Doctor of Philosophy / Department of Chemistry / Viktor Chikan / Ever depleting sources of fossil fuel has triggered more research in the field of alternate sources of energy. Over the past few years, CdSe nanoparticles have emerged as a material with a great potential for optoelectronic applications because of its easy exciton generation and charge separation. Electronic properties of CdSe nanoparticles are highly dependent on their size, shape and electronic environment. The main focus of this research is to explore the effect of different electronic environments on various spectroscopic properties of CdSe nanoparticles and link this to solar cell performance. To attain that goal, CdSe quantum dots (QDs) and nanorods (NRs) have been synthesized and either doped with metal dopants or embedded in polymer matrices. Electronic properties of these nanocomposites have been studied using several spectroscopic techniques such as absorption, photoluminescence, time-resolved photoluminescence, confocal microscopy and wide field microscopy. Indium and tin are the two metal dopants that have been used in the past to study the effect of doping on conductivity of CdSe QDs. Based on the photoluminescence quenching experiments, photoluminescence of both indium and tin doped samples suggest that they behave as n-type semiconductors. A comparison between theoretical and experimental data suggests that energy levels of indium doped and tin doped QDs are 280 meV and 100 meV lower than that of the lowest level of conduction band respectively. CdSe nanorods embedded in two different polymer matrices have been investigated using wide field fluorescence microscopy and confocal microscopy. The data reveals significant enhancement in bandedge luminescence of NRs in the vicinity of a conjugated polymer such as P3HT. Photoactive charge transfer from polymers to the surface traps of NRs may account for the observed behavior. Further study shows anti-correlation between bandedge and trap state emission of CdSe NRs. A recombination model has been proposed to explain the results. The origin of traps is also investigated and plausible explanations are drawn from the acquired data.

Doctor of Philosophy / Department of Chemistry / Christer Aakeröy / Physical properties of bulk solids are typically governed by the molecular arrangement of individual building blocks with respect to each other in the crystal lattice. Thus the ability to synthesize molecular crystals with pre-organized connectivities allows for the rational design of functional solids with desirable and tunable physical properties. A thorough understanding of the various intermolecular interactions that govern the solid-state architectures is an important pre-requisite for the rational design of molecular solids. In order to understand the role of molecular geometric complementarity in the design of solid-state architectures, we explored the structural landscape of two isomeric pyridine based acceptors (3N and 4N) with binding sites oriented along different directions, i.e. parallel and at angle of 60° respectively, with a series of even chain diacid (colinear binding sites) and odd chain diacid (binding sites oriented along 120°) using co-crystallization technique. The results obtained shows a striking correlation between the observed solid state architecture and geometric complementarity of interacting species. Combinations of 3N with odd and 4N with even chain diacid produced 1-D chains whereas 3N with even and 4N with odd chain diacid generated 0-D ring architectures. In order to exploit the possibility of fine-tuning physical properties using co-crystallization techniques, solubility measurements were performed on 3N and 4N co-crystals with the diacids. The results show that the solubilities of 3N and 4N in the co-crystal form were very different from their solubility in the pure form. Also, there was a strong correlation observed between the solubility of the co-crystals and their corresponding co-formers, i.e. diacids. To explore the dependence of crystal structure on a physical property such as melting point, we synthesized co-crystals of 3,3‟-azopyridine and 4,4‟-azopyridine with a series of even chain diacids. Structural consistency was obtained within the two groups of co-crystals. In both groups, 1-D chains were formed with the diacid as the primary building block. However, In the series of 3,3‟-azopyridine co-crystals, the co-crystal with succinic acid showed a different solid-state packing arrangement (although the primary building block was same as others) compared to the others in the same series. This difference is also reflected as a deviation in the melting point, while the others in the series showed a perfect correlation between the structural consistency and melting point behavior. It was also observed that the co-crystals of 4,4‟-azopyridine displayed higher melting points than co-crystals of 3,3‟-azopyridine which could be due to the differences in the overall packing of the crystal which is a combination of different intermolecular interactions that exist between molecules in the solid state. Using bi-functional donors (with both hydrogen and halogen bond donors on same backbone), we investigated the relative strengths of hydrogen and halogen bond donors in the presence of two isomeric acceptors, 3,3‟-azopyridine and 4,4‟-azopyridine, which exhibit geometric bias in their binding-site orientation. Based on the crystal structures, we noticed a preferential binding of hydrogen bond donors with 3,3‟-azopyridine and both hydrogen and halogen bond donors with 4,4‟-azopyridine. This shows that the two types of donors are very comparable and their binding preference is governed by the geometric complementarity between the donor-acceptor pair. Finally, we explored the scope of using co-crystallization for tuning the physical properties of two agrochemicals, cyprodinil and terbuthylazine. The crystal structures of the actives with a series of even chain diacids displayed structural consistency in the primary motifs within the two groups, while few differences were observed in the packing arrangement and secondary interactions. By forming co-crystals we were able to improve the solubility and melting point of cyprodinil, while ensuring that the hygroscopicity of the active was unaltered.

Doctor of Philosophy / Department of Chemistry / Kenneth J. Klabunde / A series of nanoparticle synthesis methods were devised with the aim of controlling shape. CuO nanorods were synthesized by a hydrothermal treatment with different chemical combinations. Physical parameters: concentration, temperature, and aging time greatly affected the size, morphology and the composition of nanorods. These CuO nanomaterials were reduced to metallic copper at elevated temperature by 4% H[subscript]2 diluted in helium while preserving the morphology. The CuO and Cu nanomaterials were employed for near infra-red (NIR) diffuse reflectance. Among them, CuO nanorods were found to be the best NIR diffuse reflectors, indicating potential application as NIR obscurants. Cu[subscript]2O and its composite samples with different morphologies, some with unique morphologies, were synthesized by reducing Cu[superscript]2[superscript]+ precursors without using any surfactant. The effects of change of Cu-precursors, reducing agents, and other physical conditions such as temperature and pressure were investigated. Since Cu[subscript]2O is a semiconductor (E[subscript]g ~ 2.1 eV), these samples were used as photocatalyst for the degradation of methyl violet B solution under UV-vis light and as dark catalysts for decomposition of H[subscript]2O[subscript]2 to investigate the effect of morphology. The photocatalytic activity was found to be morphology dependent and the dark catalytic activity was found to be dependent on both surface area and morphology. Mixed oxides of MgO and TiO[subscript]2 with different ratios, and pure TiO[subscript]2 were synthesized by two methods—flame synthesis and aerogel. These mixed oxides were employed as photo-catalysts under UV-vis light to oxidize acetaldehyde. The mixed oxides with low content of MgO (~ 2 mole %) were found to be more UV active photo-catalysts for the degradation of acetaldehyde than the degradation by TiO[subscript]2. The mixed oxides prepared by the aerogel method were found to be superior photo-catalysts than the mixed oxides of equal ratio prepared by flame synthesis. Silica aerosol gels were prepared by two methods: detonation and flame synthesis. Hexamethyldisiloxane (HMDSO) was used as a precursor during the detonation at different conditions. Interestingly, spherical silica nanoparticles were found to be formed by the detonation. Relatively smaller silica nanoparticles with larger volume fraction were found to be favorable for the formation of silica aerosol gels. During the flame synthesis, the silicon precursors, dimethoxydimethylsilane (DMDMS) and HMDSO, were used. Different shapes—spherical, oval, and non-spherical—and sizes of silica particles were formed. These silica nanomaterials were almost amorphous, and they might have many potential applications.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / The work presented in this thesis has demonstrated that supramolecular synthons can be used to make multicomponent crystals, and various synthons can be combined to make supermolecules. The synthons can also be used to construct nanoscale assemblies. Molecules containing single and multiple hydrogen-bond (HB) and halogen-bond (XB) acceptor sites have been synthesized in an effort to carry out supramolecular synthesis in order to establish a reliable hierarchy for intermolecular interactions. Pyrazole-based molecules have been made, combined with various carboxylic acids, and characterized using infrared (IR) spectroscopy to give a success rate of 55-70%. Reactions that gave a positive result were converted to solution experiments, and crystals were grown and characterized using single-crystal X-ray diffraction (XRD). The co-crystals display infinite 1-D chains with the intended stoichiometry and structural landscape on 6/6 occasions. The salts, on the other hand, display unpredictable stoichiometry and structural landscape on 5/5 occasions. Furthermore, the electrostatic charge on the primary hydrogen-bond acceptor, N(pyz), can be altered by adding a nitro, R-NO2, covalent handle to the backbone of the pyrazole molecule. Addition of a strongly electron withdrawing group significantly lowered the charge on the pyrazole nitrogen atom and, in turn, lowered the supramolecular yield to 10%. Ditopic molecules containing pyrazole and pyridine on the same molecular backbone were synthesized and characterized using 1H NMR. The molecules were co-crystallized with carboxylic acids, and the resulting solids were characterized using IR spectroscopy. The solids could then be classified as co-crystal or salt using specific markers in the IR spectrum. Single-crystal XRD was used to observe the intermolecular interactions in the co-crystals and salts, and the co-crystals were assigned to two groups: Group 1 (2) and Group 2 (2). The salts (4) show more unpredictability with stoichiometry and structural landscape. A library of ditopic molecules containing triazole and pyridine acceptor sites were synthesized and characterized using 1H and 13C NMR. The molecules were co-crystallized with carboxylic acids and the resulting solids were characterized using IR spectroscopy which demonstrated a 100% supramolecular yield whenever a pyridine moiety was present, consistent with results from Chapter 3. Single-crystal XRD was used to identify the intermolecular interactions in the co-crystals (2) and salt (1), and the results show that triazole can compete with pyridine for hydrogen bond donors. A library of ditopic molecules was also used for halogen-bonding (XB) studies with a series of activated iodine and bromine-based donors. The results show that iodine donors have a higher success rate range (12.5-75%) compared to bromine donors (16.7-50%) based on results obtained from IR spectra. Furthermore, the results from the XRD show that pyrazole nitrogen atoms can compete with pyridine for forming XB, and two groups of supramolecular synthons were observed. Finally, relatively weak non-covalent interactions, HB and XB, can influence the assembly of nanoparticles based on IR spectroscopy and TEM images. The assembly of the particles is influenced by specific capping ligands, which were synthesized and characterized using 1H, 13C and 19F NMR. The results demonstrate that relatively weak non-covalent interactions based on HB and XB interactions can influence nanoparticle assembly.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeröy / A series of four bifunctional ligands based on β-diketonate moieties bearing methyl, chloro, bromo and iodo substituents and their corresponding Cu(II) complexes were synthesized and crystallographically characterized in order to explore the possibility of using relatively weak halogen…halogen contacts for the directed assembly of predictable architectures in coordination chemistry. The four ligands have characteristic O–H...O intramolecular hydrogen bonds, and the structures of the halogenated ligands contain extended 1-D architectures based on C-O...X halogen bonds, which can be explained on the basis of electrostatic considerations. The corresponding Cu(II) complexes show a constant coordination chemistry for all the ligands, wherein the metal ion sits in a slightly distorted square-planar pocket, without any coordinated or uncoordinated solvent molecules. Furthermore, the absence of halogen-bonds in the coordination complexes is due to the depleted charge on the potential halogen-bond acceptors. As a result, the halogen-bonds are unable to compete with the inherent close packing in the crystal lattice, and thus display a head to head close-packed motif for methyl, chloro, and bromo, substituted Cu(II) complexes. The enhanced polarizability of the iodine atom, produces a more electropositive surface which means that this structure cannot accommodate a linear head-to-head arrangement due to electrostatic repulsion, and thus a unique close-packed structure very different from the three iso-structural complexes is observed for the iodo substituted Cu(II) complex.(1) Oximes offer great opportunities in supramolecular chemistry (hydrogen-bond donors), as well as in coordination chemistry (strong coordinating ligands). Hence, we established a versatile and robust mechanochemical route to aldehyde/ketone–oxime conversions for a broad range of aldehydes(2) and ketones(3) via a simple mortar–pestle grinding method. The relative reactivity of aldehydes vs. ketones under these conditions was also explored, along with an examination of the possible connection between reactivity and electronic substituent effects. The growing interest in the oxime (RR′C═N–OH) functionality, and a lack of the systematic examinations of the structural chemistry of such compounds, prompted us to carry out analysis of intermolecular oxime···oxime interactions, and identify the hydrogen-bond patterns for four major categories of oximes (R′ = −H, −CH3, −NH2, −CN), based on all available structural data in the CSD, complemented by three new relevant crystal structures.(4) It was found that the oximes could be divided into four groups depending on which type of predominant oxime···oxime interactions they present in the solid-state: (i) O–H···N dimers (R22(6)), (ii) O–H···N catemers (C(3)), (iii) O–H···O catemers (C(2)), and (iv) oximes in which the R′ group accepts a hydrogen bond from the oxime moiety catemers (C(6)). In order to explore and establish a hierarchy between hydrogen (HB) and halogen (XB) bonds in supramolecular architectures, we designed and synthesized two ditopic HB/XB donors, and screened them with a series of 20 HB acceptors. IR was used as a preliminary and reliable tool to gather information on the presence/absence of HB/XB in the different cases. We were able to get the solved single-crystal data for three of the 40 reactions. In two out of two cases with symmetric ditopic acceptors, both HB and XB were present leading to 1-D infinite chains, which suggests that in a system of “equal opportunities”, both these interactions can be tolerant of each other. In the only case with asymmetric ditopic acceptor, the HB donor binds to the best acceptor, whereas XB donor binds to the second best acceptor. This selectivity can be rationalized on the basis of electrostatic considerations, where the HB donor was shown to have a higher molecular electrostatic potential than the XB donor. Finally, we designed and synthesized a versatile and dynamic metallomacrocycle based on the 2,2'-bipyridyl backbone capable of controlling the metal-metal distance within the macrocycle cavity. The macrocycle was synthesized by high-dilution method and characterized by several spectroscopic techniques (IR, NMR, Mass, UV-Visible). Also, the macrocycle:Cu(II) stoichiometric ratio was determined by Job’s continuous variation method using UV-Visible spectroscopy, and was found to be 1:2, respectively. (1) Aakeröy, C. B; Sinha, A. S.; Chopade, P. D.; Desper, J. Dalton Trans. 2011, 40, 12160. (2) Aakeröy, C. B.; Sinha, A. S.; Epa, K. N.; Spartz, C. L.; Desper, J. Chem. Commun. 2012, 48, 11289. (3) Aakeröy, C. B.; Sinha, A. S. RSC Adv. 2013, 3, 8168. (4) Aakeröy, C. B.; Sinha, A. S.; Epa, K. N.; Chopade, P. D.; Smith, M. M.; Desper, J. Cryst. Growth Des. 2013, 13, 2687.

Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / This work examines the synthesis of novel chiral Schiff-base complexes derived from (1R,2R)-cyclohexanediamine and (R)-[1,1’-binaphthalene]-2-2’-diamine structural backbones with quinoline, isopropyl-quinoline, and benzoquinoline structural side-arms. We incorporated some degree of flexibility in the ligands and complexes so they can accommodate the sterics of different substrates during a catalytic reaction. We successfully achieved this by reducing the imine bond in the ligands to the corresponding amine bond. Therefore, the successful reduction and metallation of some of these ligands to give structures of different symmetries is reported. We had difficulty reducing ligands with the binaphthalene backbone but were able to partially reduce the ligand through a one-pot reaction with a zinc(II) salt and NaBH4. The complete 1H NMR assignments of the complexes reported in this thesis serve as a valuable tool for use in the characterization of future complexes. The complete NMR characterization of compounds reported is a complex process because they are polycyclic aromatic systems and the coupling network similarity in different parts of the molecule usually results in severe overlap of their 1H resonances. To overcome this impediment, we took advantage of various 2D-NMR techniques (COSY, NOESY, ROSEY, HSQC, and HMBC) along with other 1D-NMR experiments (1H HOMODEC, 1H, and 13C) to completely assign the desired complexes. Subsequently we also studied the coordination chemistry of several meal cations with our ligand system with the goal of obtaining single stranded monhelices. The potential use of some of the complexes in the area of NMR discrimination and kinetic resolution of racemic mixtures was examined and shown to be promising. Several NMR experiments were conducted using the racemic olefins 3-buten-2-ol and 1-penten-3-ol to demonstrate the discriminating power of our silver(I) complexes. We discovered that sterics play an important role in this resolution experiment and the bulky nature of our complexes affect the overall efficiency of the NMR discriminatory process as it diminishes the contact between the reactive metal center and the olefins involved. Temperature also plays a vital role in the chiral recognition of racemic olefins as we examined the ideal temperature needed to reduce the various dynamic processes that take place in solution at room temperature.

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / The first chapter in this thesis includes the design, synthesis, and evaluation of anti-Alzheimer and anti-norovirus activities of tricyclic pyrones (TPs). Alzheimer’s disease is a major cause of dementia and sixth leading cause of death; it is a growing problem all over the world. On the other hand, norovirus, a highly contagious agent is responsible for more than 90% of non-bacterial gastroenteritis causing severity mainly in the closed environments. No drugs exist to eradicate the symptoms developed by both of these disorders. Studies have shown that the development of Alzheimer’s disease and the infection of norovirus are dependent on cholesterol metabolism. More specifically, the inhibition of acyl-CoA: cholesterol acyltrasferase (ACAT) led to the reduction of plaques in Alzheimer’s disease as well as reduced the infection of norovirus. Mimicking the structure of CP2, a TP with promising anti-Alzheimer activities, a library of tricyclic pyrones containing phenyl, naphthyl, heterocyclic, and dipeptidyl moieties were synthesized and evaluated for their anti-Alzheimer and anti-norovirus efficacies. Several TPs containing phenyl and naphthyl groups showed sub-micromolar to nanomolar potencies for the protection of neuronal MC65 cells from Aβ-oligomers induced death. Similarly, the TPs containing pyrrolyl, imidazolyl, and quinolinyl moieties were effective to inhibit the norovirus replication in low micromolar range. The most effective TPs from MC65 cells protection assay were also effective in the inhibition ACAT and up-regulation ABCA1 gene. The second chapter in this thesis includes the design, synthesis, and anti-norovirus activity of thiouridine nucleosides. Many nucleosides have demonstrated effective inhibition of viral RNA polymerase, and some are progressing at different level of clinical trials for the treatment of hepatitis C virus. Some of the nucleosides, including 2’-C-methyl and 2’-amino substituted analogs, were found to effectively inhibit the norovirus replication. In the search of more potent anti-noroviral compounds, two thiouridine nucleosides were synthesized and evaluated as anti-norovirus agents. Both of these analogs were ineffective up to 50 μM for the inhibition of norovirus replication in cell based assay. Proposed work of converting these nucleosides to their phosphoramidate derivatives is also described.

Master of Science / Department of Chemistry / Daniel A. Higgins / The potential-dependent reorientation dynamics of double stranded DNA (ds-DNA) covalently attached to planar glassy carbon electrode (GCE) surfaces were studied in this thesis. The orientation of ds-DNA was investigated via the distance-dependent quenching of fluorescence from a 6–carboxyfluorescein (FAM6) flurophore to the electrode surface. The fluorophore was covalently bound to the distal end of the DNA. Fluorescence microscopy was employed for optical detection of FAM6 fluorescence and hence the DNA dynamics. The variation of the fluorescence from the dye with electrode potential is attributed to distance-dependent dipole-electrode energy transfer. Application of positive potentials (i.e., +0.2 V vs. open circuit potential, OCP) to the GCE caused the ds-DNA to align approximately parallel to the surface, yielding strong FAM6-electrode energy transfer and low fluorescence intensity. With the switching of the potential towards negative values (i.e., -0.4 V vs. OCP) the ds-DNA realigned perpendicular to the GCE surface leading to a reduction in energy transfer and high fluorescence intensity. Initial DNA reorientation upon a change in electrode potential is very fast. These fast dynamics have been observed and characterized in a number of previous publications. We have observed subsequent slow dynamics that we attribute to slow orientational relaxation of the DNA. Our observations were first reported by Q. Li, et al., J. Am. Chem. Soc. 2012, 134, 14467. In this thesis, this prior work is extended to verify the reproducibility of these new dynamics and to eliminate the possibility of certain artifacts as their source. Specifically, the experiments are repeated using a new cell design and a different buffer. In the primary experiments performed in this thesis, the dependence of the DNA reorientation dynamics on surface coverage was investigated by observing the fluorescence modulation as a function of probe concentration in the functionalization bath. Concentrations of 0.25, 1.0 and 1.5 µM 35-mer ds-DNA were employed. Electrodes functionalized at these concentrations have ds-DNA surface coverages of 1.18 x 10[superscript]12, 3.24 x 10[superscript]12 and 4.26 x 10[superscript]12 cm[superscript]-2, respectively. With increasing concentration of the DNA probe, the reorientation time constant at positive applied bias (vs. OCP) increased, indicting reorientation was slowed. In contrast, the time constant decreased with the negative applied bias (vs. OCP) indicating faster orientational relaxation. The possible origins for the observed trends in the reorientation time constant are discussed.

Doctor of Philosophy / Department of Chemistry / Eric A. Maatta / The thesis focuses on the design and synthesis of novel organoimido delivery reagents capable of forming bimetallic polyoxometalate (POM) hybrids, and their use in the assembly of bimetallic hexamolybdate derivatives. These delivery reagents have been designed thoughtfully and separate organic moieties have been selected for coordinating to both the POM cluster and the second metal atom. A series of three ligands [4-aminopiperidine, 4-(4-aminophenyl) piperazine, and 4-(4-aminophenyl) piperidine] were selected and used to synthesize the dithiocarbamate metal-coordinating ligands, which in turn were used for preparing the corresponding metal (M = Cr, Mn, Fe, Co, Ni, Cu, Zn, Ag) complexes. All the complexes were characterized by infrared spectroscopy (IR). Reported routes were followed for the covalent grafting of these metal complexes onto hexamolybdate. But, the poor solubility of these metal complexes was found to be a major stumbling block in our endeavors to synthesize the dithiocarbamate based polyoxometalate hybrids. The observed poor solubility of metal dithiocarbamate complexes was overcome by synthesizing [potassium(I) tris(3,5-diphenylpyrazole)borate] and [potassium(I) tris(3,5-dimethylpyrazole)borate] via thermal dehydrogenative condensation between tetrahydroborate and the respective pyrazole molecule. A series of corresponding transition metal (M = Co, Ni, Cu, Mn) complexes of tris(3,5-diphenylpyrazole)borate and tris(3,5-dimethylpyrazole)borate were synthesized, and characterized by IR and UV-visible spectroscopy, and single crystal X-ray diffraction. The single crystal structure of [manganese(II) (tris(3,5-dimethylpyrazole)borate)2] turned out to an outlier as it displayed the formation of a bis-complex, thus having no substitutable anion for further reaction with dithiocarbamates. Thereafter, a series of metal dithiocarbamate complexes of these [hydrotris(pyrazolyl)borates] (M = Co, Ni, Cu ) were prepared using [sodium 4-aminopiperidyldithiocarbamate] and were characterized by IR and UV-visible spectroscopy. A remarkable improvement in the solubility of these metal dithiocarbamates in organic solvents was observed. Furthermore, attempts to covalently graft these complexes onto hexamolybdate cluster were undertaken, and found to be unsuccessful possibly due to the strong oxidizing nature of PPh[subscript]3Br[subscript]2 and hexamolybdate. Although, we were able to successfully tailor the solubility of the dithiocarbamate complexes to suit our needs, our efforts to achieve the primary goal of synthesizing dithiocarbamate based polyoxometalate hybrids have so far been unsuccessful. A series of three pyridyl based ligands i.e., 3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-amine, 4-(pyridin-4-ylethynyl)aniline and 4-(pyridin-3-ylethynyl)aniline were synthesized and characterized. Covalent attachment of these ligands to hexamolybdate were attempted following various well-known routes. Although, no evidence of covalent attachment of 3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-amine to hexamolybdate was observed, the covalent grafting of 4-(pyridin-4-ylethynyl)aniline and 4-(pyridin-3-ylethynyl)aniline to hexamolybdate cluster was successfully achieved. Characterization of these novel organic-inorganic hybrids was done using IR and NMR spectroscopy as analytical tools. Attempts have been undertaken to obtain single crystals of these hybrids. Also, a novel route involving halogen bonding as a purification and separation technique for pyridyl functionalized hexamolybdate hybrids is also being explored. The novel acetylacetonate moiety has been explored as an imidodelivery reagent for synthesizing hexamolybdate covalent hybrids, wherein [3-(4-((4-aminophenyl)ethynyl)phenyl)-4-hydroxypent-3-en-2-one] ligand has been successfully synthesized and characterized. Traditional methods along with unconventional methods such as heating at elevated temperatures and microwave reaction conditions, have so far proved to be unsuccessful in the synthesis of the hybrids. A series of the corresponding metal complexes have been synthesized and characterized, where the ligand and its corresponding copper(II) complex have been characterized by single crystal XRD. In the crystal structure of the copper complex, the metal ion sits in a slightly distorted square-planar pocket, where no coordination to the -NH[subscript]2 group is observed, which highlights the potential of using it as an imidodelivery reagent.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / Computer simulations have provided a wealth of information concerning a wide range of systems. The precision of computer simulation results depends on the degree of sampling (time scales) achieved, while the accuracy of the results (given sufficient sampling) depends on the quality of force field used. A force field provides a description of the energy for a system of interest. Recently, we have been developing a Kirkwood Buff (KB) force field for molecular dynamics simulations of biological systems. This force field is based on the KB Theory of solutions, emphasizing the accurate description of intermolecular interactions, and reasonably reproducing a range of other physical properties from experiment. In this approach simulation results in terms of KB integrals can be directly compared with experimental data through a KB analysis of the solution properties. The approach therefore provides a simple and clear method to test the capability of a force field. Here we firstly studied a series of alcohol-water mixtures in an attempt to validate the transferability and additivity of the force field. A general fluctuation theory was applied to investigate the properties of these systems, and to compare with computer simulation results. The possible effects of cosolvents on peptides and proteins were then investigated using N-methylacetamide as model for the peptide backbone and urea as cosolvent. A possible explanation for the urea denaturation of protein structure was provided using a thermodynamics point of view involving transfer free energies and preferential interactions obtained from the KB integrals. Finally, potentials for protein backbone and sidechain torsions were developed by fitting to quantum mechanical calculations and NMR data. Simulations of a variety of peptides and proteins in aqueous solutions were then performed to demonstrate the overall reliability of the force field.