Cells process an enormous amount of information from their environment and translate this information into phenotypic behaviour that will dictate critical biologic activities. To do this, cells must collect, store, and respond to information both inside and outside the cell. This information is stored in the chemical composition of its cytoplasm, and these conditions will regulate complex biochemical pathways that relay the information from the cell’s exterior to the effector proteins that modulate behaviour. These pathways, known as signal transduction pathways, are largely regulated by phosphorylation. Protein kinases are the class of enzymes responsible catalyzing the phosphorylation of intermediary signaling enzymes (resulting in their activation), and thus, stimulate the transduction of an external stimulus to intracellular machinery. As cellular conditions change, protein kinases sensitive to these conditions will modulate their activity through a change in shape (conformation). Research shows that disregulating signaling pathways through aberrant kinase activity can lead to grievous disease, making them good drug targets for cancer treatments and other conditions. Selective pressure has lead to the 500+ kinases in the proteome to adopt well-conserved active and inactive conformations, making it difficult to understand how nature can distinguish between them. Due to low abundance of kinases, quantitative analysis of kinase conformations is difficult with existing methodology. To this end, we have developed a catch-and-release system that allows us to enrich and quantitatively distinguish between kinases of specific conformations. This project will focus on the development trifunctional probe that serves as a chemical handle to enrich kinases in the novel system. The new catch-and-release system employs improvements over existing biotin-steptavidin systems by taking advantage of bio-orthogonal chemistry and specific elution conditions that increase signal-to-noise ratios. Our probe marks significant progress towards a panel of probes that will profile kinases for diagnostic means and drug target identification.

It is well known that mammals contain several types of phospholipase A2. The cytosolic phospholipases A2 (cPLA2s) are one type, and are composed of six enzymes: cPLA2alpha, cPLA2beta, cPLA2gamma, cPLA2delta, cPLA2epsilon, and cPLA2zeta. There has been significant interest in the cPLA2alpha isoform because of the enzyme's 10 fold preference for the hydrolysis at the sn-2 position of the glycerol backbone in phospholipids, resulting in the liberation of arachidonic acid. Arachidonic acid serves as a precursor for several highly regulated inflammatory mediators that play an important role in asthma, atherosclerosis, and arthritis. To address these problems, inhibitors that target cPLA2alpha have been developed to serve as anti-inflammatory therapeutics. Wyeth pharmaceuticals has released a class of indole inhibitors that inhibit cPLA2zeta at <10 nM IC50. However, a recent study has shown that in cPLA2alpha-/-stimulated lung fibroblasts arachidonic acid production is lessened but still present. cPLA2zeta has been identified as the other enzyme involved in the release of arachidonic acid. To further our limited understanding of cPLA2zeta's role in the inflammatory process, we are developing selective and potent inhibitors of the cPLA2zeta isoform. Our synthetic strategy is to modify the scaffold of Wyeth's cPLA2alpha inhibitor. Analysis of the structure-activity relationships and 3D molecular modeling has revealed 4 different places on the scaffold to introduce substitutions. To date, we have generated and assayed a panel of inhibitors. These inhibitors display low nanomolar potency, but have only minimal selectivity for cPLA2zeta. Thus, our main focus is to increase the selectivity of our inhibitors towards cPLA2zeta in order to further our understanding of cPLA2zeta's role in arachidonic acid production.

Hybrid organic/inorganic composites of conjugated polymers with quantum dots are of interest due to their potential for low-cost, solution processable solar cells and photodetectors. We use photoinduced absorption (PIA) spectroscopy to study charge generation in hybrid bulk heterojunction blends of the conjugated polymers with PbS quantum dots. We have previously shown that selective excitation of the quantum dots leads to formation of positively charged polarons on the conjugated polymer. By computing the relative yields of long-lived holes following photoexcitation of both the polymer and quantum dot phases, we estimate that more long-lived polarons are produced per absorbed photon by the polymer phase than the quantum dot phase. In this study, we aim to determine whether the formation of long-lived charge carriers due to quantum dot photoexciation is wavelength-dependent by investigating the polaron yield resulting from selective PbS excitation at varying energies in the near infrared. These results will give insight into the process of hole transfer from photoexcited quantum dots to the organic host polymer.

Colloidal zinc oxide nanocrystals (NCs) become charged with electrons upon reduction with decamethylcobaltocene. Understanding this redox chemistry can further develop research on quantum dot sensitized solar cells and other various applications of NCs. The goal of my project is to determine whether this electron transfer can be characterized by an equilibrium constant K_eq, and if so, to see which variables in the reaction affect the K_eq. Two models were tested: (1) in which the concentration of NCs would affect the K_eq, and another (2) in which it would not. Using data from optical titrations, I found that the K_eq is affected by NC concentration and is therefore better described by model (1). Similarly, other variables are currently being tested in order to refine a working model that can accurately describe the reaction of NCs with reductants. The contribution of a simple model for these charge transfer processes can be applied to various areas.

Two strains of Botryococcus braunii algae were grown in three different sets of conditions to compare growth characteristics and lipid production. One species, UTEX LB 572, was a Race A Botryococcus braunii from the culture collection of the University of Texas in Austin. The second species, AC 762, was a Race B Botryococcus braunii from the culture collection of the University of Caen, France. UTEX 572 was found to produce two hydrocarbon chain lengths of C:16 and C:18 in a 2:3 ratio respectively. The AC 762 was found to produce hydrocarbons called botryococcenes of chain lengths between C:30 and C:36. The lipid chain lengths of both strains were evaluated by mass spectrometry. The UTEX 572 lipid content was quantified by analytical spectrometry after direct transesterification of the lipid content to biodiesel. The AC 762 lipid content was quantified by a photospectrometry technique developed by UC Berkeley researchers Eroglu and Melis (1985). Cells of both species were harvested during exponential growth phase from 400 mL of growth media and then freeze dried and analyzed gravimetrically. Nine flasks of each species were grown with 3000 lux average light intensity on a 12h:12h light:dark cycle at room temperature averaging 22° C. Three flasks of each species were grown with 1.5% CO2 in BG-11 media, three flasks of each species were grown in BG-11 media with air only and three control flasks were grown in respective carrier medias as those used in the algae collection of origin. Knowledge of the rates at which AC 762 and UTEX 572 produce hydrocarbons as well as the specific lengths and proportions of those hydrocarbons contributes to data needed for comparison of economic considerations in industrial applications.

Malaria is a parasitic infection due to Protozoa Plasmodium. This is a severe global disease with 250 million annual cases leading to 1-2 million deaths. The most virulent, P. falciparum, is responsible for severe clinical malaria and death. An array of anti-malarial treatments exist today, however parasites evolve continuously to develop resistance even to the newest frontline anti-malarial drugs. Previous studies in the Rathod laboratory have demonstrated that drug resistance can be generated in the lab and that some drugs can be utilized to characterize Accelerated Resistance to Multiple Drugs (ARMD) parasites, such as the laboratory strain Dd2, and non-ARMD parasites, such as the laboratory strain HB3. In the current study, we are using a cyclopropyl carboxamide (GSK 2645947) to select for resistant parasites. Cyclopropyl carboxamides are a chemically novel class of antimalarial agents identified recently and they prevent the growth of P. falciparum in the early trophozoite stages of the erythrocytic Plasmodium cycle. This project focuses on determining the conditions for the development of resistance against GSK 2645947 with Dd2 and HB3 by conducting a series of selection experiments utilizing different concentrations of GSK 2645947 and starting parasites populations. Unlike previous conditions which indicate that the Dd2 strain acquires resistance at a significantly higher frequency than the HB3 stain; the data from this study suggests that both Dd2 and HB3 strains respond similarly to GSK 2645947. Through this study, we can further understand the behavior of resistant P. falciparum parasites. 

Alternative energy sources have been becoming a greater necessity as fossil fuels become higher in demand and pollution endangers the world. Dye-sensitized solar cells have been of increasing interest in the last twenty years as a possible low-cost and efficient alternative to conventional fuel sources. Porphyrins are synthetic analogs of chlorophyll, the molecule responsible for molecular oxygen. Our group has synthesized a number of porphyrins and constructed solar cells using these compounds as the light harvesting pigments necessary to produce energy. Our goal is to determine the change in energy gathering potential and binding capability of the porphyrins to the cells based on the substituent groups bound to the parent molecule. These results will be presented as well as our progress toward optimizing a working dye-sensitized solar cell.

Solar technology is a potential way to help meet the growing demand for clean, renewable energy. Hybrid composites of inorganic quantum dots, with organic semiconducting polymers offer a potential means of producing low-cost, solution-processable photovoltaics. The synthesis of quantum dots typically involves the use of large surfactant molecules to facilitate particle growth and solubility. These native ligands act as electrical insulators that impede charge transport in photovoltaic devices. Therefore, it is necessary to exchange these large ligands with small molecules to achieve efficient charge carrier photogeneration and transport. In this research, we examine bulk heterojunction blends of low band gap PbS quantum dots with the conjugated polymer poly((4,8-bis(octyloxy)benzo(1,2-b:4,5-b')dithiophene-2,6-diyl)(2-((dodecyloxy)carbonyl)thieno(3,4-b)thiophenediyl)) (PTB1) treated with different ligands including cetyltrimethlammonium bromide (CTAB), tetrabutylammonium thiocyanate (TBAT), and 3-mercaptopropionic acid (MPA). We aim to elucidate how these different ligands influence the photovoltaic performance of PbS/PTB1blends by studying the differences in long-lived charge generation and recombination kinetics associated with the quantum dot ligand treatments using transient photovoltage (TPV) and photoinduced absorption (PIA) spectroscopy, respectively. We will also determine whether different ligand treatments influence film morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). We hope to gain a better understanding of how quantum dot ligand treatments may be used to optimize the performance of hybrid photovoltaics.

Titanium dioxide (TiO₂) displays a variety of interesting properties and has been intensely investigated for applications in environmental cleanup, photocatalysis, dye-sensitized solar cells, and semiconductor fabrication among others. However, the underlying mechanisms which govern TiO₂ chemistry are not well understood. Here, the tendency for reduced TiO₂ nanoparticles to donate stored electrons to other reagents is being characterized. The reduced ("charged") nanoparticles are made by UV irradiation which excites an electron from the valence band to the higher energy conduction band of the TiO₂ nanoparticles. In the absence of oxygen and other oxidants, the charged TiO₂ nanoparticles are stable and can be easily monitored by their absorption of visible light and blue color. We are exploring the chemical reactions of the charged particles. If the optical spectrum changes after the addition of other reagents, that is an indication that the nanoparticles are reducing the reagents. Removal of the electrons from the nanoparticles has been previously accomplished using aqueous Cu²⁺, but not Zn²⁺ or Mn²⁺. I am repeating this result and extending it to other metal ions such as Cr³⁺ in order to estimate the standard reduction potential of the charged particles. In addition, I am studying optically and via NMR whether dimethyl sulfoxide (DMSO) is reduced to dimethyl sulfide by charged TiO₂ nanoparticles. Because one-electron reduction of DMSO results in extremely unfavorable intermediates we are probing whether the reaction by charged TiO₂ occurs by the direct transfer of two electrons from the TiO₂ nanoparticles to the DMSO. These studies will provide valuable insight into the electronic chemistry of TiO₂ and will aid in the application of TiO₂ to other systems which require the transfer of multiple electrons.

Collective oscillations of conduction electrons in a metal nanoparticles, known as localized surface plasmon resonances (LSPRs), have been the source of much scientific study over the last decade due to their immediate and significant applications in biosensing, surface-enhanced Raman Spectroscopy (SERS), and light absorption engineering in semiconductor nanodevices used in solar cells. Due to the diffraction limit, many properties of LSPRs are undetectable by optical spectroscopies, creating a need for detection via electron-based probes. LSPRs can be generated as a result of high-energy electrons, such as those in an electron energy-loss (EEL) microscope, transferring energy to a nanometal’s electron cloud. This energy can follow a variety of pathways: it can be stored in the electric near-field of the nanoparticle (possibly generating "hot spots" - regions of very high electromagnetic field), radiated into the far field (becoming visible as light), or lost to thermal excitation of the metal. The purpose of this work is to study how nanoparticles distribute energy amongst these decay paths and to quantify the interactions between two adjacent nanoparticles. An interaction of significance is  the Fano effect - a destructive interference between the electric fields generated by two adjacent nanoparticles that leads to electromagnetically induced transparency. The Fano effect is studied from a theoretical perspective and is discussed in the context of energy transfer between different modes of a collective LSPR that spans both nanoparticles.

SRC-Family Kinases (SFKs) are a family of non-receptor tyrosine kinases that play key roles in intracellular signaling transduction.  They are multi-domain proteins containing two regulatory domains, SH2 and SH3, and a catalytic domain.  The two regulatory domains are vital in controlling kinase activity and interactions with other proteins in cell signaling events. Current therapeutic development strategies target the ATP binding site of the kinase domain to inhibit enzymatic activity. Recently, it has been shown that the binding of ligands to the active sites of these kinases can stabilize conformational changes in the SH2/SH3 domains modulating the accessibility of these domains necessary for protein-protein interactions, potentially providing novel kinase regulation through both enzymatic activity and protein-protein interaction. Disregulation of SFK kinases plays an important role in tumor metastasis. A recent unbiased screening of kinase mutations in cancer cells indicated a considerable amount of inactivating mutations, which indicates that there are important non-catalytic functions of kinases which play significant roles in cancer biology.  The long term goal of our study is to better understand these non-catalytic functions in SFK signaling pathways so as to help develop better approaches to treating cancers. Using an array of ATP competitive inhibitors, we have biochemically profiled some of these conformational changes in SFKs which modulate the accessibility of these regulatory domains in particular conformations to help elucidate the role these non-catalytic activities have in intracellular signaling.  So far, it has been shown that alpha C-helix-out inhibitors favor the SH2/SH3 intra-molecularly engaged, inactive conformation, while smaller Type1 inhibitors favor the extended, active conformations of these SFKs.  Currently, the plan is to further profile these conformations, as well as to determine how specific ATP binding site conformations affect SFK function in intracellular signaling. Towards this end, a panel of alpha C-helix-out and Type 1 inhibitors are being synthesized and tested.

Chemical modifications to histones, such as acetylation, phosphorylation, methylation and SUMOlyation, play a major role in dictating gene expression by changing the structure of chromatin. In particular, the modification of histone H4 by SUMO (called SUMOylation) was reported to be associated with gene repression. However, preliminary results from our lab show that the structure of SUMOylated chromatin resembles transcriptionally active, rather than silent chromatin. In order to comprehend how SUMO achieves gene silencing, biochemical studies with nucleosomes containing uniformly and site-specifically SUMOylated histones are necessary. Here we present a synthetic strategy to produce histone H4 modified by SUMO at Lysine 12. This strategy requires two native chemical ligation reactions. The first is between two fragments of H4- one synthetic and one recombinant. The second is a ligation between the SUMO-3 isoform and H4. In order to achieve the ligation of SUMO-3 to the side-chain of Lys in H4, we have developed a new ligation auxiliary. The synthesis of this auxiliary will be presented along with its application toward the total synthesis of SUMOylated histone H4. By understanding how SUMO-H4 controls gene function we hope to identify novel means to change cellular processes that result in diseases such as cancer.

 Transition-metal ions promote a wide range of vital enzymatic biological and chemical processes involving dioxygen (O₂), including photosynthetic H₂O splitting, biosynthesis of neurotransmitters, and DNA replication and repair. These are some of the most fundamental processes of life, and yet they are also some of the most poorly understood. A complete grasp of how these processes function at the chemical level is therefore of critical importance to our development of technology that improves our lives and the world around us. For example, understanding how to efficiently oxidize H₂O to O₂ is essential to the development of renewable solar fuels and fuel cells. The challenge for research lies in that these transition-metal containing enzymes are inherently difficult to probe by traditional spectroscopy methods because of their structural complexity. The difficulty in characterizing these species and their reactions, coupled with their importance in the natural world, has made them a subject of intense research across all scientific disciplines. The Kovacs research group studies the structure and reactivity of these transition-metal containing enzymes, or metalloenzymes. Our research method involves modeling a metal ion’s local environment with a ligand scaffold and implementing changes to these so-called biomimetic models that may elucidate how reactivity corresponds with various structural and electronic modifications. Spectroscopy is more diagnostic in these simpler models because the complex proteins that obscure the active site in the actual enzyme are not incorporated into the model. By comparing similarities in reactivity between the biomimetic model and the actual enzyme, we may help elucidate properties and chemistry of the enzyme itself. Preliminary work has been undertaken with a novel series of thiolate ligated, coordinatively unsaturated Co(II) complexes; the reactivity of these complexes with O₂ and O₂^- is currently being probed.

Quantum dots (QDs) are the precursor for numerous burgeoning technologies, including more efficient solar panels and high definition LED displays. QDs are small, soluble crystallites of a semiconductor material that have unique qualities since their electrons are confined in all three dimensions in a region of space smaller than the de Broglie wavelength of their electrons. This allows the electrons to occupy spectrally sharp energy levels like an element or a molecule. Their electronic properties can be tuned as a function of their size. In our lab, indium phosphide QDs are prepared under an inert atmosphere of dinitrogen by hot injection of a phosphine precursor into an indium salt and fatty acid solution. Taking aliquots of the reaction mixture at different time intervals during QD growth allows us to chart the rate of particle evolution and provides information about particle size and uniformity. Indium phosphide is a member of the III-V semiconductor class, meaning they are made from elements from column three and column five of the periodic table, and have desirable properties like direct band gaps which allow these materials to efficiently absorb and emit light as well as faster carrier mobility than II-VI quantum dots. The synthesis of III-V QDs has not allowed for size- uniformity or tunability to be achieved because of the uncontrolled reactivity of the precursors, in particular the group V precursors. Our group has recently uncovered an important acid-catalyzed pathway leading to phosphine speciation during indium phosphide QD growth. My project focuses on addressing this issue by incorporating new, more stable precursors and chelating capping agents to better stabilize the reaction products and intermediates, which would be crucial in controlling the formation and therefore the properties of the resulting quantum dots.

Electrospray ionization (ESI) is a powerful tool for transferring intact protein complexes from solution to the gas phase. ESI creates multiply charged ions with a net positive (cation) or negative (anion) charge. Although the structures of gas-phase protein cations have been investigated extensively, relatively little research addressing the structures of negatively charged protein ions exists in the literature. In my research, I use ion mobility (IM) to measure drift times, or the time an ion takes to traverse a gas-filled drift tube in the presence of a weak electric field. The drift times for ions depend on their charge and collision cross section (CCS), which to a first approximation, is the orientationally averaged projected cross section of its structure. Therefore, the drift times of ions depend on their structure. Preliminary CCS values that I have measured for protein complex anions are slightly smaller than values in the literature for the analogous protein complex cations, which suggests that the anions are more compact than the cations. One challenge in interpreting those results is the anions had a lower absolute number of charges than the analogous cations, so the results may not be directly comparable. The focus of my research is to make more direct comparisons between the structures of protein complex cations and anions. To this end, I am developing methods to reduce the number of charges on protein complex cations to values equal to those observed previously for the anions. CCS values determined for these charge-reduced cations will be directly comparable to those measured for the anions, and should reveal any structural differences between protein complex cations and anions. These results will also be useful for calibrating other IM experiments and determining how best to use IM to characterize the native structures of protein complexes.

Horseradish peroxidase (HRP) is part of a family of heme-containing metalloenzymes that reduce the O-O bond of peroxides while oxidizing a wide variety of substrates; in the case of HRP, hydrogen peroxide is reduced to water. In the presence of an oxidant and the absence of a substrate to oxidize, hydrogen peroxide coordinates to the iron cofactor of HRP, forming a ferric-hydroperoxide intermediate known as Compound 0, and subsequent O-O bond cleavage releases water and a very oxidizing ferryl-oxo porphyrin radical cation intermediate, known as Compound I. The goal of this project is to probe the potential reversibility of Compound I formation, a step traditionally thought to be irreversible. A key experiment will react HRP with unlabeled H₂O₂ in ¹⁸O-labeled water, and determine whether mixed-labeled H₂O₂ is formed. The presence of mixed-labeled H₂O₂ indicates that there is reversibility of the O-O bond cleavage that forms Compound I and its existence will be determined by addition of a water soluble phosphine that is too bulky to fit into the active site of HRP. In this case, the phosphine cannot be oxidized by Compound I, but can readily react with free hydrogen peroxide in solution to give the corresponding phosphine oxide. ³¹P-NMR will be used to determine whether the phosphine oxide is labeled because the NMR shifts of ¹⁶OPR3 and ¹⁸OPR3 are distinct. If this reaction proves to be reversible, this knowledge could then be used to describe other enzymes that catalyze oxidations with similar intermediates. This would not only be important to enzymatic systems, but possibly catalytic chemical processes.

Cysteine and homocysteine are two important amino acid biomarkers related to human health. The presence of homocysteine at high concentrations in the bloodstream is correlated with various disorders such as cardiovascular and Alzheimer's diseases. Healthy cysteine levels are important in preventing lethargy, edema, and liver damage. Because of their critical roles in human health, we report the development of fluorescent and chromogenic indicators to monitor homocysteine and cysteine concentrations rapidly and inexpensively using absorption and fluorescence spectroscopy. Several aldehyde-modified probes have been developed for thiol detection, with their function based on spectral changes associated with their respective heterocyclic products formed upon reaction with cysteine and homocysteine. These reaction products exhibit specific excitation, emission, and absorbance wavelengths related to the concentration of target analytes. In the case of fluorescein dialdehyde, our previously reported results indicated a UV-vis absorbance change and fluorescence quenching in response to both analytes. We hypothesize that judicious selection of experimental conditions will allow improved sensitivity and selectivity for specific analytes. The current study focuses on optimizing experimental conditions by evaluating several pH values and excitation wavelengths. The data shows that the response of fluorescein dialdehyde to thiols is pH-, wavelength-, and time-dependent, with difference in the responses toward cysteine and homocysteine. Further investigation of these and related compounds will elucidate the mechanism responsible for the selectivity and allow for increased utility of this class of aldehyde-modified probes

Protein kinases are enzymes that take phosphate groups from adenosine triphosphate (ATP) molecules, the energy in your body, and add them to other specific molecules inside the cell. This transfer of the phosphate group can activate or deactivate the target molecule, thus regulating cellular activities such as growth, replication, and respiration. The kinases studied here are hemopoietic cell kinases (Hck kinases) under the class of Scr kinases. Hck kinases are present in bone marrow and are often associated with myeloid leukemias and myeloproliferative disorders. Studies have shown that in the active conformation, the Hck kinase detaches two of its domains, SH2 and SH3, resulting in a more extended conformation. Using a Waters Synapt G2 HDMS, ion mobility mass spectrometry (IM-MS) techniques were used to probe the size of inactive and active Hck kinases by measuring drift times of their gas-phase ions traveling through a neutral background gas under the presence of a weak electric field. Drift times were then converted into collision cross section (CCS) values, which depend on the size and shape of the ion of interest. Eight different small molecules (< 500 Da) were used to inhibit Hck kinases, and changes in conformation were investigated using IM-MS. Preliminary data shows no significant changes in global conformation or size, conflicting with the previous studies. To investigate more subtle changes in conformation, collision induced unfolding (CIU) methods are used. By selecting an ion of interest using a quadrupole mass filter, protein unfolding is monitored using ion mobility as a function of ion activation prior to ion mobility analysis. This process allows an investigation of the subtle conformational changes in the Hck kinase upon the binding of small inhibitor molecules.

We present the results of a linear regression of exam scores for students in general chemistry versus performance in two online learning systems: WebAssign, which presents problems in a traditional manner, and ALEKS (Assessment and LEarning in Knowledge Spaces), which is an adaptive, tutorial-based system. Comparisons are made for students taking the same general chemistry course, taught by the same instructor, in the same quarter in subsequent years, where WebAssign was used one year, and ALEKS the next. We find that in WebAssign, a 1 point difference in homework score corresponded, on average, to a 0.46 point difference in final exam score (95% C I: 0.36, 0.56). In ALEKS, a 1 point difference in homework score corresponded, on average, to a 1.06 point difference in final exam score (95% C I: 0.98, 1.15). Controlling for gender and SAT scores did not change the overall conclusion. For a student, ALEKS homework scores provide a better predictor of exam performance, allowing them to focus their efforts where they are needed. For an educator, earlier signs of knowledge gaps arise in the lower homework scores, which can be addressed well before an assessment. 

Two 5-membered rings with a nitrogen at one of the fusion sites is the core structure for a variety of natural products known as pyrrolizidine alkaloids. Many of these compounds are produced by plants as a defense mechanism due to their hepatotoxicity. Other varieties of these compounds, however, have been shown to possess antiviral, anticancer, antidiabetic, and antiobesity drugs. Because of their inherent biological activity and the relative costliness of extracting these compounds from natural sources, they have become an important synthetic target. Previously in the Michael group, a palladium catalyst was developed to facilitate the addition of an N-H bond across a C=C bond. This transformation is known as hydroamination. When the protected amine and alkene are present in the same molecule, cyclization occurs, forming 5- and 6-membered nitrogen containing heterocycles. This most recent work sought to extend the capabilities of this reaction by replacing the amine protecting group with a highly electron deficient aldehyde. Thus after the initial addition of the N-H bond across the C=C bond occurs, the C=C bond will then perform a nucleophilic attack on the aldehyde forming a second ring fused to the first. This reaction sets 3 new stereocenters, forms 2 new rings, and generates a C-N and C-C bond in a single, diastereoselective step. The substrate synthesized in order to test this reaction was a 7 carbon terminal diene amine coupled with dimethyltartrate and subsequently oxidized to generate the desired diene-amide-aldehyde functionality. This substrate when submitted to the hydroamination conditions resulted in the diastereoselective formation of the tri-substituted pyrollizidine in 35% yield. Further work in this project will include application of these methods to the synthesis of several natural pyrrolizidine alkaloids. It is hoped that further manipulation of the substrate will allow expansion of the range of attainable targets to that of indolizidines and quinolizidines.

Organic photochromic compounds (OPC) undergo reversible chemical and physical changes when irradiated with the appropriate wavelength of light. These changes are manifested both at the molecular and bulk material level and include photo-induced shifts in color, refractive index, molecular length, and polarity. Such photo-controllable properties are of interest for bio-orthogonal control of biological processes, as well as in the fields of optical computing and data storage. A thorough understanding of molecular and material level structure-property relationships is imperative to enable effective design and optimization of organic photochrome structures for each specific application. Our lab is trying to create a azobenzene dye that isomerizes at about 120 hrz, within milliseconds, in the visual range of wavelength, and can be tethered to proteins. The focus was placed on physical and photophysical properties, such as isomerization wavelength, quantum yield, and decay rate to create such an azobenzene. If a usable azobenzene were created, it could be tethered to the sodium or potassium channels in the eye to initiate an action potential similar to the innate response in the eye’s photoreceptors that causes a release of neurotransmitters that, in turn, affect sodium and potassium channels causing an action potential. Used in this fashion, it can help treat the most common eye disease causing blindness, retinitis pigmentosa. In lab, I used time-resolved laser spectroscopy, fluorescence, and fluorescence lifetime analysis to analyze the three photochromic Azobenzene dyes: PheNAQ, TVI, TVI acid, and MeNAQ created by my mentor, Phillip Sullivan. 

Lily blooming has recently been suggested to result from differential growth of the petals. The tissue expands along the edges, making them longer than the midrib. To accommodate for this excess length, the petal reverses its curvature, causing the bud to open. This is the growth driven mechanism for lily blooming. We inquired into the shape of the ripples resulting from edge growth and if we could observe direct evidence of the growth. We first investigated rippling, another consequence of edge growth. When the growth rate is high enough, lily petals ripple and their edges adopt their characteristic wavy shape. Using time-lapse imaging, we observed lily petals' edges rippling. We monitored the formation of several generations of ripples, with a fractal-like pattern of smaller waves superimposed onto larger ones. We also measured the temporal evolution of the ripples' wavelength, amplitude and arc length. We found that these quantities could be related using a geometric argument. Agreement between our prediction and observations is excellent. This indicates that in addition to biology, physics plays a significant role in determining the shape of lily petals. Second, we sought to quantify edge growth. We took quantitative measurements of the different growth rates, by tracking the positions of marks along the edge and along the midrib. We found that the growth rate is 35% larger along the edge than along the midrib, supporting the edge growth driven blooming model. We now want to measure the growth rates of different lily species, and investigate whether smaller growth rates can correlate to the absence of ripples. The purpose was to understand the 3D shape resulting from growth in a 2D sheet to supply knowledge leading to understanding plant development. It will also lead to applications in the packaging industry where flat shapes are made into 3D objects.

 Double electron electron resonance (DEER) and electron nuclear double resonance (ENDOR) are two variants of electron paramagnetic resonance (EPR) spectroscopy that are useful in investigating the structures of chemical species with unpaired electrons. DEER is used to measure the distances between unpaired electrons, and ENDOR is used to measure the effect that nearby nuclear spins have on unpaired electrons. EPR experiments are conducted using microwave frequencies, with the X band (~10 GHz) and Q band (~34 GHz) being commonly used. Pulsed variants of DEER require the use of a resonator with a wide resonant bandwidth in order to accomodate two microwave pulses of different frequencies and to minimize measurement deadtime, while ENDOR requires the device to accomodate a wire coil through which radio frequency signals are sent to induce nuclear transitions, posing a technical challenge. Based on previous computational work, an tunable cylindrical resonator with a resonant frequency of ~34 GHz, has been built. The goal of this work is to evaluate the efficacy of this resonator design in pulsed EPR experiments. In addition, a radio frequency coil for use with ENDOR will be computationally designed and optimized using CST Microwave Studio, an electromagnetics modeling software package.