Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / The work presented in this dissertation addresses the development of new methodologies and processes to form carbon-nitrogen (C-N) and carbon-fluorine (C-F) bonds. The development of methods for the formation of C-N and C-F bonds are highly important to chemistry in general and find broad application in many different areas of research. With regard to C-N bond formation, the development of new nickel and palladium catalyst for C-N cross-coupling is presented. Finally, the development of a new process to enable the rapid preparation of aryl fluorides via the Balz-Schiemann reaction is explored. Chapter 1. Development of an Air-Stable Nickel Precatalyst for the Amination of Aryl Chlorides, Sulfamates, Mesylates, and Triflates. A new air-stable nickel precatalyst for C-N cross-coupling is reported. The developed catalyst system displays a greatly improved substrate scope for C-N bond formation to include both a wide range of aryl and heteroaryl electrophiles and aryl, heteroaryl, and alkyl amines. The catalyst system is also compatible with weak base, allowing for the amination of substrates containing base-sensitive functional groups. Chapter 2. Design of New Ligands for the Palladium-Catalyzed Arylation of a- Branched Secondary Amines. In Pd-catalyzed C-N cross-coupling reactions, a-branched secondary amines are difficult coupling partners and often produce low yields of the desired product. To provide a robust method for accessing N-aryl a-branched tertiary amines, new catalysts have been designed to suppress undesired side reactions often encountered when these amine nucleophiles are used. These advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions. Chapter 3. Rapid Synthesis of Aryl Fluorides in Continuous Flow via the Balz- Schiemann Reaction. The synthesis of aryl fluorides (ArF) is of critical importance for the development of new and potent pharmaceuticals and agrochemicals. While there have been numerous and intense research efforts focused on developing new fluorination methods, the Balz-Schiemann reaction remains a valuable and efficient means of aryl C-F bond construction from a vast pool of available aryl amines. However, the harsh reaction conditions, modest yields, and often prohibitive safety concerns have limited the general application of this methodology. Here, we have developed a semi-flow process that enables safe handling of the potentially explosive aryl diazonium salt intermediates as well as improved yields of the desired aryl fluoride products. This process has been demonstrated on an array of different aryl and heteroaryl amine substrates containing a variety of different functional groups. / by Nathaniel H. Park. / Ph. D. in Organic Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / Last 29 leaves numbered "192." Vita. / Includes bibliographical references. / Chapter One: Two of the most famous tripodal ligands, Kliui's cyclopentadienyltris(dialkylphosphito)cobaltate(III) and Trofimenko's hydrotris(1-pyrazolyl)borate, were studied with respect to their reactivity towards Alberto's tris(solvento)tricarbonyltechnetium(I) and tris(solvento)tricarbonylrhenium(I) cations. The reaction of [M(H2O)3(CO)3]+ (M = Tc, Re) with Na[CpCo[PO(OR)2]3] (NaLOR; R = Me, Et) in water produced the compounds M(CO)3(LoR). The two compounds M(CO)3(LoEt) were structurally characterized by single crystal X-ray crystallography. In both cases, the ligand LOEt was bound to the metal center in a tridentate fashion utilizing an 000 donor set. The ligands LOR can be used as models for facially coordinated triaqua groups owing to their position in the spectrochemical series. Therefore, these four compounds, M(CO)3(LoR), can be considered structural models for [M(H2O)3(CO)3]+. The reaction of [Re(CO)3(sol)3]+ (sol = H20, MeOH, MeCN) with K[HB(pz)3] (KTp) has yielded a variety of products depending on the solvent used. For the two protic solvents, mixtures of TpRe(CO)3 and a byproduct (NEt4)[Re2(CO)6(jg-pz)2([t-OR)] (R = H or Me) were obtained. The methoxy-bridged species has been isolated and fully characterized, and the crystal structure has been determined. While a chemical separation of the analogous hydroxy-bridged species from TpRe(CO)3 was not accomplished, a crystal of the compound was selected from the mixture, and a partial crystal structure was solved. When an aprotic solvent such as acetonitrile was used, only TpRe(CO)3 was obtained and was recovered in high yield. / (cont.) Chapter Two: N-(2-mercaptoethyl)picolylamine (MEPAH) was studied as a potentially biologically relevant ligand for the 'fac-[M(CO)3]+" core (M = Re, 99Tc, 99mTc). To this end, the complex Re(CO)3(MEPA) was synthesized. The reaction of MEPAH with fac-[Re(CO)3(MeCN)3]+ took place over the course of seconds, showing the high affinity possessed by this ligand for the "fac-[Re(CO)3]+" core. A single crystal X-ray diffraction study was performed, confirming the nature of Re(CO)3(MEPA), a rare mononuclear rhenium(I) thiolate complex. Exploration into derivatization of the ligand backbone has afforded the analogous N-ethyl complex, Re(CO)3(MEPA-NEt). Further work has given rhenium complexes of bioconjugated ligands, whereby biologically active molecules have been tethered to the ligand framework. The high affinity of the ligand for the metal, coupled with the ease of its derivatization, implies that this ligand system is promising for the purposes of 99mTc radiopharmaceutical development. Chapter Three: The bioevaluation of 99mTc complexes of derivatives of MEPAH is described. Complexes analogous to the tricarbonylrhenium(I) complexes described in Chapter 2 were synthesized and characterized by HPLC. After confirmation of the composition of these 99mTc complexes, in vitro and in vivo studies were performed. These compounds of the "fac-[99mTc(CO)3]+' core, containing the biologically active molecules morpholine and nornicotine, were evaluated for uptake by melanoma and brain tissue, respectively, in mice. / by Daniel Joshua Kramer. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1917. / MIT copy bound with: The determination of saccharin as its mercury compounds / Benjamin M. Bond. / Includes bibliographical references (leaf 46). / by Robert S. Mulliken. / B.S.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Includes bibliographical references (leaf 18). / Cyclosporin A induced biosynthesis of colored compounds in three species of Aspergillus. Diode array HPLC MS analysis of culture extracts revealed Aspergillus terreus demonstrated the most profound response, with upregulation of more then twelve compounds from three distinct chemical families; butyrolactones, aspulvinones, and asterriquinones. Compounds from these three families are prenylated, and biosynthetically derived from homodimers of amino acids. The majority of the upregulated compounds were the aspulvinones, a class of butenolides. Structural elucidation of four isolated aspulvinones revealed both known and novel structures. Inducer concentration had a significant impact on aspulvinone profile. Bioassay revealed previously unreported antibacterial activity for the aspulvinones. A high-throughput colorimetric screen was designed to probe the response. The screen of 2480 known bioactives revealed multiple compounds capable of inducing aspulvinone production, and one compound, rapamycin, capable of inhibiting the response. Additionally, the increase in aspulvinone production was correlated with a decrease in culture density, indicating aspulvinone production is a general stress response. / by Amy Hanlon. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / In title on t.p., "[beta]" appears as the Greek letter. Vita. / Includes bibliographical references. / The biological function of a protein is in large measure determined by its three-dimensional structure. To date, however, the transition of the protein between the native and non-native conformations is not well-understood. Part of the difficulty is the large conformational space available to a poly-peptide chain, and a general lack of experimental probes that can access local structural information on the time scale of the transition. Single domain peptides are excellent model systems that reduce the size and complexity of the problem, while maintaining the essential physical interactions. In this thesis, P-hairpin peptides are used as model systems for studying P-sheet secondary structure. Hairpin folding has been studied for a number of years, but there is still debate in the literature about the relative importance of the cross-strand hydrogen bonds, tertiary side chain contacts, and p-turn in the folding pathway. In addition, the denatured state is very poorly understood, which complicates any attempt to describe the folding pathway. In this work, amide I vibrational spectroscopy is used to resolve the secondary structure of P-hairpin peptides during thermal denaturation. Spectroscopic modeling is presented to describe the amide I band of 0-hairpins and relate it to structural features. Three spectroscopic methods are used to probe the amide I band: Fourier transform infrared (FTIR) spectroscopy, two-dimensional infrared (2D IR) spectroscopy, and dispersed vibrational echo (DVE) spectroscopy. 2D IR and DVE spectroscopy are 3rd order-nonlinear methods that interrogate the system with a series of ultrafast (100 fs) laser pulses. 2D IR spectra reveal vibrational couplings and measure spectral dynamics on a picosecond time scale. . / (cont.) The 2D IR spectra of TZ2 and PG12 are used to identify 3sheet structure during thermal denaturation and to measure the amide I homogeneous line width changes with temperature. The transient folding of TZ2 and PG12 is also probed with 2D IR and DVE spectroscopy following a 10 to 20 OC temperature jump. In order to increase the structural sensitivity of amide I spectroscopy, 13C and 180 isotope labels are incorporated into specific peptide amide groups. The isotope labels red-shift vibrational frequencies and help resolve local structure at the turn and mid-strand regions of the peptides. The transient folding at each labeled site is also measured following a temperature jump. Together, the results of this work identify folding rates for the thermal disordering transition. For PG12, the unfolding time at the mid-strand region of the peptide is 130 ns, and the turn is found to be stable throughout the transition. For TZ2, the kinetic folding rates at each of the labeled sites are found to be very similar to the global unfolding time (-1 Its). Temperature jump 2D IR spectroscopy of TZ2 reveals that the disordering mechanism is unique for different regions of the peptide. The band corresponding to the turn region decouples from the other vibrations, but does not show signs of disorder. In the mid-strand region of the peptide, the isotope-shifted band decouples from the main amide I band and also broadens significantly. Local disordering and decoupling both occur on a 1 gis time scale. The observations in this work combined with previous measurements are used to describe the folding as a hybrid zipper. TZ2 folding is initiated with the formation of the P-turn, following which the tryptophan side chains form a compact, but non-native hydrophobic core. Next, the backbone native contacts are formed and finally the tryptophan side chain packing reaches the native configuration. / by Adam W. Smith. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references. / by Michael David Lawlor. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Includes bibliographical references. / by Darryl Day Spencer. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Vita. / Includes bibliographical references (leaves 198-230). / by Elizabeth Eloise Trimmer. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012. / 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. / In this work, I describe experiments utilizing high-field terahertz (THz) pulses to initiate nonlinear responses in several classes of materials. We have developed several methods for interrogating the nonlinear THz response of materials including collinear and noncollinear THz-pump/THz-probe spectroscopy, and THz-pump/optical probe spectroscopies including THz Kerr effect spectroscopy. We have observed nonlinear free-carrier absorption, occurring through the saturation of free-carrier mobility in bulk semiconductors. We have demonstrated that highly energetic electrons in the conduction band can generate electron-hole pairs in indium antimonide, and have elucidated the dynamics of the carrier generation process. We have observed nonlinear conductivity responses in graphene, showing that a strong THz pulse can heat the electron distribution leading to saturable absorption in the THz range. We have demonstrated THz-induced optical anisotropy in simple liquids, allowing for the measurement of subsequent orientational dynamics. We have driven nonlinear vibrational dynamics in ferroelectrics, demonstrating that the strong anharmonicity of lattice vibrational modes can induce an anisotropic optical response. We have begun to study nonlinear vibrational responses in molecular crystals, which is of importance in mode coupling and energy transfer processes in the THz range. Finally, we have driven nonlinear metamaterial responses in gallium arsenide and vanadium dioxide. In GaAs, we have shown that metamaterial properties may be tuned by an intense THz field if the substrate material (GaAs) is changed by the incident THz pulse, and we have demonstrated carrier multiplication locally in the metamaterial split ring resonator gaps where substantial electric field enhancement occurs. In VO2, we have shown that THz radiation can drive an insulator-to-metal phase transition, opening up new possibilities in the control of the states of matter with THz fields. This work has demonstrated only a few of the capabilities made possible by the interaction of intense THz radiation with matter, and provides a general framework to open up new research in a nascent field. / by Harold Young Hwang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998. / Includes bibliographical references. / by Frank Leon Halet Brown. / Ph.D.