O antantreno é um hidrocarboneto hexacíclico aromático (HPA) bastante difundido no meio ambiente e que não apresenta as regiões de baía ou fjord, que em geral, conferem alta reatividade a esses compostos após oxidação. Entretanto, sua mutagenicidade em bactérias após ativação metabólica é comparável à do Benzopireno (BP) e, com base na sensibilidade das linhagens de S. typhimurium utilizadas, os metabólitos do antantreno causam substituições de pares de base, trocas de fita e possivelmente dano oxidativo ao DNA. Alguns dos metabólitos que apresentam ação genotóxica em bactérias foram recentemente identificados, mas uma investigação mais ampla considerando a ligação desses e outros possíveis metabólitos a biomoléculas, com a identificação dos adutos formados, pode contribuir para um melhor esclarecimento das vias envolvidas em sua genotoxicidade. Neste trabalho investigamos a reação do antantreno (oxidado quimicamente e pelo sistema HRP/H2O2) com dG e DNA in vitro, tendo sido observada a formação de possíveis adutos nas análises por HPLC/ESI/MS, HPLC/UV/Fluorescência e espectrofluorimetria. Células de carcinoma hepatocelular humano (HepG2) e hepatócitos de fígado humano normal (THLE-2) foram incubadas com antantreno e seus produtos de oxidação (quinonas e hidroquinonas acetiladas), verificando-se citotoxicidade dose dependente em diferentes condições de cultura. Uma vez que a sobrevivência relativa das células THLE-2 cultivadas sobre filme de colágeno e em meio PFMR-4 se assemelhou à sobrevivência relativa das células HepG2 cultivadas em meio DME e sem filme de colágeno, utilizamos as células HepG2 para análise de dano oxidativo. Produtos de oxidação do antantreno (quinonas e hidroquinonas acetiladas) induziram a formação de 8-oxodGuo no DNA celular. Os dados obtidos nos indicam que duas vias podem estar envolvidas na genotoxicidade do antantreno observada nos estudos com S.typhimurium realizados por Platt et al. (2002): indução de dano oxidativo e formação de adutos com o DNA. / Anthanthrene is a polycyclic aromatic hydrocarbon (PAH) widely spread in the environment and does not have the bay or fjord regions, which in general provide high reactivity to these compounds after oxidation. However, its mutagenic activity to bacteria after metabolic activation is comparable to that of benzopyrene (BP) and, based on the sensitivity of the S. typhimurium strains used, anthanthrene metabolites cause base pair substitutions, DNA strand exchanges, and possibly DNA oxidative damage. Some of the metabolites that are genotoxic to bacteria have been recently identified, but a better investigation on how these and other possible metabolites react with biomolecules, identifying the generated adducts, can contribute to clarify the ways involved in its genotoxicity. In the present work we investigated the reaction of anthanthrene (chemically oxidized or oxidized by the HRP/H2O2 system) with dG and DNA in vitro. The formation of possible adducts was observed in the analyses by HPLC/ESI/MS, HPLC/UV/Fluorescence and spectrofluorimetry. Human hepatocelular carcinoma cell line (HepG2) and normal human liver hepatocytes (THLE-2) were incubated with anthanthrene and its oxidation products (quinones and acetyladet hidroquinones). Dose dependent cytotoxity was observed under different culture conditions. As the relative survival of the THLE-2 cells grown on a film of collagen in PFMR-4 medium was very close to the relative survival of the HepG2 cells grown in DME medium, without the collagen film, we used the HepG2 cells for analysis of oxidative damage. Anthanthrene oxidation products (quinones and acetylated hidroquinones) induced 8-oxodGuo formation in the cellular DNA. Data obtained indicate that two ways may be involved in the genotoxicity of anthanthrene observed in the S. typhimurium studies conducted by Platt et al. (2002): DNA oxidative damage and adducts formation.

Foram preparados adutos de tetracloreto de titânio com ligantes orgânicos monodentados do tipo TiC14.2L, onde L = CH3CN, CD3CN, C2H5CN, C2H3CN, C6H5CN, C5H5N, C5D5N, (CH3)2S e (C2H5)2S. Foram feitas as previsões espectrais, pela aplicação da teoria de grupo, para o esqueleto do aduto TiCl4.2L, tendo em vista as três possíveis configurações: D4h, D2d e C2v. Os espectros vibracionais foram obtidos em estado sólido, sendo que para os adutos TiC14.2CH3CN e TiC14.2C2H5CN também o foram em solução, usando como solventes os respectivos ligantes. Os espectros Raman de todos os compostos e os espectros infravermelho dos adutos com os ligantes: acetonitrila deuterada, piridina deuterada e dietilssulfeto, são originais. Para maior facilidade na discussão e interpretação dos espectros os adutos foram agrupados em três conjuntos, caracterizados pela semelhança dos espectros vibracionais, especialmente, Raman. O primeiro conjunto compreende os adutos com nitrilas, o segundo os com piridina e o terceiro os com sulfetos. A análise dos espectros sugere que: a) Os compostos de adição do primeiro conjunto pertencem à configuração cis-octaédrica, grupo pontual C2v. b) O esqueleto dos adutos do segundo conjunto possuem configuração trans-octaédrica, simetria D4h. Para os complexos do terceiro conjunto não foi possível concluir, com base nos espectros vibracionais, a configuração do esqueleto. Foi feita uma tentativa de atribuição das frequências dos esqueletos para os adutos do primeiro e do segundo conjunto, com a utilização de vários argumentos empíricos. São discutidos alguns deslocamentos de frequências do ligante devido à coordenação. A análise em coordenadas normais, usando o campo de força de Urey-Bradley com duas interações, para os adutos de tetracloreto de titânio com acetonitrila e acetonitrila deuterada, confirma a atribuição feita. / Abstract not available.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound, formed as a metabolite from nonenzymatic and enzymatic reactions and is the leading precursor of advanced glycation end products (AGEs). AGEs contribute to ageing, type 2 diabetes mellitus (T2DM), and diabetes-related complications. However, MGO also has beneficial antibacterial activity and is the bioactive ingredient of medicinal honeys such as Manuka. Flavonoids are a group of phytochemicals that are powerful antioxidants. Polyphenols including flavonoids have been reported to trap MGO, forming adducts thereby preventing AGE formation. However, there is little to no information on the effect of adduct formation on the antioxidant properties of flavonoids and the antibacterial activity of MGO. In this study, catechin (CAT), chrysin (CHRY) and naringenin (NAR) at 0.1 mM and mixtures of each flavonoid with MGO (1:1) and (1:2) were evaluated for antioxidant and antibacterial activity. Antioxidant activity/capacity were evaluated with the total polyphenolic content (TPC), total flavonoid content (TFC), Trolox equivalent antioxidant capacity (TEAC) and the oxygen radical absorbent capacity (ORAC) assays. The bovine serum albumin (BSA)/MGO model was used to evaluate the effect on glycation. The 2’, 7’-dichlorofluorescein diacetate (DCFH-DA) assay with the L929 cell line was used to evaluate cellular antioxidant activity. Cytotoxicity was determined in the L929 cell line using the crystal violet (CV) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assays. Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) were used to determine antibacterial activity using the microbroth-dilution assay and subsequent changes to morphology were evaluated using scanning electron microscopy (SEM). A reduction in antioxidant content was observed for: CHRY (TPC), CAT and NAR (TFC) and in antioxidant activity for: CHRY (TEAC) and CAT (ORAC), when combined with MGO. Overall most of the antioxidant activity of the flavonoids was not affected by the addition of MGO. In the presence of BSA and MGO, all flavonoid:MGO combinations reduced formation of AGEs except NAR in combination with MGO. All flavonoids alone and in combinations did not cause cellular oxidative damage while MGO and AAPH induced increased cellular damage indicating that MGO via AGE formation makes cells more sensitive to the effects of oxidants that form radicals. Only CAT reduced the oxidative effects of MGO/AAPH. For all combinations there was no effect on cell number, although cell viability was significantly reduced for CHRY and its combinations and for NAR and NAR:MGO1. Flavonoids at 0.1 mM CAT, CHRY and NAR had no antibacterial activity against E. coli while inhibition was observed only with NAR against B. subtilis. MGO at 0.1 and 0.2 mM inhibited bacterial growth while in combination the antibacterial activity was significantly reduced. MGO as well as NAR caused major changes to bacteria morphology. In combination, the antibacterial activity of MGO was reduced, and ultrastructure changes associated with toxicity was also observed in most groups. In conclusion, flavonoids do trap MGO and this effect does not significantly alter flavonoid antioxidant activity. However, the antibacterial activity of MGO is reduced. Future studies should focus on the chemistry and the effects involved and should include dosage dependent studies. / Dissertation (MSc)--University of Pretoria, 2019. / Anatomy / MSc / Unrestricted

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<p> A 19F nmr study has shown that SeO2F2, SeOF2 and SeOCl2 behave as bases (B) towards SbF5 forming the adducts, (SbF5)n•B where n = 1-5 and in which they are bonded to antimony through an oxygen. Structural information about these adducts was also obtained. Solutions of SbF5 in SeOF2 and SeOCl2 were also shown to contain the SbF-6 and cis and trans [SbF4 (B)2]+ ions. The order of basicity towards SbF5 for the following bases is, SeOCl2 > SeOF2 > SbF-6 > SOF2 > SeO2F2 > SO2ClF.</p> <p> A 77Se nmr study of the SeOCl2 solvent system has shown that the order of Lewis acidity for the following acids is, SbF5 ~ SO3 > SbCl5 > SnCl4 > SbCl3 > AsCl3.</p> <p> A new selenium oxyfluoride, SeOF4 has been identified and is shown to form an ionic adduct SeOF+3SbF-6 with SbF5.</p> <p> Polyselenium oxyfluorides, F(SeO3)nSeO2F, where n=1-3, were prepared and are found to have acyclic structures. The 77Se spectra of Se4^2+ and Se8^2+ were studied. </p> <p> Redistribution reactions between selenium and phosphorus halides and oxyhalides were studied using the nmr resonances of 19F, 31P and 77Se.</p> / Thesis / Doctor of Philosophy (PhD)

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DNA damage is important to understand since it has the potential to lead to disease if unrepaired. In particular, bulky C8 guanine adducts (addition products) are known to induce a variety of mutations due to their conformational flexibility. C-linked C8-phenoxyl-deoxyguanosine adducts (PhOH-dG) have been poorly understood despite their potential for genotoxicity. This thesis systematically develops a computational model to predict the conformational and base-pairing preferences of PhOH-dG by gradually increasing the size of the system. The structure of PhOH-dG in DNA is determined, where the bulky C8 group induces a syn conformation of the base similar to other C8-adducts. A stabilized guanine mismatch is identified for the syn adducts, which implies that the primary mechanism of genotoxicity may be base-substitution mutations resulting in G→C transversions. This thesis has contributed to a growing body of literature dedicated to understanding the role of conformational heterogeneity in the mutagenicity of bulky C8-adducts. / xix, 192 leaves : ill. (some col.) ; 29 cm