Medicinal-Pharmaceutical Chemistry Commons^™

Enhanced Transdermal Immunization Via Solid-In-Oil Nanodispersions Incorporating Dendritic Cell-Targeting Peptide, Md Samiul Islam, Md. Shahin Ekka Sarker, Yoshirou Kawaguchi, Rie Wakabayashi, Noriho Kamiya, Muhammad Moniruzzaman, Masahiro Goto

Publications and Research

Transdermal immunization represents a promising needle-free alternative to conventional vaccination. However, efficient antigen delivery and robust immune activation remain major challenges. In this study, a solid-in-oil (S/O) nanodispersion system comprising a dendritic cell-targeting peptide (HR8), ovalbumin (OVA), and an adjuvant was developed for transdermal immunization. The HR8 peptide along with OVA was successfully incorporated into an S/O nanodispersion with an optimal hydrodynamic diameter of particles (< 200 nm) and exhibited stable physical properties for up to 90 days. In vitro and in vivo studies demonstrated enhanced antigen delivery with insignificant skin irritation in C57BL/6N mice. Moreover, in vivo transdermal immunization studies demonstrated that the addition of the HR8 peptide enhanced OVA-specific IgG responses (~1.5-fold). Notably, the HR8 peptide also promoted an approximately 2.5-fold increase in IgG2c levels, suggesting a shift toward a more T helper type 1-biased immune response, as reflected by an increased IgG2c/IgG1 ratio. Overall, these findings demonstrate that the incorporation of HR8 peptide into an S/O nanodispersion enables efficient transdermal antigen delivery and improved immunogenicity, highlighting its potential as a simple, non-invasive, and patient-friendly immunization strategy.

Laminarin-Loaded Solid-In-Oil Nanodispersion For Enhanced Non-Invasive Transdermal Immunization, Md. Shahin Ekka Sarker, Yoshirou Kawaguchi, Rie C. Wakabayashi, Noriho J. Kamiya, Muhammad Moniruzzaman, Masahiro Goto

Publications and Research

Simple and non-invasive transdermal vaccination is an attractive alternative to conventional injection-based immunization. However, the effectiveness of transdermal vaccines is often constrained by the stratum corneum barrier. Although the use of solid-in-oil (S/O) nanodispersion technology has successfully facilitated skin permeation to induce an immunological response, the antibody titers remain suboptimal. Herein, a dectin-1 selective ligand, laminarin, was used as an immunostimulatory adjuvant to enhance the immune response. S/O nanodispersions loaded with laminarin and ovalbumin (OVA) were systematically developed and characterized in terms of particle size, in vitro OVA release behavior, and skin permeation performance using excised mouse skin. In vivo …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …

Quantum Chemical Methods And Multiscale Modeling In Computer-Aided Drug Design, Hunter W. La Force

Chemistry Theses and Dissertations

Computer-Aided Drug Design (CADD) leverages a diverse toolkit of computational methods to accelerate the discovery and development of novel therapeutics. Among these, quantum chemical calculations provide unparalleled accuracy in understanding molecular interactions, albeit at a higher computational cost. This accuracy is crucial for identifying and quantifying fundamental interactions that dictate drug efficacy and selectivity, as exemplified by our investigation of ruthenium polypyridyl complexes. These metal-based compounds are model systems for studying covalent coordination bonds between ruthenium and its ligands and noncovalent interactions with DNA and protein targets. Local Mode Vibrational Theory emerges as a powerful lens within this framework, enabling …

Trade-Off Between Limonene & Geraniol-Based Reprocessable And Non-Reprocessable Epoxy Thermosets: Role Of Aliphatic Diamines In Polymer Networks Design, Priyankkumar Kanubhai Patel

Electronic Theses & Dissertations

The growing demand for sustainable materials, driven by environmental concerns and the rapid depletion of fossil fuels, has garnered significant attention in the fabrication of bio-based epoxy thermosets as renewable alternatives to petroleum-derived thermosetting polymers. The present study focuses on the synthesis and characterization of epoxy prepolymer resins derived from limonene and geraniol via a two-step process, followed by the fabrication of thermally cross-linked flexible epoxy thermoset films using various traditional aliphatic diamine curing agents, namely 1,2-ethylenediamine (EDA), 1,4-butylenediamine (BDA), and 1,6-hexamethylenediamine (HDA). Additionally, the incorporation of cystamine, a disulfide-containing diamine, enabled the formation of a covalent adaptable network through …

The Role Of Confined Hydration And Water Reorganization In Molecular Binding, Joe Z. Wu

Dissertations, Theses, and Capstone Projects

An important factor in guiding the development of drug discovery efforts is the comprehensive assessment of a ligand or drug’s ability to bind its receptor. The metric used to measure this interaction strength is by calculating the binding free energy (BFE). To achieve this accurately, we combine two concepts: (1) Grid Inhomogeneous Solvation Theory (GIST) returns the local water thermodynamic and structural contributions to free energy; and the (2) Alchemical Transfer Method (ATM) obtains the absolute (ABFE) and relative binding free energy (RBFE) estimates between ligand pairs. In this work, we employ Alchemical Water-Transfer to tether bridging water(s) during the …

Rational Design Of Small Molecules Targeting Mitochondrial Redox Proteins, Matheus Barbosa Belchior

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reactive oxygen species play a crucial role in many cellular processes. Despite being a natural byproduct of cellular metabolism, overexpression of these species causes damage to the cell, leading to cell dysfunction. Central to the regulation of these highly reactive molecule is the mitochondria. Impairment in its function has been associated with oxidative stress within the cell. Herein, a ligand-based and structure-based approach to design new small molecules to inhibit mitochondrial redox proteins associated with oxidative stress and reactive oxygen species. In the first project two molecules were synthesized and characterized as potential monoamine oxidase B inhibitors. Results showed two …

Phytochemistry Of Dalea Candida Var. Oligophylla, Ryan E. Galperin

All Master's Theses

The focus of this project was the plant Dalea candida and its phytochemistry. The plant compounds were isolated and purified by an array of chromatographic techniques. The structures of the pure compounds were determined by one-dimensional and two-dimensional ¹H and ¹³C NMR spectroscopy, supported by infrared and ultraviolet spectroscopy, experimental and calculated circular dichroism spectroscopy, and mass spectrometry. Plant parts were worked on separately since they typically differ in content. Purified compounds will be tested for biological activities. Based on our results, eight new or known compound were isolated, specifically four new compounds and four known compounds. Compound …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

In the first project, we describe the synthesis of an ambient stable high spin organic diradical 4 based on the Blatter moiety. The high-spin (S = 1) organic diradical 4, which consists of two Blatter radical moieties in a conjugated structure, exhibits a nearly exclusive population (88%) on triplet ground state at room temperature as a consequence of a large single-triplet energy gap (ΔEST = 0.5 kcal/mol). The target diradical molecule is synthesized over five steps with structural confirmation by single-crystal X-ray diffraction. The thermogravimetric analysis (TGA) shows the onset of decomposition at ~264 oC, indicating the diradical molecule has …

Co-Microencapsulation Of Ruellia Tuberosa L. And Cosmos Caudatus K. Extracts For Pharmaceutical Applications, Choirin Annisa, Sasangka Prasetyawan, Anna Safitri

Makara Journal of Science

This study aims to co-microencapsulate the Ruellia tuberosa L. and Cosmos caudatus K. extracts, with chitosan–sodium tripolyphosphate (Na-TPP) as coating material. α-Amylase inhibition and antioxidant assays were conducted to determine the potential of microcapsules used as antidiabetic agents. The microcapsules were manufactured under the influences of pH, Na-TPP concentration, and stirring time. The optimum microencapsulation conditions were selected based on the highest encapsulation efficiency. The optimum microencapsulation conditions were a pH of 4, Na-TPP concentration of 0.15% (w/v), and stirring time of 60 min. The microcapsules exhibited an IC₅₀ (inhibitory concentration) value of 223.64 ± 0.81 µg/mL and an …

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong

Honors Theses

Platelets are key players in our body’s inflammatory processes upon activation, which can create physiological problems. Researchers are actively seeking solutions by targeting platelets with therapeutics. The objective of the research in this thesis was to investigate a new and potentially less invasive drug delivery platform using nanoparticles. The topic of the project was to explore the world of ionic liquids and their abilities, when coated on nanoparticles, to bind to platelets. A library of choline carboxylic acid-based ionic liquids (ILs) was first synthesized via salt metathesis while PLGA-based nanoparticles were simultaneously being synthesized via the nanoprecipitation method. The ionic …

Synthesis And Characterization Of A Novel Reaction-Based Azaborine Fluorescent Probe Capable Of Selectively Detect Carbon Monoxide Based On Palladium-Mediated Carbonylation Chemistry, Samuel Moore, Carl Jacky Saint-Louis

Symposium of Student Scholars

Azaborines are fascinating compounds because they possess valuable properties such as photochemical stability, have high molar absorption coefficient and high fluorescent quantum yields, as well as large Stokes shifts and tunable absorption/emission spectra. Here, we designed, synthesized, and will examine a novel reaction-based azaborine fluorescent probe capable of selectively detect carbon monoxide (CO) based on palladium-mediated carbonylation chemistry. This novel azaborine fluorescent probe will exhibit high selectivity for CO and display a robust turn-on fluorescent response in the presence of CO in aqueous buffer solution.

Colloidal Nanomaterial Surface Chemistry And Characterization Studied By Linear And Nonlinear Spectroscopy, Asela Sampath Dikkumbura

LSU Doctoral Dissertations

Recent studies have demonstrated the use of nanomaterials such as metallic nanoparticles, liposomes, and polymer microparticles for biomedical applications, encompassing the field of nanomedicine. For developing novel core-shell metallic nanoparticles with controlled surface morphology, the in situ growth dynamics of colloidal silver-gold core-shell (Ag@Au CS) nanoparticles (NPs) in water are monitored in a stepwise synthesis approach using time-dependent second harmonic generation (SHG) and extinction spectroscopy. Transmission electron microscopy images show that the CS NP surface morphology becomes more smooth and uniform as the reaction proceeds, corresponding to lower, stable SHG signals and narrower plasmonic spectra that are compared to finite-difference …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

LSU New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Visualization Without Vision – How Blind And Visually Impaired Students And Researchers Engage With Molecular Structures, Croix J. Laconsay, Henry B. Wedler, Dean J. Tantillo

Journal of Science Education for Students with Disabilities

This article examines the tools and techniques currently available that enable blind and visually impaired (BVI) individuals to visualize three-dimensional objects used in learning chemistry concepts. How BVI individuals engage with and visualize molecular structure is discussed and recent tactile (or haptic) and auditory methods for visualization of various chemistry concepts are summarized. Remaining challenges for chemistry education researchers are described with the aim of highlighting the potential value of educational research in further enabling BVI students to pursue careers in science, technology, engineering, and mathematics (STEM) fields.

Singlet Oxygen Generation By Porphyrins And Metalloporphyrins Revisited: A Quantitative Structure-Property Relationship (Qspr) Study, Andrey A. Buglak, Mikhail Filatov, Althaf M. Hussain, Manabu Sugimoto

Books/Book chapters

state followed by formation of singlet oxygen (1O2), which is a highly reactive species and mediates various oxidative processes. The design of advanced sensitizers based on porphyrin compounds have attracted significant attention in recent years. However, it is still difficult to predict the efficiency of singlet oxygen generation for a given structure. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of singlet oxygen quantum yields for pophyrins and metalloporphyrins. We performed QSPR analysis of a dataset containing 32 compounds, including various porphyrins and their analogues (chlorins and bacteriochlorins). Quantum-chemical descriptors …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

“Treat Me Covalently” – New Tools To Improve Covalent Drug Design For Advancement Of Cancer Treatments, Yuliya Mazo

Student Theses and Dissertations

The goal of this project was to investigate the complex mechanism of covalent bonding among different molecules and their targets in a modeling software ICM-Pro. Specifically, it included the identification of fundamental aspects of a covalent bonding mechanism of the Michael addition reaction. Michael addition reaction of electrophilic α, β-unsaturated carbonyl compounds with a nucleophilic cysteine residue in thymidylate synthase, papain, and EGFR tyrosine kinase were examined. Thymidylate synthase and EGFR were chosen because they are important targets in the treatment of various types of cancer. In order to find the most optimal parameters, identification and assessment of the effect …

Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins

Undergraduate Honors Thesis Projects

In the world of pharmaceutical synthesis, research to combat foreign pathogens is always necessary. Scientists have been exploring different methods in order to synthesize the most effective compounds in antibacterial, anticancer, anti-inflammatory, and many other treatments. A key component within these versatile compounds are 1,3,4-oxadiazoles. Current methods to synthesize these compounds are inefficient. This research seeks to improve oxadiazole synthesis; however, the mechanism of this reaction is unknown. The goal of this project was to study the mechanistic pathway in the discovered, one-pot cyclodehydration synthesis of 1,3,4-oxadiazoles. In the first part of this study, a diacylhydrazine intermediate was proposed. This …

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 …

Nucleotide-Dependent Preferential Localization Of Ras In Model Membranes With Lipid Raft Nanodomains, Anna Shishina

Dissertations (1934 -)

Membrane proteins constitute a third of all proteins in the cell and more than 50% of drug targets. However, the analysis of membrane proteins has many challenges owing to their partially hydrophobic surfaces, flexibility and lack of stability. One example of an essential membrane protein is Ras superfamily. Ras is a small monomeric GTPase involved in regulation of cell growth, proliferation and differentiation. Therefore, Ras and its effectors are among the most important targets for cancer therapy. A detailed knowledge of the processes occurring during signal propagation via Ras might help to elucidate the mechanisms of the involved signal cascades. …

Conformational Studies Of Gram-Negative Bacterial Quorum Sensing 3-Oxo N-Acyl Homoserine Lactone Molecules, Darren Crowe, Alan Nicholson, Adrienne Fleming, Ed Carey, Goar Sanchez-Sanz, Fintan Kelleher

Articles

In their ¹H NMR spectra in CDCl₃ 3-oxo-N-acyl homoserine lactones (OHLs) show significant downfield chemical shifts of the amide N-H proton when compared to the parent N-acyl homoserine lactones (AHLs). NMR spectroscopic and DFT calculation studies have shown that this is most likely due to the presence of a stabilising intramolecular H-bond from the N-H to the 3-oxo group. The ¹H NMR spectra also show evidence for the enol tautomers and that the amount of enol present for a range of OHLs is 4.1-4.5% in CDCl₃ and 6.5-7.2% in CD₃CN. In …

2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin

Bioinformatics Software Design Projects

Cholesterol is carried and transported through bloodstream by lipoproteins. There are two types of lipoproteins: low density lipoprotein, or LDL, and high density lipoprotein, or HDL. LDL cholesterol is considered “bad” cholesterol because it can form plaque and hard deposit leading to arteries clog and make them less flexible. Heart attack or stroke will happen if the hard deposit blocks a narrowed artery. HDL cholesterol helps to remove LDL from the artery back to the liver.

Traditionally, particle counts of LDL and HDL plays an important role to understanding and prediction of heart disease risk. But recently research suggested that …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert

Chemistry Faculty Publications

Several potential new phosphorus-containing flame retardant molecules were evaluated for heat release reduction potential by incorporation of the molecules into a polyurethane, generated from methylene diphenyl diisocyanate and 1,3-propane diol. The heat release reduction potential of these substances was evaluated using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods to qualitatively evaluate their potential reactivity into the polyurethane prior to heat release testing. The functionality of the flame retardants was epoxide based that would potentially react with the diol during polyurethane synthesis. Flammability testing …

Green Chemistry As A Tool For Understanding The Toxic Substances Control Act: A Lecture Module For Undergraduate Students, Molly R. Blessing

Honors Scholar Theses

The Toxic Substances Control Act (TSCA) is the central form of chemical regulation existent in the United States today, yet scientists are often unaware or uncertain of its provisions. Violations of TSCA by unknowing chemists set industry and government unnecessarily at odds. A lecture on TSCA was developed for undergraduate students that uses the concept of green chemistry to promote interest and incentivize learning. Green chemistry methods are cleaner and less wasteful than traditional chemical ones, and many companies using them are at the forefront of technological innovation. The lecture explains both green chemistry and TSCA, includes company case studies, …

Magnetic Nickel Nanoparticles: Synthesis, Environmental Lmplications And Potential Role As Drug Carriers, Setare Tahmasebi Nick

Dissertations

The design and synthesis of well-defined magnetic particles with nanoscale dimensions is opening new avenues in understanding their fundamental chemical and physical properties. Our work describes a novel facile procedure for the synthesis of homogenous isotropic and anisotropic magnetic nickel nanoparticles. These nanoparticles were produced using a wet-chemical process and characterized by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), selected-area electron diffraction (SAED), powder x-ray diffraction (XRD), energy dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA). Magnetic measurements were acquired using a superconducting quantum interference device (SQUID) magnetometer. While there is significant interest in using magnetic nanoparticles for biological …

Heat Release Of Polyurethanes Containing Potential Flame Retardants Based On Boron And Phosphorus Chemistries, Vladimir Benin, Bastien Gardelle, Alexander Morgan

Chemistry Faculty Publications

Using a polyurethane of methylene diphenyl isocyanate and 1,3-propane diol, several new non-halogenated aromatic boron and phosphorus flame retardants were evaluated for heat release reduction potential using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods, and were then analyzed via spectroscopic methods to determine if the flame retardant was still present in the final product. PCFC testing on the resulting products showed that the flame retardant molecule can have different effects on heat release depending upon how it is mixed into the polyurethane. Some …

Determination Of Corrosion Inhibitor Lubricity Improver In Jet Fuel By Liquid Chromatography-Electrospray Ionization Mass Spectrometry, David W. Johnson, Milissa Flake, Ryan Adams

Chemistry Faculty Publications

Military jet fuel (JP-8) is very similar to commercial jet fuel (Jet A) except for the presence of three additives, fuel system icing inhibitor, corrosion inhibitor–lubricity improver (CI-LI), and antistatic additive, which are added to improve characteristics of JP-8. Of particular interest is the CI-LI additive; the most common active ingredient is a dimer of linoleic acid. This article focuses on quantification of the active ingredient in the CI-LI additive by liquid chromatography–mass spectrometry (LC–MS). This method will allow the determination of CI-LI content in military jet fuel samples.