Biaryl motifs are central in pharmaceutical drug design, yet conventional synthesis via palladium-catalyzed cross-coupling poses increasing sustainability and cost concerns. The study presented herein explores a greener alternative to palladium by employing iron(II) complexes supported by tetra-aza macrocyclic ligands for the direct arylation of pyrrole with phenylboronic acids. Under aerobic conditions, the optimized [Fe2+L1(Cl)2] catalyst featuring Me2Cyclam, (L1; 1,8-dimethyl-1,4,8,11-tetraazacyclotetradecane), exhibited broad substrate compatibility across 23 boronic acid derivatives. The method showed excellent functional group tolerance, including halides and esters, and provided yields up to 66%, which was clearly dependent on steric and electronic effects. Mechanistic experiments ruled out an outer-sphere radical pathway and instead suggested an Fe(III)–OOH species as the key oxidant, while DFT analysis supports enhanced boron electrophilicity for electron-withdrawing substituents, consistent with transmetalation as a central activation step. These findings highlight the potential of earth-abundant iron catalysts as sustainable, cost-effective platforms for C–C bond formation in complex molecular scaffolds.

Graphene quantum dots (GQDs) are emerging nanocarbon materials with tunable electronic structures and strong NIR emission, making them promising for bioimaging and optoelectronic applications. The chromophores responsible for GQDs’ NIR emission are often poorly characterized, limiting rational design and clinical applications. Extended π-conjugation, charge-transfer excitations, the presence of diradicaloids, stacking of multiple GQD layers, and blocking of nonradiative decay (as seen in non-aromatic fluorescence) may all contribute to GQDs’ NIR emission. Computation may help disentangle these contributions and aid development of NIR-emitting GQD nanostructures. However, predictive modeling of candidate GQD structures’ stability and NIR emission remains challenging. In this work, we develop a benchmark set of 16 well-defined GQD nanostructures known to emit in the NIR-I window, and we benchmark computational workflows for predicting these structures’ thermodynamic stability and NIR emission. Our workflows combine fast “pre-screening” of thermodynamic stability with symmetry-broken and symmetry-restricted time-dependent density functional theory (TD-DFT) predictions of absorption and emission, selected according to the open- or closed-shell nature of
each nanostructure. We find that B3LYP provides acceptable agreement with experimental absorption, while CAM-B3LYP shows good agreement with experimental emission, and that a “synthetic feasibility” descriptor provides reasonable initial screening. We believe that this workflow provides the foundation for high-throughput computational studies accelerating development of NIR-emitting GQDs.

Alkyl phosphate surfactants were synthesized for the development of a dendricore micelle as a potential drug delivery platform. Conventional surfactant micelles often dissociate under physiological dilution due to their high critical micelle concentrations, limiting their utility. To address this limitation, a dendrimer scaffold templated by surfactants is being constructed through reaction of an amine with succinic anhydride followed by iterative Boc deprotection and carbodiimide coupling. This architecture is expected to enhance micelle stability and support dual-drug delivery.

Our project focuses on Europium-doped Cerium Oxide nanotubes and their use as potential probes for bioimaging and optical sensors. Most CeO2 nanomaterials are not intrinsically fluorescent in the visible region, so these materials can be doped with rare earth ions that possess visible fluorescence. Rare earth ions that prefer the +3 oxidation state can be efficiently doped into CeO2 nanomaterials due to their similar ionic radii. Our research utilizes Europium (III) for doping, which is known for its red-orange emission and hypersensitive 5D0→7F2 transition. We choose a one-dimensional architecture for the target nanostructure because of its ideal geometry to interact with cells. A sacrificial template is employed, beginning with the synthesis of Zinc Oxide nanowires on an FTO substrate. After the nanowires are grown, a Europium (III) - Cerium (III) cycling process is performed to construct the nanotube, using the nanowire as a template.
The size and morphology of the nanotubes are measured using a Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The crystalline structure of the Europium-doped CeO2 nanotubes can be characterized using X-ray diffraction (XRD) to determine how varying Eu3+ concentration can change the XRD peaks. Their photoluminescence (PL) spectra are measured as a function of varying the percentage concentration of Eu3+. Light emission is compared as a function of dopant concentration by varying the Eu3+ concentration between 5%-15% to determine the concentration with the optimal fluorescence intensity. Ultimately, the desired characteristic fluorescence of the nanotubes enables their use in bioimaging and as optical sensors.

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

The binding of the water-soluble porphyrin tetrasodium tetraphenylporphyrintetrasulfonate (TPPS) to bovine serum albumin (BSA) in aqueous media at room temperature can be explored for developing an analytical assay for PFAS (or “forever chemicals”) detection. Indeed, we determined that spectrophotometric detection of PFAS is optimized by exploiting competitive binding of PFAS and TPPS to BSA at pH 4.7. In this poster, we spectrophotometrically investigated BSA-TPPS binding at pH 3.0, 4.7, and 7.2. Specifically, TPPS concentration was maintained constant at 80 M in our experiments and BSA concentration was varied. Interestingly, while BSA-TPPS complexes are soluble at pH 7.2, they form insoluble precipitates in acidic conditions (pH 3.0 and 4.7) at low BSA concentration. Specifically, we find that solubility of TPPS exhibits a minimum as BSA concentration increases. We therefore developed a theoretical model that successfully describes the observed behavior of TPPS solubility. Spectrophotometric calibration curves for the determination of PFAS concentration were constructed using solutions with a sufficiently high BSA:TPPS molar ratio.

The purpose of the project is to predict the redox potential of tetra-aza macrocycle copper complexes. Density functional theory combined with a continuum solvation model was used to compute the redox potentials of 23 copper–ligand complexes. Gibbs free energies for the redox reactions were evaluated at the M06-2X/Def2-SVP/Def2-TZVPP/SMD level of theory. The predicted redox potentials agree well with experimental values for tetra-aza macrocyclic copper complexes. To examine the influence of chloride, calculations were performed for ligand systems both in the presence and absence of coordinated Cl. The correlation between the computed and experimental measurements yielded R2 values of 0.92 (without coordinated Cl) and 0.89 (with coordinated Cl), reflecting trends consistent with experimental measurements. For the complexes without coordinated chloride, the predictions further demonstrated strong accuracy, with a root-mean-square error of 30.9 mV. Overall, the result highlights this computational workflow as a practical approach for estimating the redox properties of copper complexes, redox-active systems relevant to biomimetic and medicinal chemistry.

Salt-induced diffusiophoresis is the migration of a charged nanoparticle in water, induced by an imposed directional gradient of salt concentration. This transport phenomenon has emerged as a valuable tool for particle manipulation inside porous materials and microfluidics. Micelles are a common example of nanoparticles with the crucial ability of hosting small guest molecules. Thus, micelle diffusiophoresis is important in the manipulation of small molecules. Diffusiophoresis depends on the intrinsic ability of micelles to randomly move (diffuse) in water. In this poster, we report experimental micelle diffusion coefficients for the surfactant hexadecylpyridinium chloride (CPC) in the presence of aqueous NaCl and KCl. The electrical double layer theory was successfully employed to explain the effect of surfactant and salt concentrations on the observed micelle diffusion coefficient. These data were then used to characterize salt-induced diffusiophoresis of charged micelles.

Influence of a NiO Hole Transport Layer on Charge Separation in FTO|WO₃|BiVO₄ Photoanodes for TEMPO-Mediated Oxidation

Favor Igwilo, Texas Christian University, Class of 2026
Laboratory of Dr. Benjamin Sherman, PhD;
Department of Chemistry and Biochemistry

Efficient hole transport is critical for driving oxidative transformations in photoelectrochemical systems. In this study, we investigate multilayer FTO|WO₃|BiVO₄|NiO photoanodes for application in TEMPO-mediated oxidation of benzyl alcohol to benzaldehyde, an important chemical reaction used in industrial processes. The stable radical 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) enables selective alcohol oxidation under mild conditions and represents a more sustainable alternative to conventional stoichiometric oxidants that generate hazardous waste. Enhancing interfacial charge transport is essential to improve the viability of this photoelectrosynthetic process.
We hypothesize that nickel oxide (NiO), a p-type semiconductor, can function as an effective hole transport layer due to its favorable valence band alignment, hole mobility, abundance, and low cost relative to traditional materials such as titanium dioxide (TiO₂). A liquid phase deposition protocol was developed to fabricate uniform NiO thin films on fluorine-doped tin oxide substrates, which were subsequently integrated into FTO|WO₃|BiVO₄ substrates. The resulting multilayer photoanodes were evaluated to determine whether NiO enhances charge separation and hole extraction under various conditions.
Electrochemical characterization was performed using cyclic voltammetry to probe redox behavior and assess catalytic onset potentials, chronoamperometry to quantify steady-state photocurrent and operational stability, and electrochemical impedance spectroscopy to evaluate interfacial charge transfer resistance. Measurements were conducted under both dark and illuminated conditions, with and without TEMPO, in Tetrabutylammonium hexafluorophosphate (TBAPF6)in acetonitrile (ACN) solution. We anticipate that incorporation of NiO will reduce interfacial charge transfer resistance, increase photocurrent density in the presence of TEMPO, and improve kinetic parameters associated with benzyl alcohol oxidation.
Photocurrent densities of FTO–WO₃–BiVO₄ and FTO–WO₃–BiVO₄–NiO photoanodes were directly compared to quantify the effect of the NiO interlayer. Additionally, heterogeneous electron transfer rate constants (k₀) were determined under TEMPO-containing conditions to assess how the multilayer structure influences interfacial electron transfer kinetics.
This work establishes a working protocol for NiO liquid phase deposition and clarifies the role of NiO in enhancing TEMPO-mediated photoelectrosynthetic oxidation. These findings can later inform the design of cost-effective photoelectrode architectures for sustainable organic reactions.

By combining the supportive structure of alginate hydrogels, the semiconductive nature of porous silicon (pSi) membranes, and the biodegradability of both of these materials, a unique, non-invasive biosensor can ideally be created for the chemical analysis of health-relevant analytes.
Hydrogels are water-infused, biodegradable polymer networks that are easily able to interface with human skin. Alginate polymer hydrogels are particularly useful due to being derived from brown algae, making them environmentally abundant and inexpensive. The polymer is modified with acrylamide segments to add stability and shelf-life to the hydrogel material. Ultimately, these characteristics make hydrogels ideal for supporting the pSi membranes while assimilating them to a variety of tissues.
Porous silicon (pSi) is a highly porous form of the widely used elemental semiconductor and is used to conduct and measure electrical signals throughout the hydrogel matrix. When established in a 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 such as Na+, K+, and Ca2+.
Recent experiments focus on integrating pSi membranes in Acrylamide/alginate co-polymer hydrogels to test how variations in ion concentration affect the flow of current measured as a function of applied voltage. Porous silicon membranes ~110 μm thick and 79% porosity, are fabricated from the anodization of low resistivity (100) Si in methanolic HF at an applied bias of 100 mA/cm2 for 30 minutes. Membranes pieces ~2 mm by 2 mm are heated for one hour at 650°C. They are then affixed to Cu wire using Ag epoxy and annealed for 15 minutes at 95°C. The wires are then fashioned to form the membrane diodes and clear nail polish is used to coat the backs of the membranes, the Cu wire connection, and the wire itself to prevent current flow from the back of the membrane or bubble formation. The electrochemical cell is created by placing two pSi membranes parallel to each other ~2 mm apart, vertically, in a fixed electrolyte composition. The current is measured as function of applied voltage (typically from 0-5 V) for systems with different concentrations of NaCl in the nM to mM range. The NaCl solutions are injected directly into the hydrogel in between the two pSi membranes in 2 μL units.
This presentation will focus on the fabrication protocol, as well as results from experiments with varying NaCl concentrations. Previous experiments have determined linearity of the current and applied voltage function in the region of 0.25 mM to 1 mM concentration ranges of pure NaCl solution. Future experiments will seek to repeat these findings within the alginate hydrogel matrix.

Impedimetric Sensing of PFOA in Drinking Water
Qamar Hayat Khan,1 Ramachandra Legundapati,2 Gyu Leem,2 and Benjamin D. Sherman1,
1Department of Chemistry & Biochemistry, TCU, TX 76129, 2 Department of Chemistry & Biochemistry, TCU, TX 76129; 2 Department of Chemistry, SUNY, Syracuse, New York 13210, United States
Abstract
Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that pose significant risks to human health and ecosystems.1 This poster is focused on the development of a label-free impedimetric sensor2 for the detection of PFAS in aqueous systems. The sensing platform is based on fluorine-doped tin oxide (FTO) electrodes functionalized with perfluorinated self-assembled monolayers (SAMs) to promote fluorophilic interactions with target PFAS molecules, particularly perfluorooctanoic acid (PFOA).
FTO electrodes were modified using trichloro(1H,1H,2H,2H-perfluorooctyl) silane (TCPFOS) to form hydrophobic surface coatings. Successful formation of the SAM layer was confirmed through water contact drop experiment. Surface coverage of the monolayer was evaluated using cyclic voltammetry (CV) with the ferri/ferrocyanide redox couple, where cathodic peak current reduction indicates effective surface blocking by the SAM layer.
Impedance measurements were subsequently performed in 0.1 M NaCl electrolyte at controlled pH (4.5) while exposing the functionalized electrodes to varying concentrations of PFOA. The impedance data were qualitatively by plotting Cole–Cole capacitance plots to evaluate changes in effective interfacial capacitance and quantitatively by circuit fitting.3 These capacitance variations were correlated with PFAS concentration to assess sensor sensitivity and response behavior.
The results demonstrate that the TCPFOS-modified FTO surfaces produce measurable and reproducible capacitance changes in response to PFOA exposure, indicating the potential of fluorophilic surface chemistry combined with impedance spectroscopy for PFAS detection. This work contributes toward the development of a simple, label-free electrochemical sensing platform for monitoring PFAS contamination in water.
References
(1) Evich, M. G.; Davis, M. J.; McCord, J. P.; Acrey, B.; Awkerman, J. A.; Knappe, D. R.; Lindstrom, A. B.; Speth, T. F.; Tebes-Stevens, C.; Strynar, M. J. Per-and polyfluoroalkyl substances in the environment. Science 2022, 375 (6580), eabg9065.
(2) Zhang, M.; Zhao, Y.; Bui, B.; Tang, L.; Xue, J.; Chen, M.; Chen, W. The latest sensor detection methods for per-and polyfluoroalkyl substances. Crit. Rev. Anal. Chem. 2025, 55 (3), 542–558.
(3) Gabriunaite, I.; Valiūnienė, A.; Sabirovas, T.; Valincius, G. Mixed Silane‐based Self‐assembled Monolayers Deposited on Fluorine Doped Tin Oxide as Model System for Development of Biosensors for Toxin Detection. Electroanalysis 2021, 33 (5), 1315–1324.

Alzheimer’s Disease (AD) presents a significant personal and economic burden, yet therapeutic strategies targeting its progression have largely been unsuccessful. Key pathological features of AD include oxidative stress, dysregulation of metal ions, and the aggregation of amyloid-beta (Aβ) peptides into plaques. Previous work in the Green Lab has focused on the development of macrocyclic compounds capable of chelating transition metals such as copper and iron—both of which contribute to oxidative stress and Aβ plaque formation. These macrocycles also incorporate aromatic rings that mitigate oxidative damage by scavenging free radicals. However, while effective in addressing metal ion misregulation and oxidative stress, these compounds do not prevent Aβ aggregation. To address this limitation, we have incorporated the KLVFF peptide—known for its ability to bind Aβ and inhibit its aggregation—into our macrocyclic framework using solid-phase peptide synthesis. The resulting trifunctional molecule is designed to simultaneously chelate metal ions, reduce oxidative stress, and inhibit Aβ plaque formation. This multifunctional approach offers a promising therapeutic strategy for slowing or preventing the progression of AD into its more debilitating stages.

Over seven million people are currently living with Alzheimer’s disease (AD) in the United States today, with that number set to increase due to extended life expectancy. Studies have shown that amyloid-beta (Aβ) plaque accumulation, tau tangles in the brain, metal-ion dysregulation, and oxidative stress are etiological hallmarks of AD. Various treatment methods have been employed to reduce the effects of Alzheimer’s disease, but these treatments aim to reduce Aβ plaque aggregates after they’ve formed, though this strategy focuses on symptom mediation as opposed to prevention. A different approach focuses on preventative treatment of AD to provide an antioxidant that can minimize the effects of oxidative stress through scavenging reactive oxygen species, which are known to lead to oxidative stress. Using this approach, a class of pyridinophanes has been synthesized as antioxidants and metal ion chelators to minimize the effects of oxidative stress through biomimicry of enzymes such as superoxide dismutase. The Green Group has presented multiple pyridinophanes that function as these biomimics, including OH-PyN3. Continued improvement of the synthesis of this small molecule remains a focus, with the intent of a more cost-effective synthesis to facilitate clinical translation. Here we present an improved synthetic scheme, with optimizations to the chelidamic acid esterification and protection of the chelidamic acid and diethylenetriamine moieties. Through this synthetic scheme, the total chemical yield and reduce cost were doubled to 45% and decreased by 81%, respectively.

The WHO has declared antimicrobial resistance a top 10 global threat. New antimicrobials with novel modes of action are therefore desperately needed. One such mode of action would be to target the aromatic amino acid biosynthesis pathway. Several extremely potent inhibitors of Dehydroquinate Synthase have been previously synthesized. One of those, a vinylphosphonate compound, was selected as the lead compound for this study. In this project, the inhibitor was re-synthesized and several methods to prepare prodrugs have been investigated. The synthesis of prodrugs of other related compounds was also explored.

Alzheimer’s Disease (AD) is a neurodegenerative terminal disease that affects 11% of Americans who are 65+ years old. The progression of AD has been associated with the dysregulation of reactive oxygen species (ROS) via multiple mechanisms, resulting in oxidative stress and neuronal damage. One of the focuses of the Green Lab at TCU is the development of PyN3 pyridinophanes that act as antioxidants to counter the effects caused by unregulated ROS. While most compounds synthesized within the lab both have antioxidant characteristics and activate the Nrf2 pathway, they face the issue of having poor permeability to the Blood Brain Barrier (BBB), making them unable to deliver the therapeutic effects to the diseased neurons. To counter this deficit, the series of molecules proposed herein aim to increase the lipophilicity of the base PyN3 molecules while maintaining or increasing their antioxidant potential. In pursuit of these aims, we aimed to utilize Suzuki-Miyara-like carbon-carbon bond formation to add aromatic, lipophilic, antioxidant moieties to the para position of the parent PyN3 molecule. Computational studies, including the BOILED-Egg plot, were used to identify these synthetic targets for probable BBB permeability with the goal of highlighting a new route in drug synthesis to increase the delivery of active compounds to target tissues past the BBB.

Macrocycles are promising drug design frameworks because their folding can enhance stability, solubility, and membrane permeability. Recently, triazine macrocycles derived from two monomers were reported. The cyclization is quantitative, but the role of chirality in macrocycle formation remains unclear. To address this issue, triazine macrocycles were synthesized from Fmoc-protected amino acids to test whether chiral sorting occurs. Chiral sorting refers to the tendency of amino acid precursors to selectively pair as homochiral species (D-D or L-L) or heterochiral species (D-L). Understanding this behavior can dictate macrocycle folding and stability. Preliminary results with valine and isoleucine suggest strong chiral sorting favoring homochiral species. In contrast, chiral sorting does not appear to occur alanine or isovaline, both of which follow the expected 1:2:1 distribution of DD, DL, and LL. These findings highlight stereochemical influences on macrocycle formation and provide insights for designing macrocycles with improved therapeutic potential.

Reactive Oxygen Species (ROS) are associated with a broad spectrum of diseases, ranging from bone loss to cancer. One strategy to combat ROS is to treat sources of such species in the body with materials capable of generating hydrogen and reacting with ROS to neutralize it. This project involves incorporating an H₂-generating material known as Calcium Disilicide (CaSi₂) into membranes of another H₂-generating material known as porous silicon for tandem antioxidant drug delivery. Porous silicon (pSi) is an important substrate in drug delivery as its nano-network of pores allows controlled loading of drugs. Our approach centers on the use of spark ablation to deposit CaSi₂ into the pSi. Both porous silicon and CaSi₂ are nontoxic and can be resorbed over time in vivo.

To prepare CaSi₂/pSi, a piece of pSi membrane is fixed to substrate with a small drop of nail polish, and CaSi₂ powder is added. A capillary tube is placed on the pSi and spark ablated with a high-voltage Tesla coil, causing Si atoms on the porous membrane to vaporize along with CaSi₂ and the mixture resettles upon cooling. Scanning Electron Microscopy (SEM) is used to characterize morphology, and in situ Energy Dispersive X-ray Spectroscopy (EDX) to determine the percentage of calcium in the sample. We use the criterion of highest CaSi₂ loading percentage to determine the conditions for most efficient addition of CaSi₂ into the membrane. We have successfully incorporated calcium disilicide into porous Si membranes; current experiments are attempting to measure the amount of hydrogen produced synergistically to improve the performance of porous silicon as a means to treat in situ ROS production.

Density Functional Theory (DFT) is a method for simulating molecules by approximating their electron densities, with various functionals available to
model these systems. M11plus is one such functional, a range-separated hybrid meta functional that combines long-range non-local Hartree–Fock
exchange with the non-local Rung 3.5 correlation, which has demonstrated effectiveness across a broad range of chemical databases. This work
implements the M11plus functional into the PySCF open-source Python library.​

Salt-induced diffusiophoresis is the movement of a charged nanoparticle in water, driven by an imposed directional gradient of salt concentration. This transport phenomenon has become an important tool for manipulating the motion of charged nanoparticles within porous materials and microfluidic systems. Micelles are valuable nanoparticles with the ability to host small guest molecules in aqueous media. Therefore, understanding micelle diffusiophoresis is also crucial for transport of small molecules. This poster reports experimental diffusiophoresis coefficients for the cationic micelle of hexadecylpyridinium chloride (CPC) in water the presence of NaCl and KCl. Thermodynamic parameters characterizing micelle-salt interactions were also experimentally determined. We find that micelle-salt interaction is the essentially the same for both salts. In contrast, we find that diffusiophoresis of CPC micelles occurs from high to low salt concentration in the NaCl case, while it occurs in the opposite direction in the KCl case. A model describing micelle-salt interactions and micelle diffusiophoresis based on theory of electric double layer is reported. This work offers new insights into diffusiophoresis of charged nanoparticles with potential applications for enhanced-oil recovery from porous rocks, micellar ultrafiltration for the purification of industrial water, and diffusion-based mixing inside microfluidics.

This research aims to develop and characterize synthetic riboswitches for creatinine and trimethylamine N-oxide (TMAO), metabolic biomarkers for kidney and cardiovascular dysfunctions. Riboswitches are structured RNA elements located in the 5’-untranslated regions (UTRs) of bacterial mRNAs that regulate downstream gene expression through ligand-induced conformational changes with high affinity and selectivity. To select for the synthetic riboswitches specific to creatinine, the glycine riboswitch library was subjected to a dual genetic selection. In the positive selection, the riboswitches that bind to creatinine or any endogenous molecules will produce the CAT-UPP fusion protein, allowing the host cells to survive in the presence of chloramphenicol. The negative selection is carried out in media containing 5-fluorouracil (5-FU) in the absence of creatinine. Any riboswitches activated by endogenous ligands will die in the presence of 5-FU. The surviving cells should contain the riboswitches that are activated only by creatinine. After several repeated selection steps, including increased concentrations of chloramphenicol and 5-FU, no glycine riboswitch variants were identified to show chloramphenicol resistance in the presence of creatinine. We will continue the project with different riboswitch libraries. We identified a synthetic riboswitch to TMAO, a riboswitch that was derived from the genetic selection of the theophylline riboswitch library that clearly shows chloramphenicol resistance only in the presence of TMAO. We will further test this TMAO riboswitch by colorimetric or fluorescence assays using β-galactosidase and green fluorescence protein, respectively, in the presence of varying concentrations of TMAO.

Sustainable synthetic approaches to drug delivery carriers such as porous silicon are becoming increasingly important for biomedical applications such as drug delivery, where extreme electronic-grade purity is not required, even though silicon remains a critical material in electronics and energy technologies. This work develops a green, self-propagating high-temperature synthesis (SHS) approach to produce high-surface-area porous silicon using plant-derived silicon dioxide (SiO₂) as the precursor, magnesium (Mg) as the reductant, and sodium chloride (NaCl) as a thermal moderator. The exothermic magnesiothermic reaction is initiated using a controlled electrical input of less than (or equal to) 9V, enabling silicon formation while significantly reducing external energy requirements compared to conventional high-temperature silicon production methods.

In practice, Mg and SiO₂ reactants are exposed to a finite voltage for approximately 10–15 minutes to allow the SHS reaction to propagate. After synthesis, the crude product is purified by dissolving reaction byproducts in concentrated hydrochloric acid, leaving behind porous silicon. X-ray powder diffraction (XRD) is used to evaluate crystallinity and phase composition. While XRD analysis confirms the formation of silicon, persistent crystalline silica peaks indicate incomplete reduction and phase coexistence that currently limits effective separation. Ongoing work focuses on optimizing reaction conditions and refining reaction kinetics to improve phase selectivity and identify optimal synthesis parameters. Despite these challenges, the low-energy synthesis strategy and use of accessible raw materials highlight the potential of SHS-derived porous silicon as a scalable and sustainable platform for future drug delivery applications, particularly in resource-limited settings.

Oxidative stress plays a significant role in the progression of Alzheimer’s disease, making cellular antioxidant pathways attractive therapeutic targets. The Keap1–Nrf2 signaling pathway regulates the cellular response to oxidative stress, and inhibition of the Keap1 protein can activate Nrf2, promoting neuroprotective antioxidant responses. In this study, a series of quinoline-modified macrocyclic compounds were designed and synthesized to evaluate their potential as Keap1 inhibitors.
Computational and experimental approaches were employed to investigate the interaction of these compounds with the Keap1 protein. In-silico studies were conducted to analyze the binding affinity of the synthesized compounds using molecular docking, molecular dynamics simulations, and machine learning–based prediction of IC₅₀ values. These analyses provided insight into the stability of the ligand–protein complexes and the structural features that influence binding interactions.
The computational results indicate that compounds containing polar substitutions on the upper synthon exhibit stronger binding affinity and form more stable complexes with the Keap1 protein. Additionally, modification of the macrocyclic scaffold with quinoline substitution on the side nitrogen was found to enhance interactions with the protein binding pocket, suggesting a favorable structural motif for Keap1 inhibition.
Together, these findings provide insight into structure–activity relationships for this class of compounds and highlight promising molecular features for the development of Keap1 inhibitors as potential therapeutic leads for Alzheimer’s disease.

Chemotherapy relies on two therapeutic paradigms. The classic approach, most often used, employs small molecules to specifically target enzyme active sites, as represented by the new generation of kinase inhibitors. A secondary approach relies on interfering with protein-protein interactions thus requiring the use of larger compounds. While this latter strategy is garnering the attention of the pharmaceutical community, the rules for the design of these larger molecules, which are often cyclic, are not understood. The compact shape of small molecules leads to predictable behaviors including oral availability and cell uptake. For larger molecules that adopt multiple shapes, understanding the factors that control their shape and dynamic motion provides opportunities to predict similar behaviors that are critical for rational drug design. Here, the synthesis and characterization of a library of large, cyclic molecules (macrocycles) is described. The macrocycles of interest result from the dimerization of monomers. A total of 50 monomers containing different drug-like groups were synthesized. Reaction of a single monomer yields a homodimer, while combination of two different monomers leads to a 1:1:2 mixture of homodimers and a heterodimer. These combinations ultimately lead to a library of 1,275 different compounds. Liquid chromatography-mass spectrometry confirms that >99.9% of the reactions were successful. To investigate the biological activity of these compounds, we have provided this library to high throughput drug-screening facilities at Vanderbilt University and Scripps Florida. Of the several compounds created, macrocycles containing hydroxylamine groups are of special interest for two reasons. First, these molecules are similar to Hydrea, a widely-used, FDA-approved cancer drug. Second, unlike most macrocycles, both the shape and dynamics of these molecules are well understood so critical parameters such as oral availability and membrane transit can be predicted.

Reactive oxygen species (ROS) are byproducts of normal cellular metabolism and play important roles in cell signaling and immune defense. However, when their production exceeds the cell’s antioxidant capacity, ROS accumulation leads to oxidative stress, damaging proteins, lipids, and DNA. In the brain, this oxidative imbalance has been closely linked to the development and progression of neurodegenerative diseases like Alzheimer’s. Under normal conditions, superoxide dismutase (SOD) enzymes play a key role in protecting cells by breaking down harmful superoxide radicals. Yet, reduced SOD activity and impaired regulation have been consistently observed in patients with neurodegeneration, including Alzheimer’s disease. Small-molecule mimics of SOD, therefore, represent a promising therapeutic approach. In this study, we evaluate an expanded library of tetra-aza macrocyclic ligands chelating either copper or manganese metals. Mechanistic analysis reveals how structural modifications to the macrocyclic ring, particularly R-group substitutions that alter steric environment and electronic properties, directly influence catalytic reactivity and stability. Evaluation of Cu- and Mn-based complexes highlights distinct trends in activity and identifies structural motifs that enhance SOD-like function. These findings provide design principles for developing antioxidant therapeutics targeting oxidative stress.

Riboswitches are structured RNA elements that regulate gene expression through ligand-induced conformational changes and provide a platform for engineering cell-based biosensors. By coupling aptamers to reporter genes, synthetic riboswitches enable small-molecule–dependent detection of clinically relevant metabolites. This study focuses on sarcosine, associated with prostate cancer progression, and urate, linked to gout. Two sarcosine-responsive candidates were evaluated in E. coli using β-galactosidase and GFP reporter systems. Although construct integrity was confirmed, neither candidate demonstrated ligand-dependent activation in CDR or minimal media, suggesting insufficient regulatory activity under tested conditions. In parallel, a urate-responsive riboswitch library underwent dual selection with chloramphenicol resistance for positive selection and 5-fluorouracil counterselection for negative selection. After multiple selection rounds and screening of 192 colonies, no urate-specific variants were identified. Increasing chloramphenicol concentration to strengthen positive selection similarly yielded no hits. Future work will focus on further increasing both positive and negative selection intensity to enhance enrichment of functional variants and improve development of RNA-based biosensors for accessible metabolite detection. Additionally, future efforts will explore the adenine riboswitch library as a potential platform for developing novel biomarker detection systems.