Chemistry Commons^™

Elucidation Of Spin-Hamiltonian Parameters Via Spectroscopy, Magnetization, And Computation, Joshua C. Mengell

Chemistry and Chemical Biology ETDs

Molecular Quantum Information Science (QIS) is fundamentally concerned with using spin-systems as quantum bits (qubits) or as sensors. Prerequisite to using molecular systems for QIS applications, it must be understood how one can design molecules with bespoke magnetic characteristics. Herein we study various paramagnetic molecular compounds, describing their complex magnetic characteristics using a spin-Hamiltonian formalism. We utilize various (sometimes novel) methods for determining these spin-Hamiltonian parameters. Many of these molecules possess magnetic characteristics, which make them attractive as qubits or for sensing applications. These characteristics include higher total spin-states (qudits—S_T>1/2), forbidden interstate electronic transitions, systems of spatially distant …

Exploring The Nature And Role Of Local Cation Ordering In Disordered Rock Salt Cathodes For Li- And Na-Ion Batteries, You Wang

Chemistry and Chemical Biology ETDs

Cation-disordered rock-salt (DRX) cathodes provide a highly tunable platform for next-generation Li- and Na-ion batteries, but their electrochemical behavior is strongly influenced by local structural features hidden in average crystal structures. This dissertation systematically investigates local cation ordering in Li- and Na-based DRX cathodes to understand its effects on Li+/Na+ transport, redox activity, structural evolution, and electrochemical performance. In Li-based systems, Raman spectroscopy and electrochemical analysis reveal that local layered cation ordering in Mn- and Fe-based DRX cathodes is closely correlated with electrochemical behavior. Over-stoichiometric Li-based DRX oxyfluorides further demonstrate that excess Li can regulate local cation ordering, improve Li+ …

Nanoscale Structure And Spontaneous Self-Assembly Of Hydrothermal Organic Products, Glorianne P. Dorce

Chemistry and Chemical Biology ETDs

Carbon nanomaterials derived from citric acid and urea exhibit behaviors that challenge conventional structure–property models based on static bulk descriptions. This study examines how precursor pairing and reaction duration, post‑synthetic thermal history, and time‑dependent aging govern nanoscale organization and optical response. Through controlled synthesis and processing, distinct nanostructures with tunable structural and spectroscopic profiles are generated.

A multiscale framework integrating nano‑FTIR, atomic force microscopy, and thermal analysis reveals chemical heterogeneity and continuous structural reorganization across length scales. By correlating local chemical environments with optical behavior, we show that fluorescence efficiency and photostability depend on specific nanoscale architectures rather than average …

Computational Design Of Peptides And Proteins Through Machine Learning Approaches, Emily J. Hendrix

Chemistry and Chemical Biology ETDs

Advancements in machine learning have emerged as a pivotal tool in computational biochemistry, offering new advancements to address challenges in protein structure and function. However, current machine-learning approaches offer limited insight in understanding protein dynamics. The purpose of this work is to combine traditional physics-based computational tools, such as molecular dynamics and coarse-grained simulations, with recently developed AI-driven computational tools to bridge gaps and advance the understanding of proteins in both structural and dynamic aspects. I investigated several approaches such as (i) traditional physics-based methods to study protein conformation and ensembles; (ii) identifying a peptide inhibitor for the PICK1 PDZ …

A Mutational Analysis Of Thatisin: How Single Point Mutations Impact The Biosynthetic Process Of A Group 16 Graspetide, John F. Boynton Jr

Chemistry and Chemical Biology ETDs

Abstract:

Graspetides are a family of Ribosomally synthesized and Post-translationally modified Peptide (RiPP) natural products named for their ATP Grasp Macrocyclases. We identified several Graspetide Biosynthetic Gene Clusters containing common double glycine cleavage motifs and attempted characterization of the mature Graspetides. One of the resulting peptides, Thatisin, has a topology with two interlocking macrolactones installed by a single ATP Grasp Ligase named ThtC. Here we use single and double point mutations to observe the impact or variation on the installation of these macrocycles. Alanine scan mutagenesis is used to assess leader peptide residues in the precursor peptide ThtA to determine …

A Study Of Machine Learning Techniques In Solving Biochemical And Chemical Problems, Kenneth Micheal Plackowski

Chemistry and Chemical Biology ETDs

Data-driven approaches to solving problems in biology and chemistry require utilization of reliable techniques and machine learning algorithms are the modern reliable approach. This work presents three problems that involve use of supervised learning techniques when classification is the goal and unsupervised learning techniques when global data representation is the goal.

In the first problem, we demonstrate the use of unsupervised clustering techniques, self-organizing maps and K-means, to ascertain analyte detection capabilities of carbon nitride dots. In the second problem, we add scalability features to a functional group classification model applied to infrared data and evaluate its ability to inform …

The Delocalized Toolbox: Tuning Strain, Energetic And Optoelectronic Properties Of Aryl Heterocyclic Scaffolds For Application-Driven Endeavors, Michael Josef Holzmann

Chemistry and Chemical Biology ETDs

This is a three-part dissertation. Part 1 is composed of chapters 1-3 which revolves around the optimization of cyclononyne reactivity towards 1,3 dipolar cycloadditions. Specifically, the synthesis and reactivity of sulfate, sulfamate and sulfamide-bearing cyclononynes will be discussed. Chapters 4-5 comprise Part 2 which addresses optimization of ruthenium olefin metathesis towards reversible activation and inhibition. The mechanism of reversible inhibition mediated by a hexaarylbiimidazole photo-inhibitor will be elucidated. Part 3 consists of chapters 6-8 which describes structure-functional relationship studies on carbon dots and harnessing that insight for sensing applications. Data relating to assays performed with explosive analytes will be analyzed …

Drug Targets Illumination: An Evidence-Based Data Analytics & Informatics Approach To Hypothesis Generation Through Clinical Trials And Genomic Variants, Jeremiah I. Abok

Chemistry and Chemical Biology ETDs

DRUG TARGETS ILLUMINATION: AN EVIDENCE-BASED DATA ANALYTICS & INFORMATICS APPROACH TO HYPOTHESIS GENERATION THROUGH CLINICAL TRIALS AND GENOMIC VARIANTS

Target Illumination Clinical Trial Analytics with Cheminformatics (TICTAC) introduces a scalable data integration pipeline that aggregates multivariate clinical trial evidence to systematically rank disease–target associations. By harmonizing metadata from AACT and employing confidence-scoring techniques, TICTAC facilitates hypothesis-driven target selection for drug discovery, enabling a data-driven approach to therapeutic development. In parallel, a bioinformatics-driven analysis of gnomAD exome mutations in the ZPR1 gene highlights the broader role of genetic variants in disease association. By employing variant effect predictors, protein stability modeling, and …

Excited State Processes In Radical Elaborated Platinum Donor-Acceptor Complexes, Sangita Paudel

Chemistry and Chemical Biology ETDs

Organo-transition metal complexes are being widely studied to understand their photophysical properties for their wide range of applications as efficient emitters in organic light emitting diodes (OLEDs), light emitting electrochemical cells (LEECs), etc. Cyclometalated organo-transition metal complexes such as cyclometalated square planar platinum(II) complexes are becoming suitable candidates for such applications because of their highly efficient luminescence. Understanding the excited properties of such complexes is useful in designing highly efficient and color tunable phosphors with desired excited state lifetimes. We aim to explore the influence of radical substituents on electronic structure, luminescence quantum efficiencies, and excited state lifetimes by synthesizing …

Theoretical And Spectroscopic Insights Into Molybdenum- And Tungsten-Sulfur Bonding, Jesse Lepluart

Chemistry and Chemical Biology ETDs

Molybdenum and tungsten chemistry in biology is dominated by bonding interactions with sulfur and the other chalcogens. The highly-conserved structures of these enzymes’ active sites suggest an early evolution in the history of life, with molybdenum and/or tungsten enzymes likely expressed by the last universal common ancestor. Despite their active site similarities, molybdenum and tungsten enzymes catalyze a diverse array of reactions via equally diverse mechanisms. A deep understanding of the electronic structures of these enzyme active sites and their catalytic intermediates is key to understanding this remarkable chemistry.

The work presented here aims to deepen the understanding of molybdenum …

Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat

Chemistry and Chemical Biology ETDs

Human disease is often thought of as an all or nothing prospect, either one has the disease or one does not. This does not bear out in clinical or personal experiences, instead demonstrating that disease occurs within a spectrum ranging from presumed unaffected to demonstrably and detrimentally affected.Neimann-Pick disease is one example of this spectrum look into diseased states, with multiple named versions of a phenotypically similar disease. We focus on Neimann-Picktype C (NPC), which is the result of a disruption in the efflux of cholesterol and sphingolipids from the endocytic pathway. NPC demonstrates this concept of a spectrum of …

Molecular Dynamics Insights Into The Structural Behavior And Interactions Of Complex Biological Systems, Shenghan Song

Chemistry and Chemical Biology ETDs

All-atom molecular dynamics (MD) simulations are essential for examining the structural and dynamic aspects of proteins at high resolution, complementing experiments limited by resolution, size, and complexity. Advancements in algorithms and hardware have enhanced the role of computational tools in scientific research, allowing for more accurate simulations of proteins with standard residues. However, simulating real biological systems, which include non-standard residues such as lipid membranes, remains challenging despite the assistance of tools like CHARMM-GUI. My research initially focused on simulating the PICK1 BAR dimer using steered MD simulations to investigate its structure and dynamics. Simulation works expanded to include systems …

Exploring The Complex Landscape Of Proteins: From Intrinsically Disordered Proteins To Peptidomimetics Through Computational Approaches, Tongtong Li

Chemistry and Chemical Biology ETDs

Protein function is closely related to their three-dimensional structures. However, some proteins lack a well-defined structure, so-called intrinsically disordered proteins (IDPs). They prefer to interconvert among different conformations in isolation and undergo a disorder-to-order transition upon binding to a partner. IDPs or proteins with intrinsically disordered regions (IDRs), constituting a large portion of the human proteome, are involved in many cellular activities and are therefore highly relevant to our health. In my dissertation, I used computational methods to systematically study systems including dynamic proteins, disordered proteins in complex with their targets, and synthetic peptidomimetics to reveal the unique physical properties …

Investigating The Structural Ensemble And Dynamic Interactions Of Protein Interacting With C-Kinase 1 (Pick1) Using Computational Tools, Amy E. Stevens

Chemistry and Chemical Biology ETDs

Protein Interacting with C Kinase-1 (PICK1) is a scaffolding protein that offers a promising solution to support individuals suffering from substance use disorders. While many efforts have been put towards identifying small-molecule drugs with the potential to target PICK1 and ultimately support individuals suffering from the effects of substance use disorders, all efforts have so far fallen short. The purpose of this work is to use computational tools to assist the design of a small-molecule inhibitor of PICK1 while also advancing the knowledge of its biological functions. This work provides information that is currently missing the field by (1) revealing …

Syntheses And Characterization Of Photoactive Ruthenium And Iron Polypyridyl Complexes, Rajani Thapa Magar

Chemistry and Chemical Biology ETDs

Within this dissertation, two distinct classes of metal complexes have been discussed that bear significance in the field of solar energy conversion, photo redox catalysis and memory devices. The first class of the metal complexes is a series of photochromic Ruthenium polypyridyl N-heterocyclic carbene tethered sulfoxide complexes that are reported to undergo unusually slow isomerization from S-bonded to O-bonded and unusually fast thermal reversion from O-bonded to S-bonded configuration. The role of NHC in the excited state dynamics of these complexes have been discussed in detail in Chapter 3.

For the first time in two decades, structural information of the …

Synthesis And Reactivity Of Heteroatom Embedded Cycloalkynes In Spaac, Nickel Catalyzed Alkylarylation Of Alkenes, And Carbofluorination Of Alkynes, Namrata Khanal

Chemistry and Chemical Biology ETDs

Part I covers Chapters 1, 2, and 3

cycloaddition reactions, that is utilized in biorthogonal chemistry. This metal free version The strain promoted azide-alkyne cycloaddition (SPAAC) reaction is one of the popular 1,3-dipolar of click reaction offers advantage over copper catalyzed click reaction. Since it eliminates the use of copper that is toxic to cells, it is considered favorable for biocompatible reaction. Due to the increased reactivity with dipoles without the use of metal catalyst, cycloalkynes, in particular cyclooctynes, have been employed as the biorthogonal reagent in biorthogonal chemical reaction for the study of a biological processes in vivo. The …

Photophysical Properties Of Synthetic Oligomeric Phenylene Ethynylene, Hugh F. Fritz Jr.

Chemistry and Chemical Biology ETDs

Oligomeric Phenylene Ethynylenes (OPEs) are a class of synthetically prepared compounds with the basic structure of phenylene rings connected by triple-bonded carbon atoms, also known as an ethyne link. This structure can be modified by incorporating functional groups onto one or more of the phenylene rings. The addition of functional groups, such as sulfoxide or imidazole, may alter the photophysical properties in detectable ways. The photophysical techniques used in this report include fluorescence, spectroscopy in the ultraviolet and visible light range (UVVIS), and photon-based excitation using a photo chamber.

One attractive function of OPEs is their antimicrobial property. Previously published …

Methods Of Magneto-Optical Spectroscopy And Analysis For Porphyrins And Polymer Thin-Films, Emigdio E. Turner

Chemistry and Chemical Biology ETDs

This dissertation describes the construction of two high precision magneto-polarimeters for performing Faraday rotation and Magnetic Circular Dichroism (MCD) measurements of polymer thin-films. There is a focus in materials science on the development of thin-film magneto-optically active materials. These materials could allow for the construction of a thin-film optical diode, an important device for next-generation photonic technology. Upon completion of the Faraday rotation spectrometer, two publications were generated from Faraday rotation measurements of novel polymer thin-film materials.

With growing interest by materials scientists in magneto-optically active transition-metal containing materials, an MCD spectrometer was constructed to study these materials. This spectrometer …

Mechanisim Of Plasmon-Driven Photochemical Reactions, Hamed Kookhaee

Chemistry and Chemical Biology ETDs

Understanding a photocatalytic reaction condition that selectively leads to a desired product on metal surfaces is a longstanding research problem in heterogeneous catalysis. Here, using plasmon enhanced N-demethylation of methylene blue (MB) as model reaction, we show that high degree of product selectivity can be achieved by switching the mechanism from charge transfer to adsorbate electronic excitation and vice versa using surface ligands. In the presence of cetyl trimethyl ammonium bromide (CTAB) surface ligand on gold nanoparticles, MB is selectively transformed to thionine at 633 nm excitation wavelength that overlaps with the electronic transition of the adsorbate. At resonant excitation …

Synthesis, Characterization And Spectroscopic Studies Of Novel Donor-Acceptor Complexes, Shiyue Gao

Chemistry and Chemical Biology ETDs

Square-planar compounds of the (dichalcogenolene)Pt(diimine) series are possess unique photophysical properties that include long-lived excited state lifetimes, which result in their being potential candidates for numerous applications. These applications include solar energy conversion, photocatalysis, nonlinear optics, and photoluminescent probes of biological systems. The most interesting feature of the (dichalcogenolene)Pt(diimine) series of molecules is the bpydichalcogenolene ligand-to-ligand charge transfer (LL’CT) band. To better understand their photoluminescent decay mechanism, and understand their excited dark state properties, we have synthesized and characterized new compounds that include (Thp-bpy)Pt(CAT), (Thp2-bpy)Pt(CAT), (Thp-bpy)Pt(bdt), and (Thp2-bpy)Pt(bdt). Through interpretation of electronic absorption, resonance Raman, XAS, photoluminesce spectroscopy, in addition …

Toward The Yeast Surface Display Of Microviridin B, Jillian Leigh Stafford

Chemistry and Chemical Biology ETDs

Humans have turned to natural products for medicinal therapeutics for millennia. In recent years, the ribosomally synthesized and post-translationally modified peptide (RiPP) class of natural products have garnered a lot of attention due to their ability for heterologous expression, relative ease of mutation, and vast biological activates. Microviridins are a family of RiPPs that contain a tricyclic cage-like structure through the formation of two lactone rings and one lactam ring catalyzed by two ATP-grasp ligase family enzymes. Microviridins are potent inhibitors of serine proteases and mutational studies of a small number of residues indicates the potential of peptide engineering protease …

Theoretical Studies Of Molecule-Surface Interactions And Dynamics, Yingqi Wang

Chemistry and Chemical Biology ETDs

Gas-surface scattering involves the conversion of energy in different forms in the impinging molecule, possible bond breaking and forming, and the energy transfer across gas-solid interface. Possible energy dissipation channels include adiabatic energy transfer to the motion of surface phonons and non-adiabatic interactions with surface electron-hole pairs. A complete understanding of the interplay of energy dissipation and physical/chemical changes in the molecule is vital for many important applications such as materials fabrication and heterogenous catalysis.

Gas-surface encounters may occur where non-adiabatic effects are negligible. Two such systems were investigated, both with ample experimental data. One is concerned with the scattering …

Computational, Synthetic And Spectroscopic Studies On Donor Acceptor Transition Metal Complexes, Ranjana Dangi

Chemistry and Chemical Biology ETDs

Fundamental advances in our ability to design and construct electronic components at the nanoscale will require new design paradigms. One proposed nanoscale electronic component is the molecular rectifier. Molecular and molecule-based electronic components are advantageous due to their ease of synthetic manipulation, and the fact that the size dimensions of molecules are inherently at the nanoscale (0.5 - 3nm). Our group has shown how the Donor-Bridge-Acceptor biradical approach can be used to derive key structure-property relationships that allow insight into the choice of bridge fragments for molecular rectification by using constitutional isomers of the donor-bridge-acceptor biradical (NN-Th-Py-SQ) (S=1/2 ortho-semiquinonate, …

Spin Interactions In New Donor-Acceptor Complexes, Ju Chen

Chemistry and Chemical Biology ETDs

Transition metal complexes ligated by Donor-Acceptor (D-A) biradicals are of interest for probing the degree of electronic coupling between chemically biased radical fragments. The unique nature of their electronic coupling has allowed these systems to serve as ground state analogues of charge separated excited states generated by photoexcitation. We have been interested in how the nature of the acceptor radical affects the magnitude of the electronic coupling matrix element in these biradicals. As such, we have synthesized a new series of D-A semiquinone-verdazyl (SQ-VD) biradical ligands and their transition metal complexes. We have characterized these new complexes by x-ray crystallography, …

Approaches In Molecular Engineering To Optimize The Desired Properties Of Photoactive Molecules, Douglas Joseph Breen

Chemistry and Chemical Biology ETDs

Within this dissertation, photochemical systems that bear significance to next-generation photonic materials and devices are explored. Notable advances in the design, synthesis, and characterization of three distinct groups of photoactive molecules are achieved through molecular design and spectroscopic analysis. First, novel ruthenium sulfoxide complexes bearing substituted phosphine ligands are found to provide extraordinary control over photoisomerization quantum yields. A comparison of these complexes reveals ground-state characteristics that are instrumental in this reactivity, while a novel spectroscopic technique provides rare structural evidence for an O-bonded metastable isomer. Ruthenium complexes bearing chelating carbene-sulfoxide ligands rapidly thermally revert from the O-bonded metastable isomer …

A Compendium Of Inorganic Photochemistry: Synthetic And Spectroscopic Discoveries, Sebastian B. Vittardi

Chemistry and Chemical Biology ETDs

This dissertation reports and examines contributions made in the advancement of inorganic photochemistry. Empirically driven assessments are allotted to the interplay between ligand sets, excited states, and photochemistry observed in metal complexes. A methodical spectroscopic examination is provided for oligothiophene-sensitized lanthanides. Their excited state dynamics were elucidated by femtosecond pump-probe spectroscopy and used to develop a model explaining their wavelength-dependent dual functionality. Iron (II) cyanide and isocyanides are evaluated to identify the efficacy of strong-field ligands in promoting charge-transfer excited states. Fundamentals of ligand field theory helped conceptualize the synthetically tunable parameters and effects transposed to their absorption dynamics. Transition …

Mitochondrial Proteins In Mediating Colon Cancer And Potential Theraputics, Kunlun Yin

Chemistry and Chemical Biology ETDs

Cancer is one of the biggest threatens to human health. Many people died because of various types of cancer. Colon cancer is one of the leading causes of new incidence and mortality in the whole world. It is important to understand the mechanism of tumorigenesis and development. Based on the mechanisms, we may develop new therapeutics to improve survival rate. In Chapter 2, we discussed the PINK1 function in suppression colon cancer. We found that PINK1 deficiency can promote colon cancer, and PINK1 overexpression suppressed tumor growth in vivo and in vitro. PINK1 can activate its substrate P53, which activates …

Pt-Containing Conjugated Polymers And Small Molecules For Bhj Photovoltaic Devices, Yunjeong Kwon

Chemistry and Chemical Biology ETDs

The current state of organic photovoltaic (OPV) devices involve series of small molecular or polymeric systems that can absorb light from the solar spectrum in concert with another material that acts as an acceptor material. Together these materials serve to generate and split bound excitation species then transport the separate charges to their respected electrode. Several limitations have restricted the widescale use of these materials. Since these devices have their genesis in organic materials the OPV devices inherit short exitonic lifetimes, narrow absorption window and a lack of precise control over the morphology. To overcome these limitations, additional molecular engineering …

Studies Of The Rectification Behavior Of The Pdt Ligand And The Active Site Of Msrp, Laura J. Ingersol

Chemistry and Chemical Biology ETDs

Molybdenum (Mo) is an essential element that plays an important role in global nitrogen, carbon, and sulfur cycles with a critical role in human metabolism and ecological balance. It becomes catalytically active when complexed with the pyranopterin dithiolene ligand (PDT), forming the nearly ubiquitous molybdenum cofactor (Moco). The complex biosynthetic pathway of Moco, its presence in all three domains of life, and its role as a constituent cofactor in the last universal common ancestor (LUCA) all point toward the importance of the PDT in the development of life on Earth. Molybdoenzymes catalyze the two-electron oxidation or reduction of substrates that …

Synthesis And Characterization Of Regioregular Cross-Conjugated Poly(Thienylene Vinylene)S, Yousef M. Katba Bader

Chemistry and Chemical Biology ETDs

Poly(thienylene vinylene)s (PTVs) is special a class of conjugated polymers (CPs) that show remarkable optoelectronic properties and promising applications. The main reason that hinders their application, is the lack of synthetic methodologies for preparing new derivatives with various functionality. Developing new PTVs with improved structures based on structure-property relationships increases the potential of utilizing this type of polymers in advanced applications. Most available preparation methods lead to regio-random PTVs (ra-PTVs) structures due to the different placement of the sidechain in the polymer backbone, which results in reduced crystallinity. In this study, we developed a novel strategy that produces a series …