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Publication Clustering, Reorientation Dynamics, and Proton Transfer In Glassy Oligomeric Solids(2013-09) Harvey, Jacob AllenWe have modelled structures and dynamics of hydrogen bond networks that form from imidazoles tethered to oligomeric aliphatic backbones in crystalline and glassy phases. We have studied the behavior of oligomers containing 5 or 10 imidazole groups. These systems have been simulated over the range 100-900 K with constantpressure molecular dynamics using the AMBER 94 force field, which was found to show good agreement with ab initio calculations on hydrogen bond strengths and imidazole rotational barriers. Hypothetical crystalline solids formed from packed 5-mers and 10-mers melt above 600 K, then form glassy solids upon cooling. Viewing hydrogen bond networks as clusters, we gathered statistics on cluster sizes and percolating pathways as a function of temperature, for comparison with the same quantities extracted from neat imidazole liquid. We have found that, at a given temperature, the glass composed of imidazole 5-mers shows the same hydrogen bond mean cluster size as that from the 10-mer glass, and that this size is consistently larger than that in liquid imidazole. Hydrogen bond clusters were found to percolate across the simulation cell for all glassy and crystalline solids, but not for any imidazole liquid. The apparent activation energy associated with hydrogen bond lifetimes in these glasses (9.3 kJ/mol) is close to that for the liquid (8.7 kJ/mol), but is substantially less than that in the crystalline solid (13.3 kJ/mol). These results indicate that glassy oligomeric solids show a promising mixture of extended hydrogen bond clusters and liquid-like dynamics. This study prompted a continued look at smaller oligomers (monomers, dimers, trimers, and pentamers). Using many of the above statistics we found that decreased chain length decreased the tendency to form global hydrogen bonding networks (percolation pathways). We also developed an reorientational correlation for the imidazole ring which allowed us to extract a timescale for reorientation. Smaller chains produce faster reorientation timescales and thus there is a trade off between faster reorientation dynamics and long global hydrogen bonding networks. Moreover we showed that homogeneity of chain length has no effect on hydrogen bonding statistics. Initial development on a multi-state empirical valence bond model has been to study proton transfer in liquid imidazole. We have shown that GAFF produces very large proton transfer barriers created by a highly repulsive N· · ·H VDW interaction at the transition point. In order to produce an acceptable fit to the potential energy surface while still producing stable dynamics this interaction must be turned off. This is in contrary to what is reported in the literature [14]. Using our model we have produced simulations with acceptable drift in the total energy (3.2 kcal/mol per ns) and negligible drift in the temperature (.12 K/ns).Publication Assembly Of Surface Engineered Nanoparticles For Functional Materials(2013-02) Yu, XiNanoparticles are regarded as exciting new building blocks for functional materials due to their fascinating physical properties because of the nano-confinement. Organizing nanoparticles into ordered hierarchical structures are highly desired for constructing novel optical and electrical artificial materials that are different from their isolated state or thermodynamics random ensembles. My research integrates the surface chemistry of nanoparticles, interfacial assembly and lithography techniques to construct nanoparticle based functional structures. We designed and synthesized tailor-made ligands for gold, semiconductor and magnetic nanoparticle, to modulate the assembly process and collective properties of the assembled structures, by controlling the key parameters such as particle-interface interaction, dielectric environments and inter-particle coupling etc. Top-down technologies such as micro contact printing, photolithography and nanoimprint lithography are used to guide the assembly into arbitrarily predesigned structures for potential device applications.Publication Allosteric Regulation of Caspase-6 Proteolytic Activity(2012-09) Velazquez-Delgado, Elih M.Caspases are cysteine proteases best known for their controlling roles in apoptosis and inflammation. Caspase-6 has recently been shown to play a key role in the cleavage of neurodegenerative substrates that causes Huntington and Alzheimer's Disease, heightening interest in caspase-6 and making it a drug target. All thirteen human caspases have related specificities for binding and cleaving substrate, so achieving caspase-specific regulation at the active site has been extremely challenging if not impossible. We have determined the structures of four unliganded forms of caspase-6, which attain a novel helical structure not observed in any other caspases. In this conformation, rotation of the 90's helix results in formation of a cavity that can function as an allosteric site, locking caspase-6 into an inactive conformation. We are using this cavity to look for chemical ligands that target this cavity and maintain caspase-6 in the inactive, helical conformation. We found that known allosteric inhibitors of caspase-3 and -7 also inhibit caspase-6 through a cavity at the dimer interface. We have determined new structures of a phosphomimetic state and a zinc-bound conformation of caspase-6, which show the molecular details of two additional allosteric sites. The phosphomimetic form of caspase-6 inactivates caspase-6 by disrupting formation of the substrate binding-groove by steric clash of the phosphorylated residue with P201 in the L2' loop. Another allosteric site was found on the "back" of caspase-6 that coordinates a zinc molecule that leads to inactivation. In total we have uncovered four independent allosteric sites in caspase-6, structurally characterized inhibition from these sites and demonstrated that each of these sites might be targeted for caspase-6 specific inhibition by synthetic or natural-product ligands.Publication Breaking the Barriers of All-Polymer Solar Cells: Solving Electron Transporter And Morphology Problems(2012-09) Gavvalapalli, NagarjunaAll-polymer solar cells (APSC) are a class of organic solar cells in which hole and electron transporting phases are made of conjugated polymers. Unlike polymer/fullerene solar cell, photoactive material of APSC can be designed to have hole and electron transporting polymers with complementary absorption range and proper frontier energy level offset. However, the highest reported PCE of APSC is 5 times less than that of polymer/fullerene solar cell. The low PCE of APSC is mainly due to: i) low charge separation efficiency; and ii) lack of optimal morphology to facilitate charge transfer and transport; and iii) lack of control over the exciton and charge transport in each phase. My research work is focused towards addressing these issues. The charge separation efficiency of APSC can be enhanced by designing novel electron transporting polymers with: i) broad absorption range; ii) high electron mobility; and iii) high dielectric constant. In addition to with the above parameters chemical and electronic structure of the repeating unit of conjugated polymer also plays a role in charge separation efficiency. So far only three classes of electron transporting polymers, CN substituted PPV, 2,1,3-benzothiadiazole derived polymers and rylene diimide derived polymers, are used in APSC. Thus to enhance the charge separation efficiency new classes of electron transporting polymers with the above characteristics need to be synthesized. I have developed a new straightforward synthetic strategy to rapidly generate new classes of electron transporting polymers with different chemical and electronic structure, broad absorption range, and high electron mobility from readily available electron deficient monomers. In APSCs due to low entropy of mixing, polymers tend to micro-phase segregate rather than forming the more useful nano-phase segregation. Optimizing the polymer blend morphology to obtain nano-phase segregation is specific to the system under study, time consuming, and not trivial. Thus to avoid micro-phase segregation, nanoparticles of hole and electron transporters are synthesized and blended. But the PCE of nanoparticle blends are far less than those of polymer blends. This is mainly due to the: i) lack of optimal assembly of nanoparticles to facilitate charge transfer and transport processes; and ii) lack of control over the exciton and charge transport properties within the nanoparticles. Polymer packing within the nanoparticle controls the optoelectronic and charge transport properties of the nanoparticle. In this work I have shown that the solvent used to synthesize nanoparticles plays a crucial role in determining the assembly of polymer chains inside the nanoparticle there by affecting its exciton and charge transport processes. To obtain the optimal morphology for better charge transfer and transport, we have also synthesized nanoparticles of different radius with surfactants of opposite charge. We propose that depending on the radius and/or Coulombic interactions these nanoparticles can be assembled into mineral structure-types that are useful for photovoltaic devices.Publication Controlled Oxygen Activation in Human Oxygen Sensor FIH(2011-09) Saban, EvrenOne of the primary oxygen sensors in human cells, which controls gene expression by hydroxylating the hypoxia inducible transcription factor (HIFα) is the factor inhibiting HIF (FIH). As FIH is an alpha-ketoglutarate dependent non-heme iron dioxygenase, oxygen activation is thought to precede substrate hydroxylation. The coupling between oxygen activation and substrate hydroxylation was hypothesized to be very tight, in order for FIH to fulfill its function as a regulatory enzyme. Coupling was investigated by looking for reactive oxygen species production during turnover. Alkylsulfatase (AtsK), a metabolic bacterial enzyme with a related mechanism and similar turnover frequency, was used for comparison, and both FIH and AtsK were tested for H2O2, O2- and OH• formation under steady and substrate-depleted conditions. Coupling ratios were determined by comparing the ratio of substrate consumed to product formed. AtsK reacted with O2 on the seconds timescale in the absence of prime substrate, and uncoupled during turnover to produce H2O2; neither O2- nor OH• were detected. In contrast, FIH was unreactive toward O2 on the minutes timescale in the absence of prime substrate, and tightly coupled during steady-state turnover; any reactive oxygen species produced by FIH was not available for detection. Inactivation mechanisms of these enzymes were also investigated. AtsK likely inactivated due to deoligomerization, whereas FIH inactivated by slow autohydroxylation. Autohydroxylated FIH could not be reactivated by dithiothreitol (DTT) nor is ascorbate, suggesting that autohydroxylation likely to be irreversible under physiological conditions. Iron in the FIH active site is coordinated by a (His2Asp) facial triad, αKG, and H2O. Hydrogen bonding between the facial triad, the HIF-Asn803 sidechain, and various second-sphere residues suggests a functional role for the second coordination sphere in tuning the chemistry of the Fe(II) center. Point mutants of FIH were prepared to test the functional role of the αKG-centered (Asn205, Asn294) or HIF-Asn803 centered (Arg238, Gln239) second-sphere residues. The second sphere was tested for local effects on priming Fe(II) to react with O2, oxidative decarboxylation, and substrate positioning. Steady-state kinetics were used to test for overall catalytic effects, autohydroxylation rates were used to test for priming and positioning, and electronic spectroscopy was used to assess the primary coordination sphere and the electrophilicity of αKG. Asn205àAla and Asn294àAla exhibited diminished rates of steady-state turnover, while minimally affecting autohydroxylation, consistent with impaired oxidative decarboxylation. Blue shifted MLCT transitions for (Fe+αKG)FIH indicated that these point mutations destabilized the π* orbitals of αKG, further supporting a slowed rate of oxidative decarboxylation. The Arg238àMet mutant exhibited steady-state rates too low to measure and diminished product yields, suggesting impaired substrate positioning or priming; Arg238àMet was capable of O2-activation for the autohydroxylation reaction. The Gln239àAsn mutant exhibited significantly slowed steady-state kinetics and diminished product yields, suggesting impaired substrate positioning or priming. As HIF binding to Gln239àAsn stimulated autohydroxylation, it is more likely that this point mutant simply mis-positions the HIF-Asn803 sidechain. By combining kinetics and spectroscopy, it was shown that these second sphere hydrogen bonds play roles in promoting oxidative decarboxylation, priming Fe(II) to bind O2, and positioning HIF-Asn803.Publication Colloidal Microcapsules: Surface Engineering of Nanoparticles for Interfacial Assembly(2011-05) Patra, DebabrataColloidal Microcapsules (MCs), i.e. capsules stabilized by nano-/microparticle shells are highly modular inherently multi-scale constructs with applications in many areas of material and biological sciences e.g. drug delivery, encapsulation and microreactors. These MCs are fabricated by stabilizing emulsions via self-assembly of colloidal micro/nanoparticles at liquid-liquid interface. In these systems, colloidal particles serve as modular building blocks, allowing incorporation of the particle properties into the functional capabilities of the MCs. As an example, nanoparticles (NPs) can serve as appropriate antennae to induce response by external triggers (e.g. magnetic fields or laser) for controlled release of encapsulated materials. Additionally, the dynamic nature of the colloidal assembly at liquid-liquid interfaces result defects free organized nanostructures with unique electronic, magnetic and optical properties which can be tuned by their dimension and cooperative interactions. The physical properties of colloidal microcapsules such as permeability, mechanical strength, and biocompatibility can be precisely controlled through the proper choice of colloids and preparation conditions for their This thesis illustrates the fabrication of stable and robust MCs through via chemical crosslinking of the surface engineered NPs at oil-water interface. The chemical crosslinking assists NPs to form a stable 2-D network structure at the emulsion interface, imparting robustness to the emulsions. In brief, we developed the strategies for altering the nature of chemical interaction between NPs at the emulsion interface and investigated their role during the self-assembly process. Recently, we have fabricated stable colloidal microcapsule (MCs) using covalent, dative as well as non-covalent interactions and demonstrated their potential applications including encapsulation, size selective release, functional devices and biocatalysts.Publication Caspase-7 Loop Conformations as a Means of Allosteric Control(2011-05) Witkowski, Witold AndrejThe caspase family of proteins is critical to biological understanding, because they serve as the final arbiters of life and death, being the initiators and executioners of cell death. Specifically, caspase-7 plays a key role in apoptosis, however its full complement of targets within the cell has not yet been elucidated, nor has its function been targeted by drug design efforts. These factors stem from the lack of fundamental understanding of the structural dynamics of the protein, including the mobile loops that constitute the active site binding groove of caspase-7, and their ability to modulate the function of the protein. In this work, we describe the importance of the entire loop bundle for catalysis, demonstrate a novel approach for allosteric control using loop movement, develop computational methods to engineer a new binding site for an allosteric effector and discover a hereunto unseen native disulfide within caspase-7 that may contribute to specificity and catalysis. The information obtained within this study is applicable for not only the study of caspase-7, but also the greater field of apoptosis research.Publication Design and Synthesis of a New Class of Self-Cross-Linked Polymer Nanogels(2011-05) Jiwpanich, SiripornThe design and engineering of nanoscopic drug delivery vehicles that stably encapsulate lipophilic drug molecules, transport their loaded cargo to specific target sites, and release their payload in a controlled manner are of great interest in therapeutic applications, especially for cancer chemotherapy. This dissertation focuses on chemically cross-linked, water-soluble polymer nanoparticles, termed nanogels, which constitute a promising scaffold and offer the potential to circumvent encapsulation stability issues. A facile synthetic method for a new class of self-cross-linked polymer nanogels, synthesized by an intra/intermolecular disulfide cross-linking reaction in aqueous media, is described here. This simple emulsion-free method affords noncovalent lipophilic guest encapsulation and surface functionalization that may allow for targeted delivery. The encapsulation stability of lipophilic molecules sequestered within these nanoscopic containers is evaluated by a fluorescent resonance energy transfer (FRET) based method developed by our research group. We demonstrate that the encapsulation stability of noncovalently encapsulated guest molecules in disulfide cross-linked polymer nanogels can be tuned and that guest release can be achieved in response to a biologically relevant stimulus (GSH). In addition, varied hydrophobicity in the self-cross-linked nanogels affects the lipophilic loading capacity and encapsulation stability. We reveal that optimal loading capacity is limited by encapsulation stability, where over-loading of lipophilic molecules in the nanoscopic containers may cause undersirable leakage and severely compromise the viability of such systems for drug delivery and other biological applications.Publication Charge and Energy Transport in Single Quantum Dot/Organic Hybrid Nanostructures(2010-09) Early, Kevin ThomasHybrid quantum dot /organic semiconductor systems are of great interest in optoelectronic and photovoltaic applications, because they combine the robust and tunable optical properties of inorganic semiconductors with the processability of organic thin films. In particular, cadmium selenide (CdSe) quantum dots coordinated with oligo-(phenylene vinylene) ligands have displayed a number of hybrid optical properties that make them particularly well-suited to these applications. When probed on an individual particle level, these so-called CdSe-OPV nanostructures display a number of surprising photophysical characteristics, including strong quenching of fluorescence from coordinating ligands, enhanced emission from the CdSe quantum dot core, suppression of fluorescence intermittency, and photon antibunching, all of which make them attractive in the applications described above. By correlating fluorescence properties with atomic force microscopy, the effects of ligands on quantum dot luminescence are elucidated. In addition, recent studies on individual CdSe-OPV nanostructures have revealed a strong electronic coupling between the coordinating ligands and the nanocrystal core. These studies have shown that excitations in the organic ligands can strongly affect the electronic properties of the quantum dot, leading to linearly polarized optical transitions (both in absorption and emission) and polarization-modulated shifts in band edge emission frequency. These polarization effects suggest exciting new uses for these nanostructures in applications that demand the robust optical properties of quantum dots combined with polarization-switchable control of photon emission.Publication Analytical Methods to Support Design and Optimization of Protein Drug Conjugate: Focusing on Haptoglobin-hemoglobin Complex as a Drug Carrier(2017-05) Xu, ShengshengAcquired immunodeficiency syndrome (AIDS) remains one of the most serious public health challenges and a significant cause of mortality for certain populations. Despite the large number of antiretrovirals (mostly nucleotide and nucleoside analogs) developed in the past two decades, the inability of small molecule therapeutics to target HIV reservoirs directly creates a significant obstacle to their effective utilization. Indeed, achieving the desired therapeutic effect in the absence of the effective targeted delivery must rely on dosage escalation, which frequently causes severe toxicity. This problem may be solved by conjugation of antiretroviral agents to endogenous proteins (e.g., hemoglobin haptoglobin complex) that are specifically recognized by HIV reservoirs (such as macrophages) for internalization and catabolism. However, conjugation of a large class of antiretroviral agents (acyclic nucleoside phosphonates, such as adefovir) to a protein is challenging due to the rapid decay (including hydrolysis and dimerization) of the activated form of the drug (adefovir phosphonoimidazolide) during transition (ether precipitation) from organic phase to aqueous phase. This work introduces a novel synthetic strategy which overcomes the instability of the activated form of adefovir by emulating the first step of its metabolic pathway (phosphorylation), making it highly reactive towards primary amine groups of proteins. The effective conjugation of phosphorylated form of adefovir to protein via an imidazolide based intermediate was demonstrated using lysozyme as a model carrier protein. Mass spectrometry (MS) based analytical methods were used to support design and optimization of all those conjugations. Further optimization of adefovir’s conjugation with hemoglobin (Hb), a drug carrier which targets macrophage via haptoglobin (Hp)-CD163 mediated heme scavenging system, was pursued using another novel linker, phosphonoacetate, which allows reactions to be performed at neutral pH with a satisfactory yield. Successful loading of adefovir to Hp, the obligatory partner of Hb for targeted drug delivery, via Hb·Hp binding was demonstrated by MS. Lastly, a new strategy was developed for detecting and quantitating exogenous Hp·Hb complex with high sensitivity in complex biological samples using gallium as a tracer of this protein and inductively coupled plasma mass spectrometry (ICP MS) as a method of detection.Publication Characterization of Electronic and Ionic Transport in Soft and Hard Functional Materials(2017-05) Renna, Lawrence A.Control over concurrent transport of multiple carrier types is desired in both soft and hard materials. For both types of materials, I demonstrate ways to characterize and execute governance over both electronic and ionic transport, and apply these concepts in the fabrication of devices with applications in conducting composites, photovoltaics, electrochemical energy storage, and memristors. In soft materials, such as polymers, the topology of the binary polymer mesoscale morphology has major implications on the charge/ion transport. Traditional approaches to co-continuous structures involve either using blends of polymers or diblock copolymers. In polymer blends, the structures are kinetically trapped and thus have poor long term stability. In diblock polymers, such morphologies are not universally accessible to non-random coil polymers. I discuss an approach to binary polymer mesoscale morphologies via the assembly of polymer nanoparticles. In this strategy, polymers are assembled into spherical nanoparticles, which are then assembled into hierarchical mesoscale structures. First, I demonstrate, experimentally and computationally, that the electrical transport in semiconducting/insulating polymer nanoparticle assemblies can be predictably tuned according to power law percolation scaling. Then I show that nanoparticle assemblies can be utilized for tunable concurrent transport of electrons and holes for photovoltaics, and for electronic and ionic charges aimed at applications in electrochemical energy storage. For hard materials, I detail the characterization of mixed electronic and ionic transport in hybrid organic/inorganic lead triiodide perovskites. I used the understanding of mixed electronic and ionic transport in these materials to explain poorly understood phenomena such as photo-instability and current-voltage hysteresis. Then, I show several examples of interfacial materials, and the characterization and implications of their respective work functions, as charge transport materials to control selective charge extraction from perovskites. And finally, I show how interfacial charge transport materials with ionic functionality can be used to change the interfacial chemistry at perovskite/charge transport material interfaces to control both electronic and ionic transport. In this regard, I demonstrate how an adsorbing interface for mobile ions can be used to control current-voltage hysteresis and state-dependent resistance, introducing a novel paradigm of interfacial ion adsorption to fabricate novel perovskite-based memristor devices.Publication Analysis of Gold Nanoparticles and Their Use with Laser Desorption/Ionization Mass Spectrometry(2017) Marsico, AlyssaGold nanoparticles (AuNPs) have many unique properties that make them attractive for use in various biological applications. Laser desorption/ionization mass spectrometry (LDI-MS) has been used to monitor AuNPs in complex biological samples but there are still many ways in which AuNPs can be used with MS. In this dissertation, the use of AuNPs to assist in analyte ionization has been investigated. Their ability to enhance signal from biomolecules based on their surface chemistry, size, aggregation and method of deposition has been studied. The first use of an inkjet printer to create surfaces from which analytes can be sampled is discussed and revealed that the aggregation of the NPs is crucial to analyte enhancement. In addition, the investigation of the use of both AuNPs and a small amount of matrix that is typically used in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in order to detect previously difficult to ionize ligands in biological samples is reported and revealed the existence of a synergistic relationship between the two components. The method by which AuNPs dry and form a coffee ring is also taken advantage of to easily locate and enhance signal from larger biomolecules due to the concentration of the analyte, AuNP and matrix to the formed ring. Finally, desorption efficiencies and energies required for these ionization processes are all investigated and compared in order to better understand the mechanism of ionization.Publication Cell Modulation Using Functionalized Nanoparticles(2016-09) Tang, RuiMonolayer functionalized ultra-small gold nanoparticles (AuNPs) provide a versatile platform for applications in cell research. Through rational design of surface ligands, the chemistry of AuNPs are precisely regulated at atomic level. In this dissertation, applications of AuNPs in cell modulation are discussed. The topics are split into two categories. In the first category, functionalized AuNPs are harnessed to generate a robust monolayer on cell culture surface for cell modulation. The proliferation and behavior of different types of cancer cells and normal cells are modulated by tuning the surface ligands of AuNPs. Fate decision of mesenchymal stem cells are also modulated using the same strategy. In the second category, AuNPs are assembled to nanoparticle stabilized capsules (NPSCs) for the delivery of a variety of proteins to cytosol of cells. Using this method, phenotype of cells are rapidly switched without genomic disturbance. In addition, subcellular localization of proteins are also controlled by the combination of subcellular localization signals and NPSC delivery platform. The first non-peptide synthetic nuclear localization signal based on boronate is discovered using NPSC delivery platform as well.Publication A Semisynthetic Strategy Leads to Alteration of the Backbone Amidate Ligand in the NiSOD Active Site(2015-09) Campeciño, Julius OmayaoComputational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategy that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and have altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. 14N-hyperfine is observed on gz, confirming the addition of the apical histidine ligand in the Ni(III) complex. The altered electronic properties and implications for redox catalysis are discussed in light of predictions based on synthetic and computational models.Publication Conjugated Polymers in Thermoelectric Composites and Small Molecules for High Light Absorptivity(2015-09) Tonga, MuratOver the past several decades with increasing of global energy demand, thermoelectric materials have gained considerable attention due to their unique ability to directly convert heat to electricity. In addition to inorganic semiconductors, polymers are potential candidates for high-performance thermoelectric applications due to their intrinsic advantages such as low thermal conductivity, solution processability, and roll-to-roll production, lightweight, and flexible thermoelectric modules. This thesis provides an insight into the emerging field of organic thermoelectrics, more specifically, thermoelectric power generation based on the composites of conducting polymers (MEH-PPV, P3HT and PEDOT:PSS) and carbon nanotubes (SWNT, SWNT-COOH, SWNT-OH and MWNT). A substantial portion of my work at the graduate level has involved the composite materials of conductive polymers and carbon nanotubes (CNTs) for use in organic thermoelectrics (TE). This work comprised multiple iterations to test effects of chain length (molecular weight) and regioregularity, amount and type of CNT added, sample fabrication solvent, and doping duration led to substantial optimization of the TE power factors. A power factor of 148 μW m-1 K-2 was obtained in the optimized sample preparation with rr-P3HT-Rieke/50%SWnNT which is quite competitive with the PFs mentioned in section 2.3. Besides polymers, I also investigated TE properties of cross-linked network structures established from UV curable small molecules with CNTs. A variety of distinct morphological architectures -- consistent with differences in TE performances -- have been observed. I described the synthesis of new pyridinium and extended viologen molecules capturing light in the visible portion of the solar spectrum with high molar extinction coefficient (~22,000 to 278,000 M-1 cm-1) by means of intramolecular charge transfer (ICT), using electron-donor and electron-accepter groups linked through π-conjugation. Also, these compounds exhibited solvatochromic properties in absorption and emission spectra with respect to the ICT band.Publication Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells(2015-09) Hussey, Amanda MProper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in forced dimerization, unnatural movement, and at worst inactivation of the receptor. Small molecule organic dyes provide a potential advantage because they can be structurally functionalized to target the protein of interest in a non-perturbing fashion which allows for information to be gathered about the targeted receptor. The work I initiated in the Chambers lab first focused on using a ligand directed fluorophore connected via a photo-labile linker. Through the use of epifluorescence microscopy, I determined that this probe targets glutamate receptors, however questions about subtype inclusion could not be addressed The pharmacophore that our first probe is based on could be much more promiscuous than is presently appreciated in the field of neurobiology. Thus, we designed a new series of probes to allow for covalent modification and affinity purification of endogenous receptors. The second generation of probes set out to answer the questions left by the first. Purified proteins were subjected to SDS-PAGE analysis and could be applied to proteomic identification of receptors. In addition to ligand directed probes, we have also initiated a project on a new, bimolecular photoaffinity probe in which the new methodology continues to develop. The initial studies were performed to ensure that our new strategy is able to be used in biological systems.Publication Design and Synthesis of Polymeric Nanoparticles for Drug and Protein Delivery(2015-05) Ventura, Judy A.Nanoparticles are emerging as carriers in biological applications due to advances in their preparation, size control, surface modification and encapsulation capabilities. In addition, nanomaterials improve bioavailability by enhancing aqueous solubility of the guest molecule and increasing resistance time in the body. However, the delivery of guest molecules is still challenging due to the intrinsic characteristics of the guest molecule including large size and propensity to denature or degradation in the case of biomolecules and the encapsulation stability of the small guest molecules. Our group recently reported the preparation of self-cross-linked polymeric nanogels possessing surface functionalization capabilities. In this dissertation we employed the use of polymeric nanogels to explore and understand their guest encapsulation capabilities with both hydrophilic and hydrophobic molecules. We were able to encapsulate a protein in the hydrophobic core of the nanogels and recover is enzymatic activity upon release. Moreover the surface of these nanogels can be also decorated with surface exposed cysteine containing protein. We also reported a straightforward methodology for the preparation of tri-functionalized amine materials with high functional density.Publication Design and Application of Organic Electronic Materials: Pendant Tuning in Polymeric and Molecular Systems(2015-05) Tinkham, Jonathan SDesigning and synthesizing materials for use in organic electronic materials requires fine control over their optical and electronic properties. Variations through substitution can be used to tune solubility and electronic properties, but this can result in degradation of other properties. Substitution with orthogonal pendant groups in both molecular and polymeric systems has the potential for allowing tunability while decreasing the perturbation of other desirable properties of the parent system. This idea was explored through experimental and computational work. Computational modelling was used to understand and predict the properties of molecular and polymeric systems to narrow the wide number of choices of possible materials. The ability to computationally predict not just molecular orbital energy levels, but other properties of the system such as UV-Vis transitions, unpaired spin-density, and changes in dipole moment is important not just for designing new materials, but in understanding how they work. This is accomplished in modelling a modular approach to tuning of frontier orbital energy levels. Newer strategies for predicting photovoltaic performance by analysis of the ground-to-excited state dipole moment change are also explored. A series of low-bandgap polymers absorbing at a bandgap of 1.7 eV, near the ``ideal'' bandgap of 1.5 eV, were prepared by copolymerizing an electron-donating and electron-withdrawing unit to yield a low-bandgap ``push-pull'' copolymer. The donor unit was designed to study the effect of pendant phenyl substitution. The resulting copolymers were oligomeric in nature, but devices prepared using these copolymers gave very promising photovoltaic power conversion efficiencies up to 5\%. The influence of a pendant phenyl unit in the copolymers yielded a system with increased order in the solid state, and decent performance. Design and synthesis of new materials through pendant tuning was shown to be a viable strategy for developing new organic electronic materials, and methods to explore this for new materials were established.Publication Design and Syntheses of Donor-Acceptor Dyads and Triads for Improved Light Harvesting in Organic Photovoltaics(2014) Della Pelle, AndreaAll organic photovoltaics (OPVs) undergo four major processes to convert sunlight in electrical energy. The first process is the absorbance of sunlight. Due to the limit of available acceptor molecules, the burden of light absorbance weighs heavily on the donor material. This thesis focuses heavily on the development of dyes consisting of donor-acceptor dyads and triads for improved light harvesting in OPVs. Squaraine dyes show impressive light harvesting properties with absorbances in the UV to near IR region with extinction coefficients on the order of 105 M--‐1 cm--‐1. Unfortunately, improved light harvesting is not enough to insure optimized OPVs. Energy level tuning to increase VOC and insure efficient exciton dissociation is also required. Functionalizing squaraine dyes with electron donating or electron withdrawing groups allow for the systematic tuning of the HOMO energy levels. This tenability allows for the concurrent optimization of bandgap and VOC. Cyanine dyes have been explored for small molecule OPVs due to their impressive absorbance properties. The absorbance of ketocyanine dyes can be tuned by manipulating the strength of the acceptor moiety. Stronger acceptors are better able to stabilize the negative charge in the charge separated state of the dye. This stabilization allows for a greater contribution from the cyanine structure of the dye, thus red shifting the absorbance. Stronger acceptors also increase the communication between the two amine functionalities as demonstrated by cyclic voltammetry. Block copolymers show impressive morphological control through the tuning of the molecular weight of the blocks as well as the compatibility of the functional groups. This allows for the access of morphologies with small, well ordered, and continuous domains thought to be beneficial in the active layer of OPVs. Unfortunately, block copolymers often show inferior light harvesting compared to their conjugated polymer counterparts. Donor-acceptor systems are explored as sensitizers for block copolymer OPVs. Small molecules without twists or bends or acetylene linkers were found to be most effective for lowering the bandgap and aligning the energy levels.Publication Design, Syntheses and Study of BODIPY-based Materials for Use as Electron Transporters in Organic Electronics(2015) Poe, AmbataOrganic photovoltaics (OPVs) are desirable for the harvesting of solar energy. They provide distinct advantages over their inorganic counterparts, especially the high absorption coefficients of organic materials and their ability to be processed using inexpensive solution methods. This allows for potential development of lightweight and flexible devices for portable electronics. One of the drawbacks of organic photovoltaics is the low power conversion efficiency of the devices. Efforts to improve the efficiency often take place through molecular design of the electron rich donor material to improve light absorption of the active layer. However, significantly less effort has been put into modifying the acceptor. BODIPY-dye based materials are well known for their photostability, strong visible absorption and tunable optical and electrochemical properties. Incorporation of these materials into an A-D-A architecture, in which the meso coupled BODIPY moiety acts as the acceptor cap is particularly advantageous. This instills predictable absorption properties, low lying LUMO level and consistent n-type characteristics, making these materials suitable for use as light harvesting electron acceptors in OPV devices. Using these materials in bulk heterojunction OPV devices with poly(3-hexylthiophene) (P3HT) as the donor material yielded efficiencies up to 1.5%. This efficiency was reached after mild optimization using solvent additives and thermal annealing, methods similar to those used with the most commonly employed acceptor, PCBM. Analysis of the fabricated devices showed the BODIPY molecules contribute to the photogenerated current in the Vis-NIR region. In an effort to improve BODIPY absorption associated with the donor-acceptor intramolecular charge transfer (ICT) interaction, the linker between the donor core and BODIPY cap was systemically modified to increase the delocalization of the frontier molecular orbitals (m-phenylene < p-phenylene < fluoro-p-phenylene < 3-hexylthiophene < directly linked < ethynyl). This variation not only improved the red edge absorption as the delocalization increased, it also provided a method to tune the LUMO energy level, a valuable tool in the design of electron acceptors. The ethynyl linked, BDP-CC-DTP, yielded the best electron mobility (~10-3 cm2 V-1 s-1), likely due to the low lying LUMO (-4.06 eV) and its ability to form nanoscale aggregates to promote long range electron transport. Given the improved red edge absorption and higher electron mobility of BDP-CC-DTP compared to BDP-Th-DTP, which showed respectable efficiencies when used as an acceptor in BHJ OPV devices, we plan to investigate the use of this semiconductor in organic solar cells.