Cyanobacteria, also known as blue-green algae, are known to produce a number of biologically active compounds. Extracts of cultured cyanobacteria isolated from South Florida sources were screened for possible developmental toxins using the zebrafish (Danio rerio) embryo as a model of vertebrate development. A strain of cyanobacteria, Fischerella 52-1, isolated from the Florida Everglades, was found to produce metabolites that caused a consistent developmental dysfunction in embryos exposed to lipophilic extract. Initial chemical characterization of the bioactive fraction identified a series of eight apparent indole-containing compounds. The two main components were purified using the zebrafish embryo model to guide the fractionation. Chemical characterization using 1- and 2-dimensional NMR, HESIMS, HRHESIMS, and IR determined that the two main compounds were the previously identified 12-epi-Hapalindole H Isonitrile, and a novel compound 12-epi-Ambiugine B Nitrile. The major contributor of the developmental defects detected in the zebrafish embryos was 12-epi-Hapalindole H Isonitrile.

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Organoclays modelling the Athabasca oil sands were prepared in heptane and toluene showing indole loading occurring exclusively on the external surface of the clay, via a multilayer adsorption mechanism. Solvent adsorption was minimal. Vermicular microstructures, similar to natural kaolinite were formed. Isotherms were constructed and fitted to the BET equation, giving monolayer quantities (9.28mg) that matched well to the theoretical amount calculated from surface area measurements (8.87mg). Dispersing the organoclays in isopropanol and in toluene left a monolayer equivalent. Using cellulose as a competitive desorption agent in asphaltene based organoclay dispersions achieved complete disaggregation of the dispersed organoclay stacks.13 C CP - MAS NMR, showed up to a 25% increase in desorption for aliphatic and up to 40% increase in desorption for aromatic functionalities of the loaded organic matter. Investigation of other saccharides and modified celluloses as competitive agents is recommended for future work.

Becke's three-parameter hybrid density functional method in conjunction with Lee-Yang-Parr's correlation functional (B3LYP) was used to investigate the pyrolysis mechanisms of indole yielding benzyl cyanide and o- and m- tolunitriles. All equilibrium and transition state structures of the proposed reaction channels were fully optimized by B3LYP using the 6-31G** basis set. Single point energies were evaluated by B3LYP with the 6-311 + + G(2d,2p) basis set. Two hydrogen migration tautomers of indole, seemingly playing no important roles in the pyrolysis due to destruction of aromaticity of the benzene ring, were predicted to be easily accessible under the experimental conditions and may be important intermediates in the reactions. Two other transition states suggested to play important roles in the experimental study were not found and may not exist. Instead stepwise processes via hydrogen migration tautomers arriving at the same products are shown likely to be responsible for the observed products. IR spectral features of three hydrogen-migration tautomers are predicted to help future experimental identification.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21051号 / 薬科博第94号 / 新制||薬科||10(附属図書館) / 京都大学大学院薬学研究科医薬創成情報科学専攻 / (主査)教授 大野 浩章, 教授 竹本 佳司, 教授 高須 清誠 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

The first section of this dissertation (Chapter I-III) describes the development of new methodologies for the rhodium catalyzed C-N bond formation between sp3 hybridized carbon atom of phenyl substituted alpha-lactams and the nitrogen atom of indole derivatives. Phenyl substituted alpha-lactams generated in situ from the corresponding alpha-bromoamides reacted with indoles in the presence of rhodium catalyst to afford the ring opening products of alpha-lactams. The scope of this methodology was extended to various types of indole derivatives including electron donating and withdrawing substituents. Furthermore, a series of functionalized phenyl substituted alpha-lactams generated in situ reacted with indole to assess the viability of this methodology. The developed method provides an atom-economical approach for the formation of substituted alpha-amino amides in good to excellent yields. The main goal of the research described in the second section (Chapter IV-VII) is the synthesis of the corannulene-based molecular receptors with polar tethers and their immobilization on silica gel. First, we have considered a preparation of bis-corannulenoanthracene, formally possessing the pentacene core as a potential precursor for a series of barrelene based bis-corannulene receptors with polar groups. Bis-corannulenoanthracene was synthesized by the double Diels-Alder cycloaddition of isocorannulenofuran with bis-benzyne precursor, followed by deoxygenation of the endoxide adducts. While bis-corannulenoanthracene is stable enough to be isolated and stored, its pentacene core undergoes facile cycloaddition with maleic anhydride to afford bis-corannulene molecular receptor with the barrelene tether adorned with the anhydride moiety. The 1H NMR titration experiments carried out in chlorobenzene-d5 proved the high binding affinity of the receptor toward C60. In addition, the presence of polar anchors on its tether allowed for its deposition on silica gel through the (3-aminopropyl)triethoxysilane linker.

特異なルテニウムが触媒する"Borrowing hydrogen"のコンセプトに基づく有機反応を開発した。まず、Ru/JOSIPHOS触媒を用いて、1,2-ジオールとアミンの反応から光学活性β-アミノアルコールを最高99%収率ならびに77% eeで得ることに成功した。本反応は新規であり、その反応機構についても明らかにした。さらに、RuCl2(PPh3)3/DPEphos/K3PO4を組み合わせた触媒を用いることで、アルコールをアルキル化剤に用いるインドールの3位選択的アルキル化反応を達成した。高効率かつ広いタイプの基質に適用できる。 / Several novel ruthenium-catalyzed "borrowing hydrogen"-based organic reaction has been developed. For very first time optically active β-amino alcohols can be sinthesized directy by reaction of 1,2-diol and coressponding amine under Ru/JOSIPHOS catalysis in up to 99% yield and 77% ee. Since this reaction is very new, intensive investigation of the reaction mechanism was also carried out. Meanwhile, combination of RuCl2(PPh3)3/DPEphos/K3PO4 was found to be effective catalyst for alkylation of indole with alcohol as an alkylating reagent. This catalysis was highly reactive to give the corresponding alkylated indole in excellent yield for almost all types of indoles and alcohols substrates. / 博士(工学) / Doctor of Philosophy in Engineering / 同志社大学 / Doshisha University

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No description available.

<p>This thesis describes a new type of biosensor, which reports the presence of a target by generating a smell that can be easily detected by the human nose. This approach is radically different from, but complementary to, colorimetric based reporting and it paves the way for the development of multi-sensory biosensors that can be used in a variety of fields, such as diagnostic device, food processing and environmental monitoring</p> <p>Biosensors typically consist of two parts: a bio-recognition element and a signal transducer. The biorecognition element is the component that can specifically interact with its cognate target, while the transducer produces a signal that can be easily identified. The key element of the smell generating biosensor is the enzyme tryptophanase (TPase), which was used as the signal transducer. This enzyme uses either L-tryptophan or S-methyl-L-cysteine as substrates, to produce either indole or methyl mercaptan as final products- both molecules are easily detectable by the human nose. Proof-of-concept for this biosensor was achieved by performing an enzyme-linked immunosorbent assay (ELISA) on magnetic beads with detection of IgG from rabbit serum (the target) in a sample and reporting the presence of the target through the generation of a smell (either indole or methyl mercaptan, depending on the substrate used).</p> <p>The potential use of TPase for biosensing was further expanded by creating a bienzyme system that allows specifically detecting of adenosine-5’-triphosphate (ATP) and reporting its presence by generating a smell. This bienzyme system is based on the fact that TPase activity is greatly affected by the concentration of pyridoxal phosphate (PLP)- which acts as a cofactor that modulates enzyme activity. The enzyme pyridoxal kinase PKase catalyzes the phosphorylation of pyridoxal to PLP in the presence of ATP. The more ATP presents, the more PLP is produced per unit time. If this occurs in the presence of TPase, larger concentrations of ATP in samples will result in higher amounts and faster rates of PLP formation, leading to increased activity of TPase, hence faster generation of either indole or methyl mercaptan is achieved. This bienzyme was used for the detection of DNA molecules with a specific sequence as well as for the detection of microbial cells through smell generation.</p> <p>Most widely used biosensors require immobilization of the biologically active elements on a stable surface. Paper, being a cheap and easy accessible substrate, was used for fabrication of the olfactory-based biosensor. Poly(N-isopropylacrylamide-co-vinylacetic acid) (PNIPAM-VAA) microgels with functional groups present on their surface were modified by biotinylation and loaded with streptavidin/avidin (to be prepared as a platform for further biomolecule immobilization). The microgels were then used as a supporter for the bienzyme system on filter paper to construct a paper-based smell-generating biosensor, which opens the way for the creation of printable smell-reporting printable bio-inks.</p> / Doctor of Philosophy (PhD)