Tacrolimus is an immunosuppressant drug approved by the FDA for the prevention of organ transplant rejection. However, the use of this drug is hindered by its narrow therapeutic window and extreme insolubility in water. Due to these properties, the currently used tacrolimus preparations must be administered once or twice daily...
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...
Automation of computational chemistry, while only an engineering feat, has the potential to accelerating computational research be removing all by the science. The work in this thesis mainly discusses fundamental understanding of complex chemical systems. What is not obvious are the numerous tasks necessary for this fundamental understanding. Under the...
In this report, three studies are presented that utilize computations to predict transformations, identities, and properties of environmental organic molecules. Each study shows how computations can lead to models of chemical behavior. The importance of this research is rooted in the need for understanding how human behavior and health intersect...
The Kroll Process for the production of zirconium utilizes
the reduction of zirconium tetrachloride with metallic magnesium.
Control of the magnesium content of the final zirconium metal is
essential, as residual magnesium adversely influences the properties
of zirconium.
In this thesis a volumetric method has been presented for the
determination...
Atmospheric fine particulate matter (PM2.5) has been linked to the death of 7 million people per year around the planet. The organic portion of PM2.5 is responsible for increases in oxidative stress, inflammation, mutation and carcinogenesis. Anthropogenic activity releases more organic material into the atmosphere, and has increased the amount...
Many pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
(PBDEs), and polycyclic aromatic hydrocarbons are persistent, bio-accumulative, and
toxic. These semi-volatile organic compounds (SOCs) can undergo atmospheric
transport and deposition in cold, remote ecosystems. A better understanding of their
accumulation in the fish of these ecosystems is important to better predict...
In this work, three isomeric forms of N, N'-diethyl, N, N'-ditolyldipicolinamide (EtTDPA) were synthesized. The elements thorium through americium, which make up a significant portion of the actinides in used nuclear fuel (with the exception of curium), and two fission products, molybdenum and technetium, were tested for their ability to...
Pyroprocessing is an advanced technology for recycling used nuclear fuel. Pyrochemical processes encompass a wide range of chemical, physical, and electrochemical methods to partition fission products and other components from used nuclear fuel, which allows for the reuse of the actinides in nuclear fuel. This dissertation investigates two chemical systems...
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...
Due to a number of disadvantages associated with the use of antibodies as
affinity stationary phases, researchers have recently began to explore the use of RNA
and DNA aptamers for use as affinity stationary phases. These molecules have been
shown to be a viable choice for applications in many methods...
The primary focus of this work is on examining structure-property relationships of interest for high-power nonlinear optical and laser crystals. An intuitive and simply illustrated method for assessing the nonlinear optical potential of structurally characterized noncentrosymmetric materials is introduced. This method is applied to materials including common quartz and tourmaline...
An on-line trace enrichment (TE) system, based on high pressure
liquid chromatogroaphy (HPLC) and flame atomic absorption (AA), has
been developed for trace metal analysis. The sample is pumped through
a column filled with a cation exchange resin which traps metal ions.
The ions are subsequently stripped from the column...
Studies toward synthesis of subunits of sanglifehrin A, an immunosuppressant featuring a highly substituted [5,5]-spirolactam moiety as well as a 22-membered macrocycle are described. The macrolactone contains a peptidic backbone characterized by an unusual [beta]-substituted (S)-piperazic acid and (S)-m-hydroxyphenylalanine units. These studies resulted in the synthesis of advanced intermediate 358...
Plasma sources with multiple electrodes have been developed and
characterized in this research for atomic emission spectroscopy.
Multi-electrode plasma sources use electrodes to shape the plasma in
order to continuously entrain a sample stream in the center of hot
plasma, in a manner similar to an inductively coupled plasma (ICP)...
Fungi have long been used for discovery of new chemical scaffolds. In the clinical setting, the fungal natural products penicillin, statins, and cyclosporine have revolutionized medicine to treat diseases and infections. In the environment, fungal natural products have been used as herbicides, fungicides, and insecticides to protect crops, livestock, and...
Fungi have long been a prolific source of clinically approved drugs. The antibiotic penicillin, the cholesterol lowering statins, and the immunosuppressant cyclosporine have changed the treatment of human diseases in the last century. Recently, genome analysis of filamentous fungi has revealed that the biosynthetic potential for natural product expression is...
Quaternary Ammonium Compounds, Qams, are an important class of
chemicals which present interesting challenges to analysts. This thesis
reports results of investigations on uses of ion-pairing techniques for
separations and detection of Qams. Special apparatus for post-column
solvent extraction of liquid chromatographic eluates was developed as
part of this work....
Porous carbon is indispensable in modern technology applications. It is used for energy storage, gas separation, water purification, catalyst support, and chromatography. The diversity of its applications stems from its unique properties, including high specific surface area, tunable pore volume, and chemical stability. Specifically, the large surface area provides high...
The Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding....
Ultrafast spectroscopy has recently gained momentum as a powerful, noninvasive characterization toolset capable of studying a diverse array of samples with applications in chemistry, physics, biology, engineering, and more. Two popular ultrafast spectroscopic techniques include femtosecond transient absorption (fs-TA) and femtosecond stimulated Raman spectroscopy (FSRS). The latter of these techniques...
The study of natural products (NPs) and their application has shaped humanity. Starting with the idea of using plants as medicine, it has now grown into the science of purifying and identifying organic molecules from nature to study their inherent biological activities. Understanding the molecular structures of NPs is the...
Small molecule drugs have been instrumental in our fight against diseases, beginning when some of the earliest ancient cultures used plant remedies to treat illnesses. More recently, the skill of isolating and characterizing the active ingredients within bioactive plants and microbial extracts has led to the isolation and design of...
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...
A new approach towards a total synthesis of paeoniflorigenin is discussed. The approach involves the application of regio- and stereoselective [2+2] photocycloaddition for the preparation of a key intermediate, cyclobutanone 86, and model studies on diiodosamarium (Sm12) mediated pinacol coupling of a diketone. Intermolecular [2+2] photocycloaddition of a,13unsaturated lactam 33...
The epoxide deoxygenation reaction is formally the reverse of theepoxidation reaction. Compared to epoxidation, which has reached its fullmaturity, epoxide deoxygenation has not been as intensively developed.Among the few deoxygenation reagents, a handful are catalytic in a metalcomplex, show high stereospecificity and operate under mild conditions. Acommon feature of all...
A survey of the methods of purification of KC1, for use in
preparing single crystals by growth from the melt, was made. Two
methods, fractional recrystallization and ion exchange, were used.
The purity of the salt and crystals grown from the same salt were
compared with the findings of other...
The work described herein details the synthesis and application of
biphenyls that probe the effects of hydrogen, Cl / Br, and methyl substituents
on the aryl ring of the terminal acetylenic carbon. From this work, we
successfully developed the rapid synthesis of phenyl acetylenes in 3-4 steps
from inexpensive commercially...
The aqueous chemistries of two transition metal cations, Zr⁴⁺ and Nb⁵⁺, are examined and then used to develop inorganic precursor solutions. The oxides of these cations (ZrO₂ and Nb₂O₅) are deposited and characterized, and their morphological and optical properties discussed. Due to the obstacles created by niobium's aqueous chemistry, an...
The objectives of this study were to isolate 2, 4-diaminobutyric
acid and to attempt cyclizing the acid and its disulfonamide derivative.
The original synthetic method by Adamson was followed but a
modified isolation procedure for the acid was employed.
Following the synthesis, the acidic solution was passed through
Dowex-3 ion-exchange...
The rhenium (V) complex Tp'ReO₂ (Tp' = hydrido-tris-(3,5-
dimethylpyrazolyl)borate), generated in situ from PPh₃ reduction of
Tp'Re0₃, reacts with small ring heterocycles such as epoxides and
episulf ides. The strained trans-cyclooctene ring provides an unusual
thermodynamic bias against direct atom transfer, but trans-cyclooctene
oxide still produces substantial amounts of trans-cyclooctene....
Over the last decade, the miniaturization of analytical systems has become an increasingly important and interesting research area. Miniaturized systems offer many advantages, including reduced reagent and sample consumption, shorter analysis times, portability and disposability. This dissertation describes novel approaches in this direction, focusing on two areas: the miniaturization 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...
Rapamycin (5) was isolated in 1975 from the soil bacteria Streptomyces hygroscopicus and its structure was determined from spectroscopic techniques and an x-ray crystallographic analysis. Although it was initially found to exhibit antibiotic activity, it was subsequently shown to possess potent immunosuppressive activity as well.
Three approaches to the synthesis...
An atmospheric pressure argon glow discharge is shown
to detect trace levels of carbohydrates in aqueous flowing
systems, using either of two glow discharge solution
interface configurations. The first configuration consists
of an oscillating glow discharge sustained between a flowing
aqueous cathode and platinum anode. Picomole and micromolar
mass and...
In Part I, (4S,5R)-4,5-dimethyl-4-phenylcyclohex-2-enone (19a) was prepared in 73% yield with high enantio- and diastereo-selectivity (er > 98:2, dr > 20:1) on a multigram scale by a Yamada-Otani condensation between (E)-pent-3-en-2-one and 2-phenylpropanal catalyzed by a sulfonimide derivative of (S)-proline (18, HuaCat®). Synthetically useful transformations of the cyclohexenone product 19a...
In an attempt to find a laboratory species which develops an
experimental myopathy similar to white muscle disease (WMD) in
lambs, comparative studies of nutritional muscular dystrophy of
chicks were initiated. This condition was grossly visible as white
striations running parallel with the fibers of the pectoral muscles and
was...