Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 161-175). Also available on the Internet.

Title from title page of PDF (University of Missouri--St. Louis, viewed Mar. 3, 2010). Includes bibliographical references.

Semi-crystalline polymers have shown increased crystalline order and size when confined in multilayered films by coextrusion1. The resulting large crystals lead to dramatic improvements in gas barrier properties. Ordered polymers whose characteristics are between that of the liquid phase and the crystalline phase are known as liquid crystalline polymers. The highly ordered mesogens in liquid crystalline polymers contribute to their exceptional bulk properties. In this research, side-chain liquid crystalline polymers were confined in multilayered films, made by either multilayer coextrusion or spin coating, with a non-liquid crystalline polymer in an attempt to improve the ordering of the liquid crystalline mesogens. The liquid crystalline behavior and morphology was studied to understand the correlation between the confinement size and the properties of the multilayer films. Commercial main chain liquid crystalline polymers and hydrogen bonded liquid crystalline polymers were also explored in this research for their use in multilayer coextrusion. / text

In the context of pharmaceutical development, it is abundantly clear that there is a need for greater understanding and control of crystalline phases. The field of crystal engineering is poised to address such issues and has matured into a paradigm for the supramolecular synthesis of new compounds with desired properties. Crystal structures are unpredictable by nature, however, the interactions that lead to crystal formation are becoming much more predictable. By means of model compound studies, the delineation of the hierarchy of hydrogen bonding between complementary functional groups or supramolecular heterosynthons can be accomplished. Competitive co-crystallization studies along with data extracted from the Cambridge Structural Database (CSD) can be utilized in understanding the reliability of supramolecular heterosynthons without the need for endless co-crystallization experiments. In effect, this ability to understand supramolecular heterosynthons can allow crystal engineers to rationally design co-crystals with a high rate of success. It has been suggested that pharmaceutical co-crystals could play a significant part in the future of API formulation since in principle they will outnumber pharmaceutical salts, polymorphs and solvates combined. The focus of this thesis is the understanding of the primary amide functional group and its hydrogen bonding capabilities; as well as the synthesis of model compounds in order to develop a blueprint for the design of pharmaceutical co-crystals using APIs that contain a primary amide functional group.

D. Tech. Polymer Technology. / Addresses the aim of generating new knowledge on: 1) the effect of supercritical CO2 on H-bond behaviour between polymers, and on 2) drug-loaded interpolymer complex preparation in supercritical CO2.

No description available.

Hydrogen bonding is seen extensively in Nature. It is manifest in DNA/RNA nucleic acid (nucleobase) pairing, the defining feature of the double helix, as well as in secondary structures in protein folding such as hairpin loops. This importance, thus coupled with the aesthetic appeal of nucleobase hydrogen-bonding interactions, has inspired us to design and synthesize new hydrogen-bonded assemblies that make use of Watson-Crick and Hoogsteen interactions. Currently, novel supramolecular architectures are being developed for the formation of supramolecular polymers via Watson-Crick hydrogen bonding of guanosine and cytidine. Supramolecular polymer formation occurs through hydrogen bonding, electronic interactions, and metal chelation, and allows for a highly thermodynamic system that can easily be broken and reformed through external stimuli. By synthesizing linear, metal-nucleobase, and functionalized guanosine entities, a variety of new “monomers” have been obtained. Their use in construction of main chain and side chain polymers, and G-quartet hydrogels are now being explored. The hydrogen bonding motifs used to develop supramolecular polymers are also attractive for developing through bond electron transfer systems. One inspiration for developing artificial donor-acceptor systems (i.e., linked through non-covalent interactions) comes from the light harvesting systems found in Nature. Triggered by a pulse of UV light, electron transfer across bridges, including charge separation and charge recombination processes can occur and the rates can be determined. As one part of this study, collaborators Igor Rubtsov and David Beratan studied how perturbing the vibrational modes of the bridge via IR pulse excitation, affected electron transfer. Mid-IR excitation of the donor-acceptor systems slowed the rate of electron transfer, likely because the molecular vibrations either disrupted the bridging hydrogen bonds or distorted the electronic interactions of the bridge. This observance could lend itself to the possibility of designing IR-controlled molecular switches and other devices Another mode of hydrogen bonding, Hoogsteen interactions, was explored in the context of developing a guanosine-quadruplex binder. Specifically, a pyrrole-based inosine was designed to direct hydrogen bonding via an extended Hoogsteen interaction in order to bind to quadruplex DNA. Quadruplex DNA has been studied as a folded form of DNA and, if stabilized, can inhibit gene replication especially amongst cancer strands. In summary, the candidate’s research efforts have focused on exploiting hydrogen bonding in nucleobases to construct novel supramolecular assemblies that could see eventual applications in materials chemistry, nanotechnology, and gene therapy. / text

La presente tesis consta de dos vertientes interrelacionadas. La primera se centra en intentar cuantificar experimentalmente la contribución energética en disolución de la interacción anión-, mediante el uso de calix[4]pirroles aril substituidos en las posiciones meso- como moléculas modelo. El trabajo realizado muestra que la interacción anión- es repulsiva para anillos con valores de ESP negativos y a medida que el efecto electrón atrayente de los sustituyentes aumenta la interacción se vuelve menos repulsiva, hasta que, cuando el valor de ESP en el centro del anillo aromático es positivo la interacción se vuelve ligeramente atractiva. La segunda en el uso de estos receptores simples para obtener arquitecturas supramoleculares más complejas, y su autoensamblaje en capsulas. Los estudios muestran que calix[4]pirroles sustituidos con grupos urea en sus anillos aromáticos se autoemsamblan en capsulas diméricas en presencia de un huesped adecuado como los N-óxidos de alquil aminas y piridinas en disolventes apolares. / This thesis consists of two interrelated aspects. The first one pretends to quantify experimentally the energetic contribution in solution of the anion- interaction, using aryl extended calix[4] pyrroles substituted in their meso- positions as a model system. The work performed shows that the anion- interaction is repulsive for aromatic rings with negative ESP values, as the electron withdrawing character of the substituent increases the interaction becomes less repulsive, until eventually, when the ESP value in the center of the aromatic ring is positive the interaction turns into slightly attractive.The second one is based on the use of these simple receptors as scaffolds to obtain complex structures and their self-assembly into capsules. The studies performed show that aryl extended calix[4]pyrroles substituted with urea functions on their upper rim self-assemble into dimeric capsules in the presence of a suitable guest like the N-oxides of alkyl amines and pyridines in non-polar solvents.

This thesis is based on nine research publications (I – IX) on structure and reactivity of RNA vis-à-vis DNA. The DNA and RNA are made of flexible pentose sugar units, polyelectrolytic phosphodiester backbone, and heterocyclic nucleobases. DNA stores our genetic code, whereas RNA is involved both in protein biosynthesis and catalysis. Various ligand-binding and recognition properties of DNA/RNA are mediated through inter- and intra-molecular H-bonding and stacking interactions, beside hydration, van der Waal and London dispersion forces. In this work the pH dependant chemical shift, pKa values of 2'-OH group as well as those the nucleobases in different sequence context, alkaline hydrolysis of the internucleotidic phosphodiester bonds and analysis of NOESY footprints along with NMR constrained molecular dynamics simulation were used as tools to explore and understand the physico-chemical behavior of various nucleic acid sequences, and the forces involved in their self-assembly process. Papers I – II showed that the ionization of 2'-OH group is nucleobase-dependant. Paper III showed that the chemical characters of internucleotidic phosphate are non-identical in RNA compared to that of DNA. Papers IV – VI show that variable intramolecular electrostatic interactions between electronically coupled nearest neighbor nucleobases in a ssRNA can modulate their respective pseudoaromatic character, and result in creation of a unique set of aglycons with unique properties depending on propensity and geometry of nearest neighbor interaction. Paper VII showed that the cross-modulation of the pseudoaromatic character of nucleobases by the nearest neighbor is sequence-dependant in nature in oligonucleotides. Paper VIII showed that the purine-rich hexameric ssDNA and ssRNA retain the right-handed helical structure (B-type in ssDNA and A-type in ssRNA) in the single-stranded form even in absence of intermolecular hydrogen bonding. The directionality of stacking geometry however differs in ssDNA compared to ssRNA. In ssDNA the relatively electron-rich imidazole stacks above the electron-deficient pyrimidine in the 5' to 3' direction, in contradistinction, the pyrimidine stacks above the imidazole in the 5' to 3' direction in ssRNA. Paper IX showed that the pKa values of the nucleobases in monomeric nucleotides can be used to show that a RNA-RNA duplex is more stable than a DNA-DNA duplex. The dissection of the relative strength of base-pairing and stacking showed that the relative contribution of former compared to that of the latter in an RNA-RNA over the corresponding DNA-DNA duplexes decreases with the increasing content of A-T/U base pairs in a sequence.

Solid-state NMR spectroscopy is used to investigate strong hydrogen bonds in a variety of solids. NMR measurements of the 2H nuclear quadrupole coupling (CQ) and nuclear magnetic shielding tensors are performed on samples of trimethylammonium chloride (TMAC), protonated 1,8-bis(dimethylamino)napthalene (DMANH+), and potassium and sodium bifluoride. 2H CPMAS is used to obtain high quality spectra while reducing experimental time. From spectral simulations, values of 127, 36, 59 and 58 kHz are determined for the 2H CQ of TMAC, DMANH+ CF3SO3-, NaHF2 and KHF2, respectively. The 2H CPMAS spectrum of TMAC shows a minor secondary component resulting from a solid phase in which the trimethylammonium cation is experiencing precessional motion. At high temperature the 2H CPMAS spectrum of DMANH+ shows unexpected spinning sideband lineshapes because of residual dipolar coupling to 14N. The experimental 2H CQ values are corroborated by ab-initio and DFT calculations; for DMAN and the bifluorides the 2H CQ values are averaged over the potential energy surface to improve the computational quality. Large values of the isotropic chemical shift (>10 ppm) are observed for all of the hydrogen-bonded deuterons. To complement the 2H NMR work, other nuclei in the compounds of interest are investigated, for TMAC these include: 35Cl, 37Cl, 1H, 14N, 15N. The 35Cl CQ shows a small, but observable deuterium/proton isotope effect. Quadrupolar and chemical shift parameters for assorted nuclei in TMAC are calculated at various N-H distances, demonstrating the strong dependence of the chlorine and hydrogen parameters on the proton position. For DMANH+ the 15N CPMAS spectrum of a static sample of DMANH+-d1 provides a value for the average dipolar 15N-D coupling constant of 870±30 Hz, corresponding to a distance of 1.29 A. Spectra of the counterions in the bifluoride salts are obtained, providing CQ values of 123 kHz and 1.141 MHz for 39K and 23Na, respectively.