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This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.

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Chemisorption of an organic monolayer to tune the surface properties of a transparent conductive oxide (TCO) electrode can improve the performance of organic electronic devices that rely on efficient charge transfer between an organic active layer and a TCO contact. Here, a series of perylene diimides (PDIs) was synthesized and used to study relationships between monolayer structure/properties and electron transfer kinetics at PDI-modified indium-tin oxide (ITO) electrodes. In these PDI molecules, one of the imide substituents is a benzene ring bearing a phosphonic acid (PA) and the other is a bulky aryl group that is twisted out of the plane of the PDI core. The size of the bulky aryl group and the substitution of the benzene ring bearing the PA were both varied, which altered the extent of aggregation when these molecules were absorbed as monolayer films (MLs) on ITO, as revealed by both attenuated total reflectance (ATR) and total internal reflection fluorescence spectra. Polarized ATR measurements indicate that, in these MLs, the long axis of the PDI core is tilted at an angle of 33-42 degrees relative to the surface normal; the tilt angle increased as the degree of bulky substitution increased. Rate constants for electron transfer (k(s,opt)) between these redox-active modifiers and ITO were determined by potential-modulated ATR spectroscopy. As the degree of PDI aggregation was reduced, k(s,opt) declined, which is attributed to a reduction in the lateral electron self-exchange rate between adsorbed PDI molecules, as well as the heterogeneous conductivity of the ITO electrode surface. Photoelectrochemical measurements using a dissolved aluminum phthalocyanine as an electron donor showed that ITO modified with any of these PDIs is a more effective electron-collecting electrode than bare ITO.

Interfaces between semiconductors and adsorbed molecules form a central area of research in surface science, occurring in many different contexts. One such application is the so-called Dye-Sensitized Solar Cell (DSSC) where the nanostructured dye-semiconductor interface is of special interest, as this is where the most important ultrafast electron transfer process takes place. In this thesis, structural and electronic aspects of these interfaces have been studied theoretically using quantum chemical computations applied to realistic dye-semiconductor systems. Periodic boundary conditions and large cluster models have been employed together with hybrid HF-DFT functionals in the modeling of nanostructured titanium dioxide. A study of the adsorption of a pyridine molecule via phosphonic and carboxylic acid anchor groups to an anatase (101) surface showed that the choice of anchor group affects the strength of the bindings as well as the electronic interaction at the dye-TiO2 interface. The calculated interfacial electronic coupling was found to be stronger for carboxylic acid than for phosphonic acid, while phosphonic acid binds significantly stronger than carboxylic acid to the TiO2 surface. Atomistic and electronic structure of realistic dye-semiconductor interfaces were reported for RuII-bis-terpyridine dyes on a large anatase TiO2 cluster and perylene dyes on a periodic rutile (110) TiO2 surface. The results show strong influence of anchor and inserted spacer groups on adsorption and electronic properties. Also in these cases, the phosphonic acid anchor group was found to bind the dyes significantly stronger to the surface than the carboxylic acid anchor, while the interfacial electronic coupling was stronger for the carboxylic anchor. The estimated electron injection times were twice as fast for the carboxylic anchor compared to the phosphonic anchor. Moreover, the electronic coupling was affected by the choice of spacer group, where unsaturated spacer groups were found to mediate electron transfer more efficiently than saturated ones.

For grafting polypyrrole on oxidized surfaces, 3-substituted pyrrole alkyl phosphonic acids, 11-(pyrrol-3-yl undecyl) trimethoxysilanes and 1-substituted pyrrole alkyl organosilanes with different chain length were designed and successfully synthesized as adhesion promoters. These new derivatives were studied for their adsorption behavior on oxide substrates and chemical or electrochemical deposition of polypyrrole over modified oxide surface or electrodes. Several analytical techniques such as contact angle measurement, surface plasmon resonance spectroscopy (SPR), UV-VIS Spectroscopy, grazing incident FTIR, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to characterize the adsorbed layers on different substrates. Contact angle measurement and ellipsometry data showed that high concentrations in apolar hydrocarbon solvent and long reaction times are sufficient to form tightly packed monolayer of 1-substituted pyrrole alkyl monochlorosilanes (PMCS) on substrates. Adsorption kinetics were studied by SPR and showed that the adsorption took place within a few seconds, then continuously increased and reached a plateau. The orientation of these synthesized monomers is investigated to be well-suited for use as adhesion promoter. CV-measurements showed that 3-substrated pyrrole derivatives had lower oxidation potential, whereas 1-substituted pyrrole derivatives had higher oxidation potential compared with pyrrole. Surface deposition of polypyrrole on the adhesion promoter modified (silane-modified and phosphonic acid-modified) substrates by chemical and electrochemical polymerization were investigated. PPy films formed on the modified surfaces by surface chemical polymerization showed a better adhesion compared to those on the unmodified surfaces. The morphology of PPy films was influenced by the alkyl chain length of the adhesion promoter and the deposition condition, such as choice of oxidant and solvent. The thickness of the resulting PPy films were controlled by the polymerization conditions, such as choice of solvent, deposition time, pyrrole to oxidant ratio and monomer concentration. The thickness of the deposited PPy film was estimated in the range of 10-400 nm by AFM and ellipsometry. The electrical properties were studied by current-voltage (j-V) measurement. Temperature dependence of j-V characteristics of Si/SiO2/PPy/PMCS-16/Al films revealed that the current increases with temperature, the film shows a typical semiconductor behavior. The use of these adhesion promoters modified electrode for electrochemical polymerization resulted in adhesive polypyrrole films.Also the 3-substituted pyrrole phosphonic acids were found to be homo-and co-polymerizable (with pyrrole) under chemical methods. TGA showed that homopolymers are less stable than polypyrrole due to the 3-substitution. he homopolymer of 3-substituted phosphonic acid derivatives of pyrrole is soluble. Films coated from the MeOH solution of homopolymer could be successfully used as humidity sensors. It is observed that the resistivity of the 3-substituted homopolypyrrole sensors increases and capacitance decreases during exposure to humid air. The polypyrrole films obtained by surface chemical polymerization was also used as humidity sensors.

The goal of the work described in this dissertation was to investigate the structure of metal phosphonate frameworks which were composed of conforma-tionally flexible ligands. This goal was achieved through investigating new syn-thetic techniques, systematically changing structural aspects (i.e. chain length), and conducting in situ X-ray diffraction experiments under non-ambient condi-tions. First, the use of ionic liquids in the synthesis of metal phosphonates was in-vestigated. Reaction systems which had previously been studied in purely aqueous synthetic media were reinvestigated with the addition of a hydrophobic ionic liq-uid to the reaction. Second, the structural diversity of zinc alkylbisphosphonates was investigated through systematically varying the chain length and reaction conditions. Last, the structural changes associated with externally applied stimuli (namely temperature and pressure) on conformationally flexible metal phospho-nates were investigated. Elevated temperature was used to investigate the structur-al changes of a 1-D cobalt chain compound through three stages of dehydration and also applied pressures of up to 10 GPa were used to probe the structural resili-ence of two zinc alkylbisphosphonate materials under. The iminobis(methylphosphonic acid) type ligands are a good example of a small, simple, conformationally flexible ligand. There are three distinct different structural types, utilizing this ligand with cobalt metal, described in the literature, all of which contain bound or solvated water molecules. The addition of a hydrophobic ionic liquid to an aqueous synthesis medium resulted in new anhydrous compounds with unique structural features. Systematic investigations of zinc alkylbisphosphonate materials, construct-ed with three to six carbon linker ligands, resulted in four new families of com-pounds. Each of these families has unique structural features which may prove in-teresting in future applications developments. Importantly, it is shown that wheth-er the chain length is odd or even plays a role in structural type although it is not necessarily a requirement for a given structural type; furthermore, chain length itself is not strictly determinative of structural type. Dehydration in a cobalt phosphonate was followed via in situ single crystal X-ray diffraction. The compound goes through a two-stage dehydration mecha-nism in which the compound changes from a 1-D chain to a 2-D sheet. This pro-cess is reversible and shows unique switchable magnetic properties. The high pressure studies of an alkyl chain built zinc metal phosphonate showed that the chains provide a spring-like cushion to stabilize the compression of the system allowing for large distortions in the metal coordination environment, without destruction of the material. This intriguing observation raises questions as to whether or not these types of materials may play a role as a new class of piezo-functional solid-state materials.

Les superplastifiants sont des adjuvants permettant de considérablement fluidifier les pâtes cimentaires sans en changer le rapport eau/ciment. Parmi eux, les polycarboxylates sont les plus utilisés et les plus étudiés. Ces copolymères en peigne sont porteurs de fonctions acide carboxylique et de chaînes latérales de poly(ethylène glycol). Leurs fonctions anioniques leur permettent de s’adsorber sur les grains de ciment, tandis que les chaînes latérales génèrent de la répulsion stérique entre ces derniers. Cela conduit à la désagglomération des agglomérats, et donc la dispersion des particules. Macroscopiquement, la pâte cimentaire devient plus fluide, plus facile à mettre en oeuvre. Mais dans certaines circonstances, la présence d’anions compétiteurs peut réduire la capacité d’adsorption et donc l’efficacité des polycarboxylates. De nombreux auteurs ont tenté d’améliorer les performances de ces structures en modifiant l’architecture macromoléculaire. Parmi ces travaux, des chercheurs ont remplacé les acides carboxyliques par des fonctions acide phosphonique, et cela a considérablement amélioré la résistance des superplastifiants au phénomène de compétition ionique.Ce travail de thèse rapporte la synthèse d’une dizaine de nouveaux copolymères en peigne, de structure proche de polycarboxylates classiques mais possédant des fonctions phosphonées. Ces copolymères ont été obtenus par télomèrisation ou bien par polymérisation radicalaire RAFT. Leurs performances ont ensuite été évaluées sur des suspensions minérales de carbonate de calcium, un matériau modèle souvent utilisé pour modéliser le comportement du ciment aux premiers âges de son hydratation. Les efficacités d’adsorption, de dispersion des particules minérales et de fluidification des suspensions ont ainsi été investiguées et mises en relation avec la structure macromoléculaire. De plus, leur résistance à la compétition ionique a également été examinée à travers l’augmentation de la force ionique par ajouts de sulfate de sodium et de nitrate de sodium.Enfin, ce manuscrit rapporte la tentative de conception d’un superplastifiant biosourcé à travers la fonctionnalisation d’oligomères de chitosan par des fonctions phosphonées et des chaînes latérales de poly(éthylène glycol). Les efficacités d’adsorption, de dispersion et de fluidification des suspensions de calcite de ce composé biosourcé ont finalement été évaluées et comparées à celles des copolymères en peigne de synthèse. / Superplasticizers are admixtures allowing the fluidification of cement pastes without any changes of the water/cement ratio. Among them, polycarboxylates are the most used and the most studied. These comb-like copolymers have carboxylic acid moieties and poly(ethylene oxide) side chains. Their anionic functions make possible their adsorption onto cement grains while side chains create steric repulsion between these latter. This leads to deagglomeration and dispersion of particles. From a macroscopic point of view, cement paste becomes more fluid, easier to place. But in some cases, competitive anions can reduce their adsorption ability and thus polycarboxylates dispersion efficiency. Lots of authors tried to improve structures performances by modifying macromolecular architecture. Among these works, some searchers have replaced carboxylic acids by phosphonic acid moieties, and this greatly improved superplasticizers resistance to ionic competition phenomenon.This work focuses on the synthesis of several new comb-like copolymers, whose structures are similar to conventional polycarboxylates but with phosphonic acid functions instead of carboxylic acids. These copolymers were obtained from telomerization or RAFT copolymerization. Their performances were evaluated on calcium carbonate suspensions, a model material widely used to simulate early-age cement behavior. Adsorption, dispersion and fluidification efficiencies of synthetized copolymers were examined and linked to their macromolecular structures. Moreover, their resistance to ionic competition was investigated through the increase of ionic strength by addition of sodium sulfate and sodium nitrate.Finally, this manuscript relates the conception of a biobased superplasticizer through the functionalization of oligomers of chitosan by phosphonated functions and poly(ethylene oxide) side chains. Adsorption, dispersion and fluidification efficiencies of this biobased compound were evaluated on calcite suspensions and compared to those of previously synthetized comb-like copolymers.

For grafting polypyrrole on oxidized surfaces, 3-substituted pyrrole alkyl phosphonic acids, 11-(pyrrol-3-yl undecyl) trimethoxysilanes and 1-substituted pyrrole alkyl organosilanes with different chain length were designed and successfully synthesized as adhesion promoters. These new derivatives were studied for their adsorption behavior on oxide substrates and chemical or electrochemical deposition of polypyrrole over modified oxide surface or electrodes. Several analytical techniques such as contact angle measurement, surface plasmon resonance spectroscopy (SPR), UV-VIS Spectroscopy, grazing incident FTIR, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to characterize the adsorbed layers on different substrates. Contact angle measurement and ellipsometry data showed that high concentrations in apolar hydrocarbon solvent and long reaction times are sufficient to form tightly packed monolayer of 1-substituted pyrrole alkyl monochlorosilanes (PMCS) on substrates. Adsorption kinetics were studied by SPR and showed that the adsorption took place within a few seconds, then continuously increased and reached a plateau. The orientation of these synthesized monomers is investigated to be well-suited for use as adhesion promoter. CV-measurements showed that 3-substrated pyrrole derivatives had lower oxidation potential, whereas 1-substituted pyrrole derivatives had higher oxidation potential compared with pyrrole. Surface deposition of polypyrrole on the adhesion promoter modified (silane-modified and phosphonic acid-modified) substrates by chemical and electrochemical polymerization were investigated. PPy films formed on the modified surfaces by surface chemical polymerization showed a better adhesion compared to those on the unmodified surfaces. The morphology of PPy films was influenced by the alkyl chain length of the adhesion promoter and the deposition condition, such as choice of oxidant and solvent. The thickness of the resulting PPy films were controlled by the polymerization conditions, such as choice of solvent, deposition time, pyrrole to oxidant ratio and monomer concentration. The thickness of the deposited PPy film was estimated in the range of 10-400 nm by AFM and ellipsometry. The electrical properties were studied by current-voltage (j-V) measurement. Temperature dependence of j-V characteristics of Si/SiO2/PPy/PMCS-16/Al films revealed that the current increases with temperature, the film shows a typical semiconductor behavior. The use of these adhesion promoters modified electrode for electrochemical polymerization resulted in adhesive polypyrrole films.Also the 3-substituted pyrrole phosphonic acids were found to be homo-and co-polymerizable (with pyrrole) under chemical methods. TGA showed that homopolymers are less stable than polypyrrole due to the 3-substitution. he homopolymer of 3-substituted phosphonic acid derivatives of pyrrole is soluble. Films coated from the MeOH solution of homopolymer could be successfully used as humidity sensors. It is observed that the resistivity of the 3-substituted homopolypyrrole sensors increases and capacitance decreases during exposure to humid air. The polypyrrole films obtained by surface chemical polymerization was also used as humidity sensors.

Nano-structured materials are widely applied for various applications like photovoltaics, electrochromics and sensors. A challenging task in all these fields is the functionalization of these materials with a molecule of interest for the desired application. This work demonstrate the post grafting of the most important and commonly used nano-structured material, mesoporous TiO2, with different bifunctional molecular linkers. These compounds basically have two functional groups, the phosphonic acid group which coordinates to the TiO2 surface and a positive and negative head group which controls the surface charge and the potential interaction of the surface with species in solution. These two groups are systematically separated by alkyl group of different chain length which controls the hydrophobicity of the surface. It is shown that the new surface modification technique simplifies the molecular requirements for functional surface modifiers considerably. Using a limited set of organic anchors with adjustable head group charge and hydrophobicity, broad range of molecules can be adsorbed onto TiO2. Different applications based on such modified surfaces were explored and demonstrated. The modified surfaces can be used to incorporate different charged guest molecules, electrochromophores and dyes which enable to probe their electrochemistry and photovoltaic properties on the surface. Supra-molecular self assembly inside the modified pores is possible which can be monitored by different methods. The study includes the prepartaion of the modified surfaces and their characterization using different electrochemical methods, FTIR spectroscopy, Quartz Crystal Microbalance, Contact angle and Scanning Electron Microscopy measurements.