Effect of Season, Body Size, and Sex on the Mercury Concentrations of Orb-Weaving Spiders
Cale Perry, Garrett Helburn, Olivia Eberwein, Madeline Hannappel, Matthew Chumchal, and Ray Drenner
Mercury (Hg) is an anthropogenic contaminants found in all aquatic ecosystems across the world. One of the methods to monitor levels of Hg contamination in an ecosystem is using sentinel organisms: abundant and widely distributed organisms within the food web that accumulate contaminants in body tissues without negative effects. Riparian spiders are a potential sentinel organism for the study of Hg contamination in aquatic ecosystems, as they accumulate mercury through the consumption of contaminated emergent aquatic insects. The present study will examine the effects of spider body size, sex, and season on 2 taxa of orb-weaving spiders [Family Araneidae: Larinioides sp., Metazygia sp.]. 575 orb-weaving spiders were collected from a boat dock on the South side of Eagle Mountain Lake, Texas, USA, from May to September 2019. The spiders were preserved in 95% ethanol and sorted based genera, month collected, sex, and size class. Size class was determined by measuring the spiders front left leg length (tibia + patella) and served as an indicator of body size. Mercury contamination will be analyzed through direct Hg analysis.

Plants with threatened habitats and fragmented populations may require repatriation efforts to maintain healthy populations. Populations of Sarracenia alata, the pale pitcher plant, are severely fragmented, and the species is near threatened. A complete understanding of its reproduction will be crucial in establishing and maintaining healthy populations. The goals of this study were to determine if 1) S. alata is capable of selfing (reproducing with pollen from the same individual); 2) S. alata is capable of autogamy (selfing without intervention); and 3) pollen load affects reproductive success. We used seed set to measure individual fitness. Thus, it was necessary to determine a reliable method of counting seeds. Two methods were examined, and these gave statistically similar results. We found that while S. alata is capable of selfing, it is not autogamous. Seed set was significantly higher in outcrossed individuals than in selfed individuals . In 2019, plants receiving supplemental pollen yielded more seeds than those in either the control group or a group in which pollinator access was restricted. During 2021 (a year with higher pollinator activity), there was no significant difference between the number of seeds produced by control plants and those receiving supplemental pollen. This study demonstrates the important role of pollinators in maintaining healthy populations in this system.

Due to habitat loss the Texas horned lizard (THL) (Phrynosoma cornutum) population has declined across its historic range. To date, reintroduction attempts for the species have been unsuccessful, calling into question the suitability of the habitat. Texas horned lizards require suitable thermal habitat to meet their thermoregulatory needs, because of this, understanding the thermal habitat requirements of THLs is important. While the critical temperature limits and preferred body temperatures of THLs are established from laboratory studies, thermal habitat preferences for THLs in the wild are poorly understood. The objective of this study was to determine thermal habitat preferences and home range sizes of reintroduced THLs at Mason Mountain WMA compared to a nearby natural population of THLs on the White Ranch. We also compare the thermal conditions of different microhabitats between the two sites. To compare thermal conditions between the two sites, we used thermal dataloggers to record the temperatures in different microhabitats throughout the day at each study site, then compared how much of the time these data loggers were within the lizard’s optimal temperature range between the two study sites. Home ranges were calculated for lizards from the two study sites and average home range sizes between the two study sites were compared for significant differences. The ground temperature selected by the lizards versus random points were compared between the two study sites. These findings will improve our understanding of THL thermal ecology and reintroduction requirements.

Migration, which is defined as the seasonal movement for survival or reproductive advantage such as access to resources, is a behavioral phenomenon exhibited by many species including the salmonid Oncorhynchus mykiss. More commonly known as rainbow trout, O. mykiss exists in two life histories: migrants (steelhead trout), and residents (rainbow trout). While there are many factors that contribute to this variation in migration behavior, one of the reasons is their genetic makeup since there is an apparent correlation between the migratory behavior of parents and their offspring. The primary objective of this research project is to identify single nucleotide polymorphisms (SNPs), or genetic differences, which are associated with migratory behavior in rainbow trout. To that end, I used whole genome sequence data from five migrant and five resident rainbow trout. These data were aligned to the trout genome and used to locate genetic differences between the two migratory types. Quantitative PCR (DMAS-qPCR) approaches were used to validate the SNPs and genotype them in a larger set of twenty-five migratory steelhead. Research findings exhibited that Sashin Lake is producing smolts (young migratory steelhead) that are successfully returning to the lake and reproducing at the end of their life cycle. Additionally, while there was not a significant difference seen in terms of marine survival between the sexes, females were more likely to migrate compared to their male counterparts due to the reproductive advantage and greater access to resources that migration offers. This data will support future studies observing trout migratory behavior with larger sample sizes and from different generations and settings and will benefit conservation studies regarding population decline in migratory species.

BRCA1 is a gene whose protein (also named BRCA1) is found throughout all human cells and engages in DNA repair, cell cycle regulation, gene transcription regulation, and apoptosis. However, mutations in BRCA1 typically confer a higher risk of cancer in estrogen-responsive tissues, including breast epithelial tissue. This increase in incidence of tissue-specific cancers is thought to be in part due to the role of BRCA1 in the estrogen response pathway and interaction with the estrogen receptor alpha (ERα). Previous studies identified possible regions of each protein involved in the binding interface between BRCA1 and ERα. Using these regions (amino acids 177-240 in BRCA1 and the ligand binding domain of ERα) as our constructs, our studies further analyzed the molecular details of this direct interaction and determined methods conducive to studying the BRCA1-ERα interaction. A pull down assay qualitatively confirmed binding between the constructs of BRCA1 and ERα. Data collected from NMR spectroscopy reaffirmed the direct interaction between BRCA1 and ERα first seen in the pull down assay and provided evidence demonstrating that the presence of estrogen in the samples increased binding affinity. Finally, fluorescence spectroscopy of quenching experiments confirmed the previous two results – that a direct interaction between the constructs of BRCA1 and ERα used occurs and the binding affinity increases in the presence of estrogen – and allowed us to describe the binding curve of the system being studied. The molecular details confirmed here provide further avenues of study, such as documenting variants of unknown significance or studying the role estrogen plays in the function of the BRCA1-ERα complex, which could lead to novel findings that expand our understanding of the role either protein plays in cancer development.

Alzheimer’s disease (AD) affects about 6 million Americans, and hallmark pathologies of AD include amyloid beta (Aβ), inflammation, and oxidative stress. Microglial cells (MGCs) are brain cells that function like immune cells, and they respond to Aβ by secreting pro-inflammatory cytokines. Cytokines induce inflammation at sites of infection, and Aβ continually increases inflammation, resulting in neuronal death. Inflammation is also connected to oxidative stress, and prior research has demonstrated that Nrf2 (a transcription factor) protects cells from oxidative stress by increasing antioxidant enzymes. We will test potential benefits of molecules with antioxidant capabilities, created by Dr. Green (TCU Chemistry), on inflammation and Nrf2 expression in MGCs. Previously, we demonstrated that these compounds, L2 and L4, are powerful antioxidants that protect MGCs from oxidative stress. Currently, we aim to study the effects of L2 and L4 on inflammation, Nrf2 expression and heme oxygenase-1 (antioxidant) production following an inflammatory insult. We will pre-treat MGCs with different concentrations of L2 and L4, and then stimulate MGCs with lipopolysaccharide (LPS), a bacterial mimetic. Subsequently, we will measure pro-inflammatory cytokines, Nrf2 expression and antioxidant response genes. Overall, it is crucial for researchers to investigate effective therapeutics that could relieve AD symptoms, such as antioxidant treatment.

Testing of chemicals that enter our waterways is necessary to keep marine environments healthy. The current method of toxicity testing is the larval growth and survival (LGS) test, which exposes larval fish to varying concentrations of an effluent or chemical. Given recent legislation that calls for improvements in the welfare of animals used in toxicity testing, there is a need to identify alternatives to the LGS test. In light of this, the objective of the current study was to determine whether toxicity tests featuring fish embryos or shrimp could be used in place of LGS tests.

To accomplish this, we compared the results of the standard LGS test using inland silverside larvae with the results from two alternative tests, a mysid (e.g., shrimp) test and an inland silverside fish embryo toxicity (FET) test. The results of this study show that both the mysid and FET tests are promising alternative testing methods to the LGS test. The adoption of either test type will meet legislative goals and improve the welfare of fish used in toxicity testing.

The Effect of Body Size on Mercury Concentration of Orb-Weaving Spiders (Araneidae) from the Clear Fork and West Fork of the Trinity River

Authors: Tyler Williams, Iris Schmeder, Morgan Capone, Matthew Chumchal, Andrew Todd, Ray Drenner, Cale Perry, Tori Martinez, Macyn Willingham, Robby Peterson, Chris Allender

Mercury (Hg) is a contaminant threatening all ecosystems. Inorganic Hg is released into the atmosphere from power plants and artisanal gold mines before being deposited over the landscape. Inorganic Hg deposited in the water can be converted by aquatic bacteria to methylmercury (MeHg). Methylmercury is one of the most toxic forms of Hg due to its capability of bioaccumulating within the tissues of organisms. Overexposure of methylmercury can cause damage to the nervous, genetic, and enzyme systems in the body, leading to a multitude of health complications. Evaluating the amount of Hg in an ecosystem, and thus the risk to organisms, is not straightforward. For example, the concentration of Hg in water or sediment may not be representative of aquatic organisms’ exposure to Hg because not all the Hg in water or sediment is bioavailable. As a result, scientists measure Hg concentrations in sentinels, defined as: an organism that can accumulate Hg within its tissue without significant adverse effects and serve as a representation of the level of Hg present within an ecosystem. Riparian spiders consume emerging aquatic insects and are therefore sentinels of Hg contamination in aquatic ecosystems. The objective of the study was to evaluate the concentration of total Hg in orb-weaving spiders (Family Araneidae) from the Clear Fork and West Fork of the Trinity River and determine how Hg concentration changes with spider body size. Spiders were preserved in 95% ethanol and body size was measured. Spiders were then dried and analyzed using a Direct Mercury Analyzer (DMA).

The long-term goal of exploring macrocycles is to be able to produce drugs that can interfere with certain protein-protein interactions within cells. This strategy could have the potential to change the way scientists think about drug design. Aspartic acid is a particularly useful to incorporate because it is one of the top five amino acids that contribute to binding at protein-protein interfaces. The acid sidechain of aspartic acid presents significant challenge because of the potential for side reactions. This research has established that an aspartic acid macrocycle can be synthesized quickly in three steps. The route is remarkably efficient and has the characteristics of those that could be used to make drugs. This poster details the chemical synthesis and characterization of this molecule, discusses potential side reactions, and identifies the next steps in advancing this project.

N-terminal acetylation plays an important role in the stability, activity, and targeting of proteins in eukaryotes. Most proteins expressed in bacteria are not acetylated, although the N-terminal acetylation is critical for the activities of a handful of biologically important proteins. Therefore, it is of practical significance to control N-terminal acetylation of recombinant proteins in bacteria. This study is aimed to alter the substrate specificity of RimJ, a protein N-terminal aminotransferase (NAT) that is known to acetylate a few recombinant proteins including the Z-domain in E. coli. The RimJ-mediated protein acetylation occurs at a higher rate when the substrate’s N-terminal amino acid is small. Because of this narrow substrate specificity, RimJ is not applicable for a broad range of recombinant proteins. Based on the AlphaFold-predicted structure of E. coli RimJ (AF-P0A948_F1), we predicted that five amino acids (Y106, M142, N144, Y170, and L171) may recognize substrate proteins in the active site. We created RimJ variants, in which one or two of these five 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. Then, the substrate specificity of RimJ was investigated by co-expressing two Z-domain variants T2I and S3K, which were not acetylated by the wild-type RimJ. The expressed Z-domain variants were purified by immobilized metal affinity chromatography and subsequently analyzed by mass spectrometry, by which a 42-Da mass increment indicates the presence of an N-terminal acetyl group. The RimJ single mutants such as N144A, M142A, and Y106A showed little acetylation on both T2I and S3K Z-domain variants. In contrast, the RimJ double mutants, Y106A M142A, Y106A N144A, and Y170A L171A showed higher acetylation rates on the Z-domain T2I variants. Little acetylation was observed for the Z-domain S3K variant by any of these double mutants. We also created more RimJ variants in which three different amino acids located on the other side of the active site were changed to alanine. These variants will be used to co-express the Z-domain variants, whose N-terminal acetylation patterns will be analyzed by mass spectrometry.

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.

In the lab, molecules used as drugs are made either in solution (wherein the reactive agents dissolve) or on solid supports referred to as 'beads' (wherein reactive agents are washed over beads and become attached only to be liberated later). The virtue of bead-based synthesis comes with the savings in time and energy normally required to purify the reaction products. That is, solution phase synthesis is work intensive. Here, a route to cyclic molecules synthesized on beads is described. The molecules produced by these bead-based methods have already been prepared in solution for comparison. In addition to evaluating the relative efficiencies of these two routes, the bead-based method can be used to rapidly make 100s-1000s of cyclic molecules. Such numbers are not possible using solution phase methods due to the burdens of purification. The effort relies on tethering an acetal to a reactive bead, followed by a protection and deprotection sequence, the addition of an amino acid using standard peptide coupling strategies and a reaction with a core group that offers the potential for the attachment of 100s-1000s of different groups. Cleavage of this linear molecule from the bead leads to spontaneous cyclization to the desired products. The products will be characterized by NMR spectroscopy and mass spectrometry as well as be assayed for biological activity in a disease model of breast cancer.

Salt-induced diffusiophoresis is the migration of a colloidal particle in water caused by a salt concentration gradient. Recent studies have shown that diffusiophoresis can be used for controlling particle motion, with potential applications in separation science, microfluidics, and enhanced oil recovery. These applications are especially appealing for nanoparticles with host-guest properties such as micelles. In this work, Rayleigh interferometry was used to experimentally characterize diffusiophoresis of tyloxapol micelles in the presence of the strong salting-out agent, sodium sulfate, in water at 25oC. Our results show that micelle diffusiophoresis occurs from high to low salt concentration. A model based on micelle preferential hydration was used to quantitatively explain our findings. At relatively high salt concentrations, liquid-liquid phase separation (LLPS) was observed. Near this phase transition, micelle Brownian mobility was found to dramatically decrease, making micelle diffusiophoresis the dominant transport mechanism. Our work suggests that salting-out agents and proximity to LLPS can be used to control the motion of micelles and hydrophilic nanoparticles in general.

Tissue engineering encompasses many important medical applications that pertain to the repair and regeneration of various tissues throughout the human body that have been adversely affected by disease or injury. Through combining the body’s cells with synthetic scaffolds, tissue engineering promotes proliferation of cells at damaged sites. Recent advances have demonstrated that using biocompatible materials such as alginate hydrogels—polymer networks derived from brown algae—are a cheap and environmentally-friendly approach to this. Alginate hydrogels are effective because they mimic the extracellular matrix of tissues, which provides structural support to cells that comprise human tissues.
One necessary modification to these scaffold materials is to load them with drugs that can facilitate healing. More complex designs can ideally deliver more than one therapeutic species simultaneously. In addition to hydrogels, drugs can also be loaded into a material known as porous silicon (pSi). pSi nanoparticles can be physically entrapped inside alginate hydrogels to create a two-system drug delivery mechanism with sustained release. This allows drugs such as growth factors, substances that stimulate cell growth, to be released at different times as the pSi and alginate hydrogel degrade.
This project entails the construction of alginate hydrogels that incorporate model dye-loaded pSi particles. The release of two dye molecules known as curcumin and rhodamine were monitored to assess the efficacy of the two-system drug delivery mechanism. It was first found that curcumin was too hydrophobic of a dye to achieve significant loading in the pSi. Rhodamine was found to be released from the pSi/alginate hydrogel system in a more incremental (sustained) manner over time compared to a relatively large initial ‘burst’ release observed for the release of rhodamine from pSi only. Sustained release in drug delivery is important to ideally reduce the amount of drug necessary and contrasts a burst release where large amounts of the loaded molecules are released prior to achieving a stable release profile. Furthermore, the localization of pSi in the alginate hydrogels was achieved by inserting loaded pSi membranes into pre-gelled alginate hydrogels, which is important to control the spatial delivery of the loaded molecule from pSi. Overall, it is believed that this pSi/alginate hydrogel material can greatly benefit the field of tissue engineering by creating dual delivery platforms with more diverse control over drug release.

Catalases are a class of metalloenzymes responsible for the protection of cells from damage caused by hydrogen peroxide by converting it into water and oxygen. Manganese-based catalase (MnCAT) has been identified in different organisms as an antioxidant, raising the interest in developing small molecules as biomimetic models. A Mn(III) complex of pyclen, a 12-membered ring pyrinophane macrocycle, has previously shown to be a functional mimic of MnCAT in our laboratory. In the present study, modifications of the pyridinophane macrocycle were used to evaluate their impact on the catalytic disproportionation of hydrogen peroxide. Two series of ligands were studied: (1) varying the number of pyridine moieties within the macrocycle, and (2) substitutions in the 4-position of the pyridine ring. pH-potentiometric titrations were used to determine the formation constants (log ß) of each manganese complex, which allowed us to derive speciation curves in solution. The initial rates method was used to calculate the kinetic-relevant parameters for the disproportionation reaction. The results emphasize the effect of structural differences of the ligand on modulating the reactivity of manganese, which are the basis of a mechanistic study of the reaction that is currently underway.

N-alkylation of amino acid-containing pharmaceuticals has been shown to increase their respective oral availability and membrane diffusion. Macrocycles, too, have been an interest in modern drug design due to their ability to have a dynamic conformation and adopt a chameleon-like property to enhance the ability for the drug to be properly delivered in a multitude of environments, and similarly macrocycle's ability to fully envelope an active site to block enzymatic activity. In this project, four novel N-alkylated amino acid-linked triazine macrocycles were synthesized from cyanuric chloride using BOC-hydrazine, an N-alkylated amino acid, and dimethylamine. Coupling of the amino acids with EDC to form the acetal product and further acidification and removal of protecting groups with trifluoroacetic acid yielded macrocycles in good yield. Characterization via 1D and 2D NMR reveals the emergence of different conformations in varying proportions. These conformations result from by the restricted rotation around the Ar-N bonds of both the hydrazine and amino acid of the macrocycles. A previous, non N-alkylated, glycine macrocycle was used as a reference compound, and the emergence of the different conformations was not observed for this molecule. Furthermore, the N-methylated glycine macrocycle displayed an asymmetric configuration, whereas the proline macrocycle was too rigid around the Ar-N of the amino acid to form the different rotamers. The successful synthesis of these N-alkylated amino acid macrocycles shows that further customization of these triazine macrocycles is possible.

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.

This project aims to incorporate unnatural amino acids into proteins using an ortogonal pair composed by a leucyl synthetase from Methanobacterium thermoutotropicum (MLRS) and tRNA from Halobacterium sp. NRC-1 (HL-TAG3). A plasmid called pRCG was designed to contain a cat-upp fusion gene with amber stop codons at permissible sites of the chloramphenicol acetyl transferase protein (CAT). Three variations of the pRCG plasmid were tested: Q98TAG, D111TAG, and a double mutant containing both mutations. To study the amber codon suppression ability of the mutants, a functional leucyl-tRNA synthetase lacking the editing domain was tested for the incorporation of its endogenous amino acid using the three pRCG variants. To show that the amber stop codon is being suppressed, E. coli GH371 cells must survive when grown in the presence of leucine and chloramphenicol because the full-length CAT is expressed. In contrast, when grown in the presence of 5-fluorouracil (5-FU) and leucine, cells will not survive because the MLRS produces a full-length uracil phosphoribosyl transferase protein (UPRT) that converts 5-FU to a toxic product, causing the cells to die. Only Q98TAG or D111TAG mutant was able to suppress the amber stop codon when E. coli GH371 cells were grown in the presence of leucine under positive and negative selection conditions. The Q98TAG variant showed higher suppression ability. A library of MLRS with five randomized amino acids in the active site was designed and selected using the pRCG Q98TAG system and two unnatural amino acids (UAAs): 4-nitro-1-phenylalanine and 2-amino-3-(5-(dimethylamino)naphthalene-1-sulfonamide)propanoic acid (Dansyl-Dap). The obtained variants are currently under study to test their ability to incorporate these UAAs into a model protein called Z-domain

It is estimated that 50 million individuals worldwide live with Alzheimer’s disease (AD), a neurodegenerative progressive disorder that, along with other chronic dementias, cost the United States $355 billion in 2021. Previous research links AD with amyloid beta (A𝛽) aggregation in the brain. Possible therapeutic drugs, including antioxidants and metal chelating agents, need efficient delivery systems that can cross the blood-brain barrier and release drugs appropriately. Recent discoveries in nanoscale materials as targeted drug delivery and controlled release agents have shown that such materials can release therapeutic drugs in a slow manner and increase efficacy. Chief among these carriers are porous materials with high surface areas because of their tunable pore structure, surface chemistry and drug loading capacity. This project focuses on using porous silicon derivatives as a carrier because, in addition to the above properties, it is a known biocompatible material.
This research deals with developing efficient protocols for loading mesoporous silica (pSiO2) with selected metal ion binding agents through systematic manipulation of external variables in order to achieve the highest percentage of loading. Once this has been determined, release and complexation studies are conducted. Known spectrophotometric methods are used to monitor diffusion over time and evaluate the profile of the sustained release. Different derivatives of chelating agents are tested and compared to determine the best suited candidates. The macrocyclic molecule Pyclen was the first tested candidate, followed by its dimer form, and finally a halogen substituted derivative. Stoichiometric complexation ratios with copper ions are measured followed by testing their success of inhibiting amyloid beta aggregation. Developing a slow and steady rate at which drugs capable of inhibiting neurotoxic A𝛽 aggregates in the brain can be released should be more effective and lead to more promising solutions for AD.

The misregulation of reactive oxygen species (ROS) and transition metal ions contributes to the onset of Alzheimer’s Disease (AD). A series of new pyridinophane ligands with indole (L2 and L3) and 4-methyl-8-hydroxyquinoline (L4) modifications were evaluated as a means of targeting the molecular features of AD. These studies contribute to the overall understanding of the therapeutic potential of the pyridinophane backbone as a means of treating AD. In comparison to the parent molecule L1, the order of radical scavenging activity was determined to be L4 > L1 ~ L3 > L2, which is likely related to the reactivity and position of the substitutions. These results demonstrate that the addition of (1) the indole moiety to the pyridine, and (2) the addition of the 4-methyl-8-hydroxyquinoline moiety to the secondary amine on the tetra-aza macrocyclic pyridinophane both disrupt radical scavenging ability, warranting future exploration of these modifications in therapeutic design for AD.

Catalase is one of the most efficient antioxidants metalloenzymes in biology responsible for the decomposition of hydrogen peroxide into water and oxygen. The desired antioxidant activity of catalase for medical and industrial application has inspired the study of metal-based mimics of catalase activity. However, very few of these studies explored iron-based mimics, their mechanism of action and the impact of the metal center environment on the activity of the complex. In this study, the first goal is to investigate pyridine containing macrocyclic Fe (III) complex (L1) as catalase mimic. Mass spectroscopy and UV-Visible spectrophotometry were used to follow the mechanistic activity of FeL1. The second goal is to evaluate the impact of adjusting the electronic properties (L2 and L3) and the structural rigidity (L1 and L4) of the ligand on the activity of the complex. Cyclic voltammetry, X-ray structural analysis, potentiometric titration, and UV-Visible spectrophotometry were conducted to characterize and study the properties of all the complexes. Kinetic studies following the initial rate method and TON studies were conducted to compare their activity.

To accomplish many critical reactions and interactions mediated by metals like zinc and copper, Nature uses the amino acid cysteine—often in pairs—that are preorganized in space by a protein. Cysteine proteases are illustrative of the former; zinc finger transcription factors of the latter. Small molecule models of these proteins can serve many roles. They can shed light on the chemical process or ape them for therapeutic gain. Here, a macrocycle is used to preorganize two cysteine residues. These macrocycles are synthesized in three steps. The route begins with a stepwise substitution of a BOC-protected hydrazine group, a protected cysteine, and dimethylamine onto a triazine ring. Next, an acetal is appended onto the compound. Finally, a macrocycle is produced using an acid-promoted homodimerization. The macrocycle product has been characterized using 1H and 13C NMR in 1D and 2D experiments. Additionally, logP, variable temperature NMR, and H/D exchange experiments will be performed to understand the shape of the macrocycle in solution. These studies conclude with a study of how these cysteines bind metal ions. The results of this work will guide their development for biomedical applications including their use as drugs.

Three b-branch substituted macrocycles featuring a b-branched amino acid linked acetal, a trans-hydrazone, and dimethyl amine were synthesized via acid condensation to yield homodimer macrocycles near quantitative yield without need for further purification. Previous attempts at the dimerization of triazine monomers utilized glycine or b-alanine that do not contain steric bulk. Here, L-valine, L-threonine, and L-isoleucine were used to probe the effects of steric bulk upon macrocycle formation. The resulting macrocycles are symmetrical species that are characterized by 1H-NMR, 13C-NMR, 1H-COSY spectroscopy, and 1H-rOesy spectroscopy. The symmetrical macrocycles containing valine exists as one species while threonine and isoleucine macrocycles exist as two isomers in a 9:1 and 6:4 ratio respectively. All three macrocycles exist as one rotamer state out of four possible. The minor isomer of the threonine macrocycle has an inconclusive rotamer state where the isoleucine macrocycle shows the same rotamer state as the major isomer. Well-tempered MetaDynamics Simulations tell us the rotamer state seen in the rOesy favors a folded state in all cases with barriers to interconversion decreasing as size of the side chain increases.

Various semiconductor metal oxides such as ZnO, TiO2, WO3, and BiVO4 have been utilized for photoelectrochemical (PEC) water-splitting as well as for value added alternative reactions. However, single-phase materials often face multiple challenges including poor charge separation efficiency and surface degradation especially in aqueous environment. BiVO4 is well known as a promising photoanode material, but the above-mentioned shortcomings are still present. Therefore, in order to enhance the PEC performance of BiVO4,our group has focused on doping techniques for BiVO4 with tungsten (W) to yield tungsten doped BiVO4 (W:BiVO4). In addition, polyethylene glycol (PEG) has also been introduced to the material as a morphological control agent. The addition of polymer to the precursor solution helps to control the porosity of the resulting surface film by promoting a less porous and more compact formation of BiVO4 on FTO. The mixture of PEG (1% MW 100,000 : 1% MW 20,000) has been tested. The photochemical oxidation of a solution containing (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) has been performed in acetonitrile with 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF6) electrolyte. As a result, photocurrent density of PEG (1% MW 100,000 : 1% MW 20,000) - W:BiVO4 (0.58 mAcm-2 with an applied biased of 0.3 V vs. SCE) has outperformed that of W:BiVO4 without PEG (0.32 mAcm-2). Based on the data obtained, PEG(1% MW 100,000 : 1% MW 20,000) -W:BiVO4 outperformed W:BiVO4 by about 2 times. In the future, the best performing electrode samples will be studied for driving TEMPO-mediated benzyl alcohol oxidation.

Cancer is a disease worldwide, and every year millions of people are diagnosed with it. Platinum compounds play an important role as anticancer agents. Their ability to bind to DNA in the nucleus (by a process known as intercalation within DNA base pairs) result in DNA damage and cell death. Unfortunately, these platinum-containing compounds lack specificity toward cancer cells and attack normal healthy cells that results in significant side effects as a consequence (loss of hair, nausea, among others).
Drug carriers (inert structures that house a given drug) that can deliver relatively large amounts of one of these drugs in a small volume (which are often chemically metastable) with some degree of specificity toward the tumor (thereby sparing the healthy cells) are clearly desirable. Our research group has developed a straightforward method to produce a well-defined nanoscale drug carrier known as silicon nanotubes (SINTs), along with a way to incorporate platinum on their surface using (3-Aminopropyl) triethoxysilane (APTES) as a functional arm. These silicon nanotubes have attracted great attention in applications relevant to diagnosis and therapy, owing in part to its biocompatibility and biodegradability in cells.
Once inside the cell, platinum is released slowly, thus allowing an interaction with DNA. Our previous results using this technology showed significant toxicity on a type of cancer cell known as HeLa. While these findings are promising, specificity has not yet been achieved.
Cancer activates signaling pathways that translates on overexpression of specific proteins/receptors. Particularly, folate receptors (FR) are present in 90-98% of ovarian, prostate, uterus, breast, as well as some adenocarcinomas. FR expression is very limited in normal cells and generally not accessible to blood flow which makes it a suitable and promising system to target cancer. These receptors are glycopolypeptides that present a high affinity for folic acid (FA). We propose to incorporate folate to our silicon-based Pt nanoparticles to enhance selectivity.
A viable strategy has been identified, involving the conjugation of a molecule known as glutathione to act as a linker to the surface of the silicon-based platinum nanoparticles through N-Hydroxysuccinimide (NHS) activation, followed by substitution with folic acid. This presentation will highlight some of our recent progress in this approach.