Ph.D. - Chemistry

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Concerted dehydrogenation reactions of magnesium borohydride with oxygen and nitrogen heterocyclic compounds
(University of Hawai'i at Manoa, 2025) Prager, McKinley A.; Jensen, Craig M.; Chemistry
This dissertation focuses on work resulting from the progress in developing a two-way hy-drogen carrier system consisting of solutions of furans and pyrroles containing Mg(BH4)2 and an irridum pincer complex catalyst. Previous studies have focused on magnesium borohy- dride (Mg(BH4)2) due to its high hydrogen content and favorable thermodynamics. Further studies have shown the kinetic enhancement of the addition of sub-stoichiometric amounts of Lewis bases on cycling. While the kinetic enhancement of the addition of O-heterocycles has been explored the effects of N-heterocycles have not been. Since the discovery in 1997 of the first reported homogeneous catalyst for the dehydrogenation cycloalkanes to arenes, the “pincer” complex IrH2(2,6 -C6H3-(CH2PtBu2)2) and related pincer complexes, are known to be highly active catalysts for the dehydrogenation of heterocyclic liquid or- ganic hydrogen carriers (LOHC). While attempting the tandem dehydrogenation of magne- sium borohydride and pyrrolidine, we found Mg(BH4)2 reacts with pyrrolidine to produce tris(pyrrolidino)borane and bis(pyrrolidino)borane, irreversibly releasing up to 6 wt% H2. The proportions of the pyrrolidino boranes are highly dependent on reaction times and conditions. We have also observed that the iridium pincer complex catalyzes the direct de- hydrogenation of tris(pyrrolidino)borane to tris(1H-pyrrole-1-yl)borane, a significant finding in view of its theoretical, 5.2 wt% gravimetric and >80 g/L volumetric hydrogen capacities. Full characterization of the products along with their hydrogen cycling behavior is discussed.
Development and Analysis of Mechanochemically Treated Magnesium Diboride Based Materials for Hydrogen Storage
(University of Hawai'i at Manoa, 2024) Sugai, Cody Lee Akihiro; Jensen, Craig; Chemistry
With the technical progression of humanity marching ever onwards, new energy carriers are needed to address growing energy and environmental concerns. Hydrogen is one of the most promising energy carriers for the future as it stores much more energy than non-renewable sources while creating no environmentally destructive byproducts during combustion. However, hydrogen utility has yet to overcome challenging transportation and storage hurdles due to a lack of effective storage materials and infrastructure. The cycle between magnesium borohydride (Mg(BH4)2) and magnesium boride (MgB2) is a promising hydrogen storage solution due to the high gravimetric weight % of H2 stored within it, as well as the favorable dehydrogenation enthalpy of Mg(BH4)2. The major challenge faced by the utility of this system is the kinetic limitations in the hydrogenation of MgB2, as the 400° C and 1000 bar of H2 pressure needed are far outside the realm of practicality. Contained in this dissertation is a mechanochemical exploration of reagent and ball milling effects that greatly reduced the hydrogenation requirements of MgB2, as well as an exploration and discussion of a graphenic phase discovered during that exploration that is capable of permanently confining H2 gas. These materials and mechanochemical effects were examined via Fourier Transformation Infrared Spectroscopy (FTIR), Solution and Solid State 11B and 1H Nuclear Magnetic Resonance Spectroscopy (NMR), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning/Transmission Electron Microscopy(S/TEM), High- Angle Annular Dark/Bright Field Imaging (HAAD/BF), Selected Area Electron Diffraction (SAED), Energy-Dispersive X-ray Spectroscopy (EDS), Electron Energy Loss Spectroscopy (EELS), utilized with Focused Ion Beam (FIB) slicing.
MOLECULAR DYNAMICS SIMULATIONS TOWARD ENHANCING MEMBRANE PERMEABILITY AND DYNAMICS
(University of Hawai'i at Manoa, 2024) Kang, Christopher Alan; Sun, Rui; Chemistry
This dissertation focuses on biophysical simulations, with a particular focus on membranes, permeability calculations and enhancing permeability. Molecular dynamics (MD) simulations are used here for bridging the gap between microscopic atomic details and macroscopic experimental properties, such as the equation of state, phase behavior, and structural order. As a complement to traditional experimental techniques, MD simulations have proven to be an indispensable tool for understanding complex biological processes at the atomic level. However, the limited time scales accessible by current computer hardware necessitate the development of importance sampling techniques to estimate free energy landscapes. These methods have highlighted the growing significance of biomolecular simulations, especially given the challenges of sampling multiple low free-energy states using conventional MD approaches. The ability to quantify free energy changes enables the prediction of molecular tendencies such as aggregation, reactivity, and binding affinity. I show below how MD alone, or MD enhanced with importance sampling methods can shed light on a multitude of biological phenomena.
ELUCIDATING MECHANISMS OF GAS-PHASE REACTIONS WITH DYNAMICS SIMULATIONS
(University of Hawai'i at Manoa, 2024) LUO, YUHENG; Sun, Rui; Chemistry
This thesis focuses on enhancing our understanding of chemical reaction dynamics through computational methods, addressing the limitations inherent in experimental techniques. While experimental methods provide valuable insights, they often lack the resolution and sensitivity required to capture the full complexity of chemical reactions.To predict and analyze reaction dynamics more effectively, computational studies initially employ Potential Energy Surface (PES) calculations. PES is instrumental in mapping the energy landscapes that govern chemical reactions, helping to visualize how potential energy varies with molecular configurations and to identify stable intermediates, transition states, and energy barriers. However, PES calculations have limitations, especially in dynamically complex systems where assumptions such as a maintained statistical ensemble for all intermediates do not hold. Situations involving non-Intrinsic Reaction Coordinate behaviors, insufficient intramolecular vibrational redistribution, and direct reactions without long-lifetime intermediate formations where PES alone may not provide complete insights. In response to these challenges, Ab Initio Molecular Dynamics (AIMD) simulations are employed. AIMD goes beyond the limitations of PES by simulating a statistical ensemble of trajectories that reflect experimental conditions, including various impact parameters and orientations of collisions. This method calculates the interactions between atoms using ab initio techniques and updates atomic positions iteratively based on classical equation of motion. By allowing the real-time tracking of atomic motions, AIMD provides a dynamic and detailed view of the molecular transformations during reactions which are often challenging to model with PES-based methods.
UNTANGLING THE FOLDING AND FUNCTION OF LEPTIN
(University of Hawai'i at Manoa, 2024) Simien, Jennifer Michelle; Haglund, Ellinor; Chemistry
Protein biological function is finely tuned by specific three-dimensional structures where biophysical characteristics drive intermolecular interactions. The fundamental principles encoding structure and function in the amino acid sequence is not yet understood. The discovery of protein entanglements has emerged as a topological complexity that adds ruggedness to the folding free energy landscape by introducing a threading event. Pierced Lasso Topology (PLT) proteins consist of a covalent intramolecular loop that is threaded through by a free terminus of the polypeptide chain. How entangled proteins fold into their active native structures and their roles in biology are unanswered phenomena of nature. The model PLT leptin regulates energy expenditure, cellular proliferation, and immune response upon binding to the cognate leptin receptor (LEP-R). Although the structure of the extracellular complex has been solved, the series of events driving formation of the leptin signaling complex has not yet been elucidated. This dissertation investigates the introduction of PLTs in nature, the leptin folding and threading landscape, and structural elements integral for biological activity. I found that PLTs are conserved in protein superfamilies indicating there is a biological advantage to their complexity. Leptin folding experiments suggest threading is a reversible event in a relatively flat folding landscape and revealed a previously overlooked leptin region is essential for function. These findings are foundational in uncovering the biophysical properties driving self-assembly of protein entanglements essential for human health.
Synthesis and Applications of Organobismuth(III) Complexes: Novel Materials and Catalysts
(University of Hawai'i at Manoa, 2024) Louis-Goff, Thomas Aiwei Finfgeld; Hyvl, Jakub; Chemistry
PART IOrganobismuthanes have tremendous potential for utility ranging from optical and semiconductor materials to metallodrugs and catalysts in organic synthesis. Their potential stems from the unique properties of the bismuth atom: its large atomic size imparts high polarizability, available coordination sites from Bi-X bonds (Lewis acidity), and relativistic effects such as spin-orbit coupling. Importantly, bismuth is non-toxic and benign to the environment. As such, bismuth chemistry has experienced increased interest over the past decade. However, some classes of organobismuthanes are still elusive, due to relatively weak Bi-C bonds responsible for dismutation, a substituent scrambling process. In the first chapter, bismuth the element is introduced. Next, bismuth complexes and their applications are briefly reviewed. Then, the issue of their synthesis, specifically dismutation, is addressed, and a detailed study of dismutation modes on the synthesis of heteroleptic triarylbismuthanes is conducted. Although the dismutation is a mechanistically diverse phenomenon, at ambient or lower temperatures, dismutation is triggered mainly by an electrophilic bismuth source. Therefore, the selection of the electrophile, Ar12BiX (X = tosylate or iodide if Ar1 = mesityl) or Ar1BiX2 (X = tosylate), and its use in low concentration during the reaction is key to suppressing the dismutation, leading to new, streamlined protocols utilizing direct arylations of Ar12BiX (X = OTs or I) or Ar1Bi(OTs)2 with organozincs affording heteroleptic triarylbismuthanes Ar12Ar2Bi. In the second chapter, the syntheses of bismuth-bearing monomers based on the diaryl bismuth styrene are described. These new procedures utilize our newly developed method that avoids dismutation. The use of protecting groups on the styryl fragment improves purification of the monomers. Radically induced co-polymerization of the bismuth monomers with p-methyl and p-bromostyrene produce soluble polymers with high refractive indices, low glass transition temperatures, and high temperature degradation properties. Moreover, by varying the ratio of bismuth monomer and organic monomer, these properties can be tailored in a consistent and controlled manner. PART IIThe introduction of C-F bonds into organic molecules imparts favorable properties due to the strength of the C-F bond, including increased chemical and thermal stability, increased hydrophobicity and lipophilicity, and low friction coefficients. Because of this, fluorinated compounds are highly represented in lubricants, refrigerants, and pharmaceuticals, and new methods to install C-F bonds is an active field of synthetic chemistry. 1,1-Difluorocyclopropanes are a specific class of fluorinated compounds that have added utility due to the cyclopropane geometry and reactivity related to the release of ring-strain. However, current methods are either inefficient, or rely on toxic or expensive stoichiometric reagents. In the first chapter, a brief discussion of carbenes and their reactivity is presented, followed by strategies for stabilizing reactive intermediates. The importance of asymmetric catalysis is also highlighted, specifically in carbene and difluorocarbene transformations. Then, the development of an efficient, catalytic olefin difluorocarbenation affording 1,1-difluorocyclopropanes is presented. The catalyst, a hypervalent organobismuth complex bearing a tert-butyl (tBu) amine 5,6,7,12-tetrahydrodibenz[c,f][1,5]azabismocine scaffold, uses the inexpensive trifluoromethyltrimethylsilane (TMS-CF3) as a stoichiometric difluorocarbene source. A wide range of alkenes, including electron-deficient alkenes, and alkynes are viable substrates, demonstrating the generality of this new system. Ease of catalyst recovery from the reaction mixture and catalyst recyclability are other attractive features of this method. In-depth experimental and theoretical studies show that the key difluorocarbene generating step proceeds through a non-redox concerted mechanism generating highly reactive free CF2 in an endergonic pre-equilibrium with the bismuth complex. The reversible difluorocarbene generation and resulting low concentration leads to a high reagent efficiency while minimizing CF2-recombination side reactions. Then, two chiral hypervalent trifluoromethyl organobismuth complexes based on the 5,6,7,12-tetrahydrodibenz[c,f][1,5]azabismocine catalyst scaffold were prepared from commercially available chiral amines, (R)-1-cyclohexylethylamine and (1R, 2R, 3R, 5S)-(–)-isopinocampheylamine; however, only the complex from the latter amine was prepared as a single stereoisomer. The complexes were catalytically active in olefin difluorocarbenation with (TMSCF3), which was used as a terminal source of CF2. The enantiopure catalyst derived from isopinocampheylamine was screened with three prochiral olefins of various reactivity in DCM and toluene. All reactions afforded the 1,1-difluorocyclopropanes in good yields, but no enantiomeric excess was observed. In the second chapter, three new hypervalent trifluoromethyl organobismuth complexes were prepared from previously reported ligand scaffolds: azabismocine, thiabismocine and sulfoximine-bismocine. All three organobismuth complexes were fully characterized by NMR spectroscopy and single-crystal X-ray crystallography, revealing that the structures were similar to their previously reported parent complexes with a hypervalent Bi–N, Bi–O, and Bi–S bonds. The three new complexes were less reactive than the original tBu amine complex from our original study. We probed the catalytic cycle’s two steps to identify that the new complexes are significantly slower in the transmetallation step.
KINETICS, MODELING, AND MECHANISTIC ANALYSIS FOR THE DEHYDROGENATION OF MAGNESIUM BOROHYDRIDE
(University of Hawai'i at Manoa, 2023) Shrestha, Sunil; Jensen, Craig M.; Chemistry
The continuing rise in global population, its growing dependence on technological advances, and the rising prices seen for both natural gas and crude oil, have led to an unrelenting strain on the energy resources of our planet. Increased utilization of fossil fuels, the primary energy source of humans for more than 200 years, has currently led to estimates for their depletion before the turn of the century. In addition to this, increased fossil fuel use results in higher concentrations of greenhouse gases (GHG) released into the atmosphere, contributing to climate change and global warming. Such issues therefore make it imperative to find alternative energies that are abundant, energy-dense, and also environmentally friendly. Hydrogen has long been considered such an ideal fuel because it is non-toxic, naturally abundant, and able to be produced from a wide variety of resources. It is also extremely energy-dense with the energy contained within the hydrogen atom to be the largest of any fuel. The energy derived from hydrogen is considered clean energy when produced from electrolysis, and when combined with O2 in a Polymer Electrolyte Membrane (PEM) fuel cell, produces electricity with the only waste products being heat and water. Its extensive use in everyday fuel applications, however, is constrained by its storage considerations in a safe, compact, and cost-effective manner. A considerable amount of research on hydrogen storage today focuses on using material-based methods of storage, for example, within chemical compounds such as magnesium borohydride, Mg(BH4)2 , an extremely promising candidate for hydrogen storage. This is due to its favorable thermodynamics during hydrogen release, its demonstrated reversibility, and its ability to store large quantities of hydrogen, both by volume and by weight. Unfortunately, as is true for most complex hydrides, slow kinetics appear to be the main obstacle to its utilization. To further understand these issues, this thesis investigates the kinetics of Mg(BH4)2 using line-fitting analysis to model isotherms produced at various temperatures during its dehydrogenation to Mg(B3H8)2 , a system known to be readily reversible under moderate conditions. The dehydrogenation kinetics were also investigated following the addition of tetrahydrofuran (THF) to the borohydride, resulting in rapid hydrogen release at lower temperatures compared to the regular borohydride. The dehydrogenation of Mg(BH4)2 with THF also led to the formation of a second product, the highly stable closoborane, MgB10 H10 . Prior work exploring the reversibility of this system indicated hydrogen cycling under even more mild conditions than that of the unsolvated borohydride. The implications of this claim led to its further investigation. Analyses conducted in this thesis utilized Pressure Composition Temperature (PCT) instrumentation, X-ray Diffraction (XRD), 11B/1H Nuclear Magnetic Resonance (NMR) spectroscopy, and Temperature Programmed Desorption (TPD) with Quadrupole Mass Spectrometry (QMS), the latter conducted at the National Renewable Energy Laboratory (NREL) in Golden, CO, USA.
THE DESIGN AND SYNTHESIS OF NOVEL CHIRAL 2,2’-BIPYRIDINE LIGANDS
(University of Hawai'i at Manoa, 2023) Liu, Chaolun; Tius, Marcus A.; Chemistry
Camphor as a chiral starting material has been widely used in the preparation of chiral auxiliaries and asymmetric ligands. Among the variety of applications, the camphor skeleton with pyridine has been a target for the synthesis of chiral bipyridine ligands. The 2,2’-bipyridine ligand is one of the most commonly used ligands in coordination chemistry. Thus, the development of new chiral bipyridine ligands is of great importance in synthetic chemistry. This thesis describes the design and synthesis of a novel tunable camphor-derived chiral 2,2’-bipyridine ligand. Additionally, the progress towards the synthesis of a planar chiral DMAP catalyst will be discussed. In Chapter 1, the use of camphor in the synthesis of asymmetric pyridine ligands is introduced. The -facial selectivity of camphor-derived cyclopentadiene will be described as well. Next, the development, applications, and limitations of chiral 2,2’-bipyridine ligands are discussed. Lastly, a planar chiral DMAP catalyst is introduced. In Chapter 2, the preparation of a novel camphor-derived bipyridine ligand precursor is described. The discussion includes the careful design of the ligand structure based on several considerations and a 10-step synthesis starting from camphor. In Chapter 3, the stereoselective functionalization of the ligand precursor and the synthesis of bipyridine ligands are discussed. Two chiral 2,2’-bipyridine ligands are prepared as a proof of concept of the tunability. In Chapter 4, we discuss ongoing work towards the development of a planar chiral DMAP catalyst that avoids the chiral resolution during the preparation. The synthesis of the catalyst precursor is described.
Low Coordinate and Low Valent Phosphorus Intermediates for the Synthesis of Multidentate Ligands and New PN Heterocycles
(University of Hawai'i at Manoa, 2023) Miura-Akagi, Preston; Cain, Matthew F.; Chemistry
Phosphorus has proven to be a versatile asset in the chemist’s repertoire. Its initial uses as nucleophiles in organic synthesis and ligands in transition metal chemistry is well documented, but more recently, unusual bonding, structures, and reactivity at the P-center have been described. Herein, we report fundamental advancement in organophosphorus chemistry by utilizing monovalent phosphinidenes (R–P) as an intermediate to complex ligand architectures and new heterocyclic scaffolds. Specifically, we synthesized a tetradentate tris(phosphaalkene)phosphine ligand that supports sterically shielded trigonal bipyramidal transition metal complexes and developed a streamlined route to new 10-electron benzazaphospholes that upon dearomatization feature exceedingly long and reactive exocyclic P–X bonds.
Probing Hydrogen Mesosorption by High Pressure Nuclear Magnetic Resonance Spectroscopy
(University of Hawaii at Manoa, 2022) Nakamoto, Bryson Yoshio; Jensen, Craig M.; Chemistry
Concerns related to fossil fuels as an energy source has driven studies to shift focus to renewable energy. Specifically, the development of hydrogen as an onboard energy carrier. Hydrogen possesses a large amount of energy and has the potential to be a viable renewable energy carrier. Chemisorption and physisorption are two types of material-based interactions researched for hydrogen storage. Physisorption interactions have low binding energies which results in fast kinetics and complete reversibility. However, low binding energies also require liquid nitrogen temperatures to hold the hydrogen to sorbents. Carbon materials have a binding energy of 4-7 kJ/mol to H2, however doped carbon material have shown to improve the binding energy of specific binding sites. Overall, the materials have a relatively low hydrogen storage capacity, but the high energy binding sites supplies valuable information about the possibilities of future dopants. Binding energies needed to facilitate near ambient conditions are found in a region between physisorption and chemisorption, known as mesosorption. Current techniques cannot reliably characterize mesosorption interactions as they are observed on specific high energy binding sites. The technique developed for the observation of strong binding sites utilizes 1H Nuclear Magnetic Resonance (NMR) spectroscopy to examine the change in free and bound hydrogen under high pressures and variable temperatures. Based on the temperature dependent equilibrium, the ΔHdes of a specific high energy binding site was calculated. Studies presented in this dissertation are based on this specialized NMR technique and are used to analyze boron-doped carbon and other materials to identify limitations. Employing high pressure NMR analysis in this manner has shown to be versatile and provides valuable thermodynamic data on compounds typically difficult to investigate.
Catalytic Asymmetric Nazarov Cyclizations & Methods for the Synthesis of Fluorenes and Advanced Geodesic Polyaromatic Hydrocarbons
(University of Hawaii at Manoa, 2022) Dickinson, Cody Francis; Tius, Marcus A.; Chemistry
PART I: CATALYTIC ASYMMETRIC NAZAROV CYCLIZATIONS The synthesis of all-carbon quaternary stereocenters remains a significant challenge in organic synthesis. Even more challenging is the synthesis of vicinal all-carbon quaternary stereocenters. While there are a small number of methodologies that have attempted to address both of these problems, there are very few reports on the catalytic asymmetric synthesis of the latter type. The Nazarov cyclization offers a unique opportunity to address this problem, in that the orbital symmetry-controlled process can be catalyzed in a number of different ways because of the diversity of the acyclic precursors. This thesis will describe a new catalytic asymmetric synthesis of compounds containing vicinal all-carbon quaternary stereocenters through a Nazarov cyclization. In the first chapter the Nazarov cyclization is introduced and briefly reviewed. A brief review on catalytic asymmetric variants of this reaction is given. In the second chapter an (R)-BINOL-derived N-triflyl phosphoramide-catalyzed Nazarov cyclization of geometrically pure dienones to α-hydroxycyclopentenones is described. This follow up work describes an expanded substrate scope to all-alkyl C1,C2-tetrasubstituted cyclopentenones containing vicinal quaternary centers and to C1,C5-trisubstituted cyclopentenones containing vicinal quaternary and tertiary centers. The mode of asymmetric induction is discussed.In the third chapter a novel Lewis acid-Brønsted base-catalyzed cyclization of α-diketoesters to α-hydroxycyclopentenones is described. The chiral-at-rhodium catalyst for this metal enolate Nazarov cyclization is unique and demonstrates high catalytic activity and enantioselectivity. The substrate scope of all-aliphatic α-hydroxycyclopentenones bearing either vicinal quaternary or vicinal quaternary and tertiary stereocenters is described. PART II: METHODS FOR THE SYNTHESIS OF FLUORENES AND ADVANCED GEODESIC POLYAROMATIC HYDROCARBONS Polyaromatic hydrocarbons (PAH) have a long and rich history in organic synthesis. At the forefront today is the synthesis of highly strained geodesic compounds, for example, buckminsterfullerene, C60 (buckyball). Interest in non-planar PAHs has grown because of their unique UV-vis, electronic, and structural properties. The use of these compounds in asymmetric catalysis has not been described to date, possibly because their synthesis is impractical on scale. As such, our group has an interest in developing new methodologies to address these shortcomings. We have focused on the fluorene motif as an initial starting point in the synthesis of more advanced PAHs, since many others have identified it in geodesic hydrocarbons. In the first chapter a new methodology for the preparation of fluorenes and dibenzo[g,p]chrysenes through an oxidative cascade process using copper(II) bromide is described. A novel dibenzo[g,p]chrysene containing an ether linkage is reported. In the second chapter a synthesis of a geodesic, C30 semibuckminsterfullerene “buckybowl” is described. The synthetic route used to access this compound is versatile and modular. The scalable and simple synthesis of a strategic precursor 1,8-difluoro-9H-fluorene is also described.
Isolation, structure elucidation and analytical methodologies for natural products
(University of Hawaii at Manoa, 2022) O'Donnell, Timothy Joseph; Williams, Philip G.; Chemistry
Several chemically diverse natural products were isolated from cyanobacterial media and cell mass from both marine and terrestrial sources. The media investigations led to the discovery of six new stereochemically rich sesquiterpenoids from two structural classes. Their full characterization was a challenging effort that led to development of a comprehensive approach to the structure elucidation of each class of compound utilizing common spectroscopic analyses heavily supported with computational NMR and ECD prediction. A series of studies involving the cyanobacterial consortium HT-58-2 were conducted. The first study has assessed tolyporphin production in various growth conditions and searched for tolyporphin production in other cyanobacterial strains. The second, a cell mass extraction, led to two new tolypodiol analogs and the final project, a time-course study, used molecular networking to provide insights into secondary metabolite production over time and identify potential targets for future natural product projects. Two other cell mass extraction projects of Moorea producens 11-Kauai-92 and Calothrix sp. R-3-1, led to the isolation and partial characterization of a potentially new malyngamide and a new glycoside, respectively. Finally, a series of projects focused on analytical method development and data analysis are presented starting with a targeted method development for LCMS analysis of carotenoids, followed by a second method development utilizing an LCMS Omics approach and its data analysis, and a final section with a series of projects highlighting the integral nature of computational prediction on the interpretation of ECD spectra.
Synthesis and Coordination Chemistry of Multidentate Phosphaalkene Ligands
(University of Hawaii at Manoa, 2021) Nakashige, Mika Lyn; Cain, Matthew F.; Chemistry
Phosphaalkenes (R’P=CHR) contain low-lying π* orbitals that can accept electron density, leading to the stabilization of electron-rich metal centers. In addition, phosphaalkenes are capable of undergoing redox-active/non-innocent processes, and we will explore if these properties can be exploited by constructing multidentate phosphaalkene-based ligands that create well-defined metal complexes with a single open and reactive coordination site. In the following chapters, we will discuss the coordination chemistry of new PN bidentate ligands, the synthesis of a PNP pincer, and the generation of sterically shielded Rh(I) and Ir(I) complexes supported by a tetradentate tris(phosphaalkene)phosphine ligand.
Methionine Salvage Pathway is Promiscuous Towards 5′-Deoxyadenosine and 5′-Methylthioadenosine
(University of Hawaii at Manoa, 2020) Tran, Don Luong; Jarrett, Joseph T.; Chemistry
S-Adenosylmethionine (aka. SAM or AdoMet) is a highly reactive metabolite that can be useful by many organisms for a variety array of biosynthesis and regulatory purposes. Common enzymes and biosynthetic pathways that require SAM include certain methyltransferase enzymes, polyamine biosynthetic pathways and the radical SAM enzyme superfamily. Overall, from these common biological pathways, as SAM is consumed to perform several unique functions, S-adenosylhomocysteine (SAH), 5’-methylthioadenosine (MTA), and 5’-deoxyadenosine (5’-dAH) are produced as byproducts. There are known pathways to recycle or degrade SAH and MTA. However, for 5’-dAH, no recycling or degradation pathway has yet been discovered. Recent works by the Jarrett laboratory has found that certain enzymes in Escherichia coli have sequence homology to characterized enzymes from the eukaryotic methionine salvage pathway that normally recycle MTA to form methionine. Our findings suggest that these E. coli methionine salvage pathway enzymes can likely also degrade 5’-dAH, suggesting that the methionine salvage pathway is highly promiscuous towards degrading MTA, 5’-dAH, and possibly even SAH. So far, research on the methionine salvage pathway (including the Jarrett laboratory) has shown that the first pathway enzyme: 5’-methylthioadenosine nucleosidase (MtnN) is promiscuous and cleaves adenine from MTA, 5’-dAH, and SAH to produce 5-methylthioribose (MTR), 5-deoxyribose, and S-ribosylhomocysteine (SRH) respectively. To expand upon the theme of enzyme promiscuity, I turned my attention to the second methionine salvage pathway enzyme in E. coli: 5-methylthioribose kinase (MtnK). This dissertation will discuss investigations of E. coli MtnK and the reaction catalyzed by this enzyme with MTR, 5-deoxyribose, and SRH substrates.
Dynamic Behavior In Polyhydrogen Iridium Complexes
(University of Hawaii at Manoa, 2019) Sartain, Hope Tennyson; Jensen, Craig M.; Chemistry
In 1984, Kubas and co-workers determined the molecular structure of W(η2- H2)(L)3(PR3)2 by a single crystal neutron diffraction study. This seminal study established that molecular hydrogen could bind to a metal center in a “side-on” fashion without cleavage of the H-H bond forming the classical dihydride, M-(H)2. The terms “Kubas compound” and “Kubas-interaction” are now familiar to all scientists working in the areas of metal hydrides and physi-sorbed hydrogen. The bonding in a Kubas complex is described as involving a donation of electrons from the H2 σ orbital to a linear empty metal valence orbital and a back-bonding donation from a filled metal dπ orbital to the empty σ* orbital of the H2. In the Kubas interaction, the H2 ligand is primarily considered a σ base and a σ* acid. Alternatively, the bonding of an H2 ligand to a metal center could involve an “end-on” interaction, a 3-center 4-electron bond rather than a non-classical 3- center 2-electron bond (Kubas interaction). In the end-on bonding model, the H2 ligand is primarily considered a σ* acid. We recently determined the molecular structure of IrHx{2,6-C6H3-(OAs(tBu2))2} through a single crystal X-ray diffraction study. Surprisingly, upon refinement of both occupancy and position, the H2 ligand was found to be oriented in an “end-on” rather than “side-on” coordination motif. This defense will discuss the details of the M-(η1-H2) bonding mode and alternative characterization methods, most notably NMR spectroscopy. Through the studies of IrHx{2,6-C6H3-(OAs(tBu2))2}, and the possible discrete M-(η1-H2) coordination, an earlier project of the Jensen lab was revisited. In order to gain insight into the dynamic polyhydrogen bonding of M-(H)2 and M-(η2-H2) in an alternate iridium system, neutron diffraction data of IrBrHx(iPr3P)2·C10H8 and IrClHx(iPr3P)2 have been obtained and will be discussed. Surprisingly, upon refinement of IrClHx(iPr3P)2, the H2 ligand was found in an unusual eclipsed conformation of one of the complexes in the crystal structure.
Development of Magnesium Borohydride Etherates as Hydrogen Storage Materials
(University of Hawaii at Manoa, 2019) Nguyen, Phuong Quang Hoang; Jensen, Craig M.; Chemistry
The studies presented in this dissertation are to aim at understanding the kinetic enhancement of Lewis base THF-adduct of Mg(BH4)2 and evaluating the potential for hydrogen storage under moderate reaction conditions. The physiochemical properties of independently synthesized Mg(BH4)2(THF)x (x = 0.25 - 3) are studied using in-situ XRD and NMR spectroscopy, and differential scanning calorimetry (DSC). We find that the complex mixture undergoes solid-solid phase transformation and endothermic melting at temperature <100 oC. Further heating to 180 - 200 oC results in release of H2 to form MgB10H10 as the major product. Using Pressure-Composition-Temperature (PCT), the reaction can be cycled between MgB10H10 and Mg(BH4)2 by maintaining the supervicous state of the material. Ca. 25% conversion through 3 cycles, dehydrogenation at 4 bar H2 back pressure and rehydrogenation at 90 bar H2, is observed. It is noted that crystallization of the dehydrogenated state at reaction times longer than 10 hours or cooling of the melt to room temperature curtails the reversibility. We also examine the role of magnesium tetrabutoxyborate, proposed to arise from the ring opening of THF by Mg(BH4)2 attack, in the reversible cycling between MgB10H10 and Mg(BH4)2. No reversibility of MgB10H10 is observed upon introducing independently synthesized Mg[B(OBu)4]2 (Bu = C4H9) in the hydrogenation attempts. Intrigued by the reversibility of THF-solvate Mg(BH4)2/ MgB10H10, similar approach is conducted for newly independently synthesized MgB12H12(THF)3. No melting of MgB12H12(THF)3 upon heating and no formation of BH4-, characterized by NMR analysis, is observed.
A Photoionization Reflectron Time-of-Flight Investigation of Phosphorus Chemistry in Extraterrestrial Ices
(University of Hawaii at Manoa, 2018-05) Turner, Andrew M.; Chemistry
Multiple phosphorus-containing compounds have been detected in the Solar System (planetary atmospheres, comets, meteorites) along with interstellar and circumstellar environments. Of particular astrobiological interest are alkyl phosphonic acids (RH2PO3, R = methyl, ethyl, propyl, and butyl) extracted from the Murchison meteorite. These phosphonic acids are the only extraterrestrial phosphorus-containing organic compounds thus far discovered and offer a bioavailable and highly soluble form of phosphorus due to its reduced oxidation state. The research of this dissertation investigates the synthesis of phosphorus-containing products of electron-irradiated interstellar ice analogues containing phosphine (PH3), water (H2O), carbon dioxide (CO2), and hydrocarbons such as methane (CH4). Phosphine is known to exist in circumstellar envelopes (IRC +10216), is hypothesized to exist in comets (67P/Churyumov-Gerasimenko), and may serve as the phosphorus source of complex organic compounds such as the alkyl phosphonic acids. Utilizing in situ analysis techniques such as quadrupole mass spectrometry (QMS), tunable-photoionization reflectron time-of-flight mass spectrometry (PI-ReTOF-MS), and infrared spectroscopy (FTIR) in addition to ex situ analysis by secondary-ion mass spectrometry (SIMS) and two-dimensional gas chromatography mass spectrometry (GC×GC-TOF-MS), the intermediates and products of these irradiated ice analogues are characterized to demonstrate the potential to synthesize organic phosphine-containing molecules in astrophysical environments. Notable results include phosphanes (PxHx+2), methylphosphanes (CH3PxHx+1), and phosphorus oxoacids (H3POx, x=1−4, and pyrophosphoric acid (H4P2O7)) along with their alkylated equivalents such as prebiotically significant methylphosphonic acid (CH3P(O)(OH)2) and methylphosphate (CH3OP(O)(OH)2).
Isolation and Elucidation of Structures of Biologically Active Secondary Metabolites from Various Organisms, Including Cyanobacteria, Sponges, and Areca catechu.
(University of Hawaii at Manoa, 2017-12) Neupane, Ram P.; Chemistry
Investigation of extracts of several biological specimens, including cyanobacteria, sponges and Areca nut, for activity in various biological assays led to the isolation of several known and new secondary metabolites. Sesquiterpene quinones and hydroquinones isolated from the sponge Dactylospongia elegans Thiele (Thorectidae) showed strong to moderate cytotoxicity (CC50 between 2.4 and 22.6 μM) against human glioblastoma (U251MG) and human pancreatic carcinoma (Panc-1) cell lines. Furthermore, ilimaquinone (IC50 65 μM) and smenospongine (IC50 78 μM) exhibited moderate inhibition of BACE1, an enzyme implicated in the pathogenesis of Alzheimer’s disease. The aqueous fractions of the extracts of Areca catechu L. (Arecaceae) displayed Ca-signaling effects in immune (Jurkat, U937 and RBL-2H3) cell lines and the components responsible for this activity may be oligomeric or polymeric flavonoids. The utility of prediction of 1H and 13C NMR chemical shifts using density functional theory computations was demonstrated in the elucidation of structures of three new molecules.
Isolation and Structure Elucidation of New Marine Natural Products Isolated from Hawaiian Invertebrates
(University of Hawaii at Manoa, 2017-08) Parrish, Stephen M.; Chemistry
Extracts of three species of sponge and an egg mass of the nudibranch Hexabranchus sanguineus were examined because they displayed biological activity against either BACE1 or HSV-1 and VSV. In some cases bioactivity guided isolation led to the purified active agent, while in others a loss of activity led to chemical investigations of the extract. The fruits of this labor were identification, characterization, and, in most cases, biological evaluation of 7 new and 10 known compounds from four separate structural classes. The structures of these compounds were elucidated through analyses of NMR experiments(1H, 13C, TOCSY, HMBC, HSQC, COSY, ROESY, and NOESY), HR-MS data, computational simulations, and optical rotations.
Crystal Structure Determination Of Two New Red Fluorescent Proteins By X-Ray Crystallography
(University of Hawaii at Manoa, 2017-08) Huang, Mian; Chemistry
Recently scientists are interested in developing new variants of red fluorescent proteins (RFPs), because biosensors basing on RFPs show visual superiority in live-cell imaging. In this thesis, the structures of two RFP variants, K78BoF and mRuby0.4-3, were investigated by X-ray crystallography. A monomeric crystal structure of K78BoF was obtained at pH 6 with resolution at 2.13Å, while a dimeric crystal structure of mRuby0.4-3 was determined at pH 8.2 with resolution at 2.63Å. Both of their chromophores are formed by Met-Tyr-Gly with K78BoF in the cis state and mRuby0.4-3 in trans. Hydrogen bonds connecting water molecules and residues to K78BoF chromophore probably stabilize the conformation of the chromophore and contribute to the red fluorescence emitted. However, the substitution of an unnatural amino acid pboronophenylalanine breaks two hydrogen bonds, causing a deviation of the conformation. Analysis of hydrogen bonds on mRuby0.4-3 chromophore was limited by the relatively low resolution of the crystal.

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