Water utilities in Nova Scotia face numerous challenges treating low turbidity water and complying with stringent guidelines and treatment standards. Problems associated with the treatment of low-turbidity water are not confined to Nova Scotia; several other provinces, British Columbia, Manitoba and Ontario share similar water characteristics of drinking water sources. The treatment of low turbidity water is a challenge for these utilities as it requires maintaining the appropriate coagulant dosage that will ensure adequate particle and natural organic matter removal, while at the same time not enhancing the formation of disinfection by-products. Another concern associated with the treatment of such water is that when the particle content of the water is very low, charge neutralization will not be effective due to the weak contact between destabilized particles. Currently, nanoparticles are not regulated as water contaminants, and thus it is unclear whether the existing filtration treatment practices are capable of removing them from drinking water. Obtaining in-depth information on nanoparticle characteristics in drinking water sources will provide a valuable resource that can assist in the development of future treatment strategies. In this research, characteristics of four synthetic nanoparticles cerium dioxide (CeO2), ferric oxide (Fe2O3), silicon dioxide (SiO2) and titanium dioxide (TiO2) were investigated in Milli-Q water for particle size, surface area, and surface potential using different characterization techniques. Water samples from Pockwock Lake were also characterized for naturally occurring nanoparticles. After initial testing, titanium dioxide (TiO2) nanoparticles were selected to examine particle removal at bench-scale filtration experiments, under operating conditions similar to those practiced at the J.D. Kline Water Supply Plant, Halifax, NS, Canada. Filter performance for the deposition of TiO2 nanoparticles was evaluated through the calculation of its attachment efficiency and coefficient under various water chemistry conditions. The calculated filter efficiency was then applied to simulate natural nanoparticles removal from water. The results of the research indicate that the investigated nanoparticles behaved similar to natural particles and formed aggregates with larger particle sizes in Milli-Q water. Among the tested nanoparticles, only titanium dioxide could be coagulated with alum, as its negative surface charge and zero point of charge were closer to that of alum. Filtration experiments revealed that TiO2 nanoparticles, when present in water, could successfully be removed by an alum dose of 8 mg/L. Indeed, removal in excess of 99.5% was achieved under the study conditions. Under the investigated water chemistry conditions, very low attachment efficiencies (?) of 0.001, 0.002 and 0.01, and filter coefficients (?) of -0.003, -0.001 and -0.02 were determined for the filters. Based on the calculated attachment efficiencies, and under the studied conditions, natural nanoparticles remain dispersed in the water and would not likely to be removed by direct filtration. The overall research findings represent a major step forward in nanoparticle removal by direct filtration.

This thesis research investigates the surface properties and performances of gold nanoparticles, microarc oxidation coating, and epitaxial nano-twinned copper film. The research aims to understand the critical behavior of material surfaces in order to facilitate design and development of new materials for tribological applications. The research will focus on improving of the gun barrel performances. Experimental approaches will be used for combining analysis with basic thermal energy transfer principles. Results obtained here will be used for developing new materials to be used in facilitating gun barrels. Experimental approach includes scanning calorimetry-thremogravimetric analysis, tribological testing, and potentiodynamic polarization. The fundamental understanding obtained here will be beneficial for the gun barrel design, manufacturing, and military technologies followed by the results of experiments with different three types of materials. The results of this research showed that the coatings with microarc oxidation and nano-twinned structure improved wear resistance from the tribological examinations and size of AuNPs affected their thermal behaviors measured by differential scanning calorimetry and thermogravimetric analysis method.

This Ph.D. thesis reports the discovery and study of several morphologies of ABC triblock copolymer assemblies in block selective solvents. One block copolymer self-assembled into helices (mostly double and some triple helices), and the other block copolymer formed a mixture of structures resembling hamburgers and striped cylinders. The helices, biomimmetic structures which are unusual from block copolymer self assembly, were prepared from the triblock copolymer poly(n-butyl methacrylate)-block-poly(2-cinnamoyloxyethyl methacrylate)-block-poly(tert-butyl acrylate) (PBMA-b-PCEMA-b-PtBA). They were formed spontaneously in several binary solvent mixtures including dichloromethane/methanol, tetrahydrofuran (THF)/methanol, and chloroform/methanol. They were formed in the composition ranges where the mixtures were good for the PtBA block, poor for the PCEMA block, and marginal for the PBMA block. The structure was studied and established by TEM, AFM, DLS and 1H NMR and by TEM tomography. The mechanism and kinetics of helix formation was examined. The Hamburger and striped cylinder structures were produced from poly(tert-butyl acrylate)-block-poly(2-cinnamoyloxyethyl methacrylate)-block-poly(succinated glyceryl monomethacrylate) or (PtBA-b-PCEMA-b-PSGMA) in mixtures of THF, (-)-sparteine and 1- or 2-propanol. Here THF solubilized all the blocks of the copolymer, while propanol was a precipitant for the middle block (PCEMA), and the chiral amine, (-)-sparteine, complexed with PSGMA and made it insoluble. Within the Hamburger-like structure, the “filling” was made of the complexed PSGMA chains and the "buns" were made of PCEMA. The striped cylinders were made of stacking alternating PCEMA and PtBA stubs. The PtBA chains were located on the outer surfaces of both of these structures. With the hamburger structures, after PCEMA crosslinking, we were able to remove the chiral amine by dialysis and make the PSGMA chains soluble again in solvents such as N, N dimethylformamide. The hamburgers were thus separated into two halves, with each half existing as a Janus particle, which had PtBA chains on one side and PSGMA chains on the other side. The Janus particles might have interesting applications, such as in Pickering emulsion stabilization. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-04-30 18:01:06.281

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<p>In this thesis, I present the electrochemical studies of three dendrimeric polypropylene imine (PPI) nanomaterials and their applications as a platform in the development of a novel label free DNA nanobiosensor based on electrochemical impedance spectroscopy. Cyclic voltammetry (CV), differentia pulse voltammetry (DPV), square wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS) techniques were used to study and model the electrochemical reactivities of the nanomaterials on glassy carbon electrode (GCE) as the working electrode.</p>

One of the largest obstacles in drug development is to overcome solubility and bioavailability problems. Preformulation strategies such as nanoparticle formation are often employed but sometimes create new issues and are limited in their effectiveness and applications. Since the majority of drugs are marketed and sold as solid forms, drug delivery systems are not always desirable. This is where solid-state chemistry becomes important. Traditional solid-state chemistry approaches are often successful but are sometimes too restrictive and cannot be applied to certain compounds. Cocrystals have emerged as an alternative solid-state technique that can be applied to a broad range of compounds. However, the technology is still very new and its effectiveness in certain conditions had previously not been evaluated. The studies detailed herein investigated the ability of two different technology platforms for overcoming drug design challenges for two promising bioflavonoids: EGCg and quercetin. Studies have shown that EGCg might be useful for the treatment of Alzheimer's disease and other neurodegenerative diseases. Quercetin is being investigated for numerous bioactivities and is currently being marketed as an energy dietary supplement. Both of these bioflavonoids exhibit poor bioavailability and water solubilities that are at opposite ends of the spectrum. In the chapters to follow, nanoparticle technology was applied to EGCg and evaluated in cell models of AΒ production, a hallmark of Alzheimer's disease. Bioavailability improvements were also evaluated in rats. Additionally, new forms of both flavonoids were created using cocrystallization. These new cocrystals were characterized using powder and single crystal x-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Solubility and bioavailability changes were also evaluated. These data have strong implications in drug development since they elucidated the strengths and weaknesses of two major technologies in compounds with different design challenges.

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

The advent of numerous tools, ease of techniques, and concepts related to nanotechnology, in combination with functionalization via simple chemistry has made gold important for various biomedical applications. In this dissertation, the development and characterization of planar gold surfaces with responsive hydrogel patterns for rapid point of care sensing and the functionalization of gold nanoparticles for drug delivery are highlighted. Biomedical micro- and nanoscale devices that are spatially functionalized with intelligent hydrogels are typically fabricated using conventional UV-lithography. Herein, precise 3-D hydrogel patterns made up of temperature responsive crosslinked poly(N-isopropylacrylamide) over gold were synthesized. The XY control of the hydrogel was achieved using microcontact printing, while thickness control was achieved using atom transfer radical polymerization (ATRP). Atomic force microscopy analysis showed that to the ATRP reaction time governed the pattern growth. The temperature dependent swelling ratio was tailored by tuning the mesh size of the hydrogel. While nanopatterns exhibited a broad lower critical solution temperature (LCST) transition, surface roughness showed a sharp LCST transition. Quartz crystal microbalance with dissipation showed rapid response behavior of the thin films, which makes them applicable as functional components in biomedical devices. The easy synthesis, relative biocompatibility, inertness, and easy functionalization of gold nanoparticles (GNPs) have made them useful for various biomedical applications. Although ATRP can be successfully carried out over GNPs, the yield of stable solution based GNPs for biomedical applications prove to be low. As an alternative approach, a novel method of ISOlating, FUnctionalizing, and REleasing nanoparticles (ISOFURE) was proposed. Biodegradable poly(β-amino ester) hydrogels were used to synthesize ISOFURE-GNP composites. ATRP was performed inside the composite, and the final hydrogel coated GNPs were released via matrix degradation. Response analysis confirmed that the ISOFURE method led to the increased stability and yield of the hydrogel coated ISOFURE-GNPs. The ISOFURE protocol was also utilized in functionalizing GNPs with enzyme catalase in the absence of a stabilizing reagent. Biotin-streptavidin affinity was used as the bioconjugation method. Activity analysis of the conjugated enzyme showed that the ISOFURE-GNPs showed enhanced biomolecular loading relative to solution based stabilizing reagent passivated GNPs.

Despite indications that they are potential contaminant transport systems and threats to groundwater quality, very little effort has been invested in comparing contaminant transport behavior of natural environmental nanocolloids and their corresponding macrocolloid fractions in the presence of As, Se, Pb, and Cu contaminants. This study involved physico-chemical, mineralogical, stability and contaminant-transport characterizations of nano- (< 100 nm) and macro-colloids (100-2000 nm) fractionated from three Kentucky soils and one biosolid waste. Particle size was investigated with SEM/TEM and dynamic light scattering. Surface reactivity was estimated using CEC and zeta potential. Mineralogical composition was determined by XRD, FTIR, and thermogravimetric analyses. Sorption isotherms assessed affinities for Cu2+, Pb2+, AsO3-, and SeO4-2 contaminants, while settling kinetics experiments of suspensions at 0, 2 and 10 mg/L contaminants determined stability and transportability potential. Undisturbed 18x30 cm KY Ashton Loam soil monoliths were also used for transport experiments, involving infusion of 50 mg L-1 colloid suspensions spiked with 2 mg L-1 mixed contaminant loads in unsaturated, steady state, unit gradient downward percolation experiments. Overall, nanocolloids exhibited greater stability over corresponding macrocolloids in the presence and absence of contaminants following specific mineralogy trends. Physicochemical characterizations indicated that extensive organic carbon surface coatings and higher Al/Fe:Si ratios may have induced higher stability in the nanocolloid fractions, in spite of some hindrance by nano-aggregation phenomena. In the transport experiments, nanocolloids eluted significantly higher concentrations of colloids, total, and colloid-bound metals than corresponding macrocolloids. Contaminant elutions varied by colloid type, mineralogy and contaminant, with the following sequences: soil-colloids>bio-colloids, smectitic>mixed≥kaolinitic>biosolid, and Se>Pb/Cu≥As. Our findings demonstrate that even though they behave more like nano-aggregates rather than individual nano-particles, nanocolloids may exhibit significantly higher mobility and contaminant transport potential over great distances in subsoil environments than their corresponding macrocolloid fractions.

Biological materials have ever been used by humans because of their remarkable properties. This is surprising since the materials are formed under physiological conditions and with commonplace constituents. Nature thus not only provides us with inspiration for designing new materials but also teaches us how to use soft molecules to tune interparticle and external forces to structure and assemble simple building blocks into functional entities. Magnetotactic bacteria and their chain of magnetosomes represent a striking example of such an accomplishment where a very simple living organism controls the properties of inorganics via organics at the nanometer-scale to form a single magnetic dipole that orients the cell in the Earth magnetic field lines. My group has developed a biological and a bio-inspired research based on these bacteria. My research, at the interface between chemistry, materials science, physics, and biology focuses on how biological systems synthesize, organize and use minerals. We apply the design principles to sustainably form hierarchical materials with controlled properties that can be used e.g. as magnetically directed nanodevices towards applications in sensing, actuating, and transport. In this thesis, I thus first present how magnetotactic bacteria intracellularly form magnetosomes and assemble them in chains. I developed an assay, where cells can be switched from magnetic to non-magnetic states. This enabled to study the dynamics of magnetosome and magnetosome chain formation. We found that the magnetosomes nucleate within minutes whereas chains assembles within hours. Magnetosome formation necessitates iron uptake as ferrous or ferric ions. The transport of the ions within the cell leads to the formation of a ferritin-like intermediate, which subsequently is transported and transformed within the magnetosome organelle in a ferrihydrite-like precursor. Finally, magnetite crystals nucleate and grow toward their mature dimension. In addition, I show that the magnetosome assembly displays hierarchically ordered nano- and microstructures over several levels, enabling the coordinated alignment and motility of entire populations of cells. The magnetosomes are indeed composed of structurally pure magnetite. The organelles are partly composed of proteins, which role is crucial for the properties of the magnetosomes. As an example, we showed how the protein MmsF is involved in the control of magnetosome size and morphology. We have further shown by 2D X-ray diffraction that the magnetosome particles are aligned along the same direction in the magnetosome chain. We then show how magnetic properties of the nascent magnetosome influence the alignment of the particles, and how the proteins MamJ and MamK coordinate this assembly. We propose a theoretical approach, which suggests that biological forces are more important than physical ones for the chain formation. All these studies thus show how magnetosome formation and organization are under strict biological control, which is associated with unprecedented material properties. Finally, we show that the magnetosome chain enables the cells to find their preferred oxygen conditions if the magnetic field is present. The synthetic part of this work shows how the understanding of the design principles of magnetosome formation enabled me to perform biomimetic synthesis of magnetite particles within the highly desired size range of 25 to 100 nm. Nucleation and growth of such particles are based on aggregation of iron colloids termed primary particles as imaged by cryo-high resolution TEM. I show how additives influence magnetite formation and properties. In particular, MamP, a so-called magnetochrome proteins involved in the magnetosome formation in vivo, enables the in vitro formation of magnetite nanoparticles exclusively from ferrous iron by controlling the redox state of the process. Negatively charged additives, such as MamJ, retard magnetite nucleation in vitro, probably by interacting with the iron ions. Other additives such as e.g. polyarginine can be used to control the colloidal stability of stable-single domain sized nanoparticles. Finally, I show how we can “glue” magnetic nanoparticles to form propellers that can be actuated and swim with the help of external magnetic fields. We propose a simple theory to explain the observed movement. We can use the theoretical framework to design experimental conditions to sort out the propellers depending on their size and effectively confirm this prediction experimentally. Thereby, we could image propellers with size down to 290 nm in their longer dimension, much smaller than what perform so far. / Biologische Materialien wie Knochen, Muscheln und Holz wurden von den Menschen seit den ältesten Zeiten verwendet. Diese biologisch gebildeten Materialien haben bemerkenswerte Eigenschaften. Dies ist besonders überraschend, da sie unter physiologischen Bedingungen und mit alltäglichen Bestandteilen gebildet sind. Die Natur liefert uns also nicht nur mit Inspiration für die Entwicklung neuer Materialien, sondern lehrt uns auch, wie biologische Additiven benutzen werden können, um einfache synthetische Bausteine in funktionale Einheiten zu strukturieren. Magnetotaktischen Bakterien und ihre Kette von Magnetosomen sind ein Beispiel, wo einfache Lebewesen die Eigenschaften von anorganischen Materialien steuern, um sich entlang den magnetischen Feldlinien der Erde zu orientieren. Die von den Bakterien gebildeten Magnetosomen sind von besonderem Interesse, da mit magnetischen Eisenoxid-Nanopartikeln in den letzten zehn Jahren einer Vielzahl von Bio-und nanotechnologischen Anwendungen entwickelt worden sind. In dieser Arbeit stelle ich eine biologische und eine bio-inspirierte Forschung auf der Grundlage der magnetotaktischen Bakterien vor. Diese Forschung verbindet die neuesten Entwicklungen von Nanotechnik in der chemischen Wissenschaft, die neuesten Fortschritte der Molekularbiologie zusammen mit modernen Messverfahren. Mein Forschungsschwerpunkt liegt somit an der Schnittstelle zwischen Chemie, Materialwissenschaften, Physik und Biologie. Ich will verstehen, wie biologische Systeme Materialien synthetisieren und organisieren, um Design-Prinzipien zu extrahieren, damit hierarchischen Materialien mit kontrollierten Eigenschaften nachhaltig gebildet werden.