Predicting pKas of flexible polybasic pyclen derivatives: A pKa challenge

Type: Undergraduate
Author(s): Tatum Harvey Chemistry & Biochemistry
Advisor(s): Benjamin Janesko Chemistry & Biochemistry Kayla Green Chemistry & Biochemistry
Location: Third Floor, Table 2, Position 1, 1:45-3:45

Predicting pKas is an outstanding challenge in computational chemistry. The Green group
at TCU is working to develop a library of pyclen derivatives that can successfully reduce oxidative
stress within the brain of people afflicted with neurodegenerative diseases1. Predicting the various
pKas of these flexible molecules, which are charged at neutral pH, challenges conventional
approaches to predicting pKas. For each pyclen derivative, we combine an extensive survey of
protonation site isomers, with conformational sampling using the CREST package2, DFT
calculations with continuum solvent models, followed by a linear fit to correct the solvent models
limitations for calculating energy of highly charged species. We can predict three to five measured
pKa values for each pyclen derivative with a RMSD of 0.9 pKa units, which is competitive with
the best-physics based method in the SAMPL6 blind challenge for the first pKa3. We are pushing
the boundaries of computational chemistry and its abilities to predict multiple pKas of flexible
molecules.

Models for the Next Generation of Drugs: Design, Synthesis, and Conformational Analysis of a 26-Atom Macrocycle

Type: Undergraduate
Author(s):
Advisor(s):
Location: First Floor, Table 4, Position 1, 1:45-3:45

To fight disease, pharmaceutical companies have historically prepared small molecules
designed to interfere with specific sites on proteins (enzymes) to prevent chemical reactions
from taking place. However, a second paradigm for interfering with proteins has gone largely
unexplored--blocking protein-protein interactions. To accomplish the latter, large molecules are
needed to bind to large areas on the protein target. However, large molecules present additional challenges. Typically, they are hard to synthesize, not orally available, and typically cannot cross cell membranes. Nature has designed large molecules like cyclosporin that should not work as drugs based on our current understanding. Despite its size, cyclosporin is orally available and can cross cell membranes. This research explores the design, synthesis, and conformational analysis of similar large ring-shaped molecules, so-called macrocycles. In this work, we are increasing the size of the ring-shaped molecule. By increasing the size of the ring-shaped molecule and varying the amino acid (in this case, valine), we are expanding the possible ways in which our macrocycle may interfere with protein-protein interactions. Here, a 26-atom macrocycle is reported. 1H NMR spectroscopy reveals a protonated molecule that is highly dynamic which has access to a beta-sheet conformation.

Implication of Steric Congestion on Sheet Formation: 26-Atom Macrocycles

Type: Undergraduate
Author(s): Lola Kouretas Chemistry & Biochemistry Luke Homfeldt Chemistry & Biochemistry Alex Menke Chemistry & Biochemistry
Advisor(s): Eric Simanek Chemistry & Biochemistry
Location: Second Floor, Table 1, Position 1, 1:45-3:45

Molecular engineering of larger macrocyclic compounds offers new avenues to disrupt protein-protein interfaces and potentially halt pathways that lead to neurodegenerative diseases, such as Alzheimer’s. The hallmark of Alzheimer’s disease involves the aggregation of so-called amyloid peptides that exhibit characteristic β-sheet structures. Thus, designing macrocycles that structurally/topologically mimic β-sheets should enhance the affinity of these macrocycles towards the amyloid aggregates and lead to rational design of more advanced scaffolds with superior structures. This will potentially present opportunities to interrogate protein-protein interactions, thus preventing amyloid plaque formation.

This work will describe the synthesis of structurally and functionally-diverse macrocyclic scaffolds containing leucine and isoleucine to understand the factors that contribute to β-sheet formation. Here, 26-atom macrocycles prepared in three steps will be described. Using a triazine core, a protected hydrazine group, and an amino acid constitute the base acid. In the second step the addition of an acetal of variable length forms the monomer. Acetals ranging from 2-4 carbons can be used to yield rings of 22-28 atoms. Previous work proves acetal length dictates morphology; three-carbon acetals demonstrate folded conformations and five-carbon acetals yield crinkled b-sheets. Four-carbon acetals yield the flattened b-sheets described here. Treatment with acid leads to dimerization in very high yields. Varying the amino acid choice can give way to synthesis of different homodimers and heterodimers.

These studies also address the optimization of the macrocyclization step. Early results indicate that a >300x reduction in the time of reaction (from 7 days to 30 min) might be realized. NMR spectroscopy provides confirmation of synthesis and 2D-NMR techniques offer opportunities to probe solution structure more efficiently.

Fabrication Process And Efficiency Analysis Of Organic Light-Emitting Diodes (OLEDs)

Type: Undergraduate
Author(s): Nhu Le Engineering
Advisor(s): Jeffery Coffer Chemistry & Biochemistry
Location: Second Floor, Table 1, Position 3, 1:45-3:45

Display technology is one of the industries of great significance, providing benefits for consumers with applications such as smartphones, televisions, and computer monitors. One of the current research topics in this industry of extensive interest is the development of new organic light-emitting diodes or OLEDs.

While such devices are common, fundamental challenges remain. Three pressing needs are: (1) longer device lifetimes, (2) lower fabrication costs, and (3) better control over emission color for ultrahigh definition displays and white-light lighting. Today, high-quality displays are built using high-vacuum deposition of molecular precursors, an expensive method unsuitable for ultra-large displays. Methods that rely on spin coating or printing of solutions of such precursors are far more economical, but present fabrication challenges of their own.

Our goal here is to improve device function and stability in OLEDs through simple solution-based routes with innovative fluorescent structures known as perovskites as building blocks. Ideally these new OLEDs will perform well at low voltage ranges and maintain good light emission intensity, as evaluated using techniques known as photoluminescence and electroluminescence spectroscopies.

In this research project, single-layer OLED and three-layer OLED devices are analyzed. Single-layer OLED devices consist of the substrate, anode, emissive layer, and cathode. Fluorine-doped Tin Oxide (FTO)/glass and Indium Tin Oxide (ITO)/plastic are the main substrates used, acting as anode. Ga-In eutectic, Silver Nanowire (AgNW), and Silver Epoxy are used as the interconnect / cathode layer to the emissive layer. To fabricate a three-layer OLED, the electron transport layer (ETL) is added between the cathode and emissive layer and a hole transport layer (HTL) added between emissive layer and anode, both to ideally improve energetics of electron/hole injection to the emissive layer. In our experiments, a species known as PEDOT:PSS is typically the hole transport layer and for the electron transport layer, we use ZnO or a mixture of ZnO and polyethylenimine.

The most success to date has been achieved with [Ru(bpy)3]2+ as the active emitting species in a thin polymer matrix referred to poly-vinylalcohol (PVA). Our current results show that the photoluminescence spectroscopy intensities were relatively high while the electroluminescence needs to be improved. The best result was recorded with the single-layer red OLED, which is made of FTO, [Ru(bpy)3]2+, and Ga-In eutectic. Visible light emission at low voltages from 3.5V-7V could be observed with the unaided eye under these conditions.

Bridging Theory and Practice Enhancing Drug Design Through Molecular Simulations and Solvent Stability Analysis

Type: Undergraduate
Author(s): Alejandro Munoz Chemistry & Biochemistry
Advisor(s): Benjamin Janesko Chemistry & Biochemistry
Location: Second Floor, Table 2, Position 3, 1:45-3:45

ARE GREEN ROUTES TO RED MOLECULES REAL? Sustainability and cost-effectiveness studies on the synthesis of high-value infrared emitting materials

Type: Undergraduate
Author(s): Hannah Sachs Chemistry & Biochemistry Harley Jacobs Chemistry & Biochemistry Daniel Ta Chemistry & Biochemistry
Advisor(s): Sergei Dzyuba Chemistry & Biochemistry
Location: Basement, Table 10, Position 1, 11:30-1:30

Typically, the costs associated with the synthesis, isolation, and purification of high value molecules/materials as well as environmental/health concerns related to the overall process are disregarded due to perceived profits that could be obtained from the use of the final products. However, as the scale of production of these materials increases, the need for more environmentally benign, sustainable, inexpensive, yet still facile and efficient processes increases exponentially.

Squaraine dyes are versatile, high-value fluorescent molecules, with a very broad and diverse range of applications due to their absorption and emission in the infrared spectral region. However, vast majority of literature syntheses of these dyes utilize toxic, volatile solvents. In this presentation, we will outline our current efforts on the use of green solvents, solvent-free and mechanochemical routes to various types of squaraine dyes. Furthermore, we will present sustainability and cost-effectiveness estimates as guiding tools for the future development of all around-efficient synthetic protocols for various types of squaraine dyes.

Beta-Sheet Mimics: A Step Towards Targeting Protein-Protein Interactions

Type: Undergraduate
Author(s): Brett Thorell Chemistry & Biochemistry Alex Menke Chemistry & Biochemistry
Advisor(s): Eric Simanek Chemistry & Biochemistry
Location: First Floor, Table 6, Position 1, 1:45-3:45

Small molecules are reliable and pervasive pharmaceuticals because critical drug characteristics are predictable including solubility and membrane permeability. In addition, small molecules are typically inexpensive to produce and their mechanisms of action subscribe to a common paradigm vis-à-vis blocking an enzyme active site. In contrast, nature employs elaborate machinery to make large molecules, oftentimes rings (or macrocycles). Drug companies avoid these because the rules for predicting behavior are under-explored and the paradigm used for action is different vis-à-vis blocking protein-protein interactions. Moreover, they are costly and laborious to make. To contribute to an understanding of drug design for large molecules, our group is preparing a series of large molecules (macrocycles). The lead adopts a beta-sheet conformation in the solid state, but its behavior in solution is unknown. Here, a second member of the class is described wherein alanine replaces glycine in the macrocycle to provide additional handles to study conformation and the effects that structure has on critical parameters. The 26-atom macrocycle is synthesized in a three-step process. The reaction of a triazine core, and the addition of BOC-hydrazine, alanine, and dimethylamine yields the first intermediate which undergoes elaboration with a 4-carbon acetal group using traditional peptide-coupling strategies (HBTU). Dimerization of the resulting monomer occurs in a 1:1 mixture of dichloromethane and trifluoroacetic acid. Reaction progress is followed by thin-layer chromatography and the identity of the products is confirmed by 1H and 13C NMR spectroscopy. Conformational analysis rests on 2-D 1H NMR spectroscopy. The molecule will also be subjected to analysis for solubility and membrane permeability. In the longer term, these beta-sheet mimics will be used to disrupt protein-protein interactions with an emphasis on the BRCA1-PALB2 interaction implicated in breast cancer.

INTEGRATED HYDROGEL-POROUS SILICON STRUCTURES FOR NON-INVASIVE BIOSENSING

Type: Undergraduate
Author(s): George Weimer Biology Alexa Frattini Chemistry & Biochemistry
Advisor(s): Jeffrey Coffer Chemistry & Biochemistry
Location: Basement, Table 5, Position 2, 11:30-1:30

Utilizing the supportive structure of hydrogels, the semiconducting character of porous silicon (pSi) membranes, and the biodegradability of both, a unique biosensor for the chemical analysis of health-relevant analytes can ideally be created.
Alginate-based hydrogels are water-infused, biodegradable polymer networks. These are particularly useful because of their environmental abundance, and their ability to interface well with human skin. These characteristics also make them an ideal medium for supporting pSi membranes and simultaneously assimilating them into a wide range of tissues.
Porous silicon (pSi), a highly porous form of the elemental semiconductor, is utilized to measure and conduct electrical signals throughout the hydrogel matrix. In diode form, these membranes exhibit measurable current values as a function of voltage, which can be used to detect bioelectrical stimuli such as the concentration of physiologically relevant ionic species (e.g. Na+, K+, and Ca2+).
Recent experiments center on integrating pSi membranes into various aqueous environments and hydrogels to test how variations in ion concentration affect the flow of electrical current as a function of applied voltage. pSi membranes are fashioned into diodes upon the attachment of 0.25 mm diameter copper wire using silver epoxy and annealing. An electrochemical cell is created by placing two pSi membranes parallel each other in an electrolyte composition. Current is measured as a function of applied voltage (typically from 0-5 V) for systems with differing NaCl concentration.
As expected, the magnitude of maximum current response is proportional to ion concentration present in the electrolyte, with an order of magnitude amplification or more of measured current for a given voltage upon immersion of the electrodes in an alginate hydrogel matrix relative to water alone.
This presentation will focus on initial diode fabrication protocols, as well as establishing limits of detection for simple ions species present in human sweat. More refined strategies are also envisioned, including the development of methods for stabilization of sensor performance along with miniaturization of the sensing platform itself.

Testing a Computation Workflow for Drug Design: pKa and logP from the SAMPL7 Blind Challenge

Type: Undergraduate
Author(s): Katherine Zabel Chemistry & Biochemistry
Advisor(s): Benjamin Janesko Chemistry & Biochemistry
Location: Third Floor, Table 4, Position 3, 1:45-3:45

Testing a Computational Workflow for Drug Design: pKa and logP from the SAMPL7 Blind Challenge
Katie Zabel
Advisor: Benjamin Janesko
Being able to produce accurate predictions of pKa for various molecules is an ongoing effort in computational chemistry. Drug companies and industries are constantly seeking accurate predictions of pKa and lipophilicity for molecules that are possible drug candidates. Accurate predictions of these values means that time, money, and effort won’t be wasted synthesizing molecules that aren’t going to be effective drugs. The Janesko group has developed a workflow that uses CREST for conformational analysis and (M11plus/def2TZVP/SMD) DFT calculations to identify a molecule’s pKa. The DFT calculations process and refine the relative energies of the stable conformations. The goal of this project is to benchmark the current workflow against the SAMPL7 challenge, which will test the workflow’s outperformance of the best quantum-mechanical methods from 2021. The SAMPL challenge is a competition that asks participants to predict the properties of molecules that have never been synthesized. These molecules will then be created in labs and their properties will be accurately tested. Comparison of the competitor's predicted properties to the true values measured will assess the accuracy of the competitor's predictions. If the prediction of pKa using the current workflow is accurate based off the benchmark against the SAMPL7 challenge, then the workflow could be entered into the next SAMPL Blind challenge.

Transparent Tuition: Finding your Financial Fit

Type: Undergraduate
Author(s): Paige Anderson Computer Science
Advisor(s): Michael Scherger Computer Science
Location: Second Floor, Table 3, Position 3, 1:45-3:45

During the college admissions process, students are presented with an overload of information from each school they are applying to and accepted by. A critical aspect for deciding on a school is the estimated Cost of Attendance (COA) and the financial aid package. Each school calculates their COA differently and thus offers a unique financial aid package. It is important for students to have a way of comparing and evaluating a school's cost with financial aid. While college counselors have developed excel sheets with algorithms that compare personalized cost with financial aid and scholarships, not all students are familiar with excel which may result in an inaccurate analysis. Transparent Tuition is a tool for students to accurately compare financial aid options from each university they are applying to. This project was developed using React.js and Spring Boot. These are two development libraries that will make Transparent Tuition scalable in the future. By creating a user-friendly web tool, students can better understand the school’s information and make a more educated decision when deciding on their university. Students will be able to connect with a college counselor to receive advice regarding their options when choosing a university. This will allow students to make an educated decision on their college based on both the short-term and long-term financial impact.