<p> Ligand backbones based on xanthene, thioxanthene and acridine (XPB, TXPB and APB) have been targeted as scaffolds for the formation of rare compounds containing Lewis basic phosphine and Lewis acidic borane moieties. The resulting complexes with Pt(O) and Pt(II) reagents are expected to possess diverse reactivity compared to traditional platinum phosphine adducts owing to the strategically appended borane Lewis acid. </p> <p> Two ligands, 2,7-di-(tert-butyl)-4-diphenylboryl-5-diphenylphosphino-9,9dimethylthioxanthene (TXPB) and 2,7-di-(tert-butyl)-4-diphenylboryl-5diphenylphosphino-9,9-dimethylxanthene (XPB), have been synthesized and reacted with the platinum reagents [PtCl2(COD)], [PtMe2(COD)] and [Pt(nbe)3]. In the case of TXPB, two new Pt(II) compounds [PtCl(μ-Cl)(TXPB)] and [PtMePh(TXPB^(Ph,Me))] have been formed, isolated and characterized. In both compounds, X-Ray analysis shows that the S and the P atoms bind to the Pt center drawing the metal into the vicinity of the B group. In [PtCl( μ-Cl)(TXPB)], a chloride is seen to bridge between the Pt and B, whereas [PtMePh(TXPB^(Pb,Me))] shows that a methyl groups has been transferred to the boron with concomitant transfer of a phenyl group to Pt. Reaction with the platinum(O) precursor [Pt(nbe)3] led to formation of an unstable complex, tentatively assigned as [Pt(nbe)TXPB]. Analogous studies with the new xanthene-derived ligand, XPB, led to starkly different results. In the reaction with [PtCl2(COD)], an insoluble product, perhaps a dinuclear complex with bridging chlorides, was formed. No reaction occurred with [PtMe2(COD)], presumably because of non-participation of the 0 ligand. However, with [Pt(nbe)3], a stable complex, [Pt(nbe)2XPB], was observed. </p> <p> Synthesis of a third ligand scaffold APB has been initiated where the pyridine moiety is expected to allow strong chelation of Pt as observed with TXPB. An advanced intermediate AFBr has been synthesised where the backbone has been created through a ring closure reaction positioning two different halides as required for sequential addition of the phosphine and borane groups of the target compound. </p> / Thesis / Master of Science (MSc)

v angličtině Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucie Pohanová Supervisor: Assoc. Prof.. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Chelation of ferrous ions by xanthen-3-one derivatives Iron is an essential element important for proper function of cells. Imbalance of iron levels can lead to serious diseases. Since there is no excretory mechanism, the homeostasis is regulated at the level of absorption in the intestine. The iron overload, which leads to tissue damage due to catalysis of the formation of free radicals, occur because of genetic disorders such as hemochromatosis or owing to frequent administration of transfusions. Rational therapy for iron overload is the administration of the chelators. The aim of this study was to evaluate the ability of derivatives of 2,6,7- trihydroxyxanthen-3-one (synthesized at the University of Sarajevo - Dr. Durić) to chelate iron in 4 (patho) physiologically relevant pH conditions. The ferrozine spectrophotometric method was used to determine the degree of chelation. Measurements showed dependency of the chelating effect on pH: lowering pH resulted in the decrease of the effect. At pH 7.5, most of the substances showed 100% ferrous ion chelation in the stoichiometric ratio of 1...

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18293号 / 工博第3885号 / 新制||工||1596(附属図書館) / 31151 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 中條 善樹, 教授 秋吉 一成, 教授 赤木 和夫 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

The emergence of multidrug resistance is a serious medical problem that has significantly affected the treatment of tumor cells and infectious diseases. This multidrug resistance phenotype is mediated by the action of a large family of membrane proteins that act as active transporters or energy driven efflux pumps in both of prokaryotic and eukaryotic cells. Most eukaryotic multidrug efflux pumps belong to the ATP binding cassette (ABC) family of transport proteins that include P-glycoprotein (P-gp1), Multidrug Resistance Associated Protein (MRP1), and Breast Cancer Resistance Protein (BCRP). In prokaryotic cells, Lactococcus lactis LmrA, a homolog of P-gp1, mediates drug resistance to antibiotics and cytotoxic drugs. The transport function of these proteins is facilitated by the hydrolysis of ATP. However, the mechanism by which these proteins bind to, and are able to transport structurally dissimilar drugs across the cell membrane remains poorly understood. In this thesis we have attempted to characterize the interactions of various ABC transporters (MRP1, BCRP, and LmrA) with structurally diverse drugs, using a well characterized photoreactive drug analogue of Rhodamine 123, [125I] iodoaryl azido-rhodamine 123 (IAARh123). In the case of MRP1 interaction with Rhodamine 123, it was of interest to determine the nature of MRP1 drug interactions. In that study, our results show that CHAPS (1-[(3-cholamidopropyl) dimethylamino]-1-propansulfate) and Brij35 inhibited the photolabeling of MRP1 with IAARh123, and this interaction occurred outside the lipid bilayer. These results were unexpected in light of previous results with another ABC transporter which also binds to Rhodamine 123. Consequently, we show that non-toxic concentrations of CHAPS and Brij35 potentiate the toxicity of two MRP1 substrates, vincristine and etoposide (VP16). In the second chapter, we have used IAARh123 to demonstrate for the first time that the BCRP mediates drug resi

Thesis (Ph. D.)--Ohio State University, 2007.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19006号 / 工博第4048号 / 新制||工||1623(附属図書館) / 31957 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 中條 善樹, 教授 赤木 和夫, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

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No / The tetracyclic nucleus of puupehenone, 15-oxopuupehenol and other sesquiterpene¿phenol natural products can be assembled stereoselectively in three steps, the last of these being the 6-endo-trig cyclisation of an alpha-keto radical generated from a substituted 2-(2-cyclohexenyl)ethyl 3-bromo-4-chromanone under metal-free conditions. / EPSRC

Electronic excitation triggered by the absorption of light enables numerous chemical, physical and biological processes and transformations. Accordingly, full control over the processes involving excited molecules requires an in-depth knowledge of electronic UV/vis spectra and potential energy surfaces. Unsurprisingly, most electronic spectra are acquired in the condensed phase in which molecules are dissolved and most transformations occur. However, our knowledge of excitation, transformations and processes at the level of isolated molecules is still limited, partly because such studies require unconventional experimental approaches and equipment. This Thesis describes experimental methods for recording electronic spectra of isolated molecules in the gas phase by ion spectroscopy, which combines mass spectrometry with optical spectroscopy. Using these methods, experimental factors which affect the electronic excitation and therefore the electronic spectra of ions were determined and evaluated for various fluorescent xanthene dyes, iron-containing complexes and molecular pho- toswitches. Furthermore, factors which govern photochemical processes, such as photo- oxidation, photoreduction and photoisomerization, were also analyzed in detail, with surprisingly different outcomes from previous studies...

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