In order to gain insights into the electronic interactions between metallic gold and self-assembled monolayers composed of π-conjugated thiols, a series of thiol-containing molecules based on a stilbene backbone were synthesized and assembled on gold surface. The resulted monolayers were characterized with a variety of surface-sensitive techniques and the electronic properties of the obtained surfaces were studied with the use of ultraviolet photoelectron spectroscopy. Work-function changes and alignment of the molecular energy levels with respect to the Fermi level of the metal were investigated and important insights regarding the electronic properties of the metal / organic interfaces were obtained. Another aspect of interactions between organic dyes and metallic gold was studied in the context of spectroscopic properties of systems incorporating gold nanoparticles with organic fluorophores covalently attached to the nanoparticle surface. Ultrafast dynamics of the excited-state deactivation of the organic fluorophores attached to the surface of gold nanoparticles were studied with the use of a fs transient absorption technique. It was found that the close proximity of a gold nanoparticle had a profound impact on the excited-state lifetime of the studied organic fluorophore. The influence of the structure of the studied systems on the excited-state deactivation dynamics of the organic fluorophores was described.

A few computational models currently exist to predict heat production and dissipation in tissue when a tumor containing optically-tunable gold nanoparticles such as nanoshells or nanorods is illuminated with near infrared (NIR) laser. The validity of any computational model still needs to be established by experiments before its wide use for various future clinical applications. One of the possible ways to validate the model is through the heat measurements within a phantom made with tissue-equivalent heat-sensitive gel. Currently, there are a few recipes available for this type of gel and the majority of them use severely toxic ingredients. However, none of them seems to perfectly serve the current purposes. Therefore, the primary goal of this thesis work was to develop and characterize two new types of heat-sensitive gels, using relatively non-toxic substances for the in-phantom validation of computational models. Specifically, two novel agar based phantoms, TG1 and TG2, were developed and characterized. The basic optical response of these phantoms at 808 nm NIR light was determined to test their equivalency to human tissue. Thermal damage to the phantoms was quantified by heating them to specific temperatures and obtaining calibration curves to relate temperature and R2 relaxation rates. The phantoms were scanned with magnetic resonance imaging (MRI) to obtain T2 values. TG1 gel, agar and bovine serum albumin (BSA) mixture, was found not to be optically tissue-equivalent. However, TG1 gel demonstrated unambiguous digital response capable of distinguishing temperature of at least 70 °C compared to the sample receiving no heat. Additionally, TG1 gel produced high degree of linearity in the thermal therapy temperature regime (60 - 80 °C). TG2 gel containing agar mixed with BSA and Intralipid has exhibited tissue equivalency based on laser transmission measurements. TG2 gel exhibited heat damage based on T2 values, only when the temperature reaches 80 °C. This digital response is considered less sensitive in view of the fact that BSA starts to undergo denaturing and cause optical density change at approximately 70 °C. Both gels, however, have shown to be thermally stable at temperatures up to 80 °C with no evidence of gel melting being observed.

Various solution-processed methods have been employed in this work. For the synthesis of graphene, a chemical exfoliation method has been used to generate large graphene flakes in the solution phase. In addition, chemical or electro polymerization has been used for synthesizing polyanthracene, which tends to form graphene nanoribbon through cyclodehydrogenation. For the device fabrication, graphene oxide (GO) thin films were deposited from solution phase on the vapor-silanzed aminosilane surface to make semiconducting active layer or conducting electrodes. Gold nanoparticles (AuNPs) were selectively self-assembled from solution phase to pattern nanowires.

The present thesis titled “Molecular Modulation of Material Properties: Stud- ies on Nanoparticles, Nanoassemblies and Low Molecular Mass Gelator” deals with the preparation, characterization, and investigations into the properties of gold nanoparticles coated with novel thiols. The coverage of nanoparticle surfaces with these thiols renders them with special characteristics that will be of interest in biological and sensor applications. Also, a novel low molecular mass tetrameric sugar-based hydrogelator was synthesized and its gelation properties were studied in detail. Chapter 1 gives a general introduction and an overview about Nanomaterials, with emphasis towards nanoparticles of gold, which form the basis of this work. It delves with the history of research in noble metal nanoparticles, their interesting electronic and optical properties, the present methods of synthesis of high quality nanoparticles of noble metals, numerous potential applications of these novel materials, as well as the challenges in their real-life applications, and ends with the future outlook of this field of research. Chapter 2 describes the synthesis and characterization of three cationic lipid-like disulfides whose molecular structures are shown in Fig. 2.1. Gold nanoparticles capped with these molecules were then synthesized in small size dispersion by a simple one-phase protocol. These particles exhibited remarkably different solubility properties that were dictated by the molecular structure of the capping agent. The nanoparticles were characterized by a variety of techniques like UV-visible spec- troscopy, Transmission Electron Microscopy (TEM), proton Nuclear Magnetic Resonance (1H NMR), Fourier Transform Infra-red (FTIR) spectroscopy, and Zeta Potential measurements. These nanoparticles were then examined for their interactions (structural formula) Figure 1: Chemical Structures of the cationic lipid-like thiols used for nanoparticle preparation with dipalmitoyl phosphatidyl choline (DPPC) vesicles as model biological membranes. TEM, UV-vis, and Differential Scanning Calorimetry (DSC) were employed to probe the interactions. It was found that the capping agent of the nanoparticle had a strong bearing upon the interactions of the nanoparticles with DPPC vesicles. Chapter 3 describes the assembly of hydrophilic cationic nanoparticles upon elec- trostatic interaction with a variety of anionic surfactants. The chemical structures of some of the anions employed in the study, as well as a schematic of cationic nanopar- ticle are shown in Fig. 2. Upon ion pairing with long-chain anionic surfactants, the hydrophilic cationic nanoparticles were completely hydrophobized. They could then be phase-transferred to organic layer. TEM showed that nanoparticles assemble in to a variety of mesostructures upon ion-pairing with anions. The aggregate formation was found to depend critically upon length of the hydrophobic alkyl chain as well as the head-group of the anion. Isothermal Titration Calorimetry (ITC) was employed to probe the interactions of these nanoparticles with anions. It was found that the anions that resulted in nanoparticle precipitation displayed exothermic interactions with the nanoparticle. Chapter 4 deals with the synthesis of -thiolated metal chelator derivatives whose structures are shown in Fig. 3. The molecules are based on well-known chelators viz. iminodiacetic acid and bis-(2-pyridylmethyl)amine. While the first one is carboxylic acid-based chelator, the second one is pyridine-based. Nanoparticles coated with these chelators were synthesized in a size-controlled manner. These nanoparticles exhibited pH-controlled reversible assembly. However, while S-IDA based nanoparticles aggregated at low pH values, the S-BPA based nanoparticles aggregated in high pH regimes. Mixed monolayer protected gold nanoparticles were synthesized by employing S-BPA and C12H25SH as capping agents. It resulted in the formation of nanoparticles in low size-dispersion. These nanoparticles were characterized by 1H NMR spectroscopy to infer the ratio of the two capping agents on the nanoparticle surface. These nanoparticles demonstrated metal-ion induced aggregation. It was found that the nanoparticles could differentiate Cu2+ ions from other ions, and immediately formed aggregates in presence of Cu2+ ions. Chapter 5 describes the synthesis of novel mono-thiolated “Gemini” surfactants for nanoparticle synthesis. Gemini surfactants with different spacers were prepared. These surfactants had a 12-n-12 kind of molecular structure as shown in the Fig. 4. Upon preparation of nanoparticles with these thiols, the resulting material was soluble in water in the case of rigid thiols like D2S and DBPS Chapter 6 deals with the synthesis and hydrogelation properties of a low molecular mass hydrogelator based on an azobenzene based tetrameric sugar derivative (Fig. 5). The pKa of carboxylic acids in the molecule were determined using 13C NMR. The trans-to-cis isomerization of the compound was probed by time-dependent UV-vis studies. The sugar derivative exhibited pronounced hydrogelation capacity, gelling water at micromolar concentration. The gel formed was characterized extensively (structural formula) Figure 2: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 3: Chemical structures of metal-chelator containing thiols employed for the pH-controlled and metal-ion mediated nanoparticle assembly (structural formula) Figure 4: Schematic of cationic nanoparticles and molecular structures of the anions employed for nanoparticle assembly (structural formula) Figure 5: Chemical Structure of azobenzene-based tetrameric sugar derivative exhibit- ing pronounced hydrogelation using melting temperature analysis, UV-vis, FT-IR, circular dichroism spectroscopy and scanning electron microscopy. The resultant gel exhibited impressive tolerance to the pH variation of the aqueous phase and gelated water in the pH range of 4 to 10. While UV-vis and CD spectroscopy indicated that pronounced aggregation of the azobenzene chromophores in the gelator was responsible for gelation, FT-IR studies showed that hydrogen bonding is also a contributing factor in the gelation process. The melting of gel was found to depend upon the pH of the aqueous medium in which gel was formed. The gel showed considerable photostability to UV irradiation indicating tight intermolecular packing inside gelated state that render azobenzene groups in the resultant aggregate refractory to photoisomerization. The electron micrographs of the aqueous gels thus formed showed the existence of spongy globular aggregates in such gelated materials. Addition of salts to the aqueous medium led to a delay in the gelation process and also caused remarkable morphological changes in the microstructure of the gel. Appendix A describes the employment of ligand-free palladium nanoparticles towards efficient catalysis of Heck and Suzuki reactions in aqueous medium. Hexadecyl trimethylammonium bromide was employed as the surfactant to achieve solubilization of organic compounds in aqueous medium. UV-vis and TEM investigations into the formation of nanoparticles in the reaction media were undertaken. These studies indicate that the nanoparticles were formed by reduction of potassium tetrachloropalladinate by methyl acrylate used as one of the reactants. TEM investigation indicated the formation of nanoparticle assemblies upon solvent drying. Efficient and catalytic synthesis of a number of organic compounds could be achieved in high yield.

Detection of trace elements such as organic contaminants, explosive residues, and metal ions is an intellectually challenging task in science and engineering. It is also a topic of increasing importance due to its impact on society and the environment. Designing molecularly imprinted materials is one of the most promising approaches to explore sensing and detection applications. “Stimuli-sensitive” polymer materials are ideal candidates for these imprinted sensors as they are able to respond to changes in their environment and can be tailored by cross-linking the polymer chains. The responses can be amplified and transduced into measurable signals due to macromolecular properties provided by the use of a polymer. The purpose of the research in this project is to combine organic polymers with inorganic constituents to tailor the binding properties and the responses of the composite material for detection of metals ions in aqueous solutions. The research, here, is based on a thermally responsive polymer such as poly(Nisopropylacrylamide) (PNIPAM), which exhibits a well-known reversible volume phase transition in aqueous media around approximately 32°C. Combining cross-linked microgels formed from PNIPAM and its copolymers with gold nanoparticles (GNP) imparts the composite material with optical properties such as intense visible absorption due to the unique surface plasmon absorption of these small nanoparticles. The use of copolymers allows incorporation of functional groups, such as carboxylic acid, that are potential sites for binding metal ions. Cross-linking of the metal ion binding polymer imprints the metal ion in the PNIPAM microgel network. In this research, design of the composite material was investigated using copolymers of NIPAM and acrylic acid (AA), copolymers of NIPAM and glycidyl methacrylate (GMA), and interpenetrating networks of PNIPAM and PAA. A broad spectrum of polymerization conditions were studied such as changes in cross-linking density as well as changes in the synthetic procedure. Techniques such as turbidometry, ultraviolet visible spectroscopy (UV-VIS), transmission electron microscopy (TEM), and dynamic light scattering (DLS) were employed to characterize the microgels as well as their composites with GNP. Preliminary investigation of imprinting the microgels with heavy metal ions such as copper was also performed. The novel polymer-metal nanocomposites explored here will serve as an important contribution for the current ongoing research efforts in designing materials in the nano-scale capable of sensing and detecting metal ions in solution with high selectivity.

Nanocomposite thin films with gold nanoparticles embedded in a host metal oxide prepared by spray pyrolysis deposition have been investigated. A single-step process has been developed using a one-pot solution containing precursors for both gold nanoparticles and host metal oxides. The films obtained display combined features of colouration, electrical conductivity and solar control. In this study two precursors for gold nanoparticles were used: preformed gold colloids and HAuCl₄. Three metal oxide host materials, TiO₂, SnO₂ and ZnO, were investigated. These films were deposited at a substrate temperature of 200-600 °C. Powder X-ray diffraction analysis reveals the presence of metallic gold. SEM inspection typically showed particulate gold of 5-20 nm in diameter, distributed at the surface or within the host matrix. Optical spectroscopy showed an intense absorption in the visible region due to the characteristic surface plasmon resonance (SPR) effects of gold nanoparticles. The wavelength of the SPR peaks varies depending on the refractive index of surrounding host material which is significantly influenced by the substrate deposition temperature. On the other hand, SnO₂ and ZnO, together with the introduction of dopants, were further investigated as suitable materials for transparent conducting oxides (TCO). SnO₂:F films were found to attain very low electrical resistivity, while ZnO films exhibit higher transparency in the visible. A double layered structure with a TCO layer of SnO₂:F on top of a layer embedded with gold nanoparticles has been employed to achieve the combined functionalities of conductivity and colouration. The electrical conductivity is significantly enhanced compared to a nanocomposite single layer film due to the introduction of the TCO top layer. In this thesis, spray pyrolysis deposition has demonstrated a simple and rapid approach to the production of a variety of thin films. It can be immediately integrated with current industrial coating equipment and scaled up for large-scale production process.

Regiomeric mixture of HMe2Si(CH2)3(i-Bu)6Si7O9(OH)3 (6), containing a Si-H group in one of the ligands of the silsesquioxane, was tethered onto a vinyl terminated hyperbranched poly(siloxysilane) polymer via a hydrosilation reaction to generate extremely active catalysts, P1-8 and c-P1-8. The synthesis of 6, in good yield, was accomplished via hydrosilation of CH2=CHCH2(i-Bu)7Si8O12 (1) to generate ClMe2Si(CH2)3(i-Bu)7Si8O12 (3) followed by the reduction of 3 with LiAlH4 to afford HMe2Si(CH2)3(i-Bu)7Si8O12 (4) where the base-catalyzed excision of one framework silicon was employed to generate a regiomeric mixture of 6. [Ti(NMe2){Et3Si(CH2)3(i-Bu)6Si7O12}] (7), [Ti(NMe2){HMe2Si(CH2)3(i-Bu)6Si7O12}] (8), [Ti(NMe2){(i-C4H9)7Si7O12}] (9) and [Ti(NMe2){(c-C6H11)7Si7O12}] (10) were synthesized via protonolysis of Ti(NMe2)4 with one equivalent of the trisilanol precursor in order to determine if the presence of isomers would be intrinsically different as compared to the uniformly substituted catalysts. Isomers 8 and 9, demonstrated lower activity as compared to the uniformly substituted catalysts 9 and 10, however the isomers still exhibited extremely high catalytic activity for the epoxidation of 1-octene using tert-butyl hydroperoxide (TBHP) relative to titanium catalysts used in industry. Additionally, 9, 10, P1-8 and c-P1-8 were very selective catalysts for the epoxidation of various olefins such as terminal (1-octene), cyclic (cyclohexene or 1-methylcyclohexene), and more demanding olefins (limonene or α-pinene) employing TBHP as the oxidant. Furthermore, P1-8 and c-P1-8 were recyclable with minimal loss of titanium however the catalysts could also be repaired if a loss in activity was observed. Preliminary epoxidation reactions employing P1-8 and c-P1-8 along with hydrogen peroxide (H2O2) as the oxidant were also explored using different solvents. P1-8 degraded quickly due to the hydrolysis of the titanium from the large amount of water present in the reaction mixture however c-P1-8 showed activity for the epoxidation of cyclohexene. Finally, regiomeric mixture of Ti(NMe2)(HS(CH2)3)(i-C4H9)6Si7O12) (13), was tethered onto gold nanoparticles for the conversion of propene to propylene oxide using molecular hydrogen and oxygen. While the catalysts showed low activity under our reaction conditions, numerous improvements can be investigated in order to improve upon the catalysts.

Rupture of atherosclerotic plaque is closely related to plaque composition. Currently, plaque composition cannot be clinically characterized by any imaging modality. The objective of this dissertation is to use a recently developed imaging modality – ultrasound-guided intravascular photoacoustic (IVPA) imaging – to detect the distribution of two critical components in atherosclerotic plaques: lipid and phagocytically active macrophages. Under the guidance of intravascular ultrasound imaging, spectroscopic IVPA imaging is capable of detecting the spatially resolving optical absorption property inside a vessel wall. In this study, contrast in spectroscopic IVPA imaging was provided by either the endogenous optical property of lipid or optically absorbing contrast agent such as gold nanoparticles (Au NPs). Using a rabbit model of atherosclerosis, this dissertation demonstrated that ultrasound guided spectroscopic IVPA imaging could simultaneously image lipid deposits as well as macrophages labeled in vivo with Au NPs. Information of macrophage activity around lipid rich plaques may help to identify rupture-prone or vulnerable plaques. The results show that ultrasound guided IVPA imaging is promising for detecting plaque composition in vivo. Clinical use of ultrasound guided IVPA imaging may significantly improve the accuracy of diagnosis and lead to more effective treatments of atherosclerosis. / text

The fascinating capability of cellular self-organization during tissue development and repair is a central question in developmental biology and regenerative medicine. Understanding the dynamic morphogenic and regenerative processes of biological tissues will have important implications in biology and medicine. Nevertheless, the elucidation of the cellular self-organization processes is hindered by a lack of effective tools for monitoring the spatiotemporal gene expression distribution and a lack of ability to perturb the self-organization processes in living cells and tissues. Multimodal modularities that allow both single cell perturbation and gene detection are required to enable a new paradigm in the investigation of complex tissue morphogenic processes. To address this critical challenge in the field of developmental and regenerative medicine, we are developing a multimodal gold nanorod-locked nucleic acid (GNR-LNA) composite for single cell gene expression analysis in living cells and tissues at the transcriptional level. Using antisense RNA sequences, we design LNA probes for detecting specific molecular targets in living cells. The LNA probes bind to the GNR spontaneously due to the intrinsic affinity between the GNR and LNA. In close proximity, the fluorescent probes are effectively quenched by the GNR. Therefore, a fluorescent signal is only observed when the specific target thermodynamically displaces the LNA probe from the GNR. Furthermore, the GNR also serves as a transducer for photothermal ablation. Thus, we established a novel modularity for imaging the spatiotemporal gene expression distribution in living cells and tissues. The single cell analysis capability of our techniques enables us to adopt a unique approach to study the tissue regenerative processes during normal development and diseases, and this will have a profound impact on regenerative medicine and disease treatment in future. Moreover, we applied this GNR-LNA probe to explore the endothelial cell mRNA dynamics during capillary morphogenesis. Three different types of cells were identified due to their different roles during endothelial cell capillary-like formation process. Our findings indicated that the endothelial cell behavior is directly related to the Dll4 mRNA expression, and Dll4 expression in ECs determine the cell fate. Our GNR-LNA probe enable us to investigate the correlations between Dll4 mRNA expression and cell behavior during capillary morphogenesis. Experimental results indicated that: (1) When the endothelial cells aggregate, the cells migrate with certain displacement, the Dll4 mRNA expression decreases. (2) When the endothelial cells sprout, the cells migrate with small displacement but the cell shape changes to an ellipse shape, the Dll4 mRNA expression begin to increase. (3) When the endothelial cells elongate and form cell-cell contract with adjacent cells, the Dll4 expression decreased to a certain level and keep stable until the cell activity change to another stage. Furthermore, it has been demonstrated endothelial cells compete for the leader cell position during wound healing, collective cell migration, and tip cell formation during angiogenic process. It has been demonstrated that endothelial cells compete for the tip cell formation through Notch signaling pathway. However, how the mechanical force regulates tip cell formation is still unclear, and if mechanoregulation of tip cell formation through Notch pathway still unknown. Mechanical and chemical regulations of tissue morphogenesis and angiogenesis are being investigated in both in vitro capillary-like network formation assay and in vivo mice retina angiogenesis assay. Here, we investigated the mechanoregulation of mechanotransduction of tissue morphogenesis and angiogenesis using both in vitro endothelial cell tube formation model and in vivo mice retina blood vessel development model. Our results demonstrated that (1) Notch pathway negatively regulates tip cell formation: inhibition of Notch pathway (DAPT) enhances tip cell formation, induces Dll4 and Notch1 activity, activation of Notch pathway (Jag1 peptide) inhibits tip cell formation, suppresses Dll4 and Notch1 activity. (2) Mechanical force negatively regulate tip cell formation: (a) Decrease mechanical force via Rho kinase inhibitor Y-27632, myosin II inhibitor Blebbistatin, or laser ablation, enhances tip cell formation and induces Dll4 activity through mediation of Dll4-Notch1 lateral inhibition, (b) increase mechanical force via traction force inducer Nocodazole and Calyculin A, suppresses tip cell formation and inhibits Dll4 activity through activation of Notch pathway. (3) Mechanical force negatively regulates tip cell formation partially via mediation of Notch pathway. Mechanical force is necessary for tip cell formation and negatively regulate tip/stalk selection via Dll4-Notch1 lateral inhibition. Interruption of mechanical force enhance tip cell formation via suppression of Dll4-Notch1 lateral inhibition, thus resulting the increase of Dll4 expression. Enhance of mechanical force inhibits tip cell formation via activation of Dll4-Notch1 lateral inhibition, thus resulting the decreases of Dll4 expression. All these finding wills have great significance for various biomedical applications, such as tissue engineering, cancer, and drug screening.

This dissertation describes the development of a new method for increasing the resolution of the current protein microarray technology, down to the single molecule detection level. By using a technique called size-dependent self-assembly, different proteins can be bound to different sized fluorescent nanostructures, and then located on a patterned silicon substrate based on the sized pattern which is closest to the size of the bead diameter.The protein nanoarray was used to detect antibody-antigen binding, specifically anti-mouse IgG binding to mouse IgG. The protein nanoarray is designed with the goal of analyzing rare proteins. However, common proteins, such as IgG, are used in the initial testing of the array functionality. Mouse IgG, representing rare proteins, is conjugated to fluorescent beads and the beads are immobilized on a patterned silicon surface. Then anti-mouse IgG binds to the mouse IgG on the immobilized beads. The binding of the antibody, anti-mouse IgG, to the antigen, mouse IgG is determined by fluorescent signal attenuation.The first objective was to bind charged nanoparticles, conjugated with proteins, to an oppositely charged silicon substrate. Binding of negatively charged gold nanoparticles (AuNP), conjugated with mouse IgG, to a positively charged silicon surface was successful.The second objective was to demonstrate the method of size-dependent self-assembly at the nanometer scale (<100 >nm). Different-sized, carboxylated, fluorescent beads and AuNP, which were conjugated with proteins, were serially added to a patterned polymethyl methacrylate (PMMA) coated silicon surface. Size-dependent self-assembly was successfully demonstrated, down to the nanometer scale.The final objective was to obtain a signal from antibody-antigen binding within the protein array. Conjugated fluorescent beads were bound to e-beam patterns and signal attenuation was measured when the antibodies bound to the conjugated beads. The size-dependent self-assembly is a valuable new method that can be used for the detection and quantification of proteins.