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Title: Development of visible light-mediated gold catalysis for quinolizinium synthesis and silver catalysis for bioconjugation
Authors: Deng, Jieren
Degree: M.Phil.
Issue Date: 2018
Abstract: Development of luminescent materials has been an emerging and important research area due to the wide applications of luminophores in various fields. For rational design of novel fluorescent materials and improvement of their performance, it is crucial to conduct systematic studies of their structure-photophysical property relationship (SPPR). Quinolizinium compounds, first investigated as natural products, have been demonstrated as organic dyes for the development of DNA intercalators and fluorescent probes based on the fluorescent quinolizinium skeletons. However, probably due to the complex synthetic strategies for synthesizing numerous structures, systematic studies on SPPR remain rare. Merging visible light photoredox and gold catalysis has been regarded as a promising new direction for gold-catalyzed organic transformations which overcomes the high potential barrier of Au(I)/Au(III) redox cycle by sequential single electron transfer (SET) processes. For modular synthesis of quinolizinium derivatives, a novel approach of visible light-mediated gold-catalyzed cyclization of aryl diazonium salts and phenylethynylsilanes was developed in this thesis. A library of silyl substituted quinolizinium derivatives with 26 examples were synthesized (up to 69% isolated yield). The reaction showed excellent regioselectivity with single regioisomer obtained, and control experiments indicated that this reaction was highly selective towards silyl substituted alkynes. Absorption and emission spectroscopy experiments indicated the quinolizinium derivatives with a full color tunable emission properties (λem = 478 ~ 640 nm) in visible light region, large Stokes shift (up to 6,796 cm-1) and good quantum yields (up to 59%) excited by light source with λab > 400 nm. DFT calculation of quinolizinium 1.4c suggested that the HOMO of the molecule dominated at the phenyl moiety while the LUMO dominated at the quinolizinium moiety. Incorporation of functional groups on phenyl and quinolizinium moieties by changing the electronic properties was able to tune the photophysical properties of the quinolizinium derivatives. The quinolizinium derivatives with high and tunable excited state reduction potentials could be employed as organic photocatalysts in photooxidative amidation of aldehydes with amines in up to 86% yield. Moreover, the quinolizinium derivatives could be used for cellular imaging, and co-localization experiments indicated that compound 1.4l was subcellular localized in lysosome of HeLa cells.
Chemical modification of peptides and proteins has been considered as an invaluable tool for biological studies and drug development. It is of importance to develop novel strategies for peptide and protein modifications with high efficiency and site-selectivity under mild reaction conditions. Cysteine with high nucleophilicity and low abundance is an ideal residue for selective modification. Along with our previous works in silver-catalyzed organic transformations and bioconjugations, a novel method for chemoselective cysteine modification of peptides and proteins employing isoxazolinium ions generated in situ via silver catalyzed-organic transformation of propargylamine N-oxides was studied in this thesis. α-Substituted ketone modified peptides and proteins were obtained in up to 99% conversion by treatment with 1 equivalent of isoxazolinium ion-containing reagent with 5 mol% AgNO3 in aqueous media at 25 °C for 2 h. The modified peptides were stable towards excessive thiol-containing reagents. Further application of this method has been demonstrated in sequential modification of a therapeutic anticancer protein BCArg.
Subjects: Hong Kong Polytechnic University -- Dissertations
Pages: xiii, 313 pages : color illustrations
Appears in Collections:Thesis

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