Organic Chemistry Commons^™

Transition Metal Alkoxide Complexes Synthesis Using Thallium Reagents And Design Of Iron(Ii)-Alkoxide Carbene Complexes And Their Reactivity, Lakshani Wathsala Kulathungage

Wayne State University Dissertations

ABSTRACTTRANSITION METAL ALKOXIDE COMPLEXES SYNTHESIS USING THALLIUM REAGENTS AND DESIGN OF IRON(II)-ALKOXIDE CARBENE COMPLEXES AND THEIR REACTIVITY by LAKSHANI WATHSALA KULATHUNGAGE May 2025 Advisor: Dr. Stanislav Groysman Major: Chemistry (Inorganic) Degree: Doctor of Philosophy

This dissertation focuses on the synthesis and reactivity of transition metal and main group metal alkoxide complexes. The dissertation began with exploring a novel, efficient synthetic route towards transition metal alkoxides involving thallium reagents. A novel dimeric Tl2(OCtBu2Ph)2 complex was synthesized in the reaction between a lithium alkoxide and thallium precursor TlPF6. Tl2(OCtBu2Ph)2 served as a convenient precursor to the formation of old and new transition …

Transient Transmembrane-Electrostatically Localized Protons And Transmembrane Potential In A Laser Flashed Bacteriorhodopsin Purple Membrane Open Flat Sheet - Summary, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons/cations charges (TELCs, also known as TELPs) model may serve as a unified framework to explain a wide range of bioenergetic phenomena. Transient transmembrane-electrostatically localized protons (TELPs) and transmembrane potential in a laser flash-energized bacteriorhodopsin (bR) purple membrane (PM) open flat sheet are now better analyzed. Under the Heberle et al. (1994) experimental conditions, the number of bR molecules is now calculated to be 8200 per PM open flat sheet with a diameter of 600 nm. With a single-turnover laser flash intensity of 3 mJ/cm² to photoexcite 10% of the bR molecules, the laser flash-induced peak TELCs …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

The Importance Of Solution Studies For The Structural Characterization Of The Enterovirus 5' Cloverleaf, Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5' cloverleaf (5'CL). Here, we present a biophysical analysis of the 5'CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5'CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed …

Synthesis Of Bio-Orthogonal Hydrogels For 3d Cell Culture Via Penicillamine Β-Thiolactone-Mediated Native Chemical Ligation, Kaelin E. Marshall, Matthew E. Currier, Nathan J. Oldenhuis

Honors Theses and Capstones

Many hydrogel systems designed to mimic the extracellular matrix (ECM) employ thiol-based chemistries with undesirable functional groups, including vinyl sulfones and methacrylates. In downstream applications, any unreacted functional groups are problematic and render hydrogels non-viable for human use. Here, we introduce modifications to the Native Chemical Ligation (NCL) mechanism, exploring the elimination of cytotoxic byproducts and increased reaction rate by using a β-thiolactone. The inclusion of the β-thiolactone results in retention of the thiol within the gel, as well as enhanced kinetics due to the thermodynamic favorability of the ring opening and amide formation. We achieved this by functionalizing 4-arm …

Evaluating The Chemical Reactivity Of Wildfire-Derived Dissolved Organic Molecules: Glutathione Binding Through Kendrick Mass Defect Analysis, Hannah M. Hamontree, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

The emerging risks to organisms of pyrogenic-derived dissolved organic matter (PyDOM) from forest fires are of concern due to its toxic and mutagenic potential (e.g., pro-oxidative responses in fauna through the depletion of glutathione, a nitrogen- and sulfur-containing tripeptide found in cells). This study simulates this phenomenon in a laboratory setting by identifying bonding between reduced l-glutathione and organic molecules in leachates from environmentally weathered biomass samples (charred and uncharred) using Kendrick Mass Defect (KMD) analysis from formula lists obtained from negative-mode electrospray ionization-Fourier transform-ion cyclotron resonance-mass spectrometry ((-)ESI-FT-ICR-MS). These formula lists reveal a 10-fold increase in nitrogen- and sulfur-containing …

The Importance Of Atomic Charges For Predicting Site-Selective Ir-, Ru-, And Rh-Catalyzed C-H Borylations, Shannon M. Stephens, Kyle M. Lambert

Chemistry & Biochemistry Faculty Publications

A supervised machine learning model has been developed that allows for the prediction of site selectivity in late-stage C-H borylations. Model development was accomplished using literature data for the site-selective (≥95%) C-H borylation of 189 unique arene, heteroarene, and aliphatic substrates that feature a total of 971 possible sp² or sp³ C-H borylation sites. The reported experimental data was supplemented with additional chemoinformatic descriptors, computed atomic charges at the C-H borylation sites, and data from parameterization of catalytically active tris-boryl complexes resulting from the combination of seven different Ir-, Ru-, and Rh-based precatalysts with eight different ligands. Of the over …

Modified N-Heterocyclic Carbene Catalysts For Polyurethane Synthesis, Charise D. Young

Pomona Senior Theses

Polyurethanes are widely used polymers synthesized from diisocyanate and diol molecules. They are ubiquitous polymeric materials with important industrial applications. Their increasing market value prompts the need for selective and efficient production which can be achieved through N-Heterocyclic carbene (NHC) catalysis. N-heterocyclic carbenes are heterocyclic molecules containing a carbene atom and at least one nitrogen adjacent to the carbene center. The nitrogen substituents on the adjacent nitrogen play an important role in influencing their steric and electronic properties and resultant reactivity.^1,2 There is a lack of a comprehensive understanding of the steric and electronic properties of NHCs and how …

Optimizing And Scaling Up Tcfh–Nmi Pyrrole Acylation For Organic Syntheses, Grant H. Miller

Pomona Senior Theses

Traditional ketone synthesis often depends on toxic reagents and hazardous solvents, which limits its scalability and environmental compatibility. The TCFH–NMI method has shown strong potential for amide, ester, and thioester formation, but its use in ketone synthesis has only been recently described, and only on small scales. This thesis addresses that gap by optimizing a scalable synthesis of 2-(monomethyl succinyl)-3,5-dimethylpyrrole using monomethyl succinate and 2,4-dimethylpyrrole as model substrates. Key reaction parameters were systematically refined to improve yield, reproducibility, and sustainability. The final protocol avoids chromatography, operates at room temperature, and consistently delivers high yields. These features position it as a …

Stack Bonding In Pentacene And Its Derivatives, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Understanding the nature of π-stacking interactions is important to molecular recognition, self-assembly, and organic semiconductors. The stack bonding order (SBO) model of π-stacking has shown that the conformations of dimers occur when the combinations of monomer MOs are overall stack bonding in character. DFT calculations show that minima found on the potential energy surface for the π-stacked dimers of pentacene and perfluoropentacene occur when the dimer MOs are constructed from combinations of monomer MOs with an allowed SBO. An ex-amination of the MOs of π-stacked dimers extracted from X-ray structures of alkynyl derivatives like TIPS-pentacene pack at one or more …

Experimental Demonstration And Study Of Transmembrane-Electrostatically Localized Protons Prevail, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

In this review in relation to some interesting arguments from Silverstein, it is now reaffirmed that the experimental demonstration of transmembrane-electrostatically localized protons (TELPs) was successfully accomplished through 1) using an aluminum film as a TELPs sensor in a biomimetic anode water-membrane-water cathode system, 2) analyzing the water-electrolysis current curve, and 3) measuring bulk liquid phase pH. Formation of induced TELPs was subsequently discovered in an anode water-membrane-water-membrane-water cathode system. The discovery of induced TELPs enabled clean experimental tests on the cation-TELPs exchange process by using sodium bicarbonate or potassium bicarbonate solution in the central liquid chamber. The sodium/TELPs exchange …

Identification Of Π-Stacking Motifs In Naphthalene Diimides Via Solid-State Nmr, Jennifer E. Mejia, Hannah E. Butler-Au, Nalaya E. Thompson, Karcher D. Goodman, Elizabeth R. Zengel, Robert D. Pike, Jingdong Mao, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Organic electronics, featuring π-conjugated small molecules and polymers, have gained significant attention for their potential in flexible, lightweight devices. However, characterization of the ordered, π-stacking domains within these materials using microscopy or X-ray diffraction (XRD) is challenging with complex systems or when crystallography is impractical. This study applied 1D ¹³C multiple cross-polarization magic angle spinning (multiCP/MAS) and 2D ¹H-¹³C heteronuclear correlation (HetCor) solid-state nuclear magnetic resonance (ssNMR) to systematically characterize π-stacking motifs in a series of N,N'-dialkyl naphthalene diimides (NDIs). These techniques were shown to distinguish between the electronic environments attributed to different π-stacking motifs adopted in these NDIs, such …

Purification Of Recombinant His6-Gfp-Preptin Fusion Protiens, Apoorva Kollaram

Theses and Dissertations

Preptin, a 34-amino-acid peptide derived from proinsulin-like growth factor II, has emerged as a promising therapeutic candidate for both Type 2 diabetes mellitus and osteoporosis. Its dual functionality—stimulating insulin secretion without inducing hypoglycemia and promoting osteoblast proliferation—positions it as a unique alternative to traditional sulfonylureas and osteogenic agents. In this study, we developed a purification protocol for green fluorescent-preptin fusion proteins. These fusion proteins will be used to investigate the functional significance of residues Pro17, Val18, Gly19, Trp27, Lys28, and Gln29 in rat preptin, which shares high sequence similarity with the human form. Site-directed mutagenesis was performed using NEB Q5 …

Towards Developing Glut2 Specific Probes For Biochemical And Biomedical Applications, Abdelrahman Ismail

Dissertations, Master's Theses and Master's Reports

Facilitated Glucose transporters (GLUTs) are membrane proteins responsible for the uptake of simple sugars and other structurally similar metabolites in all mammalian cells. One of the hallmarks of cancer is dysfunctional sugar metabolism, known as the Warburg effect, and one of the manifestations of that effect is abnormal GLUT expression. There are 14 known GLUT proteins with different expression patterns in different tissues, and tumors tend to express certain GLUTs that are not present in surrounding healthy tissue. Therefore, selective targeting of GLUTs presents a potentially powerful tool for diagnostics and treatment of cancer and other diseases. This has been …

Microwave Assisted Syntheses And Characterizations Of Near-Infrared Ratiometric Probes For Mitochondrial Ph Detection And Monitoring, Ronald J. Schwandt

Dissertations, Master's Theses and Master's Reports

Within the field of biochemistry, there has been a significant development of ratiometric fluorescent probes designed for mitochondrial pH detection; however, many of these probes have emissions within the visible spectrum and require long synthesis times with low-yield reactions. However, in recent years, microwave-assisted syntheses of organic molecules have led to significant increases in reaction yields and quicker reaction times. In this work, two common reactions in probe synthesis, Heck coupling, and Knoevenagel condensations are investigated using microwave-assisted synthesis. It was found the low-concentration Heck coupling reactions using palladium (II) acetate led to extremely efficient Heck coupling. Also, a novel …

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 …

Effects Of Chain Length, Saturation, And Bases On Saponification, Sarah Fenik

Williams Honors College, Honors Research Projects

This project will analyze the effects of chain length and saturation of fatty acids on saponification processes, as well as the effects of the base used in the reaction. Stearic acid, lauric acid, and oleic acid will be used for the fatty acid comparisons, and sodium hydroxide and potassium hydroxide will be used for the base comparisons. Stearic acid is considered a long chain fatty acid, while lauric acid is considered a short chain fatty acid. Oleic acid is a monounsaturated fatty acid. Five soap products are be made: sodium stearate, sodium laurate, sodium oleate, potassium stearate, and potassium oleate. …

Synthesis Of Noval Hydroxy Chalcone And Study Of Fluorescent Properties, Margaret Hilliker

Williams Honors College, Honors Research Projects

Chalcones are a class of naturally occurring compounds found in plants, which have a general structure of Ar–CO–CH=CH–Ar’. They have shown significant potential as tunable organic fluorophores due to their extended π-conjugation and structural simplicity. In this study, a 2-hydroxy-substituted chalcone featuring a terminal dimethylamino group was synthesized via a pyrrolidine-catalyzed aldol condensation and characterized for its photophysical properties. The electron-donating and -accepting ends of the molecule establish an intramolecular charge transfer (ICT) pathway, while the hydroxyl group enables excited state intramolecular proton transfer (ESIPT), leading to complex emission behavior. Room temperature fluorescence analysis revealed broad, featureless emission, while low-temperature …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Near-Infrared Fluorescent Cyanine Probes For Monitoring Nad(P)H Dynamics In Living Cells And Drosophila Larvae, May Waters

Dissertations, Master's Theses and Master's Reports

Nicotinamide adenine dinucleotide (NAD+/NADH) plays a critical role in cellular metabolism, with abnormally elevated NADH levels linked to disrupted metabolic processes and cancer. In this study, we developed near-infrared fluorescent probes to selectively measure NADH concentrations. We present five cyanine-based probes, which were optimized by modifying the connection bridges to fine tune electronics. Two NAD(P)H-biosensing probes consisting of 1,3,3-trimethyl-3H-indolium and 3-quinolinium acceptors, linked by thiophene, A, and 3,4-ethylenedioxythiophene, B, bridges are detailed. They exhibit near-infrared fluorescence at 742.1 nm and 727.2 nm for probes A and B, respectively, and generate absorbance signals at 690.6 nm and 685.9 nm. Probe A …