Asphaltenes are the heaviest component of crude oil and strongly aggregate during the oil refinement process, fouling equipment and increasing oil runoff. Understanding their propensity for aggregation at the molecular level is crucial for developing strategies to mitigate their role in equipment fouling. Using computational chemistry, we analyzed the dimerization energies of 67 previously published asphaltene structures by running CREST calculations on all possible molecular pairs. Our results reveal that diradical:diradical interactions drive strong aggregation, whereas radical-closed shell interactions are comparable in strength to closed-shell:closed-shell interactions. Additionally, we find that archipelago-type structures weaken dimerization as compared to island-type asphaltenes, likely due to self-association of archipelago structures. These findings provide key insights into asphaltene behavior and suggest potential strategies for disrupting aggregation. Future work will explore whether near-infrared light can be used to disaggregate asphaltenes, offering a novel approach to alleviate asphaltene-related challenges in industry.

Macrocycles are promising drug candidates due to their ability to selectively interact with biological targets. However, predicting their solubility and membrane permeability remains challenging. To probe this, a library of 35 triazine macrocycles was synthesized and the hydrophobicity of each macrocycle was measured using octanol:water partition coefficients (logP).

Unexpectedly, a glycine-derived macrocycle with two primary amine groups displayed high hydrophobicity, contrary to prediction based on conventional computational methods for computing logP (AlogP). Computational analysis revealed that the diamine substitution stabilizes a closed conformation, tethering the macrocycle where its polar groups are shielded from solvent interaction, thus increasing hydrophobicity. Additionally, we found that logP values of heterodimer macrocycles closely approximated the average of their corresponding homodimers, suggesting a predictable trend in partitioning behavior.

We demonstrate how small molecular changes can significantly impact physical properties. By combining synthesis, physical measurements, and computational modeling, our work provides insights into macrocycle behavior that could aid in designing membrane-permeable drug candidates.

The goal of this project is to select the variants of an archaea leucyl-tRNA synthetase (MLRS) to incorporate N-𝜀-acetyl lysine (AcLys) into specific positions of proteins in bacterial cells. Acetylation of lysine is one of the most important post-translational modifications of proteins that regulate their functions. One application of this study is using site-directed incorporation of AcLys to introduce novel functions to proteins. Previously, we successfully randomized five positions in the MLRS active site to generate millions of different variants. Genetic screening procedures were performed to select MLRS variants specific for AcLys. Positive selection is performed in the presence of AcLys where bacterial cells containing MLRS that attach any natural amino acids or AcLys onto the tRNA can survive in the presence of chloramphenicol antibiotics. In the negative selection performed in the absence of AcLys, bacterial cells containing MLRS that attach natural amino acids will die in the presence of 5-FU as a toxic substance is produced. Only cells containing MLRS variants that attach AcLys can survive in the presence of 5-FU, because no toxic substance is produced. Two clones made it through multiple rounds of selection and are being tested for successful incorporation of AcLys at the 7th position of the Z-domain protein. Mass spectrometry will be used to detect the presence of AcLys.

Impact of Sensor Design on Hydrogel-Porous Silicon Structures Capable of Detecting Ion Concentrations in Human Sweat

Dylan Walters1, George Weimer1, Leigh T. Canham,2 and Jeffery L Coffer1

1Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX 76129
2Nanoscale Physics, Chemistry and Engineering Research Laboratory, University of Birmingham, Birmingham, B15 2TT UK

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.
Hydrogels are water-infused, biodegradable polymer networks. Alginate based hydrogels are particularly useful because of environmental abundance, along with their ability to interface well with human skin. The addition of acrylamide segments to the polymer chains adds stability and useful shelf-life to the material. 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 in Acrylamide/alginate co-polymer hydrogels to test how variations in ion concentration affect the flow of current as a function of applied voltage. pSi membranes ~110 m 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 min. Membrane pieces ~ 2 mm by 2 mm are heated for one hour at 650°C. They are then fashioned into diodes upon the attachment of Cu wire using Ag epoxy and annealed for 15 minutes at 95°C. The backs of the membranes, the connection to the copper wire, and the copper wire itself are sealed using clear nail polish to prevent current flow from the back of the membranes and bubble formation. In each ion sensing experiment, an electrochemical cell is created by placing two pSi membranes parallel each other ~2 mm apart vertically in a fixed electrolyte composition. Current is measured as a function of applied voltage (typically from 0-5 V) for systems with different NaCl concentrations in the nM to mM range. NaCl solutions are injected directly into the hydrogel in between the two pSi membranes 2 µL at a time. At local concentrations of approximately 0.25M, the magnitude of maximum current response increases with increased volume of ion solution added.
This presentation will focus on the porous silicon hydrogel fabrication protocol, as well as results from experiments with varying NaCl concentrations. Future work is being designed to determine the saturation behavior and the ion concentration limits of the pSi membranes in hydrogels.

Fluorescent small molecule environment-sensitive probes change their emission properties (including emission wavelength, intensity or lifetime) in response to the changes of the environment around them, such as changes in temperature, viscosity, and polarity. Thus, these probes have found numerous applications in sensing and imaging, especially in biologically relevant systems. Ratiometic probes is a special group of molecules that has two or more emission wavelengths that exhibit a relative change in response to changes in the media, which provides an internal calibration, increases signal-to-noise ration, and improves the integrity of sensing. However, synthesis of such molecules is usually non-modular in nature, and it often requires multiple steps coupled with numerous purifications. In this presentation, we will highlight our synthetic efforts on the developments of several types of fluorescence ratiometric probes that are based on versatile fluorescence scaffolds, such as BODIPY and squaraine dyes.