Medicinal-Pharmaceutical Chemistry Commons^™

The Inductive Effect In Organic Chemistry, Charles A. Kingsbury

Department of Chemistry: Faculty Publications

The subtle difference between the successive polarization model and the flow of electrons through sigma bonds is explored, as well as the alternating charge model of Pople and the pervasive field model. The present paper is concerned with the ability of alkyl groups to serve as sigma inductive electron donors.

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 Monitoring Of Linear Rgd-Peptide Bioconjugation With Nanoscale Polymer Brushes, Evmorfia Psarra, Ulla Konig, Martin Muller, Eva Bittrich, Klaus-Jochen Eichhorn, Petra B. Welzel, Manfred Stamm, Petra Uhlmann

Department of Chemistry: Faculty Publications

Bioinspired materials mimicking the native extracellular matrix environment are promising for biotechnological applications. Particularly, modular biosurface engineering based on the functionalization of stimuli-responsive polymer brushes with peptide sequences can be used for the development of smart surfaces with biomimetic cues. The key aspect of this study is the in situ monitoring and analytical verification of the biofunctionalization process on the basis of three complementary analytical techniques. In situ spectroscopic ellipsometry was used to quantify the amount of chemisorbed GRGDS at both the homopolymer poly(acrylic acid) (PAA) brush and the binary poly(N-isopropylacrylamide) (PNIPAAm)− PAA brushes, which was finally confirmed …

Electrocaloric Effect In Ferroelectric Ceramics With Point Defects, Ming Wu, Qingshan Zhu, Jianting Li, Dongsheng Song, Honghui Wu, Mengyao Guo, Jinghui Gao, Yang Bai, Yujun Feng, Stephen J. Pennycoock, Xiaojie Lou

Department of Chemistry: Faculty Publications

The electrocaloric effect has drawn much attention due to its potential application in cooling devices. A negative electrocaloric effect is predicted to be induced in defect-doped ferroelectrics by computational results [A. Grunebohm and T. Nishimatsu, Phys. Rev. B 93, 134101 (2016) and Ma et al., Phys. Rev. B 94, 094113 (2016)], but it need to be confirmed by experimental results. In this work, we prepared a 1mol. % Mn-doped Pb(Zr_0.2,Ti_0.8)O₃ ceramics (Pb((Zr_0.2,Ti_0.8)_0.99,Mn_0.01)O₃), and the electrocaloric effect of the defect-containing ferroelectric ceramics has …

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 …

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 …

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 …

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) …

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 …

Xflow: An Algorithm For Extracting Ion Chromatograms, Mathew M. Gutierrez, Rob Smith

Graduate Student Theses, Dissertations, & Professional Papers

Abstract: Mass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This …

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.