Estudamos as propriedades eletrônicas, estruturais e hiperfinas, nos sítios de nitrogênio, para o composto imidazol nas fases gasosa e sólida. Utilizamos o método PAW que é um método ab initio all-electron, dentro da Teoria do Funcional da Densidade, através do código computacional CP-PAW. Nossos valores, tanto para a fase gasosa quanto para a fase cristalina do gradiente de campo elétrico no núcleo, de freqüência de acoplamento quadrupolar (ν) e parâmetro de assimetria (η) estão em ótima concordância com os resultados experimentais da literatura e são os primeiros resultados obtidos, por método ab initio no espaço recíproco, para os átomos de nitrogênio no imidazol cristalino. Utilizamos resultados da literatura e também aqui calculados para estudar a tendência de comportamento tanto de ν quanto de η para diferentes meros (um, dois, três, cadeia infinita) e cristal investigando, assim, a estreita influência das ligações de hidrogênio sobre os valores do Gradiente de Campo Elétrico nos núcleos de nitrogênio. / Here we study structural, electronic and hyperfine properties at the Nitrogen sites in imidazole in the gas and the crystal phases. We use the PAW method which is an ab initio all electron method in the framework of the Density Functional Theory, as embodied in the computer code CP-PAW. The results for quadrupole coupling (ν) and asymmetry parameter (η) at the gas and at the crystal phases are in excellent agreement with the experimental values in the literature. This is the first time that such calculations are performed for the crystalline imidazole through a reciprocal space approach. We also study the behavior of both ν and η trends studing diferent meres (one, two, three and infinite chain) and cristal to investigate the influence of hydrogen bonding on the Electric Field Gradient at the nucleus.

As inspired by the coordination environment of nickel in NikR and NiSOD, imidazole ligands were incorporated into N2SNiII square planar complexes in order to investigate the electronic and structural features of NiII species containing both imidazole and thiolate ligation. Rare examples of nickel complexes containing such ligand sets in continuous tetradentate (N2N'S) and discontinuous (N2S---N') coordination were synthesized and characterized. A significant finding in these studies is that the plane of the imidazole ligand is oriented perpendicular to the N2SNi plane. Further investigations addressed the orientational preference and stereodynamic nature of flat monodentate ligands (L = imidazoles, pyridine and an N-heterocyclic carbene) bound to planar N2SNi moieties. The solid state molecular structures of planar [N2SNiL]n+ complexes accessed through bridge-splitting reactions of dimeric, thiolate-S bridged [N2SNi]2 complexes, reveal that the plane of the added monodentate ligand orients largely orthogonal to the N2SNiL square plane. Variable temperature 1H NMR characterization of dynamic processes and ground state isomeric ratios of imidazole complexes in their stopped exchange limiting spectra, readily correlate with DFT-guided interpretation of Ni-L rotational activation barriers. Full DFT characterization relates the orientation mainly to steric hindrance derived both from ligand and binding pocket. In the case of the imidazole ligands a minor electronic contribution derives from intramolecular electrostatic interactions (imidazole C-2 C-H[superscript delta]+- - S[superscript delta]- interaction). Our group has firmly established the versatility of the (bme-daco)2-, (bme-dach)2-, and (ema)[left arrow]- ligands to accommodate a number of metals (M = Ni, Zn, Cu, and Fe ), and have demonstrated reactivity of such N2S2M complexes occurs predominately at the S-thiolate sites. As vanadium is of interest for its biological, pharmacological and spectroscopic/analytical probe abilities, vanadyl analogues were explored as mimics of possible chelates formed from Cys-X-Cys binding sites in vivo. The structural and electronic changes from the incorporation of V=O2+ in such dianionic and tetraanionic N2S2 binding pockets is investigated and compared to Ni2+ and Zn2+ in similar N2S2 environments. The nucleophilicity of the S-thiolate in these systems is explored with alkylating agents and W(CO)x. Furthermore, the vanadyl interaction with the CGC peptide, the biological analogue of the tetraanionic N2S2 ligand, was produced and characterized by EPR; its W(CO)x adducts were indentified by ?(CO) infrared spectroscopy.

Thèse (M.Sc.)--Université Laval, 2007. / Titre de l'écran-titre (visionné le 18 septembre 2007). Bibliogr.

Estudamos as propriedades eletrônicas, estruturais e hiperfinas, nos sítios de nitrogênio, para o composto imidazol nas fases gasosa e sólida. Utilizamos o método PAW que é um método ab initio all-electron, dentro da Teoria do Funcional da Densidade, através do código computacional CP-PAW. Nossos valores, tanto para a fase gasosa quanto para a fase cristalina do gradiente de campo elétrico no núcleo, de freqüência de acoplamento quadrupolar (ν) e parâmetro de assimetria (η) estão em ótima concordância com os resultados experimentais da literatura e são os primeiros resultados obtidos, por método ab initio no espaço recíproco, para os átomos de nitrogênio no imidazol cristalino. Utilizamos resultados da literatura e também aqui calculados para estudar a tendência de comportamento tanto de ν quanto de η para diferentes meros (um, dois, três, cadeia infinita) e cristal investigando, assim, a estreita influência das ligações de hidrogênio sobre os valores do Gradiente de Campo Elétrico nos núcleos de nitrogênio. / Here we study structural, electronic and hyperfine properties at the Nitrogen sites in imidazole in the gas and the crystal phases. We use the PAW method which is an ab initio all electron method in the framework of the Density Functional Theory, as embodied in the computer code CP-PAW. The results for quadrupole coupling (ν) and asymmetry parameter (η) at the gas and at the crystal phases are in excellent agreement with the experimental values in the literature. This is the first time that such calculations are performed for the crystalline imidazole through a reciprocal space approach. We also study the behavior of both ν and η trends studing diferent meres (one, two, three and infinite chain) and cristal to investigate the influence of hydrogen bonding on the Electric Field Gradient at the nucleus.

Plusieurs études expérimentales et théoriques ont montré la capacité des structures de type zéolites (zeolitic "imidazolate, triazole" frameworks ou ZIFs) à capturer le CO2. Dans cette étude, nous nous intéresserons à l’interaction de CO2 avec une sous entité des ZIFs i.g. les complexes entre l’imidazole et le zinc (Im-Zn+q; q = 0,1,2) ou le triazole sans Zinc. Divers sites d'adsorption ont été examinés..Les calculs électroniques ont été effectués par les programmes GAUSSIAN et MOLPRO. Les optimisations de géométrie sur les petites structures (avec ou sans CO2) ont été réalisées avec les méthodes ab initio MP2, CCSD(T)-F12 et les bases atomiques aug-cc-pVDZ, aug-cc-pVTZ. Pour comparer les résultats, et assurer la continuité de notre travail, ces structures ont été aussi étudiées à l’aide de la DFT, en utilisant les fonctionnelles PBE, PBE0, M11 et M05-2X avec la base 6-311++G(d,p). La correction de dispersion empirique de Grimme (DFT-D3) est également incluse.Nos résultats montrent que leurs structures stables sont formées à la fois par des liaisons covalentes fortes (liaisons chimiques des ligands organiques) et des liaisons de nature plus faibles (liaisons van der waals, liaison hydrogène). Les deux types sont en compétition. Ceci nous a permis de mieux comprendre les observations expérimentales. / Several experimental and theoretical studies have shown the ability of zeolitic-imidazole frameworks (ZIFs) materials to capture the CO2 gas. In this study, we have focused on the interaction of CO2 with one of the sub-unit of ZIFs ie the complex between the imidazole and zinc (Im-Zn+q, q = 0 ,1, 2) or triazole without zinc. Various adsorption sites are examined for these complexes.The calculations were performed using ab initio methods MP2; CCSD(T)-F12 and density functional theory with PBE PBE0, M1 and M05-2X functionals with different basis set (aug-cc-pVDZ, aug-cc-pVTZ and 6-311++G(d, p), tightly integrated in GAUSSIAN and MOLPRO packages. The Grimme corrections for dispersion forces description (DFT-D3) are also included.Our results shows that the stability of our complex structures is achieved by the presence of strong covalent bonds (chemical bonds of organic ligands) and also by Van der Waals and hydrogen weak bonds. Both types of bonding are in competition. This allowed us to better understand the experimental observations.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20929号 / 理博第4381号 / 新制||理||1630(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 杉山 弘, 教授 三木 邦夫, 教授 秋山 芳展 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

No description available.

学位プログラム名: 京都大学大学院思修館 / 京都大学 / 新制・課程博士 / 博士(総合学術) / 甲第23345号 / 総総博第18号 / 新制||総総||3(附属図書館) / 京都大学大学院総合生存学館総合生存学専攻 / (主査)教授 山敷 庸亮, 教授 杉山 弘, 教授 積山 薫 / 学位規則第4条第1項該当 / Doctor of Philosophy / Kyoto University / DGAM

The work is focused on the investigation of synthesis and structure of crystalline coordination networks by combining first a row transition metal ion with one anionic and one neutral bridging ligand. In the field of crystalline coordination networks, the goal is to synthesize porous 3D crystalline coordination networks with molecular sized cavities. The materials are characterized by XRD and TGA. It is important to understand the structural topologies to develop practical applications, such as gas storage, gas separation, and catalysis. The bi- and tetra-dentate flexible imidazole ligands, 9,10-bis(imidazol-1-ylmethyl)anthracene (Chapter 2) and 1, 2, 4, 5-tetrakis(imidazol-1ylmethyl)benzene (Chapter 3), are synthesized and used as linkers to construct 1D, 2D, and 3D crystalline coordination networks with cobalt(II) or zinc(II) cations and H3BTC anions under solvothermal conditions. Two 1D chain networks, [M(HBTC²⁻)(C₂₂H₁₈N₄)(H₂O)₂]•H₂O, are constructed from M(Zn(II) or Co(II)), H₃BTC, and 9,10-bis(imidazol-1-ylmethyl)anthracene (Compound 2.1 and 2.2). These two 1D zigzag chains are linked into infinite 2D sheets by inter-chain π•••π stacking and hydrogen bonding. ⁺ Two 2D and one 3D cobalt(II) coordination networks are constructed from the tetradentate imidazole ligand and H3BTC. Compound 3.1 has a 2D corrugated sheet structure that is linked by inter-layer π•••π stacking and hydrogen bonding. Compound 3.2 has a 2D sheet structure. These sheets are interconnected by hydrogen bonds at the free acid group of the HBTC²⁻ ligand. Compound 3.3 forms a two fold interpenetrated 3D network structure. Void spaces in the structure are filled with six water molecules. Six 3D cobalt (II) coordination networks are constructed with bidentate rigid imidazole containing neutral ligands, 1,4-bis(imidazol-1-yl)benzene(L1), 1,4-bis(imidazol-1-yl)naphthalene(L2), and 9,10-bis(imidazol-1-yl)anthracene(L3), and H₂BDC or H₃BTC anion (Chapter 4). In 4.1-4.3, L1-L3 affects on degree of interpenetrations constructed with H₂BDC ligand. In 4.1 and 4.2 are interpenetrating 3D networks with no accessible void space. In 4.3, void spaces of 3D networks are filled with 2D sheets. Compounds 4.4-4.6 are prepared by different concentrations of starting materials and different solvents. In 4.4-4.6, L3 serves as a pillar building block to construct 3D networks by applying with H₃BTC ligand. The solvent exchange experiment for 4.4 is further discussed. / Ph. D.

La protéine MDM2 lie la protéine suppresseur de tumeur p53 avec une grande affinité et module négativement son activité. Les Nutlins peuvent lier MDM2 en bloquant le compartiment de liaison pour p53 et ainsi activer la voie de p53 dans les cellules cancéreuses, menant à l'arrêt du cycle cellulaire et à l'apoptose. L'effet cytotoxique de la Nutlin a été confirmé dans différentes lignées tumorales du colon (HCT-116) portant un gène p53 sauvage, tandis qu'aucun effet n'est observé dans les cellules p53-/-. La Nutlin révèle un effet d'inhibiteur intermédiaire dans le clone HCT-116 p21-/-. Des analyses par FACS indiquent que la surexpression de p21 médiée par p53 active les voies pro-apoptotiques, tandis que l'action p21-indépendante du suppresseur de tumeur p53 détermine la mort cellulaire via la nécrose. La plupart des lignées cancéreuses traitées avec la Nutlin subissent un arrêt du cycle cellulaire en phases G1+G2. Cependant, un des clones HCT-116 montre un arrêt en phase G1. Des analyses par microarray ont été exécutées afin d'élucider les mécanismes moléculaires de l'action antiproliférative et cytotoxique de la Nutlin. Différents gènes impliqués dans le contrôle du cycle cellulaire et la prolifération cellulaire sont sous-exprimés, alors que certains gènes de la voie pro-apoptotique p53 sont sur-exprimés. La comparaison de l'expression génique des cellules HCT-116 bloquant en G1+G2 avec celles bloquant en G1 a indiqué une implication possible de plusieurs gènes régulateurs du cycle cellulaire. Nos résultats confirment le fort potentiel thérapeutique de la Nutlin pour les tumeurs préservant une p53 de type sauvage.