<p> Coal tar is a rich source of polycyclic aromatic compounds (PAC) which include hydrocarbons (PAH), sulfur-containing aromatics (PASH), nitrogen-containing aromatics and high molecular mass PAH. The separation of coal tar into four fractions was carried out on activated (170°C, 48 hrs) neutral alumina. Low mass aromatics and aliphatics were eluted with hexane in fraction A1 (2.2% recovery), while PAH/PASH were eluted by benzene in fraction A2 (25%). High molecular mass PAH were eluted by dichloromethane in fraction A3 (5.5%) and nitrogen-containing aromatics were eluted by methanol in fraction A4 (21%). These fractions were characterized by normal phase liquid chromatography, GCMS, probe mass spectrometry (for fractions A3 and A4) and LC-MS (for fraction A3).</p> <p> While ratio of PASH to PAH in fraction A2 was rather unfavorable (25:1), the separation of PASH from PAH was attempted using two methods: an oxidation/reduction method and a ligand exchange method. The oxidation/reduction method of Lee was a complete failure. The PdCl2-silica method of Nishioka was partially successful. Of the 25 thia-arenes identified in fraction A2, 12 eluted with the PAH while the other 13 were either partially (5) or fully (8) retained by the PdCl2-silica gel column and then eluted later to give a sulfur-enriched fraction. This fraction was further separated using normal phase HPLC to afford sulfur-containing compounds with molecular masses between 184 amu and 258 amu which exhibited almost no contamination due to PAH. Thus, it would be possible to purify about one-half of the PASH from a complex mixture such as coal tar.</p> <p> Fraction A3 which contained high mass PAH was subjected to semi-preparative normal phase HPLC to afford several high molecular mass PAH fractions. The 326 amu PAH fraction was selected because it contributed to 10% of the genotoxic of the mixture. This fraction was further separated by normal phase HPLC and the subfractions were analyzed by reversed-phase HPLC with diode-array detection. Thirty-five peaks were collected from the reversed-phase HPLC analysis and were characterized by probe mass spectrometry and fluorescence spectroscopy (in part). Of the 35 peaks, 8 peaks were eluted in the mutagenic active range; these eight compounds will be evaluated using the Ames assay to determine which are active mutagens.</p> / Thesis / Master of Science (MSc)

No description available.

La reconnaissance moléculaire énantiosélective est un processus fondamental et universel qui est au cœur de tous les systèmes biologiques. Ce travail a pour but de contribuer à la compréhension des phénomènes, mis en jeu lors de cette reconnaissance, par l’utilisation de récepteurs artificiels, capables de complexer et discriminer des acides aminés. De par leurs rigidités et leurs modularités fonctionnelles, les calix[4]arènes constituent des plateformes de choix pour la conception de ces récepteurs organisés. Une série de 12 ligands calixarèniques et thiacalixarèniques chiraux homo et hétéroditopiques, portant des groupements fonctionnels dérivés d’acides aminés, a donc été synthétisée. La synthèse de ces ligands a nécessité la mise au point d’une méthode originale et sélective, qui a permis d’obtenir une série de calix[4]arènes mono-O-fonctionnalisés par des groupements fonctionnels variés. Une étude mécanistique a permis de mettre en évidence les intermédiaires réactionnels. Après caractérisation de tous les composés synthétisés, des études de complexation des ligands avec des dérivés tosylés d’acides aminés neutres ont été effectuées. Les investigations, menées par spectrométrie de masse, par microcalorimétrie et par RMN 1H, nous ont permis de mettre en évidence la capacité de certains ligands à complexer et discriminer des acides aminés. La stœchiométrie et les constantes d’association des complexes formés ont ainsi pu être déterminées. Des études par RMN 2D ont permis de déterminer les liaisons impliquées dans la formation des complexes et ont révélé un réarrangement spatial des ligands, au sein des complexes, afin d’améliorer la stabilité de ceux-ci / Molecular recognition is a fundamental and universal process in biological systems. This work aims to contribute to the understanding of phenomena involved in this recognition by the use of artificial receptors able to complex and discriminate amino acids. Because of their rigidity and their functional modularity, calix[4]arenes and thiacalix[4]arenes are good starting materials for the design of these receptors. A series of 12 chiral homo and heteroditopic calix[4]arenes and thiacalix[4]arenes bearing amino acids derivatives has been synthesized. In order to improve the synthesis of heteroditopic receptors, an original and selective method for the preparation of mono-O-functionalized calix[4]arenes was developed. This procedure, based on the de-O-functionalization of 1,3 di-O-substituted calix[4]arenes by titanium tetrachloride (TiCl4), yielded a series of calix[4]arenes, mono-O-substituted by various functional groups (alcohol, halogen, nitrile, ester, alkyne ...). A mechanistic study revealed the formation of two titanium calixarene complexes during the reaction. After characterization of all these compounds, complexation studies of chiral receptors with neutral N-tosyl amino acids derivatives (valine, leucine, and phenylalanine) were done. Various investigations carried out by mass spectrometry, microcalorimetry and 1 H NMR allowed us to establish the ability of some ligands to complex and discriminate amino acids. Stoichiometry and association constants of the complexes were determined. 2D NMR (NOESY, COSY) studies were used to specify the bonds implied in complex formation

<p>This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ.</p><p>Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields.</p><p>In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates.</p><p>The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three.</p><p>The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.</p>

This thesis presents Quantum Chemical calculations on the Photochemistry of Halogenated benzenes, Phytochromobilin, Ruthenium Polypyridyl complexes and 6-4 photoadducts in DNA. The work is focused on improving the understanding of a number of experimentally observed photochemical processes in these systems. New results regarding the mechanism of photodissociation of halogenated arenes, photointerconversion of phytochromobilin are presented, as well as of the photoprocesses of Ruthenium Polypyridyl complexes and new mechanistic insights in the repair of 6-4 photoadducts in DNA.

This MSc. Thesis deals with electrochemical studies of the analytical utilization of self-assembled monolayers of thiolated calix[4]arene (C4A) and/or undecanthiole (C11SH) on the surface of a polycrystalline gold electrode. Hydroquinone, nitrobenzene, 2-nitrophenole and 4-nitrophenole have been used as tested model compounds. The real surface area of the electrode was determined using these two methods: From the charge of desorption peak of α-gold oxides (5.72±0.48 mm2 ) and using the Randles- Ševčík equation. (6.14±0.59 mm2 ). The preparation of the electrode consisted of polishing on alumina, immersing into piranha solution and cyclic voltammetry. The area of electrode surface was well reproducible. Stability of thiol monolayer in the area of negative potentials was tested. The C11SH layer is very stable; the desorption peak was recorded in basic solutions only (at −1.3 V vs. 3M Ag/AgCl). The position of the desorption peak of C4A is more pH dependent and it was recorded at −1.08 V at pH 13. The properties of the electrode modified by C11SH and or C4A were investigated using the model compound hydroquinone. It is assumed that the oxidation of the hydroquinone does not take place inside the C4A cavity; hence the hydroquinone molecule is too big to pass through the cavity. C11SH and C4 + C11SH act...

This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ. Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields. In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three. The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.

Ce manuscrit décrit d'une part la synthèse et la fonctionnalisation de dérivés de types azacalix[4]arènes et d'autre part l'élaboration d'une nouvelle voie de synthèse des ligands benzoquinonediimines.La première partie, consacrée aux azacalix[4]arènes, détaille les différents procédés utilisés pour fonctionnaliser des azacalix[4]arènes après leur macrocyclisation. L'introduction de groupes amides a généré des récepteurs d'anions qui présentent une sélectivité non usuelle pour les ions chlorures. Les complexes hotes-invités formés reposent sur des intercations supramoléculaires et constituent l'une des principales thématiques de ce manuscrit.La seconde part du manuscrit porté sur une nouvelle voie de synthèse des ligands benzoquinonediimines qui reposent sur la transamination du 1,2,4,5-tétraaminobenzène en présence d'un excès d'amine primaire. La simplicité de cette procédure permet d'obtenir une grande variété de benzoquinondiimines diversement substiuées. L'impact de cette substiution est illusté via l'étude de nouveaux complexes bimétalliques contenant un ligand benzoquinonediimine pontant. / The first pat of this manuscrit deals with the synthetis and fonctionalization of azacalix[4]arnes derivatives while the second part describes a new syntetic access of benzoquinonediimines ligands.In the first part, differents approaches were used to introduce fonctional groups on the peripheral positions of alrealdy formed azacalix[4]arenes. the introduction of hydrogen donor groups such as amides groups generated azacalix[4]arnes based anions receptor that preferentially bind chloride anions. These host-guest complexes are built on supramolecular interations and are one of the main topic of this manuscrit.In the second part, a new synthetic procedure of benzoquinonediimines is described and studied. The simple and efficient one-pot reaction involves a transamination between 1,2,4,5-tetraaminobenzene and primary amine and allows to prepare a large range of N-substituted benzoquinonediimines derivatives. The impact of the N-substitution is enlightened through the study on bimetallic complexes containing a bridging benzoquinonediimine unit.

We have investigated the noncovalent interactions in carbohydrate-aromatic interactions which are pivotal to the recognition of carbohydrates in proteins. We have employed quantum mechanical methods to study carbohydrate-aromatic complexes. Due to the importance of dispersion contribution to the interaction energy, we mainly use density functional theory augmented with an empirical correction for the dispersion interactions (DFT-D). We have validated this method with a limited number of high level ab initio calculations. We have also analysed the vibrational and NMR chemical shift characteristics using the DFT-D method. We have mainly studied the complexes involving β-glucose with 3-methylindole and p-hydroxytoluene, which are analogues of tryptophan and tyrosine, respectively. We find that the contribution for interaction energy mainly comes from CH/π and OH/π interactions. We find that the interaction energy of complexes involving CH/π and OH/π interactions is reflected in the associated blue and red shifts of vibrational spectrum. We also find that the interactions involving 3-methylindole are somewhat greater than those for p-hydroxytoluene. The C-H blueshifts are also in parallel with the predicted NMR proton shift. We have also tested different density functionals including both standard density functionals and newly developed M0x functionals and MP2 method for studying carbohydrate-aromatic complexes. The DFT-D method and M06 functionals of the M0x family are found to perform better, while B3LYP and BLYP functionals perform poorly. We find that the inclusion of a dispersion term to BLYP is found to perform better. The dispersion energy dominates over the interaction energy of carbohydrate-aromatic complexes. From the DFT-D calculations, we found that the complexes would be unstable without the contribution from dispersive energy. We have also studied the importance of noncovalent interactions in functionalization of nanotubes by nucleic acid bases and aromatic amino acids by using semi-empirical methods with dispersion term such asPM3-D and PM3-D*. We find that the both semi-empirical schemes give reasonable interaction energies with respect to DFT-D interaction energies. We have also used PM3-D method to study the adsorption of organic pollutants on graphene sheet and on nanotubes. We found that the semi-empirical schemes, which are faster and cheaper, are suitable to study these larger molecules involving noncovalent interactions and can be used as an alternative to DFT-D method. We have also studied the importance of dispersion interaction and the effect of steric hindrance in aggregation of functionalized anthracenes and pentacenes. We have also employed molecular dynamics simulation methods to study the aggregation of anthracene molecules in toluene solution.

Une antisepsie-désinfection (ATS-D) efficace est fondamentale si l'on considère le manque de traitements antiviraux spécifiques, l'émergence de nouveaux virus et l'accroissement du nombre d'infections nosocomiales virales. A ce jour, une seule norme Européenne, la norme NF EN 14476+A1, propose un cadre pour évaluer l'activité ATS-D antivirale en médecine Humaine et certaines améliorations sont encore nécessaires.Dans ce but, nous avons développé et validé, biologiquement et physico-chimiquement, un protocole pour évaluer l'activité ATS-D antivirale. Ce dernier est basé sur une méthode originale de filtration sur gel faisant appel à des colonnes de Séphadex™ G-25 et G-10 de notre conception comme moyen de neutralisation. Nous avons ainsi évalué, sur le coronavirus Humain 229E (HCoV 229E), les activités ATS-D de deux molécules de référence, la chlorhexidine (CHX) et l'hexamidine (HXM), ainsi que de deux calixarènes : le tetra-para-sulfonato-calix[4]arène (C[4]S) et le 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arène (C[4]S-BTZ). Selon la norme Européenne, pour qu'une formulation puisse prétendre à une activité ATS-D antivirale, il faut qu'elle induise une diminution de 4 log10 dans les titres viraux. L'HXM et le C[4]S n'ont montré qu'une très faible activité vis à vis du HCoV 229E. La CHX a montré quant à elle une activité beaucoup plus intéressante bien qu'elle ne puisse néanmoins pas prétendre à une activité ATS sur le HCoV 229E. Enfin, le C[4]S-BTZ a montré une activité comparable, voire meilleure, que la CHX. Son activité s'est en effet avérée plus rapide, rémanente et dénuée de cytotoxicité, contrairement à la CHX / Efficient antisepsis-disinfection is fundamental, considering the lack in antiviral treatments, the emergence of new viruses and the raising of viral nosocomial infections. Only one European Standard (NF EN 14476 + A1) proposes a frame to evaluate antiseptic antiviral activity in Human medicine and some improvements are still needed. We thus developed and validated, biologically and physico-chemically, a virucidal assay based on an original gel filtration method, using “in-house” G-25 and G-10 Sephadex™ columns, as neutralization method. We evaluated, on the Human coronavirus 229E (HCoV 229E), the antiseptic activity of two reference molecules, chlorhexidine (CHX) and hexamidine (HXM), and of two new potent antiviral drugs: the tetra-para-sulfonatocalix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato calix[4]arene (C[4]S-BTZ). A 4 log10 reduction in viral titers is required, according to the European Standard.HXM and C[4]S showed almost no activity on the HCoV 229E. Considering the CHX, it showed a quite interesting activity, even if it did not reach the threshold to pretend to an antiseptic activity on the HCoV 229E. Finally, The C[4]S-BTZ showed a comparable activity to the CHX, and even better. Thanks to this original method, we could highlight a new interesting molecule, the C[4]S-BTZ, which showed a close activity to the CHX, but faster, residual and exempt of cytotoxicity, whereas chlorhexidine did