Human glutathione synthetase (hGS) is a homodimeric enzymes that catalyzes the second step in the biological synthesis of glutathione, a critical cellular antioxidant. The enzyme exhibits negative cooperativity towards the γ-glutamylcysteine (γ-GC) substrate. In this type of allosteric regulation, the binding of γ-GC at one active site significantly reduces substrate affinity at a second active site over 40 Å away. The presented work explores protein-protein interactions, substrate binding, and allosteric communication through investigation of three regions of hGS: the dimer interface, the S-loop, and the E-loop. Strong electrostatic interactions across the dimer interface of hGS maintain the appropriate tertiary and quaternary enzymatic structure needed for activity. The S-loop and E-loop of hGS form walls of the active site near γ-GC, with some residues serving to bind and position the negatively cooperative substrate. These strong interactions in the active site serve as a trigger for allosteric communication, which then passes through hydrophobic interactions at the interface. A comprehensive computational and experimental approach relates hGS structure with activity and regulation. ATP-grasp enzymes, including hGS, utilize ATP in the nucleophilic attack of a carboxylic acid in a reaction thought to proceed through the formation of an acylphosphate intermediate. Small metal cations are known …

The purpose of this study was to determine the factors affecting the acid degradation of chrysotile asbestos (Mg_3Si_2O_5(OH_4)) . Millions of tons of asbestos have found use in this country as insulative or ablative material. More than 95 percent of the asbestos in use is of the chrysotile variety. The remaining 5 percent is composed of various types of fibrous amphiboles. The inhalation of asbestos can lead to several diseases in humans. Asbestosis, lung cancer and mesothelioma are the most common afflictions associated with asbestos inhalation, and they may occur up to 40 years after the initial exposure. It has previously been reported that if more than 50 percent of the magnesium is removed from a chrysotile sample its carcinogenicity is reduced to nil. Several inorganic acids were studied to determine their ability to leach magnesium from chrysotile. It was found that the ability to leach magnesium was dependent upon the acidic anion in addition to the concentration of the acid. The ordering of the efficiency of the acids in their ability to remove magnesium from chrysotile was found to be HCl > H_2SO_4 > H_3PO_4 > HNO_3. Predictive equations were developed to allow the calculation of the amount of …

Huian plasma high-density lipoprotein (HDL) were isolated by a procedure employing polyanion precipitation and column chromatography. Lipid and protein composition of the HDL isolated by this method was found to be similar to another HDL preparation isolated by ultracentrifugation. However, minor differences were noted, including a higher phospholipid and apoproteinE content and lower triglyceride content of the HDL isolated by column chromatography. Four subfraction of HDL were obtained following chromatography on an anion exchange column. The subfraction four had the highest esterified to free cholesterol ratio, the second highest phospholipid to unesterified cholesterol, and the lowest molecular weight. In addition it was consistently coincided with lecithin: cholesterol acyltransferase (LCAT) activity and found to be the best substrate for the enzyme.

Density functional theory is an efficient and useful method of solving single-reference computational chemistry problems, however it struggles with multi-reference systems. Modifications have been developed in order to improve the capabilities of density functional theory. In this work, density functional theory has been successfully applied to solve multi-reference systems with large amounts of non-dynamical correlation by use of modifications. It has also been successfully applied for geometry optimizations for lanthanide trifluorides.

The oxidative elimination reactions of (5-X-phen)Mo(C0)₄ (X = H, CH₃, Cl, NO₂; phen = o-phenanthroline) and (3,4,7,8-(CH₃)₄-phen)Mo(CO)₄ with mercuric chloride in acetone have been investigated. In these reactions, a carbon monoxide group is replaced by two univalent ligands, accompanied by the corresponding increase in coordination number and formal oxidation state of the central metal atom, to give products of the type, (X-phen)Mo(CO)₃(Cl)HgCl. With the exception of (3,4,7,8-(CH₃)₄-phen), the substituted o-phenanthrolines were selected so as to minimize steric differences from one substrate to another while obtaining the widest range of pKₐ of the ligand.

A variety of optically active macrocyclic crown ethers that serve as "host" systems that are capable of differentiating between enantiomeric "guest" molecules during host-guest complexation have been prepared via incorporation of chiral elements into the crown ring skeleton. The ability of these crown ethers to recognize the enantiomers of guest salts, i.e., (+) a-methyl benzylamine and to transport them enantioselectively in W-tube transport experiments were studied. The ability of these crown ethers to perform as chiral catalysts in an enantioselective Michael addition was studied. The extent of asymmetric induction, expressed in terms of the enantiomeric excess (%ee), was monitored by measuring the optical rotation of the product and comparing to the literature value.

Computational methods were employed to investigate catalytic processes. First, DFT calculations predicted the important geometry metrics of a copper–nitrene complex. MCSCF calculations supported the open-shell singlet state as the ground state of a monomeric copper nitrene, which was consistent with the diamagnetic character deduced from experimental observations. The calculations predicted an elusive terminal copper nitrene intermediate. Second, DFT methods were carried out to investigate the mechanism of C–F bond activation by a low-coordinate cobalt(I) complex. The computational models suggested that oxidative addition, which is very rare for 3d metals, was preferred. A π–adduct of PhF was predicted to be a plausible intermediate via calculations. Third, DFT calculations were performed to study ancillary ligand effects on C(sp3)–N bond forming reductive elimination from alkylpalladium(II) amido complexes with different phosphine supporting ligands. The dimerization study of alkylpalladium(II) amido complexes indicated an unique arrangement of dative and covalent Pd-N bonds within the core four-membered ring of bimetallic complexes. In conclusion, computational methods enrich the arsenal of methods available to study catalytic processes in conjunction with experiments.

The objective of this study was to synthesize and characterize new energetic polycyclic "cage" compounds. As part of a program involved in the synthesis of new polynitropolycyclic compounds, 2,6-dinitro-5-methoxy- 7-carbomethoxypentacyclo[5. 3 .0 . 0* • * . CP • i ° . 0* •8]decane has been synthesized. This is a model system which can be used to study (1) the effect of nitro substitution on the photolability of carbon-carbon double bonds and (2) to develop methods for avoiding Haller-Bauer cleavage in cage /3-keto esters when synthesizing polynitro-substituted cage compounds.

The direct epitaxial growth of multilayer BN by atomic layer deposition is of critical significance forfo two-dimensional device applications. X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED) demonstrate layer-by-layer BN epitaxy on two different substrates. One substrate was a monolayer of RuO2(110) formed on a Ru(0001) substrate, the other was an atomically clean Ni(111) single crystal. Growth was accomplished atomic layer deposition (ALD) cycles of BCl3/NH3 at 600 K substrate temperature and subsequent annealing in ultrahigh vacuum (UHV). This yielded stoichiometric BN layers, and an average BN film thickness linearly proportional to the number of BCl3/NH3 cycles. The BN(0001)/RuO2(110) interface had negligible charge transfer or band bending as indicated by XPS and LEED data indicate a 30° rotation between the coincident BN and oxide lattices. The atomic layer epitaxy of BN on an oxide surface suggests new routes to the direct growth and integration of graphene and BN with industrially important substrates, including Si(100). XPS and LEED indicated epitaxial deposition of h-BN(0001) on the Ni(111) single crystal by ALD, and subsequent epitaxially aligned graphene was deposited by chemical vapor deposition (CVD) of ethylene at 1000 K. Direct multilayer, in situ growth of h-BN on magnetic substrates such as …

The problem with which this research is concerned is the determination of inorganic anions and cations with single injection ion chromatography. Direct detection of the separated analyte ions occurs after the analyte ions have passed through ion-exchange resins where they are separated according to their affinity for the ion-exchange resin active sites. The techniques involve the use of essentially a non-suppressed ion chromatographic system followed by a suppressed ion chromatographic system. With this system it is possible to accomplish both qualitative and quantitative determinations.

The purpose of the present work is to study the bonding interactions between the substituents and the ring π system for a series of ortho and para MeₙH₃₋ₙM (M = C or Si, n = 0-3) substituted N,N-dimethylaniline . Both ground and excited-state interactions were studied and their magnitudes determined. The experimental data were then used in conjunction with molecular orbital calculations to differentiate among inductive, hyperconjugative, and d-pπ interactions on the ground and excited states. Overall, the study indicates that d orbital involvement in the interactions of organosilicon substituents with unsaturated systems is much less significant than is generally held. The importance of pₛᵢ⁻π and pₛᵢ⁻π* hyperconjugative interactions between silicon σ* orbitals and π system in producing the effects of silicon substitution on unsaturated systems has become more apparent.

Organometallic catalysis has attracted significant interest from both industry and academia due to its wide applications in organic synthetic transformations. Example of such transformations include the reaction of a zinc carbenoid with olefins to form cyclopropanes. The first project is a computational study using both density functional and correlated wavefunction methods of the reaction between ethylene and model zinc carbenoid, nitrenoid and oxenoid complexes (L-Zn-E-X, E = CH2, NH or O, L = X = I or Cl). It was shown that cyclopropanation of ethylene with IZnCH2I and aziridination of ethylene with IZnNHI proceed via a single-step mechanism with an asynchronous transition state. The reaction barrier for the aziridination with IZnNHI is lower than that of cyclopropanation. Changing the leaving group of IZnNHI from I to Cl, changes the mechanism of the aziridination reaction to a two-step pathway. The calculation results from the epoxidation with IZnOI and ClZnOCl oxenoids suggest a two-step mechanism for both oxenoids. Another important example of organometallic catalysis is the formation of alkyl arenes from arenes and olefins using transition metal catalysis (olefin hydroarylation). We studied with DFT methods the mechanism of a novel Rh catalyst (FlDAB)Rh(TFA)(η2–C2H4) [FlDAB = N,N’ -bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] that converts …

Two adsorption/microcoulometric methods have been investigated for total organic halogen (TOX) in water. TOX, a proposed water-quality parameter, is a rapid, surrogate method to detect halides microcoulometrically and does not require compound identification before water quality can be judged. An XAD resin is used to concentrate organic halides that are eluted by a two-step, two-solvent procedure, followed by analysis using :chromatography or pyrolysis to convert organic halides to halide. In the granular activated carbon (GAC) method, the entire GAC-organic halide sample is pyrolyzed. TOX measurements of model compounds are comparable by both methods, but GAC was found to be superior to XAD for adsorption of chlorinated humics in drinking water and chlorinated lake water.

This work involves synthesis and characterization of isotropic and anisotropic noble metal nanoparticles for applications ranging from antimicrobial uses to anticancer applications. These nanomaterials are stabilized in genuinely benign biomaterials ranging from polymers to cross linked proteins for targeted cancer treatments. The nanoparticles are found to have tunable optical properties.

In this work, copper bimetallic corrosion and inhibition in ultra large scale interconnect fabrication process is explored. Corrosion behavior of physical vapor deposited (PVD) copper on ruthenium on acidic and alkaline solutions was investigated with and without organic inhibitors. Bimetallic corrosion screening experiments were carried out to determine the corrosion rate. Potentiodynamic polarization experiments yielded information on the galvanic couples and also corrosion rates. XPS and FTIR surface analysis gave important information pertaining inhibition mechanism of organic inhibitors. Interestingly copper in contact with ruthenium in cleaning solution led to increased corrosion rate compared to copper in contact with tantalum. On the other hand when cobalt was in contact with copper, cobalt corroded and copper did not. We ascribe this phenomenon to the difference in the standard reduction potentials of the two metals in contact and in such a case a less noble metal will be corroded. The effects of plasma etch gases such as CF4, CF4+O2, C4F8, CH2F2 and SF6 on copper bimetallic corrosion was investigated too in alkaline solution. It was revealed that the type of etching gas plasma chemistry used in Cu interconnect manufacturing process creates copper surface modification which affects corrosion behavior in alkaline solution. The learning …

Porphyrins offer a very synthetically flexible template which can be modified in numerous ways to synthesize molecules with very useful properties applicable in areas such as non-linear optical properties, photodynamic therapy, dye-sensitized solar cells, chemical sensors and organic electronic devices. β-Substituted π-extended porphyrins offer unique capabilities in tuning the properties of the molecule towards practical applications. Increased π-conjugation allows the HOMO-LUMO gap to decrease and hence to redshift the absorption into the near-IR region. β-Fused benzoporphyrins offer additional benefits in which the benzene ring itself can be further modified using electron donating substituents and electron donating substituents to electronically tune these porphyrins for various uses. The goal of the research pursued in this dissertation was to develop new methods for the development of β-Substituted π-extended porphyrins and to study their optical and electronic properties. To accomplish this goal, we developed new method to synthesize A2B2 type tetrabenzoporphyrins and we studied the electron transfer in such systems. We also studied the effectiveness of such systems in dye sensitized solar cells. A new method to synthesize functionalized naphthalene fused porphyrins was also developed and we were also able to use this method to synthesize a push-pull naphthalene fused porphyrin.

Machine learning and artificial intelligence are increasingly becoming mainstream in our daily lives, from smart algorithms that recognize us online to cars that can drive themselves. In this defense, the intersection of machine learning and computational chemistry are applied to the generation of new PFAS molecules that are less toxic than those currently used today without sacrificing the unique properties that make them desirable for industrial use. Additionally, machine learning is used to complete the SAMPL6 logP challenge and to correlate molecules to best DFT functionals for enthalpies of formation.

The first study investigated the deposition and characterization of the CoO and Co3O4 phases of cobalt oxide. It was determined that both phases can be easily distinguishable by XPS, LEED and EELS and grown by only altering the oxygen partial pressure during MBE deposition. This fundamental knowledge gives a foundation for further experiments involving graphene growth on cobalt oxides. The second study focused on the layer-by-layer growth of graphene on another metal oxide, MgO. Past research gives promise of favorable interfacial interactions at the graphene/MgO interface though the exact growth mechanism is unknown. Layer by layer growth by MBE resulted in the characterization of a complex graphene oxide/buckled graphene/ graphene heterostructure confirmed by XPS, AES, LEED and EELS and supported by DFT calculations performed by the project's collaborators at the California Institute of Technology. This detailed look into graphene growth give valuable information that can be allied to graphene growth on similar oxide surfaces. The last project deviates from graphene-based studies and instead focused on interfacial interactions between two metal oxides, chrome oxide and titanium oxide. A corundum phase TiO2-x film was grown on Al2O3 via MBE and characterized using XPS, AES, LEED, and EELS. Data taken gives evidence of …

Pulsed laser flash photolysis with both visible and infrared detection has been applied to the study of the displacement of weakly coordinating ligands (Lw) by strongly "trapping" nucleophiles (Ls) containing either an olefinic functionality (Ls = 1-hexene, 1-decene, 1-tetradecene) or nitrogen (Ls = acetonitrile, hydrocinnamonitrile) from the photogenerated 16 electron pentacarbonylchromium (0) intermediate. 5-Chloropent-l-ene (Cl-ol), a potentially bidentate ligand, has been shown to form (ol-Cl) pentacarbonylchromium (0), in which Cl-ol is bonded to Cr via a lone pair on the chlorine, and isomerize to (Cl-ol) pentacarbonylchromium (0), in which Cl-ol is bonded to the olefinic functionality on the submillisecond time scale. This process has been studied in both the infrared and visible region employing both fluorobenzene or n-heptane as the "inert" diluent. Parallel studies employing 1-chlorobutane and 1-hexene were also evaluated and showed great similiarity with the Cl-ol system. The data supported a largely dissociative process with a possibility of a small interchange process involving the H's on the alkyl chain. Studies were also carried out for various Cr(CO)6/arene/Ls systems (arene = various alkyl or halogenated substituted benzenes). The data indicated that for both C6H5R (R=various alkyl chains) or multi-alkyl substituted arenes (i.e. o-xylene, 1,2,3-trimethylbenzene) containing an "unhindered" ring-edge, bonding …

The objectives of these investigations were (1) the purification of MG reductase from sheep liver and (2) studies of some of its characteristics. MG reductase was purified 40 fold and showed a single band on SDS-PAGE. Molecular weight estimations with SDS-PAGE showed a molecular weight of 44,000; although gel filtration with Sephadex G-150 gave a molecular weight of 87,000 indicating that the enzyme might be a dimer. The Km for MG is 1.42 mM and for NADH it is 0.04 mM. The pH optimum for the purified enzyme is pH 7.0. Isoelectric focusing experiments showed a pI of 9.3. In vivo experiments involving rats treated with 3,3',5-triiodothyronine (T_3) and 6-n-propyl-2-thiouracil (PTU) indicated that MG reductase was depressed by T_3 and elevated by PTU.

As countries pledge their commitment to a net-zero future, much of the previously forgotten climate change research were revitalized by efforts from both governmental and private sectors. In particular, the utilization of lignocellulosic materials saw a special spotlight in research interest for its abundance and its carbon removal capability during photosynthesis. The initial effort in mimicking enzymatic active sites of β-glucosidase will be explored. The crystalline covalent organic frameworks (COFs) allowed for the introduction of a variety of noncovalent interactions, which enhanced the adsorption and the catalytic activity against cellobiose and its glycosidic bonds. The physical processes associated with this reaction, such as the kinetics, equilibrium, and activation energies, will be closely examined and compared with existing standard materials and comparable advanced catalysts. In addition, several variants of COFs were synthesized to explore the effect of various noncovalent interactions with cellobiose. A radical-bearing COF was synthesized and characterized. The stability of this radical was examined by electron paramagnetic resonance spectroscopy (EPR) and its oxidative capability tested with model lignin and alcoholic compounds. The reaction products are monitored and identified using gas chromatography-mass spectroscopy (GC-MS). An oxidative coupling of phenol was explored, and its initial results are presented in chapter 5.

This dissertation details the use of computational methods to understand the effect that cancer-related mutations have on proteins that complex with nucleic acids. Firstly, we perform molecular dynamics (MD) simulations of various mutations in DNA polymerase κ (pol κ). Through an experimental collaboration, we classify the mutations as more or less active than the wild type complex, depending upon the incoming nucleotide triphosphate. From these classifications we use quantum mechanics/molecular mechanics (QM/MM) to explore the reaction mechanism. Preliminary analysis points to a novel method for nucleotide addition in pol κ. Secondly, we study the ten-eleven translocation 2 (TET2) enzyme in various contexts. We find that the identities of both the substrate and complementary strands (or lack thereof) are crucial for maintaining the complex structure. Separately, we find that point mutations within the protein can affect structural features throughout the complex, only at distal sites, or only within the active site. The mutation's position within the complex alone is not indicative of its impact. Thirdly, we share a new method that combines direct coupling analysis and MD to predict potential rescue mutations using poly(ADP-ribose) polymerase 1 as a model enzyme. Fourthly, we perform MD simulations of mutations in the protection of …

Multimodular designs of electron donor-acceptor systems are the ultimate strategy in fabricating antenna-reaction center mimics for artificial photosynthetic applications. The studied photosystems clearly demonstrated efficient energy transfer from the antenna system to the primary electron donor, and charge stabilization of the radical ion pair achieved with the utilization of secondary electron donors that permits either electron migration or hole transfer. Moreover, the molecular arrangement of the photoactive components also influences the route of energy and electron transfer as observed from the aluminum(III) porphyrin-based photosystems. Furthermore, modulation of the photophysical and electronic properties of these photoactive units were illustrated from the thio-aryl substitution of subphthalocyanines yielding red-shifted Q bands of the said chromophore; hence, regulating the rate of charge separation and recombination in the subphthalocyanine-fullerene conjugates. These multicomponent photosystems has the potential to absorb the entire UV-visible-NIR spectrum of the light energy allowing maximum light-harvesting capability. Furthermore, it permits charge stabilization of the radical ion pair enabling the utilization of the transferred electron/s to be used by water oxidizing and proton reducing catalysts in full-scale artificial photosynthetic apparatuses.

This investigation deals with the preparations of cyclic organosilanes via two different types of organometallic precursors: borane adducts to chlorovinylsilanes and tertbutyllithium adducts to chlorovinylsilanes. The regiospecificity of the hydroboration of various types of boranes to chlorovinylsilanes was studied by three different methods. It was found that, by using bulky hydroborating agents, about 80% isomerically pure terminal borane adducts to chlorovinylsilanes could be obtained. While the adducts are potential precursors to silacyclopropanes, when these borane adducts were treated with bases such as sodium methoxide and methyl Grignard, no evidence for silacyclopropane formation was found.