Physical Sciences and Mathematics Commons^™

Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky

Department of Chemistry: Dissertations, Theses, and Student Research

High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.

The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …

Development And Application Of Combined Quantum Mechanical And Molecular Mechanical Methods, Rui Lai

Department of Chemistry: Dissertations, Theses, and Student Research

Compromising of computational cost and accuracy, combined quantum mechanical and molecular mechanical (QM/MM) methods are practical methods for studying large molecular systems. The use of induced dipole polarizable force fields can significantly improve the accuracy of MM and QM/MM methods. However, induced dipole models tend to overestimate the polarization energy at short interaction distances. Damping functions can be applied to reduce the over polarization. MM-MM damping schemes have been developed to correct the overestimated polarization between MM atoms; QM-MM damping scheme has not been developed. In this thesis, a QM-MM damping scheme is developed for the damping of the MM …

Hydrolytically Stable Analogues Of Sugar Phosphates And A Miniaturized In Situ Enzymatic Screen, Xiang Fei

Department of Chemistry: Dissertations, Theses, and Student Research

The glmS riboswitch undergoes self-cleavage upon binding its metabolic product GlcN6P, thereby providing a negative feedback mechanism limiting translation of the glmS protein when GlcN6P is abundant. As a first step toward the development of novel antimicrobials, we have synthesized a series of GlcN6P analogues bearing phosphatase-inert surrogates in place of the natural phosphate ester functionality. The self-cleavage assay identified two such compounds that display significant riboswitch actuator activity; namely those bearing a 6-phosphonomethyl group or a 6-O-malonyl ether. These two analogues exhibit a 22-fold and a 27-fold higher catalytic efficiency, respectively, than does glucosamine. Docking experiments were …

Syntheses Of Aminyl Diradicals And Nitroxide Tetra- And Octaradicals, Arnon Olankitwanit

Department of Chemistry: Dissertations, Theses, and Student Research

This dissertation comprises of two main research projects: aminyl diradicals and calix[4]arene nitroxide tetra- and octaradicals. The design, multi-step synthesis and characterization, including NMR, EPR spectroscopy, magnetic measurements and X-ray crystallography of precursors and target compounds will be discussed.

Aminyl radicals, nitrogen-centered radicals, are typically short-lived and considered as reactive intermediates. Because of their unique magnetic properties, aminyls are attractive building blocks for high-spin di-and polyradicals. The challenge is in the design and synthesis of aminyls with increased stability. In this chapter, we have prepared triplet (S = 1) ground state aminyl diradicals, which are derivatives of aza-m …

Application Of Nuclear Magnetic Resonance Based Metabolomics To Study The Central Metabolism Of Staphylococci, Bo Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

Metabolomics studies the collection of small molecules (metabolites) involved in enzymatically catalyzed reactions, cell signaling and cellular structure. Perturbations in metabolite concentrations have been used to reflect the activity of corresponding enzymes or proteins. Nuclear magnetic resonance (NMR) spectroscopy is a well-known approach for the structure determination of biological macromolecules. Alternatively, NMR has recently been established as a valuable tool of metabolomics, in which NMR spectral signals correlate small molecules with cellular activities. This has been accomplished through the chemometric analysis of high-throughput one dimensional ¹H spectra (metabolic fingerprinting) and quantitative metabolite identification based on two dimensional ¹H, …

Implementation And Application Of The Mmff94 Force Field, Hongbo Zhu

Department of Chemistry: Dissertations, Theses, and Student Research

MMFF94 is implemented for molecular mechanics calculation in the quantum chemistry polarizable force field program (QuanPol). As a general force field for organic molecules, the availability of MMFF94 expends the capability of the QuanPol program. The MMFF94 force field atom type determination and parameter matching methods are established and corresponding program routines are written in the FORTRAN language. In this implementation, the MMFF94 atom types can be determined automatically from the connectivity of the input atoms with no or minimum information of formal charges. This implementation of MMFF94 is validated using the 761 standard tests, thus is a complete implementation. …

Studies In Asymmetric Synthesis: Supramolecular Catalysis, C-H Activation, And D-Cycloserine Synthesis, Nathan C. Thacker

Department of Chemistry: Dissertations, Theses, and Student Research

Rh-catalyzed asymmetric hydrogenation has emerged as a powerful tool for the manufacturing of chiral pharmaceuticals. While the mechanism is well understood, catalyst design a priori is not yet possible. Supramolecular catalysis, the use of non-covalent forces to affect a catalytic process, can afford the catalyst diversity required to uncover efficient catalysts and further our understanding. Using a modular design and self-assembly, a large scale supramolecular catalyst screening in a catalyst scaffold optimization study of rhodium-catalyzed asymmetric hydrogenation was carried out. Analyzing the data yields some new insights into the roles of each module making up the supramolecular catalyst. Perhaps most …