In macromolecular X-ray crystallography, typical data sets have substantial multiplicity. This can be used to calculate the consistency of repeated measurements and thereby assess data quality. Recently, the properties of a correlation coefficient, CC[subscript 1/2], that can be used for this purpose were characterized and it was shown that CC[subscript...
The function of a protein is defined by its three-dimensional structure, and in understanding the three-dimensional structure of a protein, we gain an understanding of its function and mechanism. Protein structures, especially at high resolution, can provide detailed insights into many elements of enzyme function and catalysis – identifying residues...
This thesis includes three studies involving different aspects of modeling protein structure. The first study illustrates the levels of insight available from atomic-resolution protein structures. The second study derives general trends of protein geometry from atomic-resolution structures and shows their implications for modeling. The third study creates a model of...
Peroxiredoxin (Prx) enzymes catalyze the reduction of hydrogen peroxide, peroxynitrous acid, and organic peroxides, and are extremely efficient peroxidases, with k[subscript cat]/K[subscript M] on the order of 10⁷ - 10⁸ M⁻¹ s⁻¹. Besides their role in oxidative stress defense, evidence has accumulated that some eukaryotes, including humans, use Prxs as...
The nucleocapsid protein (N protein) of the severe acute respiratory syndrome coronavirus 2 is known to play an essential part of the virus’ functions. The N protein can protect and package the large 29,903 nucleotide genomic RNA whilst also interacting with structural membrane protein M and the spike protein S....
The solution structure determination of DNA molecules has been an important part of structural biology. NMR solution structures are a complement to structures solved via X-ray crystallography; the two methods are the only ways of obtaining three dimensional coordinates of macromolecules. Because of the nature of the molecule, the solution...
We explore the application of deep learning to the disparate fields of natural language processing and computational biology. Both the sentences uttered by humans as well as the RNA and protein sequences found within the cells of their bodies can be considered formal languages in computer science, as sets of...
Ascorbic acid, or vitamin C, is well known as a co-factor for proline-hydroxylase and as an anti-oxidant. However, it is also capable of forming covalent bonds, particularly in the role of a nucleophile, henceforth termed 'ascorbylation'.
The ascorbylation of electrophiles can occur under physiological conditions. Furthermore, there are a number...
Nanoparticles (NPs), defined as materials having at least one dimension (height, width, diameter) in the nanoscale, are increasingly being incorporated into a wide variety of products and are replacing traditional bulk materials in many applications. This is because they can be more efficacious, more sustainable, and can have unique characteristics...
7,7'-Dihydroxy-8,8'-biquinolyl (azaBINOL) was prepared from 7-hydroxyquinoline via N,N-dimethyl O-quinol-7-yl carbamate by directed ortho-metallation followed by FeCl₃-mediated oxidative coupling of the 8-lithioquinoline intermediate. Saponification of the resulting dicarbamate provided crystalline (±)-azaBINOL in 56% overall yield. 6,6'-Bis(dimethylaminocarbonyl)-7,7'-dihydroxy-8,8´-biquinolyl was prepared from the same dicarbamate by a double anionic-Fries rearrangement in 43% yield. 7,7'-Bis(diethylamino-carbonyloxy)-6,6'-diiodo-8,8´-biquinolyl...
The three dimensional structure of both a ligand and its cognate receptor are required for the success of structure-assisted drug design. This thesis reports the crystal structure of hectochlorin, a small, bioactive molecule, and the steps toward determining the crystal structure of an RNA molecule that is an attractive target...
This dissertation details the investigation of an alternate pathway to
isoprenoids that occurs in plants and microorganisms, the non-mevalonate
pathway. This exploration of the pathway focuses on the second step, the
conversion of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methylerythritol-4-phosphate (MEP) by the enzyme DXP isomeroreductase (DXR). These studies led to an appreciation...
The factors influencing the direct nitridation of silicon, including the effects of the native oxide layer covering the surface of silicon, the effects of hydrogen contained in the nitridation gas and the catalytic effects of metals added to the raw material silicon, were investigated, using a tubular flow reactor and...
High purity single crystals of zirconium were produced and
mechanically strained in the temperature range from 4.2°K to 293°K.
The crystals were produced by thermal treatment with a specially
constructed electron beam zone refiner which provided the abrupt
temperature gradient necessary for crystal growth. Specimens were
electrolytically machined to have...
Naturally occurring assemblies, such as DNA and proteins, utilize intermolecular forces (i.e H-bonding and van der Waals) to assemble. Utilizing these electrostatic interactions has only just started in the past five decades to be a tool used in synthetic chemistry in what is known as supramolecular chemistry. Supramolecular chemistry has...
In this dissertation, I present electronic spectroscopy of a few biologically relevant species and their complexes with solvent molecules in the gas phase using a variety of techniques, including resonantly enhanced multiphoton ionization (REMPI), laser induced fluorescence (LIF), and zero kinetic energy (ZEKE) photoelectron spectroscopy. My work on several methylated...
Metal-oxides are very important in industrial applications such as thermal barrier coatings, corrosion protection, and heterogeneous catalysis. The wide variety of applications for metal-oxides are derived from the array of properties of metal-oxides. It is, therefore, important to understand and predict the conditions of synthesis and operation to optimize the...
Exploring bioactive natural products has contributed largely to clinically approved drugs we have been using over the last 100 years. Especially among the anti-infective drugs, around 70% of currently used antibiotics were discovered or derived from microbial secondary metabolites, among them compounds like vancomycin, chloramphenicol, and erythromycin. Facing the unavoidable...
Near-surface advanced argillic hydrothermal alteration zones, also referred to as lithocaps, are characterized by quartz, alunite, clays (pyrophyllite and kaolinite group minerals), and minor F-bearing aluminosilicates (i.e., topaz, zunyite, diaspore, and APS) that form where water-, SO2-, and HF-rich gas condenses into shallow groundwater, acidifies, and reacts with rocks. The...
Nickel or nickel alloys are common materials used in under bump metallization (UBM) in flip chip technology. Nickel is used because of its slow reaction rate with tin-based solder at
elevated temperatures. However, nickel is ferromagnetic at room temperature, hence cannot be easily deposited with magnetron sputtering. In this study,...
As the aging population continues to grow worldwide, age-related complications are becoming more apparent within the aging population. One of the first age-related complications to become apparent is age-associated memory impairment and it can make the elderly more dependent on caregivers early on. The N-methyl-D-aspartate (NMDA) receptor is important to...
A simple matrix method for the analysis of protein circular dichroism (CD) spectra is presented and used to compute the secondary structure of globular proteins in their native and denatured states. The method uses singular value decomposition and generalized inverse algorithms, and a basis set of CD spectra for proteins...
Uses for materials with a large surface area and high porosity have grown sig-nificantly in recent years. Porous materials have found usage in applications such as separation, gas storage, sensing, purification and more, prompting researchers to find and discover numerous new porous materials to suit a specific purpose. Hundreds of...
We have performed fluorescence extended X-ray absorption fine structure (EXAFS) measurements on the Cd K-edge of partial electrolyte (PE) treated Cu(In[subscript 0.7]Ga[subscript 0.3])Se₂ (CIGS) thin film samples using synchrotron X-ray radiation. This data was compared to the EXAFS spectra of CdSe and CdO standards. Cd local structure models were constructed...
The role of the nonionic surfactant Tween 80 on the behavior of the therapeutic recombinant protein Factor VIII (rFVIII) was investigated at solid/liquid and air/water interfaces. In order to provide a model system to compare results obtained for the complicated rFVIII-Tween system, a well-characterized globular protein lysozyme was used. The...
Mycoplasma pneumoniae is the primary cause of community-acquired pneumonias, including what is commonly known as walking pneumonia. This disease affects people from all demographics, but especially children and older adults. Outbreaks are a significant public health concern and work to develop new pharmacological agents is currently being researched. How M....
A preparative method for a new compound n-octadecylcycloazadi-boron (CAB), in high yield has been developed. CAB was isolated as
an intermediate in the octadecylamine-catalyzed hydrolysis of pentaborane.
The most probable structure of CAB can be regarded as a
derivative of the three membered ring cycloazadiboron with a
n-octadecyl group substituted...
Solid solution alloying was employed in an attempt to produce some
relatively ductile form of beryllium. If the c/a ratio could be significantly
altered, it was felt new or different slip systems could be activated. The
following elements were selected on the basis of atomic size, melting point,
crystal structure...
Sugar phosphate cyclases (SPCs) are enzymes involved in the biosynthesis of many important natural products. SPCs form a unique cyclitol during the early steps in the biosynthesis of many natural products. These natural products include rifamycin, which is chemically modified to rifampicin and used clinically as an antituberculosis drug, and...
In an effort to isolate and characterize cardiac glycosides C-17
binding site(s), we have synthesized different affinity and photoaffinity
C-17 side chain probes. These probes were screened for their
ability to inhibit Na⁺,K⁺-ATPase enzyme, a pharmacological receptor
of cardiac glycosides. The enzyme was isolated from hog kidney.
Screening of these...
In order to better predict the aggregation state of nanomaterials, the factors that influence aggregation must be understood. The combined effects of natural and engineered coatings have been shown to factor into nanoparticle aggregation behavior in preliminary research. In this study, aggregation behaviors of gold nanoparticles with two different engineered...
First order prism slip in yttrium single crystals containing a total interstitial impurity content of about 200 wt ppm is almost entirely stage II deformation with a work hardening rate θ/μ of 2·10⁻ ³ . The athermal temperature is about 300°K. Below this temperature an interstitial mechanism is rate controlling...
Nickel (Ni)-based alloys with a high chromium (Cr) content are frequently employed in applications where elevated temperatures and/or corrosive environments are present due to their excellent corrosion resistance and mechanical properties. However, a gap exists around the formation, and kinetics of long-range order (LRO) Ni2Cr phase in both model binary...
Certain 2- chioroethyl nitrosoureas have been demonstrated
to be highly specific inactivators of chymotrypsin
in vitro and glutathione reductase, both in vivo and in
isolated rat hepatocytes. The inactivation of glutathione
reductase in isolated hepatocytes resulted in an increased
sensitivity toward an adriamycin induced oxidative
challenge.
Prolonged incubation of 1-(2-chloroethyl)-3-([1-¹⁴...
Part I. The total synthesis of (+)-leptosphaerin (2), a metabolite of the marine
Ascomycete Leptosphaeria Oraemaris (Linder) was achieved, unambiguously
establishing both the relative and absolute stereochemistry of this natural product. This
synthesis also resolved the long-standing question of which of the isomeric structures 1
or 2 correctly represents the...
Several approaches to the synthesis of penicillin from 2-iminothioazolidine
50, from 2-thiothiazolidine 66 and by photocyclization of
77 and 78 were investigated. 2-Iminothiazolidine 50 was prepared
from dibromoester 45 by the action of benzylamine followed by treatment
of aziridine 46 with potassium or ammonium thiocyanate. Attempted
introduction of a two-carbon...
Recent interest in oxy-fuel combustion for carbon capture, as well as advancements in technologies such as magnetics, materials, and computational modeling has sparked renewed interest in magnetohydrodynamic (MHD) power generation. The increased temperatures of oxy-fuel combustion versus air-fuel combustion poses a challenge in the selection of materials for plasma exposed...
Studies were carried out to determine the absolute stereochemistry of
botryococcene (1). The natural product was degraded to two sets of 'y- and 8-
valerolactones. All enantiomeric variations of these lactones were synthesized in
optically pure form starting from (S)- and (R)-methyloxiranes. 1H NMR correlation of
natural and synthetic materials...
Digital printing techniques offer several advantages in manufacturing electronics such as direct writing of materials, reduction of chemical waste, and scalability. In particular, printing can significantly simplify manufacturing processes by directly defining the channel area, the gate, and the source and drain contacts, allowing for lower costs and higher throughput...
PART I. The preparation of (-)-ibogamine (1) in fourteen steps from benzoquinone and in 10% overall yield is a powerful illustration of the value of the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis. All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl₂ complex...
PART I. Asymmetric syntheses of both natural (+)- and nonnatural (-)-byssochlamic acid via a [2+2] photoaddition-cycloreversion strategy are described. X-ray crystallographic analysis of the cyclohexylamine salt 99 showed that the structure of the monomethyl ester 100 from esterase hydrolysis of 44 was originally misassigned as 56. The enantiomeric relationship of...
This thesis describes the development of a new enantioselective synthetic method employing chiral cis-2,5-diaminobicyclo[2.2.2]octane-based organometallic catalysts. The significance of this new method to organic synthesis is illustrated with preparation of enantioenriched products that are transformed to important pharmaceutical agents. Chapter 1 provides a brief historical overview of asymmetric catalysis, especially...
The level of reactive oxygen species (ROS) is tightly regulated in biological systems as overproduction can lead to oxidative stress and result in a number of diseases. Due to its negative effects, antioxidants are studied and used against ROS in medicine, pharmaceuticals and therapeutics. Because of issues with the uptake...