Photoredox catalysis has been a flourishing field in synthetic organic chemistry. Organic chemists have been inspired by Nature and the conversion of photons into potential energy by light-harvesting biomolecules. Recent developments in photoredox catalysis have led to a rapid increase in development of new methodologies in synthetic organic chemistry. The use of transition metal photocatalysts and organic dyes in photo-mediated processes has been proven to be an effective alternative to the harsh and toxic reaction conditions that area needed in classical radical formation. Photoredox catalysis eliminates the need of initiators, stoichiometric additives, and strong oxidants, and allows for the highly efficient formation of new C-C bonds under mild conditions. Photochemistry and radical chemistry work in unison in their ability to undergo photoinduced single electron transfers (SET) or photoinduced electron transfers (PET) and enable one electron reaction pathways. A plethora of photocatalysts have been developed, mainly using Ir- and Ru-based polypyridyl complexes. Polynuclear gold complexes have come to light in the last decade as another class of photocatalysts. This bench stable complex is marked by its unique photophysical and electrochemical properties, most notable the relatively long-lived excited state. This triplet excited state can be used as a powerful reductant or oxidant when irradiated with UVA light. A class of organic substrates that can be used when working with this gold photocatalyst, is nonactivated bromoalkanes, which could not be used if working with other photocatalysts. First, the alkylative semi-pinacol using gold photoredox chemistry and nonactivated bromoalkanes was described. A new mode of reactivity of the gold binuclear photocatalyst was found where it was shown to work as a photocatalyst and a Lewis acid. Next, a follow-up to that report was the halogen atom transfer radical addition (ATRA) using gold photoredox catalysis. A mild ATRA reaction was presented where the dual reactivity of the gold photocatalyst was exploited. Mild bromine and iodine transfer reactions, without the use of strong oxidants or toxic additives, are largely unknown, and a metal-based mechanistic pathway was proposed to explain this transformation. Minisci-type alkylation is of high-interest in the field of medicinal chemistry and drug discovery. With this is mind, a photoredox catalysed Minisci reaction was presented, where the alkylation of an activated heteroarenes was achieved by HAT via chlorine atom generation. Knowing this, the alkylation using primary alcohols was presented, were a the 𝛼-alkoxy radical is formed after a HAT by chlorine atom. When secondary alcohols were used, a reduction of the heteroarene occurred and was described. Finally, a photo-mediated [3 + 2] cycloaddition using N-aryl cyclopropylamines and α, β- unsaturated carbonyl systems was described. This simple method that was presented does not require the use of photocatalysts or added additives, as it is self-catalyzed. The reaction is proceeding through a single electron transfer (SET) and offers a wide scope for the synthesis of N-arylaminocycloalkyl compounds. Overall, the collection of work described in this thesis represents the growth of photoredox catalysis in organic synthetic chemistry and the ability to form highly reactive radical without the need of harsh conditions, toxic reagents, or strong oxidants. The use of binuclear gold(I) complexes as a photocatalyst with unique photophysical and electrochemical properties was shown. Compared to Ir- and Ru-based polypyridyl complexes, which cannot react with nonactivated bromoalkanes, the binuclear gold(I) complexes offer broader redox potentials and a newfound dual mode of reactivity. Furthermore, photo-mediated synthetical useful reactions were shown. The application of photoredox catalysis in synthetic chemistry will continue to flourish, and this work is sample of all the possibilities that a simple photon can bring.

The synthesis and characterization of complexes analogous to the novel anti-arthritis gold drug auranofin is presented. The general composition of these compounds is L-Au-X where L=triethyl-phosphine and X=tetraacetylthioglucose or chloride in the case of auranofin or its synthetic precursor. Incorporation of ligands (L) such as isocyanides and aromatic nitrogen donors fail to impart the same stability to gold(I) that phosphines or thiols are capable of. Complexes of aromatic nitrogen ligands are prone to decomposition and those of isocyanides, although thermodynamically stable, are labile and subject to relatively rapid isocyanide substitution as well as the expected substitution of the halide group. Complexes have been investigated with regard to their in vitro and in vivo DNA-binding capabilities in light of the reported anticancer properties of auranofin itself. Isocyanide and phosphine gold(I) complexes as well as a series of gold(lll) complexes have shown their ability to bind to DNA in vitro but lose their viability in vivo. This is likely a result of reduction of the gold by thiol groups present in a living system and is associated with the observed cytotoxicity at increasing concentrations. The tris-2-pyridylphosphine (TPP) ligand has also been utilized as a choice for L which has led to the synthesis of the auranofin analogue, (tris-2-pyridylphosphine)(tetraacetylthioglucose)gold(l). Metal ions such as Zn(ll), Co(lll), Cu(ll), Fe(II), Fe(III) and Cr(lll) have been incorporated at the pyridyl nitrogen sites and this series of complexes has been studied crystallographically. N-bound and mixed N-and P-bound complexes have been studied by other techniques as well, depending on the nature of the metal ion involved. Copper(ll) complexes have been investigated by E.S.R. and UV/Visible spectroscopies, Moessbauer data is presented for iron(ll) and iron(lll) complexes and infrared data has been collected and summarized for all complexes. In general, the TPP ligand is an accomodating chelate; N-bound complexes are octahedral and little ligand strain is observed upon coordination. The nitrogen and phosphorus sites are independent in that there appear to be no electronic effects exerted by one site on the other. An important effect of coordinating metal ions to the nitrogen sites is to alter the solubility of the hydrophobic ClAuTPP complex to one with hydrophilic properties. / Thesis / Doctor of Philosophy (PhD)

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Doxorubicin is one of the most widely used and effective anticancer agents to treat a wide spectrum of tumors. But its success in cancer therapy is greatly compromised by its cumulative dose-dependent side effects of cardiotoxicity and tumor cell resistance. For the purpose of addressing these side effects, a gold nanoparticles-based anticancer drug delivery system was designed. Five novel thiolated doxorubicin analogs were designed and synthesized and their biological activities have been evaluated. These doxorubicin analogs and the poly(ethylene glycol) (PEG) stabilizing ligands were conjugated to gold nanoparticles via formation of a gold-thiol bond. The systems were evaluated in vitro and in vivo, and the results show that controlled drug release can be achieved either by acidic conditions or by reducing agents in cancer cells, depending on the design of the thiolated drug construct. The overall drug delivery system should achieve enhanced drug accumulation and retention in cancer cells and favorable drug release kinetics, and should demonstrate therapeutic potential and the ability to address some of the current problems of doxorubicin in cancer therapy. / Master of Science

Nanoporous gold is an exciting topic that has been highly researched due to its potential in applications including sensing, catalysts, gas storage, and heat exchangers, made possible by its high surface area to volume ratio and high porosity. However, these applications tend to require a specific morphology, which is often difficult to control. In this work, significant strides have been made in tuning the morphology of nanoporous gold by studying the effect of different fabrication parameters on the ligament diameter, pore diameter, and ligament length, three characteristics which are most discussed in previous studies concerning nanoporous gold. This material also, generally shows a brittle behavior despite it consisting of a normally ductile constituent element, limiting many commercial applications. There have been multiple simulated studies on the tensile mechanical properties and the fracture mode of this material, but limited experimental tensile testing research exists due to technical difficulty of conducting such experiments with small fragile samples. We examine the tensile mechanical behavior of nanoporous gold with ligament sizes ranging from 10 to 30 nm using in situ tensile testing under an environmental scanning electron microscope (ESEM). A specially designed tensile stage and sample holders are used to deform the sample inside the ESEM, allowing us to observing both the macro and microscopic structure changes. Our experimental results advance our understandings of how porous structure influence the mechanical properties of nanoporous gold, and they also serve to increase the accuracy of future simulation studies that will take this material a step towards commercial use by providing a thorough understanding of its structural mechanical limitations. / MS

Although it is known that gold (Au) is diamagnetic in bulk form, it has been reported that Au displays magnetic properties when reduced to the nano-scale. Researchers found magnetism in Au nanoparticles (NPs) in a size range from 2 to 10 nanometers. Moreover, the Au nanoparticles are usually coated by thiol-containing organic caps, which are believed to be responsible for the magnetism. However, others suggest that organic capping is not necessary to observe magnetism in Au NPs, and magnetism may be an intrinsic property for nano-structured gold. For this investigation, we used pulsed laser deposition to prepare nano-structured gold of different sizes and concentrations to investigate the magnetic properties. Our experiment results confirmed that for the samples in which Au is in the metallic state as nanoparticles with ~5 nm diameter, as well as inthe alloy form, bonded with indium, the samples show ferromagnetism when embedded in an Al2O3 matrix without any thiol-containing organic capping. Our results suggest that ferromagnetism is an intrinsic property of Au nano-structures, which means that it is not necessary to incorporate Au-S bonds with organic coatings in order to observe this phenomenon. We believe due to the significant broken symmetry at the surface of the nanoparticles, holes are generated in d bands of the surface Au atoms. These holes are most possibly responsible for ferromagnetism in Au nanoparticles. The realization of magnetism in Au coupled with the lack of clear understanding of its origin makes the investigation of magnetism of diamagnetic metals ripe for further inquiry. / Ph. D.

Improved technologies, increases in global demand for metals, and lax environmental policies and regulations are causing a shift of large-scale mining activities to the tropics. This shift of mining to the tropics has the potential to modify natural ecosystems and disrupt the social structures of rural and indigenous peoples in some of the most remote areas of the planet. This thesis encompasses research done in two villages of Guyana's Essequibo River basin after the 1995 Omai cyanide spill, and illustrates the local social consequences of a large-scale gold mining operation in the tropics. It documents not only the degradation of the local river ecology, but also the changes in local people's perceptions of their environment. That environment, once viewed as pristine, is now viewed as unsafe, leading to disrupted livelihoods and lifestyles. The finding of this study points to a direct link between international economic liberalization policies (which emphasize privatization, foreign direct investment, and economic growth) and the creation of disaster circumstances in developing countries. This thesis research is the result of a total of ten weeks of participant observer research in the area of the Essequibo River, Guyana. It utilizes the methodology of taped interviews of head-of-households. Interviews were conducted with approximately 85 percent of heads-of household of the villages of Rockstone and Riversview. Additionally, interviews were conducted with national and regional governmental officials, regional health officials, local and indigenous leaders, personnel of the Guyana Geology and Mines Commission, and the Environmental Protection Agency in Guyana. Interviews were supplemented with archival research. The findings of this thesis research closely mirror those of other researchers who contend that the social impacts of technological disasters are long-term and more severe than those related to natural disasters. Seven years after the cyanide spill, disruptions in livelihood activities, diet, and household behaviors continued to be evident in the two villages. There is little indication that the high negative perceptions of the villagers as a result of the disaster will change in the near future. The research found that macroeconomic policies, crafted by national governments and overseen by international financial institutions without the involvement of local citizenry, disproportionately affected the poor and rural populations through the degradation of local ecosystems. The thesis also illustrates the usefulness of ethnographic research-in particular, interviews in disaster studies of developing countries. / Master of Science

Yes / Peptides have demonstrated unique capabilities to fabricate inorganic nanomaterials of numerous compositions through noncovalent binding of the growing surface in solution. In this contribution, we demonstrate that these biomolecules can control all facets of Au nanoparticle fabrication, including Au3+ reduction, without the use of secondary reagents. In this regard using the AuBP1 peptide, the N-terminal tryptophan residue is responsible for driving Au3+ reduction to generate Au nanoparticles passivated by the oxidized peptide in solution, where localized residue context effects control the reducing strength of the biomolecule. The process was fully monitored by both time-resolved monitoring of the growth of the localized surface plasmon resonance and transmission electron microscopy. Nanoparticle growth occurs by a unique disaggregation of nanoparticle aggregates in solution. Computational modeling demonstrated that the oxidized residue of the peptide sequence does not impact the biomolecule’s ability to bind the inorganic surface, as compared to the parent peptide, confirming that the biomolecule can be exploited for all steps in the nanoparticle fabrication process. Overall, these results expand the utility of peptides for the fabrication of inorganic nanomaterials, more strongly mimicking their use in nature via biomineralization processes. Furthermore, these capabilities enhance the simplicity of nanoparticle production and could find rapid use in the generation of complex multicomponent materials or nanoparticle assembly. / Air Force Office of Scientific Research, grant FA9550-12-1-0226.

Yes / We combine single molecule force spectroscopy measurements with all-atom metadynamics simulations to investigate the cross-materials binding strength trends of DNA fragments adsorbed at the aqueous graphite C(0001) and Au(111) interfaces. Our simulations predict this adsorption at the level of the nucleobase, nucleoside, and nucleotide. We find that despite challenges in making clear, careful connections between the experimental and simulation data, reasonable consistency between the binding trends between the two approaches and two substrates was evident. On C(0001), our simulations predict a binding trend of dG > dA ≈ dT > dC, which broadly aligns with the experimental trend. On Au(111), the simulation-based binding strength trends reveal stronger adsorption for the purines relative to the pyrimadines, with dG ≈ dA > dT ≈ dC. Moreover, our simulations provide structural insights into the origins of the similarities and differences in adsorption of the nucleic acid fragments at the two interfaces. In particular, our simulation data offer an explanation for the differences observed in the relative binding trend between adenosine and guanine on the two substrates.