Organic Chemistry Commons^™

The Effect Of Metalation On Antimicrobial Piscidins Imbedded In Normal And Oxidized Lipid Bilayers, Ana Dreab, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Metalation of the N-terminal Amino Terminal Cu(II)- and Ni(II)-binding (ATCUN) motif may enhance the antimicrobial properties of piscidins. Molecular dynamics simulations of free and nickelated piscidins 1 and 3 (P1 and P3) were performed in 3 : 1 POPC/POPG and 2.6 : 1 : 0.4 POPC/POPG/aldo-PC bilayers (POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine: POPG, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol; aldo-PC, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine) bilayer models. Nickel(II) binding decreases the conformation dynamics of the ATCUN motif and lowers the charge of the N-terminus to allow it to embed deeper in the bilayer without significantly changing the overall depth due to interactions of the charged half-helix …

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been …

Thermotrophy Exploratory Study, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The question of whether environmental heat energy could be utilized as a source of energy for biological metabolism is the center of this exploratory research. In 1979, this author postulated a hypothesis for the existence of thermotrophs that could isothermally utilize environmental heat energy as a source of their energy on Earth. According to this hypothesis, the thermotrophs could be the first primitive forms of life in the early Earth environment. The chemotrophs and phototrophs that we currently are all well familiar with might have been evolved somehow from the primitive thermotrophs. Furthermore, all the organisms currently regarded as the …

Halogen Bonding Interactions Of Haloaromatic Endocrine Disruptors And The Potential For Inhibition Of Iodothyronine Deiodinases, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Halogen bonding (XB) is a potential mechanism for the inhibition of the thyroid-activating/deactivating iodothyronine deiodinase family of selenoproteins through interactions with halogenated endocrine disrupting compounds (EDCs). Trends in XB interactions were examined using density functional theory for a series of polyhalogenated dibenzo-1,4-dioxins, biphenyls, and other EDCs with methylselenolate, a simple model of the Dio active site selenocysteine. The strengths of the interactions depend upon the halogen (Br>Cl), the degree of substitution, and the position of the acceptor. In terms of donor-acceptor energies, interactions at the meta position are often the strongest, suggesting a link to the topology of THs, …

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives As Ph-Responsive Gelators And Their Applications For Drug Delivery, Jonathan Bietsch, Logan Baker, Anna Duffney, Alice Mao, Mary Foutz, Cheandri Ackermann, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π–π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good …

Telp Theory: Elucidating The Major Observations Of Rieger Et Al. 2021 In Mitochondria, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons (TELP) theory may represent a complementary development to Mitchell's chemiosmotic theory. The combination of the two together can now excellently explain the energetics in mitochondria. Our calculated transmembrane-attractive force between an excess proton and an excess hydroxide explains how TELP may stay within a 1-nm thin layer at the liquid-membrane interface. Consequently, any pH sensor (sEcGFP) located at least 2–3 nm away from the membrane surface will not be able to see TELP. This feature as predicted from the TELP model was observed exactly in the experiment of Rieger et al., 2021. In contrast to their …

Renewable Fuels: Molecular Dynamics Investigations Into Pyrolysis Of Methyl Linoleate, Elson Osakpolor Eguaosa

Graduate Theses/Dissertations

With the rapid depletion of the world’s supply of fossil fuels, especially petroleum products, petroleum prices have risen by approximately 800% between the 1970s and now and are projected to continue rising. It is also expected that the world’s consumption of energy will increase commensurate with its growing population. Although biodiesel is a good renewable alternative, it has its limitations including high production costs and poor low-temperature performance. We seek to improve conventional biodiesel with pyrolysis to produce low molecular-weight compounds with high energy densities. Understanding the pyrolysis path on the atomic scale is key as it will allow us …

Reduced Metal Nanocatalysts For Selective Electrochemical Hydrogenation Of Biomass-Derived 5-(Hydroxymethyl)Furfural To 2, 5-Bis(Hydroxymethyl)Furan In Ambient Conditions, Baleeswaraiah Muchharla, Moumita Dikshit, Ujjwal Pokharel, Ravindranath Garimella, Adetayo Adedeji, Kapil Kumar, Wei Cao, Hani Elsayed-Ali, Kishor Kumar Sadasivuni, Naif Abdullah Al-Dhabi, Sandeep Kumar, Bijandra Kumar

Chemistry & Biochemistry Faculty Publications

Selective electrochemical hydrogenation (ECH) of biomass-derived unsaturated organic molecules has enormous potential for sustainable chemical production. However, an efficient catalyst is essential to perform an ECH reaction consisting of superior product selectivity and a higher conversion rate. Here, we examined the ECH performance of reduced metal nanostructures i.e., reduced Ag (rAg) and reduced copper (rCu) prepared via electrochemical or thermal oxidation and electrochemical reduction process, respectively. Surface morphological analysis suggests formation of nanocoral and entangled nanowire structure formation for rAg and rCu catalysts. rCu exhibits slight enhancement in ECH reaction performance in comparison to the pristine Cu. However, the rAg …

Synthesis And Evaluation Of Sorbicillinoids, Noah Devolve

Honors Program Theses

Sorbicillinoids are a rich family of natural products that have intrigued and inspired scientists since their initial discovery in 1948. A recent report by Zhang et al. detailed the discovery of several new monomeric sorbicillinoids that are particularly interesting as they show nitric oxide (NO) inhibition in RAW264.7 monocyte cell assays and thus possess potential as anti-inflammatory agents. Based on this information, obtaining more of these novel compounds and establishing a preliminary structure activity relationship (SAR) could be achieved by modulating the substitution pattern on the molecules’ benzene ring and varying the alkyl chain length. To this end, a flexible …

Design, Synthesis, And Biological Evaluation Of Novel Steroidal Analogs: Potential Anticancer Agents, Trevor Ostlund

Electronic Theses and Dissertations

Cancer is a malicious disease with low survivability rates primarily due to lack of reliable treatment options. Treatments are often non-specific for patients, and cancer resistance to treatment is becoming more prevalent as fast as new therapies are created. Previous studies in our laboratory have focused on the Epidermal Growth Factor Receptor (EGFR) and its downstream kinase family members as a key target for cancer. This cascade controls cell proliferation, anti-apoptotic effects, cell regulation, and other survival factors. Additionally, ABC transporters, responsible for efflux of chemotherapeutic material from cells, are key targets to combat drug resistance. We first evaluated a …

Copper-Catalyzed Dehydrogenative Decarboxylation Reactions Of Carboxylic Acids To Alkenes, Michael P. Stanton

Graduate Theses, Dissertations, and Problem Reports (ETD)

Linear alpha olefins (LAOs) are important building blocks in the production of linear low-density polyethylene, a plastic used in products such as shrink wraps, plastic bags, tubing, plasticizers, among others. Commercial methods for generating LAOs utilize ethylene oligomerization, but this method is reliant on fossil fuels and leads to unselective product formation. Synthesis of LAOs from renewable resources, namely carboxylic acids, by decarbonylative dehydration strategies has been well studied, however, this method has inherent drawbacks rooted in the formation of internal olefin side-products through isomerization pathways. With the goal of avoiding internal isomerization, this thesis explores a dehydrogenative decarboxylation strategy …

Enabling Technologies For Chemical Synthesis: I. Selective Microwave Heating; Ii. Synthesis And Regioselective Cyclotrimerizations Of Tethered 1,6-Diynes, Amir Tavakoli

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reaction discoveries, method developments, and technology advancements lie at the heart of synthetic organic chemistry. These innovations are essential for creating and manipulating complex molecules, which are the building blocks of many important chemical compounds, including pharmaceuticals, materials, and agrochemicals. Here, we first describe new methods to prepare neopentylene-tethered (NPT) 1,6-diynes which are valuable substrates for reaction discovery and target-oriented synthesis, especially in benzannulation strategies toward illudalane natural products. NPT 1,6-diynes have been employed as coupling partners in cyclotrimerization reactions for the synthesis of highly substituted benzene rings which present a persistent challenge in chemical synthesis and are underrepresented scaffolds …

Enantioselective Dearomatization Facilitated By Non-Covalent Interactions Of N-Heterocyclic Carbene Catalysts And Pyridinium Salts, Jack A. Patterson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Dihydropyridines are a practical organic scaffold commonly used for their pharmaceutical properties. Nucleophilic dearomatization of pyridines has proven to be a useful method in obtaining dihydropyridines. By using N-heterocyclic carbene (NHC) organocatalysts, dihydropyridines can be synthesized with high regioselectivity of the 1,4 regioisomer over the 1,2- regioisomer but often with low enantioselectivity. By incorporating non-covalent interaction contact points, we hypothesize that enantioselectivity can be enhanced. By synthesizing numerous NHCs, each proposed to exhibit a different type of non-covalent interaction (i.e., hydrogen bonding or ion pairing), an understanding of the secondary interactions within this reaction system can be studied and …

Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The intestinal pathogen Clostridioides difficile encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023, https://doi.org/10.1128/jb.00164-23) have identified both for the novel C. difficile TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in C. difficile.

I. Preparation Of Strategic Synthetic Building Blocks For World Health Organization Essential Medicines. Ii. Applying The Principles Of Process Intensification To The Synthesis Of Fluoroquinolone Antibiotics., Jeffrey M. Noble

Theses and Dissertations

The synthesis of active pharmaceutical ingredients is often a time-consuming and expensive process. Due to the nature of pharmaceutical manufacturing, these costs are carried forward to the final purchase price by the consumer. Although there are many factors which are involved in the final costing of a pharmaceutical, the cost associated with the synthesis is the primary one which can be managed by chemists and engineers.

This work discusses the synthetic routes of four active pharmaceutical ingredients as well as the synthetic techniques and equipment used with an emphasis on how the application of specific techniques can be applied to …

Asymmetric Cuh-Catalyzed Reductive Coupling Of Allenamides With Carbonyl Electrophiles & Development Of Nanocatalysts For Heterogeneously Catalyzed Buchwald-Hartwig Amination, Raphael K. Klake

Theses and Dissertations

Many drugs and natural products contain multiple stereogenic carbons bearing heteroatoms throughout their carbon framework. Therefore, methods that can efficiently install multiple heteroatoms on a molecule are valuable. Reductive coupling reactions have been extensively studied, and the allylation of carbonyls via the reductive coupling approach has been a key method for generating chiral tertiary and secondary allylic alcohols. This work utilizes inexpensive Cu for the asymmetric reductive coupling of allenamides with carbonyls to simultaneously install two heteroatoms (oxygen and nitrogen) on the product. These molecules have a polarity profile that make them difficult to make using traditional methods. Herein, we …

Synthesis And Application Of Redox-Active Covalent Organic Frameworks In Rechargeable Batteries, Mohammad K. Shehab

Theses and Dissertations

Synthesis and Application of Redox-Active Covalent Organic Frameworks in Rechargeable Batteries

Mohammad K. Shehab

Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284, United States

Abstract

In recent years, lithium-ion batteries (LIBs) have been considered the dominant energy storage devices for portable electronics and electric vehicles due to their high energy density, low self-discharge rate, and long cycle life. In LIBs, the traditional positive electrodes employed are mainly derived from metal-containing inorganic compounds composed of cobalt, iron, nickel, or manganese (LiCoO₂, LiMn₂O₄, and LiFePO₄) coupled with graphite as the negative electrode. Despite …

Translating Chemistry, Structure, And Processing To The Solid-State Morphology And Function Of Organic Semiconductors Through Computational Modeling And Simulations, Chamikara D. Karunasena

Theses and Dissertations--Chemistry

The immense synthetic design space and material versatility have driven the exploration and development of organic semiconductors (OSC) over several decades. While many OSC designs focus on the chemistries of the molecular or polymer building blocks, a priori, multiscale control over the solid-state morphology is required for effective application of the active layer in a given technology. However, molecular assembly during solid-state formation is a complex function interconnecting the building block chemistry and the processing environment. Insufficient knowledge as to how these aspects engage, especially at the atomistic and molecular scales, has so far limited the ability to predict …

Water-Soluble Palladium, Copper, And Nickel Catalysts And Their Formation In Ligand-Free Suzuki-Miyaura Cross-Coupling Reactions, Priya Karna

Theses and Dissertations--Chemistry

Transition-metal catalyzed Suzuki-Miyaura (SM) cross coupling is a powerful synthetic method for constructing carbon-carbon and carbon-heteroatom bonds in designing organic compounds, agrochemicals, pharmaceuticals, and precursors for materials. However, the nature of catalysis and identity of the transition metal catalysts used in these reactions remain under debate or unknown. This dissertation reports the studies of three metals: Pd, Cu, and Ni. Pd-nanocluster catalysts and their formation in ligand-free SM reactions with Pd(II) nitrate as a precatalyst was investigated. The catalysts are water-soluble neutral Pd tetramer and trimer in their singlet electronic states as identified by UV-Vis absorption spectroscopy and are formed …

Development Of An Effective Au:Pd Bimetallic Heterogeneous Catalyst For Oxidative Lignin Depolymerization To Low Molecular Weight Aromatics, Gayan P. Karunasinghe

Theses and Dissertations--Chemistry

The principal concept behind biorefining involves the transformation of lignocellulosic biomass into valuable products and energy resources. Historically, biorefinery strategies for lignocellulosic biomass have primarily focused on improving the conversion of cellulose into ethanol, often neglecting the underutilized lignin component. Lignin consists of phenolic subunits, from which it follows that value-added products can be obtained from lignin depolymerization. Unfortunately, lignin utilization is particularly challenging due to its high structural irregularity and recalcitrance. The goal of this study was to develop an AuPd/Li-Al layered double hydroxide (LDH) bimetallic catalyst for efficient lignin depolymerization, resulting in the production of high-value aromatic compounds. …