Medicinal-Pharmaceutical Chemistry Commons^™

Probing The Bifunctional Catalytic Activity Of Ceria Nanorods Towards The Cyanosilylation Reaction, Gonghua Wang, Lu Wang, Xiang Fei, Yunyun Zhou, Renat F. Sabirianov, Wai-Ning Mei, Chin Li Cheung

Department of Chemistry: Faculty Publications

Ceria nanorods were demonstrated to be an active, bifunctional catalyst for the cyanosilylation of aldehydes. The catalytic activity of ceria was shown to be positively correlated with a decrease in the coordination numbers of neighbouring oxygen atoms around cerium atoms in the catalyst. Chemisorption and density functional theory studies suggested that the coordinatively unsaturated cerium sites exposed by the surface oxygen vacancy defects functioned as Lewis acid sites and the neighbouring oxygen atoms behaved as Lewis base sites in the catalytic cycle.

Porous Polymer Coatings As Substrates For The Formation Of High-Fidelity Micropatterns By Quill-Like Pens, Michael Hirtz, Marcus Lyon, Wenqian Feng, Andrea E. Holmes, Harald Fuchs, Pavel A. Levkin

Department of Chemistry: Faculty Publications

We explored the potentials of microarray printing using quill-like microcantilevers onto solid supports that are typically used in microspot printing, including paper, polymeric nitrocellulose and nylon membranes. We compared these membranes with a novel porous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) support (HEMA) with narrow pore size distribution in the 150 nm range, which demonstrated advantages in pattern definition, spot homogeneity, and consistent spot delivery of different dyes (phloxine B and bromophenol blue) with diameters of several micrometres. The bromophenol blue arrays on HEMA support were used to detect the presence of bovine serum albumin (BSA). In the presence of BSA, …

Single Transcriptional And Translational Preq1 Riboswitches Adopt Similar Pre-Folded Ensembles That Follow Distinct Folding Pathways Into The Same Ligand-Bound Structure, Krishna C. Suddala, Arlie J. Rinaldi, Jun Feng, Anthony M. Mustoe, Catherine D. Eichhorn, Joseph A. Liberman, Joseph E. Wedekind, Hashim M. Al-Hashimi, Charles L. Brooks Iii, Nils G. Walter

Department of Chemistry: Faculty Publications

Riboswitches are structural elements in the 50 untranslated regions of many bacterial messenger RNAs that regulate gene expression in response to changing metabolite concentrations by inhibition of either transcription or translation initiation. The preQ₁ (7-aminomethyl-7-deazaguanine) riboswitch family comprises some of the smallest metabolite sensing RNAs found in nature. Once ligand-bound, the transcriptional Bacillus subtilis and translational Thermoanaerobacter tengcongensis preQ₁ riboswitch aptamers are structurally similar RNA pseudoknots; yet, prior structural studies have characterized their ligand-free conformations as largely unfolded and folded, respectively. In contrast, through single molecule observation, we now show that, at nearphysiological Mg²⁺ concentration and pH, …

Iodonium Cyclophanes For Secure Arene Functionalization, Stephen Dimagno

Department of Chemistry: Faculty Publications

This disclosure relates to compounds, reagents, and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18F labeled radiotracers. For example, this disclosure provides universal “locked” aryl substituents that result in StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) from diaryliodonium salts. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …

Supercharging: An Investigation Into The Effects Of External Amino Acid Residue Charge On The Solubility And Internal Electric Character Of Bound Ligands In A Heme-Binding De Novo-Designed Protein, Cooper French

Dissertations and Theses

De novo protein design offers many interesting prospects both as a means to better understand natural protein dynamics and as a potential resource in biomedical and industrial applications. In this work I describe the modification of a simple, well-characterized heme-binding protein by altering side chain residue identities on the hydrophilic surface of the protein to produce variants with a range of net external charges. These charge modifications had a significant impact on nearly every measurable character of the protein. This work establishes the hard limits of supercharging within our experimental protein scaffold system, demonstrating that excessive positive charge increased the …

New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson

Graduate Theses and Dissertations

Mass spectrometry is an important tool used in many different disciplines and settings that include forensics, drug discovery, environmental analysis, and proteomics. Gas chromatography - mass spectrometry (GC-MS) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI - TOF MS) are two of the most important instruments used for analysis of compounds. Chapters 1 and 2 of this discussion use GC-MS for the investigation of synthetic cannabinoids in `K2' incense products and the detection of metabolites in urine samples from individuals suspected of consuming these mixtures. Analytical standards were synthesized and used for identification and confirmation of structures. Detection of …

Restricted Access Media And Methods For Making Restricted Access Media, David S. Hage, Chunling Wa, Abby Jackson, Hai Xuan

David Hage Publications

The present invention is directed to restricted access media (RAM), methods for preparing restricted access media, and kits for preparing restricted access media that contain protected ligand binding agents or protected enzymes. Certain RAM provided contain a plurality of protected regions of the Support that contain ligand binding agents that are protected by blocking agents. Certain RAM provided contain a plurality of protected regions of the support that contain unbound ligand binding agents or enzymes that are retained in the protected regions by a capping agent. Methods of making the RAM of the invention and associated kits are also provided.

Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell–matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo …

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …

Insights On Cytochrome P450 Enzymes And Inhibitors Obtained Through Qsar Studies, Jayalakshmi Sridhar, Jiawang Liu, Maryam Foroozesh, Cheryl Stevens L. Klein Stevens

Faculty and Staff Publications

The cytochrome P450 (CYP) superfamily of heme enzymes play an important role in the metabolism of a large number of endogenous and exogenous compounds, including most of the drugs currently on the market. Inhibitors of CYP enzymes have important roles in the treatment of several disease conditions such as numerous cancers and fungal infections in addition to their critical role in drug-drug interactions. Structure activity relationships (SAR), and three-dimensional quantitative structure activity relationships (3D-QSAR) represent important tools in understanding the interactions of the inhibitors with the active sites of the CYP enzymes. A comprehensive account of the QSAR studies on …

Discrimination Of Colon Cancer Stem Cells Using Noncanonical Amino Acid, Xinrui Duan, Honglin Li, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells (CSCs) may be responsible for tumor recurrence. Metabolic labelling of newly synthesized proteins with non-canonical amino acids allows us to discriminate CSCs in mixed populations due to the quiescent nature of these cells.

Synthesis Of Methylene Γ-Lactones Using Carbon Dioxide, Bryan P. Ferrell, Shizue Mito, Giber Martinez, Intesar El-Feitouri

COURI Symposium Abstracts, Summer 2012

Many industrial processes generate the greenhouse gas, carbon dioxide, as a byproduct. Carbon dioxide can be captured and recycled by using it in organic synthesis to prepare beneficial compounds. The goal of this project is to develop a new method of synthesizing methylene γ-lactones using CO₂-metal complexes. Many gamma lactones are biologically active, and their synthesis is of importance to pharmaceutical and other industries. Allenes can react with a transition metal-CO₂ complex. It is proposed that a titanium metal complex prepared with an aldehyde will bind to an allene, and a seven-membered ring forms as CO_{2 …}

One-Pot Γ-Amino Acids Synthesis From Co2 Via Zirconacycle, Teresita J. Maldonado, Diego A. Pedroza, Shizue Mito

COURI Symposium Abstracts, Summer 2012

One-pot γ-amino acids synthesis from CO₂ via zirconacycle was studied. It has been reported that ketone and isocyanides are viable substrates for insertion into Zr‒C bonds of zirconocene‒1-aza-1,3-diene complexes. The purpose of this project is to explore the viability of CO₂ insertion to develop a new method for γ-amino acids synthesis in which all the reactions are executed in a single pot. In this method, first zirconocene‒1-aza-1,3-diene complex is prepared by using Cp₂Zr₂Cl₂ and an α, β-unsaturated imine. Second, CO₂ was introduced into the zirconocene complex solution to form the seven-membered ring …

Solar Synthesis Of Acyl Hydroquinones And Their Bioactivity., Fernando De Leon, Shizue Mito

COURI Symposium Abstracts, Summer 2012

Without the Sun, we would not enjoy the benefits of life here on the Earth. This energy is essential and crucial for sustaining life: playing important roles in circadian rhythms and photosynthesis in plants. In our research, this endlessly renewable clean energy source is utilized for photo-Friedel-Crafts acylation of 1,4 - benzoquinones and 1,4 - naphthoquinones. Photo-Friedel-Crafts acylation was first discovered in 1891 and although there have been reported examples of acylated products, the substrates are still limited. In this project a variety of aldehydes having different substituents are examined, and bioassays were performed. While conventional methods for photochemistry use …

Characterization Of Polymeric Phthalocyanine Nanoparticles Using Dynamic Light Scattering Laser, Satish Kumar Murarishetty

All Capstone Projects

The objective of this study is to use DLS (Dynamic Light Scattering) to analyze polymeric copper phthalocyanine nanoparticles (CuPcNPs). CuPcNPs are synthesized in order to facilitate drug penetration of bacterial biofilms for the treatment of chronic wounds. Microorganisms that reside inside the biofilms of chronic wounds are very resistant to any kind of treatment, even to the host’s own immune system. Therefore we have proposed an alternative method to destroy the microorganisms existing within the biofilms. Photodynamic anti-bacterial chemotherapy (PACT) has received much attention for the past decade due to the multi-drug resistant strands. PACT uses photons, a photosensitizer, and …

Design And Synthesis Studies Of New S-Adenosyl-L-Methionine Analogues, Shanshan Wu

Theses

S-Adenosyl-L-Methionine (SAM), which is involved in methyl group transfers, is the second most abundant coenzyme in the human body. It is made from adenosinetriphosphate (ATP) and methionine catalyzed by adenosyltransferase. Methyltransferases (MTs) transfer the activated methyl group from the sulfur center to a specific position in a variety of substrates, e.g., DNA, RNA, proteins, and secondary metabolites. Methyltransferases have been linked to various diseases, including cancer.

In recent years, more and more SAM analogues have been reported. These analogues show activities in biological target labeling. The purpose of this thesis is to design and synthesize new SAM analogues to inhibit …

Size Dependent Antimicrobial Properties Of Sugar Encapsulated Gold Nanoparticles, Lakshmisri Manisha Vangala

Masters Theses & Specialist Projects

The antimicrobial properties of dextrose encapsulated gold nanoparticles (dGNPs) with average diameters of 25 nm, 60 nm, and 120 nm (± 5 nm) synthesized by green chemistry principles were investigated against both Gram-negative and Gram-positive bacteria. Studies were performed involving the effect of the dGNPs on the growth, morphology and the ultrastructural properties of bacteria. dGNPs were found to have significant dose dependent antibacterial activity which was directly proportional to their size and also their concentration. The microbial assays revealed the dGNPs to be bacteriostatic as well as bactericidal. The dGNPs exhibited their bactericidal action through the disruption of the …

Synthesis And Development Of Potential Cb1 Receptor Neutral Antagonists, Kimari Slaughter

LSU New Orleans Theses and Dissertations

Cannabis and its derivatives have been used for both medicinal and recreational purposes. The study of this plant led to the discovery of over 60 cannabinoids, found exclusively in cannabis, that contribute to the behavioral effects of cannabis use, the most common is delta-9-tetrahydrocannabinol. Cannabinoid receptors function to increase activity in the mesolimbic dopamine reward system. Dopamine is a neurotransmitter that plays a major role in addition and its regulation plays a crucial role in mental and physical well-being. There is evidence that CB₁ receptors are important to the reinforcing effects and the development of physical dependence on opiate …

Synthesis And Biological Evaluation Of Rigid Analogues Of Methamphetamines, Andrea N. Forsyth

LSU New Orleans Theses and Dissertations

A series of rigid azetidenyl-based methamphetamine analogs were synthesized from commercially available N-Boc-azetidinone. The benzylideneazetidine analogs were prepared via a Wittig olefination via the ylides generated from the corresponding triphenylphosphonium benzylhalide salts. The substituted benzylazetidine analogs were synthesized from the corresponding benzylideneazetidienes via hydrogention over palladium and platinum catalysts. The benzylideneazetidine and benzyliazetidine analogs were evaluated at monoamine transporters as a part of preliminary structure-activity study for the development of novel monoamine transporter ligands. The binding affinities of the azetidine analogs were determined at dopamine (DAT) and serotonin (SERT) transporters in rat brain tissue preparations. The preliminary in vitro …