A facile and efficient base-mediated protocol for debromination of vic-dibromides in perfluoroalkyl(aryl) compounds in aqueous medium has been demonstrated. With mild reaction conditions, the developed strategy has a good substrate scope and electron-deficient olefin products were obtained in good yields. A mechanistic explanation of the debromination is offered with three key experimental observations: (1) the reactions are accelerated by the more electron-rich nucleophiles, (2) the reactions are promoted by the more electron poor vic-dibromides in perfluoroalkyl compounds, and (3) the nucleophilic side reaction is preventable. It is evident that the electronic factors strongly dictate vic-dibromides elimination to the perfluorovinyl ethers, which are the precursors for various perfluorinated polymers. The different reaction conditions were tested in implicit solvent (water) conditions, which helped to confirm the E2-like mechanism.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20392号 / 工博第4329号 / 新制||工||1671(附属図書館) / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 村田 靖次郎, 教授 近藤 輝幸, 教授 小澤 文幸 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

No description available.

Yes / Half-sandwich metal complexes are of considerable interest in medicine, material, and nanomaterial chemistry. The design of libraries of such complexes with particular reactivity and properties is therefore a major quest. Here, we report the unique and peculiar reactivity of eight apparently 16-electron half-sandwich metal (ruthenium, osmium, rhodium, and iridium) complexes based on benzene-1,2-dithiolato and 3,6-dichlorobenzene-1,2-dithiolato chelating ligands. These electron-deficient complexes do not react with electron-donor pyridine derivatives, even with the strong σ-donor 4-dimethylaminopyridine (DMAP) ligand. The Ru, Rh, and Ir complexes accept electrons from the triphenylphosphine ligand (σ-donor, π-acceptor), whilst the Os complexes were found to be the first examples of non-electron-acceptor electron-deficient metal complexes. We rationalized these unique properties by a combination of experimental techniques and DFT/TDFT calculations. The synthetic versatility offered by this family of complexes, the low reactivity at the metal center, and the facile functionalization of the non-innocent benzene ligands is expected to allow the synthesis of libraries of pseudo electron-deficient half-sandwich complexes with unusual properties for a large range of applications.

Yes / A 16-electron iridium organometallic is reacted with carbon monoxide to form an 18-electron CO-adduct. This CO-adduct is stable for weeks in the solid state, but quickly reverts to its parent 16-e complex in tetrahydrofuran solution, releasing CO(g). Using a simple methodology, we show that this gas can subsequently be used to perform a carbonylation reaction on another molecule. / Royal Society; Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation Springboard Award

Yes / An evaluation of the in vitro cytotoxicity of nine electron-deficient half-sandwich metal complexes towards two colorectal cancer cell lines (HCT116 p53+/+, HCT116 p53-/-) and one normal prostate cell line (PNT2) is presented herein. Three complexes were found to be equally cytotoxic towards both colorectal cancer cell lines, suggesting a p53-independent mechanism of action. These complexes are 12 to 34  more potent than cisplatin against HCT116 p53+/+ and HCT116 p53-/- cells. Furthermore, they were found to exhibit little or no cytotoxicity towards PNT2 normal cells, with selectivity ratios greater than 50. To gain an insight into the potential mechanisms of action of the most active compounds, their effects on the expression levels of a panel of genes were measured using qRT-PCR against treated HCT116 p53+/+ and HCT116 p53-/- cells, and cell cycle analysis was carried out. / The Royal Society grant UF150295, The Academy of Medical Sciences grant SFB003\1170

xx, 281 p. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / More than two-thirds of all enzyme substrates and cofactors are anionic, emphasizing the essential role that anions play in biological processes. Moreover, anions can have detrimental effects on the environment by causing ground water contamination when anions such as perchlorate, phosphate and nitrate develop in intolerable levels. Owing to the prevalent nature of anions, traditional strategies employed to target anions--including hydrogen bonding, metal ion coordination and electrostatic interactions--have been extensively studied. An alternative approach to anion binding would complement the powerful array of existing techniques. Recently, in the supramolecular chemistry community, new insight has been cast on how anions attractively interact with electron-deficient arenes, suggesting that aromatic rings are a viable anion binding strategy to balance existing methods. Chapter I provides a historical perspective of anions interacting with electron- deficient arenes. This outlook has its origins in the late 1800s with the discovery of colored charge-transfer complexes between donor and acceptor molecules and continues with the progression of the field leading up to the recent supramolecular fascination. Chapter II represents our initial efforts at measuring anion/arene interactions in solution. In particular, sulfonamide based hydrogen bonding receptors were developed with pendant aromatic rings to test the strength of anion/arene interactions in solution. Complementary computational chemistry and crystallography were utilized to supplement the solution studies. Chapter III describes our quantum calculations and crystallographic efforts at using only electron-deficient arenes to bind halides. A Cambridge Structure Database survey supports our emphasis of understanding multiple anion/arene interactions. Chapter IV illustrates how tripodal anion receptors can be developed to bind anions using only electron-deficient aromatic rings. Furthermore, subtle changes in anion binding geometries are observed with isomeric receptors and corroborated with Density Functional Theory calculations. Chapter V is dedicated to the preparation of electron-deficient anion receptors that are conformationally stabilized by hydrogen bonds. Chapter VI is committed to using our knowledge of anion binding to study a series of ethynyl-pyridine sulfonamides capable of hydrogen bonding to small molecules and anions. In conclusion, Chapter VII is a summary and future prospective for the field of anion/arene interactions. This dissertation includes previously published and co-authored material. / Adviser: Darren W. Johnson

Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Ondřej Kratochvíl Supervisor: prof. RNDr. Milan Pour, Ph.D. Supervisor - specialist: Mgr. Rastislav Antal Title of Thesis: Reduction of electron-deficient dendralenes by hydride reagents This diploma thesis is focused on the preparation of electron-deficient [3]dendralenes containing electron withdrawing groups such as carbonyl and ester functionalities. The synthesis is based on a palladium-catalyzed Migita-Stille coupling between stannylated diene and iodinated alkene (cycloalkene). Subsequent reaction of these substituted [3]dendralenes with hydride anion leads to a 1,2- or 1,4-addition to the α, β-unsaturated carbonyl group, resulting in the formation of an enolate or alcoholate, which are further transformed to various products depending on the type of the [3]dendralene.

No / Half-sandwich complexes of precious metals are a versatile class of organometallic compounds. Their accessibility, robustness, and air-stability are examples of the unique properties that allow their applications in various fields of chemistry (e.g. catalysis), and as anticancer drug candidates. Half-sandwich complexes generally follow the 18-electron rule, although some stable 16-electron (16-e) complexes have been isolated. The latter are generally coordinatively unsaturated leading to potential applications in catalysis and as precursors for 18-electron (18-e) complexes. Six 16-e complexes [Ru(η6-p-cymene)(1,2-benzene-1,2-dithiolato)] (1), [Os(η6-p-cymene) (1,2-benzene-1,2-dithiolato)] (2), [Ir(η5-pentamethylcyclopentadiene) (1,2-benzene-1,2-dithiolato)] (3), [Ru(η6-p-cymene)(1,2-dicarba-closo- dodecaborane-1,2-dithiolato)] (4), [Os(η6-p-cymene)(1,2-dicarba-closo- dodecaborane-1,2-dithiolato)] (5), and [Ir(η5-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecaborane-1,2-dithiolato)] (6) were synthesised by reactions between 1,2-benzenedithiol (1, 2, 3) or 1,2-dicarba-closo-dodecaborane-1,2-dithiol (4, 5, 6) and the corresponding metal dimers. In solution (10-4 M) at ambient temperature, the six complexes are stable electron-deficient 16-electron monomers, although the formation of a more electronically stable 18-electron dimer is observed for complex 1 at millimolar concentrations. The six complexes exhibit dramatic differences in reactivity towards electron-donor molecule. The in-vitro anti-inflammatory activities of the 16-e complexes 1 – 6 were investigated on MRC 5-fibroblast and lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Cells were exposed for 24h to the 16-e complexes 1 – 6 in the concentrations range of 10, 20, 50 and 100uM. After this, drugs were removed and nitric oxide (NO) concentration in the cultured medium was determined by the Griess reaction. Cells were then washed and placed in fresh growth medium for a further 24h as a recovery period. Cell viability was then assessed by MTT assay. Our preliminary data showed that complex 1 – 6 showed some anti-inflammatory effect on both lines, but with slightly differences between them, suggesting that the M-S2C2 scaffold of the electron-deficient complexes is the main structural moiety responsible for such effect. Further studies will focus on the matching these effects with their structures. / Abstract of conference paper.

Yes / Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt-resistance mechanisms. Electron-deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron-deficient organoruthenium complex [(p-cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53−/−), and non-small cell lung H460 cancer cell lines. It shows no cross-resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53-independent. In vivo evaluation in the hollow-fibre assay across a panel of cancer cell types and subcutaneous H460 non-small cell lung cancer xenograft model hints at the activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow-up, this work is the first preclinical study of electron-deficient half-sandwich complexes and highlights their promise as anticancer drug candidates. / UF150295/Royal Society; University of Bradford; Government Department of Business, Energy and Industrial Strategy; SBF003\1170/British Heart Foundation Springboard Award; AMS_/Academy of Medical Sciences/United Kingdom