Open Access Publications - Department of Chemistry and Biochemistry
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Open access publications by faculty, postdocs, and graduate students in the Department of Chemistry and Biochemistry.
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Item Cryo-EM structures of HBV capsids from human cells at near-atomic resolution(Structure, 2025-11-27) Bianchini, Emily N.; Pérez-Segura, Carolina; Liu, Haitao; Luckenbaugh, Laura; Flanagan, John; Cai, Yuanheng; Shanklin, John; Zlotnick, Adam; Hadden-Perilla, Jodi A.; Hu, Jianming; C.-Y. Wang, JosephHBV causes chronic infections that can lead to severe liver disease, yet current treatments rarely achieve a cure. The HBV capsid is a critical therapeutic target, but structural insights have largely relied on E. coli-derived particles lacking native modifications. Here, we present near-atomic resolution cryo-electron microscopy (EM) structures of HBV capsids purified from human embryonic kidney (HEK-293T) cells, capturing authentic architecture and post-translational modifications. A hydrophobic pocket at the intradimer interface harbors lipid-like densities corresponding to stearic and palmitic acids, confirmed by gas chromatography- mass spectrometry. Molecular dynamics simulations revealed that pocket accessibility is regulated by rotamer states of Lys96, Phe97, and Gln99, supporting an induced fit model of fatty acid binding. Reduced phosphorylation and increased RNA content further modulate capsid conformation and pocket openness. These findings highlight the dynamic regulation of HBV capsid structure and provide a framework for understanding how capsid conformational dynamics contribute to viral assembly and envelopment.Item Designing Biochemical Visual Literacy Assessments: Insights from Classroom Testing and Student Interviews(Journal of Chemical Education, 2024-11-24) Procko, Kristen; Beckham, Josh; Acevedo, Roderico; Agrawal, Swati; Austin, Shane; Burch, Charmita; Engelman, Shelly; Fox, Kristin; Genova, Lauren; Mertz, Pamela; Mitton-Fry, Rachel; Vardar-Ulu, DidemA critical skill that biochemistry students must develop is the interpretation of molecular images, ranging from macromolecular representations to the chemical structures of the building blocks that comprise them. Such analysis requires biomolecular visual literacy, which is not often explicitly taught, and can be challenging for instructors to assess. In this work, we examine student responses to assessments designed to probe biomolecular visual literacy. Analysis of sets of assessments with classical test theory indicates that items which have undergone an iterative validation process, including expert review, perform well in classroom testing. However, the evaluation of multiple-choice and multiple-select assessment items based on classroom testing alone has limitations. Therefore, semistructured student interviews were used to explore student approaches to molecular visualization problem solving. Qualitative analysis of interview transcripts identified several common strategies among students when solving image-based questions, including relying on color in the images to answer questions, drawing on familiar terminology in the prompt, and using process-of-elimination to identify the best answer. Image complexity was identified as a common challenge for students. Instructors can craft more effective assessments by paying careful attention to the use of color in images, using terminology students are familiar with, carefully creating distractors, and using images with complexity appropriate to the learner level. This work underscores the importance of the student perspective in the design of assessments used by educators to evaluate learning.Item Asymmetric Synthesis of Quaternary Hydantoins via a Palladium-Catalyzed Aza-Heck Cyclization(Journal of the American Chemical Society, 2025-11-14) Meck, Ellie A.; Omer, Humair M.; Edwards, Montana J.; Idowu,Temidayo D.; Murray, Mariah L.; Korch, Katerina M.; Watson, Donald A.An asymmetric, palladium-catalyzed aza-Heck cyclization to prepare enantioenriched 5,5-disubstituted hydantoins (quaternary hydantoins), which are medicinally important compounds but are classically challenging to prepare, is reported. The required substrates can be prepared readily from α,β-unsaturated amides in a single operation, and aza-Heck cyclization provides a wide range of topologically complex, highly substituted, pharmaceutically relevant hydantoins. The capacity of this method to impact the synthesis of drug substances is demonstrated by the first asymmetric synthesis of the anticonvulsant (R)-mephenytoin.Item Synthesis of Solid-Solution MnxZn1–xO Nanoparticles and their Electrochemical Oxidation of Furfural(Inorganic Chemistry, 2025-08-25) Oteroa, Kayla; Armstronga, Cameron; Moreno-Pizaa,Oscar J.; Hollis, Emma; Scalia, Jordan C.; De Jesús Báezc, Luis R; Hernández-Pagána, Emil A.Electrochemical valorization of biomass-derived substrates has become a prominent area of research due to its potential to produce value-added products from renewable feedstocks in a more sustainable way. First-row transition metal electrodes are compelling candidates for these conversions due to their stability, abundance, and cost-effectiveness. Herein, we report on the colloidal synthesis of MnxZn1-xO (x=0.3-0.7) nanoparticles and their electrocatalytic activity towards furfural oxidation. We find that the hindrance of a MnO impurity can be achieved by leveraging the oxidation state of the Mn precursor. The MnxZn1-xO composition closely follows the ratio of precursors, with all the nanoparticles having a wurtzite structure as determined by ICPMS and PXRD, respectively. XANES and XPS revealed the presence of Mn in different oxidation states with the ratio of these varying based on the composition. When comparing the electrocatalytic activity of the monometallic and bimetallic oxides for furfural oxidation, a decrease in current density was observed with increasing Zn content. We find the MnxZn1-xO nanoparticles favor the formation of the 6 e- oxidation product 5-hydroxy-2(5H)-furanone, while both monometallic oxides primarly yield CO2 and other deeply oxidized products. These findings can contribute towards the design and synthesis of more active and selective electrocatalyst.Item Elucidation of the solution synthesis and growth of non-noble metal TE3-type intermetallics (T= Fe, Co; E= Ga, In)(Chemistry of Materials, 2025-09-25) Boski, Devin J.; Ross, Ryan C.; Hernandez-Pagan, Emil A.Due to challenging synthetic routes, non-noble metal intermetallic nanomaterials are seldom studied despite having promising thermoelectric, magnetic, and catalytic properties. To initiate these materials’ further study, we present a facile, quick, and modifiable solution-based procedure for the synthesis of FeGa3, CoGa3, CoIn3, and Fe0.5Co0.5Ga3, which are characterized by pXRD, TEM, SEM, EDS, ICP-MS, and XPS. Reaction insights for these isostructural intermetallics demonstrate a reliance on long-chain secondary amines, fast injection rates, as well as select aluminum hydride reductants, such as diisobutylaluminum hydride (DIBAL-H), whereas other strong reductants like alkoxyaluminum hydrides and borohydrides inhibit the formation of Ga-containing intermetallics. Our results suggest that these reactions can be tailored to proceed through either a coreduction or rapid amalgamation (seeded growth) mechanism, in which liquid Ga nanoseeds are formed, followed by rapid diffusion of the first-row transition metals, leading to crystallization of a thermodynamically stable intermetallic. These results lay foundational groundwork for accessing and understanding other underexplored non-noble metal intermetallic nanomaterials, and we believe it may be succeeded by further developments to improve control over composition, morphology, and thus physical properties.Item Boron-Containing Analogs of Fosmidomycin: Benzoxaborole Derivatives Exhibit Promising Activity Against Resistant Pathogens(ACS Omega, 2025-07-19) Gamrat, James M.; Orme, Christopher L; Mancini, Giulia; Burke, Sarah J.; Alhthlol, Latifah M.; Colandrea, Rebecca C.; Figula, Bryan C.; Tomares, Dylan T.; Jason E. Heindl,; Tomsho, John W.The rise of antimicrobial resistance presents an urgent challenge that necessitates the development of novel therapeutic agents with distinct mechanisms of action. This research explores boron-containing compounds as potential neutral phosphate/phosphonate isosteres of fosmidomycin, a potent inhibitor of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (IspC) within the nonmevalonate isoprenoid biosynthesis (MEP) pathway, with limited clinical utility due to poor pharmacokinetics. We report the synthesis of a library of 15 boron-containing analogs of fosmidomycin and their comprehensive evaluation as IspC inhibitors and antimicrobial agents. The compounds did not demonstrate significant activity against the intended IspC target, thus providing evidence that these boron moieties may have limited utility as phosphonate isosteres in this system. However, our investigation yielded unexpected and valuable antimicrobial discoveries. Several benzoxaborole compounds demonstrated significant activity against pathogenic microbes, including methicillin-resistant Staphylococcus aureus (MRSA), E. coli, and C. albicans. Mechanistic studies confirmed that these compounds operate through alternative pathways distinct from MEP pathway inhibition. These results provide a foundation for the rational design of next-generation boron-containing antimicrobials with enhanced potency and selectivity against resistant pathogens, including MRSA.Item Lipid–GPCR interactions in an asymmetric plasma membrane model(Faraday Discussions, 2025-01-30) Ji, Jingjing; Lyman, EdwardWe report simulations and analysis of the A2A adenosine receptor in its fully active state, in two different membrane environments. The first is a model in which the lipids are distributed asymmetrically according to recent lipidomics, simulations, and biophysical measurements, which together establish the distribution of lipids and cholesterol between the two leaflets. The second is the symmetrized version, which captures the membrane state following loss of lipid asymmetry. By comparing lipid–protein interactions between these two cases we show that solvation by phosphatidyl serine (PS) is insensitive to the loss of asymmetry—an abundance of positively charged sidechains around the cytoplasmic side of the receptor enriches solvation by PS in both membrane states. Cholesterol interactions are sensitive to the loss of asymmetry, with the abundance of cholesterol in the exoplasmic leaflet driving long-lived cholesterol interactions in the asymmetric state. However, one cholesterol interaction site on helix 6 is observed in both cases, and was also observed in earlier work with different membrane models, supporting its identification as a bona fide cholesterol binding site.Item A Hybrid BN-Doped Nanographene with Narrow Emission Bandwidths for OLEDs(Chemistry - A European Journal, 2025-01-29) Diev, Vyacheslav V.; Zou, Yunlong; Kondakov, Denis; Yap, Glenn P. A.We describe synthesis of BN-doped nanographene containing five phenylene units, boron and nitrogen atoms with alternating ortho-disposition, as well as direct B−N connections. Resulting BN doped nanographene exhibits blue fluorescence at 441 nm with an extraordinarily narrow fluorescence peak with a full width at half maximum (FWHM)=10–11 nm. Crystallography reveals supramolecular organization of this compound in the crystal phase. Initial organic light emitting device (OLED) data suggest that the presence of a directly connected B−N isostere can lead to devices with sufficiently long lifetime as well as narrow emission electro-luminescence peaks necessary for OLED applications. Graphical Abstract available at: https://doi.org/10.1002/chem.202404078 Computational screening, synthesis and characterization identified BN-containing candidate 1 as a promising narrow bandwidth chromophore. BN doped nanographene exhibits blue fluorescence at 441 nm with an extraordinarily narrow fluorescence peak with full width at half maximum (FWHM)=10–11 nm that outperforms narrow bandwidths of the incumbent references. Utility of the compound for long lifetime narrow bandwidth OLEDs has also been demonstratedItem The Zintl pnictides Yb10CdSb9 and Yb14CdSb11: New candidate thermoelectric materials(Journal of Applied Physics, 2025-02-19) Ogunbunmi, Michael O.; Ghosh, Kowsik; Donnelly, Connor; Baranets, Sviatoslav; Bobev, SvilenThe synthesis of new materials is the lifeline of solid-state science, and it continues to offer us unique opportunities for testing various theoretical formulations and models on a practical material. Such an avenue, therefore, provides a breeding ground for technological innovations and advancements that can completely revolutionize our world. Here, we report the results of our exploratory syntheses in the Yb–Cd–Sb compositional space that lead to the identification of two new Zintl antimonides, namely, Yb10CdSb9 and Yb14CdSb11. Their crystal structures were established via single-crystal X-ray diffraction methods; the basic electronic and transport properties of the new materials were also characterized. Yb10CdSb9 crystallizes in a disordered variant of the tetragonal Ca10LiMgSb9 structure type with unit cell parameters a = 11.8473(8) Å and c = 17.1302(12) Å (space group P42/mnm). Yb14CdSb11 crystallizes in the tetragonal Ca14AlSb11 structure type with unit cell parameters: a = 16.605(3) Å and c = 12.144(7) Å (space group I41/acd). Although the structures of both compounds can be rationalized within the framework of the Zintl formalism, based on the partitioning of the valence electrons in the much disordered Yb10CdSb9 phase, the charge is indicative of a slightly electron-rich composition. Electronic structure calculations in both cases support the notion of intrinsic semiconductor behavior, as expected for a Zintl phase. The temperature dependence of the electrical resistivity of a single crystal of Yb10CdSb9 is in line with that, and the evolution of the Seebeck coefficient indicates an electron-dominated transport mechanism, and a respectable power factor of 0.71 μW/cm K2 at 460 K can be calculated for Yb10CdSb9. The electrical resistivity of Yb14CdSb11, however, evolves in a semimetallic manner, which could suggest an overdoped sample or degenerate semiconducting behavior.Item PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection(Nature Communications, 2025-02-21) Chen, Shuyuan; Putnik, Rachel; Li, Xi; Diwaker, Alka; Vasconcelos, Marina; Liu, Shuzhen; Gondi, Sudershan; Zhou, Junhui; Guo, Lei; Xu, Lin; Temme, Sebastian; Bersch, Klare; Hyland, Stephen; Yin, Jianyi; Burstein, Ezra; Bahnson, Brian J.; Gildersleeve, Jeffrey C.; Grimes, Catherine Leimkuhler; Reinecker, Hans-ChristianPeptidoglycan recognition proteins (PGLYRPs) are implicated in the control of the intestinal microbiota; however, molecular requirements for peptidoglycan (PGN) binding and receptor signaling mechanisms remain poorly understood. Here we show that PGLYRP1 is a receptor for the disaccharide motif of lysine N-acetylglucosamine N-acetylmuramic tripeptide (GMTriP-K). PGLYRP1 is required for innate immune activation by GMTriP-K but not muramyl dipeptide (MDP). In macrophages, intracellular PGLYRP1 complexes with NOD2 and GEF-H1, both of which are required for GMTriP-K-regulated gene expression. PGLYRP1 localizes to the endoplasmic reticulum and interacts at the Golgi with NOD2 upon GMTriP-K stimulation. PGLYRP1 and dependent gene expression signatures are induced in both mouse intestinal inflammation and human ulcerative colitis. Importantly, PGLYRP1 activation by GMTriP-K can result in the protection of mice from TNBS-induced colitis. Mammalian PGLYRPs can function as intracellular pattern recognition receptors for the control of host defense responses in the intestine.Item ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis(Molecular Microbiology, 2024-12-03) Presloid, Christopher J.; Jiang, Jialiu; Kandel, Pratistha; Anderson, Henry R.; Beardslee, Patrick C.; Swayne, Thomas M.; Schmitz, Karl R.Drug-resistant tuberculosis infections are a major threat to global public health. The essential mycobacterial ClpC1P1P2 protease has received attention as a prospective target for novel antibacterial therapeutics. However, efforts to probe its function in cells are constrained by our limited knowledge of its physiological proteolytic repertoire. Here, we interrogate the role of mycobacterial ClpS in directing N-degron pathway proteolysis by ClpC1P1P2 in Mycolicibacterium smegmatis. Binding assays demonstrate that mycobacterial ClpS binds canonical primary destabilizing residues (Leu, Phe, Tyr, Trp) with moderate affinity. N-degron binding restricts the conformational flexibility of a loop adjacent to the ClpS N-degron binding pocket and strengthens ClpS•ClpC1 binding affinity ~30-fold, providing a mechanism for cells to prioritize N-degron proteolysis when substrates are abundant. Proteolytic reporter assays in M. smegmatis confirm degradation of substrates bearing primary N-degrons, but suggest that secondary N-degrons are absent in mycobacteria. This work expands our understanding of the mycobacterial N-degron pathway and identifies ClpS as a critical component for substrate specificity, providing insights that may support the development of improved Clp protease inhibitors. Graphical Abstract available at: https://doi.org/10.1111/mmi.15334 Many bacteria possess an N-degron pathway that links the proteolytic stability of proteins to the identity of their N-terminal residue. Here, we report that Mycolicibacterium smegmatis possesses a physiological N-degron pathway that is less complex than those described in other bacteria.Item A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer(Proceedings of the National Academy of Sciences, 2025-01-15) Messina, Marco S.; Torrente, Laura; Pezacki, Aidan T.; Humpel, Hanna I.; Li, Erin L.; Miller, Sophia G.; Verdejo-Torres, Odette; Padilla-Benavides, Teresita; Brady, Donita C.; Killilea, David W.; Killilea, Alison N.; Ralle, Martina; Ward, Nathan P.; Ohata, Jun; DeNicola, Gina M.; Chang, Christopher J.Significance Copper is an essential element for life, where it mediates copper-dependent cell growth and proliferation (cuproplasia) and cell death (cuproptosis) processes that underpin health and disease. We present a histochemical activity-based sensing strategy that enables systematic profiling of bioavailable copper levels, termed the labile copper pool, across many cell lines in parallel to assess their copper dependencies. We identified that cancer cells with heightened activation of the antioxidant response transcription factor NRF2 have reciprocally lower levels of labile Cu(I). In turn, these cells are more susceptible to cell death induced by copper chelation. By revealing a cuproplasia-dependent vulnerability in cancer, this work showcases the utility of chemical copper detection methods for studying metals in biology and medicine. Abstract Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel. Coppermycin-1 reacts selectively with Cu(I) to release puromycin, which is then incorporated into nascent peptides during protein translation, thus leaving a permanent and dose-dependent marker for labile copper that can be visualized with standard immunofluorescence assays. We showcase the utility of this platform for screening labile Cu(I) pools across the National Cancer Institute’s 60 (NCI-60) human tumor cell line panel, identifying cell types with elevated basal levels of labile copper. Moreover, we use Coppermycin-1 to show that lung cancer cells with heightened activation of nuclear factor-erythroid 2-related factor 2 (NRF2) possess lower resting labile Cu(I) levels and, as a result, have reduced viability when treated with a copper chelator. This work establishes that methods for labile copper detection can be used to assess cuproplasia, an emerging form of copper-dependent cell growth and proliferation, providing a starting point for broader investigations into the roles of transition metal signaling in biology and medicine.Item Post-synthetic modification of amine-functionalized permanently porous coordination cages(Chemical Communications, 2024-12-04) Hoq, Jahidul; Dworzak, Michael R.; Dissanayake, Duleeka; Skalla, Rebecca X.; Yamamoto, Nobuyuki; Yap, Glenn P. A.; Bloch, Eric D.This manuscript explores the post-synthetic modification (PSM) of amine-functionalized porous coordination cages, specifically focusing on the formation of imine bonds through reactions with aldehydes. Targeting various cage topologies, including zirconium-, magnesium-, and molybdenum-based structures, we demonstrate the tunability of cage solubility and porosity through selective functionalization where the proximity of amine groups on the parent cage impacts the extent of modification. The work highlights the reversible nature of imine formation, offering potential applications in solubility switching and mixed-metal solid synthesis.Item Phonons reveal coupled cholesterol-lipid dynamics in ternary membranes(Biophysical Journal, 2024-12-03) Fitzgerald, James E.; Soloviov, Dmytro; Cai, Yong Q.; Heberle, Frederick A.; Ishikawa, Daisuke; Baron, Alfred Q.R.; Bolmatov, Dima; Zhernenkov, Mikhail; Lyman, Edward R.Experimental studies of collective dynamics in lipid bilayers have been challenging due to the energy resolution required to observe these low-energy phonon-like modes. However, inelastic x-ray scattering (IXS) measurements—a technique for probing vibrations in soft and biological materials—are now possible with sub-meV resolution, permitting direct observation of low-energy, phonon-like modes in lipid membranes. Here, IXS measurements with sub-meV energy resolution reveal a low-energy optic-like phonon mode at roughly 3 meV in the liquid-ordered ðLoÞ and liquid-disordered phases of a ternary lipid mixture. This mode is only observed experimentally at momentum transfers greater than 5 nm 1 in the Lo system. A similar gapped mode is also observed in all-atom molecular dynamics (MD) simulations of the same mixture, indicating that the simulations accurately represent the fast, collective dynamics in the L o phase. Its optical nature and the Q range of the gap together suggest that the observed mode is due to the coupled motion of cholesterol-lipid pairs, separated by several hydrocarbon chains within the membrane plane. Analysis of the simulations provides molecular insight into the origin of the mode in transient, nanoscale substructures of hexagonally packed hydrocarbon chains. This nanoscale hexagonal packing was previously reported based on MD simulations and, later, by NMR measurements. Here, however, the integration of IXS and MD simulations identifies a new signature of the Lo substructure in the collective lipid dynamics, thanks to the recent confluence of IXS sensitivity and MD simulation capabilities.Item Composition Quantification of SiGeSn Alloys Through Time-of-Flight Secondary Ion Mass Spectrometry: Calibration Methodologies and Validation With Atom Probe Tomography(IEEE Journal of Selected Topics in Quantum Electronics, 2024-09-09) Zhao, Haochen; Liu, Shang; Park, Suho; Feng, Xu; Zeng, Zhaoquan; Kolodzey, JamesTime-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is a powerful technique for elemental compositional analysis and depth profiling of materials. However, it encounters the problem of matrix effects that hinder its application. In this work, we introduce a pioneering ToF-SIMS calibration method tailored for SixGeySnz ternary alloys. SixGe1-x and Ge1-zSnz binary alloys with known compositions are used as calibration reference samples. Through a systematic SIMS quantification study of SiGe and GeSn binary alloys, we unveil a linear correlation between secondary ion intensity ratio and composition ratio for both SiGe and GeSn binary alloys, effectively mitigating the matrix effects. Extracted relative sensitivity factor (RSF) value from SixGe1-x (0.07 < x < 0.83) and Ge1-zSnz (0.066 < z < 0.183) binary alloys are subsequently applied to those of SixGeySnz (0.011 < x < 0.113, 0.863 < y < 0.935 and 0.023 < z < 0.103) ternary alloys for elemental compositions quantification. These values are cross-checked by Atom Probe Tomography (APT) analysis, an indication of the great accuracy and reliability of as-developed ToF-SIMS calibration process. The proposed method and its reference sample selection strategy in this work provide a low-cost as well as simple-to-follow calibration route for SiGeSn composition analysis, thus driving the development of next-generation multifunctional SiGeSn-related semiconductor devices.Item Flexible Cation Exchange Environment via Ligand-Free Metal Chalcogenide Thin Films(ACS Nanoscience Au, 2024-11-07) Lacey, Hannah R.; Dobson, Kevin D.; Hernández- Pagán, Emil A.Cation exchange (CE) has emerged as a premier postsynthetic method to carefully tune the chemical composition and properties of nanocrystals with excellent morphology retention. However, reaction conditions are typically dictated by the ubiquitous ligands bound to their surface, limiting their solubility and influencing the thermodynamics/kinetics of the reaction. To bypass these challenges, we report on CE reactions with Cu+, Ag+, Cu2+, Cd2+, Zn2+, and Mn2+ utilizing ligand-free CdS and CuxSey thin films as host templates. The exchange reactions could be performed sequentially or simultaneously (i.e., two guest cations) to access compositionally diverse products. The incorporation of cations on the host films was confirmed using SEM-EDS, XPS, and ICP-MS analyses, as well as tracking wavelength shifts in the UV–vis absorption spectra. The flexibility of this approach was demonstrated as reactions were carried out using an array of different guest precursor salts and solvents with a range of polarities. Moreover, the reactions were generalizable among selenide and sulfide films and proceeded under milder conditions in comparison with reported nanocrystal reactions. A ligand-free environment with flexible reaction conditions, as the work herein, could aid in deconvoluting the different factors involved in CE reactions and further expand its use for fundamental research and applications like photovoltaics, optoelectronics, and catalysis.Item Self-assembled thin films as alternative surface textures in assistive aids with users who are blind(Journal of Materials Chemistry B, 2024-09-05) Swain, Zachary; Derkaloustian, Maryanne; Hepler, Kayla A.; Nolin, Abigail; Damani, Vidhika S.; Bhattacharyya, Pushpita; Shrestha, Tulaja; Medina, Jared; Kayser, Laure V.; Dhong, Charles B.Current tactile graphics primarily render tactile information for blind users through physical features, such as raised bumps or lines. However, the variety of distinctive physical features that can be created is effectively saturated, and alternatives to these physical features are not currently available for static tactile aids. Here, we explored the use of chemical modification through self-assembled thin films to generate distinctive textures in tactile aids. We used two silane precursors, n-butylaminopropyltrimethoxysilane and n-pentyltrichlorosilane, to coat playing card surfaces and investigated their efficacy as a tactile coating. We verified the surface coating process and examined their durability to repeated use by traditional materials characterization and custom mesoscale friction testing. Finally, we asked participants who were both congenitally blind and braille-literate to sort the cards based on touch. We found that participants were able to identify the correct coated card with 82% accuracy, which was significantly above chance, and two participants achieved 100% accuracy. This success with study participants demonstrates that surface coatings and surface modifications might augment or complement physical textures in next-generation tactile aids.Item Mechanistic differences between linear vs. spirocyclic dialkyldiazirine probes for photoaffinity labeling(Chemical Science, 2024-08-13) O'Brien, Jessica G. K.; Conway, Louis P.; Ramaraj, Paramesh K.; Jadhav, Appaso M.; Jin, Jun; Dutra, Jason K.; Evers, Parrish; Masoud, Shadi S.; Schupp, Manuel; Saridakis, Iakovos; Chen, Yong; Maulide, Nuno; Pezacki, John P.; Ende, Christopher W. am; Parker, Christopher G.; Fox, Joseph M.Dialkyldiazirines have emerged as a photo-reactive group of choice for interactome mapping in live cell experiments. Upon irradiation, ‘linear’ dialkyldiazirines produce dialkylcarbenes which are susceptible to both intramolecular reactions and unimolecular elimination processes, as well as diazoalkanes, which also participate in intermolecular labeling. Cyclobutylidene has a nonclassical bonding structure and is stable enough to be captured in bimolecular reactions. Cyclobutanediazirines have more recently been studied as photoaffinity probes based on cyclobutylidene, but the mechanism, especially with respect to the role of putative diazo intermediates, was not fully understood. Here, we show that photolysis (365 nm) of cyclobutanediazirines can produce cyclobutylidene intermediates as evidenced by formation of their expected bimolecular and unimolecular products, including methylenecyclopropane derivatives. Unlike linear diazirines, cyclobutanediazirine photolysis in the presence of tetramethylethylene produces a [2 + 1] cycloaddition adduct. By contrast, linear diazirines produce diazo compounds upon low temperature photolysis in THF, whereas diazo compounds are not detected in similar photolyses of cyclobutanediazirines. Diazocyclobutane, prepared by independent synthesis, is labile, reactive toward water and capable of protein alkylation. The rate of diazocyclobutane decomposition is not affected by 365 nm light, suggesting that the photochemical conversion of diazocyclobutane to cyclobutylidene is not an important pathway. Finally, chemical proteomic studies revealed that a likely consequence of this primary conversion to a highly reactive carbene is a marked decrease in labeling by cyclobutanediazirine-based probes relative to linear diazirine counterparts both at the individual protein and proteome-wide levels. Collectively, these observations are consistent with a mechanistic picture for cyclobutanediazirine photolysis that involves carbene chemistry with minimal formation of diazo intermediates, and contrasts with the photolyses of linear diazirines where alkylation by diazo intermediates plays a more significant role.Item Chemomechanical damage prediction from phase-field simulation video sequences using a deep-learning-based methodology(iScience, 2024-09-12) Zeng, Quan; Rezaei, Shahed; Carrillo, Luis; Davidson, Rachel; Xu, Bai-Xiang; Banerjee, Sarbajit; Ding, YuHighlights • Deep-learning-based method to predict chemo-mechanical processes in electrode materials • Prognostication of crack development and propagation based on machine learning • Potential to integrate in battery management systems of large-format batteries Summary Understanding the failure mechanisms of lithium-ion batteries is essential for their greater adoption in diverse formats. Operando X-ray and electron microscopy enable the evaluation of concentration, phase, and stress heterogeneities in electrode architectures. Phase-field models are commonly used to capture multi-physics coupling including the interplay between electrochemistry and mechanics. However, very little has been explored regarding developing predictive models that would forecast imminent failure. This study explores the application of convolutional long short-term memory networks for damage prediction in cathode materials using video sequence from phase-field simulations as a proxy for video microscopy. Two models are examined making use of, respectively, the damage video only and the damage and hydrostatic stress videos combined. We use customized quantitative metrics to compare the performance of the models. Our work demonstrates the outstanding capability of deep learning models using limited data to predict fracture behavior of battery materials, including crack propagation angle and length. Graphical abstract available at: https://doi.org/10.1016/j.isci.2024.110822Item Glycolysis Can Be Fun: Rediscovering Glycolysis as a Problem-Solving Introduction to Metabolism(CourseSource, 2024-08-19) Genova, Lauren A.; Procko, Kristen; Grimes, Catherine L.; Williams, Caroline; Cornely, Kathleen; Shor, Audrey; Greene, Amy Styer; Bibel, Brianna; Kumar, Sanjana V.; White, Harold B.A thorough understanding of glycolysis forms a foundation for students to analyze subsequent topics in metabolism, a core competency recognized by multiple national societies for biology and biochemistry. However, when confronted with the names of over ten chemicals and enzymes, along with various energy inputs and outputs, students can regard glycolysis as a daunting memorization task. Here we describe a card sorting activity in which small groups of students work out the steps of the glycolysis pathway before any lectures on the topic. They examine the chemical structures of glycolytic intermediates and deduce their logical order. Subsequent analysis of the reactions and the role of cofactors and substrates is reinforced with a POGIL®-inspired worksheet. In the process, the students engage in productive discussions of topics often introduced didactically in lecture. The activity was implemented at six different institutions in small (~12 students) and large classrooms (100+ students), and can be adapted to hybrid/online formats. This highly engaging exercise has been well-received by students and instructors in various undergraduate course contexts.