abstract: Converting solar energy into electricity is a reasonable way to ameliorate the current untenable energy situation. One way to harness solar energy is to mimic the mechanisms already present in natural photosynthesis. A key component of many artificial photosynthetic systems is the linker connecting the dye to an electrode. Studying the associated electron transport process is important for improving linker efficiency. Similarly it is important to be able to control the electron transfer to the dye from a water oxidation catalyst, and to be able to improve the lifetime of the charge separated state. Natural photosynthesis provides a blueprint for this in the tyrosine-histidine pair in photosystem II. In this work, research on these topics is described. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2015

abstract: Changes to a cell's DNA can result in cancer, which is permanently sustained cellular proliferation. When malfunctioning genes, oncogenes, were verified to be of human origin in the 1970s, drugs were designed to target their encoded, abnormal enzymes. Tyrosine kinases have been established as an oft-modified oncogene enzyme family, but the protein tyrosine phosphatases (PTPs) were not investigated as thoroughly. PTPs have gradually been established as relevant enzymes that work in tandem with tyrosine kinases in cell signaling and are not just "house-keeping" enzymes. Some PTPs are thought to initiate tumorigenesis, and others may play a complementary role after the onset of cancer by extending the duration of cellular signals. Reversible inhibition of these enzymes by an oxalylamino group substituted on an ortho-carboxy aryl have been described in the literature. Modification of the oxalylamino group to favor irreversible inhibition of these cysteine-dependent enzymes may prevent inhibitor efflux by cells and subsequent mutation to gain resistance. Replacement of the oxalylamino group with halogenated propanoate and propenoate esters minimally inhibited cancer cell growth but did not inhibit activity of PTPs. Of the ortho-carboxy aryl structures, a methyl dichloropropanoate (compound 24) and a lactone alkene (compound 29) inhibited cell growth by 50% (GI-50) at micromolar concentrations. The GI-50s for compounds 24 and 29 were 19.9 (DU-145, prostate carcinoma) and 9.4 micromolar (A549, lung cancer), respectively. In contrast, brominated nitro lactones were able to inhibit both cancer cell growth and the activity of PTPs. In a sulforhodamine B assay, these compounds were able to achieve GI-50s as low 5.3 micromolar (compound 33 against BXPC-3, pancreatic adenocarcinoma), and some killed 50% of cancer cells (LC-50) at micromolar concentrations. Compound 33 displayed LC-50 of 23.3 micromolar (BXPC-3), and compound 35 had LC-50s of 32.9 and 32.7 micromolar against BXPC-3 and colon adenocarcinoma (KM20L2), respectively. A single concentration (100 micromolar) inhibition assay of inhibitor PTPs resulted in no enzyme activity for 4 out of 5 PTPs tested with compound 33. Similar results were obtained for compounds 35 and 37. Future analysis will determine if these bromo nitro lactones are irreversibly inhibiting PTPs. / Dissertation/Thesis / Ph.D. Chemistry 2012

abstract: Reactive oxygen species (ROS) are a series of molecules, ions, and radicals derived from oxygen that possess remarkable reactivity. They act as signaling molecules when their concentration in cells is within a normal range. When the levels of ROS increase, reaching a concentration in which the antioxidants cannot readily quench them, oxidative stress will affect the cells. These excessive levels of ROS result in direct or indirect ROS-mediated damage of proteins, nucleic acids, and lipids. Excessive oxidative stress, particularly in chronic inflammation, has been linked with mutations and carcinogenesis. One of the main targets of ROS in severe oxidative stress is mitochondrial DNA (mtDNA). The synthesis of analogues of alpha-tocopherol is described as potential compounds with the ability to remediate defective mitochondria. An interesting possibility for eradicating cancer cells is to selectively target them with oxidative species while avoiding any deleterious effects on healthy cells. To accomplish this, analogues of the beta-hydroxyhistidine moiety of the antitumor agent bleomycin (BLM) were synthesized. The first part of this thesis focuses on the synthesis of simplified analogues of alpha-tocopherol. These analogues possess a bicyclic pyridinol as the antioxidant core and an alkyl group as the lipophilic chain to mimic alpha-tocopherol. Additionally, analogues with a completely oxidized pyridinol core were synthesized. Some of these analogues showed promising properties against ROS production and lipid peroxidation. The protection they conferred was shown to be tightly regulated by their concentration. The second part of this thesis focuses on the synthesis of analogues of beta-hydroxyhistidine. BLMs are glycopeptides that possess anticancer activity and have been used to treat testicular carcinomas, Hodgkin's lymphoma, and squamous cell carcinomas. The activity of BLM is based on the degradation of DNA, or possibly RNA, caused by a Fe(II)-BLM complex in the presence of O2. The beta-hydroxyhistidine moiety of BLM contributes to metal coordination via two ligands: the N-3 nitrogen atom of imidazole and possibly the nitrogen atom of the amide. A series of beta-hydroxyhistidine analogues has successfully been synthesized. / Dissertation/Thesis / Ph.D. Chemistry 2014

<p> Sialic acids are acidic monosaccharides with 9-carbon backbone that are found at the outermost of the mammalian cell membrane. They are a family of about 50 naturally derivatives of neuraminic acid, with N-acetyl neuraminic acid being the most common member. Its biological importance, as a terminal component of glycoconjugates, ranges from cell-cell interactions to pathogens attacks. Thus, the stereoselective synthesis of sialic acid-containing glycoconjugates with high yields is very important but unfortunately also a synthetic challenge in the carbohydrate synthesis field.</p><p> Regardless tremendous advancement in the field, sialic acid glycosylations (sialylations) are still a limiting factor in the synthesis of complex carbohydrates, which are biologically relevant for the design of therapeutics.</p><p> Based on the recent finding by De Meo <i>et. al.</i> on the existence of a conformational equilibrium at the oxacarbenium ion level that suggested positions C-4 and C-7 might be relevant in sialylation reactions; and on the recent reports by Demchenko et. al. on Hydrogen-bond-mediated aglycone delivery (HAD), we report herein the introduction of Picoloyl at C-4 and C-7 on thiosialyl donors. We also report the testing of the corresponding sialyl donors in several sialylation reactions, to elucidate the hypothesis of a Hydrogen-bond-mediated aglycone delivery (HAD) mechanism. However, exceptionally high stereoselectivities, yields and decreased reaction times were observed in the presence of an excess of triflic acid as a co-promoter.</p><p>

<p> Styryl phosphonic and cinnamic acid derivatives have been gaining attention as key candidates to modulate specific electrode properties in organic electronic devices such as work function, surface energies, wettability, and electron charge transfer kinetics that lead to increased efficiency, operational range, and device lifetimes. Very few of these acids are commercially available. The driving factor behind this research is to explore simple, high yield, and inexpensive synthetic routes towards synthesis of these acids. Herein, the novel synthesis of vinyl phosphonic acids (VPAs) and their subsequent influence on interface properties compared to their phenyl phosphonic acids (PPAs) and benzyl phosphonic acids (BPAs) analogues are explored. This includes an in depth comparison of varying polar VPA, BPA, and PPA &ldquo;families&rdquo; attachment on conductive oxides as they allow for careful work function tuning of band edge energy and chemical properties on these surfaces.</p><p> By leveraging similar techniques of VPA synthesis we can produce analogous cinnamic acids in which these same surface control concepts are applied on the surface of lead sulfide (PbS) colloidal semiconductor nano-crystals, or quantum dots (QDs). In order to do this, first a development of a simple solution-phase ligand exchange was necessary, from which we selectively replace native solubilizing ligands with these fictionalized cinnamic acids. This application achieved remarkable control allowing the band edge position to be tuned over an unprecedented 2.0 eV.</p><p> This cinnamic acid synthetic chemistry can then be extended to functionalize multi acrylate containing molecules creating organic linkers to be integrated into Metal Organic Frameworks (MOFs). MOFs have increasingly gained attention for many high impact applications including but not limited to catalysis, gas storage and release, sensors, energy harvesting, conductivity, and filtration. A great amount of research is presently being conducted in developing new MOFs from the same handful of commercially available linkers. We introduce synthetic techniques for 18 isoreticular series of linkers that can be formulated with similar, if not identical, conditions giving way to the formation of previously unknown frameworks. This technique led us to incorporate a number of these linkers into Ni-MOFs and investigate catalytic activity for conversion of oleic acid to liquid hydrocarbons.</p><p>

Four new stable radicals were synthesized. 2-(tert-butylaminoxyl)benzimidazole, 2-(4-tert-butylnitroxylphenyl)benzimidazole, 5-(6)-chlorobenzimidazole-2- tert-butylnitroxide, 2-(N-tert-butyl-N-aminoxyl)-5,6-dimethylbenzimidazole. According to magnetic studies antiferromagnetic behavior was observed for every sample. However a structure property relationship could be established based on the crystalline packing pattern observed. J exchange coupling was of higher dimensionality where the crystal structure was more ordered (herringbone interactions present), while the coupling was large but merely dimeric for the systems that exhibited lower dimensional, dimeric behavior. DFT calculations for dimeric pairs formed in 5-(6)-chlorobenzimidazole-2- tert-butylnitroxide, 2-(N-tert-butyl-N-aminoxyl)-5,6-dimethylbenzimidazole predicted ferromagnetic interaction opposite to antiferromagnetic behavior observed. These results suggest that the hydrogen bond does not have an appreciable participation in the spin-polarization exchange component of the magnetic behavior in these systems.

The sol-gel process is a convenient technique to prepare silicate materials with a variety of functions. These functional materials are formed via a ‘top-down’ fabrication process in which dopants are added at the commencement of the sol-gel process. However, despite the incredible versatility of these systems, issues remain regarding the mechanism of covalent entrapment of dopants. Therefore, we demonstrated how Flavin Mononucleotide acted as a dynamic conformational probe to study the covalent cross-linking of dopants into silica. It was shown that covalent entrapment occurs early in the sol, contrary to that observed for unbound probes. Self-assembly is prevalent in nature and is responsible for a vast array of highly ordered architectures observed in living organisms. It is only recently, however, that self-assembly has become an important tool for ‘bottom-up’ fabrication of complex multi-scale macroscopic composites. Attachment of recognition units onto nanoparticles and polymers provides a modular approach to precisely programmed assemblies in a relatively rapid fashion. Even though the macrosystems may be mechanically robust, they are able to retain the reversible and dynamic attributes of self-assembly. We exploited self-assembly to create ‘building-block’ and ‘bricks and mortar’ approaches to highly reactive, recyclable heterogeneous catalysts. By attaching complementary amines and carboxylic acids onto nanoparticles and polymers and mixing at different ratios, aggregates with distinct architectures were observed driven by electrostatics. Active catalysts were prepared by calcination, and the investigations showed substantial improvements in catalytic performance compared to their commercial counterparts were observed for hydrogenation and Heck reactions. A further application of controlled assembly was established when we encapsulated a recognition-derived guest into the polar pocket of folded ‘micellar’ polymer. Diaminotriazine-functionalized polymer folds into unimolecular ‘micelles’, in which the diaminotriazine units are inwardly directed to form polar pockets providing a complementary environment to the guest. Encapsulation was verified by NMR and cyclic voltammetry studies. Finally, self-assembly was adapted to polymer systems. Polymers comprised of complementary recognition units formed giant vesicles through specific interchain hydrogen bonding. It was also shown that recognition-derived nanoparticles could be specifically incorporated into the walls, providing a potential route to new templated nanocomposite macrosytems.

The scope of our copper(I)-catalyzed synthesis of diaryl acetylenes have been extended to the synthesis of 2 classes of heterocycles; 2-aryl benzo[ b]furans and 2-aryl indoles, by the cross-coupling of aryl acetylenes to 2-iodophenol and 2-iodoaniline, respectively. In addition, we demonstrated the scope of the copper(I) catalysts in catalyzing the cross-coupling of vinyl iodides. The aryl acetylenes and aryl/alkyl thiols were successfully coupled to vinyl iodides to synthesize 1,3-enynes and vinyl sulfides, respectively, using the well-defined copper(I)-complexes based on triphenylphosphine and nitrogen chelating ligand such as phenanthroline and bipyridine. The advantages of these protocols over the conventional copper-based methods are their simplicity, generality, and high functional group tolerances. We also demonstrated improvements of copper-assisted method of CF3 coupling to aryl iodide using metal trifluoroacetate salt, this reaction is not known with palladium chemistry. The possible mechanism of copper(I)-catalyzed reaction is also discussed and the application of our copper(I)-catalyzed protocol to the synthesis of interesting materials in cases where palladium catalyst failed is also shown.

This work has involved designing and synthesizing conjugated molecular and polymeric materials which are highly functionalized through structural modifications in order to enhance their electronic, photonic and morphological properties. The main objective is to synthesize novel organic luminophores which have efficient photoluminescence, as well as to optimize electroluminescence properties for organic light emitting diodes (OLEDs). A series of well-defined 2,7-bis(phenylethenyl)fluorenes/fluorenones (OFPVs/OFOPV) and 2,7-bis(phenyl)fluorenes/fluorenones (OFPhs) have been synthesized. The main synthetic methodologies used are palladium-catalyzed Heck coupling, Suzuki coupling and Knoevenagel condensation. The structure-property relationships---especially the effect of the fluorenone moiety on the photophysical and electroluminescent properties of these OFPVs, OFPhs and OFOPVs---were systematically investigated. The origin of an unwanted low-energy emission (g-band) in fluorene derivatives was evaluated by single-molecule and controlled luminophore/impurity blending photoluminescence studies (SMPL). OFPV and its segmented copolymer, poly-FPV (1-2) exhibit highly blue fluorescence in chloroform solution with quantum efficiencies of 0.93 and 0.68 respectively. Electroluminescence characteristics in an LED configuration ITO/PEDOT-PSS/(1 or 2)/Ca-Al of both were evaluated and OFPV gave much better EL performances with compared to its analogous segmented copolymer. The luminance efficiency of LEDs with OFPV was over 10-fold higher than those with copolymer 2, 0.515 versus 0.040 cd/A, with turn-on voltages of 3 and 5 V, respectively. Blends of 1 with PMMA gave stronger luminance than neat 1, with only a modest increase in turn-on voltage. A 10%(w/w) 1:PMMA based LED showed a maximum luminance of 450 cd/m2 at 7 V, with a luminance efficiency of 4.5 cd/A and a turn on voltage of 4.5 V. Among the structurally functionalized OFPVs, terminal heptyloxy substitution to make OFPV (8) gave the best electroluminescence performance as a blue emitter. It shows maximum luminance efficiency of 1.02 cd/A with maximum brightness of 1500 cd/m2 at 12 V. Unlike the OFPVs, shorter conjugation length OFPhs gave poor LED performance with an undesired longer wavelength green component at 500-550 nm in EL spectra. Blending the OFPhs with PMMA eliminated this long wavelength component and gave better color purity blue LED emission up to 25%(w/w) blends, even though these still gave poor overall LED emission efficiencies compare to the OFPVs.

This dissertation focuses on water-soluble phenylenevinylene (PV) and sensor-capable PV systems. All oligo PVs and poly(phenylenevinylenes) (PPVs) described below were synthesized using standard Heck coupling methodology. New water-soluble PV systems have been made by two different strategies. As ionic side chain substituted water-soluble PVs, two oligo-PV systems with pyridinium groups were made and shown to be more water-soluble than analogous systems with triethylammonium groups, even though two out of three systems of the triethylammonium-based systems were polymeric and so had numerous ionic side chains. The triethylammonium-bearing systems showed blue fluorescence in solution but emission of the pyridinium-based systems was not visible due to photoinduced electron transfer quenching. Another type of water-soluble, segmented copolymer based on PPV was made that incorporated a nonionic but hydrophilic poly(ethylene glycol) (PEG). This PEGylated PPV was readily soluble in water, and exhibited strong blue fluorescence. Cleavable amide bonds were tested as a basis for producing model systems for making sensors. A functionalizable diamino side-chain 2.5-oligo PV was used as a basic core synthetic unit. This system is described as “sticky molecule” since the amino groups can be easily functionalized. Two types of electron transfer quenchers, phthalimide and pyridinium, were attached to the sticky molecule by amide linkages. The luminescence of both systems was drastically quenched, but was shown to increase greatly when the amide bonds were cleaved by bases. These systems can be considered as "turn-on" sensor systems. Two pyrene units were also linked to the sticky molecule. This multichromophoric system displayed energy transfer from the pyrene to the PV core, such that the emission spectrum only shows the PV core peak, even when excited at wavelengths where the pyrene is the absorber. The energy transfer efficiency was calculated to be ∼60%. After the amide bonds were cleaved by acids, the pyrene emission was observed upon excitation at pyrene absorption wavelengths, which showed disruption of the energy transfer by allowing the pyrene the "escape" the core PV group. This can be considered either a "turn-off" process for the core PV, or a "turn-on" process for the pendant pyrene group.