Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 307-320).

Thesis (M. Sc.)--University of Canterbury, 2009. / Typescript (photocopy). "March 2009." Includes bibliographical references (leaves 92-94). Also available via the World Wide Web.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 193-213).

Thesis (Ph. D.)--University of Canterbury, 2006. / Typescript (photocopy). Includes bibliographical references (leaves 285-305). Also available via the World Wide Web.

Neste trabalho foram realizados as sínteses, caracterização e o estudo da reatividade química dos complexos trans-[RuCl(NO)(py)4](PF6)2½H2O e trans-[RuCl(NO)(py)4]Cl23H2O. Os compostos foram isolados e caracterizados através de técnicas espectroscópicas (UV-vis, infravermelho e 1H RMN), eletroquímicas (voltametria cíclica e polarografia de pulso diferencial) e análise elementar. Os dados espectroscópicos, eletroquímicos e os resultados da análise elementar foram consistentes com as fórmulas dos complexos analisados. Foram utilizados como precursores os compostos [RuCl2(DMSO)4], trans-[RuCl2(py)4] e trans-[Ru(NO2)2(py)4]. O composto com NO foi obtido a partir do complexo trans-[Ru(NO2)2(py)4] em ácido clorídrico concentrado e precipitado como sal de PF6-, formando o complexo trans-[RuCl(NO)(py)4](PF6)2½H2O. O trans-[RuCl(NO)(py)4]Cl23H2O foi obtido a partir de uma solução do complexo trans-[RuCl(NO)(py)4](PF6)2.½H2O, adicionando-se uma solução de cloreto de tetrabutilamônio para precipitar o composto na forma de cloreto. Os espectros na região do UV-vis dos complexos trans-[RuCl(NO)(py)4](PF6)2½H2O e trans-[RuCl(NO)(py)4]Cl23H2O apresentaram três bandas nas regiões ao redor de 230 nm, 260nm e 450 nm. Os espectros de infravermelho apresentaram freqüência de estiramento NO entre 1900 e 1925 cm-1, cujo valor variou dependendo das condições em que foram obtidos os espectros. O ciclovoltamograma do composto trans-[RuCl(NO)(py)4](PF6)2½H2O, obtido em solução de acetonitrila, apresentou um processo redox atribuído ao par NO+/0 e um outro processo com E2c = -0,59 V vs Ag/AgCl atribuído à redução do NO0. A atribuição do processo redox com E½ = +0,30 V vs Ag/AgCl foi confirmada através do experimento de espectro eletroquímica na região do infravermelho, onde a banda atribuída ao NO foi diminuindo à medida que o composto ia sendo reduzido. Na espectroeletroquímica na região de UV-vis em acetonitrila foi possível observar uma reação acoplada à redução do composto trans-[RuCl(NO)(py)4](PF6)2½H2O, podendo ser a substituição do NO0 por uma molécula de solvente. O comportamento eletroquímico do composto trans-[RuCl(NO)(py)4]Cl23H2O foi estudado em solução aquosa. O ciclo voltamograma do composto apresentou um processo redox com E½ =+0,13 V vs Ag/AgCl, que é atribuído ao par NO+/0, um processo em +0,25 V e outro em 0,59 V. Dois processos redox dependentes do processo em +0,25 V foram observados nas faixa entre 0,4-0,7 V e podem ser devidos a produtos formados após uma provável saída do Cl- seguido da liberação do NO, como ocorre com o complexo trans-[RuCl(NO)(cyclam)](PF6)2. No estudo da reatividade do ligante NO no complexo trans-[RuCl(NO)(py)4]2+, observou-se que o NO é pouco reativo ao ataque nucleofílico do OH-, apresentando um pKa do equilíbrio entre as espécies nitro e nitrosilo em 11,5 e um Keq = 6,2.104 L2.mol-2. / In this work, the syntheses, characterization and chemical reactivity of trans-[RuCl(NO)(py)4](PF6)2½H2O and trans-[RuCl(NO)(py)4]Cl23H2O were studied. The complexes were isolated and characterizated by elemental analyses UV-vis, infrared and 1H NMR spectroscopies, cyclic voltammetry and spectroelectrochemistry. [RuCl2(DMSO)4], trans-[RuCl2(py)4] and trans-[Ru(NO2)2(py)4] were used as precursor complexes. The compound with NO ligand was obtained from the reaction of trans-[Ru(NO2)2(py)4] with chloridric acidic, and precipitation with PF6-, resulting in trans-[RuCl(NO)(py)4](PF6)2½H2O. The trans-[RuCl(NO)(py)4]Cl23H2O complex was obtained from a trans-[RuCl(NO)(py)4](PF6)2½H2O acetonitrile solution adding a tetrabutylammonium chloride acetonirile solution. The complex was precipitated as a chloride salt. The UV-vis spectra of trans-[RuCl(NO)(py)4](PF6)2½H2O and trans-[RuCl(NO)(py)4]Cl23H2O displayed three bands around the 230 nm, 260 nm and 450 nm regions. The infrared spectra showed the stretching frequencies NO in the 1900-1925 cm-1 range whose values depend on the conditions with which the spectra were recorded. The cyclic voltammetry of the trans-[RuCl(NO)(py)4](PF6)2½H2O in acetonitrile solutions showed a pair of peaks (E½ = +0.30 V vs Ag/AgCl) corresponding to the NO+/0 redox processes, and other process at E2c = -0.59 V vs Ag/AgCl assigned to NO0 reduction. The assignment of the redox processes was confirmed through infrared spectroelectrochemistry, where the band of NO decreases while the compound was reduced. The UV-vis spectroelectrochemistry in acetonitrile solution, showed a coupled reaction following the trans-[RuCl(NO)(py)4]2+ reduction. This coupled reaction is probably the NO substitution by a solvent molecule. The electrochemical behavior of trans-[RuCl(NO)(py)4]Cl23H2O was studied in aqueous solution. The cyclic voltammetry of this complex displayed a pair of peaks (E½ = +0.13 V vs Ag/AgCl) corresponding to NO+/0 redox processes, a process at -0,25 V and other at 0,59 V. Two other couples dependent on the process at 0.25 V, were observed between +0,4 V and +0,7 V. These may be due to products of the Cl- release followed by the NO release, as occurs in trans-[RuCl(NO)(cyclam)](PF6)2. The trans-[RuCl(NO)(py)4]2+ complex showed a low affinity for OH-, with a pKa of the equilibrium between nitro and nitrosyl species at 11.5 and a Keq = 6.2 x 104 L2.mol-2.

Despite progress in the metal-catalyzed synthesis of aromatic heterocycles, annulation routes towards 6-membered heterocycles remain underdeveloped. Specifically, routes towards pyridines are rare in spite of the prevalence of this moiety in novel drug candidates. Our initial efforts towards pyridines featured oximes as competent nucleophiles in the intramolecular, 6-exo dig annulation of alkynes using Brønsted acid catalysis. Two of the oxidation states required for subsequent aromatization are contained within the oxime via loss of water. An extension of this chemistry is presented and discussed, and involves the intramolecular metal-catalyzed 6-endo dig annulation of analagous alkynyl-oximes. Additionally, the discovery of a 5-exo dig annulation of related systems is discussed.

Pyridine nucleotide transhydrogenase catalyzes the reversible transfer of hydride ion equivalents between NADP(H) and NAD(H). In this study, the activity of the enzyme was measured by following the rate of reduction of an analogue of NAD⁺ , 3-acetylpyridxne-NAD⁺ (APNAD⁺ ) by NADPH. The enzyme was solubilized by detergents such as lysolecithin, sodium cholate (in the presence of ammonium sulphate) or Triton X-100. The molecular size of the solubilized enzyme was examined using sucrose density gradient centrifugation in the presence of Brij 58. These detergents gave soluble fragments of different sizes. That solubilized by Triton X-100 or sodium cholate (in the presence of ammonium sulphate) existed as large aggregates with sedimentation coefficients of 24.5 to 25.4S, whereas that obtained with lysolecithin consisted mainly of a species with a sedimentation coefficient of 7.3 to 16.5S. The fragment resulting from the solubilization with Triton X-100 could be cleaved into a smaller species (8.4S) by lysolecithin. Analysis by chromatography on Sepharose 6B of the enzyme preparation solubilized by sodium cholate (in the presence of ammonium sulphate), revealed the presence of other constituents of the membrane, such as succinate dehydrogenase, ATPase and cytochrome b₁. The molecular weight of the aggregate was estimated to be between 0.25 x 10⁶ and 4 x 10⁶. The enzyme in this preparation could not be further disaggregated by Tween 80, Brij 3 5 or Triton X-100. Chromatography of this preparation on DEAE-Sepharose CL-6B yielded a maximum purification of 37 to 68-fold over that of the membrane particle suspension. The specific activity of the enzyme was 8.8 to 15.7 umol per min per mg protein. Analysis of the partially purified enzyme on poly-acrylamide gels in the presence of sodium dodecyl sulphate revealed enrichment of several major polypeptide bands of molecular weights 90 000, 57 000, 50 000 and 40 000, coinciding with the transhydrogenase activity. The partially purified enzyme could be activated by detergents of the Tween or Brij series and by lysolecithin, palmitic acid and phospholipid extracts from E. coli. Measurements of the steady-state kinetics of the membrane-bound enzyme gave values of 45.6 and 106.7 uM for the substrates APNAD+ and NADPH, and dissociation constants of 3.6 and 16.2 uM, respectively. Lineweaver-Burk plots for each substrate at different fixed concentrations of the other substrate revealed a unique pattern of lines that is characteristic of rapid equilibrium random bireactant mechanisms with two dead-end products. In this type of mechanism each substrate is able to interact at the binding site of the other substrate to cause inhibition of enzyme activity. This mechanism was confirmed by kinetic studies using the alternate substrates deamino-NADPH and NAD⁺ , as well as by product inhibitxon studies. The adenine nucleotides 5’-AMP and ADP were competitive inhibitors of the APNAD+-binding site, while 2'-AMP was a competitive inhibitor of the NADPH-binding site on the enzyme. Studies on the active site using 2,3-butanedione or phenyl glyoxal revealed the presence of one modifiable arginyl residue per active site on the enzyme. Protection against modification by 2,3-butanedione was afforded by 2'-AMP, 5'-AMP, NAD+ and NADP+. Inhibition by 2,3-butanedione was enhanced in the presence of low concentrations of NADH or NADPH suggesting that binding of the reduced pyridine nucleotides, possibly at an allosteric site, causes a conformational change in the enzyme. Enhancement of in-activation of the enzyme by TPCK-trypsin was also observed in the presence of reduced pyridine nucleotides. NAD(P)H was oxidized by 2,3-butanedione in the presence of light. The rate of photooxidation was greatest at pH 7 and when the wavelength of incident light was 410 nm. This indicates that absorption of light by the diketone was necessary for the occurrence of the photooxidation reaction. The stochiometry of the reaction between NADH and 2,3-butanedione was 1:1. The possible nature of the reaction product is discussed in the thesis. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

The purpose of this study, then, is to prepare and characterize the complexes produced by the reaction of these ligards with rhodium III chloride. Of particular interest will be the mode of bonding of the ligand to the metal ion. For the first two groups, the potential exists for bonding to the metal from different parts of the ligand molecule. Bridging and chelation are also possibilities. Examination of the infrared spectrum of each complex should produce information as to the position of bonding. For one complex of the aminopyridines an N.M.R. spectrum will be examined.

This work is predominantly devoted to the 4-phenylpyridine ligand and the role that it plays in the formation of a series of inorganic coordination complexes termed Werner Clathrates. The synthesis and characterization by single crystal X-ray diffraction techniques are reported for 18 structures, the majority of which, upon crystallization, have the ability to include solvent or guest molecules within the host framework. The compounds are divided into four broad classes with the host complex of each as follows: Class A [Ni(NCS)₂(4-PhPy)₄]; Class B [NiCl₂(4-PhPy)₄]; Class c [Ni(NCS)₂(4-MePy)₂(4-PhPy)₂]; Class D [NiX₂(dmso)₂(4-PhPy)₂] where X= Ncs- or Cland [Ni(NCS)₂(4-RPy)₄] where R = 4-t-Bu or 4-Bz. The guest molecules, anionic ligand and substituent on the pyridine ligand have all been varied to try to establish the role that they each play in the formation of a structure. Much effort has been spent on the location and refinement of disordered guest molecules. Use has been made of statistical disorder and molecular scattering factors to try and successfully model these guests. The shapes of the cavities containing the guest molecules have been mapped by volume calculations and comparisons made between the packing of the compounds. Several of the complexes pack in space groups which are subsets of others and attempts have been made to determine the cause of the reduction in symmetry. A new technique to analyze competition experiments, with two guest solvents competing for occupation of the voids within the host lattice, has been established. Preliminary results for competition between p-xylene/benzene, p-xylene/toluene and p-xylene/ethylbenzene with the host complex [Ni(NCS)₂(4-ViPy)₄] are reported. The ability of the host complex [Ni(NCS)₂(4-MePy)₂(4-PhPy)₂] to separate a series of straight chain alcohols is demonstrated. The preference, by this host complex, for guest molecules containing a linear skeleton of 5 non-hydrogen atoms, is explained in terms of potential energy and residual volume calculations. Thermal analysis, consisting of thermogravimetry and differential thermal analysis, has been performed on several of the compounds. Temperatures of guest release, host decomposition and the enthalpies involved at each of these steps are reported.

No description available.