The mis-regulation of reactive oxygen species (ROS) and transition metals contribute to the onset of Alzheimer’s Disease (AD). A tetra-aza macrocyclic pyridinophane with an indole moiety, (Ind)PyN3, was evaluated on its radical scavenging reactivity and ability to chelate and stabilize the copper (II) oxidation state; these evaluations contribute to the overall therapeutic efficacy of the ligand in treating AD. Compared to a congener replacing the indole moiety with a hydroxyl moiety, (OH)PyN3, (Ind)PyN3 displayed comparable radical scavenging reactivity to (OH)PyN3. The fluorometric CCA assay revealed that (Ind)PyN3 was able to the stabilize the copper (II) oxidation state and prevent it from generating ROS via redox cycling at both 1 and ½ equivalents, albeit (OH)PyN3 was more effective at copper (II) oxidation state stabilization than (Ind)PyN3 at half molar equivalence. Our results demonstrate that the addition of the indole moiety to a tetra-aza macrocyclic pyridinophane does not disrupt radical scavenging reactivity by the indole moiety nor the ability of the pyridinophane to stabilize transition metal ions, warranting future exploration of the indole moiety in therapeutic design for AD.

Dispersion interactions also known as van der Waals interactions are essential for everything from nanomaterials to organic chemistry to biological chemistry. Modeling that chemistry requires modeling van der Waals interactions. Approximations that start from “freshman chemistry” molecular orbital (MO) theory do not account for dispersion. For example, helium-helium interactions are unbound in molecular orbital theory as two electrons are placed in antibonding orbital, but in reality, the interactions are weakly bound and can form a liquid. We have developed a density functional theory method embodying MO theory and corrections. Dispersion corrections can be added to noncovalent interactions in order to model them by using a standard model with different parameters. By fitting these parameters, the accurate known bond energies of real noncovalent complexes can be reproduced.

This project is aimed to develop triazine-based fluorescent bivalent antibody mimics against the epidermal growth factor receptor (EGFR), a protein disease marker for cancer. A synthetic gene for the anti-EGFR Z-domain was constructed by overlapping extension PCR and inserted into the pET-Z plasmid to produce pET-Z anti-EGFR. The anti-EGFR Z-domain variant was expressed as a C-terminal His-tag fusion in BL21(DE3) E. coli cells transformed with the pET-Z anti-EGFR plasmid and purified by immobilized metal ion affinity chromatography. A dansyl fluorophore was attached to the first position of a triazine core that has three positions available for modification. To the second available position of the dansyl-triazine conjugate, an anti-EGFR Z-domain molecule was selectively attached to generate a monomeric conjugate. Another anti-EGFR Z-domain molecule will be attached to the remaining position of the triazine core to produce a dimeric conjugate. We will test the fluorescent monomeric and dimeric anti-EGFR Z-domain conjugates for binding to the EGFR by a standard ELISA method and isothermal titration calorimetry.

Alzheimer's disease is a neurodegenerative disorder that is characterized by amyloid-beta plaques, neurofibrillary tangles, and unregulated reactive oxygen species. The production of reactive oxygen species in the brain is exacerbated by an excess of free-metal ions in nervous tissue. Our team and others have shown a library of tetra-azamacrocycles to have the ability to scavenge free-metal ions and quench reactive oxygen species. These macrocyclic ligands have, thus, been considered as potential therapeutic agents for combatting Alzheimer’s disease. The ability of a neuro-active pharmaceutical to cross the blood-brain barrier is crucial to its pharmacological success and has proven to be a significant challenge to date in moving molecules from the bench to clinical treatment paradigms. The aim of this work is to enhance the pharmacological potential of these macrocyclic ligands. To accomplish this, computational analyses were performed on two tetra-azamacrocycles to predict their baseline blood-brain barrier permeability. The structures of these macrocycles were then modified with various moieties and analyzed via the same computational methods to predict their blood-brain barrier permeability potential. One target modification this project is focused on is the attachment of omega-3 fatty acids to these tetra-azamacrocycles. Omega-3 fatty acids have been shown to have beneficial anti-inflammatory properties in vivo and have the ability to assist in transporting molecules across the blood-brain barrier. Thus, the inclusion of these moieties to the structure of the Green Group ligands are attractive in regard to enhancing their pharmacological potential. To accomplish this attachment, the synthetic approach of one of the Green Group’s flagship tetra-azamacrocycles, OHPy-N3, had to be completely reimagined. New synthetic approaches and protection strategies were employed to achieve a suitable intermediate molecule primed for the addition omega-3 fatty acids. These novel synthetic methods and subsequent results are discussed in this work herein.

The objective of this project is to make a vaccine that will negate the effects of the powerful opioid fentanyl in the long term. Fentanyl is a strong synthetic opioid that is 50 to 100 times more potent than morphine. According to the CDC, there were over 70,000 deaths due to street drug overdoses, which has increased in the last ten years. 40 % of these deaths are related to fentanyl overdoses, therefore it is imperative that approaches are developed to combat this alarming increase in deaths. The vaccine against fentanyl will be synthesized out of molecules that will take advantage of fentanyl’s amide functional group to be hydrolyzed into safe byproducts. Any patient that is administered with the vaccine, will not feel the effects of the opioid because the immune system will hydrolyze the drug as soon as it enters. This project will exploit the properties of both catalytic antibodies (CAbs) and transition state analogs. If the molecule resembles the transition-state of fentanyl hydrolysis, then the antibodies can cleave the fentanyl in a fast and efficient manner due to their catalytic properties. Therefore, after immunization, a person who is addicted to fentanyl would no longer feel the effects of the opioid because it will be degraded as soon as an immune response is triggered, creating a long-term possible solution to one factor of the “opioid crisis.”

Alkenyl phosphorus compounds appear in multiple industrial products, from flame retardants to fungicides. Although several methods are available to synthesize these compounds, many require expensive catalysts, inaccessible starting materials, or multi-steps sequences. In response to these issues, this project sought to develop an efficient, two-step method to synthesize alkenyl phosphorus compounds from simple ketones. We compare acid and base catalysts and find both are effective in the first reaction step; furthermore, a one-pot reaction provides comparable yields to the reactions conducted with a purified intermediate. These findings lay the foundation for the exploration of more complex substrates, including those utilized in industrial applications.

Pyridine macrocycles have useful applications due to their ability to complex with metals. A library of substituted pyridine macrocycles exists along with how modifications at Carbon 4 impact compound reactivity. Despite literature about similar pyridine macrocycle structures, little is known about how an iodo-substituted pyridine macrocycle will alter the properties of the compound when complexed to Copper. To understand the fundamental characteristics of an Iodo-substituted pyridine macrocycle, the ligand is synthesized followed by electronic environment analysis via 1H NMR. Ultraviolet-Visible Spectroscopy is used to verify ligand complexation with Copper (II) metal followed by X-ray diffraction to determine metal binding nature of the complex. Cyclic Voltammetry analysis is used to support the theory that the iodo functional group behaves as an electron withdrawing group. This compound serves as a comparison to explain the results of the Chloro-substituted pyridine macrocycle as well as a gateway molecule for the synthesis of new pyridine macrocycles.

The TCU and UNTHSC School of Medicine requires its students to participate in service learning with various non-profit partner organizations in the community. Our team's goal is to make the volunteer sign-up process easier and more convenient for med students, to automate the tracking of students' hours, and to ease the burden on faculty in charge of managing the entire process. We aim to accomplish these goals with a web application that will streamline the volunteer scheduling and hour-tracking process for students and faculty.

The TCU Computer Science Department has launched an AlphaGo research project. Currently, it can only be used by those directly involved with the project, and only at certain computers on campus. In addition, the interface for conducting research is difficult to use. Our goal is to make this project more widely accessible to students and faculty alike, whether they wish to help in research, or simply want to learn to play Go. We have developed a web application for the project that allows users to play against various Go AI agents, as well as allowing researchers to train new AI. In addition, our site allows various admin functions to control and edit users and AI agents alike.

This is a brief report on a comprehensive assessment of AlphaZero-type algorithms from the viewpoint of optimal play. This study does not join an already crowded field in seeking to enhance the efficiency of these algorithms, but sets sights on more conceptual questions and more quantitatively precise results. In particular, we show that the AlphaZero-type algorithms tend to behave more conservatively when winning and more aggressively when losing. We illustrate our results with a specific example on the 7x7 board.