Chemistry Commons^™

Catalytic Mechanism Of Amyloid-Β Peptide Degradation By Insulin Degrading Enzyme: Insights From Qm/Mm Mp2 Calculation, Rui Lai, Wei-Jen Tang, Hui Li

Department of Chemistry: Faculty Publications

Insulin degrading enzyme (IDE), a metalloprotease that degrades amyloid-β (Aβ) peptides and insulin, is associated with Alzheimer’s disease and diabetes. The mechanism of IDE catalyzed degrading of Aβ peptides, which is of fundamental importance in the design of therapeutic methods for Alzheimer’s disease, has not been fully understood. In this work, combined quantum mechanics and molecular mechanics (QM/MM) style Møller-Plesset second order perturbation theory (MP2) geometry optimization calculations are performed to investigate the catalytic mechanism of the Aβ40 Phe19-Phe20 peptide bond cleavage by human IDE. The analyses using QM/MM MP2 optimization suggest that a …

Molecular Insights Into Organic Particulate Formation, Manoj Kumar, Emily Burrell, Jason C. Hansen, Joseph S. Francisco

Department of Chemistry: Faculty Publications

Carboxylic acids have been detected in particles collected in various regions of the world. Here, we use experiments and Born–Oppenheimer molecular dynamics simulations to better understand the mechanism of particle formation from gas phase mixtures of formic acid (HCOOH), (CH₃)₃N, and water vapor. A flow reaction cell coupled to two scanning mobility particle sizers has been used to measure particle size, absolute number of particles and kinetics of particle formation. Experimental results show that the addition of (CH₃)₃N to a mixture of HCOOH and water vapor results in a dramatic increase in …

In-Situ-Investigation Of Enzyme Immobilization On Polymer Brushes, Meike Koenig, Ulla König, Klaus-Jochen Eichhorn, Martin Muller, Manfred Stamm, Petra Uhlmann

Department of Chemistry: Faculty Publications

Herein, we report on the use of a combined setup of quartz-crystal microbalance, with dissipation monitoring and spectroscopic ellipsometry, to comprehensively investigate the covalent immobilization of an enzyme to a polymer layer. All steps of the covalent reaction of the model enzyme glucose oxidase with the poly(acrylic acid) brush by carbodiimide chemistry, were monitored in-situ. Data were analyzed using optical and viscoelastic modeling. A nearly complete collapse of the polymer chains was found upon activation of the carboxylic acid groups with N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide and N-Hydroxysuccinimide. The reaction with the amine groups of the enzyme occurs simultaneously with re-hydration of the …

Development Of A Microcolumn One-Site Immunometric Assay For A Protein Biomarker: Analysis Of Alpha1-Acid Glycoprotein In Serum, Chenhua Zhang, Shae Lott, William Clarke, David S. Hage

Department of Chemistry: Faculty Publications

A one-site immunometric assay based on affinity microcolumns was developed for the analysis of alpha₁-acid glycoprotein (AGP) as a model protein biomarker. In this assay, a sample containing AGP was incubated with an excess amount of a labeled binding agent, such as fluorescein-labeled anti-AGP antibodies or F_ab fragments. The excess binding agent was removed by passing this mixture through a microcolumn that contained an immobilized form of AGP, while the signal was measured for the binding agent-AGP complex in the non-retained fraction. Theoretical and practical factors were both considered in selecting the concentration of labeled binding agent, …

Nmr Metabolomics Protocols For Drug Discovery, Fatema Bhinderwala, Robert Powers

Department of Chemistry: Faculty Publications

Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective and effective is a daunting proposition because disease biology is complex and highly variable across patients. Metabolomics enables the discovery of disease biomarkers, which provides insights into the molecular and metabolic basis of disease and may be used to assess treatment prognosis and outcome. In this regard, metabolomics has evolved to become an important component of the drug discovery process to resolve efficacy and toxicity issues, and as a tool for precision medicine. A detailed …

Reversible Mechanical Deformations Of Soft Microchannel Networks For Sensing In Soft Robotic Systems, Abhiteja Konda, Donghee Lee, Taesun You, Xiaoyan Wang, Sangjin Ryu, Stephen Morin

Department of Chemistry: Faculty Publications

Microfluidics has enabled numerous applications in, for example, analytical chemistry, medical diagnostics, microelectronics, and soft robotics. In most of these applications, the geometries of the microchannels are of fixed dimensions that (ideally) remain invariant during operation. In soft robotics, however, the geometries of the microchannels contained in soft actuation systems are inherently dynamic, and the specific dimensions are expected to change during operation, and, by extension, the fluid transport properties of the system are variable. If this characteristic is not properly considered, or if methods are not developed to control it, the progress of soft robotic devices with distributed fluid …

Design Of Single-Molecule Multiferroics For Efficient Ultrahigh-Density Nonvolatile Memories, Qing Yang, Tingting Zhong, Zhengyuan Tu, Lin Zhu, Menghao Wu, Xiao Cheng Zeng

Department of Chemistry: Faculty Publications

It is known that an isolated single-molecule magnet tends to become super- paramagnetic even at an ultralow temperature of a few Kelvin due to the low spin switching barrier. Herein, single-molecule ferroelectrics/multiferroics is proposed, as the ultimate size limit of memory, such that every molecule can store 1 bit data. The primary strategy is to identify polar molecules that possess bistable states, moderate switching barriers, and polarizations fixed along the vertical direction for high-density perpendicular recording. First- principles computation shows that several selected magnetic metal porphyrin molecules possess buckled structures with switchable vertical polarizations that are robust at ambient conditions. …

Glycoform Analysis Of Alpha1-Acid Glycoprotein By Capillary Electrophoresis Using Electrophoretic Injection, Chenhua Zhang, William Clarke, David S. Hage

David Hage Publications

Human alpha₁-acid glycoprotein (AGP) is an acute phase glycoprotein that has a heterogeneous glycosylation pattern. This pattern can change in certain diseases, which has resulted in interest in using AGP glycoforms as potential biomarkers for these diseases. This report describes a method that uses capillary electrophoresis to characterize and analyze AGP glycoforms both in purified samples of AGP and in human serum. This method uses static and dynamic coatings of poly (ethylene oxide) that are applied to a silica capillary for separation of AGP glycoforms in the reversed-polarity mode of CE and in the presence of negligible electroosmotic …

Synthesis And Conformational Studies Of Various Amides, Marcos Beltran-Sanchez

University of the Pacific Theses and Dissertations

In the past, aminocyclohexanol rings have been successfully utilized as pH-triggered molecular switches in various trans-2-aminocyclohexanol derivatives. By changing the groups on the amine nitrogen, these models provided a wide pH range in which a switch can occur. The pH-induced switch of conformation was monitored by 1H-NMR spectroscopy. The models were also incorporated into the bilayer membrane of liposome structures and tested for their ability to disrupt their membrane upon their conformational flip induced by a decrease in pH.

In this work, the amide bond has been studied as a molecular switch and various amide derivatives have been tested for …

Avoiding Adverse Effects: New Ideas In Drug Discovery For Targeting Pparγ, Trey M. Patton

Graduate Student Theses, Dissertations, & Professional Papers

Peroxisome proliferator-activated receptor gamma (PPARγ) has been a drug target to treat type 2 diabetes for the last 20 years when rosiglitazone and pioglitazone were approved by the FDA in 1999. While effective at increasing insulin sensitivity, these drugs cause serious adverse effects due to their full agonist characteristics. For that reason, drug discovery efforts have attempted to reduce or prevent the amount of agonist character of new PPARγ targeting ligands. Unfortunately, there have been no new FDA approved drugs for the receptor. There is a need for new ideas to produce better quality pharmaceuticals that lessen the impact of …

Development And Characterization Of Ldv Peptide Targeted Nanocarriers For Paclitaxel Delivery: A Comparative Study Of Micelles, Liposomes And Solid Lipid Nanoparticles, Poonam Dattani

University of the Pacific Theses and Dissertations

Nanocarriers have been established as delivery vehicles to target cancer tumors. However, premature drug leakage is one of the major reasons for inefficient drug delivery of nanocarriers to the tumor. Drug diffusion out of the nanocarriers or destabilization of drug loaded nanocarriers by physiological interactions with blood cells, serum proteins, and cell membranes upon systemic administration contribute to premature drug release. In this study, targeted micelles, liposomes and solid lipid nanoparticles (SLNs) of similar composition were prepared and characterized to compare physicochemical characteristics, in vitro stability, in vitro release rates in release media and in vivo performance. Peptide Amphiphiles (PAs) …

Syntheses Of A Tin (Iv) Meso-Tetra(4-Pyridyl) Porphyrin Dichloride-Tetrachlorobis (Bipy)2 Ruthenium (Ii) Complex And Studies Of Photophysical Properties Of 1-Nitropyrene, Phillip Sharp

Electronic Theses and Dissertations

Development of a photosensitizer that can work in both aerobic and anaerobic environments would increase the robustness of the cancer treatment known as photodynamic therapy. The development of a photosensitizer was first attempted by synthesizing a tin (IV) meso-tetra (4-pyridyl) porphyrin dichloride-tetrachlorobis (Bipy)₂ ruthenium (II) complex. The synthesize of the tin porphyrin was done by a method from literature and had a percent error of 31.58 and 37.31 when comparing the theoretical percentages of carbon (55.39) and nitrogen (12.92) meaning that photosensitizer was not synthesized.

The second type of chromophore that was studied was 1-nitropyrene do determine if it …

Synthesis And Evaluation Of Troponoids As A New Class Of Antibiotics, Feng Cao, Cari Orth, Maureen J. Donlin, Patrick Adegboyega, Marvin J. Meyers, Ryan P. Murelli, Mohamed Elagawany, Bahaa Elgendy, John E. Tavis

Publications and Research

Novel antibiotics are urgently needed. The troponoids [tropones, tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial activity. We synthesized or purchased 92 troponoids and evaluated their antibacterial activities against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Preliminary hits were assessed for minimum inhibitory concentrations (MIC80) and cytotoxicity (CC50) against human hepatoma cells. Sixteen troponoids inhibited S. aureus/E. coli/ A. baumannii growth by ≥80% growth at <30 >μM with CC50 values >50 μM. Two selected tropolones (63 and 285) inhibited 18 methicillin-resistant S. aureus (MRSA) strains with similar MIC80 values as against a reference strain. Two selected thiotropolones (284 and 363) …

Mass Spectrometry And Nuclear Magnetic Resonance In The Chemometric Analysis Of Cellular Metabolism, Eli Riekeberg

Department of Chemistry: Dissertations, Theses, and Student Research

The development and awareness of Machine Learning and “big data” has led to a growing interest in applying these methods to bioanalytical research. Methods such as Mass Spectrometry (MS), and Nuclear Magnetic Resonance (NMR) can now obtain tens of thousands to millions of data points from a single sample, due to fundamental instrumental advances and ever-increasing resolution. Simple pairwise comparisons on datasets of this magnitude can obfuscate more complex underlying trends, and does a disservice to the richness of information contained within. This necessitates the need for multivariate approaches that can more fully take advantage of the complexity of these …

‘Cassette’-Ises (In Situ Enzymatic Screening) Identifies Complementary Chiral Scaffolds For Hydrolytic Kinetic Resolution Across A Range Of Epoxides, Sangeeta Dey, Douglas R. Powell, Chunhua Hu, David B. Berkowitz

Department of Chemistry: Faculty Publications

‘Cassette’-ISES (In Situ Enzymatic Screening) Identifies Complementary Chiral Scaffolds for Hydrolytic Kinetic Resolution Across a Range of Epoxides

A new ‘Cassette’-In Situ Enzymatic Screen (ISES) for combinatorial catalysis is introduced. This allows the experimentalist to obtain an information-rich readout, in real time, providing an estimate of the sense and magnitude of enantioselectivity across more than one substrate. In its first iteration, the screen identified Co^III-salen catalysts with β-pinene- and α-naphthylalanine-derived chiral scaffolds with broad, yet complementary, substrate specificities.

Development Of Betulinic Acid Triazole Conjugates As Potential Anti-Cancer Agents, Gayathri Jampana

Theses and Dissertations

Betulin and betulinic acid are pentacyclic triterpenoid natural product isolated from the bark of birch trees. While betulin is abundantly available in the bark, betulinic acid is present in scarce quantities in nature. However, betulinic acid can be conveniently synthesized from betulin via simple redox manipulations. Betulinic acid shows selective cytotoxicity profile against cancer cells in vitro while being relatively safe for normal cells. One of the challenges for the clinical development of betulinic acid is its lack of aqueous solubility. The three key structural features of betulin/betulinic acid that have been routinely exploited for structural modifications to enhance their …

Guanidinium Compounds, Stephen Dimagno, Bao Hu

Department of Chemistry: Faculty Publications

The present application provides , inter alia , chemical com pounds useful as synthesis intermediates , said compounds comprising one or more guanidinium moieties and a hyper valent iodine atom . Methods for making these compounds are also provided.

Efforts Towards The Discovery Of Novel Methods For The Synthesis Of Pharmacologically Relevant Molecular Scaffolds, Graham Joseph Haun

Theses and Dissertations

With the introductions of pharmaceuticals into modern day society many people have been using them to improve their lives. Due to this high increase in demand along with the ever-growing concern of environmental impact pharmaceutical companies have been pressed to synthesis new and existing drugs at a higher rate. This increased rate can cause low yield drugs or have a heavy environmental impact. As the use of pharmaceuticals becomes more widespread the need for greener and simpler organic synthesis methods to make these pharmaceuticals becomes more needed.

Herein is reported the methodological development of different pharmacologically relevant scaffolds. This work …

Radioiodinated Compounds, Stephen Dimagno, Bao Hu

Department of Chemistry: Faculty Publications

This disclosure relates to reagents and methods useful in the synthesis of aryl iodines ,for example , in the preparation of iodine labeled radiotracers . 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 com pounds .

Synthetic And Theoretical Studies For Cyclization Reactions To Form C-C And C-N Bonds, Nicholas Jentsch

Dissertations

Natural product total synthesis provides an alternative method for obtaining medicinally relevant compounds in a more efficient process with higher yields than what nature can provide. Natural products pose significant synthetic challenges due to the unique heterocyclic skeletons with fused and spirocyclic ring systems. Therefore, it is paramount to develop efficient reaction methodologies targeting substructures such as cyclic ureas and spiro[4.5]decanes which are prominent among marine natural products and Lycopodium alkaloids, respectively. Presented here is a compilation of research seeking to develop synthetic methods for the construction of cyclic moieties such as those previously mentioned. The objectives that are addressed …

Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt

Graduate Theses and Dissertations

The resin glycoside, ipomoeassin F has been shown to be extremely potent against multiple cancer lines (IC50 = 4.2-36 nM). However, the mechanism of action of this potent and complex natural product is still not fully understood. The α,β-unsaturated esters of the glucosyl moiety have been shown to be vital for the overall cytotoxicity of ipomoeassin F. Nevertheless, the importance of the tigloyl ester of the glucosyl moiety is still largely unknown. This work aimed to study the pharmacophore importance of the tigloyl ester by creating, an efficient, scalable, and flexible synthesis route for various analogs. The 18-linear step synthesis …

The Effects Of Cold Plasma Treatment On Sweet Basil (Ocimum Basilicum), Sauvelson Auguste

Seton Hall University Dissertations and Theses (ETDs)

The study discussed herein looks both to continue and to expand upon previous work conducted here at Seton Hall University, which investigated the effect of cold plasma processing on sweet basil and their essential oils. It was found that the application of cold plasma treatment increases plant growth and eugenol concentration, which is an essential oil component and one of the potential natural antioxidants used in food preservation. In this study, we considered methods for increasing the production and harvesting of plants that produce essential oils such as sweet basil (Ocimum basilicum). The study also incorporated more controls …

Hiv-1 Integrase-Targeted Short Peptides Derived From A Viral Protein R Sequence, Xue Zhi Zhao, Mathieu Métifiot, Evgeny Kiselev, Jacques Kessl, Kasthuraiah Maddali, Christophe Marchand, Mamuka Kvaratskhelia, Yves Pommier, Terrence R. Burke Jr.

Faculty Publications

HIV-1 integrase (IN) inhibitors represent a new class of highly effective anti-AIDS therapeutics. Current FDA-approved IN strand transfer inhibitors (INSTIs) share a common mechanism of action that involves chelation of catalytic divalent metal ions. However, the emergence of IN mutants having reduced sensitivity to these inhibitors underlies efforts to derive agents that antagonize IN function by alternate mechanisms. Integrase along with the 96-residue multifunctional accessory protein, viral protein R (Vpr), are both components of the HIV-1 pre-integration complex (PIC). Coordinated interactions within the PIC are important for viral replication. Herein, we report a 7-mer peptide based on the shortened Vpr …

Nmr Structural Investigation Of Chlamydial Protein Complex And Lysine Glycomimetic For Drug Design, Abigael Chebichiy Songok

LSU Doctoral Dissertations

Research and design of drugs for treatment against microbial infections require the study of pathogenic proteins involved during infection and replication. Drugs can be designed to interfere with the interaction network of these pathogenic proteins and inhibit the infection process. Determination of the structure and ligands of the target proteins in microbes is essential for designing mechanistic-based drugs. Two Chlamydia proteins involved in host cell invasion were investigated in this study. The goal is to identify amino acids involved at the binding interface of Chlamydia chaperon proteins Scc1 and Scc4 by solution NMR spectroscopy. This information will give a lead …

Photochemical Investigation Of High-Valent Metal-Oxo Intermediates Containing Corrole And Light-Harvesting Porphyrin Ligands, Jonathan Malone

Masters Theses & Specialist Projects

In enzymatic and synthetic catalytic oxidations, high-valent iron-oxo intermediates play a vital role as the active oxidant. In this regard, many synthetic metal catalysts are designed as biomimetic models to resemble the active site of Cytochrome P450 enzymes (P450) which are the predominant oxidation catalysts in nature. Vitamin B12 cofactors, with a corrole-like structure corrin, are also utilized in some of the more difficult reactions in nature such as rearrangement and reductase reactions.

In this work, application of the promising photochemical method to corrolecontaining ligands systems showed much success in the generation of manganese(V)-oxo corrole intermediates using two electron-deficient corrole …

Visible Light Generation Of High-Valent Corrole-Manganese(V)-Oxo Intermediates And Biomimetic Studies Of The Oxidation Of Organic Sulfides Catalyzed By Manganese Corroles With Iodobenzene Diacetate, Davis Ray Ranburger

Masters Theses & Specialist Projects

High-valent transition metal-oxo intermediates play essential roles as active oxidizing species in enzymatic and biomimetic catalytic systems. Extensive research has been conducted on a variety of transition metal catalysts being studied as models for the ubiquitous cytochrome P450 enzymes. In doing so, the production of enzyme-like oxidation catalysts and probing studies on the sophisticated oxygen atom transfer mechanism are taking place.

In this work, visible-light irradiation of highly-photo-labile corrole-manganese(IV) bromates and chlorates was studied in two corrole systems with differing electronic environments, i.e. 5,10,15-trisphenylcorrole (H3TPC) and 5,10,15- tris(pentafluorophenyl)corrole (H3TPFC). In both systems, homolytic cleavage of the O- …

Glucosamine From Hydrolysis Of 3d Printing Chitosan For Osteoarthritis Treatment, Ruj Dansriboon, Laphon Premcharoen

The International Student Science Fair 2018

This project aims to introduce a new way for osteoarthritis treatment which is expected to increase in the future. Glucosamine is the main subject for a treatment, which can be derived by hydrolyzing chitosan. This project also includes extraction of chitosan from shrimp waste to make a worthy use of food waste from industry. In this project, 3D printer is applied to print chitosan gel since 3D printing is adjustable to form various shapes of the gel.

The research process begins with the extraction of chitosan from shrimp shells. For the next step, the percent of deacetylation of chitosan was …

Microgel Core/Shell Architectures As Targeted Agents For Fibrinolysis, Purva Kodlekere, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We demonstrate the utility of microgel core/shell structures conjugated to fibrin-specific peptides as fibrinolytic agents. Poly(N-isopropylmethacrylamide) (pNIPMAm) based microgels conjugated to the peptide GPRPFPAC (GPRP) were observed to bring about fibrin clot erosion, merely through exploitation of the dynamic nature of the clots. These results suggest the potential utility of peptide–microgel hybrids in clot disruption and clotting modulation.

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Tumor-Targeting Fluorinated Phthalocyanines For Theranostic Applications, Erik Nathaniel Carrión

Seton Hall University Dissertations and Theses (ETDs)

Hydrocarbon-based therapeutics and imaging agents are prone to chemical oxidation and degradation resulting in loss of activity and limited functional utility. Thus, more material is required to achieve long-lasting therapeutic effects. Phthalocyanines (Pcs) and their metal complexes (PcMs) can be utilized as prodrugs requiring only renewable energy resources namely, air and light, for cancer therapy and diagnostic (theranostic) applications related to photodynamic therapy (PDT). Replacement of labile C-H bonds in the Pc scaffold with a combination of fluoro and perfluoroisopropyl groups has resulted in a stable yet reactive oxidation catalyst of biological significance and importance. For example, F₆₄PcZn, …