Digital Commons Network^™

Reiq-Mediated Alarmone Signalling Regulates Growth, Stress-Induced Biofilm Formation And Spore Accumulation In Clostridioides Difficile, Areej Malik, Adenrele Oludiran, Asia Poudel, Orlando Berumen Alvarez, Charles Woodward, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signalling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in Clostridioides difficile, a biofilm- and spore-forming pathogen that causes resilient, highly recurrent C. difficile infections. The role of the SR in other processes and the effectors by which it regulates C. difficile physiology are unknown. C. difficile RelQ is a clostridial alarmone synthetase. Deletion of relQ dysregulates C. difficile growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors and drastically reduces biofilm formation. While wild-type C. difficile displays increased biofilm …

Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …

The A²Π-X²Σ⁺ Band System Of Sco For M-Type Star Spectral Analysis, Léo Lavy, Adam Pastorek, Peter F. Bernath

Chemistry & Biochemistry Faculty Publications

M-type stars are the most abundant stars in our Galaxy. Their visible spectra are characterized by strong TiO and VO absorption bands with occasional ScO bands near 6000–6100 Å. This region corresponds to the A²Π–X²Σ⁺ band system and can be used to measure the abundance of ScO. In this work, a new Doppler-limited resolution spectrum of ScO obtained in a hollow-cathode experiment is presented. The A²Π–X²Σ⁺ electronic transition is analyzed with special care dedicated to fitting the A′²Δ(v+2) ∼ A²Π(v) perturbation. Spectroscopic constants of the A²Π(v) states are reported for v ≤ 9, and a partial fit of …

A Breast Cancer Stem Active Cobalt(Iii)-Cyclam Complex Containing Flufenamic Acid With Immunogenic Potential, Jiaxin Fang, Owamagbe N. Orobator, Chibuzor Ngozi Olelewe, Ginevra Passeri, Kuldip Singh, Samuel G. Awuah, Kogularamanan Suntharalingam

Chemistry Faculty Publications

The cytotoxic and immunogenic-activating properties of a cobalt(III)-cyclam complex bearing the non-steroidal anti-inflammatory drug, flufenamic acid is reported within the context of anti-cancer stem cell (CSC) drug discovery. The cobalt(III)-cyclam complex 1 displays sub-micromolar potency towards breast CSCs grown in monolayers, 24-fold and 31-fold greater than salinomycin (an established anti-breast CSC agent) and cisplatin (an anticancer metallopharmaceutical), respectively. Strikingly, the cobalt(III)-cyclam complex 1 is 69-fold and 50-fold more potent than salinomycin and cisplatin towards three-dimensionally cultured breast CSC mammospheres. Mechanistic studies reveal that 1 induces DNA damage, inhibits cyclooxygenase-2 expression, and prompts caspase-dependent apoptosis. Breast CSCs treated with 1 exhibit …

Unlv Title Iii Aanapisi & Mcnair Scholars Institute Research Journal 2024, Jesica Godinez-Paredes, Kian Hassankhan, Apia Hickman, Robin Ruth Kee, Kevin Ayala Pineda, Briana Melendez, Kalli Ramos, Saturn L. Reyes, Fabian Leija, Selena Pepe, Silva Topchyan, Celeste Ainsley, Mayra Arzate, Jessica Balistreri, Zantana Ephrem, Mirella Jasso, Karl Panou, Nichole Pelaez, Miklo Alcala, Akshay Dave, Mey Mey Heng, Michael Finkle, Janessa Montenegro, Reynafe Naol Aniga, Victor Mejia, Angelica G. Diaz, Anayeli Flores-Garibay, Kari Lee Joe Goold, Samantha Hernandez, Lianelys Cabrera Martinez, Caitlin Reynolds, Kimberly N. Usbeck, Abdulrahman Alahdal, Angelica Diaz, Willaine Mae Kahano, Raquel Jackson, Cecia Ruiz-Hernandez, Kers Ung-Watson, Yessenia Henriquez, Vanessa Marie Booth, Alexia Brown, Darlyn Magana, Bianca Navarro, Nicholas Pereira, Gia Renemae Calip, Lucky Heng, Ralph Sagun, Lucas Abreu, Alexandra Maria Acosta, Tristan Benally, Cosset Hernandez Pena, Adrian Montenegro, Cierra Paaaina-Daquioag, Nicole Torosian, Tracy Fuentes, Julissa Martinez, Medina Mcallister, Michal Newhouse-Van Vlerin, Tiria Carr, Nima Abkenar, Isabella Aceituno, Yuhan Bi, Victoria Campos, Melika Cummings, Zachary J. Johnigan, Alexis Sotolongo-Marin

McNair Journal

Journal articles based on research conducted by undergraduate students in the AANAPISI, LSAMP, and McNair Scholars Program.

Table of Contents

About AANAPISI

Dr. Chris Heavey, Interim President

Dr. Keith Rogers, Vice President for Student Affairs

Ms. Zhanna Aronov, Associate Vice President for Retention & Outreach

Volume 15, Connor Thompson, Emily Steffenhagen, Emily Robertson, Luis Fernando Dos Reis, Emily Farmer, Samuel Villa, Robert Allison, Zachary Chessor, Megan Borden, Austin Burnett, Larry W. Grant Jr., Tristan Marowski, Emma Moore, Pearl Siff

Incite: The Journal of Undergraduate Scholarship

Introduction Dr. Amorette Barber, Director, Office of Student Research

From the Editor Dr. Hannah Dudley-Shotwell

Artist’s Statement Connor Thompson

On Mentorship Dr. John Miller

The Meat of the Matter: Alien, Human, and Animal in Terry Bisson’s “They’re Made Out of Meat” by Emily Steffenhagen

“Please REBLOG!”: An Ethical Analysis of Doxxing, Internet Vigilantism and Racists Getting Fired by Emily Robertson

Journaling: Paper Has More Patience Than People by Luis Fernando Dos Reis

The Effects of Climate Change on the Archaeological World by Emily Farmer

Lowered Seat Height Does Not Impair Wingate Performance in Untrained Cyclists by Samuel Villa, Robert Allison, …

Development Of Radiochemistry Of 52mn For Pet Imaging Applications, James Mokaya Omweri

All ETDs from UAB

No abstract provided.

Impact Of Solar Radiation On Perchlorate Formation In The Atmosphere: Evidence From Ice Core Measurements, Bishnu Kunwar

Electronic Theses and Dissertations

Perchlorate, which derives from both anthropogenic and natural sources in the current environment, poses a substantial health hazard to humans as it competes with iodine uptake in the thyroid gland. Consequently, there has been considerable concern about minimizing human exposure to environmental perchlorate by restricting its release from man-made sources. However, the absence of a clear understanding regarding the respective contributions of man-made and natural sources has hindered widespread regulation efforts. A 300-year (1700–2007) Summit, Greenland ice core record from a previous study showed relatively stable perchlorate concentrations in Greenland snow prior to 1980, with some elevated perchlorate levels associated …

Studies Towards High Surface Area Porous Polymers Via Cross-Coupling Methodology, Anthony Lybrand

Wayne State University Theses

Porous polymers, known for their high internal surface area and robust chemical stability, are promising candidates for applications in gas storage, water purification, energy storage, and catalysis. The Yamamoto-type Ullmann reaction, known for yielding high porosity polymers, serves as a benchmark in this study. However, its limitations as a homocoupling reaction restricts the synthesis of ordered A-B type copolymers. This research addresses this challenge by investigating the use of cross-coupling reactions, particularly the Negishi reaction, to synthesize A-B type copolymers with reduced defectivity and enhanced surface area. The synthesis of fully-metalated intermediates and their subsequent polymerization are discussed in detail. …

Probing Microscopic Properties Of Next Generation Materials Using Coherent Vibrational And Electronic Spectroscopy, S Mudiyanselage Sachithra Tikiri Kumara Wanasinghe

Wayne State University Dissertations

The dissertation research focused on understanding the relationship between the chemical structure of organic molecules and their photophysical properties, particularly examining coherent electronic and vibrational coupling within and between molecules, with implications for next-generation energy technologies. In Chapter 2, we employed both steady-state and transient optical and magnetic spectroscopic techniques to understand the electronic delocalization in both singlet and triplet exciton delocalization in weakly bound porphyrin dimeric molecules. Our results highlight that the delocalization of singlet exciton delocalization does not guarantee the delocalization of triplet excitons between weakly bound porphyrin macromolecules. Our studies demonstrate how one can access the electronic …

Design, Synthesis, And Evaluation Of Class Iia Histone Deacetylase (Hdac) Inhibitors, Lauren Nicole Kotsull

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are linked to disease states, including cancer, and have become important targets for therapeutic development. Many inhibitors have been developed to target HDAC proteins, including FDA-approved inhibitors Vorinostat (SAHA), Belinostat, Romidepsin, and Panobinostat. These inhibitors non-specifically influence most of the 11 metal-dependent HDAC isoforms, which might contribute to the side effects that patients experience during treatment. The lack of selectivity also diminishes the use of HDAC inhibitors as biomedical research tools. To address these drawbacks, the development of selective inhibitors has been heavily studied. Yet, reported inhibitors are predominantly selective for class I HDAC isoforms (HDACs …

Development Of Small Ligands Targeting Pathogenic Rna Repeats In Neurodegenerative Diseases, Zhihua Chang

Legacy Theses & Dissertations (2009 - 2024)

Pathogenic microsatellite RNA expansions are toxic and can cause neuronal degeneration and dysfunction. Therapeutics that eliminate or neutralize these RNA repeats hold great promise for the treatment of many neurodegenerative diseases because they are uniformly fatal but there is no effective treatment available today. New compounds targeting these pathogenic RNA repeat sequences represent new hope to treat these diseases. The overall goal of my dissertation is to develop a high-throughput screening assay to identify small ligands as potential drug candidates against disease-associated RNA repeats and probe binding mechanisms to guide the design of optimized drug candidates, and eventually validate therapeutic …

Harnessing Oxidizing Potential Of Nickel For Sustainable Hydrocarbon Functionalization, Thomas M. Khazanov, Anusree Mukherjee

Research, Publications & Creative Work

While the oxidative chemistry of transition metals such as iron and copper is a highly developed area of investigation, the study of similar chemistry with nickel is much younger. However, nickel offers rich coordination chemistry with oxygen and other oxidants and is a promising avenue of research for applications such as sustainable hydrocarbon functionalization. Herein, we summarize the progress made recently in nickel coordination chemistry relevant to hydrocarbon functionalization and offer our perspectives on open questions in the field.

Pharmacology Of Veratrum Californicum Alkaloids As Hedgehog Pathway Antagonists, Madison L. Dirks, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Veratrum californicum contains steroidal alkaloids that function as inhibitors of hedgehog (Hh) signaling, a pathway involved in the growth and differentiation of cells and normal tissue development. This same Hh pathway is abnormally active for cell proliferation in more than 20 types of cancer. In this current study, alkaloids have been extracted from the root and rhizome of V. californicum, followed by their separation into five fractions using high performance liquid chromatography. Mass spectrometry was used to identify the presence of twenty-five alkaloids, nine more than are commonly cited in literature reports, and the Bruker Compass Data Analysis software …

Developing Methods For Analysis Of Chiral Small Molecules And D-Amino Acid Containing Peptides, Joshua I. Putman

Chemistry & Biochemistry Dissertations - Archive

This dissertation covers the development of methods to analyze chiral small molecules and d-amino acid containing peptides. The first section covers the development of liquid chromatographic chiral screening approaches for newly synthesized chiral molecules. The next part of the dissertation covers methodologies for the analysis of d-amino acid containing peptides. Lastly the bacterial degradation of three commonly used pesticides by bacteria harvested from Colorado potato beetles (Leptinotarsa decemliniata) is presented.

Twelve new azole compounds and eleven racemic ethanolamine derivatives were synthesized. These twenty-three compounds were evaluated using eight chiral columns, four macrocylic glycopeptides, a cyclodextrin derivative …

Opacities Of S-Type Stars: The Singlet B¹⊓−X¹Σ⁺, B¹⊓−A¹Δ, And C¹Σ⁺−X¹Σ⁺ Band Systems Of Zro, Peter F. Bernath, Manish Bhusal, Jacques Liévin

Chemistry & Biochemistry Faculty Publications

The ZrO B¹Π–X¹Σ⁺, B¹Π–A¹Δ, and C¹Σ+–X¹Σ⁺ band systems are important opacity sources in the near-infrared and optical spectra of S-type stars. A total of 21 rovibronic bands with v'' ≤ 7 and v' ⩽ 5 were observed and fit for the B¹Π–X¹Σ⁺ transition, five bands for the ⁹⁰ZrO B¹Π–A¹Δ transition and one band for the ⁹⁰ZrO C¹Σ⁺–X¹Σ⁺ transition. All band …

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

The A²Π–X²Σ⁺ Band System Of Yo, Peter F. Bernath, Manish Bhusal, Adam Pastorek

Chemistry & Biochemistry Faculty Publications

YO bands are conspicuous in the spectra of S stars. The laboratory spectrum of the A²Π–X²Σ⁺ electronic transition has been recorded with a Fourier transform spectrometer using a composite-wall hollow cathode lamp source. The A²Π–X²Σ⁺ transition with v ' ≤ 4 and v'' ≤ 4 has been rotationally analyzed using the modern spectral fitting program PGOPHER. Vibronic band strengths were calculated using an ab initio transition dipole moment function. A line list for the A²Π–X²Σ⁺ transition is provided and can be utilized in the modeling …

Synthesis Of Bis-Thioacid Derivatives Of Diarylethene And Their Photochromic Properties, Pramod Aryal, Jonathan Bietsch, Gowri Sankar Grandhi, Richard Chen, Surya B. Adhikari, Ephraiem S. Sarabamoun, Joshua J. Choi, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Diarylethenes (DAEs) are an important class of photoswitchable compounds that typically undergo reversible photochemical conversions between the open and closed cyclized forms upon treatment with UV light or visible light. In this study, we introduced thioacid functional groups to several photochromic dithienylethene (DTE) derivatives and established a method that can be used to prepare these photoswitchable thioacids. Four thioacid-functionalized diarylethene derivatives were synthesized through the activation of carboxylic acids with N-hydroxysuccinimide, followed by reactions with sodium hydrosulfide with yields over 90%. These derivatives exhibited reversible photoswitching and photochromic properties upon treatment with ultraviolet (UV) and visible lights. The thioacid groups …

Quantification Of Antiretroviral Drug Emtricitabine In Human Plasma By Surface Enhanced Raman Spectroscopy, Marguerite R. Butler, Terry A. Jacot, Sucharita M. Dutta, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

In this study, reproducible label-free detection and quantification of the antiretroviral drug emtricitabine (FTC) down to 78 ng/mL in human plasma by surface enhanced Raman spectroscopy (SERS) is presented. A novel plasma sample pretreatment method using silver nitrate and silver colloidal nanoparticles (Ag CNPs) was used to prepare the plasma samples for analysis. The pretreated plasma samples were evaporated to dryness on an aluminum surface and a computer-controlled Raman scanning system was used to collect spatially resolved SERS spectra of the entire surface. Calibration curves of commercial human plasma samples containing FTC in a concentration range of 5000 to 78 …

Synthesis And Evaluation Of 5-(Heteroarylmethylene)Hydantoins As Glycogen Synthase Kinase-3Β Inhibitors, Nicholas O. Schneider, Keandra Gilreath, Daniel J. Burkett, Martin St. Maurice, William A. Donaldson

Chemistry Faculty Research and Publications

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3β. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17–29) were prepared and evaluated for the inhibition of GSK-3β at 25 μM. The IC50 values of five of these compounds was determined; the two best inhibitors …

Mixed Quantum/Classical Calculations Of Rotationally Inelastic Scattering In The Co + Co System: A Comparison With Fully Quantum Results, Dulat Bostan, Bikramaditya Mandal, Carolin Joy, Michał Żółtowski, François Lique, Jérôme Loreau, Ernesto Quintas-Sánchez, Adrian Batista-Planas, Richard Dawes, Dmitri Babikov

Chemistry Faculty Research and Publications

An updated version of the CO + CO potential energy surface from [R. Dawes, X. G. Wang and T. Carrington, J. Phys. Chem. A 2013, 117, 7612] is presented, that incorporates an improved treatment of the asymptotic behavior. It is found that this new surface is only slightly different from the other popular PES available for this system in the literature [G. W. M. Vissers, P. E. S. Wormer and A. Van Der Avoird, Phys. Chem. Chem. Phys. 2003, 5, 4767]. The differences are quantified by expanding both surfaces over a set of analytic functions and comparing the behavior of …

Visible Opacities Of S-Type Stars: The D³Φ–A³Δ Band System Of Zro, Peter F. Bernath, Manish Bhusal, Jacques Liévin

Chemistry & Biochemistry Faculty Publications

ZrO is a well-studied metal monoxide because of its astrophysical importance in characterizing S stars. The bands of the d³Φ–a³Δ system (γ system) with v′≤4 and v" ≤ 5 are rotationally analyzed using the PGOPHER program to provide spectroscopic constants. The high-resolution ZrO emission spectrum was recorded with a Fourier transform spectrometer using a high-temperature carbon furnace source. New ab initio calculations of the transition dipole moment were carried out in order to determine the vibronic band strengths. The spectroscopic constants, along with the band strengths, are used to calculate a line list for the γ system. This line list …

Assessing Interatomic Potentials For Molecular Dynamics Simulation Of Soybean Oil Pyrolysis, Tanner Garrett Rust

Graduate Theses/Dissertations

The world today relies on hydrocarbon combustion for many reasons, including its high energy density that provides ease of transportation. However, hydrocarbons sourced from fossil fuels are not expected to last forever. Biodiesel, a renewable alternative, has many attractive benefits but comes with other downsides. Biodiesel can gel in cold environments and may leave residue in an engine. Pyrolysis of biodiesel has shown promise in addressing these common detriments. Inducing pyrolysis on biodiesel feedstock (commonly soybean oil in the USA) would be an attractive option presuming it continues to produce fossil fuel analogs similar to biodiesel pyrolysis. Herein, Langevin molecular …

The Kinetic Modulation Of Α - Synuclein Fibrillation And Toxicity By 4-Phenylbutyric Acid, Kristos Awuah Baffour

Graduate Theses/Dissertations

ABSTRACT

The Protein misfolding and aggregation of alpha-synuclein (α-syn) into neurotoxic amyloids underlies the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). 4-Phenylbutyrate (PBA), an FDA drug approved for treating urea cycle disorders, has garnered significant attention as a potential chemical chaperone for targeting alpha-synuclein (α-syn) aggregation. Using in vitro assays, we demonstrated that PBA treatment alters the pattern of α-syn aggregation, as evidenced by reduced formation of oligomeric species and its increased susceptibility to proteolytic cleavage under the influence of PBA. Proteinase K assay, surface plasmon resonance, and Nile red studies indicate that PBA interacts with the extensive …

Geochemistry Of Rare Earth Elements In Simulated Natural Waters: Experiments And Modelling Of Precipitation, Complexation, And Bioavailability., Samantha Zulian

Theses and Dissertations (Comprehensive)

Rare earth elements (REEs) are an important part of modern technology and used for many applications. Mining, agriculture, improper recycling and medical applications can increase the concentration of these elements in surface waters. Metals in the environment including REEs can be found naturally but understanding the implications increase concentrations from anthropogenic inputs is important. REE mobility, persistence and toxicity is imperative to risk assessment as Canada begins to mine REE. Ultimately, as with other metals, the impacts of REEs in the environment should be dependent on the specific physical and chemical forms of the elements. Fractionation provides a practical method …

Coordination Chemistry Using Strategic Design Of Ligands For Switchable Properties, Delara Joekar

Theses and Dissertations (Comprehensive)

Coordination-driven self-assemblies are multifunctional molecular systems that provide an efficient method for miniaturization towards functional devices with diverse applications. Herein, the synthesis of novel pyrazole-based ligands suitable for construction of coordination assemblies is reported. These were designed using a strategy that incorporates the presence of both cationic and anionic coordination sites, and a third site for further functionalization. This design strategy has been used because there is still a knowledge gap for controlling the directionality of weak molecular forces in the presence of stronger competing forces. The structural characterization of these ligands, their Hirshfeld surface analysis, and select coordination complexes …

Chirality Determination Using Three-Wave Mixing Microwave Spectroscopy, Nicole Taylor Moon

Doctoral Dissertations

"Rotational spectroscopy has established itself as a reliable gas-phase spectroscopic technique for the structural determination of molecules. This reliability has stemmed from both advancements in microwave technology and a willingness from the community to push the boundaries of the field. In this dissertation, the boundaries are tested in both how well the technique can determine the structure of molecules exhibiting large amplitude motion and through chirality determination. The first half of this dissertation explores the use of deep averaging to determine the structure of silicon containing molecules in collaboration with Dr. Guirgis from the College of Charleston. For each of …

Design, Synthesis, And Characterization Of Complex Chalcogenides For Energy Storage And Energy Conversion Applications, Srikanth Balijapelly

Doctoral Dissertations

"Through this investigation, complex chalcogenides with the combination of main group metals, transition metals, and rare earth metals have been synthesized using the building block approach and their structure-property relationships are evaluated. The main emphasis of research is on rationally designing new materials for applications in sodium and lithium ion conducting solid electrolytes, cathodes, thermoelectrics, and nonlinear optics. Along with the experimental studies, theoretical calculations are also employed to better understand the physicochemical properties of the synthesized compounds.

The first part of the research will discuss designing alkali ion containing complex chalcogenides using the building block approach. This investigation resulted …

Analytical Methods For Monitoring Traumatic Brain Injury Biomarkers/Treatment And Pharmaceutical Residual Solvents, Olajide Philip Adetunji

Doctoral Dissertations

"The development of highly sensitive and efficient analytical methods utilizing advanced instrumentation is necessary to help improve disease diagnosis and therapeutics. A major neuro-consequence of traumatic brain injury (TBI) is oxidative stress from the generation of reactive oxygen species and the depletion of antioxidant defenses. Alteration in concentrations of certain small molecules also occurs with the disease progression and can help understand TBI pathophysiology. Two analytical methods employing liquid chromatography with tandem mass spectrometry (LC-MS/MS) were developed and validated to monitor the potential small-molecule TBI biomarkers at sub-ppb levels. Subsequently, the neuroprotective effect of an antioxidant prodrug, N-acetylcysteine amide (NACA), …