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School of Chemistry and Biochemistry

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College of Sciences

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Now showing 1 - 10 of 166

Remediation Mercuric Ions via Functionalized Magnetic Nanoparticles

(Georgia Institute of Technology, 2013-12-12) Bennett, Austin Landry

Mercuric ions, Hg2+, display a unique affinity for sulfur-containing biomolecules because of the soft acid/soft base interaction between Hg2+ and sulfur.1 Many of these biomolecules are used in signal processing and response;2 therefore, Hg2+ is a potent neurotoxin. Chronic exposure to high Hg2+ levels can lead to mercury-poisoning and even death. This research focused on removing Hg2+ from water. Cobalt ferrite nanoparticles were used to separate Hg2+ ions from water. A fair amount of research has been conducted using ferromagnetic nanoparticles and various nitrogenous and oxygen-based ligands, such as triazene compounds and tartrate ligands, to remediate mercuric ions.3,4 Magnetic nanoparticles (MNPs) were coated with thiol-containing carboxylic acid ligands to bind Hg2+ ions. To combat thiol oxidation, the weak reducing agent dithiothreitol (DTT) was introduced into the Hg2+ solutions. The density of the particles in the Hg2+ solutions and exposure times were varied in order to determine the optimal density and exposure time for Hg2+ removal. In future work, thiol-containing organosilane ligands will be coated onto the particles and tested for Hg2+ removal to be compared against the carboxylic acid ligands.
The evaluation of novel anti-inflammatory compounds in cell culture and experimental arthritis and identification of an inhibitor to early-stage loblolly pine somatic embryo growth

(Georgia Institute of Technology, 2013-11-19) Lucrezi, Jacob

The interactions between the immune and nervous systems play an important role in immune and inflammatory conditions. Substance P (SP), the unidecapeptide RPKPQQFFGLM-NH2, is known to upregulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α. We report here that 5 (Acetylamino) 4 oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me) and 4 phenyl 3 butenoic acid (PBA), two anti-inflammatory compounds developed in our laboratory, reduce SP stimulated TNF-α expression in RAW 264.7 macrophages. We also show that AOPHA Me and PBA both inhibit SP stimulated phosphorylation of JNK and p38 MAPK. Furthermore, molecular modeling studies indicate that both AOPHA Me and PBA dock at the ATP binding site of apoptosis signal regulating kinase 1 (ASK1) with predicted docking energies of -7.0 kcal/mol and 5.9 kcal/mol, respectively; this binding overlaps with that of staurosporine, a known inhibitor of ASK1. Taken together, these findings support the conclusion that AOPHA Me and PBA inhibition of TNF-α expression in SP-stimulated RAW 264.7 macrophages is a consequence of the inhibition JNK and p38 MAPK phosphorylation. We have previously shown that AOPHA-Me and PBA inhibit the amidative bioactivation of SP, which also would be expected to decrease formation of pro-inflammatory cytokines. It is conceivable that this dual action of inhibiting amidation and MAPK phosphorylation may be of some advantage in enhancing the anti-inflammatory activity of a therapeutic molecule. We also encapsulated AOPHA-Me separately in polyketal and poly(lactic co glycolic acid) microparticles. The in-vitro release profiles of AOPHA-Me from these particles were characterized. We have also shown that AOPHA-Me, when encapsulated in PCADK microparticles, is an effective treatment for edema induced by adjuvant arthritis in rats. In separate work, it was determined that myo inositol 1,2,3,4,5,6 hexakisphosphate is an inhibitor to early-stage Loblolly pine somatic embryo growth. In addition, it was determined that muco inositol 1,2,3,4,5,6 hexakisphosphate is not an inhibitor to early-stage Loblolly pine somatic embryo growth. These experiments demonstrate the stereochemical dependence of myo inositol 1,2,3,4,5,6 hexakisphosphates inhibitory activity.
Dynamical simulation of structured colloidal particles

(Georgia Institute of Technology, 2013-11-06) Hagy, Matthew Canby

In this thesis, computer simulations are used to study the properties of new colloidal systems with structured interactions. These are pair interactions that include both attraction and repulsion. Structured colloids differ from conventional colloids in which the interactions between particles are either strictly attractive or strictly repulsive. It is anticipated that these novel interactions will give rise to new microscopic structure and dynamics and therefore new material properties. Three classes of structured interactions are considered: radially structured interactions with an energetic barrier to pair association, Janus surface patterns with two hemispheres of different surface charge, and striped surface patterns. New models are developed to capture the structured interactions of these novel colloid systems. Dynamical computer simulations of these models are performed to quantify the effects of structured interactions on colloid properties. The results show that structured interactions can lead to unexpected particle ordering and novel dynamics. For Janus and striped particles, the particle order can be captured with simpler isotropic coarse-grained models. This relates the static properties of these new colloids to conventional isotropically attractive colloids (e.g. depletion attracting colloids). In contrast, Janus and striped particles are found to have substantially slower dynamics than isotropically attractive colloids. This is explained by the observation of longer-duration reversible bonds between pairs of structured particles. Dynamical mapping methods are explored to relates the dynamics of these structured colloids to isotropically attractive colloids. These methods could also facilitate future nonequilibrium simulation of structured colloids with computationally efficient coarse-grained models.
Seeded growth of noble metal nanocrystals

(Georgia Institute of Technology, 2013-11-06) Zheng, Yiqun

This research emphasizes on the use of seeded growth in synthesis of noble metal nanocrystals with precise control over the size, shape, and composition. In the first part of this work, I have produced Au nanocrystals with single-crystal structure and truly spherical profiles and investigated their optical properties and self-assembly as induced by dilution with water. These Au nanospheres were generated in high yield and purity, together with controllable sizes continually increased from 5 to 150 nm. I also found these Au nanospheres self-assembled into dimers, larger aggregates, and wavy nanowires, respectively, as diluted with water. In the second part of this work, I demonstrate the kinetic control can be implemented to control the shape of mono- and bi-metallic nanocrystals in seeded growth. The as-prepared single-crystal nanospheres of Au were employed as seeds to synthesize of tetrahedral Au nanocrystals and Au@Pd core-shell nanocrystals with six distinct shapes. The success of the two demonstrations relies on manipulation of reaction kinetics to achieve different product shapes. The reaction kinetics was controlled by varying a set of reaction parameters, including the type and concentration of capping agent, the amount of reductant, and the injection rate of metal precursor solution. In the final part of this work, I will discuss an unusual change in crystallinity observed in seeded growth of Au nanocrystals on Au seeds. In particular, single-crystal Au seeds treated with a chemical species could develop twin defects during the seed-mediated growth process to yield multiply twinned products.
Thermal desorption, photodesorption, and photodissociation of water on amorphous ice and lunar surfaces

(Georgia Institute of Technology, 2013-11-06) DeSimone, Alice Johnson

The temperature-programmed desorption profiles of water from three lunar analogs were measured. These experiments showed that glassy materials were hydrophobic, that water on multiphase materials occupied a continuum of adsorption sites, and that feldspar exhibited significant chemisorption of water. The competition between photodissociation and photodesorption of amorphous solid water (ASW) was investigated on three substrates: copper with a thin oxide coating, an impact melt breccia from Apollo 16, and a mare basalt from Apollo 17. The rotational temperature of desorbing H₂O did not vary significantly with substrate, but the H₂O time-of-flight spectra were broader on the lunar slabs than on copper. Additionally, the cross sections for water removal at low coverages were higher on the lunar slabs than on copper. O(³PJ) produced by 157-nm irradiation of ASW on the same three substrates was measured as a function of spin-orbit state, H₂O exposure, and irradiation time. The same Maxwell-Boltzmann components were present in each case, with translational temperatures of 10,000 K, 1800 K, 400 K, and the surface temperature, but the relative intensities of these components differed widely between substrates. Evidence for diffusion out of pores in the ASW and in the lunar slabs was observed for H2O exposures of at least 1 Langmuir. Cross sections for H2O and O(3PJ) depletion due to 157-nm irradiation of ASW were applied to icy grains in the rings of Saturn, and corresponding cross sections on the lunar substrates were used to estimate the flux of water desorbing from the Moon and the density of oxygen atoms in the lunar atmosphere.
Towards a low temperature synthesis of graphene with small organic molecule precursors

(Georgia Institute of Technology, 2013-09-03) Vargas Morales, Juan Manuel

Graphene, a 2D honeycomb lattice of sp² hybridized carbons, has attracted the attention of the scientific community not only for its interesting theoretical properties but also for its myriad of possible applications. The discovery of graphene led to the Nobel Prize in physics for 2010 to be awarded to Andrei Geim and Konstantin Novoselov. Since its discovery, many methods have been developed for the synthesis of this material. Two of those methods stand out for the growth of high quality and large area graphene sheets, namely, epitaxial growth from silicon carbide (SiC) and chemical vapor deposition (CVD). As it stands today, both methods make use of high concentrations of hydrogen (10-20%) in N₂ or Ar, high temperatures, and a vacuum system. Epitaxial growth from SiC in addition requires very expensive single crystal SiC wafers. In the case of CVD, organic molecules are used as the carbon source to grow graphene on a metal substrate. Although graphene has been grown on many metal substrates, the experiments highlighted here make use of copper as the metal substrate of choice since it offers the advantage of availability, low price, and, most importantly, because this substrate is self-limiting in other words, it mostly grows single layer graphene. Because the CVD method provides with a choice as for the carbon source to use, the following question arises: can a molecule, either commercially available or synthesized, be used as a carbon source that would allow for the synthesis of graphene under low temperatures, low concentrations of hydrogen and at atmospheric pressure? This dissertation focuses on the synthesis of graphene at lower temperatures by using carbon sources with characteristics that might make this possible. It also focuses on the use of forming gas (3% H₂ and 97% N₂ or Ar) in order to make the overall process a lot safer and cost effective. This dissertation contains two chapters on the synthesis of organic molecules of interest, and observations about their reactivity are included. CVD experiments were performed at atmospheric pressure, and under vacuum. In both instances forming gas was used as the annealing and carrier gas. Results from CVD at atmospheric pressure (CVDAP), using organic solvents as carbon sources, show that at 1000℃, low quality graphene was obtained. On the other hand, CVD experiments using a vacuum in the range of 25 mTorr to 1 Torr successfully produced good quality graphene. For graphene growth under vacuum conditions, commercially available and synthesized compounds were used. Attempts at growing graphene at 600℃ from the same carbon sources only formed amorphous carbon. These results point to the fact that good quality graphene can basically be grown from any carbonaceous material as long as the growth temperature is 1000℃ and the system is under vacuum. In addition to the synthesis of graphene at low temperatures, there is a great amount of interest on the synthesis of graphene nanoribbons (GNR’s) and, as with graphene, several approaches to their synthesis have been developed. One such method is the synthesis of GNRs encapsulated in carbon nanotubes. Experiments were conducted in which aluminosilicate nanotubes were used. These nanotubes provided for an easier interpretation of the Raman spectrum since the signals from the nanotubes do not interfere with those of the GNR’s as in the case when carbon nanotubes are used. The use of aluminosilicate nanotubes also allowed for the successful synthesis of GNR’s at temperatures as low as 200℃ when perylene was used as the carbon source.
High χ block copolymers for sub 20 nm pitch patterning: synthesis, solvent annealing, directed self assembly, and selective block removal

(Georgia Institute of Technology, 2013-09-03) Jarnagin, Nathan D.

Block copolymer (BCP) thin film patterns, generated using directed self-assembly (DSA) of diblock copolymers, have shown excellent promise as templates for semiconductor device manufacturing since they have the potential to produce feature pitches and sizes well below 20 nm and 10 nm, respectively, using current 193 nm optical lithography. The goal of this work is to explore block copolymers with sufficient thermodynamics driving force (as described by the Flory Huggins interaction parameter, χ) for phase separation at these smallest lengths scales. Here, poly(styrene)-b-poly(hydroxystyrene) is investigated since the PHOST domain is known to form extensive hydrogen bond networks resulting in increased χ due to this strong enthalpic interaction. In this work, nitroxide mediated polymerization (NMP) techniques were utilized to produce PS-b-PHOST diblock copolymers with a range of molecular weights (5000-30000) with low PDI approaching 1.2. The phase separation of low molecular weight PS-b-PHOST on neutral underlayer substrates via solvent annealing provided thin film vertical lamellae with 13 nm pitch. These results illustrate the improved resolution of PS-b-PHOST compared with the current industry standard of PS-b-PMMA (with 20 nm pitch). The directed self assembly of lamellar PS-b-PHOST patterns with 18 nm pitch via graphoepitaxy is demonstrated. Also, a highly selective atomic layer deposition (ALD) and etch technique was investigated which provided selective block removal of (PS-b-PHOST) block copolymer patterns which initially exhibited no inherent etch contrast. In this process, the PS domain is removed leaving a high fidelity etch relief pattern of the original block copolymer template. Finally, an alternative system is presented, namely Poly(trimethylsilylstyrene)-block-poly(hydroxystyrene) (PTMSS-b-PHOST), which utilizes silicon containing functionality in one of the blocks, providing high etch contrast. PTMSS-b-PHOST patterns were also exposed to oxygen plasma allowing selective block removal of the PS domain without the need for additional ALD processing steps.
Design and synthesis of molecular resists for high resolution patterning performance

(Georgia Institute of Technology, 2013-08-28) Cheshmehkani, Ameneh

In this thesis, different approaches in synthesizing molecular resist are examined, and structure-property relations for the molecular resist properties are studied. This allows for design of resists that could be studied further as either negative or positive tone resists in photolithography. A series of compounds having different number of acrylate moiety, and different backbones were investigated for photoresist application. Thermal curing of acrylate compounds in organic solvent was also examined. Film shrinkage, as well as auto-polymerization was observed for these compounds that make them unsuitable as photoresist material. Furthermore, calix[4]resorcinarenes (C4MR) was chosen as backbone, and the functional groups was selected as oxetane and epoxy. Full functionalized C4MR compounds with oxetane, epoxy and allyl were synthesized. Variable-temperature NMR of C4MR-8Allyl was studied in order to get a better understanding of the structure’s conformers. Energy barrier of exchange (ΔG#) was determined from coalescence temperatures, and was 57.4 KJ/mol for aromatic and vinyl hydrogens and 62.1 KJ/mol for allylic hydrogens.
Gold nanoparticles in some chemical and photothermal applications of cancer therapy

(Georgia Institute of Technology, 2013-08-23) Mackey, Megan A.

Gold nanoparticles exhibit an array of properties, both intrinsic (chemical) and extrinsic (photothermal), that can be exploited for their use in cancer therapeutics. Owing to their size and ease with which they can be functionalized with various ligands, gold nanoparticles represent a class of highly functional biomedically relevant nanostructures. Here, we explore the use of gold nanoparticles as intrinsic (chemical) antineoplastic agents, with their ability to cause DNA damage and cytokinesis arrest, to induce apoptosis in a metallic composition-dependent manner, as well as their ability to enhance sensitivity to chemotherapy by regulation of the cell cycle. The extrinsic (photothermal) properties of gold nanoparticles are also examined, in detail, through both theoretical and experimental assessment, for their use as photothermal contrast agents in vitro. Based on this assessment, the gold nanoparticles are tested in the plasmonic photothermal therapy of head and neck cancer in a mouse model.
New insights into targeting the androgen receptor for cancer therapy: from selective delivery of gold nanoparticles and histone deacetylase inhibitors, to potent antagonists and inverse agonists

(Georgia Institute of Technology, 2013-08-23) Gryder, Berkley Eric

Cancer is the second leading cause of death in the United States (more than half a million people each year), and even with billions of dollars in medical effort patients are rarely cured. This dissertation research is devoted to meeting this medical need by providing new cancer therapeutics that are more potent and safer than current chemotherapies. This is achieved by using two state of the art anticancer “warheads”: 1) gold nanoparticle (AuNP) technology and 2) a new class of epigenetic anticancer small molecules, histone deacetylase inhibitors (HDACi). These warheads are then selectively delivered to cancer cells via “homing devices” targeted to receptors that are overexpressed in the cancers. This work primarily focuses on the androgen receptor (AR) to target prostate cancer. The 1st chapter sets the stage, providing scientific rationale and background for the central hypothesis: small molecules that engage the AR can, upon conjugation to a therapeutic agent, enable selective delivery of that agent to prostate cancer cells. Chapter 2 delves into the structural molecular biology of the androgen receptor. There is a survey of the crystallographic data for all nuclear receptors, providing structural information which is used to build AR homology models for antagonist and inverse agonist modes of ligand binding. These models are used to design AR targeting ligands (Chapters 3, 5, 6 and 7). The application of the targeting technology is illustrated by attaching them to AuNPs for selective delivery to prostate cancer cells (Chapter 3). Next, in order to appreciate the importance of using targeting agents in HDACi cancer therapeutics, we reviewed this recently emerged field in Chapter 4. In this chapter we argue that the failure of HDACi in solid tumors, despite more than 500 clinical trials in the last decade, is primarily due to an inability of these small molecules to accumulate at effective concentrations in the cancer. We provide an analysis of the paradigms being pursued to overcome this barrier, including HDAC isoform selectivity, localized administration, and targeting cap groups to achieve selective tissue and cell type distribution. In Chapter 5, this last approach (targeting cap groups, or a “homing device”) is illustrated with HDACi targeted to prostate cancer via antiandrogens that bind the AR. The second generation of improved “homing devices” is disclosed in Chapter 6 (for both AuNPs and HDACi), in addition to preliminary ADMET data and safety studies in mice. Excitingly, our three dimensional understanding of binding to the AR allowed design and structure-activity-relationship studies that lead to the first reported examples of AR inverse agonists (Chapter 7) Several points of significance: • AuNP targeted to AR ∙ have the strongest binding affinity ever reported (IC50 ~14 picomolar) ∙ are actively recruited to prostate cancer cells ∙ overcome treatment resistance in advanced prostate cancer cells ∙ exhibit nanomolar anticancer potency ∙ resolved the identity of the “membrane AR” as the GPRC6A • HDACi targeted to AR ∙ have HDACi activity and AR binding affinity superior to their clinical precursors ∙ exhibit potent AR antagonist activity ∙ induce AR translocation to the nucleus in a HDACi dependent fashion ∙ selectively and potently kill prostate cancer cells that express AR ∙ are safer than Tylenol®, as tested in small animals • Pure AR binding ligand studies ∙ resulted in the discovery of the first examples of AR inverse agonists, which are vastly more potent that clinically available antiandrogens for prostate cancer ∙ work via a never-before-seen mechanism of action, by localizing to the nucleus and recruiting corepressors to actively shut off AR genes