Chemistry Commons^™

Beyond The Phonon Gas Model (Pgm): Unraveling The Unique Mechanistic Processes Dictating Thermal Transport In Highly Anharmonic And Disordered Materials, Sandip Thakur

Open Access Dissertations

Thermal transport in nonmetallic solids has traditionally been described by the phonon gas model (PGM), in which heat is carried by weakly interacting phonon quasiparticles in an ordered crystalline lattice. However, this model breaks down in materials characterized by strong anharmonicity, dynamic disorder, or structural complexity, features prevalent in many next-generation materials used in energy conversion, optoelectronics, and thermal management. This dissertation investigates thermal transport in such complex materials, including metal halide perovskites (MHPs), covalent organic frameworks (COFs), metal organic frameworks (MOFs), and 2D-3D heterostructures, through large-scale molecular dynamics (MD) simulations and frequency-resolved spectral analyses.

In MHPs, the work reveals …

Long Oligos: Direct Chemical Synthesis Of Genes With Up To 1728 Nucleotides, Yipeng Yin, Reed Arneson, Yinan Yuan, Shiyue Fang

Michigan Tech Publications

The longest oligos that can be chemically synthesized are considered to be 200-mers. Here, we report direct synthesis of an 800-mer green fluorescent protein gene and a 1728-mer Φ29 DNA polymerase gene on an automated synthesizer. Key innovations that enabled this breakthrough include conducting the synthesis on a smooth surface rather than within the pores of traditional supports, and the use of the powerful catching-by-polymerization (CBP) method for isolating the full-length oligos from a complex mixture. Conducting synthesis on a smooth surface not only eliminated the steric hindrance that would otherwise prevent long oligo assembly, but also, surprisingly, drastically reduced …

Enhancing Crispr-Cas12a Activity Through Guide Rna Methylation, Hilal Dagci

Electronic Theses & Dissertations (2024 - present)

CRISPR-Cas12a is a rapidly evolving technology for improved gene editing in cells, as well as in vivo. The system, consisting of Cas12a nuclease and approximately 40-nt long guide RNA (gRNA), can efficiently recognize and cut genomic double-stranded DNA (dsDNA). Chemical modifications to the gRNA can potentially improve its dsDNA binding and enhance Cas12a-mediated nuclease activity. In this work, 5-methyl cytidine (m5C) and N6-methyl adenosine (m6A) were explored to improve the binding between gRNA and target DNA. Phosphoramidites of m5C and m6A were used to construct a library of gRNAs using solid phase RNA synthesis. Tm studies were carried out …

Fabrication Of Functional Microparticles For Biological Analysis, Justin George

Electronic Theses & Dissertations (2024 - present)

To better advance our knowledge of cellular behavior, development of an organism, and disease mechanisms understanding cellular heterogeneity in the functional proteome is essential. Bulk measurements across a cell population often fail to capture the variations which exist between individual cells, however single cell proteomic technology has increasingly demonstrated the characterization of cellular heterogeneity. A single cell functional proteomics assay needs to be both high-throughput and multiplexed to effectively identify biomarkers and provide a quantitative correlation to better understand the interrelationships within complex protein networks. Janus particles have the ability to be engineered to have good compatibility and stability in …

Synthesis And Characterization Of Eco-Engineered Hollow Fe2o3/Carbon Nanocomposite Spheres: Evaluating Structural, Optical, Antibacterial, And Lead Adsorption Properties, Islam Gomaa

Nanotechnology Research Centre

This work presents a facile mechano-thermal route for the synthesis of carbon-decorated, hollow, mesoporous α-Fe2O3 microspheres. Comprehensive characterization (XRD, XPS, FT-IR, SEM/EDX, TGA, zeta-potential) confirmed the formation of phase-pure hematite with nanoscale crystallites (~19 nm), substantial residual surface carbon (~40 wt%) consistent with Fe–O–C linkages, and a positive surface charge (+15.9 mV). The hierarchical hollow/mesoporous architecture enables fast ion transport and provides extensive interior binding sites, resulting in rapid Pb(II) uptake that reaches 92% removal in ≈15 min at pH 5.0. The adsorption follows a Langmuir isotherm (qmax ≈ 70.6 mg/g) and pseudo-second-order kinetics, indicative of chemisorption coupled to efficient …

Investigating The Impact Of Pfas Contamination On Mental Health, Jihyun Kim

Open Educational Resources

To explore the intersection of environmental injustice, racial disparities, and public health through an examination of PFAS contamination in drinking water and its impact on communities of color. This study will address environmental, social, and health implications of PFAS exposure, with a specific emphasis on promoting equity and advocating for policy changes to rectify systemic inequalities.

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Chemoproteomic Profiling Of A Carbon-Stabilized Gold(Iii) Macrocycle Reveals Cellular Engagement With Hmox2, Sailajah Gukathasan, Chibuzor Ngozi Olelewe, Libby Ratliff, Jong H. Kim, Alyson M. Ackerman, J. Robert Mccorkle, Sean Parkin, Gunnar F. Kwakye, Jill M. Kolesar, Samuel G. Awuah

Chemistry Faculty Publications

In this work, we discovered a novel organometallic gold(III) macrocycle, Au-Mac1, that demonstrates anticancer potency in a panel of triple-negative breast cancer cells (TNBC), and based on this complex, a biotinylated-Au-Mac1 probe was designed for target identification via chemoproteomics, which uncovered the engagement of HMOX2 of the heme-energy metabolism pathway. Using orthogonal chemical biology and molecular biology approaches, including immunoblotting, flow cytometry, and cellular thermal shift assays, it was confirmed that Au-Mac1 engages HMOX2 in cells. Downstream effects of Au-Mac1 on the depletion of mitochondrial membrane proteins and bioenergetics point to the potential role of HMOX2 in cancer. Importantly, Au-Mac1 …

Electrochemical Observation And Ph Dependence Of All Three Expected Redox Couples In An Extremophilic Bifurcating Electron Transfer Flavoprotein With Fused Subunits, Debarati Das, Wassim El Housseini, Monica Brachi, Shelley D. Minteer, Anne-Frances Miller

Chemistry Faculty Publications

Bifurcating enzymes employ energy from a favorable electron transfer to drive unfavorable transfer of a second electron, thereby generating a more reactive product. They are therefore highly desirable in catalytic systems, for example, to drive challenging reactions such as nitrogen fixation. While most bifurcating enzymes contain air-sensitive metal centers, bifurcating electron transfer flavoproteins (bETFs) employ flavins. However, they have not been successfully deployed on electrodes. Herein, we demonstrate immobilization and expected thermodynamic reactivity of a bETF from a hyperthermophilic archaeon, Sulfolobus acidocaldarius (SaETF). SaETF differs from previously biochemically characterized bETFs in being a single protein, representing a …

Functional Utility Of Gold Complexes With Phosphorus Donor Ligands In Biological Systems, Adedamola S. Arojojoye, Samuel G. Awuah

Chemistry Faculty Publications

Metallo-phosphines are ubiquitous in organometallic chemistry with widespread applications as catalysts in various chemical transformations, precursors for organic electronics, and chemotherapeutic agents or chemical probes. Here, we provide a comprehensive review of the exploration of the current biological applications of Au complexes bearing phosphine donor ligands. The goal is to deepen our understanding of the synthetic utility and reactivity of Au-phosphine complexes to provide insights that could lead to the design of new molecules and enhance the cross-application or repurposing of these complexes.

Purification Of Recombinant His6-Gfp-Preptin Fusion Protiens, Apoorva Kollaram

Theses and Dissertations

Preptin, a 34-amino-acid peptide derived from proinsulin-like growth factor II, has emerged as a promising therapeutic candidate for both Type 2 diabetes mellitus and osteoporosis. Its dual functionality—stimulating insulin secretion without inducing hypoglycemia and promoting osteoblast proliferation—positions it as a unique alternative to traditional sulfonylureas and osteogenic agents. In this study, we developed a purification protocol for green fluorescent-preptin fusion proteins. These fusion proteins will be used to investigate the functional significance of residues Pro17, Val18, Gly19, Trp27, Lys28, and Gln29 in rat preptin, which shares high sequence similarity with the human form. Site-directed mutagenesis was performed using NEB Q5 …

Structural Optimization And Stability Enhancement Of Uba(2) And Ntl9 Using The Computational Tool: Emcast, Bahar Ghazi Esfahani

Graduate Student Theses, Dissertations, & Professional Papers

This study enhances protein stability prediction by refining EmCAST (Empirical C-Alpha Stability Tool), a computational tool used to identify stabilizing mutations in protein domains. We applied EmCAST to two model proteins: the α-helical ubiquitin-associated domain 2 (UBA(2)) and the α/β N-terminal domain of ribosomal protein L9 (NTL9). Protein stability is critical for proper function, and mutations can lead to misfolding and disease. To validate EmCAST’s predictions, guanidine hydrochloride-induced denaturation was monitored using circular dichroism (CD) spectroscopy for both wild-type and mutant variants. Results guided refinements to EmCAST’s algorithm, incorporating new experimental datasets to improve accuracy. Additionally, we examined the assumption …

Development Of Fast And Comprehensive Approaches For Gunshot Residue Interpretation Using Ambient Ionization, Mass Spectrometry, And Microparticle Sampling Studies, Thomas Dimmey Ledergerber

Graduate Theses, Dissertations, and Problem Reports (ETD)

The information derived from the forensic examination of gunshot residue (GSR) can be critical during the investigative and trial stages in the criminal justice system. However, the complexity of the GSR deposition, transfer, and persistence mechanisms calls for meticulous handling and identification processes. Novel advances in evidence interpretation and analysis via instrumental methods are current areas of growing interest that must be pushed along the chain from research to practice in a timely manner. Therefore, this research focuses on developing both rapid and comprehensive methods for detecting gunshot residue evidence and effectively communicating its significance to the investigators or trier …

3d Printed Microfluidic Platforms For Elisa-Based Diagnostics: Advancing Toward Point Of Care, Brandi Marie Binkley

Graduate Theses, Dissertations, and Problem Reports (ETD)

Protein biomarker detection is a critical analytical method for quantifying proteins in biological samples. It is relevant not only in medical diagnostics and research but also numerous other fields such as environmental monitoring, pharmacology, food safety, and biotechnology. Sensitive detection at picogram-per-milliliter (pg/mL) levels is essential for diagnosing diseases, monitoring progression, and tailoring treatments, especially for low-abundance biomarkers like troponin, interleukin 6, carcinoembryonic antigen (CEA), activin A, and vascular endothelial growth factor (VEGF). Immunoassays, particularly enzyme-linked immunosorbent assays (ELISAs), are the gold standard for protein biomarker detection due to their high specificity and sensitivity. The development of point-of-care (POC) diagnostic …

Developing Consensus-Based Methods For The Examination And Interpretation Of Contemporary Vehicle, Architectural, And Portable Electronic Device Glasses By Micro-X-Ray Fluorescence Spectrometry, Zachary Bailey Andrews

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glass is a trace material that is commonly encountered during investigations of violent crimes. When glass is recovered at crime scenes, it can be used to establish links between suspects, victims, and the scene itself. The most discriminatory form of analysis for glass evidence is elemental analysis, and micro-X-ray fluorescence spectrometry (µXRF) is becoming an increasingly common technique used for this purpose. Recent advances in µXRF technology, such as the introduction of silicon drift detectors (SDD) and improved polycapillary optics are promising in enhancing the capabilities for the examination of glass evidence in forensic investigations. However, along with these advances …

Functionalized Carbon Nanohoops: Synthesis, Structural Insights, And Pathways To Carbon Nanobelts, Liu Li

Graduate Theses, Dissertations, and Problem Reports (ETD)

The development of structurally defined carbon nanostructures has gained significant attention due to their unique electronic, optical, and mechanical properties. Cycloparaphenylenes (CPPs), also known as carbon nanohoops, and carbon nanobelts (CNBs) represent key molecular segments of carbon nanotubes (CNTs), offering a bottom-up approach to precise nanotube construction. This dissertation focuses on the synthesis, structural characterization, and functionalization of CPPs, as well as the development of novel synthetic pathways for CNBs. A series of functionalized CPPs, including [9]-, [12]-, [15]-, and [18]CPPs, were synthesized using a modular approach involving a Diels-Alder adduct formation followed by a Ni(cod)2/bpymediated macrocyclization reaction. The influence …

Individual And Collective Properties Of Tunable Photochemical Belousov-Zhabotinsky Micro-Reactors, Kudakwashe Benedict Shumba

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cell-like model chemical systems are powerful tools that can be used to explore the role of intercellular coupling on population level behaviors in communities of biological cells. Firstly, we present a new method for fabricating such micro-reactors using the photosensitive Belousov–Zhabotinsky (BZ) reaction system employed in silica microparticles. These BZ micro-reactors have a tunable response to photochemical coupling, varying from a fully excitatory response to a fully inhibitory response. Their response can be tuned through variations in either the reactive mixture or, on an individual micro-reactor level, by changes in the synthesis temperature used during the fabrication of the silica …

Rational Design Of Small Molecules Targeting Mitochondrial Redox Proteins, Matheus Barbosa Belchior

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reactive oxygen species play a crucial role in many cellular processes. Despite being a natural byproduct of cellular metabolism, overexpression of these species causes damage to the cell, leading to cell dysfunction. Central to the regulation of these highly reactive molecule is the mitochondria. Impairment in its function has been associated with oxidative stress within the cell. Herein, a ligand-based and structure-based approach to design new small molecules to inhibit mitochondrial redox proteins associated with oxidative stress and reactive oxygen species. In the first project two molecules were synthesized and characterized as potential monoamine oxidase B inhibitors. Results showed two …

Microwave Assisted Syntheses And Characterizations Of Near-Infrared Ratiometric Probes For Mitochondrial Ph Detection And Monitoring, Ronald J. Schwandt

Dissertations, Master's Theses and Master's Reports

Within the field of biochemistry, there has been a significant development of ratiometric fluorescent probes designed for mitochondrial pH detection; however, many of these probes have emissions within the visible spectrum and require long synthesis times with low-yield reactions. However, in recent years, microwave-assisted syntheses of organic molecules have led to significant increases in reaction yields and quicker reaction times. In this work, two common reactions in probe synthesis, Heck coupling, and Knoevenagel condensations are investigated using microwave-assisted synthesis. It was found the low-concentration Heck coupling reactions using palladium (II) acetate led to extremely efficient Heck coupling. Also, a novel …

Multiscale Computational Chemistry Studies Of The Catalytic Mechanisms Of Non-Heme Fe(Ii)/2-Oxoglutarate-Dependent Oxygenases, Simahudeen Bathir Jaber Sathik Rifayee

Dissertations, Master's Theses and Master's Reports

Enzymes catalyze complex biological transformations. Non-heme Fe(II)/2-oxoglutarate (2OG)–dependent enzymes are highly versatile catalysts capable of selective C–H oxidation, enabling transformations such as hydroxylation, halogenation, desaturation, demethylation, ring rearrangements, epoxidation, and electrophilic aromatic substitution. These enzymes are involved in various biological processes, including fatty acid metabolism, hypoxic signaling, collagen maturation, and transcriptional regulation. Computational Modeling provides detailed knowledge of the enzymes including atomistic details of the important catalytic species, conformational and electronic effects, which are crucial to enzyme engineering and drug design efforts. This dissertation implements advanced multi-scale molecular modelling techniques including Molecular dynamics and Quantum Mechanic / Molecular Mechanics calculations …

Chromatographic And Electrophoretic Analysis Of Lignin-Derived Monomers And Dimers: Extraction Method Development And Evaluation Of Cyclodextrins For Recovery, Anjam Sadik

Theses and Dissertations--Chemistry

Biorefineries play a vital role in reducing dependence on fossil fuels and addressing global warming concerns. Unfortunately, investment in biorefineries remains limited due to economic sustainability concerns. One approach to enhance the economic viability of biorefineries is by fully utilizing the potential of feedstocks, particularly lignocellulosic biomass, which is commonly used in these processes. Traditional processing methods often alter the lignin portion of biomass, making it unsuitable for further utilization. However, when retained in its native form, lignin can serve as a valuable source of chemicals that contribute to the economic sustainability of biorefineries.

The lignin-first approach, which removes lignin …

Catalytic Deoxygenation Of Oleaginous Biomass To Renewable Diesel And Sustainable Aviation Fuel Via Decarboxylation/Decarbonylation, Chukwudalu Great Umenweke

Theses and Dissertations--Chemistry

Several technologies have been developed to produce hydrocarbon biofuels – renewable diesel (RD) and sustainable aviation fuel (SAF) – from fats, oils, and greases (FOG), with the hydroprocessing of esters and fatty acids (HEFA) representing one of the most mature pathways. In its current form, HEFA is mainly reliant on the hydrodeoxygenation (HDO) reaction, which has several drawbacks since HDO requires large amounts and pressures of hydrogen, feedstocks of high purity and cost, as well as problematic sulfided catalysts that risk contaminating the biofuel product with sulfur. A process based on decarboxylation/decarbonylation (deCO_x) offers an attractive alternative to …

Insights Into Factors Influencing Radical Coupling Chemistry Of Monolignols During Lignification And Induced Changes In Plant Secondary Metabolism, Rachel Poornima Sutherland

Theses and Dissertations--Chemistry

Lignin is a complex aromatic biopolymer and an important constituent in plant cell walls. The process of lignin biosynthesis, known as lignification, is poorly understood and challenging to study but has important implications in a variety of fields including sustainable energy, bioengineering, and materials science and is therefore of interest to pursue. In the final stage of lignification, H-, G-, and S-monolignols are oxidized by laccase and peroxidase enzymes to generate radical species that couple to form dimers and further oligomeric species to ultimately produce the lignin polymer. Biomimetic lignin model systems utilize in vitro oxidative coupling reactions as an …

Development And Applications Of Capillary Vibrating Sharp-Edge Spray Ionization Coupled With Atmospheric Pressure Chemical Ionization (Cvssi-Apci), Madison Elizabeth Pursell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mass spectrometry (MS) is a technique that is used in fields in which both complex and non-complex mixtures are analyzed. The state-of-the-art ion sources that are utilized for MS are being demonstrated to be functional for direct infusion of samples as well as for use with online separations. However, ion sources, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) can encounter problems such as ion suppression and an inability to ionize based on size and/or polarity, respectively. Further these sources are bulky and require gas flow, heat sources, and additional high voltage power supplies for optimal performance. …

Redox Control In A Fused Electron Transfer Flavoprotein From A Thermophilic Archaeon And Expanded Significance Of A Hydrogen Bond From A Conserved Histidine Residue That Contributes To Flavin Redox Tuning And Activation For Covalent Modification, Debarati Das

Theses and Dissertations--Chemistry

In absence of O₂ as terminal electron acceptors in anaerobic bacteria and archaea, carbohydrate metabolism is 15 times less efficient compared to aerobic energy metabolism resulting in energy deficit conditions. Despite their meager resources these anaerobes were able to generate H₂ and a chemiosmotic potential able to drive energy demanding reactions such as CO₂ or N₂ fixation. These observations raised concerns as production of high energy reductants (H₂) from mediocre fuels (NADH) defied the laws of thermodynamics.

In 2008, a known mechanism “electron bifurcation” but with flavins as redox mediators instead of quinones was …

Towards Automating The Study And Discovery Of Electroactive Π-Conjugated Molecules, Rebekah Ann Duke-Crockett

Theses and Dissertations--Chemistry

Chemistry is entering a new paradigm of automation and data-driven discovery. Automated discovery is grounded in well-curated “big data.” As generative and predictive models fueled by simulation data see growing success, emerging robotic automation enables the generation of unprecedented volumes of experimental data. Automation-powered, data-driven approaches hold tremendous potential for groundbreaking insights and innovations, particularly in the study and discovery of electroactive π-conjugated molecules. Realizing this potential, however, requires democratizing chemical data and the automation needed to generate and use it. There is a need to expand access to the tools for findable, accessible, interoperable, and reusable (FAIR) data management …

Design And Synthesis Of Novel Ligands For Bioorthogonal Catalysis, Asymmetric Synthesis, And Ferromagnetic Behavior, Alexander G. Olivelli

Theses and Dissertations--Chemistry

Small molecule metal complexes have diverse applications including usage as catalysts, single molecule magnets, photosensitizers and pharmaceuticals. The first research project in this work reports a new ligand which dimerizes upon coordination to afford a trinuclear Cu(I) complex. Due to the coordination geometry of the Cu(I) metal centers, paired with the strong nitrogen coordinating groups, the resulting complex is resistant to oxidation even in the presence of strong oxidants. The complex is shown to be efficient in the CuAAC reaction and used to tag anticancer drug candidates in vitro. The next project focuses on a series of amidine-based ligands featuring …

Machine Learning Models For Molecular-Based Functional Organic Materials, Moses Ogbaje

Theses and Dissertations--Chemistry

Organic semiconductors (OSC) are of interest for a wide range of flexible optoelectronics applications, including transistors, solar cells, and sensors, to name a few. Despite their promise, the design and optimization of OSC pose significant challenges due to the complexity of the structures of the molecular building blocks, varied packing configurations of these building blocks in the solid state, which impacts the optical and electronic response, and sensitivity of the solid-state packing to material processing conditions. Accurately predicting the solid-state properties of OSC traditionally requires high-level quantum mechanical methods. These methods, however, can be computationally demanding, particularly for large molecules …

Investigation Of D-Π-A Re (1) Complexes For The Homogenous Photocatalytic Reduction Of Co2, Ryan M. Chafin

Theses and Dissertations--Chemistry

Increasing anthropogenic emission of CO₂ into the atmosphere is a global issue that shows no signs of deceleration due to the current trends in dependencies on fossil fuels for energy demand. Although deleterious in nature, this greenhouse gas can serve as a useful feed-stock for the production of small-carbon-chain commercial chemicals if the factors owing to its inertness can be overcome. Fortuitously, CO₂’s chemically inert nature is already circumvented in nature through an elegant cascade of biochemical reactions known as photosynthesis, which nearly all plants and some families of bacteria exploit to produce simple sugars for metabolic …

Investigation Of Protein-Ligand Binding Interactions Through The Computational Methods Of Molecular Dynamics And Graph Neural Networks, Alexander Benjamin Wroe

Graduate Theses, Dissertations, and Problem Reports (ETD)

Studies in protein ligand binding are a significant focus in the field of medicinal chemistry

and biochemistry, facilitating a greater understanding of the structure-function relationship

of the protein and controlling function via drug development. In this research, we identify

new binding sites for lipids on the microbial membrane protein, proteorhodopsin, and apply

machine learning approaches to accelerate the generation of binding affinity-like data for the

use in the identification of potential small molecule drugs. The platelet activating factor

receptor. Cardiolipin, a lipid in membranes, and proteorhodopsin, a microbial proton pump,

are both commonly found in microbial membranes, but little is …