http://hdl.handle.net/1721.1/7595 2017-06-08T00:19:39Z 2017-06-08T00:19:39Z Hess, Whitney Rochelle http://hdl.handle.net/1721.1/109683 2017-06-07T06:18:25Z 2017-01-01T00:00:00Z

Exploring the versatility of lead sulfide quantum dots in low-temperature, solution-processed solar cells Hess, Whitney Rochelle Solution processability and optoelectronic tunability makes lead sulfide quantum dots (PbS QDs) promising candidates for low-temperature, solution-processed thin film solar cells. Central to this thesis is the crucial role of QD surface chemistry and leveraging surface modification to prepare QDs suitable for optoelectronic device applications. The work presented here explores the versatility of PbS QDs integrated into two main device architectures, where the primary role of the QD is unique in each case. In p-i-n planar perovskite solar cells, efforts to utilize PbS QDs as a hole transport material and the effects of size tuning and surface passivation with cadmium on device characteristics are discussed. A combination of QD size reduction and minimal cadmium-to-lead cation exchange is found to improve the open circuit voltage and hole extraction into the PbS QD layer. In ZnO/PbS QD heterojunction solar cells, the feasibility of preparing fully inorganic, halometallate-passivated PbS QD inks for use as the absorber layer is discussed. A modified biphasic ligand exchange strategy is presented and in order to further elucidate electronic passivation in these QD ink systems, optical properties were investigated with steady state and time-resolved photoluminescence. Significantly, PbS QDs exhibit comparable quantum yields in solution before and after ligand exchange and no significant trap state emission was observed in solution and in film. Ink devices were fabricated with one- and two-layer depositions, which significantly reduce fabrication time compared to traditional layer-by-layer deposition, and devices exhibit anomalous efficiency improvement throughout storage in air. Thesis: Ph. D. in Physical Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2017.; Page 161 blank. Cataloged from PDF version of thesis.; Includes bibliographical references (pages 151-160).

2017-01-01T00:00:00Z White, Kolby Lyn http://hdl.handle.net/1721.1/109682 2017-06-07T06:18:24Z 2017-01-01T00:00:00Z

Mechanistic investigation of the interrupted Bischler-Napieralski reaction and its application to the total synthesis of the aspidosperma alkaloids White, Kolby Lyn I. Direct Observation of Intermediates Involved in the Interruption of the Bischler- Napieralski Reaction. The first mechanistic investigation of electrophilic amide activation of [alpha], [alpha]-disubstituted tertiary lactams and the direct observation of key intermediates by in situ FTIR, 1H, 13C, and 19F NMR in our interrupted Bischler-Napieralski based synthetic strategy to the aspidosperma alkaloids is described. Importantly, when considering base additives during electrophilic amide activation, more hindered c-quaternary tertiary lactams require the use of non-nucleophilic pyridine additives in order to avoid deactivation via a competing desulfonylation reaction. The isolation and full characterization of a tetracyclic iminium trifluoromethanesulfonate provided additional correlation between in situ characterization of sensitive intermediates and isolable compounds involved in this synthetic transformation. II. Total Synthesis of (+)-Fendleridine, (+)-Acetylaspidoalbidine, and (+)-Limaspermidine. An Tf2O-mediated electrophilic amide activation of a readily available C21-oxygenated lactam, followed by transannular cyclization and in situ trapping of a transiently formed C19-iminium ion, expediently provides access to the hexacyclic C19-hemiaminal ether alkaloids (+)- fendleridine, (+)-acetylaspidoalbidine, and (+)-limaspermidine. A highly effective enzymatic resolution of a non-[beta]-branched primary alcohol (E=22) allowed rapid preparation of both enantiomeric forms of a C21-oxygenated precursor for synthesis of these aspidosperma alkaloids. III. Development of an Ortho-Acetoxylation of Indoline Amides and its Application to the Total Synthesis of (+)-Haplocidine and (+)-Haplocine. The first total syntheses of (+)-haplocidine and its NI-amide congener (+)-haplocine is described. The concise synthesis of these alkaloids required the development of a late-stage and highly selective C-H oxidation of complex aspidosperma alkaloid derivatives. A versatile, amide directed ortho-acetoxylation of indoline amides enabled the implementation of a unified strategy for late-stage diversification of hexacyclic C19-hemiaminal ether structures via oxidation of the corresponding pentacyclic C19-iminium ions. Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2017.; Vita. Scanning issues: Page 114 contains text that has been cropped/deleted from the right-side page margin. Appendix B section contains several graph pages with faint/illegible images. Cataloged from PDF version of thesis.; Includes bibliographical references.

2017-01-01T00:00:00Z Parker, Mackenzie James http://hdl.handle.net/1721.1/109681 2017-06-07T06:18:22Z 2017-01-01T00:00:00Z

Discovery and investigation of the novel overall activity allosteric regulation of the Bacillus subtilis class Ib ribonucleotide reductase Parker, Mackenzie James Ribonucleotide reductases (RNRs) catalyze the reduction of nucleotides to 2'-deoxynucleotides in all organisms. Class lb RNRs consist of two subunits: a houses the catalytic and allosteric effector binding sites, and p houses a catalytically essential dimanganic-tyrosyl radical (Mn(III)2-Y*). The allosteric regulation of lb RNR activity has only been studied with the Salmonella enterica enzyme, which exhibits substrate specificity allosteric regulation by ATP and 2'-deoxynucleoside 5'-triphosphates (dNTPs), but not overall activity regulation by ATP and dATP. However, the S. enterica enzyme is not a good general model for Ib RNRs because it is not essential under most growth conditions, including pathogenesis. Other bacteria pathogenic to humans utilize lb RNRs as their sole source of dNTPs for DNA replication and repair. As RNR regulation plays a critical role in the high fidelity of these processes, the allosteric regulation of lb RNRs used as the primary dNTP supplier for a bacterium should be distinct from the S. enterica enzyme and, therefore, could provide a potential target for therapeutic development. Herein, the results of characterizing the allosteric regulation of the Ib RNR from the model organism Bacillus subtilis are presented. To facilitate these studies, we identified, cloned, and isolated the physiological reductant for RNR (thioredoxin/thioredoxin reductase/NADPH), thus allowing us to monitor activity spectrophotometrically. We discovered the effector dATP was a potent inhibitor of enzymatic activity at physiologically relevant concentrations, thereby demonstrating the first example of overall activity allosteric regulation in a class lb system. In other RNRs, overall activity regulation is mediated by a domain called the ATP-cone. This domain is absent from the B. subtilis enzyme; therefore, the inhibition represents a new mechanism of overall activity regulation. Analytical ultracentrifugation studies suggest dATP inhibition may be mediated by formation of large protein complexes. Biophysical studies also led to the discovery of tightly bound dAMP associated with a that increases the susceptibility of RNR to dATP inhibition. The potential physiological importance of dAMP is supported by studies examining YmaB, the unique fourth member of the B. subtilis RNR operon, which revealed this enzyme can hydrolyze dATP into dAMP and pyrophosphate and, therefore, might insert dAMP into a. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017.; Page 490 blank. Cataloged from PDF version of thesis.; Includes bibliographical references.

2017-01-01T00:00:00Z Vinogradov, Alexander Alexandrovich http://hdl.handle.net/1721.1/109680 2017-06-07T06:18:19Z 2017-01-01T00:00:00Z

New methods for synthesis and modification of peptides and proteins Vinogradov, Alexander Alexandrovich Chemical modification of peptides and proteins is an enabling suite of tools for tailoring the properties of these biomolecules to specific applications. A number of bio-conjugation reactions allows fine-tuning of the biological activity, proteolytic stability, and immunogenicity of peptides and proteins, as well as equipping them with completely novel functions such as cell penetration, fluorescence, unique chemical reactivity, and much more. Described herein are a number of new methods for the synthesis of modified peptides and proteins, and an approach to the discovery of such methodologies. Applications of fast-flow solid phase peptide synthesis - a technique recently developed to accelerate and improve peptide synthesis- towards the synthesis of difficult sequences and the refinement of associated protocols is described. The utility of the system is demonstrated via rapid total synthesis of barnase, a model 110-residue RNase, in the L- and D-forms. Systematic characterization of the biochemical properties of the synthesized proteins revealed that barnase is able to hydrolyze substrates of various chiralities, and that D-barnase is fully proteolytically stable. Separately, a method for the preparation and utilization of unprotected peptide isocyanates in water was developed. It was shown that easily accessible C-terminal peptide isocyanates can be conjugated to a number of strong nucleophiles in the presence of unprotected amino acid side chains for peptides and proteins of various structures. Two-component macrocyclization of peptide isocyanates with bifunctional linkers was developed as an extension of the described chemistry. The resulting cyclic peptides were shown to be more proteolytically stable and more bioactive than their linear analogs. In pursuit of generalizing the C-terminal protein modification chemistry to fully proteogenic peptides and proteins, a number of library screening approaches was developed. Liquid chromatography coupled to tandem mass spectrometry was employed to screen and reliably decode synthetic peptide libraries in a high-throughput manner. These protocols were used to discover proteogenic sequence tags reactive towards substituted hydrazine derivatives in a transpeptidation reaction. The discovered C-terminal tripeptide tag His-Gly-Cys underwent transpeptidation with a number of structurally different nucleophiles in various sequence contexts. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017.; Cataloged from PDF version of thesis.; Includes bibliographical references.

2017-01-01T00:00:00Z