Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 142-150).

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references. Also available in electronic version.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references. Also available in electronic version.

Yes / The problems of acquired resistance associated with platinum drugs may be addressed by chemotherapeutics based on other transition metals as they offer the possibility of novel mechanisms of action. In this study, the cellular uptake and induction of apoptosis in A549 human non-small cell lung cancer cells of three promising osmium(II) arene complexes containing azopyridine ligands,[Os(Z6-arene)( p-R-phenylazopyridine)X]PF6, where arene is p-cymene or biphenyl, R is OH or NMe2, and X is Cl or I, were investigated. These complexes showed time-dependent (4–48 h) potent anticancer activity with highest potency after 24 h (IC50 values ranging from 0.1 to 3.6 mM). Cellular uptake of the three compounds as quantified by ICP-MS, was independent of their log P values (hydrophobicity). Furthermore, maximum cell uptake was observed after 24 h, with evident cell efflux of the osmium after 48 and 72 h of exposure, which correlated with the corresponding IC50 values. The most active compound 2, [Os(Z6-p-cymene)(NMe2-phenylazopyridine)I]PF6, was taken up by lung cancer cells pre-dominately in a temperature-dependent manner indicating that energy-dependent mechanisms are important in the uptake of 2. Cell fractionation studies showed that all three compounds accumulated mainly in cellular membranes. Furthermore, compound 2 induced apoptosis and caused accumulation in the S-phase of the cell cycle. In addition, 2 induced cytochrome c release and alterations in mito-chondrial membrane potential even after short exposure times, indicating that mitochondrial apoptotic pathways are involved. This study represents the first steps towards understanding the mode of action of this promising class of new osmium-based chemotherapeutics.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

The semiconducting silicides offer significant potential for use in optoelectronic devices. Full implementation of the materials, however, requires the ability to tailor the energy gap and band structure to permit the synthesis of heterojunctions. One promising approach is to alloy the silicides with Ge. As part of an investigation into the synthesis of semiconducting silicide heterostructures, a series of β-Fe(Si1−xGex)2 epilayer samples, with nominal alloy content in the range 0 < x < 0.15, have been prepared by molecular beam epitaxy on Si(100). I present results of the epitaxial and crystalline quality of the films, as determined by reflection high-energy electron diffraction, Rutherford backscattering spectroscopy, and double crystal x-ray diffraction, and of the band gap dependence on the alloy composition, as determined by Fourier transform infrared spectroscopy. A reduction in band gap was observed with increasing Ge content, in agreement with previous theoretical predictions. However Ge segregation was also observed in β-Fe(Si1−xGex)2 epilayers when x > 0.04. Osmium silicide films have been grown by molecular beam epitaxy on Si(100). The silicides have been grown using e-beam evaporation sources for both Os and Si onto Si(100) substrates at varying growth rates and temperatures ranging from 600-700ºC. The resulting films have been analyzed using reflection high-energy electron diffraction, Raman spectroscopy, reflectivity measurements, in-plane and out of plane X-ray diffraction and temperature dependent magnetotransport. A change in crystalline quality is observed with an increase in Si overpressure. For a lower silicon to osmium flux ration (JSi/JOs=1.5) both OsSi2 and Os2Si3 occur, whereas with a much larger Si overpressure (JSi/JOs>4), crystalline quality is greatly increased and only a single phase, Os2Si3, is present. The out-of-plane X-ray diffraction data show that the film grows along its [4 0 2] direction, with a good crystal quality as evidenced by the small FWHM in the rocking curve. The in-plane X-ray diffraction data show growth twins with perpendicular orientation to each other.

With the advent of photoredox catalysis, new synthetic paradigms have been established with increasing numbers of novel transformations being achieved. Nevertheless, modern photoredox chemistry has several drawbacks in efficiency, scalability, and light penetration. In this dissertation, we document developments in photoredox catalysis that harvest red light (600- 800 nm) and demonstrate its applications in polymer science and chemical biology. First, a method towards the red-light activation and control of olefin metathesis will be discussed. This system employs a mixed, bis-N-heterocyclic carbene coordinated ruthenium indenylidene complex in conjunction with an osmium(II) complex under red light irradiation. Mechanistic investigation suggests a reduction of a cationic Ru species, to lead to the active metathesis species. Expectedly, polymerization through barriers is achieved with red light only. Material penetration, including mammalian tissue, and limited photocytotoxicity brings red light photoredox catalysis in the forefront of biological applications such as photoproximity labeling. This proceeds through the photocatalytic generation of reactive intermediates, the lifetimes of which dictate the spatial resolution of labeling. We thus describe a method to activate aryl(trifluoromethyl) diazos using an osmium(II) catalyst and red light, providing highly reactive, short-lived carbenes. The short lifetime of the carbene is highlighted by its ability to map small molecules to target proteins, a feat even nitrenes cannot achieve. Finally, efforts towards the synthesis of a wash-free fluorogenic photocatalyst with applications for intracellular red light photoproximity labeling will be described.

Herein is presented the doctoral research of Logan Rockwell Beck. We first report the development a library of osmium(II) polypyridyl complexes and characterize them for use in photoredox catalysis. We then report a triplet-triplet annihilation upconversion system that produces an oxidizing excited state and exhibits a remarkable 1.25 eV anti-Stokes shift. This upconversion system is then applied to dual nickel/photoredox catalyzed C-O cross-coupling. Finally, we discuss efforts towards the remote arylation of aliphatic amines through 1,5-HAT.