Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 193-199). Available also in a digital version from Dissertation Abstracts.

published_or_final_version / Chemistry / Master / Master of Philosophy

Ferroelectric liquid crystals (FLCs) exhibit a bulk electric polarization (PS) that can be coupled to an electric field to produce an ON-OFF light shutter, and are being investigated as an alternative to nematic liquid crystals in display applications. Commercial FLC mixtures normally consist of a small amount of chiral dopant in an achiral smectic C (SmC) liquid crystal host. Because the switching time of FLC display is inversely proportional to the induced polarization, the design of chiral dopants with high polarization powers (p) is a key aspect of FLC research. Such work requires an understanding of the relationship between molecular structure and polar order in the chiral SmC* phase. Previous work in the Lemieux group focused on 2,2’-spirobiindan-1,1’-diones dopants, and a conformational model was proposed to explain the observed host dependence of the polarization power (p) of these dopants. In order to test this model, the 2,2’-spirobiindan-1,1’-dione core has been modified by introducing polar substituents and by modifying the functional groups linking the core to the alkyl side-chains. Specifically, this thesis focuses on implementing this approach via the synthesis and characterization of chloro- and methyl-substituted 2,2’-spirobiindan-1,1’-dione dopants. Four chiral dopants (2.1a, 2.1b, 2.2a and 2.2b) were synthesized, resolved and their absolute configurations assigned by CD spectroscopy. Their polarization powers were measured in four SmC hosts with different core structures. For both the ether-linked and ester-linked dopants, the addition of a substituent at the 6-position of one indanone ring results in lower polarization powers regardless of the size and polarity of the substituent, which is contrary to the original conformational distribution model. A comparative study of the data suggests that the ester-linked dopants exert much stronger perturbations on the host environment than the ether-linked dopants, especially when the 6-position is substituted. We postulate that this perturbation is chiral in nature, and that the feedback effect of chirality transfer causes a shift in the conformational distribution of the dopant favoring conformers with negative polarity. Probe experiments were performed to detect the effect of chirality transfer feedback (CTF) in the case of the chloro-substituted diester dopant (2.1b), showing consistent results with the postulate. / Thesis (Master, Chemistry) -- Queen's University, 2007-09-28 12:26:06.486

The effect of hydrogen bonding on the conformation of organic moleculesunifies two projects in this thesis. In one project, the stability of the intramolecularhydrogen bond in derivatives of 2-guanidinobenzimidazole was studied bydynamic 1H NMR spectrometry. The impact that this intramolecular hydrogenbond had on the bond order of the neutral guanidino group and on the dynamicconformation of these aromatic structures was related to the concept of hydrogenbond-assisted resonance. In another project, an oligomer possessing repetitiveconformation and capable of much inter- and intramolecular hydrogen bondingwas designed and synthesized. The sensitivity of this oligomer to changes inanion concentration, as well as its own propensity to self-aggregate weremeasured.Hydrogen bonds found in many biological oligomers are connected thougha system of conjugated bonds. Guanidinobenzimidazole is a conjugated systemof carbon and nitrogen, connected by an intramolecular hydrogen bond. Severalderivatives of guanidinobenzimidazole were synthesized, and the effect ofseveral simple alkyl for hydrogen substitutions were studied.Guanidinobenzimidazole was used as a model to study what effect theconjugation and the intramolecular hydrogen bond have on each other.The formation of redundant low energy hydrogen bonds is universal inbiological oligomers. In DNA and RNA multiple hydrogen bonds are formed witha typical energy contribution of only 1-2 kcal/mol. Individually, these interactionsdo not give the biological oligomers their conformational stability, but togetherthey are very stable. The urea and amide based oligomers designed in the workand discussed in the thesis should form multiple hydrogen bonds withthemselves and/or with anionic guests. Chiral oligoureas were designed topossess this characteristic of cooperative conformation that so many biologicaloligomers and polymers share.

An empirical approach to the study of phosphine compounds was completed using Molecular Mechanics 2 (MM2), and several computer programs written to descibe and analyze the final geometric orientations of the molecules. The calculations were performed on 64 conformers of 16 different phosphines. Results from these calculations were compared to those previously obtained for MNDO and MINDO/3 calculations, and to experimental data. Cone angles calculated from the MM2 optimized geometries, were compared to Tolman's original work, and to values obtained from semiempirical calculations, and to experimental results. In general, it was found that weighted average cone angles best represent the size of phosphine ligands. / Department of Chemistry

Thesis (Ph.D.) -- University of Adelaide, Department of Organic Chemistry, 1981.

Thesis (Ph. D.)--Michigan State University. Dept. of Chemistry, 2008. / Title from PDF t.p. (viewed July 31, 2009). Includes bibliographical references (p. 179-187). Also issued in print.

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Zhu, Cheng; Committee Member: Babensee , Julia; Committee Member: Garcia, Andres; Committee Member: McIntire, Larry; Committee Member: Selvaraj, Periasamy; Committee Member: Springer, Timothy

The main focus of my dissertation is on the conformational motion of DNA, studied by applying tools from the computational chemistry field. In addition, studies of relative α- and 310 helical stabilities in peptides/mini-proteins, and a molecular flooding study of the retinoid X-receptor as part of a continuing drug design effort are presented. In molecular biology, it has been well known that sequence determines structure, and structure controls function. For proteins or DNA to work properly, the correct configuration is required. Mutations may alter the structure, which can cause malfunction. Non-mutational effects, such as a change in environment may also cause a configurational change and in turn change the functionality of the protein or DNA. Many experimental technics have been developed to investigate the structural or configurational aspects of biological systems, and molecular dynamics simulation has been proven to be a useful complementary tool to gain insights into this problem due to its ability to explore the dynamics and energetics of biomolecular processes at high spatial and time resolution. Molecular dynamics simulations are constrained by the available computational power, but several computational techniques have been developed to reduce computational costs. Also, development of hardware has helped the issue. Years of hard work on force field parameter optimization built a solid foundation for molecular dynamics simulations, so that the computational model can satisfactory describe many biochemical systems in detail. Techniques such as umbrella ix sampling and reweighting methods have allowed researchers to construct free energy landscapes to reveal the relative stabilities of each major configurational state and the free energy barriers between configurations from relatively short simulations, a process which would otherwise require many microseconds of unbiased simulations. My dissertation applies multiple advanced simulation techniques to investigate several DNA conformational problems, including the coupling between DNA bending and base flipping, the anisotropy of DNA bending, and intercalation of the dye in a Cy3 labeled DNA system. The main part of this work addressed a long standing question about DNA bending: does DNA prefer to bend toward the major or minor groove. My simulations not only answered this question, but also identified the mechanism by which the one direction is favored. Another part describes peptide/mini-protein helical transitions and studies benefiting ligand design for the retinoid X-receptor.

Yes / Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing dataset of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identify deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, alpha-helices have lower entropy on average than do beta-sheets, and both are lower than coil regions. / National Institutes of Health, US Department of Energy Office of Biological Research, National Energy Research Scientific Computing Center, Swedish Research Council, Knut and Alic Wallenberg Foundation