Three distinct methods to achieve the stereoselective synthesis of carbon-carbon bonds were investigated, encompassing: (i) the formation of axially chiral biaryl molecules by enantioselective Suzuki cross-coupling, (ii) the synthesis of α-phenylalkylboronic esters by enantioselective chain extension, and (iii) the stereospecific synthesis of alkenes by eliminative cross-coupling of enantioenriched sp³-hybridized carbenoids....
Enantioenriched sp³-hybridized carbenoid reagents CR1R2MX (X = nucleofuge, M = electrofuge) of different types were investigated for the synthesis of polysubstituted alkyl chains by iterative stereospecific reagent-controlled homologation (StReCH) and for the stereospecific connective synthesis of alkenes by eliminative cross-coupling.
In the first part, putative enantioenriched α-chloroalkyllithiums (CHRLiCl) were employed...
In this report, three studies are presented that aid in the development of drug discovery and their synthesis. In each, the importance of the marriage between computations and experiments is highlighted. Continued efforts in this vein are essential for future efforts towards improving human health.
The first case study investigated...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants formed from the incomplete combustion of organic material. These contaminants are of concern because of their widespread presence in the environment and toxic properties. In addition, PAHs encompass a class of diverse compounds with varying physicochemical properties and exist in the environment as...
• Bladder Cancer in the United States has
progressively been one of the more common
cancers and is estimated to have 74,000 new
cases as well as 16,000 deaths in 2015.1
• This type of cancer also has one of the highest
rates of recurrence with an average of 60%...
Perdeutero-spiropentane (C₅D₈) has been synthesized and infrared and Raman spectra are reported for the first time. Wavenumber assignments are made for most of the fundamental vibrational modes. Gas phase infrared spectra were recorded at a resolution (0.002 cm⁻¹) sufficient to resolve individual rovibrational lines and show evidence of strong Coriolis...
In this Dissertation, the mechanism and stereomechanics of complex organocatalysis and reaction processes are disclosed. The technologies and protocols currently being developed and utilized to efficiently investigate these systems using theory are highlighted.
A detailed computational study of peptide-catalyzed acylations is disclosed. In particular, the magnitude of all possible non-bonding...
Oxidative stress is defined as an imbalance that favors the production of reactive oxygen species (ROS) over an organism's antioxidant defense. ROS have the ability to damage, either directly or indirectly, biomolecules including DNA, proteins, carbohydrates, and lipids. Various pathological conditions and environmental and chronic diseases have been associated with...
The discovery of novel compounds with antibacterial properties continues to be critically important.3 One potential source of such compounds is the cryptic genome of fungi known to produce biologically active molecules. A kmt6 mutant of the cereal pathogen Fusarium graminearum was previously developed through a histone H3 lysine 27 methyltransferase...
With increasing use of new pesticide formulations worldwide to repel and kill unwanted organisms, negative consequences on non-target species such as honey bees and other pollinators are of increasing concern and not well studied. This study compares the nanotechnology based pesticide (NBP) Safari and its base neonicotinoid, dinotefuran, and their...
There has been a tremendous growth in interest in carbon nanodots (C-dots) in the past several years. As a nascent nanomaterial, C-dots have shown great promise in applications that benefit from their superior water dispersibility, low toxicity, non-blinking fluorescent output, chemical and biological compatibility, ease of functionalization and resistance to...
In this dissertation, I describe the experimental investigation of catching ions in superfluid helium droplets. The ultimate goal of our project is to build a coherent electron diffraction apparatus for atomic structure determination from oriented single macromolecules. This involves generating protein ions from electrospray ionization (ESI) and doping them in...
This dissertation describes the racemic and enantioselective synthesis cavicularin. Cavicularin is a macrocyclic bisbibenzyls family member natural product. It has been an attractive synthetic target due to its intriguing structure: the macrocyclic core imparts sufficient strain on the system to force one benzene rings to adopt a boat-shaped conformation, out...
In this dissertation, I describe spectroscopic studies of jet-cooled polycyclic aromatic hydrocarbons (PAH) and one nitrogen substituted PAH (PANH) using pulsed field zero kinetic energy (ZEKE) photoelectron spectroscopy and resonantly enhanced multiphoton ionization (REMPI) spectroscopy. Recently, there has been a demand for far-infrared (FIR) spectral information of astrophysically relevant molecules...
The enantioselective total synthesis of quinolizidine-containing natural product cermizine D and formal syntheses of senepodine G and cermizine C has been achieved. These natural products are members of the lycopodium alkaloids, which have attracted significant attention due to their exciting biological activities and the diverse structural scaffolds. Key steps in...
Two distinct strategies were explored for the enantioselective synthesis of α-heteroatom substituted alkyl boronic esters by stereoselective reagent-controlled homologation using transient chiral carbenoid reagents CHYMX (Y = heteroatom, X = nucleofuge, M = electrofuge). In the first case, a stereospecific reagent-controlled homologation (sStReCH) approach to α-alkoxyalkylboronates using α-metalated S,O- and...
The yields of 235 projectile-like and target-like fragments from the interaction of ¹³⁶Xe with a thick target of ²⁰⁸Pb at a center-of-mass energy, E[subscript cm], of 450 MeV were measured using γ-γ-γ coincidence data from Gammasphere and off-line γ-ray spectroscopy. The results give an expansive picture of the production cross...
Complex organic transformations, such as the addition of pyrrole to ketene using planar chiral organocatalyst (*PPY), the four-component anhydride- Manniach reactions, and the site-selective desymmetrization of meso-1,2-diol, are remarkable synthetic reactions that provide high yield and high selectivity. However, the exact mechanism and origins of stereocontrol for theses synthetic organic...
This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society and can be found at: https://doi.org/10.1021/acs.est.5b00499
Propolis is a gummy material produced by honey bees to protect their hives and currently has drawn the attention of researchers due to its broad clinical use. It has been reported, based only on observations, that honey bees also collect other non-vegetation substances such as paint or asphalt/tar to make...
Molecular chirality plays a critical role in chemistry, biology, and medicine. To study and better understand conformational chirality, it is necessary to obtain structurally interesting molecules that exhibit this form of chirality. Our lab utilizes total synthesis and methodological development to obtain conformationally chiral natural products of interest. We believe...
Novel synthetic strategies are developed to prepare new intercalation compounds and nanocomposites with several layered hosts (NiPS₃, Na-montmorillonite, MoS₂ and MoO₃). In these products, alkali metals are ionic intercalates and linear polymers, dendrimers or amines act as co-intercalates. In addition to new synthetic approaches, new structures are identified and characterized....
Signal transduction within and between cells is at the core of biological activity in all living systems. Signaling networks are required for regulating biological functions, including growth, development and survival. Deregulation of signaling cascades has been linked to chronic and acute diseases and disorders This thesis focuses on mass spectrometry...
Aminal radical intermediates were generated by the method of radical translocation and reacted in C-C bond forming reactions with electronically deficient alkenes (Schiedler et al. Org. Lett. 2012, 14, 6092). Aminal radical intermediates can participate in inter- and intra-molecular reactions using both Bu3SnH and (TMS)₃SiH as hydride donors. Carbon–carbon bonds...
In this thesis, I present a new method we developed to study low frequency (< 700 cm⁻¹) vibrational dynamics: Time-resolved third-harmonic generation (TRTHG) spectroscopy. Among a variety of vibrational spectroscopy techniques, TRTHG differentiates itself with robustness, versatility, and simplicity. In TRTHG experiment, that involves only two ultrashort laser pulses, the...
Sodium-ion batteries are emerging as a highly promising technology for large-scale energy storage applications. However, it remains a significant challenge to develop an anode with superior long-term cycling stability and high-rate capability. Here we demonstrate that the Na⁺ intercalation pseudocapacitance in TiO₂/graphene nanocomposites enables high-rate capability and long cycle life...
Endophytes are bacteria or fungi that live within a host plant. The plant host provides a home for endophytes, and in return endophytes produce primary and secondary metabolites, of which many of the secondary metabolites possess biological activities. When microorganisms are grown under various media conditions, they produce different natural...
My work on computing complex catalyzed organic transformations reveals that only a few subtle chemical factors, e.g. non-classical hydrogen bonding, (hyper)conjugation and steric effects, common across different catalyst manifolds are critical for catalysis and selectivity. Rational manipulation and exploitation of these factors has led to improved catalyst designs, which has...
The relative influences of trans-Pacific and regional atmospheric transport on measured concentrations of polycyclic aromatic hydrocarbons (PAHs), PAH derivatives [Nitro- (NPAH) and Oxy-(OPAH)], organic carbon (OC), and Particulate Matter (PM) less than 2.5 μm in diameter (PM₂.₅) were investigated in the Pacific Northwest, USA in 2010-2011. Ambient high volume PM₂.₅...
Research and public concern of poly and perfluoroalkyl substances (PFASs) as environmental contaminants has increased significantly due to the increasing number of reports of their detection in humans and wildlife. PFASs have a number of commercial applications including surfactants, coatings, polymers, and levelers, which are used on consumer products like...
The heterogeneous reactions of ambient particulate matter (PM)-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) with NO₃/N₂O₅, OH radicals, and O₃ were studied in a laboratory photochemical chamber. Ambient PM[subscript 2.5] and PM₁₀ samples were collected from Beijing, China and Riverside, California, and exposed under simulated atmospheric long-range transport conditions...
While properties are extremely important from an application point of view, it is crucial to have a detailed understanding of the underlying structural influence. Once a concrete correlation between the structure and the observed property is established, rational design of novel materials with optimized properties can be realized. These optimized...
Organic compounds which contain one or more nitrogen atoms are especially important as they are disproportionately represented among biologically active molecules. As a result, significant effort has been focused on the development of methods for the synthesis of nitrogenous molecules. We identified the aminal as an under-explored functional group. Despite...
In this dissertation, my research work on excited state dynamics of small organic molecules in solutions is presented. Using femtosecond stimulated Raman spectroscopy (FSRS) as the main experimental tool, the excited state hydrogen-bonding dynamics (ESHBD) of Coumarin 102, a common laser dye molecule, in ethanol solution is examined with <150...
Atmospheric measurements of semivolatile organic compounds (SOCs) were made at Mt. Bachelor Observatory (MBO), located in Oregon’s Cascade Range, to understand the trans-Pacific and regional transport of SOCs from urban areas. High volume air sampling (~644 m³ for 24 hour periods) of both the gas and particulate phases was conducted...
The regiodivergent O- to C- or N-carboxyl transfer of pyrazolyl carbonates is described, with DMAP giving preferential N-carboxylation and triazolinylidenes promoting selective C-carboxylation (both with up to >99 : 1 regioselectivity). An enantioselective O- to C-carboxyl variant using NHC catalysis is demonstrated (up to 92% ee), while mechanistic and DFT studies outline...
Lycopodium alkaloids have shown widespread and noteworthy biological activity, consisting of over 250 known natural products. Moreover, their structural complexity and diversity have attracted considerable attention from numerous laboratories including our own. Recently, we have developed a unified approach that would provides access to numerous, previously unprepared C₁₀-functionalized lycopodium alkaloids....
The synthesis of isoindazoles bearing α-ketoester and α-hydroxyester groups via the coarctate cyclization of ester terminated azo-ene-yne precursors is described. Whereas previous studies on isoindazole formation have shown the reaction to proceed through a kinetic coarctate pathway, functionalization of the terminal acetylene with a methyl ester sufficiently stabilizes the carbene...
Historic and current use pesticides (HUPs and CUPs), with respect to use in the United States and Canada, were identified in trans-Pacific and regional air masses at Mt. Bachelor Observatory (MBO), a remote high elevation mountain in Oregon’s Cascade Range located in the United States, during the sampling period of...
This chapter describes a mass spectrometry-based strategy that facilitates the unambiguous identification and characterization of proteins modified by lipid peroxidation-derived 2-alkenals. The approach employs a biotinylated hydroxyl amine derivative as an aldehyde/keto reactive probe in conjunction with selective enrichment and tandem mass spectrometric analysis. Methodological details are given for model...
This research is the first to quantify complex PAH mixtures in NIST SRMs using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/ToF-MS), with and without extract cleanup, and reports previously unidentified PAH isomers in the NIST SRMs. We tested a novel, high orthogonality GC column combination (LC-50×NSP-35), as...
After the April 2010 explosion on the Deepwater Horizon oil rig, and subsequent release of millions of barrels of oil, two Corexit oil dispersant formulations were used in unprecedented quantities both on the surface and sub-surface of the Gulf of Mexico. Although the dispersant formulations contain four classes of surfactants,...