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 oM11plus functional, a tweaked version of M11plus, 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.