This work comprises two main parts. The first part outlines our efforts to expand on the recent work of Gütlich et.al. by synthesizing Co(II) based spin crossover systems within a dendritic framework. We wanted to investigate the possibility of synthesizing different first generation, triazole containing dendrimers using “click” type reactions and their coordination ability with Co(II) ions. To this end we have had limited success mainly due to the numerous challenges in synthesizing a pure dendrimer product. The second part details our efforts in the synthesis of a mononuclear Co(II) based single molecule magnet. This comes as an extension to recent reports by Chang and Long where they have successfully obtained mononuclear Fe(II) single molecule magnets by inducing structural distortions within the complexes to amplify the spin-orbit coupling. We postulated that the use of Co(II) in conjunction with a bulky ligand framework would lead to desirable magnetic properties. We chose the known bis(imino)pyridine ligand scaffold due to its rich chemistry and its interesting and unexpected coordination behaviour, as we have seen in previous research efforts by our lab. To this end we were successful in isolating and characterizing 4 compounds, and we have carried out detailed magnetic measurements on the two most magnetically interesting species.

This work comprises two main parts. The first part outlines our efforts to expand on the recent work of Gütlich et.al. by synthesizing Co(II) based spin crossover systems within a dendritic framework. We wanted to investigate the possibility of synthesizing different first generation, triazole containing dendrimers using “click” type reactions and their coordination ability with Co(II) ions. To this end we have had limited success mainly due to the numerous challenges in synthesizing a pure dendrimer product. The second part details our efforts in the synthesis of a mononuclear Co(II) based single molecule magnet. This comes as an extension to recent reports by Chang and Long where they have successfully obtained mononuclear Fe(II) single molecule magnets by inducing structural distortions within the complexes to amplify the spin-orbit coupling. We postulated that the use of Co(II) in conjunction with a bulky ligand framework would lead to desirable magnetic properties. We chose the known bis(imino)pyridine ligand scaffold due to its rich chemistry and its interesting and unexpected coordination behaviour, as we have seen in previous research efforts by our lab. To this end we were successful in isolating and characterizing 4 compounds, and we have carried out detailed magnetic measurements on the two most magnetically interesting species.

The development of new chemical processes and efficient catalysts for the formation of carbon-carbon bonds is an important topic in organic chemistry. In particular, the [2+2+2] cycloaddition reaction involving different insaturations mainly alkynes, alkenes and nitriles is a highly efficient synthetic tool that allows polysubstituted benzenic, cyclohexadienic and pyridinic compounds to be obtained in one reaction step and in an atom economy process, resulting in the simultaneous formation of three new bonds in the formed ring. In recent years, research to produce new catalysts that can work effectively in mild reaction conditions has attracted great interest, as has the use of these processes in the synthesis of products of potential biological interest. This doctoral thesis is based on the methodological study of the rhodium(I)-catalyzed [2+2+2] cycloaddition reaction. / El desenvolupament de nous processos químics i catalitzadors eficients per a la formació d’enllaços C-C és un tema d’especial importància en química orgànica. Concretament, la reacció de cicloaddició [2+2+2] involucrant diferents tipus d’insaturacions, principalment alquins, alquens i nitrils, és una eina sintètica molt eficaç que permet l’obtenció de compostos benzènics, ciclohexadiènics i piridínics polisubstituïts en un sol pas de reacció i en un procés d’economia d’àtoms, generant-se simultàniament els tres nous enllaços de l’anell format. En els darrers anys, la recerca per a aconseguir catalitzadors que permetin treballar eficientment en condicions suaus de reacció ha despertat un gran interès, així com la utilització d’aquests processos en la síntesi de productes amb potencial interès biològic. La present tesi doctoral es basa en l’estudi metodològic de les reaccions de cicloaddició [2+2+2] catalitzades per rodi(I).

Dans ce document, serons détaillées les résultats de mes travaux de recherche d’études doctorales. Tout d’abord, nous discuterons de la synthèse totale de la lépadine B, la plus courte à paraître dans la littérature à ce jour. Cette synthèse, en plus de valoriser la synthèse asymétrique de pipéridines poly-substituées développée par l’équipe du professeur Charette, mettra à profit une utilisation originale d’une séquence de fermeture-ouverture de cycle par la réaction de métathèse d’alcènes. De plus, nous détaillerons une brève étude mécanistique de cette dernière nous ayant permis la proposition d’un mécanisme peu commun de ce type de séquence réactionnel et dont les conséquences expérimentales sont impressionnantes. Au cours de cette synthèse, nous avons identifié un synthon d’une grande valeur synthétique. En effet, ne comportant pas moins que quatre centres chiraux, ce synthon pouvait être obtenu énantiopure en seulement trois étapes à partir de la pyridine. Ainsi, nous avons effectué une analyse structurale de ce synthon et avons envisagé une valorisation supplémentaire par une utilisation originale de la fragmentation de Grob. Dans ce contexte, nous avons développé une toute nouvelle synthèse de pipéridines 2,3,6-trisubstituées hautement régio- et diastéréosélective. Afin de pouvoir réaliser la précédente méthodologie, nous avons dû étudier la réduction d’une amide en présence de groupements fonctionnels sensibles dans les conditions usuelles. Heureusement, l’année précédente nous avions développée une réaction hautement chimiosélective d’amides tertaires. Cette nouvelle réaction, qui a été fondamentalement inspiré par une méthodologie du professeur Charette sur l’activation d’amides, a permis la réduction d’amides tertiaires en présence de fonctions telles les cétone, ester, nitrile, époxyde, insaturations, etc. Enfin, l’ensemble des connaissances acquises au cours de ces projets a permis l’élaboration d’une toute nouvelle stratégie de synthèse pour la préparation d’indolizidines et quinolizidines. Plus spécifiquement, nous avons développé la première séquence d’activation intramoléculaire et déaromatization asymétrique de la pyridine. Ceci permet d’avoir un accès aux squelettes indolizidine et quinolizidine avec des stéréosélectivités élevées, la nature insaturée de ces derniers laissant également place à une grande flexibilité synthétique. Dans ce contexte, nous allons détailler une très courte synthèse de trans-indolizidines. / In this document, the results of Ph.D. thesis will be detailed. First, we will discuss the synthesis of alkaloid lepadin B, the shortest to appear in the literature to date. This synthesis, in addition to validating the asymmetric synthesis of polysubstituted piperidines developed earlier by the group of Professor Charette, will highlight an original use of a ring-closing ring-opening alkene metathesis sequence. Also, a brief mechanistic study of the latter reaction will be detailed, a study which led us to propose an unusual mechanism for this reaction sequence and for which the experimental concequences are impressive. During the total synthesis of lepadin B, we identified a synthon of great synthetic value. Indeed, containing not less than four chiral centres, that synthon could be obtained enantiopure through a short three-step synthesis from pyridine. We performed a structural analysis of this synthon and we envisaged an additional validating through an original use of the Grob fragmentation. Consequently, we developed a new highly regio- and diastereoselective synthesis of 2,3,6-trisubstituted piperidines. To succesfully realize the latter methodology, it was required to perform an amide reduction in the presence of sensitive functionnalities under usual reduction conditions. Fortunatly, we had recently developed a set of conditions for the highly chemoselective reduction of tertiary amides. This new reaction, fundamentaly inspired by an amide activation methodology from Charette’s group, allowed the reduction of amides in the presence of functionalities such as ketone, ester, nitrile, epoxide, unsaturations, etc. Finaly, the knowledge acquired by conducting this research allowed for the elaboration of a new methodology for the synthesis of indolizidines and quinolizidines. Specifically, we developed the first intramolecular pyridine activation-asymmetric dearomatization reaction of the pyridine. This led us to the highly stereoselective access to indolizidine and quinolizidine backbone, the unsaturated nature of which permitting a good degree of synthetic flexibility. In that context, we will detail a short synthesis of trans-indolizidines.

Under the electric dipole approximation, second harmonic of the incident light is scattered by a collection of randomly oriented molecular dipoles in solution due to instantaneous orientational fluctuation which is directional. If two such dipoles are correlated in space through intermolecular or other interactions, the intensity of the second harmonic scattered light (SHSL) will be related to the extent of such interactions. If two dipoles are arranged in a particular geometry by design, the geometry will determine the intensity of the SHSL. If a molecule has no dipole moment, the intensity of the SHSL will be less and is only allowed by higher order electric multipoles. If two such zero-dipole molecules interact with each other and transfer some amount of electronic charge from one to the other, the induced dipole moment will give rise to an enhanced SHSL. However, along with the direction of the dipole moment from the donor to the acceptor, the actual geometry of such molecular dimer/complex should also play an important role to determine the nature of the SHSL response. If all the isotropic nonzero components of first hyperpolarizability (β) are taken into account, from the measurement of β and related quantities such as depolarization ratios, in solution it should be possible to derive information about the geometry of the dimer/complex. This is precisely the motivation behind this thesis. Chapter 1 gives a brief introduction of 1:1 charge transfer (CT) complexes between a donor and an acceptor and their importance in chemistry. It also contains an introduction to nonlinear optics, various spectroscopic techniques to characterize CT complexes, etc. The motivation of extracting the geometry of such complexes from hyper-Rayleigh scattering (HRS) measurements in solution is presented in this chapter. In Chapter 2, all the experimental details of the unpolarized and polarization resolved HRS measurements at various excitation wavelengths have been described. Generation of infrared wavelengths (1543 nm and 1907 nm) using stimulated Raman scattering in gases have also been discussed. In Chapter 3, the first hyperpolarizability (βHRS) for two series of 1:1 molecular complexes between methyl substituted benzene donors with tetrachloro-p-benzoquinone (CHL) and dicyanodichloro-p-benzoquinone (DDQ) acceptors in solution at 1543 nm have been presented. Enhancement of βHRS due to charge transfer from the donor to the acceptor molecule which was predicted theoretically has been verified. Using linearly (electric field vector along X direction) and circularly polarized incident light, respectively, two macroscopic depolarization ratios D = I2ω,X,X/I2ω,Z,X and D' = I2ω,X,C/I2ω,Z,C in the laboratory fixed XYZ frame by detecting the SHSL in a polarization resolved fashion have been measured. The experimentally obtained first hyperpolarizability (βHRS), D and D' values, are then matched with the theoretically calculated values from single and double configuration interaction calculations using the Zerner’s intermediate neglect of differential overlap and the self-consistent reaction field (ZINDO–SDCI– SCRF) approach by adjusting the geometrical parameters. It has been found that in most of the CT complexes studied here, there exists a significant twist in the equilibrium geometry at room temperature which is not a simple slipped parallel geometry as was believed. In chapter 4, the βHRS, D and D' values of 1:1 pyridine (PY)-chloranil (CHL) complex at 1064 nm have been described. Previous theoretical studies have shown that there is a tilt angle of 77.9 degree in the gas phase PY-CHL complex. In this chapter, this prediction about the geometry of 1:1 PY-CHL complex has been probed. The experimentally found βHRS, D and D' are matched well with theoretically calculated values, using ZINDO–SDCI–SCRF, for a cofacial geometry of PY-CHL complex in solution indicating that the solution geometry is different from the gas phase geometry. In Chapter 5, the βHRS, D and D' for a series of 1:1 complexes of tropyliumtetrafluoroborate and methyl-substituted benzenes in solution at 1064 nm have been reported. The measured D and D' values vary from 1.36 to 1.46 and 1.62 to 1.72, respectively and are much lower than the values expected from a typical sandwich or a T-shaped geometry. The lowering in D and D' indicates that these complexes have higher symmetry than C2v. The value of D close to 1.5 indicates there is a significant octupolar contribution in such complexes. In order to probe it further, βHRS, D and D' were computed using the ZINDO-SDCI-SCRF technique in the presence of BF4-anion. By arranging the three BF4-ions in a C3 symmetry around the complex in such a way that electrical neutrality is maintained, the computed values are brought to agreement with experiments. This unprecedented influence of the anion on the HRS, D and D' values of these complexes are discussed in this chapter. In Chapter 6, the effect of dipolar interactions, within a multichromophoric system, on the second order nonlinear optical properties have been studied. It has been found that the βHRS response of the multichromophoric system is always larger than expected for uncorrelated chromophores demonstrating that the dipole moment of individual chromophores are not merely additive within the multichromophoric system but contribute cooperatively to the SHSL signal. Also the relative orientation and nature of the chromophores and the angle of interaction between them alter the HRS values. Chapter 7 is the concluding chapter in which all the work done in the thesis has been summarized and future direction has been proposed.

Face à l'apparition grandissante de souches bactériennes multi-résistantes à l'arsenal d'antibiotiques actuels, les thiopeptides antibiotiques, bien que connus depuis plus de 60 ans, suscitent actuellement un fort regain d'intérêt. En effet, cette classe de molécules présente une forte activité antibiotique contre des souches bactériennes résistantes et multirésistantes, et met en œuvre deux modes d'inhibition originaux de la synthèse protéique encore inexploités en thérapie antibiotique humaine. Leur développement pharmacologique est en particulier freiné par la difficulté de préparation de ces molécules très complexes. L'élaboration d'une stratégie innovante de synthèse de la partie la plus complexe de ces molécules, le cœur hétérocyclique est étudiée dans ce travail. Cette approche repose sur l'étude et la valorisation de nouvelles méthodologies de fonctionnalisation directe des liaisons C-H et C-X de mono- et bis-thiazoles avec une large gamme d'hétéroaromatiques. Sa viabilité est démontrée par la préparation du cœur hétérocyclique commun aux amythiamicines.

Ce travail est en relation avec la thématique "Chimie Verte" en particulier, le rôle de la catalyse,l'utilisation des matières premières renouvelables et l'élimination des produits nocifs.- Quatre échantillons commerciaux de zircone tungstatée de Mel-Chemicals.- deux séries de zircone tungstatée préparées par deux méthodes différentes avec une teneuren WO3 de 1 à 20 % en masse.- des oxydes binaires tels que WO3-ZrO2, B2O3-ZrO2, Al2O3-ZrO2, Ga2O3-ZrO2 et In2O3-ZrO2.- des oxydes binaires tels que WO3-Me2O3 (Me = B, Al, Ga et In) et finalement des oxydesternaires WO3/(Me2O3-ZrO2) (Me = B, Al, Ga et In) ont été étudiés et préparés lors de cettethèse.La performance catalytique de ces catalyseurs a été évaluée dans l'hydrolyse de la cellobiose, ladéshydratation du fructose et la réduction catalytique sélective des NOx. Les propriétés acides etredox de surface ont été corrélées aux performances catalytiques. En général, la conversion totale est liée à l'acidité des catalyseurs. Les catalyseurs les plus sélectifs pour la déshydratation du fructose et en deNOx sont ceux présentant une acidité modérée.

This work comprises two main parts. The first part outlines our efforts to expand on the recent work of Gütlich et.al. by synthesizing Co(II) based spin crossover systems within a dendritic framework. We wanted to investigate the possibility of synthesizing different first generation, triazole containing dendrimers using “click” type reactions and their coordination ability with Co(II) ions. To this end we have had limited success mainly due to the numerous challenges in synthesizing a pure dendrimer product. The second part details our efforts in the synthesis of a mononuclear Co(II) based single molecule magnet. This comes as an extension to recent reports by Chang and Long where they have successfully obtained mononuclear Fe(II) single molecule magnets by inducing structural distortions within the complexes to amplify the spin-orbit coupling. We postulated that the use of Co(II) in conjunction with a bulky ligand framework would lead to desirable magnetic properties. We chose the known bis(imino)pyridine ligand scaffold due to its rich chemistry and its interesting and unexpected coordination behaviour, as we have seen in previous research efforts by our lab. To this end we were successful in isolating and characterizing 4 compounds, and we have carried out detailed magnetic measurements on the two most magnetically interesting species.

CYP17 is an ACTH/cAMP inducible gene in the human adrenal cortex encoding a cytochrome P450 enzyme with sterol 17α-hydroxylase activity and 17,20 lyase activity essential for biosynthesis of cortisol and androgens. Studies carried out during the past decade have shown that acclerated transcription of inducible eukaryotic genes involves sequential chromatin modifications by cooperative promoter-specific transcription factors and the class of proteins called transcriptional coregulators. In the present work, we aimed to first identify important chromatin modifications and chromatin modifying complexes at the CYP17 transcription start site and nearby steroidogenic factor-1 (SF-1) binding site. Then, we asked what modifications to SF-1 occur during the interaction of this nuclear receptor with the CYP17 promoter, and what their function may be. Finally, we asked how ACTH/cAMP signaling affects SF-1-containing chromatin-modifying complexes during the early phase of transcriptional induction of CYP17. Results from chromatin immunoprecipitation (ChIP) and mammalian two hybrid experiments identified complexes including one comprised of SF-1, steroid receptor coactivator-1 (SRC-1), and the histone acetyltransferase general control nonderepressed 5 (GCN5) as cAMP-inducible, but sensitive to the SF-1 antagonist sphingosine, and able to act in stimulating CYP17 transcription. Moreover, ATPases on the promoter coincided with manipulation of nucleosome histone H2 dimer content. Next, we found that SF-1 phosphorylation by glycogen synthase kinase 3beta (GSK3beta), reciprocal dephosphorylation by phosphatase(s), and acetylation by GCN5 at nearby sites at the ligand binding pocket opening were required for efficient CYP17 transcription. This leads us to propose that ligand binding to SF-1 is controlled by these post-translational modifications. Finally, we determined that the corepressors E1A C-terminal binding proteins (CtBP) 1 and 2 are protein kinase A (PKA) targets and are sensitive to PKA-dependent NADH accumulation. These effects of PKA activation by ACTH/cAMP in adrenal cortex cells enforce CYP17 transcription concomitant with dimerization of CtBP1 and CtBP2.

xxi, 199 p. ： ill. (some col.) / Mimicking the simplicity and efficiency of Nature in the synthesis and design of non-covalent receptors for ions in solution has piqued the interest of the chemical community since the mid 20th century. Until recently most of that focus has been on the binding, sensing, or remediation of inorganic cations instead of their anionic counterparts. With the realization of the role anions play in biological function or dysfunction, the development of selective probes for these highly solvated and elusive targets has become an important goal in the chemical and biological communities. Concurrently the optoelectronic properties of planar extended π-systems have been exploited in the development of novel light absorbing and emitting organics and carbon-rich materials with tunable optical outputs. While many of these compounds exhibit desirable sensor properties, their insolubility and non-specificity has hindered the inclusion of these materials in probes for biologically relevant substrates. This body of research seeks to combine our knowledge of supramolecular structure-function relationships with novel extended aromatic topologies to yield highly specific probes for anions in competitive media that exhibit discrete, tunable outputs upon interaction with their target substrates. Chapter I provides a brief overview of phenylacetylene topologies as they have been used in supramolecular assemblies and sensor design, with an emphasis on their use in anion-directed complexes. Chapter II focuses on our choice of specific arylethynylpyridine architectures upon which we can build a modular synthetic scheme to access working receptors. Chapter III encompasses the synthesis of urea and sulfonamide derivatives of phenylethynylpyridine and binding studies with these receptors and halide salts in organic media. Chapters IV and V focus upon the optoelectronic properties of these receptors, the tunability of their outputs and how we utilized their behavior in aqueous media to develop in vitro sensors for halides. This chapter concludes with recent results regarding their self-assembly on the micro-scale. This dissertation contains my previously published and co-authored work. / Committee in charge: Victoria DeRose, Chairperson; Michael Haley, Co-Advisor; Darren Haley, Co-Advisor; Shih-Yuan Liu, Member; David Schmidt, Outside Member