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Washington University in St. Louis

Theses/Dissertations

2011

Chemistry

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Part I Development Of Nucleophilic Acylation Catalysts Part Ii Chiral Brønsted Acid Catalyzed Enantioselective Alcoholysis, Guojian Lu Jan 2011

Part I Development Of Nucleophilic Acylation Catalysts Part Ii Chiral Brønsted Acid Catalyzed Enantioselective Alcoholysis, Guojian Lu

All Theses and Dissertations (ETDs)

Chiral bicyclic amidines and isothioureas developed in our group have been showed as a new type of nucleophilic acyl transfer catalysts. Based on the previous achievement in our group, several aza-analogues and a 5,7-menbered ring bicyclic analogue of THTP were prepared. Its synthesis proved to be more laborious than that of the THTP analogue derivative, and the enantioselectivity was substantially lower. Based on the previous discovery in our group that 1,2,4-triazole anion, as an active acyl transfer catalyst, can promote aminolysis and transesterification of moderately activated or even unactivated esters, a systematic study of pyrazole derivatives in this transformation was …


Quantitative Perfusion-Sensitive Mri Phantoms, Jeff Anderson Jan 2011

Quantitative Perfusion-Sensitive Mri Phantoms, Jeff Anderson

All Theses and Dissertations (ETDs)

Perfusion-sensitive MR methods are increasingly utilized in preclinical and clinical MR research studies with the promise of providing quantitative estimates of parameters that describe in vivo microvasculature. One of these techniques, dynamic contrast enhanced: DCE) MRI, has found particularly common use in oncology for the detection, staging, and monitoring of highly vascularized tumors. DCE-MRI has been qualitatively validated by various studies that show a high correlation between modeled parameters from DCE and histologically measured microvascular density: MVD). However, in the absence of a matching "gold-standard" technique, DCE-MRI has not yet been quantitatively validated: i.e., the accuracy of the estimated parameters …


Design, Synthesis And Characterization Of Lipidated Pna-Peptide Conjugates As Potentialtherapeutic And Diagnostic Reagents, Yinyin Song Jan 2011

Design, Synthesis And Characterization Of Lipidated Pna-Peptide Conjugates As Potentialtherapeutic And Diagnostic Reagents, Yinyin Song

All Theses and Dissertations (ETDs)

Peptide Nucleic Acids: PNAs), are an ideal choice for antisense and antigene tools and probes because of their stability and high binding affinity, but have limited application as therapeutic and diagnostic agents because of poor membrane permeability. To increase membrane permeability, we conjugated hydrophobic lipids or phospholipid molecules and hydrophilic cell penetrating peptides to the N and C terminus of PNAs, and studied their physical and biological properties. After solid-phase automated synthesis, PNA-CPPs: TAT/Arg9) were coupled with lipids or phospholipids before cleavage from the support and then purified by HPLC. The conjugates were characterized by UV-vis and MALDI, and by …


Well-Defined Molecular Brushes: Synthesis By A "Grafting Through" Strategy And Self Assembly Into Complicated Hierarchical Nanostructures, Zhou Li Jan 2011

Well-Defined Molecular Brushes: Synthesis By A "Grafting Through" Strategy And Self Assembly Into Complicated Hierarchical Nanostructures, Zhou Li

All Theses and Dissertations (ETDs)

This dissertation focuses on the development of a "grafting through" methodology to synthesize molecular brushes with well-defined structures, as an attempt to construct nanostructures by covalent bonds totally. Detailed synthetic procedures for and characterization of molecular brushes, as well as complicated hierarchical nanostructures resulted from their self-assembly are reported. The synthesis of molecular brushes is achieved by combining orthogonal living polymerization techniques rationally, such as living/controlled radical polymerization, ring opening polymerization and ring opening metathesis polymerization. Generally, the strategy can be divided into two steps: the first step involves the preparation of linear macromonomers whose chain ends are functionalized with …


Novel Plasmonic Nanostructures For Applications In Sensing, Imaging, And Controlled Release, Weiyang Li Jan 2011

Novel Plasmonic Nanostructures For Applications In Sensing, Imaging, And Controlled Release, Weiyang Li

All Theses and Dissertations (ETDs)

This research placed emphasis on engineering the properties of novel plasmonic nanostructures, especially silver: Ag) and gold: Au) nanostructures with well-defined shapes, for biomedical applications in sensing, imaging and drug delivery. The first part of this work focused on the development of novel dimeric nanostructures of Ag for surface-enhanced Raman scattering: SERS) applications. In this section, I successfully demonstrated the synthesis of well-defined Ag dimers consisting of nanospheres with a broad range of sizes by using two methods. The first method was based on polyol process and the second was based on wet etching. The key for the dimerization process …


Mass Spectrometry-Based Structural Proteomics: Bottom-Up Protein Footprinting And Top-Down Native Electrospray Of Protein Assemblies, Hao Zhang Jan 2011

Mass Spectrometry-Based Structural Proteomics: Bottom-Up Protein Footprinting And Top-Down Native Electrospray Of Protein Assemblies, Hao Zhang

All Theses and Dissertations (ETDs)

Converting gene-sequence information into functional information about a protein is a major challenge of post-genomic biology. Proteins have a variety of functions from serving as catalysts to acting as structural components; all these functions are closely related to protein structure. The first step to understand protein function is often a structural study of that protein. Two major approaches, NMR spectroscopy and X-ray crystallography, can provide an atomic-level, 3D structural model of a protein. The applications of these high resolution approaches, however, are limited by protein size, conformational flexibility, and aggregation propensity. To obtain complementary structural information about proteins, a variety …


Examination Of Uv-Cross-Linkable Di-Block Copolymer Strategy For Functionalized Reaction Surface On Microelectrode Arrays, Libo Hu Jan 2011

Examination Of Uv-Cross-Linkable Di-Block Copolymer Strategy For Functionalized Reaction Surface On Microelectrode Arrays, Libo Hu

All Theses and Dissertations (ETDs)

Microarrays are powerful tools for high-throughput screening of small molecule libraries. Our group is using a microelectrode array variant on these efforts that allows us to construct and screen the libraries in a rapid, cost effective fashion. In this approach, the small molecules are attached to polymer-coated microelectrodes, which can be used to detect ligand-receptor interactions as they happen by means of impedance. Impedance experiment work by monitoring the current associated with a redox couple in solution. When a protein binds a ligand on the array, it sterically prevents the redox couple from reaching the electrode surface and thus causes …


Studies Of Fluorescent Imaging For Mrna Detection In Living Cells, Zhenghui Wang Jan 2011

Studies Of Fluorescent Imaging For Mrna Detection In Living Cells, Zhenghui Wang

All Theses and Dissertations (ETDs)

This dissertation focuses on the study of imaging mRNA in living cells. To achieve this research objective, three approaches have been utilized:: 1) Imaging of a transgenic mRNA tagged by multiple repeats of malachite green: MG) binding aptamer.: 2) Imaging of inducible nitric oxide synthase: iNOS) mRNA by strand-displacement activated Peptide Nucleic Acid: PNA) probes.: 3) Imaging of iNOS mRNA by binary fluorescently labeled PNA probes. The first approach was based on the work of our former lab member Dr. Huafeng Fang, who had constructed a multiple MG binding aptamer tagged transgene: Flag-mβ2AR-GFP-MGVI), which could also express a green fluorescence …