Along with the rapid growth of the nanotechnology, nanoparticles (NPs) have found many applications in commercial products. However, there are only a few studies on the toxicity and the environmental effects of NPs in biological systems. <p>In the study described in this thesis, I have used water-soluble Au NPs that were synthesized using the Brust method and then modified by small molecules. I explored the interactions of these modified Au NPs with self-assembled monolayer films on gold surfaces.<p>Three types of self-assembled monolayer (SAM) modified gold surfaces were used in this study. The surfaces had SAMs that could be positively or negatively charged or carry no charge, or be able to engage in hydrogen bonding. <p>Cyclic voltammetry (CV) was used to characterize SAMs of disulfide-glycine conjugate, disulfide-aspartic conjugate, and 11-mercaptoundecanoic acid (MUA) on gold surface electrodes. The possible interactions of Au NPs with the disulfide-aminoacid conjugates and alkanethiol modified surfaces were evaluated by cyclic voltammetry and by electrochemical impedance spectroscopy (EIS). An apparent decline in current density observed in CV along with an electron transfer resistance increase in EIS measurements upon exposure of the films to the MUA-modified anionic Au NPs clearly indicate interactions of the NPs with the films. Likewise, upon exposure of the films to cationic NPs, electron transfer resistance decreases dramatically in EIS experiments. In addition, the current increase in CV measurements provided further evidences for the interactions. The interactions between modified Au NPs and the SAMs were investigated in more detail by infrared spectroscopy and by employing quartz crystal microbalance. These studies clearly showed that upon exposure of these SAM films to the water-soluble Au NPs, significant changes occur. As would be expected for the adsorption of the Au NPs onto the SAMs, the weight of the film increased due to the addition of the NPs on the surface. Moreover, there are significant increases in the carbonyl stretching vibration at 1735 cm-1 along with the appearance of the amide hydrogen stretching band, between 3160-3380 cm-1, which indicate the adsorption of Gly-CSA modified Au NPs onto the MUA film.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is prevalent among the elderly population. Aß protein has been heavily implicated in the pathogenesis of AD. This protein in its fibrillar form is a major component in the senile plaques that form on neuronal cellular membranes during the course of AD. Despite substantial efforts the exact mechanism of Aß toxicity towards a cell membrane is not well-understood. The determination of this mechanism, however, is of utmost importance, since the membrane presents the first site of Aß interaction with neurons, which in turn maybe the origin of Aß neurotoxicity. The purpose of this study was to find a lipid composition that can be used as a model of neuronal membrane for subsequent studies of the role of topographical heterogeneity (domain formation) on Aß-membrane interaction as related to AD. The lipids used in the study were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), cholesterol (Chol), sphingomyelin (SM) and ganglioside GM1 (GM1). These lipids were combined in different proportions and deposited on a mica substrate to form supported monolayers. They were then imaged with an atomic force microscope (AFM) to determine if any of them exhibited domain formation. Three of the studied samples: POPC/POPG/SM 40:40:20 +5%Chol, POPC/SM/Chol 75:20:5 and POPC/SM/GM1/Chol 74:2:1:23 were found to possess interesting topography, rich in structural features: pores and domains. The average height difference between the domain features for each sample was found to be 0.58±015 nm, 0.61±0.12 nm and 0.27±0:07 nm.

Understanding electron-transfer (ET) processes in proteins is of fundamental importance. In a series of photophysical studies of well-behaved peptide model systems, it has become evident that the ET through peptide spacers is greatly influenced by the separation between the acceptor (A) and the donor (D), the nature of the peptide backbone, the amino acid sequence, and the resulting flexibility of the peptide conjugates. In particular, it was suggested in the literature that the presence of H-bonding will increase the rate of ET, and there is experimental evidence, mostly in proteins, to suggest that H-bonding indeed increases the rate of ET.<p>My aim was to develop a potential-assisted deposition method for ferrocene peptide disulfides onto gold surfaces and investigate the electrochemical properties of these films. We made use of two classes of Fc-peptides: acylic ferrocenoyl (Fc)-peptide disulfides and cyclo-1,1-Fc-peptide disulfides, allowing the preparation of tightly packed films of cyclic and acylic Fc-peptides on gold surfaces within 30 minutes. This is a significant benefit compared to the conventional soaking method of self-assembly requiring several days for the assembly of well-packed films. Such films exhibited considerably improved stability. This electrodeposition method should find wide-spread applications for the formation of tightly-packed films from disulfides. Our studies allowed a direct comparison of the electron transfer kinetics of cyclic and acyclic Fc-peptide disulfide systems. Our results showed faster ET kinetics for films prepared from cyclic Fc-peptide conjugates compared to the acyclic systems, presumably as a result of the enhanced rigidity of the Fc-peptide conjugates on the surface and/or an increase of the number of conductive peptide wires to the surface. Following the idea of peptide dynamics as a major contributor to the observed electron transfer rate in peptides and peptide conjugates, variable temperature electrochemical studies of Fc-peptide films were performed. An estimation of the reorganization energy associated with ferrocene/ferrocenium (Fc/Fc+) redox process allowed us to probe the role of peptide dynamics. Three counter-ions were tested, exhibiting different strengths of association with the Fc+ group (BF4- < ClO4- < PF6-) and the reorganization energies were evaluated in each case. The highest reorganization energy was obtained for the weakly interacting anion BF4-. Weakly interacting anions also showed significant broadness in the redox peaks and emergence of the second oxidation peak which is attributed to phase separation of the ferrocene group. Ferrocene agglomeration was not observed for any of the cyclic Fc-peptide conjugates but occurred for some of the acyclic systems. In particular, for acyclic Val and Leu containing Fc-peptide conjugates agglomeration were observed and was presumably caused by lateral interactions between the hydrophobic side-groups of the peptides. Further experiments involving the interaction of Fc-peptide films with alkali metal ions gave additional evidence that electron transfer is influenced significantly by peptide dynamics.

Along with the rapid growth of the nanotechnology, nanoparticles (NPs) have found many applications in commercial products. However, there are only a few studies on the toxicity and the environmental effects of NPs in biological systems. <p>In the study described in this thesis, I have used water-soluble Au NPs that were synthesized using the Brust method and then modified by small molecules. I explored the interactions of these modified Au NPs with self-assembled monolayer films on gold surfaces.<p>Three types of self-assembled monolayer (SAM) modified gold surfaces were used in this study. The surfaces had SAMs that could be positively or negatively charged or carry no charge, or be able to engage in hydrogen bonding. <p>Cyclic voltammetry (CV) was used to characterize SAMs of disulfide-glycine conjugate, disulfide-aspartic conjugate, and 11-mercaptoundecanoic acid (MUA) on gold surface electrodes. The possible interactions of Au NPs with the disulfide-aminoacid conjugates and alkanethiol modified surfaces were evaluated by cyclic voltammetry and by electrochemical impedance spectroscopy (EIS). An apparent decline in current density observed in CV along with an electron transfer resistance increase in EIS measurements upon exposure of the films to the MUA-modified anionic Au NPs clearly indicate interactions of the NPs with the films. Likewise, upon exposure of the films to cationic NPs, electron transfer resistance decreases dramatically in EIS experiments. In addition, the current increase in CV measurements provided further evidences for the interactions. The interactions between modified Au NPs and the SAMs were investigated in more detail by infrared spectroscopy and by employing quartz crystal microbalance. These studies clearly showed that upon exposure of these SAM films to the water-soluble Au NPs, significant changes occur. As would be expected for the adsorption of the Au NPs onto the SAMs, the weight of the film increased due to the addition of the NPs on the surface. Moreover, there are significant increases in the carbonyl stretching vibration at 1735 cm-1 along with the appearance of the amide hydrogen stretching band, between 3160-3380 cm-1, which indicate the adsorption of Gly-CSA modified Au NPs onto the MUA film.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is prevalent among the elderly population. Aß protein has been heavily implicated in the pathogenesis of AD. This protein in its fibrillar form is a major component in the senile plaques that form on neuronal cellular membranes during the course of AD. Despite substantial efforts the exact mechanism of Aß toxicity towards a cell membrane is not well-understood. The determination of this mechanism, however, is of utmost importance, since the membrane presents the first site of Aß interaction with neurons, which in turn maybe the origin of Aß neurotoxicity. The purpose of this study was to find a lipid composition that can be used as a model of neuronal membrane for subsequent studies of the role of topographical heterogeneity (domain formation) on Aß-membrane interaction as related to AD. The lipids used in the study were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), cholesterol (Chol), sphingomyelin (SM) and ganglioside GM1 (GM1). These lipids were combined in different proportions and deposited on a mica substrate to form supported monolayers. They were then imaged with an atomic force microscope (AFM) to determine if any of them exhibited domain formation. Three of the studied samples: POPC/POPG/SM 40:40:20 +5%Chol, POPC/SM/Chol 75:20:5 and POPC/SM/GM1/Chol 74:2:1:23 were found to possess interesting topography, rich in structural features: pores and domains. The average height difference between the domain features for each sample was found to be 0.58±015 nm, 0.61±0.12 nm and 0.27±0:07 nm.

Self-assembled monolayers (SAMs) of 4-aminothiophenol (4-ATP) has been successfully deposited onto nanometer-sized gold (Au) electrodes. The cyclic voltammograms obtained on a 4-ATP SAMs modified electrode show peaks and the peak height is proportional to the scan rate, which is similar to that on an electroactive SAMs modified macro electrode. The electrochemical behavior and mechanism of outer-sphere electron transfer reaction on the 4-ATP SAMs modified nanometer-sized electrode has also been studied. The 4-ATP SAMs modified electrode is further modified with platinum (Pt) nanoparticles. Electrochemical behaviors show that there is electrical communication between Pt nanoparticles and Au metal on the Pt nanoparticles/4-ATP SAMs/Au electrode. However, scanning electron microscopic image shows that the Pt nanoparticles are not evenly covered the electrode.

Yes / Ligands like alkanethiol (e.g. dodecanethiol, hexadecanethiol, etc.) and polymers (e.g. poly(vinyl pyrrolidone), polyethylene glycol-thiol) capped to the gold nanoparticles (AuNPs) are widely used in biomedical field as drug carriers and as promising materials for probing and manipulating cellular processes. Ligand functionalised AuNPs are known to interact with the pulmonary surfactant (PS) monolayer once reaching the alveolar region. Therefore, it is crucial to understand the interaction between AuNPs and PS monolayers. Using coarse-grained molecular dynamics simulations, the effect of ligand density, and ligand length have been studied for two classes of ligands on a PS model monolayer consisting of DPPC, POPG, cholesterol and SP-B (mini-peptide). The ligands considered in this study are alkanethiol and polyethylene glycol (PEG) thiol as examples of hydrophobic and hydrophilic ligands, respectively. It was observed that the interaction between AuNPs and PS changes the biophysical properties of PS monolayer in compressed and expanded states. The AuNPs with hydrophilic ligand, can penetrate through the monolayer more easily, while the AuNPs with hydrophobic ligand are embedded in the monolayer and participated in deforming the monolayer structure particularly the monolayer in the compressed state. The bare AuNPs hinder to lower the monolayer surface tension value at the interface, however introducing ligand to the bare AuNPs or increasing the ligand length and density have an impact of lowering of monolayer surface tension to a minor extent. The simulation results guide the design of ligand protected NPs as drug carriers and can identify the nanoparticles' potential side effects on lung surfactant. / ZEH thanks the Royal Society of Chemistry (RSC) Research Fund grant R19-0326 for providing funding. NSG acknowledges support from Advance Queensland Industry Research Fellowship.

Yes / Colloidal nanoparticles, such as gold nanoparticles (AuNPs), are promising materials for the delivery of hydrophilic drugs via the pulmonary route. The inhaled nanoparticle drug carriers primarily deposit in lung alveoli and interact with the alveolar surface known as lung surfactants. Therefore, it is vital to understand the interactions of nanocarriers with the surfactant layer. To understand the interactions at the molecular level, here we simulated model lung surfactant monolayers with phospholipid (PL)-wrapped AuNPs at the vacuum-water interface using coarse-grained molecular dynamics simulations. The PL-wrapped AuNPs quickly adsorbed into the surfactant layer, altered the structural properties of the monolayer, and at high concentrations initiated the compressed monolayer to collapse/buckle. Among the surfactant monolayer lipid components, cholesterol adsorbed to the AuNPs preferentially over PL species. The position of the adsorbed PL-AuNPs within the monolayer, and subsequent monolayer perturbation, vary depending on the monolayer phase, monolayer composition, and species of PL used as a ligand. Information provided by these molecular dynamic simulations helps to rationalize why some colloidal nanoparticles work better as nanocarriers than others and aid the design of new ones, to avoid biological toxicity and improve efficacy for pulmonary drug delivery.

This work has centered on the interface dipoles arising at heterojunctions between metals, semiconductor nanoparticles, self-assembled monolayers, and organic semiconductor materials. Alkanethiol self-assembled monolayers, CdSe nanocrystals, and the organic semiconductors zinc phthalocyanine (ZnPc) and Buckminster fullerene (C60) were the basis of these investigations. UV photoemission spectroscopy has proven to be an invaluable tool to observe the vacuum level shifts for these analyses while using XPS to corroborate surface structure. With a full evaluation of these surfaces, the shifts in the vacuum level, valence ionizations, and core ionizations, the impact of these interfaces, as well as their influence on the subsequent deposition of organic semiconductor layers is established.Alkanethiols possessing varying dipole moments were examined on gold and silver substrates. The viability of these alkanethiols was demonstrated to predictively adjust the work function of these metals as a function of their intrinsic dipole moments projected to surface normal, and established differences between Ag--S and Au--S bonds. The capability of the SAMs to modify the work function of gold provided an opportunity for mixed monolayers of the alkanethiols to produce a precise range of work functions by minimal adjustments of solution concentration, which were examined with a simple point dipole model.Photoemission spectroscopy offers a thorough analysis of CdSe nanoparticle films. Despite a plethora of research on these nanocrystals, there still is controversy on the magnitude of the shift in the valence band with diameter. In our research we found the majority of the valence band shift could be attributed to the interface dipole, ignored previously. Meanwhile, the valence band tethered films was obscured by the sulfur of the thiol tether.Finally, organic semiconductor layers deposited on SAMs on gold exhibited various interface dipole effects at these heterojunctions. Charge transfer states of ZnPc did not favor energy level alignment on the SAM/Au substrates used; C60 demonstrated vacuum level shifts on C15 and C12ph alkanethiol monolayers consistent with the interface charge transfer (ICT) model. These results provide credibility to models recently demonstrated in the literature for other passivated metal surfaces, and include the viability of SAMs in these discussions.

This thesis outlines a study of the physical changes that hybridisation imposes on single-stranded DNA (ssDNA) immobilised by one end to a substrate, and of how such physical changes can be exploited to detect specific sequences of DNA in a target solution. The system studied was composed of a mixed monolayer of 20mer ssDNA with C6 alkanethiolate modifications on their 3??? ends and short-chain hydroxyterminated alkanethiolates, on a gold substrate. It was prepared using the self-assembly properties of alkanethiols on gold. Atomic force microscopy images showed that the end-immobilised ssDNA is flexible enough to lie over the diluent hydroxy-terminated self-assembled monolayer (SAM). Hybridisation was shown to cause the DNA to become more rigid and stand up off the substrate due to an increase in persistence length. Such physical changes of the DNA upon hybridisation were significant enough to be exploited in the development of a DNA recognition interface. The recognition interface was designed with the view of keeping it both simple to make and simple to use, and was coupled with electrochemical transduction. A label-free recognition interface was developed that relied on the oxidation of the sulfur head group of the alkanethiolate SAM to detect hybridisation (firstly air oxidation and then electrochemical oxidation). It produced a positive signal upon hybridisation with complementary target DNA. Improvements in the reliability and robustness of the recognition interface were made using a labelled approach. The labelled version employed electroactive molecules as labels on the 5??? ends of the probe DNA strands. Two labels were investigated ??? anthraquinone and ferrocene. The flexibility of the ssDNA ensured that the redox labels were able to directly access the underlying gold electrode. Hybridisation was expected to remove the labels from the electrode due to an increase in the DNA???s persistence length, and thus perturb the electrochemical signal. The use of ferrocene as a label provided a ???proof-of-concept??? for the system. The labelled recognition interface provides a foundation for the future development of a simple, reliable, and selective DNA hybridisation biosensor.