POTENTIAL MRI CONTRAST AGENT WITH SELECTIVE DIAGNOSTIC AND THERAPEUTIC FUNCTIONS
Jose Alvarenga, Carlos Gutierrez.
California State University, Los Angeles, Los Angeles, CA.
1,3,5,7-Tetrakis(aminomethyl)adamantane (TAA) is our parent core and has a tetrahedral symmetry (Td). We propose to convert the Td TAA symmetry to a C3v where 3 substituents are identical HOPO units and the 4th will be a targeting/solubility domain to make a molecular shuttle. This molecular shuttle will be designed to include a built-in GPS system to direct our molecule to a desired location and an antenna to track the location of the molecular shuttle at any given time. Furthermore, the proposed molecule will be designed to deliberately address its bio-distribution by inclusion of deliberate solubility and targeting domains. We are using a targeting domain that is a linear somatostatin analog. This analog targets somatostatin receptors in carcinoid tumors that are highly expressed in certain cancer cells and also meditates tumor cell growth inhibition. We are using a solubility domain that is a polyethylene glycol base group. We synthesized 1,3,5,7-Tetrakis(aminomethyl)adamantine in 80% yield to reach the target molecule. Also, MRI ligand 3-hydroxy-2-oxo-1,2-dihydropyridine-4-carboxilic acid has been synthesized in 75% yield, and the targeting domain linear somatostatin has been synthesized in 80% yield.
FULLERENE-STABILIZED GOLD NANOPARTICLES FOR PLASMONIC SOLAR CELLS
Md Islam, Juan Noveron.
The University of Texas at El Paso, El Paso, TX.
Plasmonic solar cells (PSC) are a type of solar cell which use the surface plasmon absorption generated by the nanoparticles. Because of the high molar absorption coefficient and chemical robustness, gold nanoparticles are widely used in this type of thin film solar cell. Here, we report a simple and one-step method of generating gold nanoparticles stabilized directly with fullerenes C60 that led to C60-AuNPs having high fullerenes C60 load and stability. C60-AuNPs are soluble in DMF or a mixture of DMF and water which was followed by characterized UV-Vis, FTIR, DLS, Zeta potential, XRD, TEM, and AFM. The C60-AuNPs were used in fabricating PSCs making a blend with TiO2 varying the ratio of C60-AuNPs to TiO2 to investigate thephoto-conversion efficiency.
QUANTIFICATION OF SMALL MOLECULE-PROTEIN INTERACTIONS BY FRET BETWEEN ENDOGENOUS TRYPTOPHAN RESIDUES AND THE PACIFIC BLUE FLUOROPHORE
Molly M. Lee, Kelsey E. Knewtson, Blake R. Peterson.
The University of Kansas, Lawrence, KS.
In early stage drug development, candidates are identified based on many factors, often starting with the affinity of the active compound for their biological target. For some receptor-ligand systems of medical importance, traditional binding assays can be problematic. We are investigating new methods for measuring receptor-ligand binding affinities, especially in systems where traditional binding assays have proven difficult. We hypothesize that these limitations can be overcome through the development of new assays utilizing Förster resonance energy transfer (FRET). We are investigating the utility of FRET between protein tryptophan residues and Pacific Blue as a readout for small molecule-protein interactions. Tryptophan residues are commonly found near ligand binding sites, so this assay could be applicable to a wide range of systems. To create these and related molecular probes, we have developed a new, practical synthesis that allows the preparation of multigram quantities of the Pacific Blue fluorophore. We demonstrate here the utility of this assay using 3 different receptor-ligand pairs. These include streptavidin-biotin as a model system and the known antibody-antigen binding partners, anti c-myc and c-myc tag peptide. Additionally, we describe the application of this assay to interactions of co-activator proteins with nuclear receptors, a superfamily known for its involvement in cancer progression.
INVESTIGATING THE ROLE OF PYRENE ON THE OXIDATIVE CAPACITY OF THE ATMOSPHERE
Adrian Gomez, Krishna Foster.
California State University, Los Angeles, Los Angeles, CA.
Polycyclic aromatic hydrocarbons (PAHs) are chemically generated compounds produced through incomplete combustion. PAHs are found ubiquitously in the atmosphere and are known to be carcinogenic. PAHs and volatile organic compounds (VOCs) can eventually undergo chemical aging, which is caused over time by degradation via oxidation. Furthermore, chemical aging affects the oxidative capacity of the atmosphere through the production of hydroxyl radicals. The process that induces oxidation of VOCS is called photosensitization, which is caused by a sensitizer (pyrene) becoming excited and reacting with oxygen and transferring its energy to create excited singlet oxygen (1O2), which then can react with 2,3-dimethyl-2-butene. The objective of this research is to measure the oxidation of 2,3-dimethyl-2-butene by photosensitization of 1O2 formed through energy transfer from pyrene in the condensed phase. The products formed will be separated and analyzed using high performance liquid chromatography (HPLC) equipped with ultraviolet-visible and fluorescence detectors, and its chemical structure will be elucidated using nuclear magnetic resonance spectroscopy. The results of the photosensitization reaction show that a product was formed with a vinyl doublet at 5.1ppm, suggesting a terminal alkene was formed.
IN SITU SEED-GROWTH METHOD TO FABRICATE GOLD NANOCUBES AND GOLD NANOOCTAHEDRONS
Maria T. Perez-Cardenas, Zhihong Nie.
University of Maryland, College Park, MD.
Nano materials are of great interest due to their novel physiochemical properties not found in bulk materials. The physiochemical properties arise from the material’s size, shape, and composition. One of the challenges in the field of nano science is to obtain reproducible and scalable high quality homogeneous nanostructures, i.e., structures with a single shape and size. Chemical vapor deposition and lithography provide the highest quality nanostructures; but these methods rely on complex, expensive techniques. On the other hand, wet chemical methods such as seed-mediated-growth and in situ seed growth are simple and inexpensive methods; however, they generate nanostructures with low quality and low reproducibility. To address this challenge, we investigated the kinetic parameters that drive gold nanostructures’ growth in aqueous wet chemical methods. Our study indicates that the final shape of gold nanostructures, either gold cube or gold octahedron, is subjected to the nucleation rate, which is highly dependent on the reduction rate of the gold precursor. We conducted a systematic study of gold precursor reduction with L-ascorbic acid under different conditions such as pH, temperature, and mole ration as well as using other reducing agents analogous to L-ascorbic acid. Based on our data analysis, we found that the major factor affecting the fabrication of high quality of gold nanostructures is the interaction of L-ascorbic acid with gold precursor. Our results reveal useful information that can be used to develop cost-effective, scalable methods to fabricate high quality gold nanostructures suitable for biosensors and photovoltaic devices.
Catalysis is a remarkable synthetic tool enabling the efficient preparation of complex molecules valued in today’s society such as medicines, pesticides, and materials. To date, transition metals have typically been the catalysts of choice. However, as concerns grow about the sustainability of catalytic processes, small organic molecules are emerging as environmentally friendly alternatives to transition metals. Specifically, urea catalysts have demonstrated valuable transformations in the formation of carbon-carbon and carbon-heteroatom bonds. We envisioned that ureas would activate nitrimine reagents for the cross coupling of a variety of nucleophiles to create new sterically hindered bonds. We found that nitrimines readily participate in the urea catalyzed cross coupling of amines to afford previously inaccessible enamines and in carbon-to-carbon cross coupling reactions to yield highly substituted alkenes. This sustainable approach for cross coupling reactions benefits from mild, metal-free conditions and provides an attractive avenue toward the construction of biologically active target molecules. The results of our discoveries, including substrate scopes and proposed modes of action, will be presented.
MANIPULATION OF LIGHT AND ELECTRONS WITH SUBMOLECULAR RESOLUTION
Laura Rios, Nick Tallarida, Joonhee Lee, Ara Apkarian.
University of California, Irvine, Irvine, CA.
Recent spectroscopic experiments reveal machinations of single-molecule chemistry with sub-molecular spatial resolution. This presentation encompasses highlights from 2 major experiments, introducing viewers to single-molecule chemistry and exploring the frontiers of the field as technological applications become apparent. Both experiments have significant implications in hetereogenous catalysis, which we hypothesize is the most important physical problem to be elucidated. It is clear that out of many catalytic sites, few offer catalytic activity. In our experiments, it is clear that the presence of a catalytic site (e.g., an adatom on the surface) may not necessarily provide the catalytic activity for the reaction (isomerization) to take place. Therefore, it is important to study these systems to gain insight into catalytic physics. In both experiments, a scanning tunneling microscope (STM) was used to image the molecules and manipulate their electronic environments. Our ultimate goal was to observe single-molecule, tip-enhanced Raman spectroscopy (TERS). Initially, we injected electrons into a porphyrin derivative to create a Jahn-Teller active anion. The electron density was visualized as the molecule underwent a conductance switch. These experiments have implications in molecular electronics. In the second set, an azobenzene derivative was interrogated spectroscopically with a 532 nm laser. Our results included 2 distinct, anti-correlated spectra, suggesting 2 forms of the molecule existed in mutual exclusivity, and indicating single-molecule behavior. We came away with several innate questions of light-adsorbate interaction such as the catalytic role of the nano-metallic junction of the STM, and the origin of selective, large shift of the Raman spectra.
SUPER LIPOSOMES: TARGETED COMBINATION THERAPIES FOR INDUCING CELL DEATH IN CANCER CELLS
Magaly Salinas, George R. Negrete.
The University of Texas at San Antonio, San Antonio, TX.
A cysteine-derived acrylamide platform was envisaged as a chemical core to which lipid and peptide ligands or reporter groups could be readily attached in a highly modular process. The L-cysteine-derived core supports carboxylic acid, aryl nitro, and acryloyl substituents. A thiol lipid module was conjugated to the thiazolidine acrylamide, and the nitro group was reduced to the corresponding amine to generate a novel cysteine lipid analogue (CLA). Fmoc protection generates a construct that functions as a component in solid-phase peptide synthesis (SPPS) of lipopeptides such as EPDIM-CLA. The EPDIM sequence, known for binding to α3β1 integrin receptors and inducing apoptosis in cancer cells, serves a dual function as a targeting ligand and as a therapeutic agent. The synthesized EPDIM-CLA lipopeptide will be incorporated into PEGylated liposomal doxorubicin formulation (DOXIL®) to demonstrate that 1) the targeting lipopeptide attaches to the surface of DOXIL®, 2) enables binding of the targeting liposome to cancer cells, and 3) the targeted liposomes promote cell death in cancer cells. In future work, this multi-component system can be tailored to incorporate any targeting lipopeptide or drug-releasing ligand while encapsulating a chemotherapeutic drug, such as doxorubicin, in a liposomal formulation yielding a “super liposome” for targeted combination therapies. [Support for this research was provided by NIGMS RISE GM060655.]