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1	Detection of reactive intermediates from quinol esters and O-aryl-N-methanesulfonyl hydroxylamine Wang, Yue-Ting 01 August 2009 (has links) No description available. Chemistry reactive intermediate kinetics aryloxenium ion photolysis
2	Synthesis of analogues of nordihydroguaiaretic acid and their oxidative metabolism Maloney, Katherine Ann 01 June 2010 In order to investigate the structural features responsible for the cytotoxicity of the naturally occurring lignan nordihydroguaiaretic acid, the synthesis of four structural analogues of NDGA is proposed for the purpose of studying their oxidative metabolism. One analogue in particular (1), a mono-catechol analogue, is successfully synthesized employing a double Stobbe condensation approach. Following synthesis of this compound a series of oxidation experiments is performed consisting of: incubation in rat liver microsomes with and without the trapping agent glutathione (GSH), oxidation with mushroom tyrosinase, oxidation with silver oxide, and oxidation with horseradish peroxidase. Results are analyzed via HPLC and UPLC-MS. It is found that 1 does not autoxidize at pH 7.4 as NDGA does. Two products are produced during incubation of 1 in rat liver microsomes with UPLC-ESI(-)-MS results giving m/z of 879.2 and 574.18. This is consistent with 1 plus 2 GSH and 1 plus 1 GSH respectively; confirming 1 will oxidize to an electrophilic moiety. Oxidation with mushroom tyrosinase is found to produce high levels of product two with m/z 574.2. Oxidation with horseradish peroxidase is found to produce high levels of the m/z 879.2 product. Silver Oxide produced multiple products rather than the expected one major product, but most are found to be inconsistent with the products seen during rat liver microsomal incubation, and are not pursued. cytochrome P450 bioactivation reactive intermediate lignan anhydrosecoisolariciresinol quinone nordihydroguaiaretic acid stobbe condensation glutathione adduct
3	Synthesis of analogues of nordihydroguaiaretic acid and their oxidative metabolism Maloney, Katherine Ann 01 June 2010 (has links) In order to investigate the structural features responsible for the cytotoxicity of the naturally occurring lignan nordihydroguaiaretic acid, the synthesis of four structural analogues of NDGA is proposed for the purpose of studying their oxidative metabolism. One analogue in particular (1), a mono-catechol analogue, is successfully synthesized employing a double Stobbe condensation approach. Following synthesis of this compound a series of oxidation experiments is performed consisting of: incubation in rat liver microsomes with and without the trapping agent glutathione (GSH), oxidation with mushroom tyrosinase, oxidation with silver oxide, and oxidation with horseradish peroxidase. Results are analyzed via HPLC and UPLC-MS. It is found that 1 does not autoxidize at pH 7.4 as NDGA does. Two products are produced during incubation of 1 in rat liver microsomes with UPLC-ESI(-)-MS results giving m/z of 879.2 and 574.18. This is consistent with 1 plus 2 GSH and 1 plus 1 GSH respectively; confirming 1 will oxidize to an electrophilic moiety. Oxidation with mushroom tyrosinase is found to produce high levels of product two with m/z 574.2. Oxidation with horseradish peroxidase is found to produce high levels of the m/z 879.2 product. Silver Oxide produced multiple products rather than the expected one major product, but most are found to be inconsistent with the products seen during rat liver microsomal incubation, and are not pursued. cytochrome P450 bioactivation reactive intermediate lignan anhydrosecoisolariciresinol quinone nordihydroguaiaretic acid stobbe condensation glutathione adduct
4	Oxidative metabolism and cytochrome P450 enzyme inhibition potential of creosote bush and flaxseed lignans Billinsky, Jennifer Lynn 22 September 2009 The rising use of natural products creates an imperative need for an enhanced awareness of the safety of current and new products making their way into the marketplace. An important example is natural products containing lignans as the principal active component. Despite their structural similarity the lignan of creosote bush can cause hepato- and renal toxicity while the lignans of flaxseed have no reported serious toxicity. This dissertation aimed to investigate the oxidative metabolism of such lignans to determine whether reversible, competitive interactions and/or bioactivation may explain the differences in their apparent toxicity.<p> The first objective was to study the metabolism and bioactivation of nordihydroguaiaretic acid (creosote bush) and secoisolariciresinol (flaxseed). Nordihydroguaiaretic acid metabolism in rat liver microsomes led to the production of three glutathione adducts formed via ortho¬-quinone reactive intermediates. This metabolism was independent of NADPH and thus attributed to autoxidation. Secoisolariciresinol metabolism yielded lariciresinol and no glutathione adducts suggesting an absence of bioactivation to reactive quinone intermediates.<p> The second objective was to study the autoxidation of nordihydroguaiaretic acid. The major autoxidation product was a unique, stable schisandrin-like cyclolignan which was the result of nordihydroguaiaretic acid cyclization. The half-life of nordihydroguaiaretic acid in aqueous solution, pH 7.4, 37ºC is 3.14 hours suggesting the cyclolignan may be responsible for some of the biological effects of nordihydroguaiaretic acid.<p> The third objective was to study the inhibition of cytochrome P450 isoforms 1A2, 2B, 2C11 and 3A by lignans derived from creosote bush and flaxseed. None of the lignans caused irreversible inhibition. Both creosote bush and flaxseed lignans caused reversible inhibition of P450 enzyme activity that involved competitive or mixed-type inhibition, however the inhibition was present at nonphysiologically relevant concentrations. Activation of cytochrome P450 isoforms was also observed at low lignan concentrations. The results suggest that P450-mediated bioactivation or reversible inhibition cannot explain the differences in toxicity noted between the lignans of creosote bush and flaxseed.<p> This work suggests a minimal risk for drug-lignan interactions at P450 enzymes. Further studies are warranted to determine the presence and biological and toxicological role of the nordihydroguaiaretic acid cyclolignan in herbal preparations. Secoisolariciresinol Nordihydroguaiaretic acid Flaxseed quinone Creosote bush Anhydrosecoisolariciresinol Enterolactone Enterodiol Dibenzocyclooctadiene Cytochrome P450 bioactivation inhibition reactive intermediate lignan hepatotoxicity autoxidation Glutathione adduct
5	Oxidative metabolism and cytochrome P450 enzyme inhibition potential of creosote bush and flaxseed lignans Billinsky, Jennifer Lynn 22 September 2009 (has links) The rising use of natural products creates an imperative need for an enhanced awareness of the safety of current and new products making their way into the marketplace. An important example is natural products containing lignans as the principal active component. Despite their structural similarity the lignan of creosote bush can cause hepato- and renal toxicity while the lignans of flaxseed have no reported serious toxicity. This dissertation aimed to investigate the oxidative metabolism of such lignans to determine whether reversible, competitive interactions and/or bioactivation may explain the differences in their apparent toxicity.<p> The first objective was to study the metabolism and bioactivation of nordihydroguaiaretic acid (creosote bush) and secoisolariciresinol (flaxseed). Nordihydroguaiaretic acid metabolism in rat liver microsomes led to the production of three glutathione adducts formed via ortho¬-quinone reactive intermediates. This metabolism was independent of NADPH and thus attributed to autoxidation. Secoisolariciresinol metabolism yielded lariciresinol and no glutathione adducts suggesting an absence of bioactivation to reactive quinone intermediates.<p> The second objective was to study the autoxidation of nordihydroguaiaretic acid. The major autoxidation product was a unique, stable schisandrin-like cyclolignan which was the result of nordihydroguaiaretic acid cyclization. The half-life of nordihydroguaiaretic acid in aqueous solution, pH 7.4, 37ºC is 3.14 hours suggesting the cyclolignan may be responsible for some of the biological effects of nordihydroguaiaretic acid.<p> The third objective was to study the inhibition of cytochrome P450 isoforms 1A2, 2B, 2C11 and 3A by lignans derived from creosote bush and flaxseed. None of the lignans caused irreversible inhibition. Both creosote bush and flaxseed lignans caused reversible inhibition of P450 enzyme activity that involved competitive or mixed-type inhibition, however the inhibition was present at nonphysiologically relevant concentrations. Activation of cytochrome P450 isoforms was also observed at low lignan concentrations. The results suggest that P450-mediated bioactivation or reversible inhibition cannot explain the differences in toxicity noted between the lignans of creosote bush and flaxseed.<p> This work suggests a minimal risk for drug-lignan interactions at P450 enzymes. Further studies are warranted to determine the presence and biological and toxicological role of the nordihydroguaiaretic acid cyclolignan in herbal preparations. Secoisolariciresinol Nordihydroguaiaretic acid Flaxseed quinone Creosote bush Anhydrosecoisolariciresinol Enterolactone Enterodiol Dibenzocyclooctadiene Cytochrome P450 bioactivation inhibition reactive intermediate lignan hepatotoxicity autoxidation Glutathione adduct
6	Oxidative Lipid Fragmentation; New Mechanisms, Synthesis and Reactions of Putative Intermediates Gu, Xiaodong January 2010 (has links) No description available. Chemistry -hydroxyl alkenals
7	Experimental observation and quantum chemical investigation of thallium(I) (Z)-methanediazotate: synthesis of a long sought and highly reactive species Singh, Neeraj, Fiedler, Benjamin, Friedrich, Joachim, Banert, Klaus 28 April 2017 (has links) (PDF) For the first time, successful synthesis and characterisation of the missing (Z)-isomer of thallium(I) methanediazotate has been accomplished, utilising low-temperature NMR monitoring analysis. The title compound was synthesised from N-methyl-N-nitrosourea and thallium(I) propoxide, under sub-ambient temperature conditions, as a highly moisture sensitive entity. Quantum chemical calculations, performed at the CCSD(T) level, depict excellent conformity to experimental results. Indeed, compared to its (E) counterpart, the formation of the title compound is thermodynamically less favoured, but preferred by means of kinetic control owing to a hindered isomerisation. Isomerie Computerchemie Magnetische Kernresonanz Technische Universität Chemnitz Publikationsfonds reactive intermediate nuclear magnetic resonance computational chemistry urea isomerism Chemnitz University of Technology Publication funds ddc:547 Isomerie Computational chemistry Magnetische Kernresonanz Harnstoff
8	Experimental observation and quantum chemical investigation of thallium(I) (Z)-methanediazotate: synthesis of a long sought and highly reactive species Singh, Neeraj, Fiedler, Benjamin, Friedrich, Joachim, Banert, Klaus 28 April 2017 (has links) For the first time, successful synthesis and characterisation of the missing (Z)-isomer of thallium(I) methanediazotate has been accomplished, utilising low-temperature NMR monitoring analysis. The title compound was synthesised from N-methyl-N-nitrosourea and thallium(I) propoxide, under sub-ambient temperature conditions, as a highly moisture sensitive entity. Quantum chemical calculations, performed at the CCSD(T) level, depict excellent conformity to experimental results. Indeed, compared to its (E) counterpart, the formation of the title compound is thermodynamically less favoured, but preferred by means of kinetic control owing to a hindered isomerisation. info:eu-repo/classification/ddc/547 ddc:547
9	From Copper to Gold: Identification and Characterization of Coinage-Metal Ate Complexes by ESI Mass Spectrometry and Gas-Phase Fragmentation Experiments Weske, Sebastian 30 January 2019 (has links) No description available. 540 coinage metal copper silver gold cuprate argentate aurate ate complex organocuprate organoargentate organoaurate magnesium organocuprate normant cuprate Cu(I) Cu(III) Ag(I) Ag(III) trifluoromethylation copper-mediated trifluoromethylation ruppert prakash c-c coupling cross coupling silver-mediated cross-coupling reactive intermediate reductive elimination counter ion effect esi ms esi-ms gas-phase fragmentation collision-induced dissociation cid gas-phase experiment gas-phase chemistry ion chemistry curiosity driven research Chemie (PPN62138352X)

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