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

The direct, reductive coupling of two electrophilic carbons has become an attractive alternative to traditional cross-coupling methodologies, which traditionally rely on the presence of a nucleophilic and electrophilic component. A renaissance in electrochemical techniques have helped to facilitate these transformations owing in part to the tunability of reaction potentials to facilitate electron transfer. Although these transformations are robust, there are still many incompatible/unknown combinations of Csp2-Csp3 couplings from various sources. Recently, reports have led to the reevaluation of the established cross-electrophile coupling (XEC) mechanism, invoking NiI as the catalytic intermediate responsible for activating both the alkyl and aryl component. This creates a scenario in which successful couplings are entirely dictated by their ease of activation. Tertiary substrates are easier to activate than primary and as such undergo deleterious side reactions. This also creates a scenario in which more difficult to activate aryl halides remain untouched during these processes. Critical to the success of this methodology was the application of a dual-catalyst system in which each catalyst is responsible for activating a single component. Ligand design and detailed mechanistic studies were crucial to guide the development of a wide scope of traditionally incompatible substrates (Chapter 2). Despite the successes of this work, there still exist several limitations in the ability to activate several classes of coupling partners. Other radical precursors (absent of aryl halides) were not tolerated under these conditions owing to their low reduction potentials. Heteroatom containing arenes were also unable to perform the reactions. Stoichiometric analysis showed that NiII-Ar complexes were capable of capturing radicals generated in situ from several of these challenging precursors. Utilizing a simple redox-non innocent ligand system, were developed a library of NiII (open full item for complete abstract)

Committee: Christo Sevov (Advisor); Dennis Bong (Committee Member); T. V. Rajanbabu (Committee Member) Subjects: Chemistry; Organic Chemistry

Doctor of Philosophy, Miami University, 2022, Chemistry and Biochemistry

Biomacromolecules are the inspiration for synthetic foldamers that mimic their function. ortho-Phenylenes are simple class of aromatic foldamers that fold into compact helical conformations because of arene-arene stacking interactions parallel to the helical axis. o-Phenylenes do not have internal cavity in their folded state, unlike many other aromatic foldamers. However, macrocycles, like benzo crown ethers, can be functionalized externally on the o-phenylene backbone for guest binding. Chapters 2 and 3 focus on crown-ether-functionalized o-phenylene oligomers and the effect on their folding behavior of binding to different secondary ammonium ion guests. In Chapter 2 we have focused on the shortest o-phenylene foldamer, a tetramer. Our design is to attach crown ethers at the terminal phenylene rings so that they stacked in the folding state and distant in the misfolded state. Our goal is study the effect of guest binding to the o-phenylene tetramer with achiral and chiral monotopic and ditopic guests. The o-phenylene tetramer remains in well-folded on binding to the achiral monotopic guest, whereas binding of the achiral ditopic guest unfolded it. Binding of chiral ditopic guests induces a preferred helical handedness. In Chapter 3 we have focused on higher o-phenylenes functionalized with crown ethers at the termini. An o-phenylene hexamer with only one crown ether attached at the end as a control and an o-phenylene heptamer and decamer functionalized with two crown ethers were studied. Our focus was to study the folding behavior of longer o-phenylenes having multiple turns by binding of achiral monotopic and ditopic secondary ammonium ion guests. The hexamer and heptamer remain in the folded state on binding with the achiral monotopic guest. The heptamer improves its folding with the binding of achiral ditopic guest by locking its well folded conformation. Chapter 4 focus on the external control of chiral induction in centrally functionalized o-phenylenes. o- (open full item for complete abstract)

Committee: C. Scott Hartley (Advisor); Dominik Konkolewicz (Committee Chair); Benjamin Gung (Committee Member); Neil Danielson (Committee Member); Jason Berberich (Committee Member) Subjects: Chemistry; Organic Chemistry; Physical Chemistry

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, Miami University, 2019, Chemistry and Biochemistry

Foldamers are synthetic organic oligomers/polymers, inspired by the structures and functions of biomolecules, that adopt predictable and well-defined secondary structures stabilized by noncovalent interactions. These structures are strongly influenced by exterior functionalization and external surroundings such as the solvent. Studying these factors could allow control over oligomer folding, allowing the generation of new structures complementary to biopolymers. ortho-Phenylenes are a class of aromatic foldamers that fold into helices. Their folding is controlled by arene-arene stacking interactions parallel to their helical axes. This dissertation discusses how their folding behavior is affected by the surrounding solvent polarity, covalently connected terminal chiral groups and external functionalization with fluoro groups. Solvent polarity plays a major role in stabilizing structural conformations in most of the aromatic foldamer systems. Chapter 2 presents a detailed investigation of the folding behavior of o-phenylenes oligomers in different solvents with varying polarities. A clear trend has been observed in these systems: misfolded conformations are stabilized in polar solvents. These misfolded conformers are found to be more polar than the perfectly folded conformation. Chapter 3 examines structure-property relationships on the folding of o-phenylene hexamers with various chiral groups substituted at their termini through imine functionalization. Terminal substitution with point chirality biases the helical twist sense in these oligomers producing a mixture of different populations of right- and left-handed helices. However, the proximity of the chiral center has a huge impact on the effectiveness of chiral induction. In addition, the position and sterics of the groups around the asymmetric carbon relative to the helix determine the effectiveness of twist sense biasing. The terminal chiral groups in these systems are found to be “ambidextrous”, indu (open full item for complete abstract)

Committee: Scott Hartley Prof. (Advisor); Dominik Konkolewicz Prof. (Committee Chair); Benjamin Gung Prof. (Committee Member); Rick Page Prof. (Committee Member); Andrew Paluch Prof. (Committee Member) Subjects: Organic Chemistry; Physical Chemistry

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

The spacing and relative packing of aromatic chromophores highly affects the performance of molecular electronic devices and materials, such as organic light-emitting diodes (OLEDs) and conductive polymers. In this work, a novel supramolecular approach for the construction of ordered aromatic chromophore arrays is presented. Our approach consists of embedding aromatic chromophores within robust metal-organic materials through self-assembly of predesigned chromophore-functionalized organic ligands and transition metals. Utilizing our approach, we enforced representative aromatic chromophores (such as carbazole) to adopt unique packing motifs that are beneficial for their photophysical characteristics. By embedding carbazole in a rigid copper-based metal-organic framework (MOF), we constructed 1D infinite columnar stacks of carbazoles that have potential in anisotropic charge-transport. We achieved significant enhancement of solid-state fluorescence originating from carbazole via embedding the carbazole moiety within a rigid zinc-based MOF, which holds chromophores spaced out, thus preventing aggregation-caused fluorescence quenching. We discovered room-temperature phosphorescence in addition to fluorescence when the carbazole moiety was embedded within zinc-based metal-organic chains instead of zinc-based MOF. We expanded our approach towards mixed-chromophore MOFs and demonstrated that the mixed-chromophore (carbazole:anthracene 1:1) zinc MOF serves as a platform for carbazole-to-anthracene energy transfer. Through the combination of thorough analysis of crystal structures and detailed photophysical studies, we established a correlation between chromophore packing motifs and bulk photophysical properties of metal-organic materials and their parent ligands. We concluded that extended cofacial aromatic interactions are detrimental for solid-state fluorescence, and disruption of cofacial stacks achieved via embedding of chromophores in zinc-based metal-organic materi (open full item for complete abstract)

Committee: Jeremy Klosterman PhD (Advisor); Moira van Staaden PhD (Other); Ksenija Glusac PhD (Committee Member); H. Peter Lu PhD (Committee Member) Subjects: Chemistry

Master of Arts, The Ohio State University, 1923, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1924, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1966, Graduate School

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Master of Arts, The Ohio State University, 1925, Graduate School

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Master of Arts, The Ohio State University, 1925, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1922, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1922, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 1920, Graduate School

Committee: Not Provided (Other) Subjects:

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

Master of Science, The Ohio State University, 2024, Chemistry

Camptothecin-dilysine (CPT-KK) self-assembles into nanotubes which may serve as a pH-responsive drug delivery vehicle. The nanotubes provide a carrier that allows camptothecin to enter the cell before inactivation by hydrolysis. As a drug delivery vehicle, one issue is monitoring drug release in vitro. Co-assembling CPT-KK with a rhodamine B-dipeptide conjugate (RhB-KE) provides a pH-responsive means to track the assembly through endocytosis and eventual release into the cytosol. Since CPT-KK is positively charged and RhB-KE is negatively charged at pH 7.4, electrostatic co-assembly is the preferred means for assembly as the positive charged CPT-KK will interact with RhB-KE than itself. This is due to the stabilizing attractive interactions between CPT-KK and RhB-KE and destabilizing repulsive interactions with itself. Pre-assembling RhB-KE provides a template for CPT-KK to wrap around. Mixing CPT-KK with RhB-KE in equimolar amounts produces co-assemblies within 1 h and produces mature tubes after 24 h. Since the incubation time is established, varying the ratio of CPT-KK/RhB-KE was done in order to optimize the co-assembly for drug loading and CPT-KK templating onto RhB-KE. Centrifugation at 5,000 rpm for 5 min gives the optimal ratio of 1:5 (CPT-KK/RhB-KE), while centrifugation at 13,400 rpm for 15 min gives 1:1 (CPT-KK/RhB-KE) as the ideal ratio. With this knowledge, determining the exact composition of the co-assembly can be determined via analytical high-performance liquid chromatography (HPLC) and further optimized using zeta-potential measurements. Live-cell imaging and cell viability assays will be used to investigate the efficacy of CPT-KK/RhB-KE as a drug delivery vehicle compared to self-assembled CPT-KK.

Committee: Jonathan Parquette (Advisor); Davita Watkins (Committee Member); Christopher Hadad (Committee Member) Subjects: Chemistry; Organic Chemistry

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

Petroleum-based plastic has caused devastating effects on the health of the natural world and people from its derivation from non-renewable resources and complex recycling processes. Polylactic acid (PLA) is a bio-based plastic that has the potential to alleviate these issues. In this experiment, the ring-opening polymerization of lactide to PLA is catalyzed by two organic catalysts, resulting in a low molecular weight polymer with a degradation temperature around 300 – 340 °C and glass transition temperatures between 27 and 33 °C. The polymer is successfully degraded upon exposure to 50 % aqueous ethanol at high temperatures, resulting in a decrease in theoretical number average molecular weight. With further research, PLA exhibits considerable potential for chemical recycling to close the loop of the production process and achieve a circular economy.

Committee: Lauren McMills (Advisor); Katherine Cimatu (Advisor) Subjects: Chemistry

Master of Science, The Ohio State University, 2024, Environment and Natural Resources

It is important to understand how environmental factors drive variability in aquatic nutrient cycling in streams. Controls on variability in production and transformation of dissolved organic matter (DOM), a carbon-based nutrient, are not well understood on spatial scales spanning many streams. This knowledge gap leaves questions as to how environmental factors influence DOM characteristics. In water year 2023, we investigated nitrogen and carbon chemistry seasonally in 80 tributaries on the United States side of Lake Erie. Watershed area and modeled discharge had no clear effect on total dissolved nitrogen (TDN) or DOM concentrations. Land use was a significant factor influencing stream chemistry; watersheds with different dominant land uses produced different seasonal chemistry patterns and had different environmental factors influencing stream chemistry. In watersheds dominated by agricultural land use, nitrate was the dominant form of nitrogen contributing to high TDN concentrations, likely driven by fertilizer use. DOC concentration and chemistry varied moderately with season and were impacted differently in watersheds with greater forest cover as compared to watersheds with greater cover of anthropogenically impacted land uses. Dominant land use of a watershed dictated how watershed factors, such as soil hydrology, watershed size, and degree of natural or anthropogenic land use, influenced stream chemistry, indicating that differences in DOM chemistry may be due to differential processes controlling DOM source and transformation.

Committee: Rachel Gabor (Advisor); Rachel Eveleth (Committee Member); Gil Bohrer (Committee Member); Matt Davies (Committee Member) Subjects: Aquatic Sciences; Biogeochemistry; Environmental Science

PhD, University of Cincinnati, 2024, Arts and Sciences: Chemistry

Mechanochemistry has witnessed remarkable growth as an effective method for performing chemical transformations in minimal or solvent-free conditions, this aligns with the global shift towards environmentally friendly, green protocols in chemical processes. Unique reaction selectivity and reactivity exhibited by mechanochemical processes offer the potential for discovering novel products and processes not achievable through conventional solution-based approaches. Additionally, mechanochemistry facilitates reactions involving reactants with low solubility, a challenging task in solution-based setups, and allows for shorter reaction times and more convenient setups for synthetic transformations. Despite these advantages, further investigation is needed to fully comprehend the potential of mechanochemistry for various synthetic purposes and applications. This dissertation explores mechanochemistry, emphasizing its interplay with electrochemistry, solvent-free reductions, its scalability using a twin-screw extruder, and diverse applications. Initially, water and metal combination mediated carbonyl group reduction under mechanochemical conditions was explored. The aim was to comprehend the precise temperature control required for mechanochemical reactions and unravel the reaction mechanisms in greater detail. The study also explored the galvanic cell's similarity to the mechanochemical vial with metal combinations in the presence of water. However, tuning the metal combination to selectively reduce the carbonyl group proved difficult in the presence of water. Water promoted hydrogen gas evolution and hydrogenation of the organic substrates, which rendered it challenging to isolate the effect of metal combinations on selective reduction, Furthermore, the development of a mechanoelectrochemical cell allows for the integration of mechanochemistry and electrochemistry, examining various metal combinations for electrochemical reduction. The designed cell which was connected t (open full item for complete abstract)

Committee: James Mack Ph.D. (Committee Chair); Ashley Ross Ph.D. (Committee Member); Hairong Guan Ph.D. (Committee Member) Subjects: Chemistry

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

To keep pace with newly emerging and evolving diseases, the field of drug discovery requires the development of modern synthetic strategies. Limiting the number of chemical steps and generation of waste in the construction of complex molecular scaffolds is essential to improving this process. The ubiquity of the C-H bond in both natural products and pharmaceuticals makes it an ideal target for late-stage synthetic modifications. However, selective C-H activation, specifically in complex molecular settings, remains a major challenge. Taking inspiration from Nature's enzymatic C-H oxidizing catalyst, cytochrome P450, uniquely reactive organic intermediates were discovered and designed to selectively modify inert C-H bonds. The radical and iodane selective functionalizations of C-H bonds described herein aim to expedite the drug discovery process by innovations in organic synthesis.

Committee: David Nagib (Advisor); Christopher Hadad (Committee Member); Jon Parquette (Committee Member) Subjects: Chemistry; Organic Chemistry

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

Cucurbit[n]urils (CB[n]s) are a family of supramolecular hosts known for their ability to bind hydrophobic, cationic guests with high affinity in aqueous solutions. While CB[7] and smaller members of the family can typically only bind one guest, CB[8] is capable of binding two guests within its cavity at once. CB[8] exhibits a unique recognition pattern with Pt(II) terpyridines, where the positively charged platinum centers are stacked one on top of the other in a ternary complex. Herein, studies exploring potential applications of the complexes between CB[8] and Pt(II) in the fields of molecular machines and antiviral drugs are presented. First, it was found that grafting two Pt(II) terpyridine groups to a flexible central connecting group allows for templation of that central unit to a separate rigid central unit upon complexation with CB[8]. This behavior has potential applications in the field of molecular switches. Second, the capability of the (Pt(II) terpyridine)2·CB[8] complexes to simultaneously bind cysteine and histidine residues in peptides is studied. This new recognition motif could be exploited to develop a new class of antiviral drug. Third, the possible gear-like rotation of (Pt(II) terpyridine thiolate)2·CB[8] complexes is explored. Attempts were made to prove gear-like rotation through modulation of the terpyridine ligands, but attempts have been hitherto unsuccessful. Finally, an attempt to develop a water-soluble strapped porphyrin capable of recognition by CB[7] is discussed. It is believed such a complex could be useful in the development of artificial oxygen carriers.

Committee: Eric Masson (Advisor); Sergio Ulloa (Committee Member); Wenyang Gao (Committee Member); Stephen Bergmeier (Committee Member) Subjects: Chemistry