Doctor of Philosophy, Case Western Reserve University, 2025, Chemistry

Nonadiabatic molecular dynamics (NAMD) simulations are a powerful tool for uncovering atomic-scale mechanisms of light-driven processes of molecules. However, these processes involve ultrafast nuclear motions that are tightly coupled to electronic motion, and it is uncertain if the feld of NAMD has progressed to the point of being truly predictive. To encourage the development of NAMD methods, the Journal of Chemical Physics arranged for a double-blind test of NAMD predictive capabilities against time-resolved ultrafast electron difraction (UED) experiments on the photodynamics of cyclobutanone. In Chapter 2, we present our contribution to this 2024 prediction challenge special collection. We apply a “workhorse” NAMD methodology of time-dependent density functional theory with trajectory surface hopping to simulate several picoseconds of cyclobutanone after excitation with 200 nm light, generating time-resolved electron difraction patterns to directly compare with yet-to-be-released experimental results.We also include an overview of the prediction outcomes of the full complement of contributions to the prediction challenge. A key component of NAMD simulations is the selection of the electronic structure method used to generate on-the-fy forces and nonadiabatic couplings that determine the motion of nuclei. However, excited states remain a frontier of electronic structure method development. In Chapter 3, we introduce the resonating Hartree-Fock (ResHF) method as a promising candidate for excited state applications. We then present a detailed overview of the nonorthogonal, multiconfgurational ResHF method. In Chapter 4, we present a unique formulation of ResHF that uses the matrix adjugate to remove numeric instabilities of the method.We demonstrate improved convergence to the ResHF wavefunction as a result, and benchmark ResHF against complete active space self-consistent feld in the computation of excited state energy surfaces.

Committee: Shane Parker (Advisor); Clemens Burda (Committee Chair); Robert Warburton (Committee Member); Daniel Scherson (Committee Member); Carlos Crespo-Hernández (Committee Member) Subjects: Chemistry; Physical Chemistry; Physics; Quantum Physics

Doctor of Philosophy, The Ohio State University, 2024, Chemistry

Nobel prize winner Jean-Marie Lehn defined supramolecular chemistry nearly 40 years ago as “the chemistry beyond the molecule.” This field strives to not only build novel molecular structures, but also to investigate their interactions with other molecules. Within this field, host-guest chemistry specifically focuses on the ability of a molecule called a “host” to covalently interact, encapsulating a “guest” molecule. In the 40-50 years since the birth of supramolecular chemistry as a field, a wide variety of cavitands, or molecules with cavities, have been synthesized. This large chemical space constitutes a myriad of potential host molecules which are now being applied in areas such as medicine, consumer goods, and sensors. In the Badjic group at OSU, a benzocyclotrimer known as the molecular basket has been extensively researched, showing affinities for molecules such as anti-cancer agents and nerve agent mimics. In the past, the groups work has been focused on the development of synthetic routes toward these molecular baskets, after which guest molecules are sought out which bind to the synthesized hosts. In recent years, the synthesis of molecular baskets has become more feasible with decagram scale preparations becoming the norm. Further advancement of these methods culminated in the ability for a tris-differentiated and chiral molecular basket to be synthesized in efforts to more accurately mimic the asymmetric environments of proteins (Chapter 2) As the focus of the group has moved from synthesis to application, the need has arisen for targeted selection of guest molecules to take place. While one can imagine designing molecular baskets on paper with some idea of chemical complementarity, this is burdensome and may result in the synthesis of hosts without affinities for target guest. Seeing a gap in the design process, it was suggested that computational chemical methods could potentially be used to investigate libraries of molecular baskets affinities (open full item for complete abstract)

Committee: Jovica Badjic (Advisor); Christo Sevov (Committee Member); Christopher Hadad (Committee Member) Subjects: Chemistry

Bachelor of Science (BS), Ohio University, 2024, Chemistry

Due to the ever-growing health concern of antibiotic resistance, there is a need for novel drug development that can target bacteria in a way that is not resisted. In Gram positive bacteria, one of these potential targets is the T-box Riboswitch, which is a regulatory, non-coding region of RNA involved in amino acid regulation. Within the T-box Riboswitch is an antiterminator region, which dictates whether or not the downstream genes are transcribed. The genes that are regulated by the T-box riboswitch are directly involved in protein synthesis. The antiterminator is stabilized by the binding of uncharged tRNA, and when unbound forms the more stable terminator form, in which transcription is terminated. Drug design can be employed to target the antiterminator to prevent antitermination from occurring and cause the bacterial cell to die due to lack of protein synthesis. This thesis explores fragment-based computational docking studies to determine compounds that bind to the antiterminator with specificity and in regions that could potentially result in an inhibitory effect on antitermination. A compound library of 180 amino acid R groups were prepared and docked to the antiterminator as well as a control model without the tRNA-binding bulge region. Of the initial 180 amino acid R groups, 47 were determined to bind to the antiterminator in regions that may lead to inhibition with more specificity than in the control model. Additionally, 10 peptide links that were produced from these 47 compounds were further docked and each showed some level of binding to the regions of interest in the antiterminator. The results of this project indicated 47 amino acids that could potentially be used as building blocks for drug synthesis, in addition to 10 peptides that may produce an inhibitory effect on the antiterminator. Further studies can be performed on these compounds, such as fluorescence assays and transcriptional assays, to further te (open full item for complete abstract)

Committee: Jennifer V. Hines (Advisor) Subjects: Biochemistry; Chemistry

Doctor of Philosophy, The Ohio State University, 2024, Chemistry

Molecular docking and molecular dynamics simulations are two commonly used computational techniques for the in silico evaluation of receptor-ligand binding and characterization of biomacromolecules. This work presents two independent projects to elucidate the molecular interactions in different prospective protein targets and provide physical insights into structure-based drug design. The focus of the first part is the “interacts-with-Spt6” protein (IWS1), a eukaryotic transcription elongation factor present in the RNAP II polymerase (RNAP II) complexes. IWS1 is gaining increasing attention as recent works revealed its collaborative actions with many formerly identified transcription factors of known regulatory effects and its direct interaction with the catalytic alpha subunit of RNAP II (RPB1). However, having about 70% of residues in human IWS1 being intrinsically disordered, its structure and function are not fully understood. Motivated by the recently discovered connection between IWS1 and liposarcoma (LPS), a cancer that can grow and spread aggressively, we initiated the effort of finding drug molecules targeting IWS1 to suppress transcriptional activities in cancer cells. To begin with, we analyzed the supermolecular arrangement, the protein interactions within the structured core, and the potential interactions with chromatin in the intrinsically disordered region of hIWS1 based on various recent studies of the structures and biological functions of IWS1. We then identified a potential binding pocket on IWS1's interface with Spt6 for a drug molecule to act as a competitive inhibitor that downregulates the transcriptional activity of RNAP II by diminishing the association of IWS1/Spt6. Next, we designed and performed a series of molecular docking calculations. Among the top-ranked compounds from the virtual screening of FDA-approved drugs, Ketotifen and Desloratadine were selected for experimental validation and were shown to reduce the association of IWS (open full item for complete abstract)

Committee: Christopher Hadad (Advisor); Rafael Bruschweiler (Committee Member); Alexander Sokolov (Committee Member) Subjects: Chemistry

Doctor of Philosophy (PhD), Ohio University, 2024, Chemistry and Biochemistry (Arts and Sciences)

In this dissertation, the gas-phase fragmentation chemistries of deprotonated carbohydrates were characterized. Tandem mass spectrometry and density functional theory (DFT) reaction pathway calculations were applied to rationalize the gas-phase fragmentation mechanisms. The fragmentation behavior of singly charged deprotonated glucose-α-glucose positional isomers: b,b-trehalose and isomaltose was investigated. The gas-phase chemistry of two other glucose-α-glucose positional isomers was studied: kojibiose and nigerose. The fragmentation mechanisms of singly deprotonated glucose- 1,4-glucose stereochemistry isomers α/β for maltose and cellobiose, respectively were examined. Finally, the fragmentation chemistry of acidic glycan galacturonic acid is studied, both singly and doubly deprotonated precursor ions were individually fragmented, and theoretical modeling was used to compare the charge-state effect on the fragmentation behavior of digalacturonic acid.

Committee: Benjamin Bythell Mr (Advisor); Howard Dewald Mr (Committee Member) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 2023, Chemistry

Over the past several decades, the noble metals (Au, Pt, Ru, Rh, Pd, Os, and Ir) have proliferated in many industrially relevant processes. With steady growth in world population, increases in anthropogenic climate change, and negative socioeconomic impacts of sustained use of noble metals, the necessity for catalysts based on readily available, earth-abundant frst-row transition metals has grown considerably in recent years. Despite their clear sustainability advantage, the frst-row metals suffer from a reduced proclivity toward the productive two-electron processes upon which the mechanisms of their precious metal counterparts are based. Metal-ligand cooperativity (MLC) has emerged as a strategy to counteract the frst-row metals' propensity toward one-electron processes by appending a non-innocent ligand to the metal center to mitigate the redox burden associated with substrate activation. The MLC examples most relevant to the present work involve activation of substrates across metal–ligand bonds. Often, this activation event brings about a chemical change in the ligand—e.g., the conversion of amides to amines. Herein, substrate activation across the Fe–Namide bond in a square planar S = 1 FeII complex supported by an aryl-linked bis(amido)bis(phosphine) ligand is described. In a previous work, this (PNNP)Fe complex was shown activate B–H bonds across each Fe–N linkage, producing an iron dihydride species that maintained its FeII oxidation state by virtue of MLC. Expanding on this previous result, the work herein reports activation of Si–H and C–H bonds across the Fe–N linkage in addition to functionalization of the Fe–P linkage. Upon treatment of (PNNP)Fe with a slight excess of primary silanes, a unique bridging structure in which two of the Si–H bonds of the primary silanes are activated across the Fe–N bonds of two different (PNNP)Fe units is obtained. Treatment with manifold excess primary silane, however, is shown to result in the formation of a Si–Si bond (open full item for complete abstract)

Committee: Christine Thomas (Advisor); Shiyu Zhang (Committee Member); Christopher Hadad (Committee Member) Subjects: Chemistry

Bachelor of Science (BS), Ohio University, 2023, Chemistry

We investigate deprotonated and regiospecifically labeled glucosamine phosphate derivatives using tandem mass spectrometry. The spectral results were supplemented with computational modeling of each analyte's key gas-phase dissociation reactions to calculate specific reaction energetics. The dissociation chemistries underpinning dihydrogen phosphate anion (H2PO4-, m/z 97) loss, phosphenate anion loss (PO3-, m/z 79), and formation of the structurally informative cross-ring anion (0,2A1, C4H8PO7-, m/z 199 and 0,4A1, C2H4PO5-, m/z 139) products were examined. Deprotonated α-1-phosphate glucosamine anion analytes fragment primarily through the loss of phosphenate anions and dihydrogen phosphate. In contrast, deprotonated 6-phosphate glucosamine anion analytes exhibit multiple active fragmentation patterns. The phosphate group at the 6-position enables cross-ring cleavage to occur, producing 0,2A1 and to a lesser extent 0,4A1 ion products. Furthermore, analytes with a 6-phosphate also exhibited dissociation via ejection of H2PO4- and PO3-.

Committee: Lauren McMills (Other); Benjamin Bythell (Advisor) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 0, Biophysics

This dissertation explored the creation of positive inotropes targeting the regulatory domain of cardiac troponin C (cNTnC). Upon calcium binding to cNTnC, a series of conformational changes occur in the muscle tissue ultimately leading to muscle contraction. The chapters in this dissertation discuss two approaches to increase cardiac muscle contractility and functionality in the diseased state. In the first approach, computational free energy method protocols were created for characterization of single point mutation effects on the calcium sensitivity of cNTnC. In the second, a structure-based drug design approach was taken to identify important features of previously identified calcium sensitizing small molecules and propose new directions for lead optimization. Chapter 2 introduced the free energy method adaptive steered molecular dynamics (ASMD). We developed a protocol for applying ASMD to determine the effects of previously deigned calcium sensitivity modulating mutations on cNTnC that have been well characterized in the literature. We observed the correct trends for all calcium sensitizing and desensitizing mutants, in conjunction with loop II alanine perturbations. Additionally, the potential of mean force accuracy was shown to increase substantially with increasingly slower speeds and using fewer trajectories. This study lays the foundation for ASMD as a valuable potential tool to support the design and characterization of novel mutations with potential therapeutic benefits. Chapter 3 explored the structure of cNTnC through an exhaustive single point mutagenesis study. Based on computational protein stability predictions focused on the loop regions of the EF-hand motifs, we identified and characterized eight mutations for their potential effects on calcium binding affinity in site II of cNTnC. We utilized two distinct methods to estimate calcium binding: adaptive steered molecular dynamics and thermodynamic integration (TI). We observed a sensitizin (open full item for complete abstract)

Committee: Steffen Lindert (Advisor); Jonathan Davis (Committee Member); Sherwin Singer (Committee Member); Christopher Hadad (Committee Member) Subjects: Biophysics

Master of Science in Chemistry, Youngstown State University, 2022, Department of Biological Sciences and Chemistry

The mechanism of proton transport was studied computationally using ab initio molecular dynamics (AIMD) in three protic ionic liquid (PIL) systems to determine how charge diffusion was impacted by various factors. Such ionic liquids can be used to increase the efficiency of proton-conducting layers in hydrogen fuel cells so the fuel cells can operate at higher temperatures without expending as much labor and cost to do so. The first system used n-ethylimidazolium (C2HIm+) as a cation and determined how the addition of a solvent changed the rate of diffusion as well as changing the anion, using both the anion form of bis(trifluoromethanesulfonyl)imide (TFSI-) and acetate ion. The second set of simulations were similar to the first, but used a simpler [HIm+][TFSI-] and determined the effect of temperature on PILs with added solvent over an 80 K range. Finally, a third set of simulations was run to determine the mechanism of proton transport in a solvate ionic liquid (SIL) system with 18-crown-6-ether●H3O+ used as the cation and running simulations containing both TFSI- and acetate as the anion. The research outlined in this thesis shows that these systems can be reliably studied computationally with AIMD and allows insight for a greater understanding of these systems.

Committee: Christopher Arntsen PhD (Advisor); Brian Leskiw PhD (Committee Member); Clovis Linkous PhD (Committee Member) Subjects: Chemistry; Physical Chemistry

Doctor of Philosophy, The Ohio State University, 2021, Chemistry

In the following work, we discuss the development and application of efficient techniques either aimed at extending the applicability of the currently available methods in the liquid phases to larger system sizes, or at eliminating the artifacts with the existing techniques for several open-shell systems encountered in condensed phases. First, we have investigated the local solvation structure of aqueous hydroxyl radical and absorption spectrum by employing both the mixed quantum mechanics\slash molecular mechanics (QM/MM) framework and periodic density functional theory (DFT) framework. Theoretically, the presence of a hemibond (a two-center, three-electron bond) in this system has been debated for a long time. This structural motif has been explained as either an artifact arising from the self-interaction error (SIE) in DFT or an artifact because of the finite-size effects of the simulation cell but shown to play an important role in the absorption spectrum based on some theoretical studies on smaller representative clusters. Our investigations based on simulations with various DFT simulations suggest that a pseudo-hemibonded motif still persists in this system. We have also demonstrated that the population of hemibonds is extremely sensitive to the amount of exact Hartree-Fock (HF) exchange employed in the simulation. However, we have concluded that these hemibonded motifs play an outsized role in the absorption spectrum, even when present as a rare configuration, due to an intense charge-transfer transition in the hemibonded structures. To eliminate the artifacts arising from this SIE, we have then implemented the density-corrected DFT (DC-DFT) formalism along its analytical gradient, which has been proven to be powerful for the systems with larger density-driven errors. Afterward, we have applied this technique for studying the electronic structure descriptions of the hole defects in Al-doped silica and electron-polarons in anatase titanium oxide where most of (open full item for complete abstract)

Committee: John M. Herbert (Advisor); Marcos Sotomayor (Committee Member); Alexander Y. Sokolov (Committee Member) Subjects: Chemistry; Physical Chemistry

Doctor of Philosophy (PhD), Ohio University, 2021, Chemistry and Biochemistry (Arts and Sciences)

This dissertation is focused on the study of the fragmentation chemistry of carbohydrates by mass spectrometry and computational methods. By investigating the behavior of model systems, we hypothesize that a general model for carbohydrate fragmentation can be found. The model systems studied are sodiated cellobiose and gentiobiose (Chapter 2), deprotonated lactose (Chapter 3), and β-cyclodextrin (Chapter 4), each representing a different aspect of carbohydrate fragmentation. Experimental techniques, including tandem mass spectrometry, stable isotopic labeling, and infrared multiphoton dissociation were employed. Throughout, we also utilize computational modeling to add a dimension of clarity to the experimental results and provide values usable in subsequent predictive efforts.

Committee: Benjamin Bythell (Advisor); Martin Kordesch (Committee Member); Peter Harrington (Committee Member); Jixin Chen (Committee Member) Subjects: Chemistry; Molecular Chemistry

Bachelor of Arts, Wittenberg University, 2021, Biochemistry/Molecular Biology

Nucleophilic acyl substitution (NAS), specifically as it proceeds through the associative pathway, is a fundamental chemical reaction that is found as a component in many biochemical pathways. A defining feature of nucleophilic acyl substitution is the formation of a tetrahedral intermediate, which functions to stabilize the reaction complex and lower the overall energy of reaction. This formation of an energetically favorable tetrahedral intermediate is a key aspect in the discussion of NAS as an important mechanistic component of biochemical and organic reactions. However, there is evidence to suggest that given the correct reaction conditions the dissociative pathway of nucleophilic acyl substitution, in which no tetrahedral intermediate is formed, is energetically favored over the associative pathway. The potential for the dissociative pathway's favorability provides great incentive to explore this pathway by way of computational chemistry, and also grants the opportunity to model the energetics and geometry of the reaction and explore changes to them under varying conditions. In order to do so, ab initio calculations were utilized at every level of analysis within this research to determine the energy of the acyl system under different conditions modeled within the Wittenberg computing cluster (WARP2). By using these calculations, model systems were created for the NAS system in which correct transition state geometries and energetics were identified, and these data provide potential avenues for further development of the dissociative pathway model in the future.

Committee: Justin Houseknecht (Advisor); Margaret Goodman (Committee Member); Michael Anes (Committee Member) Subjects: Biochemistry; Chemistry; Molecular Biology

Doctor of Philosophy, The Ohio State University, 2020, Chemistry

The products of chemical synthesis touch every aspect of life in a modern industrial world, from the materials in our devices and tools, to the fuels that power them, and the medicines that keep us healthy. Steady improvements in these chemistries yield commensurate gains in quality of life, and realizing those improvements is a fundamental drive for the discovery of new, efficient methods. Efficient synthesis enables the transfer of time and resources spent on preparing molecules instead to their study and application. Classical synthetic strategies involve iterative transformation of pre-installed functionality, which can be both laborious to perform and limiting to starting functional groups. This stepwise approach can be effectively side-stepped by transformation of ubiquitous and inert C-H bonds to desired motifs in a strategy known as C-H functionalization. While many different methods to effect C-H functionalization exist, perhaps the most direct is achieved via hydrogen atom abstraction to access reactive carbon-centered radicals. These radicals can be engaged with a variety of radical traps, generating a wide range of different bonds, and enabling more streamlined synthesis. In line with the spirit of more deliberately designed, and therefore efficient, synthesis, computational methods have become increasingly more popular and provide prospective insights into experimental design and reaction discovery. Retrospective study and analysis of known reactivity via computation modeling also provides a framework that synthetic chemists can leverage for the design of new chemistry. These insights are rendered with a level of detail that is either difficult to attain with traditional experiments (e.g. molecular structure, bond strengths, electronegativities, etc.) or impossible (e.g. transition state structures). The physical chemical parameters of radicals, in particular, can be well-modeled with the theoretical chemical approaches of density functional theory. (open full item for complete abstract)

Committee: David Nagib Ph.D. (Advisor); Dehua Pei Ph.D. (Committee Member); Craig Forsyth Ph.D. (Committee Member); Steffen Lindert Ph.D. (Committee Member) Subjects: Chemistry; Organic Chemistry

Doctor of Philosophy, The Ohio State University, 2019, Pharmaceutical Sciences

The use of data-driven methods and machine learning has become increasingly pervasive in many industries, including drug discovery and design, as computing power and large amounts of data become increasingly available. In an effort to efficiently leverage this data, cheminformatics has emerged as a data-driven, interdisciplinary field that focuses on storing, accessing, and applying chemical information. Cheminformatics methods and tools facilitate the management and analysis of large annotated chemical datasets that would be difficult or impossible to do manually. A famous application of leveraging large amounts of chemical data was performed by Christopher A. Lipinski in 1997. Lipinski analyzed a large set of bioavailable synthetic drug molecules and identified trends in their molecular properties, which has since been referred to as the “Lipinski's Rule of 5”. While these rules are far from absolute, Lipinski's analysis demonstrates the utility of leveraging large amounts of chemical data to gain important insights. This thesis describes the application of cheminformatics methods to tackle two very different research problems: 1) the analysis and binding of a class of protein degraders called proteolysis targeting chimeras (PROTACs) and 2) the development of a target fishing application for the prediction of mechanism of action of natural products. PROTACs are a novel class of small molecule therapeutics that are garnering significant interest. Unlike traditional small molecule therapeutics, PROTACs simultaneously bind to both their protein target and an E3 ligase to induce degradation. The requirement to simultaneously bind two proteins necessitates a high molecular weight as PROTACs must contain two unique binding moieties that are connected by a linker. As a result, PROTAC molecules are expected to lie outside of the traditional drug-like chemical space described by Lipinski. To gain a better understanding of the physicochemical properties of PROTACs curre (open full item for complete abstract)

Committee: James Fuchs (Advisor); Xioalin Cheng (Advisor); Karl Werbovetz (Committee Member); Lara Sucheston-Campbell (Committee Member) Subjects: Chemistry; Computer Science; Molecular Chemistry; Molecules; Pharmacy Sciences

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2019, Photochemical Sciences

The primary event in vision is induced by the ultrafast photoisomerization of rhodopsin, the dim-light visual pigment of vertebrates. While spectroscopic and theoretical studies have identified certain vibrationally coherent atomic motions to promote the rhodopsin photoisomerization, how exactly and to what degree such coherence is biologically related with its isomerizing efficiency (i.e. the photoisomerization quantum yield) remains unknown. In fact, in the past, the computational cost limited the simulation of the rhodopsin photoisomerization dynamics, which could be carried out only for a single molecule or a small set of molecules, therefore lacking the necessary statistical description of a molecular population motion. In this Dissertation I apply a hybrid quantum mechanics/molecular mechanics (QM/MM) models of bovine rhodopsin, the verterbrate visual pigment, to tackle the basic issues mentioned above. Accordingly, my work has been developing along three different lines comprising the development, testing and application of new tools for population dynamics simulation: (I) Development of a suitable protocol to investigate the excited state population dynamics of rhodopsins at room temperature. (II) A correlation between the phase of a hydrogen-out-of-plane (HOOP) motion at the decay point and the outcome of the rhodopsin photoisomerization. (III) A population “splitting” mechanism adopted by the protein to maximize its quantum yield and, therefore, light sensitivity. In conclusion, my Dissertation reports, for the first time, a connection between the initial coherent motion of a population of rhodopsin molecules and the quantum efficiency of their isomerization. The photoisomerization efficiency is ultimately determined by the way in which the degree of coherence of the excited state population motion is modulated by the protein sequence and conformation.

Committee: Massimo Olivucci Ph.D (Advisor); Andrew Gregory Ph.D (Other); Hong Lu Ph.D (Committee Member); Alexey Zayak Ph.D (Committee Member) Subjects: Biochemistry; Chemistry

Master of Science in Chemistry, Cleveland State University, 2018, College of Sciences and Health Professions

Gaussian and GaussView software were utilized to characterize interactions between choline salts and urea, which form a deep eutectic solvent (DES). The initial system studied was choline chloride and urea, at a 1:2 molar ratio, which is also known as reline. Subsequent systems, substituting the chloride anion with other anions (fluoride, bromide, and hydroxide), were studied to show that the system with greater calculated strength of interaction will have more non-ideal physical properties, such as melting point (found in literature). Observations regarding structure related to counterion electron density and hydrogen bonding were made throughout the studies.

Committee: David Ball Ph.D. (Committee Chair); John Turner Ph.D. (Committee Member); Warren Boyd Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2018, Photochemical Sciences

The need for a detailed mechanistic understanding of the photoisomerization of retinal chromophore (retinal protonated Schiff base, rPSB) is becoming increasingly important, not only due to its fundamental importance in vision but also owing to the growing number of applications in various fields. The development of microbial rhodopsin based fluorescent probes and actuators essential in neuroscience, synthetic bio-mimetic molecular switches and motors useful in material science and synthetic biology are examples of such applications. The work presented in this dissertation is devoted to unveil and understand a novel mechanistic factor with significant impact on the photoisomerization of rPSB-like systems. This factor corresponds to the interaction between the first electronic excited state and higher states (usually the second excited state) occurring during the excited state lifetime or, in other words, along the excited state photoisomerization coordinate. This "electronic state mixing" effect is studied by employing different computer tools including hybrid quantum mechanics/molecular mechanics (QM/MM) methods. The investigated systems include representative animal and microbial rhodopsins, bio-mimetic N-alkyl-indanylidene-pyrrolinium (NAIP) molecular switches and a recently reported water soluble rhodopsin mimic. Our results unveil two type of effects due to changes in the electronic mixing: an impact on the excited state lifetime and an impact on vibrational coherence as we now briefly describe. The impact on excited state lifetime is first demonstrated by uncovering the variation of rPSB photoisomerization speed in different environments is due to an increase or decrease of electronic state mixing and that this effect can be controlled by the electrostatic field of the environment. This leads us to hypothesize that animal rhodopsins, which isomerize within 200 fs, have been evolved to minimize the electronic state mixing such that biological functions are car (open full item for complete abstract)

Committee: Massimo Olivucci Ph.D (Advisor); Alexander Tarnovsky Ph.D (Committee Member); R. Marshall Wilson Ph.D (Committee Member); Salim Elwazani Ph.D (Other) Subjects: Biophysics; Chemistry; Organic Chemistry; Physical Chemistry

Doctor of Philosophy, The Ohio State University, 2018, Chemistry

The mechanistic transformations of three fundamental classes of reactive intermediates are explored: singlet and triplet carbenes, carbene radical cations, and carbon-centered radicals. Through a marriage of theory and ultrafast spectroscopy, the identities of unique carbene species and photochemical transformations were characterized from nitrogenous (diazo and diazirine) precursors. The photochemistry of a novel trifluoro-diazo, carbenic precursor (ethyl 2-diazo-3,3,3-trifluoropropanoate) is explored by ultrafast time-resolved infrared spectroscopy in multiple solvents and the results do not reveal a prototypical 1,2-migration product via rearrangement in the excited state or through a carbene intermediate. The primary photochemical process is the interconversion of a diazo functional group to the corresponding diazirine. A completely new mechanistic pathway is detailed for the conversion of diazo and diazirine containing nitrogenous precursors to their corresponding products. This theoretical report accounts for the partially unexplained and curious bifurcation in photochemical vs thermal decomposition of nitrogenous precursors. Using a phenanthrene precursor, the first ultrafast time-resolved spectroscopic observation of a vinyl carbene (singlet ¿-methylbenzylidenecarbene) is reported and the results are supported and rationalized by computational data. Electronic factors affecting the regioselectivity of aryl radical hydrogen-atom abstraction reactions in benzyl-alkyl tethered species is explored in order to guide efforts of selective remote C–H functionalizations. The system can be biased towards or away from the standard abstraction pathway by the use of electron-donating and electron-withdrawing groups strategically placed on the benzene ring. The mechanistic aspects of the oxidative transformation of C2 symmetric o-aminophenol species and C3 symmetric formyl fragments to form benzobisxazole based covalent organic frameworks (COFs). Computational data (open full item for complete abstract)

Committee: Christopher Hadad PhD (Advisor); Jon Parquette PhD (Committee Member); David Nagib PhD (Committee Member); Karl Werbovetz PhD (Committee Member) Subjects: Chemistry

Master of Science (MS), Wright State University, 2017, Physics

The bottom-up analysis of Carbon Nanotube synthesis is not well understood. Specifically, the question as to how carbon adsorbs to a substrate inclusive of a sup- ported catalyst may lead to the energetically favorable structure of a hexagonal close- packed structure along the wall, or walls, of the tube. A first time simulation using COMSOL Multiphysics has been generated in order to capture the gas-phase mech- anism which leads to carbon production. It is thought that the carbon adsorbs and the walls are formed from the bottom up and the inside out for multi-wall CNTs. The studies involved accurately setting up a simulation to capture chemical kinetics, mass transport, heat transfer, and fluid flow. It is shown that a variation in inflow velocity yields a variation in efficiency of ethylene cracking in the reactor. When the residence time is increased the outlet concentration of ethylene is lowered, as expected. This means that variations in con- centrations can be accounted for through varying initial parameters. Chemical reactions involving ethylene decomposition from GRI-Mech 3.0 [4] is imported and the validity of the Troe Form chemical kinetics was tested. Using equilibrium calculations with the use of an ICE (Initial, Concentration, Equilibrium) table, 0-D studies using the high pressure limit of the rate constant and the Troe Form of the rate constant were used in separate tests for comparison. It was subse- quently showed that the Troe Form kinetics do not accurately determine the expected concentrations. The chemical species concentration, gas pressure, temperature, and velocities were calculated for a final set of approximately 32 gas-phase reactions. A nearly completed set of gas-phase and surface reactions were compiled but only the most important chemical reactions were implemented in the present studies to form a basis for future analysis. The results of the present study shows production of amorphous carbon wit (open full item for complete abstract)

Committee: Amit Sharma Ph.D. (Advisor); Gregory Kozlowski Ph.D. (Committee Member); Brent Foy Ph.D. (Committee Member) Subjects: Physics

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2016, Photochemical Sciences

This work gives the detailed description of the dynamics and mechanism of the previously unsuspected photochemical reaction path of diiodomethane (CH2I2), a paradigmatic haloalkane, which is direct intramolecular isomerization upon the excitation of this molecule to the lowest singlet S1 state. The previous liquid-phase ultrafast spectroscopy experiments on the UV photochemistry of di- and polyhalomethanes suggest that following excitation of these molecules, the carbon-halogen bond breaks, leading to formation of the initial radical pair. The radical pair, trapped by a solvent cage collapses into an isomer product species with halogen-halogen bond on a picoseconds timescale (1 ps = 10-12 s). Yet, the results recently obtained in our research group, clearly suggest that in addition to this conventional, in-cage isomerization process, there is another, unconventional isomerization mechanism, which occurs on a sub-100 fs timescale (1 fs = 10-15 s) and does not require the solvent environment around the excited CH2I2 solute. Indeed, the ultrafast sub-100 fs timescale observed suggests two main considerations: • The sub-100 fs photoisomerization in polyhalomethanes is direct, i.e. proceeds via the intramolecular reaction mechanism proceeding without any intermediates (such as a radical pair) and, likely, is mediated by a crossing of excited and ground electronic states. • The solvent cage may not be needed, because the timescale of the aforementioned isomerization process is shorter than the 100-200 fs timescale for a single collisional encounter between solvent and solute molecules. iii Femtosecond transient absorption spectroscopy is a very valuable tool in studying the photochemical reactivity on short timescales. The measured ultrafast time-resolved spectra are complicated by relaxation processes in far from equilibrium solutes, such as intramolecular energy redistribution and flow, and can be understood in detail with the help from state-of-t (open full item for complete abstract)

Committee: Alexander Tarnovsky Ph.D. (Advisor); Massimo Olivucci Ph.D. (Committee Co-Chair); Robert McKay Ph.D. (Committee Member); John Cable Ph.D. (Committee Member) Subjects: Chemistry; Physics