Significant advances in the design, synthesis, and chemistry of verdazyl radicals have been made, including (i) the systematic study of the electrochemistry of verdazyl radicals, (ii) the development of formazans as ancillary ligands en route to inorganic verdazyl radicals, and (iii) magnetostructural studies of verdazyl diradicals and copper (II) verdazyl complexes. The electrochemical properties of a family of verdazyl radicals were explored. Type I and type II verdazyl radicals were reversibly oxidized and reduced, and the potentials of such processes observed to be sensitive to substituent effects. The incorporation of electron-withdrawing substituents made verdazyl radicals harder to oxidize and easier to reduce, while the presence of electron-donating groups had the opposite effect. Type II verdazyls were harder to oxidize and less delocalized (based on relative cell potentials) than type I analogues. The difficulty in oxidation of type II verdazyls relates to the electron-withdrawing nature of the carbonyl functionality, while the decreased delocalization relates to twisting of the N-substituents. Twisting of the N-substituents was confirmed through the use of X-ray crystal structures, and DFT calculations were used to illustrate the decrease in delocalization of the unpaired electron associated with the twisting. The similarities of formazans to -diketiminate ligands prompted the study of their coordination chemistry. Boratatetrazines, the first main group complexes of formazans illustrated their ability to mimick beta-diketiminate ligands. Reduction of boratatetrazines with cobaltocene afforded highly reactive borataverdazyl radical anions isolobal to parent organic systems. The radicals were readily oxidized back to the boratatetrazine precursors limiting their characterization to the solid-state. Synthetic pathways to 3-substituted formazans allowed for the incorporation of bulky N-substituents, a feature of -diketiminates that has influenced their utility as catalysts. 3-Cyanoformazans were shown to exist as either the open or closed structure in solution and the solid-state, while 3-nitroformazans exist exclusively as the closed strcutre due to the presence of the relatively large nitro-substituent. A number of transition metal complexes of 3-substituted formazans were synthesized, and their X-ray crystal structures used to establish a correlation between steric bulk at the ligand and complex structure. When ortho-substituents are incorporated the N-aryl substituents twist relative to the formazan backbone, while relatively smaller N-aryl substituents remain relatively planar. Palladium hexafluoroacetylacetonate complexes of formazans were anticipated to have utility as precursors to palladaverdazyls due to their electron poor nature. However, although the complexes did allow for the structure property relationship of metal-formazan complexes to be further developed, palladaverdazyls were not realized. Comparison with boratatetrazines suggests the nature of the Pd-N bond may play a role in the instability of palladaverdazyls. The synthesis and characterization of verdazyl-based spin dimers was reported. The incorporation of iso-propyl N-substituents allowed for the first truly stable verdazyl diradicals to be isolated. Electrochemical, electronic, and magnetic properties of diradicals bridged by para- and meta-benzene were explored. Diradicals bridged by para-benzene were antiferromagnetically coupled while meta-benzene bridged diradicals were ferromagnetically coupled. Magnetostructural studies of copper (II) complexes of verdazyls were complicated by the coordinative flexibility of copper (II) ions and the presence of Jahn-Tellar distorted ligand fields. However, a correlation between structure and properties was established: axially bound verdazyl radicals were weakly ferromagnetically coupled to copper (II) ions, and equatorially bound verdazyl radicals were strongly antiferromagnetically coupled to copper (II).

Variable temperature ESR studies of radicals generated photolytically from simple aliphatic alcohols and ethers in cyclopropane solution reveal complex linewidth effects. Isotropic modulation of the proton hyperfine splittings (hfs) through restricted rotation about C-0 and C-C single bonds is observable in the region 230>T>150K. Such effects can be distinguished from anisotropic viscosity-dependent line broadening. In spectra from alcohol radicals resolved 2nd order structure causes no ambiguity in the interpretation. Restricted rotation about Ca-0H modulates aaH and aBH out-of-phase with a0H in the series RCHOH [R= CH3, C2H5, C2H5CH2, (CH3)2CHCH2, (CH3)3CCH2]. A general model for the process is discussed. In cases three and four restricted Co-C rotation allows the diastereotopic inequivalence of the 6-protons to be manifested as a broadening of MB = 0 components. Preferred conformations consistent with all the foregoing modulation effects and with observed HB and HY splittings are presented. The analysis is supported by results for radicals RCHOR' from related ethers and by spectral simulation. The spectrum of the 1-hydroxycyclohexyl radical demonstrates previously unobserved fine structure and a low-temperature linewidth effect tentatively attributed to radical site inversion. A second series of alcohol-derived radicals R1R2R3CCHOH with an increasingly bulky Ca substituent has been studied. The Ha hfs provide evidence of a steric flattening not hitherto observed. This effect correlates well with literature values of steric parameters for the R1R2R3C substituent. In the case R1,R2 = CH3, R3 = C2H5 an observed specific y-H interaction is assigned to a locked conformation of the crowded system. A series of highly alkylated cyclic ethers has been examined. The dramatic temperature-dependent changes in the spectrum of the 5,5-dimethyl-l,3-dioxan-2-yl radical are attributed to restricted ring flipping. A fast exchange limit spectrum has been obtained for the first time in such systems, allowing evaluation of thermodynamic parameters. the 2,4,8,10-tetraoxyspiro[5,5]undecan-3-yl radical exhibits similar behaviour. The 2,2,5,5-tetramethyl and 5,5-diethyl-2,2-dimethyl-l,3--dioxan-4-yl radicals have fixed conformations which give rise to enhanced values of ayH in agreement with theoretical calculations. In the latter case a splitting of 4.27 G is assigned to a single y-methylene proton in behaviour analogous to R1R2R3CCHOH.

No description available.

Una dieta rica en frutas y verduras parece ser importante para la prevención de enfermedades relacionadas con el estrés oxidativo y por tanto es posible que alguno de sus compuestos constituyentes o la interacción de varios de ellos sean los responsables del efecto protector que presentan. Los flavonoides son los principales candidatos debido su abundancia en el reino vegetal y la actividad antioxidante que presentan en su estado natural. Existe una gran variedad de flavonoides que difieren en su estructura. Las pequeñas diferencias en la estructura química resultan en grandes diferencias en el efecto biológico. Además cuando los flavonoides son ingeridos sufren biotransformaciones que modifican la estructura química de los compuestos y por lo tanto, la actividad biológica se ve modificada. Una gran parte de los flavonoides que forman parte de frutas y verduras se encuentra en forma polimérica y fundamentalmente son proantocianidinas. Así, el objetivo general de la presente tesis fue contribuir al establecimiento de las bases científicas para el uso de fracciones polifenólicas y fibra dietética constituidas básicamente por proantocianidinas en la prevención de enfermedades como el cáncer. Para ello, se realizó un estudio de la relación entre el grado de polimerización y porcentaje de galoización y el efecto antioxidante y biológico de fracciones de proantocianidinas de diferente composición en diferentes medios físico-químicos. Así, fracciones obtenidas de corteza de pino (exentas de galato), de subproductos del prensado de la uva (porcentaje de galoización media) y de Hamamelis (de elevada galoización) fueron caracterizadas por despolimerización ácida y posteriormente se evaluó la capacidad antioxidante (método DPPH, TEAC), antirradicalaria (método del radical HNTTM, TNPTM), inhibición a la oxidación lipídica y el efecto antiproliferativo en una línea celular de melanoma (SK-MEL-28). Los resultados mostraron que los efectos químicos y biológicos en los que están implicadas las proantocianidinas están influidos de menor a mayor grado por el grado de polimerización, porcentaje de galatos y porcentaje de grupos pirogalol. Además se realizó un estudio de las biotransformaciones que sufren las proantocianidinas utilizando como muestra rica en proantocianidinas una fibra dietética procedente de subproductos del prensado de la uva. Para ello, se realizó previamente la identificación de los compuestos fenólicos mayoritarios y posteriormente con el fin de avanzar en el conocimiento de los posibles efectos beneficiosos de los polifenoles, se realizó un estudio de identificación de metabolitos tras la ingesta de fibra antioxidante de uva en ratas. Experimentos en tándem (LC-MS/MS) permitieron identificar 18 metabolitos procedentes de epicatequina monomérica y diversos ácidos fenólicos resultantes de la fermentación colónica. PALABRAS CLAVE: Radicales libres, Actividad antioxidante, Polifenoles, Fibra dietética, Procianidinas / Many epidemiological studies indicate that a diet rich in flavonoids from vegetables and fruits appear to be inversely related to several diseases and cancer mortality. Flavonoids in food have been shown to have powerful free-radical scavenging activity, antioxidant activity, and anti-tumor promoting effect. There are more than 5000 different types of flavonoids with numerous structural variations within. Small differences in their structure are converted into great differences in their biological activity. Moreover, polyphenols are extensively metabolized in the intestinal tract and liver. Thus, it is very important to examine the action of these compounds from different angles and evaluate their effects and risks. The main objective of the present PhD has been to contribute to the knowledge of the chemical and biological effects of polyphenols, especially proanthocyanidins. The influence of the degree of polimeration and percentage galloylation and the biological activities of proanthocyanidins fractions were evaluated. The results show that the most cytotoxic /antiproliferative fractions showed also the highest electron transfer capacity. The study of the metabolization of polyphenols after the intake of antioxidant dietary fiber (GADF) rich in proanthocyanidins resulted in the identification of more than 18 metabolites such a epicatechin mono, di-, tri- conjugates and also phenolic acids from colonic fermentation and even phenolic acids conjugates with sulfated and glucuronide. KEYWORDS: Free radicals, Antioxidant capacitiy, Polyphenols, Dieraty fiber, Procianidins

Diabetes mellitus is a chronic syndrome affecting carbohydrate, protein, and fat metabolism. It is characterized primarily by relative or absolute insufficiency of insulin secretion (type I diabetes or IDDM) or concomitant insensitivity / resistance to the metabolic action of insulin on target tissues (Type II diabetes or NIDDM), both resulting in hyperglycaemia. Diabetes mellitus is known to induce microvascular changes and alterations to neuronal functions. The neurovascular system comprising of unmyelinated primary afferent sensory neurones and the microvasculature innervated by these nerves play a major role in modulating inflammatory and tissue repair processes. Sensory nerve terminals respond to injury via the release of sensory neuropeptides which mediate inflammation and tissue repair. These processes are known to be altered in diabetes. This thesis is concerned with the role of diabetes in modulating microvascular blood flow directly and indirectly via modulating sensory nerve activity and the effect of these changes on repair processes in skin of 4 weeks streptozotocin (STZ)-induced diabetic rats. The following hypotheses were examined: 1. That factors implicated in long-term diabetic vascular damage play a role in altering skin microvascular function in early diabetes. 2. That preventing the deleterious effects of these factors could improve skin microvascular blood flow and skin repair processes in early diabetes. (For complete abstract open document)

Thesis (Ph.D.)--McMaster University (Canada), 1991. / Source: Dissertation Abstracts International, Volume: 53-01, Section: B, page: 0308. Supervisor: John Warkentin.

Thesis (Ph.D. in Clinical Science) -- University of Colorado at Denver and Health Sciences Center, 2006. / Typescript. Includes bibliographical references (leaves 107-128). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph.D.) -- University of Western Sydney, 2005. / Includes bibliography.

Thesis (M.A.)--Carleton University, 2003. / Includes bibliographical references (p. 112-122). Also available in electronic format on the Internet.

Thesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007. / Bibliography: leaves 295-322.