Every 65 seconds, someone develops Alzheimer's disease, which is the seventh leading cause of death in the United States. A major barrier to potential therapeutics is the permeability of these molecules across the blood-brain barrier. We have developed small molecules with strong reactivity to combat the oxidative stress known to cause Alzheimer’s disease. However, the permeability is less than ideal. As a result, my goal is to produce a molecule that has enhanced permeability but retains the reactivity of the parent molecules. To achieve this, the BOILED-Egg model assessed different derivatives of our parent molecule, Py2N2. This model showed the differences in lipophilicity among different Py2N2 compounds and how they impact permeability into the blood-brain barrier and gastrointestinal tract. Background information on our parent molecule and its function regarding Alzheimer's development will be outlined to give a scope of what these compounds can target and how they function. Compounds with high lipophilicity reflected in the model will have schemes of synthetic synthesis for future directions.

In the pursuit of new ways to develop libraries of compounds for pharmaceutical drug discovery, the utilization of a robust and tunable macrocycle synthetic scaffold has led to the discovery of persistent and structurally well-defined conformational isomers. Targeting these macrocycles that exist as an ensemble of preorganized conformations represents a compromise between the pursuit of flexible molecules of undefined structure and rigid molecules biased towards a single conformation. This system is based on the quantitative dimerization of a monomer to afford macrocycle. When a single monomer is used, six unique structures are obtained. When two monomers are used, twenty unique structures are obtained. These different structures (conformational isomers) are accessed via hindered bond rotation with a barrier of ~18 kcal/mol and are observable by ¬1H NMR. Current drug discovery methods heavily rely on screening large chemical libraries of small, ridged molecules against protein targets and typically sacrifice entropy in favor of stronger ligand-target binding. Using our system, synthesis of 50 monomers allows for the generation of a library of over 10,000 structurally unique macrocycles. The goal of this work is to provide new chemical libraries for drug discovery.

EUK-134 is a manganese-salen complex widely used in anti-aging skincare formulations due to its potent antioxidant activity resulting from catalytic decomposition of reactive oxygen species. Despite its popularity, the fundamental kinetic properties that govern its efficacy and recyclability are not well understood, limiting its optimization in skincare products. As a result, the study presented here investigates the efficiency, sustained activity, and selectivity of EUK-134 in comparison to the Green lab ligand library by evaluating its turnover number (TON), turnover frequency (TOF), and reaction rate. Results indicate that while EUK-134 demonstrates high catalase-type activity and selectivity, the activity decreases with continuous exposure to H₂O₂, suggesting a need for re-application in real-world scenarios to achieve long-term protection. Additionally, selectivity studies show that peroxidase activity was observed, which may impact the stability of sensitive ingredients in formulations. These findings provide essential kinetic benchmarks to compare future small molecules and optimize EUK-134’s use in antioxidant skincare products. Without a clear understanding of these fundamental properties, we lack benchmarks to compare future small molecules that compete with EUK-134.

Perfluoroalkyl substances (PFAS), known as "forever chemicals", are ubiquitous environmental contaminants whose remarkable persistence poses significant risks to human health and ecosystems. Thus, it is important to develop analytical assays to determine PFAS concentrations based on widely accessible, readily available instrumentation, such as UV-VIS spectrophotometry. Tetrasodium tetraphenylporphyrintetrasulfonate (TPPS) is a water-soluble porphyrin known for its spectrophotometric property in water. It is also known that TPPS binds to the protein bovine serum albumin (BSA). We investigated the effect of BSA on the absorption spectrum of TPPS and how PFAS presence impacts BSA-TPPS interaction in water. Interestingly, we found that BSA induces TPPS precipitation. As BSA concentration increases, TPPS solubility first dramatically decreases, then increases, ultimately leading to the formation of homogeneous solutions at relatively high BSA concentration. Furthermore, addition of two different PFAS, sodium perfluorohexanoate and potassium perfluorobutanesulfonate salts, to homogeneous BSA-TPPS mixtures appreciably alter TPPS spectra. Our results show that these mixtures can be used to produce calibration curves relevant to the determination of PFAS concentrations in water.

Some of the most effective drugs from Nature are large and ring-shaped, so-called macrocycles. Macrocycles are interesting because they can interfere with protein-protein interactions, a different strategy for therapy than that used by small molecules (like aspirin). The challenge with the design of macrocycle drugs is that they are difficult to make and behave unpredictably. Here, an efficient strategy to make macrocycles is described. These molecules behave consistently (with preserved shapes) and can be tailored to optimize binding (a hallmark of drug design). The two macrocycles described differ in the choice of one group with significant (and predictable) consequences. Both groups mimic amino acid sidechains that are implicated in protein-protein interactions. One amine, N-methylbenzylamine, yields a macrocycle that will adopt six conformations in solution (an advantage when looking for drugs). The second amine, isobutylamine, gives more than eight conformations. Structural analysis was accomplished by NMR spectroscopy.

The development of novel anticancer agents with enhanced selectivity and reduced toxicity remains a critical challenge in medicinal chemistry. In this study, we investigate the influence of the quinoline moiety on the pharmacological properties of tetra-aza pyridinophanes, with a focus on their anticancer activity. A series of structurally diverse derivatives were synthesized, incorporating variations in the quinoline moiety position and R-group functionalization. The compounds were characterized using multiple spectroscopic and analytical techniques, and their biological activity was evaluated in cancer cell lines. Results indicate that the presence of the quinoline moiety significantly improves anticancer efficacy compared to its absence, suggesting enhanced interactions with cellular targets. Furthermore, permeability studies reveal that the methoxy (-OMe) substitution on the pyridine ring enhances cellular uptake relative to the hydroxyl (-OH) counterpart. These findings highlight the potential of quinoline-functionalized tetra-aza pyridinophanes as promising candidates for targeted cancer therapy. By improving the selectivity between normal and cancerous cells, this work advances the design of next-generation chemotherapeutics with reduced systemic toxicity.

This project is to synthesize a known nanomolar inhibitor of dehydroquinate synthase for evaluation as an antimicrobial agent in collaboration with TCU's Biology Professor McGillivray. It is estimated that nearly 10 million individuals could die per year due to antimicrobial resistance by the year 2050 (1). The focus will be two-fold: first, the improved synthesis of alkenylphosphonate 1, and then its elaboration into various prodrugs to improve its activity in vivo. The in vitro activity of 1 on dehydroquinate synthase is Ki = 0.29 nM, while the enzyme's substrate has Km = 4 microM (2). Dehydroquinate synthase is an enzyme that is part of the aromatic amino acid biosynthetic pathway, which is essential to bacteria and plants but does not exist in mammals - which is why we must eat vegetables and fruits. Thus, the toxicity to humans of antibacterial compounds targeting this pathway should be minimized.

Compound 1 was synthesized previously (2), but improvements to its synthesis must be made since it will be the starting material for the preparation of prodrugs. Prodrugs are compounds that are precursors of 1 but where the charge is masked. Because inhibitor 1 is highly hydrophilic, this prodrug strategy should be necessary to achieve biological activity in vivo. Initial work will aim at the large-scale preparation of 1 and particularly eliminate as much as possible the need for purification by chromatography.

Metal-halide perovskites are crystalline semiconductive materials with a tunable direct bandgap, defect tolerance, and high charge carrier mobility. These useful properties have led to application perovskites such as LEDs, solar cells, and more recently lasers.
In this project, cetyl ionic liquid (IL) enhanced Methylammonium Lead Tribromide perovskites thin films were studied on substrates with varying refractive indices to determine how refractive index impacts photophysical properties. Methylammonium Lead Tribromide perovskites have a refractive index of 2.19. In comparison glass, a common substrate, has a refractive index of 1.51 while yttrium-stabilized zirconium oxide (YSZ) is 2.15.
Thin films of Methylammonium Lead Tribromide grown on yttrium-stabilized zirconium oxide (YSZ) in the presence of an ionic liquid are found to be strongly emissive in the green at a wavelength of 535 nm (with quantum efficiency values above 60%). The associated photoluminescence excitation (PLE) spectra show an unprecedented series of distinct peaks, one set with an average energy separation of ~200 milli-electron volts, the other set with a ~100 milli-electron volt separation indicating possible Giant Rashba Splitting. The preparation and structure of these films, along with origins of this splitting, are presented.

Asymmetric chemical transformations are essential, given that most pharmaceuticals are chiral. However, the industrial implementation of an asymmetric catalyst relies on basic economic principles. For an economically viable synthesis, catalysts should be readily available, cost-effective, and environmentally sustainable. We are synthesizing and evaluating a series of chiral phosphorus acids (CPAs) as catalysts for asymmetric transformations. Building on our previous work, we are developing P-chiral phosphorus acids as Brønsted acid catalysts for the acid-catalyzed asymmetric transformations.

Lab safety across independent academic and research labs for undergraduate and graduate students is critical to creating a successful chemistry experience. Many students at Texas Christian University (TCU) are heading into the medical field where healthcare professionals work in sensitive and controlled environments every day. Others are moving to research and industrial labs where safety is a critical component of success. Safety concerns constantly arise within these environments. Understanding how to manage a hazard or safety concern is a critical skill that translates to a successful professional skillset and creates a positive professional environment. TCU is offering a groundbreaking safety course for undergraduates and graduate students starting Fall 2024. Students in the course will focus on learning objectives from American Chemical Society’s, “Guidelines for Chemical Laboratory Safety in Academic Institutions”. The TCU Chemistry Club is working to complement this new course with a campus awareness campaign and include local elementary schools that work with Chemistry Club. We will be discussing the various awareness strategies that the Chemistry Club has implemented to achieve awareness at various campuses.