Author(s): Morgan Simmons Biology Natalia Castro Lopez Biology Floyd Wormley Biology
Advisor(s): Floyd Wormley Biology Natalia Castro Lopez Biology
Location: Second Floor, Table 6, Position 3, 1:45-3:45
Cryptococcus neorformans is a fungal pathogen that mainly affects immunocompromised patients and is opportunistic as it invades the central nervous system. In the Wormley research lab, we are currently working with multiple genes that have been shown to be involved in lipid metabolism. C. neorformans. Using the TRACE procedure; Transient CRISPR-Cas9 coupled with Electroporation is hypothesized to be a reliable method in order to knock out genes in C. neoformans. This specific project we have been working on will lead to a knockout by using CRISPR methodology to create a Cryptococcus neoforman deletion construct for an associated gene. We are analyzing identified genes that have been found to be upregulated in C. neoformans, multiple of which have been shown to be involved in lipid metabolism and virulence. By characterizing the role of these genes and certain proteins this project aims to deepen the knowledge of the roles of lipids in pathogenesis and hopefully develop ways to combat infection of people with weakened immune systems. To further characterize the role of these genes in virulence we focus on the gene CNAG_00474, which was upregulated in C. neoformans in the presence of arachidonic acid. To achieve this we will generate a KO using the TRACE technique. The overall problem in this study is the implications these fungal proteins may have and the lack of understanding surrounding their involvement which is essential to research in order to create a pathway leading toward potential drug targets. The methodology of this project includes the amplifying promoter and end sequences from the unidentified protein to fuse the primer with sgRNA to create a construct ultimately. From here, amplifying the ‘arms’ of the target protein and the selection marker from a plasmid (in this case NAT) will use PCR to fuse the marker and arms together and create the deletion construct. Once we confirm the gene has been knocked out we will analyze its role in virulence by assessing phenotypic characteristics in vitro and in vivo. I am hoping in the near future to have the specific KO ready to be able to confirm it via PCR.
Marine environments are at risk of contamination from oil refinery effluents, major oil spills, and wastewater runoff. To identify and mitigate such risks, the EPA requires toxicity testing of marine effluents. The larval growth and survival (LGS) test, featuring either sheepshead minnows (SHMs) or inland silversides (INS), is currently used to screen marine effluents for acute toxicity; however, the use of fish larvae represents an animal welfare concern, especially in light of legislation calling for adherence to the 3Rs of animal research. The fish embryo toxicity (FET) test and mysid growth and survival (MGS) test may represent viable alternatives to LGS tests as the FET test uses fish embryos (which are thought to experience less pain than older fish), while the MGS test uses invertebrates. The objective of this study was to determine if the FET and/or the MGS tests produce similar results as the LGS. To accomplish this, INS LGS, SHM LGS, INS FET, SHM FET, and MGS tests were run using phenanthrene, an environmentally-relevant component of crude oil. Results revealed that the LC50 values obtained from the MGS and INS LGS tests were comparable and that both were significantly lower than that of the other test types, suggesting that the MGS test may be a viable replacement for the LGS tests. This was further substantiated when growth metrics were evaluated. In contrast, the LC50 values obtained from both FET tests were significantly higher than those of the other test types indicating a relative lack of sensitivity. However, when hatchability was included as a test metric, the sensitivity of the INS and SHM FET was enhanced indicating that the inclusion of hatch may improve FET test performance.
The Thule Defense Zone in Northwest Greenland is a region of ecological concern because of its sensitive Arctic tundra ecosystem. Anthropogenic-induced climate change and deposition of contaminants into these fragile systems has the potential to alter these ecosystems. Mercury is a toxin of global importance that is capable of contaminating landscapes far from its source of origin, including those in the high Arctic. Understanding levels of mercury contamination that persist across landscapes requires analysis of aquatic ecosystems, as these systems are where mercury is converted into its toxic form, methylmercury. In Summer 2023, the Aquatic Ecology Lab at Texas Christian University will be traveling to the Thule Defense Zone and testing six ponds for mercury contamination. To better understand how contaminants reach these ponds, nutrient inputs from the landscape need to be understood. To date, there is no available watershed map for the Thule Defense Zone that delineates the hydrological characteristics of these ponds. My project will use Geographic Information Systems (GIS) to create a formal delineation of these aquatic systems.
Biodiversity, which is important to the function and stability of ecosystems, is currently being lost to extinction at an alarming rate. Thus, cataloguing and documenting the biodiversity of the world has never been more critical. In this study, the diversity and taxonomy of the tropical blueberries (Vaccinium L., Ericaceae) of Palawan and Mindanao Islands, Philippines were revisited. A total of 27 species (24 from Mindanao and four from Palawan) were documented and recorded. Six novel species, four new island records, and clarification of three ambiguous species complexes were included. Two of the six novel species (V. jubatum and V. vomicum) were discovered among historical herbarium collections, while the rest (V. carmesinum, V. coarctatum, V. fallax, and V. gamay) were discovered during botanical excursions. Two previously island endemic blueberries, V. cebuense and V. banksii, were documented to have an extended distribution in Mindanao. Additionally, V. irigaense is also recorded in Mindanao, whereas V. pseudocaudatum is recorded for the flora of Palawan. Further, the V. barandanum, V. caudatum, and V. halconense species complexes were taxonomically explained. The nomenclatural status of these species was stabilized through assigning type specimens following specifications of the International Code of Nomenclature for algae, fungi, and plants (Shenzhen Code). We concluded that Mindanao Island is the center of Philippine Vaccinium diversity. This study underscores the crucial role of herbaria in understanding the floristic diversity of the world. This study also serves as a basis for taxonomical studies of the other blueberries in the Philippine Islands and Southeast Asia.
Author(s): Emily Van Dyck Biology Gary Boehm Psychology Paige Braden Kuhle Psychology Kelly Brice Psychology Michael Chumley Biology Catherine Shoffner Biology Buse Uras Psychology
Advisor(s): Michael Chumley Biology
Location: Basement, Table 3, Position 1, 1:45-3:45
Due to our rapidly aging population, 6.5 million Americans currently have Alzheimer’s disease (AD), and this is predicted to increase to almost 14 million in the next 40 years. AD is more prevalent in western societies, and researchers suggest that this may be due to the typical Western diet. In contrast, AD prevalence is lower in Mediterranean regions, where a healthier diet could be a contributing factor. Therefore, this research examined the neuroprotective potential of a Mediterranean diet against AD pathologies and inflammation in mice. Our lab designed two experimental rodent diets, one that mimicked a typical Western-style diet, and another that mimicked a typical Mediterranean diet. We examined the lifelong effects of diet on biological markers of AD, including amyloid beta, a protein that aggregates together to form plaques in the AD brain, and pro-inflammatory cytokines, which are associated with increased inflammation. We hypothesized that the Mediterranean diet has the potential to mitigate these AD pathologies and therefore, could potentially be used as a future preventative strategy for AD.
Author(s): Kelsey Waite Biology Voung Do Biology Salina Hona Biology Shauna M. McGillivray Biology
Advisor(s): Shauna M. McGillivray Biology
Location: Basement, Table 11, Position 2, 11:30-1:30
Bacillus anthracis is the causative agent of anthrax. Previously, our lab identified the clpX gene as critical for virulence in B. anthracis. The ΔclpX mutant exhibited decreased cell wall integrity and increased susceptibility to cell-envelope active antibiotics. ClpX is one component of the intracellular caseinolytic protease ClpXP that degrades multiple proteins including transcriptional regulators. To understand changes in gene expression in ΔclpX, a microarray comparing WT and ΔclpX was conducted. This project focuses on msrA, an upregulated gene in ΔclpX. MsrA is an antioxidant enzyme that reduces methionine-S-sulfoxide to methionine but also impacts cell wall strength in S. aureus. This study will determine if loss of the msrA gene impacts antibiotic susceptibility. We hypothesized that since ΔmsrA is upregulated in ΔclpX, ΔmsrA would exhibit the opposite phenotype. Surprisingly, we find that ΔmsrA has significant growth inhibition in the presence of penicillin. However, we do not find susceptibility with other antibiotics, such as daptomycin, nor does it appear to be more susceptible to other clpX-related stress responses such as heat or acid stress. Future research will test ΔmsrA susceptibility to additional antimicrobials, such as the antimicrobial peptide LL-37 and the antibiotic vancomycin, as well as ΔmsrA virulence in vivo with the Galleria mellonella infection model. We will also complement ΔmsrA to confirm the phenotypes are due to loss of the msrA gene. This research is important as it aids our understanding of bacterial defenses and may provide new drug targets to help combat rising antibiotic resistance.
The Great Salt Lake in Utah is an important stopover point for many migratory bird species. Birds that stop to breed or forage at the Great Salt Lake may be at risk of mercury contamination due to high levels of methylmercury that are found in the lake. The purpose of this study was to examine the transfer of mercury from the lake into the terrestrial food web using organisms at the base of the food web. During the summers of 2019-2021 western spotted orb weaver spiders (Neoscona oaxacensis) and, when possible, brine flies (Ephydra sp.) were collected from various sites on Antelope Island. These specimens were analyzed for total mercury content using a Nippon MA-3000. In addition, satellite imagery and GIS software were used to document the approximate distance from the collection sites to the water surface. We examine differences between years, study sites and spider body size. We also examined the correlation between mercury levels and environmental conditions.
The Molding Melanin Magic mentorship program through TCU Pre-Health is geared to impact minority female student populations at the Texas Academy of Biomedical Sciences (TABS) in Fort Worth. The program provides small group mentorship as high school students are paired with a college student in their area of interest. Along with mentorship, workshops are utilized as a method of increasing confidence, exposure, and overall knowledge about college and STEM careers. By coupling workshops and mentorship, the Molding Melanin Magic program seeks to encourage mentees to serve as mentors along their educational journey, and apply for college and professional school to pursue a career in STEM.
Spiders are sentinel species, organisms that serve to map the bioavailable fraction of contaminants in an ecosystem by retaining their contaminants in their tissues. For example, spiders in the families Tetragnathidae and Araneidae are frequently used as sentinels of mercury contamination of aquatic ecosystems. Spiders are frequently preserved in alcohol prior to contaminant analysis but the impact of contamination on mercury concentrations in spiders has not been assessed. The objective of the present study was to determine the effects of different preservation methods on mercury concentrations in tissues of spiders in the families Tetragnathidae and Araneidae. The spiders were collected along water sources using nets and gloved hands. The Tetragnathids were collected from grassy terrain or a bridge overhanging the water of Lake Weatherford. The araneids were collected from a boat dock overhanging Eagle Mountain Lake. On site, each spider was placed into its respective bottle of varying ethanol or Ziplock's for freezing. Individual spiders were placed into one of three different concentrations of ethanol (100%, 95% , 70%) or frozen. Following about two months of preservation, the spiders were dried and run through the DMA-80 collecting the data for data analysis. Data xxxx *insert conclusion info*
Role of ClpX in the stress response and virulence of Bacillus anthracis: protease or chaperone?
Lillian Wilson, Vuong Do, S.M McGillivray
Department of Biology, Texas Christian University
Anthrax is a lethal infectious disease caused by the bacterial pathogen Bacillus anthracis. Our lab studies the virulence and antibiotic resistance of B. anthracis and we have identified a chromosomal gene clpX, as an important virulence factor, as its loss increases susceptibility to cell-envelope targeting antibiotics such as penicillin, daptomycin, and the antimicrobial peptide LL-37. ClpX is an ATPase that can act autonomously as a chaperone, or with a proteolytic core, ClpP, to degrade proteins. To investigate the mechanism ClpX uses, a plasmid pclpXI264E was designed with a mutation in clpX (I264E) that prevents ClpP binding and inhibits the formation of the ClpXP protease but does not disrupt the chaperone activity of ClpX. We used this to create 4 strains in the unencapsulated Sterne strain: wild-type and ∆clpX containing the empty inducible plasmid pUTE657, complementation plasmid with the non-mutated clpX gene (∆clpX + pclpX), and the mutated plasmid (∆clpX + pclpXI264E). Prior research done on these strains confirmed that ClpX relies on protease activity in antimicrobial stress; however, our goal was to assess its response in other environmental stressors such as acid stress, heat stress, and its virulence in vivo with the Galleria mellonella infection model. We find that that the protease activity of ClpX is important for all of these stresses. These results build on our earlier understanding and demonstrate that formation of the ClpXP protease is critical and any future development of drugs targeting the ClpX system should focus on protease formation rather than chaperone activity.
This research is focused on gaining a better understanding of PKC-epsilon a calcium-dependent protein kinase involved in a wide range of cellular functions including cell proliferation, survival, and apoptosis. The interest in PKC-epsilon derives from the discovery of a de novo mutation in the PKC-epsilon gene in patients suffering from SHORT syndrome. This syndrome is a debilitating disorder characterized by short stature, hyperextensibility, ocular depression, Rieger anomaly, and teething decay. The project involved recapitulating the naturally occurring de novo mutation in vitro as well as determining if other mutations in PKC-epsilon could cause similar disease-state phenotypes. Using a technique known as Site Directed Mutagenesis mutations were introduced into the PKC-epsilon gene and the effects of these mutations on the protein expression were assessed. This mutational analysis will help identify the regions of PKC-epsilon that are vital for its function. This will help elucidate the effect of the same mutations in patients and could help predict the severity of disease. Obtaining a clearer picture of the different regions of the PKC-epsilon protein allows for future studies to focus on successfully fixing these regions when they become damaged and could therefore be used to help patients with SHORT syndrome.
Author(s): Anastasia Bernal Chemistry & Biochemistry Youngha Ryu Chemistry & Biochemistry
Advisor(s): Youngha Ryu Chemistry & Biochemistry
Location: Basement, Table 7, Position 1, 1:45-3:45
N-terminal acetylation is essential for the stability, activity, and targeting of proteins in eukaryotes. However, most eukaryotic proteins are not acetylated when expressed in bacteria. Therefore, it is of practical significance to control N-terminal acetylation of recombinant proteins in bacteria. RimJ is an N-terminal acetyltransferase (NAT) known to acetylate many recombinant proteins with a narrow substrate specificity in E. coli. This project is aimed to increase the applicability of RimJ for the N-terminal acetylation of a broad range of recombinant proteins.
Based on the AlphaFold-predicted structure of E. coli RimJ, we predicted that six amino acids (Y35, E46, R49, Y106, Y170, and L171) may recognize substrate proteins in the active site. We created RimJ variants, in which one or two of these amino acids are changed to alanine, a small neutral amino acid, so that the active site becomes larger to accommodate substrate proteins containing bigger N-terminal amino acid residues. The RimJ variants were created using site directed mutagenesis, confirmed by DNA sequencing, and co-expressed with Z domain mutants that were not acetylated by the wildtype RimJ. The Z domain mutants were isolated by immobilized metal ion affinity chromatography and analyzed by mass spectrometry for their N-terminal acetylation patterns.
Nature and bacteria make molecules like cyclosporine and coricidin that pharmaceutical companies do not make. They are too big, too greasy, and should not be able to be taken orally, however, these big molecules can fold to become small enough to intact with active sights on proteins. To try to replicate molecules like these we are making drug models called macrocycles. We focus on macrocycles because they are made quickly and cheaply. These molecules are big enough to block protein, protein interactions making a new way to fight diseases and illnesses. The groups universal macrocycle is made it the order: tert-butoxycarbonyl hydrazide, amino acid, dimethylacetamide, then acetal. My project moves the tert-butoxycarbonyl hydrazide to the end making the order: acetal, amino acid, in this case valine, dimethylacetamide, and tert-butoxycarbonyl hydrazide. The goal of this is to see if a bioactive macrocycle can still be made with this method and if there is any benefits in making the macrocycles this way.
Author(s): Jack Bonnell Chemistry & Biochemistry Magy Mekhail Chemistry & Biochemistry Katherine J. Smith Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Basement, Table 1, Position 3, 1:45-3:45
The goal of this project is to offer a more economic and environmentally friendly, alternative carbon-carbon coupling catalyst complex to what is used industrially today. Carbon-carbon coupling is a common reaction performed in the industrial production of organic materials through routes that use palladium and platinum catalysts. These metals, however, are both economically and environmentally costly to acquire. It has previously been demonstrated that iron containing complexes can be used as an alternative to the precious metal complexes. We have previously demonstrated the carbon-carbon coupling ability of iron PyN3 complexes and characterized the mechanism. Based on these results, we have developed a Py2N2 series and the iron congeners for C-C catalysis. We also characterized them in order to understand the relationship between the catalytic performance and the number of pyridine rings and pyridine substitution.
Metal Halide Perovskites (MHPs) are an emerging type of semiconductor for use in electronic devices that produce or utilize light. MHPs have shown advantages over traditional semiconductors such as silicon due to ease of solution processing, high defect tolerance (defects are strained chemical bonds and/or missing atoms in the crystal lattice) and tunable emission of light color. MHPs have the chemical structure ABX3 where A is a monovalent cation (+1) such as cesium, methylammonium or formamidinium; B is a divalent cation (+2) such as lead or tin, and X is a halide such as chloride, bromide, or iodide. Their favorable properties have resulted in solar cells capable of 32.5% power conversion efficiency in a tandem perovskite/silicon solar cell. However, MHPs suffer from issues with long term stability brought about by exposure to air and moisture, as well as ion migration under illumination.
Crystal engineering and chemical passivation using small molecules have been implemented to improve the long-term stability and reduce ion migration. Incorporation of small molecules with charged groups onto a MHP helps to mitigate surface defects by occupying surface sites of missing atoms or strained bonds. Recent work has shown incorporation of these small molecules during MHP synthesis results in the formation of two dimensional layers on top of the three-dimensional perovskite crystal resulting in increased long-term stability, resistance to heat and moisture, and reduction in ion migration at grain boundaries. Current work in our lab involves synthesizing thin films of methylammonium lead tribromide by spin coating and incorporating a macrocycle based on triazine molecules for this purpose. This presentation focuses on the effects of triazine treatment on the above perovskite, as evaluated by photoluminescence microscopy, powder x-ray diffraction, and scanning electron microscopy.
Author(s): Will Campa Chemistry & Biochemistry Christina Mantsorov Biology Shrikant Nilewar Chemistry & Biochemistry Kristof Pota Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Second Floor, Table 1, Position 3, 11:30-1:30
Pyridinophane molecules have recently been shown to have both antioxidant and pharmacological properties suitable for therapeutic applications targeting neurodegenerative diseases, including Alzheimer’s. We have synthesized derivatives of the parent molecules with substitutions on the pyridine ring (L1) or on the ‘side’ of the macrocycle (L2) designed to increase the antioxidant activity beyond that of the parent molecule in hopes of producing a molecule suitable for pharmacological testing in animal models. The lab is currently working towards substituting on the ‘bottom’ of the macrocycle (L3) to characterize and compare substitutions at each of the three positions.
Author(s): April Cannon Chemistry & Biochemistry Liam Claton Chemistry & Biochemistry Casey Patterson-Gardner Chemistry & Biochemistry Eric Simanek Chemistry & Biochemistry
Advisor(s): Eric Simanek Chemistry & Biochemistry
Location: Second Floor, Table 6, Position 1, 1:45-3:45
Macrocycles are molecules containing at least one ring composed of 12 or more atoms. Macrocyclic drugs have been used clinically for decades. Many interfere with protein-protein interactions. Therapeutic intervention requires that macrocycles remain flexible to facilitate the adoption of different conformations. Specifically, small compact hydrophobic conformations are required to cross cell membranes. The ability of a macrocycle to perform these contortions is predicted by its octonal:water partition coefficient, its so-called logP. Macrocycles (as well as small molecule drugs) that are suitable for oral delivery have a logP value <5. In this study, methionine containing macrocycles are studied. The studies commence with the synthesis of a macrocycle with a dimethylamine auxiliary group that allows for solution-phase NMR analysis. Upon formation of the macrocycle, oxidation to sulfone and sulfoxide derivatives was executed. These macrocycles are of interest because the impact that oxidation has on log P values has not been reported. Additionally, S-oxidation could change the conformation of the molecules. Synthesis beings with substitution of trichlorotriazine with BOC-hydrazine, followed by treatment with methionine in basic conditions. The final substitution of the triazine installs the auxiliary group, dimethylamine (NMR). Amidation with 1,1-diethoxypropyl amine using a peptide coupling reagent yields the monomer. Cyclization using TFA yields the macrocycle. NMR spectroscopy confirms macrocyclization and gives insight into the solution conformation of the molecule. Oxidation strategies and the results of logP analysis will be developed.
Proper functioning of BRCA1 and PALB2 are essential in preventing tumor formation. Upon detection of DNA damage, BRCA1 binds to PALB2, leading to formation of the BRCA1-PALB2-BRCA2 DNA repair complex which is recruited to double-stranded break sites. Mutations in the genes coding for BRCA1 and PALB2 may disrupt this binding interaction, causing obstructions in DNA damage repair and increased breast cancer risk. Variants of unknown significance (VUS) found in breast cancer patients are genetic variants whose impact on the health of individuals are not yet known. Our study characterizes the effects of these VUS on the BRCA1-PALB2 binding interaction. Site-directed mutagenesis was used to generate BRCA1 and PALB2 VUS. It was found that the binding event between BRCA1 and PALB2 is enthalpic in nature and can be measured adequately via isothermal titration calorimetry (ITC). Thus, ITC was employed to identify whether the VUS disrupted binding. ITC data suggest that several PALB2 and BRCA1 VUS exhibit disruptions of the BRCA1-PALB2 binding interaction, but to varying degrees. We will share the data for variants tested thus far and emerging themes for prediction of the roles residues in both proteins play in the vital interaction.
Barriers to rotation within triazine compounds have been previously explored by Katritzky and Birkett [1-2], but these studies have been limited to differences in the substituent groups on the triazine as well as the degree of substitution (mono, di, tri). This study explores how the barriers to rotation within triazine containing compounds are affected by solvent and protonation state. Overall, these molecules are of interest due to their wide range of applications in dendrimer and macrocycle synthesis as well as pharmaceutical drug development [3-4]. The results of this study illustrate how solvent selection can significantly impact the distribution of rotational isomers (rotamers) and how barriers to rotation can be increased by protonation of the triazine ring.
Alzheimer’s Disease (AD) affects over 6.5 million Americans over the age of 65. Previous research links AD with the aggregation of Amyloid-beta-40 (AB40) in the brain, which creates neurotoxic plaques, causing further development of AD in the brain. A potential therapeutic mechanism in the treatment of AD is using drugs that will prevent the formation of these plaques, which is possible with Metal Chelation Therapy.
Metal ion chelation ideally stops metal ions from aiding in the aggregation of AB40. However, to deliver metal chelating agents to the brain, a drug-delivery mechanism is required that will be able to deliver this medicine across the Blood-Brain Barrier. Porous silica is a potential drug delivery material due to its particle size, high loading capacity, tunability, and biocompatibility. Along with these characteristics, porous silica can create a “sustained” release of a given drug, allowing for a slow and steady release profile, reducing the risks of medication side effects.
This project seeks to establish the optimal loading capacities of a class of potential AD therapeutic molecules known as pyclens into porous silica, each with different pyridyl moieties and chemical functionalities along the rim of the molecule. Encapsulation efficiencies measurements for these pyclen derivatives reveal loading percentages in the 10-19% range, varying by pyclen identity. Additionally, release studies monitored diffusion over time to find which pyclen molecule achieved “sustained” release. All loaded pyclen species were able to show sustained release after 20 minutes. Additional release studies of these molecules in the presence of copper (Cu2+) remain to be completed to ascertain the ability of release drugs in the presence of Cu2+ to inhibit AB40 aggregation, followed by independent assays of AB40 solubility under such conditions.
Two proteins, BRCA1 and PALB2 are known to aid in DNA damage repair through homologous recombination. Both proteins are phosphorylated upon DNA damage, and we hypothesize that the phosphorylation of these proteins acts as an “on switch” to allow the proteins to interact and form the DNA repair complex. To test this hypothesis, we mimicked phosphorylation on the BRCA1 protein to test the binding affinity between BRCA1 and PALB2. Phosphomimicking mutants are created by mutating an amino acid with the ability to be phosphorylated and acquire a negative charge, such as threonine (T) or serine (S), to a negatively charged amino acid, such as glutamic acid or aspartic acid. Recent research has shown that specific phosphorylation sites, such as T1394 in BRCA1 are essential to DNA damage and repair in cells. We have created a phosphomimic mutant in this specific T1394 site by mutating threonine to glutamic acid. We are currently measuring the effect that this mutation has on the ability of BRCA1 to bind to PALB2 in vitro. The obtained data will reveal whether phosphorylation has an impact on the interaction between these two proteins or not.
Author(s): David Freire Chemistry & Biochemistry Hannah Johnston Chemistry & Biochemistry Sugam Kharel Chemistry & Biochemistry Magy Mekhail Chemistry & Biochemistry Kristof Pota Chemistry & Biochemistry Katherine Smith Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Second Floor, Table 8, Position 3, 1:45-3:45
Manganese complexes remain attractive as catalysts for oxidation reactions in biology and industry due to their abundance in nature and versatility to access different oxidation states. Macrocyclic ligands offer the advantage of substantially stabilize the metal center, hence allowing a handle to control their reactivity. Inspired by the manganese catalase enzyme, a biological catalyst for the disproportionation of H2O2 into water and O2, this work shows the impact of pyridine substitutions on the reactivity of the manganese center towards H2O2 disproportionation. Potentiometric titrations were used to study the ligand basicity as well as the thermodynamic equilibrium with Mn(II). Synthesis and isolation of the manganese complexes was followed by characterization using UV-vis spectroscopy, SC-XRD and cyclic voltammetry. Manganese complexes were also produced in situ and characterized using electrochemistry for comparison to the isolated species. Results from these studies and those with H2O2 reactivity showed a remarkable difference among the ligands studied, highlighting a distinction in the reaction mechanism from N4 and PyN3 vs. Py2N2. Moreover, electron-donating groups on the pyridine enhanced the reactivity of the manganese center for H2O2 disproportionation, demonstrating a handle for control of this type of reaction using the pyridinophane scaffold.
Author(s): Maegyn Grubbs Chemistry & Biochemistry Sergei Dzyuba Chemistry & Biochemistry
Advisor(s): Jeff Coffer Chemistry & Biochemistry
Location: Third Floor, Table 10, Position 1, 11:30-1:30
Metal-halide perovskites are crystalline materials that work as a semiconductor in both Light Emitting Diodes (LEDs) and solar cells. In general, perovskites possess the formula ABX3. For this project, the A site is an organic molecule such as Methylammonium (MA), the B site is Lead, and the X site is Bromide. While perovskites are easily fabricated, their crystal size and number of defects present are challenging to control. Defects cause LEDs to be less stable and/or less photoluminescent (bright) and cause solar cells to be less efficient at converting light to energy. One approach to reduce the number of defects is to use ionic liquids during perovskite formation. Ionic liquids are compounds made of ions in the liquid state due to a low melting temperature. They can be added to the perovskite precursor solution to slow down the crystallization process so that fewer defects are created. The goal of this project is to create new metal halide perovskites in the presence of selected ionic liquids, evaluate their structure and photophysical properties, with the long-term goal of creating new LEDs that are both stable and efficient.
In this project, cetyl-ionic liquids (cetyl meaning 16 carbon chains) were investigated for their effects on perovskite structure and light emission. The three ionic liquids were investigated: [C16-mim]Br (referred to as "IL1"), [C16-py]Br ("IL2"), and [C16-C1pyrr]Br ("IL3"). Variations on the addition method of ionic liquids to the perovskite precursor were studied as well. It was hypothesized that the inclusion of cetyl-ionic liquids will protect the perovskite films from the environment (increasing stability) by providing a hydrophobic layer on the surface and will improve the electronic properties by filling in pinholes that cause defects. It is found that perovskite films with IL3 are more photoluminescent than the perovskite films formed with IL1, IL2, or no IL (control). Preliminary experiments varying the addition method of IL3 during film formation have shown that the perovskite films are brightest when IL3 is added to both the precursor and the antisolvent layers at the beginning of the fabrication process. These results, along with detailed structural characterization of a given perovskite film, will be discussed in this presentation.
To fight many diseases, pharmaceutical companies have historically prepared small molecules designed to bind to specific sites on proteins (enzymes) to stop a chemical reaction that the protein is a part of. Examples of this include penicillin for bacterial infections and tipranavir for HIV. However, there is another paradigm for interacting with proteins to fight diseases that has gone largely unexplored--blocking protein-protein interactions. To accomplish this, large molecules are needed to bind to large areas on the protein target. Unfortunately, large molecules present additional challenges that many small molecules do not face. Typically, large molecules are hard to synthesize and not water-soluble. These characteristics make the development of oral medications virtually impossible as the molecules cannot cross cell membranes. Nature has designed molecules like cyclosporin that should not work as drugs based on current understanding. These molecules fold to hide hydrophilic groups so that they can cross cell membranes. This research explores the ability of comparable large, ring-shaped molecules, so-called macrocycles, to behave similarly. We recently showed that our macrocycles fold like door hinges with a rate that depends on the groups attached to the ring. Here, we explore how changing one of the hinge components--substituting an oxime for a hydrazone—affects folding.
Author(s): Lola Kouretas Chemistry & Biochemistry Benjamin Janesko Chemistry & Biochemistry Alexander Menke Chemistry & Biochemistry
Advisor(s): Eric E. Simanek Chemistry & Biochemistry
Location: Third Floor, Table 7, Position 2, 1:45-3:45
Macrocyclic drugs adopt multiple conformations--a behavior referred to as chameleonicity--to navigate hydrophobic cellular membranes and aqueous intracellular environments. The rules for understanding this behavior are beginning to emerge through studying existing drugs and the synthesis of model systems. Historically, one challenge to macrocycle synthesis is low yield reactions. To this end, dynamic covalent chemistry has been explored. Here, macrocycles are afforded readily by dimerization with the formation of two hydrazones.
The efficiency of the macrocyclization reaction led to the hypothesis that upon formation of the first hydrazone, the acyclic intermediate was preorganized to place the hydrazine and acetal in close proximity thereby reducing the likelihood of oligomeric or polymeric products. The preorganization could result from a network of hydrogen bonds. Moreover, in an acidic environment, wherein the triazine ring is protonated, the opportunity for bifurcated hydrogen bonds emerge. Computation has been used to identify sites for protonation and the energetic contributions of hydrogen bonding.
To explore templating and the role of protonation in the formation of hydrogen bonds, model systems were prepared that emulate ‘half’ of the macrocycle. The acetylated aminoacetal offers a well-resolved NMR spectrum. In contrast, hindered rotation about the triazine-N bond leads to a mixture of rotamers in the hydrazine component. However, upon condensation, a single rotamer is observed and resonances corresponding to the hydrogen bonded protons emerge downfield between 7-12 ppm. Computation provides estimates of the energetic contribution of the bifurcated hydrogen bond as well as the hydrogen bond formed in the absence of protonation. The results of titration and variable temperature NMR experiments will also be described.