Gold nanoparticles have been widely known for many centuries. Until the 1990’s, gold nanoparticles were able to be synthesized in aqueous solutions with little functionalization of the nanoparticle due to the synthetic procedures that existed. In 1994 a synthetic technique was developed by Brust-Schiffrin which provided for the production of gold nanoparticles that could be easily obtained. Murray further developed this synthesis to provide for nanoparticles with many different functional groups and with various sizes. These nanoparticles synthesized through this method would afford for systems that would be capable of providing for biomacromolecular surface recognition; where the characteristics needed for surface recognition include the need for a large complementary surface with multiple recognition units for specificity. Using the Brust-Schiffrin and Murry techniques we synthesized a gold nanoparticle which was functionalized with mercaptoundecanoic acid. This nanoparticle provided a water soluble nanoparticle which was easily synthesized and had pH solubility dependence. This nanoparticle was used effectively to bind α-chymotrypsin. The mercaptoundecanoic acid functionalized nanoparticle when bound to the enzyme afforded a denatured chymotrypsin which was released by the addition of a surfactant with some activity towards the substrate, succinyl-Phe-Ala- p-nitroanilide. It was found that this released enzyme had new specificity towards other substrates with limited or no activity on substrates with larger peptide side chains. The released enzyme was observed to have the most activity towards the substrate, benzoyl-Tyr-p-nitroanilide. A gold nanoparticle was synthesized that was functionalized by 2-(10-mercapto-decyl)-malonic acid. This provided for a nanoparticle that bound α-chymotrypsin and effectively inhibited the enzyme with little denaturation of the enzyme. The electrostatic nature of this complexation was probed by observing the effect of NaCl concentration upon the binding of the nanoparticle to the enzyme. Higher salt concentrations were observed to completely disrupt the binding, thus affording no inhibition of the enzyme’s activity. The nanoparticle-enzyme preformed complex was observed to be completely disrupted upon the addition of high salt concentrations. The released enzyme was observed to have 90% of the activity of native chymotrypsin.

The application of bionanotechnology in medicine has tremendously increased over past three decades. The role of synthetic polymer/supramolecular chemistry has proven to be a key component in this multidisciplinary research. Towards that direction, this thesis work describes the entry of our group research in the area of “applications of custom designed amphiphilic macromolecules in medicine or biology”. We have successfully used our amphiphilic homopolymer scaffold to recognize, bind and modulate the function of the proteins. The proof of concept was demonstrated using two proteins, chymotrypsin and cytochrome c. Further, We have also synthesized water-soluble fluorescent organic nanosensors by functionalizing the amphiphilic polymers with appropriate organic dye. These fluorescent nanosensors have been effectively used to detect the presence of metalloproteins in the presence of nonmetalloproteins. Along that direction, we have also utilized our scaffold to detect a particular metalloproteins by creating pattern using Stern-Volmer quenching studies.

Functionalized gold nanoparticles (AuNPs) provide an excellent scaffold for numerous biological applications. In these systems, the gold core imparts stability to the assembly, while the monolayer allows tuning of surface characteristics such as charge and hydrophobicity. The nano-scale size and tunable surface properties have made them an ideal candidate for manipulating protein-protein/protein-nucleic acid interactions, and delivery of therapeutics. In this thesis work, it has been demonstrated how the surface coating plays an important role in achieving a desired goal. Using organic synthesis as a tool, the monolayer was tailored to afford useful particles with biocompatibility and the ability to respond in the cellular environment. The recognition units present on the periphery of particles dictates/controls their interactions with biomolecular or cell surfaces. As described here, these engineered particles exhibited a number of bio-applications, including folding of a peptide into an α-helix, binding with DNA, and cellular delivery of genes and proteins.

We have combined the tools of organometallic chemistry with those of organic chemistry, and explored methodology and mechanism of palladium and copper-based catalysis. Organometallic chemistry plays a prominent role in industrial and academic laboratories, and developments in this field continue to expand our fundamental understating of chemical reactions. Herein, we report on a specific failure of a palladium-catalyzed coupling reaction, and the subsequent development of alternative copper-based methodologies. We have developed a new cross coupling protocol for the synthesis of unsymmetrical triarylphosphines, using copper-based catalysis. Furthermore, we conducted a thorough investigation into the mechanism of the centuryold Ullmann coupling. Our mechanistic research is based on rational experimental design intended to address fundamental questions regarding copper-based catalysis. One such question is: what is the nature of the reaction intermediate( s); our data is inconsistent with copper(III) intermediates.

The self-assembly process in solution and solution/solid interface was explored in this work. Initial work focused on the development of receptors based on 6-aryl-2,4-acyldiamino-s-triazines for investigating the recognition process with flavin in solution. Self-assembled monolayer (SAM) functionalized gold colloids and flat gold surfaces were used for the studies of interfacial recognition processes. We have incorporated molecular recognition elements and photo-switchable units into the monolayers of gold nanoparticles, allowing for exploration of the photochemical control of interfacial recognition processes. Adaptation of the self-assembly process for surface modification was also investigated. The surfaces were modified by synthetic polymers through recognition processes between thymine functional group of surface and complementary diaminopyridine functional group of polymer sidechains. Through this strategy, we have also shown the diaminopyridine (DAP) functionalized POSS derivatives self-assemble on thymine functionalized monolayers on gold surfaces. This recognition-mediated surface modification strategy could be extended onto other surfaces. Finally, a novel approach to highly ordered and modular nanoelectrode arrays (NEAs) was developed using block copolymer self-assembly. Variable scan rate cyclic voltammetry studies were performed to characterize the NEA.

Combining the tools of traditional organic synthesis with those of the emerging field of supramolecular chemistry, we have designed several interesting systems based on triarylamines. This moiety has been well established as versatile electroactive group for use in electronic and electro-optic materials. Herein, we report the development of a D3h triketone building block for potential use in the assembly of higher dimensional electronic solids. We have also developed a series of bridged triarylamines that constitute a new class of electroactive heterohelicenes. Furthermore, we have show that these systems form stable radical cations and have the ability to emit circularly polarized light. Finally, we have demonstrated the ability to direct the solid state structures of arylamines to form zig-zag, helical, tetrahedral, and porous architectures.

Copper(I) complexes of type [Cu(PPh3)3X] (where X: Br, Cl), [Cu(PPh3)2NO3], Cu(L)(PPh 3)2X (where X: PF6, NO3, ClO4 and L: phenanthroline, diimine, neocuproine), Cu(L)(PPh3)X (where X: Br and L: phenanthroline, di-imine, neocuproine) are synthesized and characterized to study their catalytic activities in carbon-heteroatom bond formation reactions. The geometrical parameters illustrate that there is a correlation between bite angles and copper-phosphorous bond lengths in mononuclear chelated copper(I) complexes. These complexes had wider bite angles than mononuclear non-chelated copper(I) complexes. Screening of the mononuclear copper(I) complexes in aryl-oxygen bond formation reactions show that the complexes [Cu(PPh3)3Br] and [Cu(neocup)(PPh3)Br] catalyzed the formation of a range of substituted diphenyl ethers at 20 mol% and 10 mol% catalyst loadings respectively. The polynuclear copper(I) complexes fail to catalyze the same reaction. In aryl-nitrogen bond formation reactions, the same complexes [Cu(PPh3)3Br] and [Cu(neocup)(PPh 3)Br] enable the formation of a range of diaryl and triaryl amines. The protocol with [Cu(PPh3)3Br] is used for the successful synthesis of o.o′.o ″-amino-trisbenzoic acid-trimethylester at 170°C in o-dichlorobenzene. This molecule is eluded by the Hartwig-Buchwald protocol. The well-defined complex [Cu(neocup)(PPh3)Br] is further investigated for the formation of aryl-sulfur and aryl-selenium bonds. Optimization and control experiments in this area show that using neocuproine as an additive with CuI, in the presence of NaOt-Bu, in toluene allows the development of protocols for a range of aryl-sulfides and aryl-selenides. In the second protocol, the change of base to K2CO3 allows the coupling of a range of electron-poor iodides to the respective diaryl selenides. The observed results point to the potential of copper(I) catalysts as alternatives to palladium-based protocols, for the formation of aryl-O, N, S and Se bonds under mild conditions.

This dissertation aims to understand the effect of incompatible side chains on the complexes of π-conjugated electron-rich donors and electron-deficient acceptors in solution. The role of incompatible side chains were studied in simple mixtures of organic donor and acceptor molecules that form donor-acceptor complexes. The incompatible branched and linear alkane side chains on the acceptor and donor respectively prevented complex formation between naphthalene diimide acceptor and naphthalene ether donor. However, the incompatible hydrocarbon-fluorocarbon and polar-non polar side chain pairs did not affect complex formation between the donor and acceptor. In quaterthiophene-naphthalene diimide dyads, the incompatibility of the side chain on the acceptor with respect to the side chain on the donor do not have any influence on the donor-acceptor complex formation. Irrespective of the attached side chains, all the dyads show charge transfer absorption bands and have similar electron transfer rates. The effect of point of attachment of the acceptor to the donor in the quaterthiophene-flavin dyad is also studied.

Amphiphilic assemblies have been extensively used in the past decades. This thesis discusses the design and synthesis of the amphiphilic molecules for the application in stimuli sensitive materials, selective labeling of biomolecules and biomarkers detection. A series of oligomers, containing ethylene glycol moieties, with the same composition of amphiphilic functionalities has been designed, synthesized, and characterized for their temperature sensitive behavior. The non-covalent, amphiphilic aggregates, formed from these molecules influence the temperature sensitivity of these molecules. Moreover, the covalent tethering of the amphiphilic units also has significant influence on their temperature sensitivity. The thermal sensitivity of these oligomers show increasingly sharp transitions with increasing numbers of OEG functional groups, indicating enhanced cooperativity in dehydration of the OEG moieties when covalently tethered. These molecules were also engineered to be concurrently sensitive to enzymatic reaction and pH. Supramolecular assemblies formed by amphiphilic homopolymers with negatively-charged groups in the hydrophilic segment have been designed to enable high labeling selectivity towards reactive side chain functional groups in peptides. The negatively-charged interiors of the supramolecular assemblies are found to block the reactivity of protonated amines that would otherwise be reactive in aqueous solution, while maintaining the reactivity of non-protonated amines. Simple changes to the pH of the assemblies' interiors allow control over the reactivity of different functional groups in a manner that is dependent on the pKa of a given peptide functional group. The labeling studies carried out in positively charged supramolecular assemblies and free buffer solution show that, even when the amine is protonated, labeling selectivity exists only when complementary electrostatic interactions are present, thereby demonstrating the electrostatically controlled nature of these reactions. The charged reverse micelle for peptide selective labeling is expanded to protein engineering. Through the labeling study of myoglobin inside both negatively and positively charged reverse micelles, as well as in free solution, we found that the macromolecules (myoglobin) behave very differently with small peptide. Not only the electrostatic interactions, but also steric effects can control the selective engineering of protein. Our carboxylate-based amphiphilic homopolymer has been used for peptide enrichment and detection, however, there is a shortcoming with this polymer. At acidic condition, the carboxylate polymer is not desirable system. The analysis of the problem and the solution for it is demonstrated in this thesis.

A series of model compounds, having phenoxyl, nitroxyl and nitronyl nitroxide radical pendant groups, were studied in order to better understand exchange coupling of several linker units. Stability of these radical containing model compounds was found to be as important as the delocalization of the radicals for further study in polymeric systems. Also, structure-property relations of different morphologies of poly(2,6-di-tert-butyl-4-$(2\sp\prime,4\sp\prime,6\sp\prime$-tri-tert-butyl-phenyloxalato) phenyl acetylene were examined using spectroscopic techniques. Stability of the polyradical and the side reactions seen within this polymer were clearly explaining to us why paramagnetic behavior is being observed instead of expected ferromagnetic coupling. Ferrocenyl radical precursors were found to be highly susceptible for auto-oxidation and further reduction under basic solution media. Similar behavior was seen for the studied (2,6-di-tert-butyl-4-nitronylnitroxyl) phenoxyl diradical. The unusual ESR spectra of these compounds implied their easy auto-oxidation due to strong electron donating ability of both ferrocene and para-hydroxyl groups. Studying nitronyl nitroxide radical precursors of the above compounds enabled us to observe step by step oxidation of these compounds for the first time using ESR spectroscopy. This study gave us important clues for studying the mechanism of the nitronyl nitroxide radical formation in our systems. High delocalization capability of phenoxyl radicals having para acetylenic units formed an important barrier preventing us from observing exchange coupling behavior of acetylenic model compounds. Further study is needed for this group of molecules in order to eliminate reactive sides within the structures. ESR study of these compounds can be possible only after synthesis of stable acetylenic radical precursors.