Benzophenone photoprobes for chemical proteomics and drug target identification
Year of Dissertation:
2011
Benzophenone photoprobes are widely used in photoaffinity-labeling studies, especially for the characterization of ligand-receptor interaction. Photolabeling studies using benzophenone, however, are by no means routine experiments. It is not uncommon that carefully designed photoligands fail to label target proteins. In order to get insights into the important factors that affect the photolabeling efficiency, we conducted a structure-activity relationship study (SAR) on adenine-benzophenone photoligands. The study suggested that conformational flexibility was the determining factor that controls the photolabeling efficiency by benzophenone photoprobes.
Chiral Sulfurization For Synthesis Of Antisense Oligonucleotides
Year of Dissertation:
2010
Chapter 1: Antisense and RNA interference (RNAi) reagents are two of the most widely studied oligonucleotide-based therapeutics. Phosphorothioate oligonucleotide, an antisense reagent, has a stereogenic center at the phosphorothioate linkage and in the absence of enantioselective synthesis, a mixture of diastereomers results. Stereodefined phosphorothioates have shown greater antisense activity; however, only a few research groups have successfully designed methods for enantioselective synthesis of phosphorothioates with >98% de, albeit in low yields. This dissertation presents a conceptually different method for enantioselective synthesis of phosphorothioate oligonucleotides via a Curtin-Hammett system that requires epimerization of the phosphite triester on the reaction time scale and selective sulfurization of one of the equilibrating epimers with a chiral sulfurizing reagent.
SYNTHESIS, CHARACTERIZATION, RAMAN, AND SURFACE ENHANCED RAMAN STUDIES OF SEMICONDUCTOR QUANTUM DOTS
Year of Dissertation:
2012
The major contributions and discoveries of the dissertation include: (1) Homogeneous nucleation processes for the formation of nanocrystals can occur at low temperature and do not need to proceed at high temperature to overcome a high energy barrier. Monodisperse PbS quantum dots (QDs) obtained with nucleation and growth at 45°C support this finding. (2) Monodisperse single elemental Se QDs can be produced by simple solution crystallization from TDE (1-tetradecene) or ODE (1-octadecene). (3) TDE is a better non-coordinating solvent compare to ODE. STDE (S dissolved in TDE) and SeTDE (Se dissolved in TDE) are stable reagents with long storage time. They can be used as universal precursors for S-containing and Se-containing QDs. (4) QDs synthesis can be carried out at low temperature and relatively short reaction time using the simple, non-injection, one-pot synthetic method. (5) The one-pot method can be extended for the synthesis of QDs and graphene oxide nanocomposites and metal and graphene oxide nanocomposites. (6) PbCl2-OLA (oleylamine) is a universal system for the synthesis of Pb-chaclogenides QDs. (7) Surface enhanced Raman spectroscopy (SERS) is used to probe both size and wave length dependent quantum confinement effects (QCEs) of PbS QDs. (8) Raman spectroscopy is a powerful tool to elucidate crystal structure of Se nanoclusters with size of 1-2 nm.
Applications of Bionanotechnology
Year of Dissertation:
2011
The aim of nanotechnology is to devise technologies at the crossroads of chemistry, physics and biology to shape matter at the atomic scale to form nanosized functional objects and to arrange them into intricate assemblies to elaborate new devices. Today, its biological aspect is largely emphasized to tackle biomedical issues such as pathogen identification, disease diagnosis and treatment. In this respect, interdigitated electrodes were employed to monitor the presence of harmful bacteria, then to attempt to detect human PC3 carcinoma prostate cells as well as the size variation of stimulus-responsive hydrogel beads designed for drug delivery. Our second project aimed at demonstrating the potential use of TiO2-labeled antibodies as substitute for horse-radish peroxidase-labeled antibodies for Enzyme-Linked ImmunoSorbent Assays (ELISA). Our last project revolved around harnessing the enzymatic activity of urease to grow silver-sulfide nanoparticles.
FACTORS AFFECTING THE REMOVAL OF AMMONIA FROM AIR ON CARBONACEOUS ADSORBENTS: INVESTIGATION OF REACTIVE ADSORPTION MECHANISM
Year of Dissertation:
2011
Air pollution related to the release of industrial toxic gases, represents one of the main concerns of our modern world owing to its detrimental effect on the environment. To tackle this growing issue, efficient ways to reduce/control the release of pollutants are required. Adsorption of gases on porous materials appears as a potential solution. However, the physisorption of small molecules of gases such as ammonia is limited at ambient conditions. For their removal, adsorbents providing strong adsorption forces must be used/developed.
PEPTIDE NANOTUBES AND THE EXPERIMENTAL DESIGN INTEGRATING NANOPARTICLES FOR USE IN NANOELECTRONICS
Year of Dissertation:
2009
Scientists have just begun to explore the world of nanotechnology, as
SELF-ORGANIZED PORPHYRIN NANOMATERIALS FOR SOLAR ENERGY HARVESTING
Year of Dissertation:
2010
New concepts in the design and function of organic dyes as sensitizers for solar energy harvesting are needed. Commercial viability constrains these designs: (a) cost effective synthesis, (b) long-term stability, and (c) an important goal is to reduce the environmental impact of the product at the end of its life cycle. Simple porphyrinoid dyes meet these constraints, but new modes of incorporation into devices are needed to increase the efficiency of charge separation that drives any photonic device designed to harvest light. In this thesis, we will show how complex material architectures on surfaces need not to be the result of complex molecular structures or strong intermolecular forces that form in solution and deposit intact onto surfaces. Varying environmental conditions we can dictate morphology of self-organized structures on surfaces. These studies provide further insights into the design principles, processing, and extent of electron and energy transfer in supramolecular porphyrin materials. We are also developing a new strategy to couple porphyrinoid dyes to oxide surfaces using hafnium and zirconium metalloporphyrins and metallophthalocyanines.
New Ruthenium (II)-Chloroquine Complexes and Metal-Free Aminoquinolines: Synthesis, Antimalarial Activity and Mechanism of Biological Activity
Author:
Chandima Rajapakse
Year of Dissertation:
2010
Advisor:
Roberto Sanchez-Delgado
New Ruthenium (II)-Chloroquine Complexes and Metal-Free
De Novo Designed Safranine Enzymes
Year of Dissertation:
2012
ABSTRACT
DESIGN AND SYNTHESIS OF SQUARAMIDE -BASED MOLECULAR MACHINES
Author:
Vijayakumar Ramalingam
Year of Dissertation:
2009
Advisor:
Prof. Rajeev Muthyala
Artificial molecular machines are sought after in a wide variety of fields. They are useful in the construction of nanodevices (molecular valves, brakes, nanocars, rotors and ratchets), for ion transport and also for optical data storage. In an effort to develop new ion-transportand drug delivery strategies we became interested in designing molecular machines based on amide derivatives of squaric acid (squaramides). In this study, we first determined that secondary diaryl squaramides, which exist in the extended ZZ conformation, are excellent neutral receptors for biologically important anions such as chloride, carboxylate, and dihydrogen monophosphate. Next, we envisioned a molecular valve approach to regulate anion binding to squaramides via changes in the external environment (for example, a change in solvent polarity). We reasoned that in non-polar solvents, intramolecular hydrogen bonding between the carbonyl groups and the squaramide NHs would block anion binding (OFF state) while in a polar solvent disruption of intramolecular hydrogen bonding and reorientation of the carbonyl allows anion binding (ON state). Using ortho benzoyl substituted squaramides, we successfully applied the molecular valve approach to chloride binding. We subsequently studied the generality of the molecular valve approach with other ortho substituents such as secondary and tertiary amides, esters, and nitro groups. We found that the success of the molecular valve approach depends on whether, in a given solvent, intra-molecular hydrogen bonding is stronger or weaker relative to intermolecular hydrogen bonding with chloride ion. A significant effort was also spent on developing tertiary squaramide-based molecular machines for drug delivery. Initial studies revealed that simple (for example, N, N'-dimethyl derivatives) tertiary diaryl squaramide exhibited a preference for folded EE conformation regardless of solvent polarity. For our goal of transforming these squaramides to functional molecular machines, we decided to exploit the hydrophobic effect. In nonpolar solvents we anticipated that the tertiary squaramides would exhibit a preference for EE conformation while in aqueous medium we reasoned that the conformation would switch to ZZ driven by the hydrophobic effect. However we soon experienced major synthetic challenges. The literature procedures for the synthesis of these tertiary aryl squaramides routinely resulted in low yields with significant squaraine impurities. We therefore developed a novel copper-based method to synthesize symmetrical tertiary diaryl squaramides. Importantly, this method also enabled synthesis of unsymmetrical tertiary diaryl squaramides. Syntheses, conformational preferences, and our attempts at developing hydrophobically driven molecular machines will also be discussed in this dissertation.