Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Vita. / Includes bibliographical references. / In Chapter 1, the first enantioselective cross-coupling reactions of racemic secondary benzylic halides are described (eq 1). This method was applied to the syntheses of intermediates employed by other groups in the generation of bioactive compounds, e.g., an androgen receptor agonist (1.1) and two members of the trikentrin family of natural products (1.2 and 1.3). In Chapter 2, the first method for the kinetic resolution of indolines through catalytic Nacylation is described (eq 2). To improve the selectivity factor, a new planar-chiral PPY-erived catalyst (2.1) was prepared, wherein the chiral environment had been modified. The method was applied to the resolution of an intermediate prepared by K. Tsuji in the synthesis of a series of novel antibiotics of core structure 2.2. This work provides a rare example of a nonenzyme-based acylation catalyst for the kinetic resolution of amines. Finally, in Chapter 3, the first examples of catalyzed, enantioselective insertion of carbenoid fragments into C-N sigma bonds are described (eq 3). The system uses commercially-available catalyst components and gives highly enantioselective rearrangements of benzylamine-, allylamine-, and [alpha]-aminocarbonyl-containing substrates. The method represents a new way to access 1,4-benzoxazinones, a subunit present in several pharmaceutical targets and chiral natural products. / by Forrest O. Arp. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / "April 29, 2010." Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / The primary focus of this thesis is the synthesis and applications of semiconductor nanocrystals, or quantum dots (QDs). Novel synthetic routes to ternary 1-III-VI QDs are presented, and we report the first highly luminescent Cu-In-Se QDs spanning the red to near-infrared region. The synthetic method is modular and is extended to Ag-In-Se, Cu-In-Zn-S, and Ag-In-Zn-S QDs, luminescent from the blue to near-infrared. The development of new core-shell InAs(ZnCdS) QDs is discussed in the context of making highly fluorescent, stable biological probes in the near-infrared region. Applications in biological systems from cellular labeling to sentinel lymph node mapping are demonstrated. In addition, we present new methods for doping InAs QDs in order to control carrier type through the introduction of acceptor defects such as cadmium. The synthesis and characterization of n and p type InAs QDs is discussed. In order to understand the differences in size distributions with current III-V QD synthetic procedures and II-VI and IV-VI QD syntheses we have explored the molecular mechanisms that lead to the formation of InP and InAs QDs. We find that current III-V QD syntheses result in the depletion of molecular precursors immediately following nucleation, preventing growth from molecular precursors, thus failing to meet the a key criterion for a monodisperse colloidal synthesis in the Dinegar and LaMer model. In the conclusion of this thesis, we explore the electrically controlled solution-liquid-solid (EC-SLS) synthesis of InP nanowires. Using the EC-SLS method, we are able to controllably place n type InP nanowires into field effect transistor geometries. / by Peter M. Allen. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998. / Includes bibliographical references. / by Aaron L. Odom. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Solar-driven electrochemical splitting of water to hydrogen and oxygen is crucial for the production of inexpensive, sustainable, and carbon-neutral fuels for future global energy requirements. Of the two half-reactions for water splitting, developing catalysts for the oxygen evolution reaction (OER) is a challenge because orchestrating the coupled transfer of four protons and four electrons is kinetically demanding. Currently, inexpensive and active OER catalysts comprised of earth-abundant elements from cobalt and nickel oxides operate in neutral and alkaline pH. These same systems corrode under acidic conditions, which is a regime important for electrolyzers and photoelectrochemical devices as well as for fundamental mechanistic studies. In this thesis, we iteratively design an active, stable, and earth-abundant acidic oxygen evolution catalyst through multiple generations. The first version focused on an electrodeposited manganese oxide (MnOx) catalyst that is stable in acid but exhibits low OER activity. Kinetic and mechanistic analysis on deposition and oxygen evolution mechanisms show that its stability manifests from strong manganese-oxygen bonds and self-healing. The second generation system improved activity while retaining acid stability by activating MnOx through a voltage cycling protocol. Structural studies show that activation induces a lower bulk manganese oxidation state and turbostratic disorder. This catalyst architecture was redesigned in the third iteration as a mixed metal oxide where functionality is decoupled into separate metals: Co was employed as the catalytic element while Mn served as the structural component. These CoMnOx films demonstrate the facile OER kinetics of Co and the acid corrosion resistance of Mn. However, these films cannot operate at high potentials since Mn dissolves as permanganate. Thus in our final fourth generation catalyst, we replaced the structural component with lead (doped with iron), an optimization discovered by potential-pH analysis. These CoFePbOx films exhibit ~70 mV/decade Tafel slopes and long-term stability at 1 mA/cm² in pH 2.5, operating at only 200 mV higher overpotential than iridium oxide. Overall, we demonstrate the ability to rationally modify and design an active, stable, and earth-abundant oxygen evolution catalyst. / by Michael Huynh. / Ph. D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Magic Angle Spinning (MAS) solid state nuclear magnetic resonance (SSNMR) is a developing method for determining the structures and studying the dynamics and functions of biological molecules. This method is particularly important for systems, such as amyloidogenic fibrous proteins, that do not crystallize or dissolve well and are therefore not amendable to X-ray or solution NMR techniques. However, due to inherently low sensitivity, NMR experiments may require weeks to obtain spectra with sufficient signal-to-noise ratio. This issue is further exacerbated for biological systems of interest due to their large size and limited mass availability. The sensitivity can be increased by two orders of magnitude by combining MAS NMR with dynamic nuclear polarization (DNP). The application of SSNMR-DNP to protein structure determination is explored using malonic acid and a model peptide system, WT-TTR105-115. A custom built MAS-SSNMR probe is modified for the purpose of MAS-SSNMR DNP experiments. / by Rebecca Maria Mayrhofer. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Linear polyethylenimine (PEI) is the "gold standard" of polycationic gene delivery vectors. However, little focus has been placed on enhancing or understanding the specificity of PEImediated gene delivery. Herein we evaluated the effect of chemical modification on the specificity of PEI-mediated nucleic acid delivery. We found that low molecular weight PEI (2 kDa) does not mediate efficient gene expression while high molecular weight (> 87 kDa) leads to toxicity. However, linear PEI of 25 kDa is an efficient gene delivery vector for both DNA and siRNA. Therefore, this PEI was chemically modified to explore the relationship between structure and specificity. First, PEI was covalently attached to a monoclonal anti-angiotensin I-converting enzyme (ACE) antibody (PEI-9B9) and evaluated for its ability to target PEI-9B9 polyplexes following intravenous delivery in a rat. Although mAb 9B9 retains affinity for its substrate ACE, PEI-9B9 does not enhance delivery to its intended target, the lung. Clearance of PEI-9B9 from circulation likely occurs before antibody binding to the surface expressed antigen. Next, we evaluated the ability of hydrophobic modification to modulate specificity of PEIbased gene delivery. Linear PEI was alkylated with variable length hydrocarbon chains at varying percent modification and evaluated for effective and specific gene delivery following intravenous delivery in mice. Modest alkylation (11% modification with ethyl chains to produce N-ethyl-PEI) enhances gene delivery in the lung 26-fold while quadrupling the ratio of gene product expressed in the lung relative to other organs. Interestingly, specificity profiles of the various alkyl chain derivatives vary among the organs examined. Additionally, a topical approach to gene delivery was investigated. Small branched PEI was cross-linked to gold to create PEI-gold nanoparticles (PEI-GNPs). These polycations were complexed with DNA and delivered topically to scratched rabbit cornea. PEI-GNPs effectively transfected corneal endothelium and evoked expression of the plasmid DNA without causing significant immunogenicity or toxicity. Finally, the effect of radiation on biologics was evaluated using a rigorously controlled experimental design with extreme conditions to unequivocally determine if radiofrequency radiation (RFR) has a non-thermal effect on biologics. Neither enzymes nor living cells (both bacterial and mammalian) were affect non-thermally by RFR. / by Jennifer A. Fortune. / Ph.D.

Thesis: Ph. D. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Oxalic acid is a two-carbon diprotic acid that is toxic to humans. In large doses, it can cause death by poisoning, and in smaller doses over time it can lead to chronic renal disease, such as the formation of kidney stones, acute renal failure, as well as other complications such as crystalline arthritis. Current strategies to mitigate oxalate toxicity focus on diet management, though recent therapeutic studies have begun to focus on both probiotic as well as enzymatic treatments for the prevention of oxalate-related illnesses. The acetogenic bacterium Moorella thermoacetica has been known for some time to metabolize oxalate, though the unique enzyme responsible was only recently discovered. M thermoacetica employs an oxalate oxidoreductase (OOR) to oxidize oxalate to two molecules of C0 2, generating two low-potential electrons. OOR uses a thiamine pyrophosphate (TPP) cofactor to cleave the C-C bond, and three [4Fe-4S] clusters to capture and transfer the electrons produced. Both of these products from oxalate degradation, CO 2 and the low-potential electrons, allow M thermoacetica to grow via the Wood-Ljungdahl pathway for acetogenesis (also known as the reductive acetyl-CoA pathway). OOR is a member of the larger superfamily of 2-oxoacid:ferredoxin oxidoreductase (OFOR) enzymes. OFORs are found in microorganisms across all domains of life, and are responsible for performing a number of essential metabolic reactions, including the conversion of pyruvate to acetyl-CoA. Though, most OFORs require coenzyme A as a co-substrate, OOR is the exception to this rule, as it is capable of metabolizing oxalate without the aid of CoA. To aid in understanding this newly discovered enzyme, we have determined three crystal structures of OOR. These structures have allowed us to visualize the resting state as well as two reaction intermediates: an oxalate-TPP adduct and a C0 2-TPP adduct. Additionally, these structures have revealed dramatic protein conformational changes in the active site that are likely to facilitate catalysis. As OOR is only the second OFOR to be structurally characterized, these structures have provided a wealth of information about the larger OFOR superfamily as well as about this novel mechanism of oxalate metabolism. / by Marcus Ian Gibson. / Ph. D. in Inorganic Chemistry

Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 15-17). / The research focuses on chemiresistive sensing of carbon dioxide (CO₂) using a series of two-dimensional (2D) conductive metal-organic frameworks (MOFs) with amine-based linkers. The 2D MOFs studied here show carbon dioxide sensitivity at concentrations as low as 1000 ppm. The identity of both the metal and ligand affects sensing performance in terms of sensitivity, reversibility, selectivity, and response to moisture. Experimental and computational data indicate that the amine groups of the ligands play a key role in the CO₂ sensing mechanism. This work represents the first use of electrically conductive MOFs for CO₂ sensing, and demonstrates a combination of sensitivity and selectivity that is promising for practical applications. / by Yicong Ge. / S.M.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1984. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Timothy Allen Blizzard. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / Vita. / Includes bibliographical references. / Glycosaminoglycans are crucial components of the extracellular matrix and cell surface and access to define sequences is required to fully appreciate their role in biology. As is the case with most complex polysaccharides, the chemical synthesis of glycosaminoglycan structures is challenging. This thesis describes efforts towards the construction of oligosaccharides with the ultimate goal of the automated synthesis of glycosaminoglycans. The use of glycosyl phosphates of glucosamine and glucuronic acid as competent glycosylating agents is illustrated. Further expansion of the glycosyl phosphates methodology to the construction of C-aryl and C-alkyl glycosides and resulted in the synthesis of the natural product 8,1 0-di-O-methylbergenin. The automated solid-phase synthesis of two complex oligosaccharides is described. The complex-type high mannose trisaccharide and the proteoglycan linkage region tetrasaccharide were synthesized in a fully automated fashion. The efforts towards the synthesis of two glycosaminoglycans - hyaluronic acid and chondroitin sulfate - are discussed. The work focuses on the discovery of a glycosylating agent suitable for the automated solid-phase synthesis. The synthesis of glucuronic acid from glucose is described using an oxidation procedure not previously explored in oligosaccharide construction. / by Emma Rose Palmacci. / Ph.D.