Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (p. 131-138). / The chirped-pulse millimeter-wave (CPmmW) technique is applied to transitions between Rydberg states, and calcium atoms are used as the initial test system. The unique feature of Rydberg{Rydberg transitions is that they have enormous electric dipole transition moments: ~5 kiloDebye at n* ~45, where n* is the eective principal quantum number. After polarization by a mm-wave pulse in the 70{84 GHz frequency region, the excited transitions re-radiate free induction decay (FID) at their resonant frequencies, and the FID is heterodyne-detected by the CPmmW spectrometer. Data collection and averaging are performed in the time domain. The spectral resolution is ~100 kHz. Because of the large transition dipole moments, the available mm-wave power is sucient to polarize the entire bandwidth of the spectrometer (12 GHz) in each pulse, and high-resolution survey spectra may be collected. Both absorptive and emissive transitions are observed, and they are distinguished by the phase of their FID relative to that of the excitation pulse. With the combination of the large transition dipole moments and direct monitoring of transitions, dynamics are observed, such as transient nutations from the interference of the excitation pulse with the polarization that it induces in the sample. Transient nutations also provide information about the sample, such as the dipole moment and the number density of Rydberg states. Since the waveform produced by the mm-wave source may be precisely controlled, states with high angular momentum may be populated by a sequence of pulses while recording the results of these manipulations in the time domain. Also, the superradiant decay of the Rydberg sample is probed both directly through FID and indirectly using photon echoes. Prospects for further manipulations, such as adiabatic rapid passage, composite pulses, and optical/mm-wave stimulated Raman adiabatic passage, are evaluated. The application of the CPmmW technique to transitions between Rydberg states of molecules is discussed. / by Anthony P. Colombo. / Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 51-53). / .Chirped-pulse millimeter wave (CPmmW) spectroscopy is a revolutionary technique that has taken advantage of advances in electronics to give high signal to noise broadband rotational spectra in a very short period of time that provides meaningful line intensities. We have implemented this technique in the 58 - 102 GHz range to study the rotational spectra of molecules with two heavy atoms. Photolysis (at 193 nm) and pyrolysis of vinyl cyanide have produced differing HCN and HNC vibrational population distributions. The photolysis experiment does not sample a collisional regime and the resulting spectra show excited states of HCN and HNC, whereas the pyrolysis experiment, which does sample a collisional regime, results in spectra that are devoid of vibrational satellites. This indicates that the intensities of vibrational satellite transitions sample the photolysis reaction only and not post-photolysis collisional effects. Mono-deuterated vinyl cyanide was photolyzed at 193 nm, in which all HCN/HNC are produced via a four-center mechanism and all DCN/DNC are produced via a three-center mechanism. The HCN and HNC products dominate, demonstrating the greater importance of the three-center mechanism. CPmmW spectroscopy is also a valuable tool in studying unimolecular and bimolecular reactions. We have studied the unimolecular decomposition of deuterated methyl nitrite which produces DNO products and bimolecular hydrogen abstraction reaction of NO with acetaldehyde resulting in HNO products. These reactions demonstrate the potential use of nitric oxide radical as a gas-phase catalyst to perform cracking of hydrocarbons and sugars. / by Rachel Glyn Shaver. / S.M.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2018. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Page 467 blank. Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references. / The study of heavier p-block analogs to unsaturated organic small molecules is of fundamental importance, allowing insight into the differing bonding and reactivity patterns that control their synthetic utility. A major complication in this pursuit is the instability of these unsaturated compounds containing heavier elements, as they can rarely be isolated without sterically encumbering substituents to provide kinetic protection. Herein, a series of anthracene-based molecular precursors are leveraged for the generation of low-coordinate phosphorus species that have been generally too unstable to isolate and use under ambient conditions. These precursors exhibit a dibenzo-7-phosphanorbornadiene framework that has allowed access to free phosphinidenes, phosphinidene sulfides, and phosphaalkynes. The thermal release of anthracene as a relatively innocuous coproduct allows for studies of these species' reactivities toward new substrates. Where possible, the intermediacy of the unstable phosphorus compound is demonstrated by direct spectroscopic detection, particularly using nuclear magnetic resonance (NMR) and microwave (rotational) spectroscopy. The mechanism and scope of thermal fragmentation of these molecular precursors is described from experimental kinetic studies bolstered by density functional theory (DFT) calculations. Initial forays into further uses of dibenzo-7-phosphanorbornadiene compounds have included the preparation of a new material of composition P2S and the transition metal-catalyzed transfer of tert-butylphosphinidene to styrene to generate phosphiranes. / by Wesley J. Transue. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references. / by Joan-Emma Shea. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011 / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / In addition to the four canonical ribonucleosides (adenosine, uridine, guanosine, cytosine), transfer RNAs (tRNA) and ribosomal RNAs (rRNA) are comprised of more than 100 enzyme-catalyzed modifications, with about 20-35 found in any one organism. Many of these modifications are highly conserved in all domains of life, which suggests important biological roles for RNA modifications in cell physiology. Several recent studies have demonstrated that individual tRNA modifications and their biosynthetic pathways affect cellular stress responses. The presence of 20-35 different RNA modifications in all translationally-related non-coding RNAs suggested the possibility of systems behavior of RNA modifications in translational facets of cellular responses. The studies presented in this thesis utilize a quantitative systems-level approach to test the hypothesis that the spectrum of tRNA modifications represents a cellular program involved in modulating stress response pathways. To initiate these studies, a novel mass spectrometric platform was developed to characterize and quantify the spectrum of modified ribonucleosides in an organism, starting with the ~25 ribonucleosides in S. cerevisiae tRNA. This approach was used to compare tRNA modification spectra from cells exposed to four mechanistically distinct toxicants: hydrogen peroxide, methyl methanesulfonate, arsenite, and hypochlorite. Multivariate statistical analysis revealed both dose- and agent-specific signatures in the relative quantities of tRNA modifications. Further, modifications that change significantly after exposure were shown to confer resistance to the cytotoxicity of the agent. These observations demonstrate the dynamic nature of tRNA modifications and their critical role in translational control of cellular stress responses. Also, application of the mass spectrometric method revealed several new biosynthetic pathways for tRNA modifications in yeast. These studies comprise Chapters 2 and 3. Chapter 4 is aimed at characterizing the link between tRNA modifications and translational control of cellular responses. One of the tRNA modifications that increased significantly following exposure of yeast to hydrogen peroxide is 5-methylcytosine (m5 C), which is located at the wobble position of the leucine tRNA for coding UUG. This suggested that it might affect translation of mRNA containing this codon. While there are 6 codons for leucine, the usage of the codon UUG for specifying leucine in the set of homologous ribosomal proteins differs widely. Using proteomics approach, it was demonstrated that m5C regulates the levels of the homologous ribosomal protein genes rp/22a and rp/22b, with hydrogen peroxide exposure causing an increase in the proportion of ribosomes containing rpI22a. Further, loss of rp/22a conferred sensitivity to hydrogen peroxide exposure. These results suggest that the system of tRNA modifications controls cellular responses partly by determining the composition of ribosomes involved in the selective translation of critical response proteins. As observed in Chapter 3, tRNA modifications spectrum changes specifically in responses to mechanistically distinct toxic agents; in Chapter 5, a series of studies was designed to test the hypothesis that each of these unique signatures represents a common response to different toxicant classes. To test this hypothesis, yeast cells were exposed to four different oxidizing agents (hydrogen peroxide, tert-butyl hydroperoxide, peroxynitrite, and gamma-radiation) and five different alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and N-nitroso-N-methylurea) at concentrations producing similar levels of cytotoxicity. The spectrum of tRNA modifications was then quantified and the results subjected to multivariate statistical analysis to identify consistent patterns. The results reveal class-specific patterns of changes, with distinct tRNA modification spectra for oxidants and alkylating agents. At a finer level of analysis, the studies revealed subclass signatures for SN1 and SN2 alkylating agents. The results from these experiments were used to develop a data-driven model that predicts exposures to the two classes of toxic agents accurately. Such a model may be useful for assessing ribonucleoside spectra as biomarkers of exposure. Appendix A describes the preliminary characterization of the spectrum of modified ribonucleosides from Mycobacterium bovis BCG tRNA. Surveys of tRNA enzymatic hydrolysates with mass spectrometric techniques reveal the presence of modified ribonucleosides that are highly conserved among various species of organisms, as well as candidates of novel modifications. / by Tsz Yan Clement Chan. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1990. / Vita. / Includes bibliographical references. / by David Albagli. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Vita. / Includes bibliographical references. / Mechanistic studies on copper and palladium-catalyzed C-N bond forming reactions are described. To understand the mechanistic details of these processes, several principles of physical organic chemistry have been employed. Chapter 1. We have investigated the mechanism of the copper-catalyzed N-arylation of amides using aryl iodides, i.e., the Goldberg reaction. The focus of the work has been directed towards amides since this reaction remains the most versatile in the presence of Cu(I)/1,2- cliamine catalyst systems. The results provide insights into the role of 1,2-diamines in modulating the coordination environment around Cu(I). The catalyst is more efficient at high concentrations of 1,2-diamine and high concentrations of amide, as revealed by a nonlinear dependence of the rate on 1,2-diamine concentration. Extended premixing times between the Cu(I) precatalyst and the amide lead to an extensive induction period which can be attenuated by replacing the Cu(I) precatalyst with a Cu(II) precatalyst. Evidence for the reduction of the Cu(II) precatalyst through the oxidation of the amide is also presented. Furthermore, we demonstrate that a 1,2-diamine ligated Cu(I)-amidate may potentially serve as the reactive species that undergoes aryl halide activation. This was established through both its chemical and kinetic competency in the stoichiometric N-arylation process. This behavior has important consequences for new catalyst development since these results show the significance of both the diamine and amide in modulating the overall reactivity of the system. Chapter 2. / (cont.) A systematic mechanistic analysis of Pd(OAc)₂/ monophosphino- biaryl-catalyzed C-N bond forming reactions with aryl chlorides has been performed. The results provide insights into the relationship between the steady-state concentration of active Pd and the size and substitution pattern of the monophosphinobiaryl ligands. These insights into the nature of catalyst activation help highlight the importance of establishing a high concentration of active catalyst. The catalyst derived from the bulkiest ligand in the series, the tri-i-propyl ligand 13, exhibits both accelerated rate and the increased stability required for practical application of this reaction. / by Eric R. Strieter / Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007. / Vita. / Includes bibliographical references. / Catalytic Asymmetric Reductive Coupling of 1,3-Enynes and Aromatic Aldehydes Nickel-catalyzed reductive coupling reactions of 1,3-enynes and aromatic aldehydes efficiently afford conjugated dienols in excellent regioselectivity and modest enantioselectivity. These reactions were conducted in the presence of a catalytic ligand (R)-ferrocenyl(2-isopropylphenyl)phenylphosphine, whose overall synthesis was improved during the course of this investigation. 1-(Trimethylsilyl)-substituted enynes are shown to be efficient coupling partners in these reactions, and the dienol products formed readily undergo protiodesilylation under mild conditions. ... Catalytic, Asymmetric, Intramolecular Reductive Coupling of 1,1-Disubstituted Epoxides and Alkynes: Total Synthesis of Pumiliotoxin 209F and 251D Pumiliotoxins 209F and 251 D were prepared using a novel nickel-catalyzed intramolecular cyclizations between alkynes and 1,1-disubstituted epoxides. These cyclizations formed exclusively endo products without the use of a directing group on the alkyne. The synthesis of the reductive coupling precursors involved a diastereoselective sulfur ylide epoxidation of a proline-derived methyl ketone, where the choice of sulfonium salt conferred a major effect on the diastereoselectivity. / by Katrina Sue Woodin. / S.M.

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Includes bibliographical references (leaves 26-29). / The occurrence of certain alkaloids in the human brain appears to be associated with the onset of Parkinson's disease (PD). Recently, a human protein bearing homology to an alkaloid synthase in plants was identified. This protein, termed BSCv, may catalyze alkaloid formation in humans. If such activity is confirmed, regulation of BSCv through the use of small molecule inhibitors could provide novel drug therapies for PD patients. This paper describes the first heterologous expression and purification of this transmembrane protein and examines its biological function through a series of enzyme assays. The assays used to evaluate enzyme activity were modeled after the Pictet-Spengler condensation catalyzed by the plant enzyme. Substrates were selected based on their potential to form alkaloids previously identified in central nervous system tissue. Product formation was monitored via high-performance liquid chromatography. Preliminary data suggest that BSCv does not function as an alkaloid synthase. However, further studies are needed to ascertain such conclusions. Alternative detergents should be evaluated to assess their influence on enzyme activity. The use of an expanded substrate pool may also provide insight into protein function since substrate specificity may have restricted product formation in the performed assays. Finally, incubation of BSCv with rat brain extract, which contains another species homologue of the protein, could provide insight into its natural substrates. If these studies are unsuccessful, consideration should be given to the possibility that BSCv may function as a receptor. Once the mechanistic and structural properties of the plant enzyme are elucidated, it may be possible to take a more direct approach to the characterization of its human homologue. / by Stavroula K. Hatzios. / S.B.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998. / Vita. / Includes bibliographical references. / by Daniel D. LeCloux. / Ph.D.