Recently, considerable interest has been devoted to the synthesis of new ferrocene derivatives since properly functionalized ferrocene derivatives could be potential antitumor substances. For this purpose, we have investigated the synthesis of ferrocenyl quinones starting from squaric acid. Thermolysis of ferrocenylsubstituted cyclobutenones, which have been prepared from ferrocenyl cyclobutenediones and alkenyllithiums, affords hydroquinones, which furnish, upon oxidation, ferrocenyl quinones. Ferrocenyl cyclobutenediones have been prepared from known cyclobutenediones by nucleophilic addition of ferrocenyllithiumfollowed by hydrolysis, Pd/Cu-cocatalyzed cross-coupling with (tri-n-butylstannyl)ferrocene or Friedel&amp / #8211 / Crafts alkylation with ferrocene. A mechanism involving electrocyclic ring opening of alkenyl substituted cyclobutenone to dienylketene and consequent electrocyclic ring closure to cyclohexadienone followed by enolization has been proposed to account for the formation of ferocenyl substituted hydroquinones. Rocket design and production is one of the hottest topics in defense industry. On this subject, significant amount of investments have been done and excellent results were obtained. Among the burning rate catalysts for composite rocket propellants, ferrocene derivatives are one of the most famous ones. Although ferrocene derivatives are superior to some other burning rate catalysts, their use has some drawbacks arising from the tendency of migration in the bulk of the material and their sensitivity toward oxidation by air. With the aim of preventing the negative aspects of ferrocene derivatives, we have investigated the synthesis of EDA (ethylenediamine), TEP (tetraethylenepentamine) and DDI (dimeryl-diisocyanate) based ferrocene derivatives.

SYNTHESIS OF FERROCENYLIDENE CYCLOPENTENEDIONES K&ouml / kt&uuml / rk, Mustafa M.S., Department of Chemistry Supervisor: Assoc. Prof. Dr. Metin Zora August 2005, 83 pages 2-Arylidine-4-cyclopentene-1,3-diones are known to be antitumor agents. Incorporation of the essential structures of such compounds with a ferrocene moiety instead of an aryl group could provide subtances with enhanced antitumor activities since some ferrocene derivatives have already proved to be active against a number of tumors. Thus, we have investigated the squarate-based synthesis of 2-ferrocenylidene-4-cyclopentene-1,3-diones. Upon thermolysis, 4-hydroxy-4-ferrocenylethynyl-2-cyclobutenones, prepared from 3-cyclobutene-1,2-diones and lithioethynylferrocene, produced exclusively 2-ferrocenylidene-4-cyclopentene-1,3-diones. In some cases, ferrocenyl quinone derivatives are obtained in very minor amounts. Moreover, the heating of a mixture of 4-ferrocenylethynyl-4-hydroxy-2-cyclobutenones and silica gel in oven at 120 oC without using any solvent provided the same type of products. More importantly, the stirring of a solution of 4-ferrocenylethynyl-4-hydroxy-2-cyclobutenone (37A-C) derivatives in ethyl acetate at the room temperature yielded the same type products, as well. It appears that 4-hydroxy-4-ferrocenylethynyl-2-cyclobutenones are more reactive than corresponding phenyl analogs. For the formation of ferrocenyl-substituted cyclopentenediones, a mechanism involving first electrocyclic ring opening of ferrocenylethynyl-substituted cyclobutenones to corresponding ketene intermediate and then ring closure, has been proposed. The exclusive formation of cyclopentenediones is attributed to the radical stabilizing ability of the ferrocenyl moiety during the course of the reaction.

ABSTRACT SYNTHESIS OF FERROCENYL QUINONES AND POLYQUINANES Eralp, Tug&ccedil / e M.S., Department of Chemistry Supervisor: Assoc. Prof. Dr. Metin Zora June 2005, 79 pages With the discovery of antitumor activity of ferrocene derivatives, research on new ferrocene derivatives have gained importance. For this purpose, we have investigated the synthesis of ferrocenyl quinones starting from squaric acid. Several quinone derivatives are known to have antitumor and antibiotic activities. In this research, by combining ferrocene and quinone moieties, we have targeted ferrocenyl quinones which are supposed to have enhanced potential antitumor activity. Thermolysis of ferrocenyl-substituted 4-alkynyl cyclobutenones, which have been prepared from ferrocenyl cyclobutenediones and alkynyllithiums, leads to the formation of ferrocenyl quinones and besides also cyclopentendiones are observed. Ferrocenyl cyclobutenediones have been prepared from known cyclobutenediones by nucleophilic addition of ferrocenyllithium followed by hydrolysis. A mechanism for the formation of ferrocenyl substituted quinones, involving first electrocyclic ring opening of alkynyl substituted cyclobutenone to ketene intermediate and then ring closure, has been proposed. Polyquinanes are widely found in nature and proved to have biological activity such as antibiotic activity. For the synthesis of ferrocenyl polyquinanes, starting from squaric acid, ferrocenyl substituted cyclobutenediones were prepared and reacted with alkenyllithium, and hydrolyzed to afford ferrocenyl substituted polyquinanes. A mechanism has been proposed that involves first the formation of cis- and trans-divinyl substituted cyclobutenes that produce cyclooctatriene-dienolate, upon hydrolysis of this dienolate, aldol-type transannular ring closure reaction takes place, producing polyquinanes.

Thesis (Ph. D.)--University of New South Wales, 2000. / Includes bibliographic references. Also available online.

Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 158-180). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Abstract Human mitochondria contain a circular genome called mitochondrial DNA (mtDNA). It encodes subunits of the respiratory chain enzymes involved in energy conservation in oxidative phosphorylation and the necessary RNA needed for their expression. Errors in these genes have been shown to cause diseases, called mitochondrial diseases, which mainly affect tissues with high energy-demand, such as brain, heart, and skeletal muscle, or to lead to the production of harmful by-products in the form of reactive oxygen species (ROS) during cellular respiration. ROS damage lipids, proteins, and DNA, especially mtDNA. Accumulation of mtDNA mutations has also been associated with aging. Mitochondrial complex I is located in the inner mitochondrial membrane and catalyzes NADH-ubiquinone oxidoreduction coupled to the translocation of four protons from the inside of the mitochondrion to the intermembranous space. Bacteria contain a homologous but simpler enzyme, NDH-1, with the same catalytic mechanism and which is therefore considered the catalytical core of mitochondrial complex I. Seven of the conserved membranous subunits in complex I are encoded in the mtDNA and are targets for mutations causing mitochondrial diseases, like MELAS syndrome or Leber hereditary optic neuropathy (LHON). We used Paracoccus denitrificans and Escherichia coli NDH-1 enzymes to reveal the role of selected conserved charged residues and MELAS or LHON amino acid substitutions in enzyme catalysis. The growth phenotypes and NDH-1-dependent activities in mutant bacterial membranes were characterized, in addition to the sensitivity to selected complex I inhibitors. In order to enable ROS production measurements in the bacterial model of human mitochondrial diseases, we evaluated the reliability of two superoxide detecting probes, lucigenin and coelenterazine. Elimination of the acidic residue in ND1 (position E228) previously found to cause MELAS, was found detrimental for NDH-1 assembly and activity. Also, elimination of the acidic residue at position E36 in ND4L resulted in an inactive enzyme. ND1-E216A, ND4L-E72Q and -E36Q/I39D/A69D/E72Q substitutions decreased NDH-1 activity somewhat (normal activity in the last mutant), but displayed a negative growth phenotype under NDH-1 dependent conditions, suggestive of impaired energy conservation in these mutants. ND1-Y229, whose substitution causes MELAS, charged residues in loop five of ND1, and ND1-E157, whose substitution causes LHON, were also found important for the enzyme activity. Coelenterazine was found a reliable probe for quantitative superoxide production measurement in mitochondrial or bacterial membranes, and its sensitivity is not affected by the reduction level of the respiratory chain. Therefore, coelenterazine is suitable for quantitative superoxide production measurements.

This dissertation explores the structural modification of indigo into its rare cis form by substitution of a short organic bridge between the two indole nitrogen atoms. The synthesized N,N′-tethered cis-indigoids are assessed for their physicochemical properties in order to understand the effect of the organic tether on cis-indigoid systems. Three literature compounds containing “simple” tether structures are synthesized and subjected to complete characterization. Among them, alkyl group based cis-indigos, 2.5 and 2.6 exhibit similar absorption wavelengths as the parent indigo while oxalyl-tethered indigo 2.7 shows a large hypsochromic shift due to the strong electron-withdrawing nature of the oxalyl group. The electronics of the tether also affected the HOMO and LUMO energy levels; the oxalyl tether lowered both energy levels in comparison to the alkyl tethers. However, the indigoid co-planarity was strongly affected by the ring size from the tether rather than electronics. A new tethered cis-indigo structure type was discovered in reactions involving quinones. This new tether type consists of a 2,2′-dihydroindigo unit connected to the cis-indigo backbone through a central C–C bond of the former. Incorporation of the quinone moiety was observed in 3.2 where the final structure is comprised of two molecules of indigo and one naphthoquinone, while structures of 3.3 and 3.4 contained two indigoid units only. Investigation by CV revealed the strength of the quinone altered the early reaction intermediates. These dimeric cis-indigos show a small hypsochromic shift in the absorption compared to the parent indigo and relatively planar cis-indigoid backbone. 3.2 demonstrates rich redox behaviours. 3.3 and 3.4 display dynamic behaviours observed by solution VT 1H NMR spectroscopy. Oxalyl-tethered cis-Nindigo 4.6a and cis-indigo monoimine 4.7a were synthesized and compared with the indigoid counterpart 2.7 to examine the influence of the arylimine groups. Absorption wavelengths of the imine group containing species depended strongly on the electronics of the tether, yet the number of imine groups affected redox potentials. Protonation of 4.6a (to give H+oxalyl Nindigo 4.6aH+) causes a bathochromic shift in the absorption and allows for much easier reduction. The acidity (pKa) of 4.6aH+ is estimated between 3.6 – 4.46 in DMSO. A protonated cis-Nindigo derivative 4.9aH+ was obtained via reduction of the oxalyl group and is compared with 4.6aH+. / Graduate / 2022-08-13

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第17775号 / 理博第3898号 / 新制||理||1562(附属図書館) / 30582 / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 中野 伸一, 准教授 奥田 昇, 教授 疋田 努 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18094号 / 理博第3972号 / 新制||理||1573(附属図書館) / 30952 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 時任 宣博, 教授 大須賀 篤弘 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 新制・論文博士 / 博士(人間健康科学) / 乙第13562号 / 論人健博第12号 / 新制||人健||8(附属図書館) / (主査)教授 高桑 徹也, 教授 藤井 康友, 教授 長尾 美紀 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM