No description available.

No description available.

No description available.

No description available.

The localized surface plasmon resonance (LSPR), arising due to the collective oscillation of free electrons in metal nanoparticles, is a sensitive probe of the nanostructure and its surrounding dielectric medium. Synthetic strategies for developing surfactant free nanoparticles using ultrafast lasers providing direct access to the metallic surface that harvest the localized surface plasmons will be discussed first followed by the applications. It is well known that the hot carriers generated as a result of plasmonic excitation can participate and catalyze chemical reactions. One such reaction is the dissociation of hydrogen. By the virtue of plasmonic excitation, an inert metal like Au can become reactive enough to support the dissociation of hydrogen at room temperature, thereby making it possible to optically detect this explosive gas. The mechanism of sensing is still not well understood. However, a hypothesis is that the dissociation of hydrogen may lead to the formation of a metastable gold hydride with optical properties distinct from the initial Au nanostructures, causing a reversible increase in transmission and blue shift in LSPR. It will also be shown that by tracking the LSPR of bare Au nanoparticles grown on a substrate, the adsorption of halide ions on Au can be detected exclusively. The shift in LSPR frequency is attributed to changes in electron density rather than the morphology of the nanostructures, which is often the case. / Chemistry

Droplets are ubiquitous microscopic systems - ranging in size from several nanometers to ~100 micrometers – that undergo abundant environmental interactions. Researchers have shown that droplets can impact both earth climate and air quality through physical and chemical processes. Droplets released from the human respiratory system, either suspended in air or deposited on surfaces, can carry pathogens (e.g., influenza viruses, the SARS-CoV-2 virus), and are thus important for disease transmission. The need to understand the role of droplets in environmental processes requires appropriate tools for droplet characterization. We used Raman and surface-enhanced Raman spectroscopy (SERS) based imaging as such tools due to their capacity for simultaneous collection of abundant molecular information inside droplets and their potential to collect detailed images of droplet component distributions. We imaged pH and chemical moiety distributions inside droplets over a wide range of: 1) droplet compositions; 2) surrounding environmental conditions (relative humidity, temperature); and 3) droplet morphologies. This dissertation describes measurement of droplet pH in droplets containing mixtures of phosphate buffer (PB), one of the most commonly used biological solvents, and ammonium sulfate (AS), arguably the most abundant chemical species in atmospheric droplets, at room temperature. We observed a pH gradient inside PB droplets while a homogeneous pH distribution was found inside AS droplets, thus showing a significant pH effect due to droplet composition. We attributed the contrasting pH distribution in the two droplet systems to different ionic interactions at the air-water interface. In addition, we obtained AS droplet images at 223K to investigate ice nucleation upon freezing. We observed variable nucleation behavior in AS droplets as a function of concentration, a finding with implications for atmospheric cloud nucleation. We also investigated virus deposition during sessile droplet evaporation using gold nanoparticles. SERS imaging enabled development of correlations between virus viability and droplet deposition pattern and related them in terms of the coffee-ring effect. Suppression of the coffee-ring effect can reduce virus infectivity on surfaces during droplet evaporation. These works collectively exhibit the potential of Raman and SERS imaging for droplet characterization. / Doctor of Philosophy / Droplets are ubiquitous in the environment. Small droplets can form clouds and fogs, and are often micro- to nano-scale in size. Droplets can either grow or shrink in the environment when they absorb or lose water. Similarly, reactions may happen when droplets contain various species. Droplets in human breath exhalate may contain pathogens, such as the SARS-CoV-2 virus that is the cause of the COVID-19 pandemic. If the virus stays viable in droplets, no matter where the droplets are located, the virus will remain infectious and may be transmitted to others through contact. The studies in this dissertation were conducted to determine the distributions of soluble and insoluble components inside droplets and to elucidate how the observed distributions correlate with important droplet properties and environmental processes. We used two methods to observe droplets: Raman spectroscopy and surface-enhanced Raman spectroscopy (SERS). Molecules are constantly vibrating, these vibrations result in characteristic Raman signals that can be monitored. Both Raman and SERS provide such measurements, except that SERS has greater sensitivity due to the signal enhancement provided by gold or silver nanoparticles. In this dissertation, we obtained images of droplets with variable compositions at both room temperature and -50 °C. We also examined virus survival inside droplets during droplet drying. Using the collected images, we related the component distribution inside a droplet to its acidity, and evaluated virus survival in terms of droplet drying patterns. The images demonstrate that Raman and SERS imaging are promising tools for the study of droplets.

The conformation of paclitaxel in the bound state on the protein has been proposed to be the T-taxol conformation, and paclitaxel analogs constrained to the T-taxol conformation proved to be significantly more active than paclitaxel in both cytotoxicity and tubulin polymerization assays, thus validating the T-taxol conformation as the tubulin-binding conformation. In this work, eight compounds containing an aza-tricyclic moiety as a mimic of the baccatin core of paclitaxel have been designed and synthesized as water-soluble simplified paclitaxel analogs, among which 3.50-3.52 and 3.55 were conformationally constrained analogs designed to bind to the paclitaxel binding site of tubulin, based on their similarity to the T-taxol conformation. The open-chain analogs 3.41-3.43 and 3.57 and the bridged analogs 3.50-3.52 and 3.55 were evaluated for their antiproliferative activities against the A2780 cell lines. Analogs 3.50-3.52 and 3.55 which were designed to adopt the T-taxol conformation showed similar antiproliferative activities compared to their open-chain counterparts. They were all much less active than paclitaxel. In the second project, a series of paclitaxel analogs with various thio-containing linkers at C-2′ and C-7 positions were designed and synthesized in our lab. These analogs were attached to the surfaces of gold nanoparticles by CytImmune Sciences for the development of mutifunctional tumor-targeting agents. The native analogs and the gold bound analogs were evaluated for their antiproliferative activities against the A2780 cell line. All the compounds tested showed comparable or better activities than paclitaxel. Stability studies were performed for selected analogs in hydrolysis buffer, which showed that the analogs released paclitaxel in buffer over time. In the third project, the synthesis of a conformationally constrained paclitaxel analog which was designed to mimic the REDOR-taxol conformation was attempted. Two synthetic routes were tried and significant progress was made toward the synthesis of the conformationally constrained analog. However, both of the current synthetic routes failed to produce the key intermediate that would serve as the precursor for a ring-closing metathesis reaction to furnish the macrocyclic ring. / Ph. D.

No / Recent studies have gained positive results using nanoparticles (NPs) in treating atherosclerosis on animals. But their toxicity and application in treating other heart diseases such as heart failure and endocarditis still need proper investigation. Gold nanoparticles (Au-NPs) were chosen as model substances as they have been successfully used in treating cancer. In this study, we use both H9C2 myoblasts and rat peripheral blood mononuclear cells to determine the influence of Au-NP size on their cytotoxicity and cell apoptosis. H9C2 cells were treated with Au-NPs of a diameter of 5, 20, 40 and 100nmfor 24 hrs before their cell viabilities tested by MTT assay, cell apoptosis measured by flow cytometry, and the generation of reactive oxygen species (ROS) detected by Fluorometric Intracellular ROS Kit. Distribution of the Au-NPs and their effects on the structure of mitochondria and lysosome were detected by electron microscopy. In addition, we obtained rat peripheral blood mononuclear cells and treated them with Au-NPs same with H9C2 cell line. Our results showed NPs of 5, 40, and 100 nm reduced cell viabilities on H9C2 cells while20nm showed no change on cell viability (Ctrl: 100±8.2 vs 20nm: 95.39±9.13, P>0.05, n=6) and some protect effect on ISO induced H9C2 cells apoptosis (ISO: 100±13.5 vs 20nm: 80.19±17.36, P>0.05, n=6). All size of Au-NPs reduced cell viabilities on rat peripheral blood mononuclear cells while 40nm showed the least reduction on cell viability (Ctrl: 100.0±3.0 vs 40nm: 76.31±3.68, P<0.001, n=6) and significant protect effect on ISO-induced rat peripheral monocytes apoptosis (ISO: 100±1.86 vs 40nm: 45.34±10.32, P<0.05, n=6). In addition, 20nm Au-NP showed some protect effect on ROS generation on ISO-induced H9C2 cells (ISO: 100±3.79 vs 20nm: 94.84±4.98, P>0.05, n=6), while 40nm produced more ROS (ISO: 100±3.79 vs 40nm: 141.63±42.81, P>0.05, n=6). Electron microscopy detection showed correlated results in structure. These results on H9C2 cell line are basically in agreeable to our animal study. The protective effect of 20nm may due to its ability to protect ISO-induced ROS generation. The results on rat peripheral monocytes are slightly different to those on H9C2 cells. Further investigation need to focus on the role of NPs size on cell apoptosis by detecting autophagy specific protein through western blotting. / Abstract of conference paper.

Yes / The use of peptides to nucleate, grow, and stabilize nanoparticles in aqueous media via non-covalent interactions offers new possibilities for creating functional, water-dispersed inorganic/organic hybrid materials, particularly for Au nanoparticles. Numerous previous studies have identified peptide sequences that both possess a strong binding affinity for Au surfaces and are capable of supporting nanoparticle growth in water. However, recent studies have shown that not all such peptide sequences can produce stable dispersions of these nanoparticles. Here, via integrated experiments and molecular modeling, we provide new insights into the many factors that influence Au nanoparticle growth and stabilization in aqueous media. We define colloidal stability by the absence of visible precipitation after at least 24 hours post-synthesis. We use binding affinity measurements, nanoparticle synthesis, characterization and stabilization assays, and molecular modeling, to investigate a set of sequences based on two known peptides with strong affinity for Au. This set of biomolecules is designed to probe specific sequence and context effects using both point mutations and global reorganization of the peptides. Our data confirm, for a broader range of sequences, that Au nanoparticle/peptide binding affinity alone is not predictive of peptide-mediated colloidal stability. By comparing nanoparticle stabilization assay outcomes with molecular simulations, we establish a correlation between the colloidal stability of the Au nanoparticles and the degree of conformational diversity in the surface-adsorbed peptides. Our findings suggest future routes to engineer peptide sequences for bio-based growth and dispersion of functional nanoparticles in aqueous media. / Air Office of Scientific Research, grant number FA9550-12-1-0226.

Yes / Inhaled nanoparticles (NPs) are experienced by the first biological barrier inside the alveolus known as lung surfactant (LS), a surface tension reducing agent, consisting of phospholipids and proteins in the form of the monolayer at the air-water interface. The monolayer surface tension is continuously regulated by the alveolus compression and expansion and protects the alveoli from collapsing. Inhaled NPs can reach deep into the lungs and interfere with the biophysical properties of the lung components. The interaction mechanisms of bare gold nanoparticles (AuNPs) with the LS monolayer and the consequences of the interactions on lung function are not well understood. Coarse-grained molecular dynamics simulations were carried out to elucidate the interactions of AuNPs with simplified LS monolayers at the nanoscale. It was observed that the interactions of AuNPs and LS components deform the monolayer structure, change the biophysical properties of LS and create pores in the monolayer, which all interfere with the normal lungs function. The results also indicate that AuNP concentrations >0.1 mol% (of AuNPs/lipids) hinder the lowering of the LS surface tension, a prerequisite of the normal breathing process. Overall, these findings could help to identify the possible consequences of airborne NPs inhalation and their contribution to the potential development of various lung diseases. / University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S.I.H.), 2018 Blue Sky scheme–Suvash Saha (Activity 2232368), N.S.G is supported by the Vice-Chancellor fellowship funded by QUT.