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.

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.

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.