicouches. Le modèle numérique développé pour le contrôle des composites plans exploite les structures particulières des matrices creuses pour réduire le temps de calcul sans limitation de nombre de modes utilisés pour la représentation du champ. Dans le cas des profils curvilignes des interfaces, le modèle permet de traiter des interfaces parallèles et quelques cas particuliers des profils non parallèles. Ce cas général présente quelques limitations qui nécessitent le développement des outils numériques complémentaires. Enfin, plusieurs configurations de contrôle ont été envisagées et les résultats numériques produits par les modèles ont été confrontés à des données de simulation par éléments finis. Quelques expérimentations ont été effectuées dans des laboratoires partenaires étrangers pour accroître notre expérience sur la validation expérimentale
This doctoral thesis work, carried out within the Laboratory of Simulation and Modeling for Electromagnetics (LSME) of CEA List, is part of the “NDTonAir” European project funded under the action “H2020-MSCA-ITN -2016- GRANT 722134”. The main goal of the project is the development of a fast and accurate simulation tool for the non-destructive eddy current testing of homogenized composite materials. As an application case, we are particularly interested in the orientation of the fibers on the one hand, and on the other hand, in defects as delamination which are manifested by a local geometrical deformation of the interfaces. The semi-analytical methods existing in the literature, based on Green's Dyad formalism, have been limited so far to multilayered and planar structures. To introduce local variations in geometry at the interfaces, we propose an innovative approach based on a change of coordinates adapted to the profile of the local perturbation. We propose a powerful numerical model based on the covariant formalism of Maxwell's equations. This unifying formalism takes in the anisotropy of specimen and the local deformations of the interfaces. The curvilinear coordinate method is usually used to solve diffraction problems on rough interfaces in the high frequency domain (diffraction on gratings). This thesis work is inspired by Fourier Modal Methods and proposes new tools which have been adapted to the field of eddy currents. The extension of the curvilinear coordinate method to the field of eddy currents non-destructive testing technique of composites constitutes the innovation of this work. Two numerical models have been developed to calculate the interaction of the field emitted by an eddy current probe with a multilayered composite material. The numerical model developed for the evaluation of planar composite exploits the particular structures of sparse matrices to reduce the computation time without limiting the number of modes used for the modal expansion of the field. In the case of the curvilinear profiles of the interfaces, the model makes it possible to treat parallel interfaces and some particular cases of non-parallel profiles. The general case of non-identical profiles presents some limitations which require the development of complementary numerical tools. Finally, several testing configurations were considered and the numerical results produced by the models were compared to finite element simulated data. Some experiments were carried out in foreign partner laboratories to increase our experience on experimental validation

A common challenge in materials science is the "inverse design problem," wherein one seeks to use theoretical models to discover the microscopic characteristics (e.g., interparticle interactions) of a system which, if fabricated or synthesized, would yield a targeted material property. Inverse design problems are commonly addressed by stochastic optimization strategies like simulated annealing. Such approaches have the advantage of being general and easy to apply, and they can be effective as long as material properties required for evaluating the objective function of the optimization are feasible to accurately compute for thousands to millions of different trial interactions. This requirement typically means that "exact" yet computationally intensive methods for property predictions (e.g., molecular simulations) are impractical for use within such calculations. Approximate theories with analytical or simple numerical solutions are attractive alternatives, provided that they can make sufficiently accurate predictions for a wide range of microscopic interaction types. We propose a new approach, based on the fine discretization (i.e., terracing) of continuous pair interactions, that allows first-order mean-spherical approximation theory to predict the equilibrium structure and thermodynamics of a wide class of complex fluid pair interactions. We use this approach to predict the radial distribution functions and potential energies for systems with screened electrostatic repulsions, solute-mediated depletion interactions, and ramp-shaped repulsions. We create a web applet for introductory statistical mechanics courses using this approach to quickly estimate the equilibrium structure and thermodynamics of a fluid from its pair interaction. We use the applet to illustrate two fundamental fluid phenomena: the transition from ideal gas-like behavior to correlated-liquid behavior with increasing density in a system of hard spheres, and the water-like tradeoff between dominant length scales with changing temperature in a system with ramp-shaped repulsions. Finally, we test the accuracy of our approach and several other integral equation theories by comparing their predictions to simulated data for a series of different pair interactions. We introduce a simple cumulative structural error metric to quantify the comparison to simulation, and find that according to this metric, the reference hypernetted chain closure with a semi-empirical bridge function is the most accurate of the tested approximations.
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In recent decades, scientific data has become available in increasing sizes and precision. Therefore techniques to analyze and summarize the ever increasing datasets are of vital importance. A common form of scientific data, resulting from simulations as well as observational sciences, is in the form of scalar-valued function on domains of interest. The Morse-Smale complex is a topological data-structure used to analyze and summarize the gradient behavior of such scalar functions. This thesis deals with efficient parallel algorithms to compute the Morse-Smale complex as well as its application to datasets arising from cosmological sciences as well as structural biology. The first part of the thesis discusses the contributions towards efficient computation of the Morse-Smale complex of scalar functions de ned on two and three dimensional datasets. In two dimensions, parallel computation is made possible via a paralleizable discrete gradient computation algorithm. This algorithm is extended to work e ciently in three dimensions also. We also describe e cient algorithms that synergistically leverage modern GPUs and multi-core CPUs to traverse the gradient field needed for determining the structure and geometry of the Morse-Smale complex. We conclude this part with theoretical contributions pertaining to Morse-Smale complex simplification. The second part of the thesis explores two applications of the Morse-Smale complex. The first is an application of the 3-dimensional hierarchical Morse-Smale complex to interactively explore the filamentary structure of the cosmic web. The second is an application of the Morse-Smale complex for analysis of shapes of molecular surfaces. Here, we employ the Morse-Smale complex to determine alignments between the surfaces of molecules having similar surface architecture.

Stabilization of highly strained organic species and altering normal reactivity norms of organic fragments by transition metals have been a triumphing feat of organometallic chemistry. A variety of saturated and unsaturated metallacycles result from the reactions of the transition metals with the organic entities. Understanding the structure and bonding of the metallacylces has been indispensable over the years in view of its involvement as intermediates or compounds for numerous synthetic and catalytic applications. In this context, Group 4 metallocenes have unlocked a fascinating chemistry by stabilizing strained unsaturated C4 organic fragments in the form of five-membered metallacyclomulenes, metallacyclopentynes and metallacycloallnes. These molecules do not conform to the existing bonding principles of chemistry. We have carried out a comprehensive theoretical study to understand the unsual stability and reactivity of these metallacycles. Our theoretical study reveals that the unique interaction of the internal carbon atoms along with the terminal carbon atoms with the bent metallocene moiety is the reason for unsual stability of the metallacycles. We have also investigated the mechanism of interesting C-C coupling and cleavage reactions involving metallacyocumulenes. It demonstrates unexpected reaction pathway for these metallacycles. Moreover, based on this understanding, we have predicted and unraveled the stabilization factors of a challenging four membered metallcycloallene complex. Indeed, our prediction about a four-membered heterometallacycle has been realized experimentally. This kind of bonding is intriguing from fundamental perspective and has great relevance in synthesizing unsual structures with interesting properties. Finally, the electronic structure and bonding of a metallocene-alkyne complex is analyzed to determine the nature of bonding. Our aim is to build a conceptual framework to understand these metallacycles and to exploit their chemistry.

Predicting the structure of complexes formed by two interacting proteins is an important problem in computation structural biology. Proteins perform many of their functions by binding to other proteins. The structure of protein-protein complexes provides atomic details about protein function and biochemical pathways, and can help in designing drugs that inhibit binding. Docking computationally models the structure of protein-protein complexes, given three-dimensional structures of the individual chains. Protein docking methods have two phases. In the first phase, a comprehensive, coarse search is performed for optimally docked models. In the second refinement and reranking phase, the models from the first phase are refined and reranked, with the expectation of extracting a small set of accurate models from the pool of thousands of models obtained from the first phase. In this thesis, new algorithms are developed for the refinement and reranking phase of docking. New scoring functions, or potentials, that rank models are developed. These potentials are learnt using large-scale machine learning methods based on mathematical programming. The procedure for learning these potentials involves examining hundreds of thousands of correct and incorrect models. In this thesis, hierarchical constraints were introduced into the learning algorithm. First, an atomic potential was developed using this learning procedure. A refinement procedure involving side-chain remodeling and conjugate gradient-based minimization was introduced. The refinement procedure combined with the atomic potential was shown to improve docking accuracy significantly. Second, a hydrogen bond potential, was developed. Molecular dynamics-based sampling combined with the hydrogen bond potential improved docking predictions. Third, mathematical programming compared favorably to SVMs and neural networks in terms of accuracy, training and test time for the task of designing potentials to rank docking models. The methods described in this thesis are implemented in the docking package DOCK/PIERR. DOCK/PIERR was shown to be among the best automated docking methods in community wide assessments. Finally, DOCK/PIERR was extended to predict membrane protein complexes. A membrane-based score was added to the reranking phase, and shown to improve the accuracy of docking. This docking algorithm for membrane proteins was used to study the dimers of amyloid precursor protein, implicated in Alzheimer's disease.R. DOCK/PIERR was shown to be among the best automated docking methods in community wide assessments. Finally, DOCK/PIERR was extended to predict membrane protein complexes. A membrane-based score was added to the reranking phase, and shown to improve the accuracy of docking. This docking algorithm for membrane proteins was used to study the dimers of amyloid precursor protein, implicated in Alzheimer’s disease.
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In bacteria, nucleoid associated proteins (NAPs) represent a prominent group of global regulators that perform the tasks of genome compaction, establishing chromosomal architecture and regulation of various DNA transactions like replication, transcription, recombination and repair. HU, a basic histone like protein, is one of the most important NAPs in Eubacteria. Mycobacterium tuberculosis produces a homodimeric HU (MtbHU), which interacts with DNA non-specifically through minor groove binding. Exploration for essential genes in Mtb (H37Rv) through transposon insertion has identified HU coding gene [Rv2986c, hupB; Gene Id: 15610123; Swiss-Prot ID: P95109)] to be vital for the survival and growth of this pathogen. MtbHU contains two domains, the N-terminal domain which is considerably conserved among the HU proteins of the prokaryotic world, and a C–terminal domain consisting of Lys-Ala rich multiple repeat degenerate motifs. Sequence analysis carried out by the thesis candidate showed that MtbHU exhibits 86 to 100 percent identity within the N-term region among all the mycobacterium species and some of the members of actinobacteria, including important pathogens like M. tuberculosis, M. leprae, M. ulcerans, M. bovis, Nocardia; while C term repeat region varies relatively more. This strikingly high cross species identity establishes the MtbHU N-terminal domain (MtbHUN) as an important representative structural model for the above mentioned group of pathogens. The thesis candidate has solved the X-ray crystal structure of MtbHUN, crystallized in two different forms, P2 and P21. The crystal structures in combination with computational analyses elucidate the structural details of MtbHU interaction with DNA. Moreover, the similar mode of self assembly of MtbHUN observed in two different crystal forms reveals that the same DNA binding interface of the protein can also be utilized to form higher order oligomers, that HU is known to form at higher concentrations. Though the bifunctional interface involved in both DNA binding and self assembly is not akin to a typical enzyme active site, the structural analysis identified key interacting residues involved in macromolecular interactions, allowing us to develop a rationale for inhibitor design. Further, the candidate has performed virtual screening against a vast library of compounds, and design of small molecules to target MtbHU and disrupt its binding to DNA. Various biochemical, mutational and biological studies were performed in the laboratory of our collaborator Prof. V. Nagaraja, MCBL, IISc., to investigate these aspects. After a series of iterations including design, synthesis and validation, we have identified novel candidate molecules, which bind to MtbHU, disrupt chromosomal architecture and arrest M. tuberculosis growth. Thus, the study suggests that, these molecules can serve as leads for a new class of DNA-interaction inhibitors and HU as a druggable target, more so because HU is essential to Mtb, but absent in human. Our study proposes that, targeting the nucleoid associated protein HU in Mtb can strategize design of new anti-mycobacterial therapeutics. Perturbation of MtbHU-DNA binding through the identified compounds provides the first instance of medium to small molecular inhibitors of NAP, and augurs well for the development of chemical probe(s) to perturb HU functions, and can be used as a fundamental chemical tool for the system level studies of HU-interactome. Section I: “Crystal structure of Mycobacterium tuberculosis histone like protein HU and structure based design of molecules to inhibit MtbHU-DNA interaction: Leads for a new target.” of this thesis presents an elaborate elucidation of the above mentioned work. The candidate has additionally carried out structure based computational and theoretical work to elucidate the interaction of amino acid based metal complexes which efficiently bind to DNA via minor-groove, major-groove or base intercalation interaction and display DNA cleavage activity on photo-irradiation. This understanding is crucial for the design of molecules towards Photodynamic Therapy (PDT). PDT is an emerging method of non-invasive treatment of cancer in which drugs like Photofrin show localized toxicity on photoactivation at the tumor cells leaving the healthy cells unaffected. The work carried out in our group in close collaboration with Prof. A.R. Chakravarty of Inorganic and Physical Chemistry Department elaborates the structure based design of Amino acid complexes containing single Cu (II), such as [Cu(L-trp)(dpq)(H2O)]+ , [Cu (L-arg) 2](NO3)2 , Amino acid complexes containing oxobridged diiron Fe(III), such as [{Fe(L-his)(bpy)}2(μ-O)](ClO4)2 , [{Fe(L-his)(phen)}2(μ-O)](ClO4)2 , and Complexes containing Binuclear Cu(II) coordinated organic moiety, such as [{(dpq) CuII}2(μ-dtdp)2], which bind to DNA through minor groove/major groove/base intercalation interactions. Docking analysis was performed with the X-ray crystallographic structure of DNA as receptor and the metal complexes as ligands, to study the mode of binding to DNA and to understand the possible mode of DNA cleavage (single/double strand) when activated with laser. Section II: “Structure based computational and theoretical analysis of metal coordinated complexes containing amino acids and organic moieties designed for photo induced DNA cleavage” of this thesis presents a detailed presentation of the above mentioned work.

Mass spectrometry with electrospray ionization is an excellent method for structural analysis of coordination compounds with outstanding sensitivity and selectivity. However, it fails to detect some low-polar rhenium complexes. This master thesis describes derivatization method of non-ionizable rhenium complexes with 1,2-dihydroxybenzene and 2,3- dihydroxytoluenene. Fragmentation mechanisms and structure of prepared complexes was studied using high resolution mass spectrometry and collision-induced dissociation (CID). Furthermore, density functional theory (DFT) computational method was used for prediction of bond cleavage based on bond lengthening.

Tesis (Lic. en Física)--Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física, 2011.
En este trabajo se presentan modelos de potencial finito que pueden ser utilizados para describir partículas atrapadas en puntos cuánticos en dos y tres dimensiones. El estudio de los modelos se realiza a partir de diferentes métodos, todos numéricos, y que se aplican luego de resolver el problema de autovalores y autovectores mediante un método aproximado: el Método de Ryleigh Ritz. En el caso de Dos Dimensiones se destacan los estados resonantes y los métodos utilizados para poder detectarlos. Mientras que en tres dimensiones sólo se realiza un estudio muy breve de un sistema, con un potencial que posee y sólo simetría azimutal, se propone una forma de controlar el espectro de energías, a partir de someter el sistema a la presencia de un campo magnético constante, sin la pérdida de estados resonantes.

Ce projet de recherche mené en collaboration industrielle avec St-Jean Photochimie Inc. / PCAS Canada vise le développement et la caractérisation de dérivés dipyrrométhène pour des applications dans le domaine du photovoltaïque. La quête du récoltage des photons se situant dans le proche-infrarouge a été au centre des modifications structurales explorées afin d’augmenter l’efficacité de conversion des cellules solaires de type organique et à pigments photosensibles. Trois familles de composés intégrant le motif dipyrrométhène ont été synthétisées et caractérisées du point de vue spectroscopique, électrochimique, structural ainsi que par modélisation moléculaire afin d’établir des relations structures-propriétés. La première famille comporte six azadipyrrométhènes au potentiel de coordination tétradentate sur des centres métalliques. Le développement d’une nouvelle voie synthétique asymétrique combinée à l’utilisation d’une voie symétrique classique ont permis d’obtenir l’ensemble des combinaisons de substituants possibles sur les aryles proximaux incluant les noyaux 2-hydroxyphényle, 2-méthoxyphényle et 2- pyridyle. La modulation du maximum d’absorption dans le rouge a pu être faite entre 598 et 619 nm. De même, la présence de groupements méthoxyle ou hydroxyle augmente l’absorption dans le violet (~410 nm) tel que démontré par modélisation. La caractérisation électrochimique a montré que les dérivés tétradentates étaient en général moins stables aux processus redox que leur contre-parti bidentate. La deuxième famille comporte dix dérivés BODIPY fusionnés de façon asymétrique en position [b]. L’aryle proximal a été modifié de façon systématique afin de mieux comprendre l’impact des substituents riches en électron et de la fusion de cycles aromatiques. De plus, ces dérivés ont été mis en relation avec une vaste série de composés analogues. Les résultats empiriques ont montré que les propriétés optoélectroniques de la plateforme sont régies par le degré de communication électronique entre l’aryle proximal, le pyrrole sur lequel il est attaché et le noyau indolique adjacent à ce dernier. Les maximums d’absorption dans le rouge sont modulables entre 547 et 628 nm et la fluorescence des composés se situe dans le proche- infrarouge. L’un des composé s’est révélé souhaitable pour une utilisation en photovoltaïque ainsi qu’à titre de sonde à pH. La troisième famille comporte cinq complexes neutres de RuII basés sur des polypyridines et portant un ligand azadipyrrométhène cyclométalé. Les composés ont montré une forte absorption de photons dans la région de 600 à 800 nm (rouge à proche- infrarouge) et qui a pu être étendue au-delà de 1100 nm dans le cas des dérivés portant un ligand terpyridine. L’analyse des propriétés optoélectroniques de façon empirique et théorique a montré un impact significatif de la cyclométalation et ouvert la voie pour leur étude en tant que photosensibilisateurs en OPV et en DSSC. La capacité d’un des complexes à photo-injecter un électron dans la bande de conduction du semi-conducteur TiO2 a été démontré en collaboration avec le groupe du Pr Gerald J. Meyer à University of North Carolina at Chapel Hill, premier pas vers une utilisation dans les cellules solaires à pigments photosensibles. La stabilité des complexes en solution s’est toutefois avérée problématique et des pistes de solutions sont suggérées basées sur les connaissances acquises dans le cadre de cette thèse.
This research project carried out in industrial collaboration with Saint-Jean Photochemicals Inc. / PCAS Canada aims at the development and characterization of dipyrromethene derivatives for photovoltaic applications. The quest for harvesting near- infrared photons was the central focus and various structural modifications were explored to improve the power conversion efficiency of organic and dye-sensitized solar cells (OPV and DSSC, respectively). Three families of chromophores which embedded a dipyrromethene motif were synthesized and characterized through spectroscopy, electrochemistry, X-ray diffraction and computationnal modelization in order to establish their structure-properties relationship. The first family includes six azadipyrromethenes with potential for tetradentate coordination on metallic centers. The development of a new asymmetric synthetic route together with the classical symmetric one allowed access to all possible combinations of derivatives including 2-hydroxyphenyl, 2-methoxyphenyl and 2-pyridyl substituents in the proximal position of the dipyrromethene. Modulation of the absorption maxima in the red ranged between 598 and 619 nm. Also, having methoxy or hydroxy substituents provided an increase of the violet absorption (~410 nm) as established by modelization. Electrochemical characterization showed that the tetradentate azadipyrromethenes were generally less stable towards redox processes as compared to their bidentate counter- parts. The second family includes ten asymmetric benzo[b]-fused BODIPYs where the proximal aryl was systematically modified in order to assess the impact of electron-rich substituents and fused aromatic cycles. The derivatives were further compared to a wide series of related BODIPYs. Empirical results showed the optoelectronic properties are dictated by the extend of electronic communication between the proximal aryl, the pyrrol to which it is attached and the adjacent indolic moiety. Absorption maxima in the red were modulated between 547 nm and 628 nm and the fluorescence was in the near-infrared. One compound proved to be a potential candidate for photovoltaic and pH probe applications. The third family includes five neutral RuII polypyridine complexes bearing a cyclometalated azadipyrromethene ligand. The compounds exhibit strong light absorption in the 600 – 800 nm range (red to near-infrared) that tails beyond 1100 nm in the terpyridine-based adducts. Analysis of the optoelectronic properties showed a significant impact of this novel cyclometalation strategy for dipyrromethene derivatives and paved the way for further incorporation of the resulting complexes as photosensitizers in OPV and DSSC. In collaboration with the group of Pr Gerald J. Meyer at the University of North Carolina at Chapel Hill, the capacity of one compound to photo-inject its electron into the conduction band of the TiO2 semiconductor was established, a first step towards their use in dye-sensitized solar cells. The structural instability in solution of the complexes hindered their full potential for photovoltaic applications and suggestions to improve them are proposed based on the knowledge acquired in the course of this thesis.