Various modern spectroscopies have been utilized with considerable success in recent years to probe the dynamics of vibrational and reorientational relaxation of molecules in condensed phases. We have studied the temperature dependence of the polarized and depolarized Raman spectra of various modes in the following dihalomethanes: dibromomethane, dichloromethane, dichloromethane-d2, and bromochloromethane. Among other observed trends, we have found the following: Vibrational dephasing times calculated from the bend) and (C-Br stretch) lineshapes are of the same magnitude in CI^B^. The vibrational dephasing time of [C-D(H) stretch] is twice as long in CD2Cl2 as in CH-^C^, and the relaxation time of (C-Cl stretch) is greater in CI^C^ than in CD2CI2. Isotropic relaxation times for all three stretching vibrations are significantly shorter in C^BrCl than in CI^C^ or CI^B^. Application of the Kubo model revealed that derived modulation times are close to equal for equivalent vibrations in the various dihalomethanes. Thus, the more efficient relaxation of the A^ modes in CE^BrCl can be attributed almost entirely to the broader mean squared frequency perturbation of the vibrations in this molecule.

L’objection générale de ces travaux est de comprendre les mécanismes d’interaction de molécules d’intérêt avec les membranes afin de faciliter la synthèse de molécules plus efficaces contre leurs cibles tout en étant moins toxique pour l’Homme. Dans la première partie de ces travaux, nous avons étudié les interactions entre ces modèles membranaires et les polyènes antifongiques, connus pour interagir avec les stérols des membranes plasmiques. Nous nous sommes particulièrement intéressés à la Nystatine et à l’Amphotéricine B, deux molécules de structure chimique très proche et actuellement utilisées dans l’industrie pharmaceutique. L’utilisation de différents modèles membranaires et de techniques adaptées a montré que la PhosphatidylEthanolamine avait très vraisemblablement un rôle primordial dans le mécanisme d’interaction de ces molécules avec les membranes. Dans la deuxième partie de ces travaux, nous nous sommes intéressés à l’inhibition de la formation du cristal d’hémozoïne formé lors de la croissance du parasite responsable du paludisme. Ce cristal est formé d’hématine, hautement toxique pour le parasite. L’hématine et l’inhibition de la formation de l’hémozoïne constituent une cible moléculaire idéale pour combattre cette maladie. La chloroquine, la méfoquine et de nouveaux inhibiteurs dérivés de la méfloquine ont été utilisés. L’étude de l’inhibition de la formation du cristal s’est faite en utilisant des monocouches de Langmuir, servant ainsi de biocapteurs. Ces travaux ont montré que l’énantiomérie, mais aussi la lipophilicité des nouveaux composés antipaludiques sont des paramètres importants en vue de la synthèse de molécules plus efficaces. / The main purpose of this work is to better understand the mechanisms of interaction between pharmaceutical relevant molecules and model membranes in order to facilitate the synthesis of new molecules, more efficient against their molecular target and less toxic for Humans. In the first part, we studied the interactions occuring between these models and antifungal polyene molecules. It has been reported that these molecules interacted preferentially with sterols. We specifically focused on Nystatin and Amphotericin B, two polyenes with a very similar chemical structure and presently used as a treatment against fungi and molds. Using different kind of model membranes, we showed PhosphatidylEthanolamine could have a very important role in the mechanism of action of these molecules. In the second part of this work, we studied the inhibition of the formation of a cristal called « hemozoïn », which is growing during the life cycle of the parasite responsible of malaria. This cristal is made of hematin, a toxic by-product of the degradation of hemoglobin, the main source of amino-acids for the parasite. Hematin and the inhibition of the growth of this cristal is a ideal molecular target to combat malaria. Chloroquine, mefloquine and new mefloquine-derivatives were studied. The study of the inhibition of the formation of the cristal was done using Langmuir monolayers as a biosensor. We showed that stereochemistry, but also lipophilicity of these compounds, are important parameters for the synthesis of more efficient antimalarial molecules.

Philosophiae Doctor - PhD / metal-containing complexes, that exhibit enhanced chemical and physical properties. This thesis describes the synthesis of new metal-containing linear polymers and dendritic molecules. Chapter 1 presents an overview of the field of metal-containing polymers, with particular attention to the synthesis of polymers via condensation polymerisation. This review includes the various types of metal-containing condensation polymers and the applications of these materials, where available. This discussion is followed by a brief summary of metal-containing dendrimers, which includes a concise description of their structure and applications in general. There are two routes to preparing metal-containing polymers. Chapter 2 describes the synthesis of three bifunctional organometallic monomers, of the general type [M]-O-{2,6-(CH2OH)2-4-CH3-C6H2}, where [M] represents the various metal-containing moieties, (η5-C5H5)(CO)2 Fe(CH2)3 (25), (η5-C5H4-CH2CH2CH2-)Re(CO)3 (26) and Fpdendr (27). These monomers were prepared using 2,6-bis(hydroxymethyl)-p-cresol as the key reagent. The monomers were used in classical polycondensation reactions with terephthaloyl chloride using ambient temperature solution techniques. This yielded new low molecular weight oligomeric polyesters, that were characterised using FTIR and 1HNMR spectroscopy, differential scanning calorimetry, thermogravimetric analysis and sizeexclusion chromatography. In Chapter 3, an alternate route to metal-containing polymers is described. In this case, bifunctional organic monomers were polymerised to give preformed organic polymers. Two types of organic polymers were prepared, viz. polyesters (with pendant vinyl moieties) and polyimines (with α-diimine units along the polymer backbone). Functionalisation of these preformed organic polymers with various metal sources was attempted. Hydrozirconation reactions of the vinyl polyesters with Schwartz’s reagent, Cp2Zr(H)Cl, were attempted and were largely unsuccessful. Competing reactions with the ester functionality prevailed, preventing the desired reaction. Reaction of the polyimines with PdCl2(COD) yielded insoluble, intractable metal-containing oligomers. Partial characterisation of the complexes is described. The synthesis of new poly(propylene imine) iminopyridyl metallodendrimers is described in Chapter 4. Schiff-base condensation reaction of the commercially available DAB dendrimers with 2-pyridinecarboxaldehyde, gave the dendrimers 51, 52, and 53, with four, eight and sixteen pyridylimine functionalities respectively on the periphery. Successful complexation reactions with PdCl2(COD), PtCl2(COD) and CuCl2 produced the corresponding metal-containing dendrimers, with either PdCl2 (54, 55, 56), PtCl2 (57) or CuCl2 (58) moieties bound on the periphery. The metallodendrimers were insoluble in the more common organic solvents, and were characterised by IR and 1H-NMR spectroscopy and microanalysis where possible. Dendrimers with salicylaldiminato ligands on the periphery were prepared by reacting the DAB dendrimers with salicylaldehyde. These ligands were reacted with various metal acetates in an attempt to prepare new metalcontaining salicylaldimine dendrimers. This work yielded either paramagnetic metal complexes or insoluble, intractable compounds. Chapter 5 describes the applications of the catalyst precursors (54, 55, 56, 57, 58), discussed in Chapter 4, in the polymerisation of ethylene and the use of complexes 54 and 55 as Heck cross-coupling catalyst precursors. The complexes all showed catalytic activity toward ethylene polymerisation. A discussion of their activity, the polyethylene molecular weight and microstructure is presented in this chapter. The precursors 54 and 55 are also effective catalysts in the Heck reactions, coupling iodobenzene with methyl acrylate, styrene and 1-octene in high conversions. / South Africa

Plusieurs molécules d’intérêt astrochimique appartenant à la famille du cyanoacétylène ont été caractérisées spectroscopiquement. Des études photochimiques ont également été menées sur ces molécules. La technique d’isolation en matrice cryogénique de gaz rare a été utilisée pour la préparation de la plupart des échantillons. Des molécules étudiées étaient : CH₃C₃N (et certains de ses isomères), CH₃C₅N, HC₅N – toutes disponibles via une synthèse organique, ainsi que celles obtenues comme produits de réactions photochimiques, principalement en matrice de Kr : HC₉N, à partir de C₄H₂ + HC₅N, et de C₁₀N₂, à partir soit de C₄H₂ + HC₅N soit de HC₅N + HC₅N. La méthode a pu être étendue à la synthèse de composés méthylés avec la formation de CH₃C₅N à partir de CH₃C₂H + HC₃N et de CH₃C₇N à partir de CH₃C₂H + HC₅N. De plus, les expériences photochimiques sur les matrices contenant HC₅N ont conduit à la détection de HC₇N et de l'anion C₅N⁻. Un mécanisme général décrivant les processus d'élongation des chaînes a été formulé. Les similarités ou différences présentes dans les règles de sélection, les écarts vibroniques, les énergies des transitions électroniques et les durées de vie de phosphorescence ont été examinées pour les séries homologues HC₂n+₁N, NC₂nN et CH₃C₂n+₁N. / Several astrochemically interesting molecules of the cyanoacetylene family have been characterized spectroscopically. Photochemical studies involving these molecules have also been performed. The cryogenic rare-gas matrix isolation technique was employed for the preparation of most of the samples. The tudied molecules were: CH₃C₃N (and some of its isomers), CH₃C₅N, HC₅N – all available via preparative organic chemical synthesis, as well as those that appeared as the products of photochemical reactions run mostly in solid Kr: HC₉N, starting from C₄H₂ + HC₅N, and C₁₀N₂, starting from either C₄H₂ + HC₅N or HC₅N + HC₅N. The method was further extended to the synthesis of methylated compounds with formation of CH₃C₅N from CH₃C₂H + HC₃N, and CH₃C₇N from CH₃C₂H + HC₅N. In addition, photochemical experiments using HC₅N containing matrices led to the detection of HC₇N and of the C₅N⁻ anion. A general scheme describing the chain elongation processes was formulated. Similarities or differences in selection rules, vibronic spacings, electronic transition energies, and phosphorescence decay times were examined for the homologous series HC₂n+₁N, NC₂nN and CH₃C₂n+₁N.

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No description available.

Deciphering the activity of chemical molecules against a pathogenic organism is an essential task in drug discovery process. Virtual screening, in which few plausible molecules are selected from a large set for further processing using computational methods, has become an integral part and complements the expensive and time-consuming in vivo and in vitro experiments. To this end, it is essential to extract certain features from molecules which in the one hand are relevant to the biological activity under consideration, and on the other are suitable for designing fast and robust algorithms. The features/representations are derived either from physicochemical properties or their structures in numerical form and are known as descriptors. In this work we develop two new molecular-fragment descriptors based on the critical analysis of existing descriptors. This development is primarily guided by the notion of coding degeneracy, and the ordering induced by the descriptor on the fragments. One of these descriptors is derived based on the simple graph representation of the molecule, and attempts to encode topological feature or the connectivity pattern in a hierarchical way without discriminating atom or bond types. Second descriptor extends the first one by weighing the atoms (vertices) in consideration with the bonding pattern, valence state and type of the atom. Further, the usefulness of these indices is tested by ranking and classifying molecules in two previously studied large heterogeneous data sets with regard to their anti-tubercular and other bacterial activity. This is achieved by developing a scoring function based on clustering using these new descriptors. Clusters are obtained by ordering the descriptors of training set molecules, and identifying the regions which are (almost) exclusively coming from active/inactive molecules. To test the activity of a new molecule, overlap of its descriptors in those cluster (interpolation) is weighted. Our results are found to be superior compared to previous studies: we obtained better classification performance by using only structural information while previous studies used both structural features and some physicochemical parameters. This makes our model simple, more interpretable and less vulnerable to statistical problems like chance correlation and over fitting. With focus on predictive modeling, we have carried out rigorous statistical validation. New descriptors utilize primarily the topological information in a hierarchical way. This can have significant implications in the design of new bioactive molecules (inverse QSAR, combinatorial library design) which is plagued by combinatorial explosion due to use of large number of descriptors. While the combinatorial generation of molecules with desirable properties is still a problem to be satisfactorily solved, our model has potential to reduce the number of degrees of freedom, thereby reducing the complexity.

Doctor of Philosophy / Physics / Brett D. Esry / In strong field physics, complex atomic and molecular motions can be triggered and steered by an ultrashort strong field. With a given pulse as an carrier-envelope form, E(t) = E₀(t) cos(ωt + φ), we established our photon-phase formalism to decompose the solution of a time-dependent Schrödinger equation in terms of photons. This formalism is further implemented into a general analysis scheme that allows extract photon information direct from the numerical solution. The φ-dependence of any observables then can be understood universally as an interference effect of different photon channels. With this established, we choose the benchmark system H₂⁺ to numerically study its response to an intense few-cycle pulse. This approach helps us identify electronic, rovibrational transitions in terms of photon channels, allowing one to discuss photons in the strong field phenomena quantitatively. Furthermore, the dissociation pathways are visualized in our numerical calculations, which help predicting the outcome of dissociation. Guided by this photon picture, we explored the dissociation in a linearly polarized pulse of longer wavelengths (compared to the 800 nm of standard Ti:Saphire laser). We successfully identified strong post-pulse alignment of the dissociative fragments and found out that such alignment exists even for heavy molecules. More significant spatial asymmetry is confirmed in the longer wavelength regime, because dissociation is no longer dominated by a single photon process and hence allowed for richer interference. Besides, quantitative comparison between theory and experiment have been conducted seeking beyond the qualitative features. The discrepancy caused by different experimental inputs allows us to examine the assumptions made in the experiment. We also extend numerical studies to the dissociative ionization of H₂ by modeling the ionization.

No description available.

Research into inorganic supramolecular chemistry is burgeoning, in particular that which focuses on the formation of capsular molecules and the effects that these unique environments have on catalytic reactions. With the aim of producing new ligand designs that could not only support reactive metals, but also partake in supramolecular aggregation to provide a capsular microenvironment, new tripodal ligands and wide span imines and amines have been synthesised. Furthermore, the exploitation of hydrogen-bonding motifs formed through pyrrole-imine tautomerisation upon metallation of these ligands has been explored, with the aim of enhancing reactivity and stabilising reactive intermediates. In Chapter one, the concept of covalent and non-covalent capsules is introduced, and includes the different aspects affecting the encapsulation of molecules and their use as nanoreactors. The use of secondary interactions, e.g. hydrogen-bonding in metal complexes of tetrapodal and tripodal ligands is discussed. Chapter two describes the synthesis of a tripodal pyrrole-imine ligand and the formation of its multi-metallic complexes of Group one metals, transition metal and the f-block elements. The complete and partial tautomerisation of this ligand upon metal complexation is also examined. In Chapter three, the formation of hangman complexes of the tripodal pyrrole-imine ligand is described and is extrapolated to the chemistry of a new pyrrole-amide ligand. The synthesis of this latter ligand and its properties with regards to anion binding are also explored. Chapter four describes the formation of wide span diamine and diimine ligands and their propensity to form adducts with cobalt and zinc chlorometallates and unusual multimetallic palladium complexes. The final conclusions of the work presented in this thesis are drawn in Chapter five. Chapter six presents experimental details and characterising data for all of the new compounds presented in this thesis.