Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. / Vita. / Includes bibliographical references. / Cell-surface carbohydrates are markers of specific cell types. These oligosaccharides are involved in recognition, adhesion, and signal transduction events. Advances in molecular glycobiology rely heavily on straightforward access to structurally defined oligosaccharides, but traditional syntheses of complex carbohydrates have been very laborious. Development of a novel linker and monitoring of each glycosylation reaction during automated solid-phase oligosaccharide synthesis allowed for the rapid synthesis of three Lewis-type cell surface oligosaccharides. The assembly of the nonasaccharide adenocarcinoma marker Le[superscript]y-Le[superscript]x monosaccharide building blocks was achieved in just 23 hours, while the syntheses of the tumor markers Lewis X, a pentasaccharide, and Lewis Y, a hexasaccharide, required only 12 and 14 hours respectively. The automation of carbohydrate synthesis greatly accelerates access to molecules for biological study and vaccine development. / by Kerry Routenberg Love. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Vita. / Includes bibliographical references. / This thesis employs colloidal semiconductor nanocrystals (NCs) as nanoscale emissive probes to investigate the physics of light emitting diodes (LEDs), as well as to unveil properties of cells that conventional imaging techniques cannot reveal. On the LED side, in particular, Chapter 2 utilizes individual NCs to alter layered organic LED structures at nanometer scale, resulting in spectrally resolved electroluminescence from single colloidal CdSe/ZnS (core/shell) NCs at room temperature. Chapter 3 takes NCs as emissive probes in layered organic LEDs, and shows that the photoluminescence of single NCs is bias dependent which helps elucidate the interactions between NCs and organic semiconductors, knowledge useful for designing efficient NC organic optoelectronics. Instead of using a planar LED geometry, Chapter 4 presents a technique for making nanoscale gap LEDs which allow the spectrally coincidental photoluminescence and electroluminescence from NCs. The work investigates the interactions between NCs and different metal gaps, and suggests electromigrating leads made of different metals as a promising route to fabricating nanoscale gaps with workfunction offsets for optoelectronic devices. On the cell biology side, we develop a three-dimensional sub-diffraction limited single fluorophore imaging method for proteins labeled with NCs. Chapter 5 applies the method to measure the endothelial glycocalyx thickness in vitro for the first time, by labeling different proteins with NCs of different emission wavelengths. Taking a step further, Chapter 6 utilizes the NC based imaging method to investigate the flow induced dynamics of endothelial glycocalyx, and measures the shear modulus of glycocalyx. / by Hao Huang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Vita. / Includes bibliographical references. / The diphosphaazide complex (MesNPP)Nb(N[CH2 tBu]Ar)3, 1 (Mes = 2,4,6-tri-tert-butylphenyl, Ar = 3,5-dimethylphenyl), releases a P2 unit upon heating to form MesNNb(N[CH2 tBu]Ar)3, 2, in a first-order process. The chemistry of the putative P2 intermediate was probed with a variety of reagents. It was successfully transferred to organic dienes to yield polycyclic diphosphines, and also to terminal phosphide complexes of the general formula P????M(N[R]Ar)3 to yield cyclo-P3 complexes. Coordination of W(CO)5 to 1 accelerates conversion to 2, with loss of the (P2)W(CO)5 fragment, such that this reaction occurs readily at 20 C. The (P2)W(CO)5 fragment was transferred to the same substrates listed above, as well as to a low-valent platinum source. In all cases, this transfer occurs in higher yields than for the uncomplexed P2. Kinetic measurements on the elimination reactions showed them to be first-order in diphosphaazide complex and independent of substrate concentration, consistent with the hypothesis that P2 and (P2)W(CO)5 are released into solution as discrete species. The above reaction chemistry was used to synthesize reactive, anionic cyclo-P3 complexes of niobium with formulas [f(OC)5Wgn(P3)Nb(N[CH2 tBu] Ar)3]- (n = 0;1; 2). These complexes were shown to react with the electrophiles Ph3SnCl, MesNPCl, and RC(O)Cl to yield coordinated h2-triphosphirene complexes. The acyltriphosphirene complexes [(OC)5W]2RC(O)P3Nb(N[CH2-tBu]Ar)3 are unstable toward loss of an RCP3[W(CO)5]2 fragment and formation of oxoniobium ONb(N[CH2 tBu]Ar)3. / (cont.) The cycloaddition chemistry of the so-generated, putative triphosphacyclobutadiene intermediate was probed through trapping reactions, including with adamantylphosphaalkyne to provide tetraphosphabenzenes complexed to W(CO)5. Silylphosphinidene complexes of niobium, R3SiPNb (N[CH2 tBu]Ar)3, were used to transfer phosphinidenes to isocyanates, carbon dioxide, and a terminal phosphorus monoxide complex of molybdenum in O-for-PR metathesis reactions. The latter reaction served as a synthesis of the unique, 3e?? donor diphosphenido ligand in the complex iPr3SiPPMo(N[tBu]Ar)3. Also investigated were the syntheses and reaction chemistry of metallacyclic phosphorylphosphinidene complexes, R2P(O)PNb(N[CH2 tBu]Ar)3. The niobaziridine hydride complex HNb(h2-C6H10?? NCy)(NCy2)2 was synthesized as a potential model for N2 binding, while independently prepared ([mu]-N2)[Nb(N[CH2tBu]Ar)3 was reductively cleaved to the anionic terminal nitride complex [NNb(N[CH2-tBu]Ar)3]-. Activation chemistry of As4 by Mo(N[tBu]Ar)3 and HNb(h2-tBuC(H)??NAr)(N[CH2 tBu]Ar)2 was used to ynthesize two terminal arsenide complexes. The syntheses of potential AsP- and PN-eliminating complexes are also described. / by Nicholas A. Piro. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Chapter 1. Introduction: The Reactivity of Bacterial Multicomponent Monooxygenases Bacterial multicomponent monooxygenases constitute a remarkable family of enzymes that oxidize small, inert hydrocarbon substrates using molecular oxygen. Three or more protein components are required for the timely reactions of electrons, protons, 02, and hydrocarbon at an active site carboxylate-bridged diiron center. This overview describes structural and biochemical studies of the BMM protein components, presents the proposed mechanisms of 02 activation by BMMs and related carboxylate-bridged diiron proteins, and discuses substrate reactivity of the oxygenated diiron units responsible for BMM catalysis. Chapter 2. Revisiting the Mechanism of Dioxygen Activation in Soluble Methane Monooxygenase from M. capsulatus (Bath): Evidence for a Multi-Step, Proton- Dependent Reaction Pathway Stopped-flow kinetic investigations of soluble methane monooxygenase (sMMO) from M. capsulatus (Bath) have clarified discrepancies that exist in the literature regarding several aspects of catalysis by this enzyme. The development of thorough kinetic analytical techniques has led to the discovery of two novel oxygenated iron species that accumulate in addition to the well-established intermediates Hroxo and Q. The first intermediate, P*, is a precursor to Hperoxo and was identified when the reaction of reduced MMOH and MMOB with 02 was carried out in the presence of a540 mM methane to suppress the dominating absorbance signal due to Q. The optical properties of P* are similar to those of H...O, with e420 = 3500 M cm- and F72O = 1250 M cm-. These values are suggestive of a peroxo-to-iron(III) charge-transfer transition and resemble those of peroxodiiron(III) intermediates characterized in other carboxylate-bridged diiron proteins and synthetic model complexes. The second identified intermediate, Q*, forms on the pathway of Q decay when reactions are performed in the absence of hydrocarbon substrate. Q* does not react with methane, forms independently of buffer composition, and displays a unique shoulder at 455 nm in its optical spectrum. Studies conducted at different pH values reveal that rate constants corresponding to P* decay/Hpeo formation and H,,,, decay/Q formation are both significantly retarded at high pH and indicate that both events require proton transfer. The processes exhibit normal kinetic solvent isotope effects (KSIEs) of 2.0 and 1.8, respectively, when the reactions are performed in D20. Mechanisms are proposed to account for the observations of these novel intermediates and the proton dependencies of P* to Hroxo and Hproxo to Q conversion. Chapter 3. Oxidation Reactions Performed by Soluble Methane Monooxygenase Hydroxylase Intermediates Hroxo and Q Proceed by Distinct Mechanisms Soluble methane monooxygenase is a bacterial enzyme that converts methane to methanol at a carboxylate-bridged diiron center with exquisite control. Because the oxidizing power required for this transformation is demanding, it is not surprising that the enzyme is also capable of hydroxylating and epoxidizing a broad range of hydrocarbon substrates in addition to methane. In this work we take advantage of this promiscuity of the enzyme to gain insight into the mechanisms of action of Hperoxo and Q, two oxidants that are generated sequentially during the reaction of reduced protein with 02. Using double-mixing stopped flow spectroscopy, we investigate the reactions of the two intermediate species with a panel of substrates of varying C-H bond strength. Three classes of substrates are identified according to the rate-determining step in the reaction. We show for the first time that an inverse trend exists between the rate constant of reaction with HPro,, and the C-H bond strength of the hydrocarbon examined for those substrates in which C-H bond activation is rate-limiting. Deuterium kinetic isotope effects reveal that reactions performed by Q, but not Hroxo, involve extensive quantum mechanical tunneling. This difference sheds light on the observation that Hrox is not a potent enough oxidant to hydroxylate methane, whereas Q can perform this reaction in a facile manner. In addition, the reaction of Hperoxo with acetonitrile appears to proceed by a distinct mechanism in which a cyanomethide anionic intermediate is generated, bolstering the argument that Hroxo is an electrophilic oxidant and operates via twoelectron transfer chemistry. Chapter 4. Dioxygen Activation and the Multiple Roles of Component Proteins in Phenol Hydroxylase from Pseudomonas sp. OX1 02 activation was also investigated in PH, a BMM that oxidizes phenol to catechol. Rapid freeze-quench M6ssbauer and stopped-flow optical spectroscopy were employed to study the reaction of the reduced, diiron(II) form of Pseudomonas sp. OXi PH hydroxylase (PHH) with 02 in the presence of the regulatory protein PHM. A single longlived diiron(III) intermediate with 6 = 0.59 mm/s and A EQ = 0.63 mm/s and no discernable optical bands accumulates along the reaction pathway. The spectroscopic parameters of this intermediate are similar to those reported recently for a diiron(III) transient generated in toluene/o-xylene monooxygenase hydroxylase but are quite different from those of peroxodiiron(III) species formed in other diiron enzymes despite the fact that the active sites of these proteins have identical first-shell coordination environments. In contrast to reactions of MMOH, there is no evidence for accumulation of a high-valent diiron(IV) intermediate in PHH. Under steady state conditions in the absence of hydrocarbon substrate, electrons are consumed and PHH generates H20 2 catalytically, suggesting that the observed diiron(III) intermediate is a peroxodiiron(III) species. Steady state biochemical studies were conducted to ascertain the functions of the PH reductase and regulatory protein. Single turnover experiments revealed that, unlike sMMO, only the complete system containing all three protein components is capable of oxidizing phenol. The yield of catechol produced under ideal conditions maximized at -50% per diiron active site in single turnover experiments, suggesting that the enzyme operates by a half-sites reactivity mechanism. Results from single turnover studies in which the oxidized form of the reductase, PHP, was added to a mixture of reduced hydroxylase and regulatory protein revealed that PHP exerts an additional regulatory effect on PHH, most likely by an allosteric mechanism. The rate of H20 2 formation by PHH in the absence of a hydrocarbon substrate was retarded when PHM was omitted from the reaction mixture, indicating that the regulatory protein controls the kinetics of 02 activation and/or blocks unproductive quenching of the oxygenated intermediate by untimely electron transfer. Chapter 5. Characterization of Iron Dinitrosyl Species Formed in the Reaction of Nitric Oxide with a Biological Rieske Center Reactions of nitric oxide with cysteine-ligated iron-sulfur cluster proteins typically result in disassembly of the iron-sulfur core and formation of dinitrosyl iron complexes (DNICs). Here we report the first evidence that these species can also form at Riesketype [2Fe-2S] clusters. Upon treatment of a Rieske protein, component C of toluene/oxylene monooxygenase (ToMOC) from Pseudomonas sp. OXI, with NO (g) or the NOgenerators S-nitroso-N-acetyl-DL-pencillamine (SNAP) and diethylamine NONOate (DEANO), the absorbance features of the [2Fe-2S] cluster bleach and a new band slowly appears at 367 nm. Characterization of the reaction products by EPR, M6ssbauer, and NRVS spectroscopy reveals that the primary product observed in the reaction is the dinuclear iron dinitrosyl Roussin's red ester (RRE), [Fe2(g-SCys) 2(NO)4], and that mononuclear DNICs only account for a minor fraction of the nitrosylated iron. The RRE reaction product can be reduced by sodium dithionite to produce the one-electron reduced Roussin's red ester (rRRE) having absorption bands at 640 and 960 nm. These results show that NO reacts readily with protein-based Rieske centers and suggest that dinuclear RRE species, not mononuclear DNICs, may be the primary iron dinitrosyl species responsible for the pathological and physiological effects of nitric oxide in the presence of iron-sulfur clusters. Appendix A. Preliminary Characterization of ''Fe-enriched MMOH. and MMOH by Nuclear Vibrational Resonance Spectroscopy Synchrotron-based 57Fe Nuclear Resonance Vibrational Spectroscopy (NRVS) is a powerful technique that allows for identification of the full set of vibrational modes of a given "Fe center. In this work we present preliminary NRVS studies of 57Fe-enriched oxidized soluble methane monooxygenase hydroxylase in complex with 2 equiv of its regulatory protein (MMOH.x:2B) and intermediate Q, the species responsible for methane oxidation in this enzyme. Although maximal protein concentrations were employed, very few vibrational peaks were resolved. Our data suggest that the sMMO protein system is not amenable to this method using the technologies that are currently available. / by Christine Elaine Tinberg. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Progress coupling of substrates, toward the total synthesis of amphidinolide B1 is described. The reductive 1,3-eynes and ketones was explored. It was found to work well with simple but failed to yield intermediates toward amphidinolide B1 [images] ... The coupling of 1,3-enyne and aldehyde fragments toward the synthesis of amphidinolides G3 and H4 is also described. The entire carbon skeleton of these natural products has been prepared from this coupling and a subsequent installation of a methyl group using an indium based reagent ... [images]. / by Andrew M. Lauer / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Progress toward the total syntheses of tamulamides A and B, two of the more recently isolated members of the marine ladder polyether family of natural products, is described. The tricyclic cores of the both the ABC fragment and the EFG fragment have been achieved. The fused tetrahydrofuran triad core of the ABC fragment has been synthesized via a base-mediated diepoxide cascade. The challenging 6,7,6 framework of the EFG fragment has been achieved through an intramolecular reductive cyclization reaction. With successful routes to the ABC and EFG cores in hand, current work is focused on elaboration of these intermediates to the desired Wittig coupling partners en route to the first total syntheses of tamulamides A and B ... [diagrams]. / by Elizabeth H. Kelley. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / Vita. / This thesis explores the spectroscopic properties of phonon-polaritons, which are admixtures of coupled electromagnetic and mechanical vibrations in polar crystals. An in-depth theoretical treatment supplemented with simulations of experimental results of a four-wave mixing impulsive stimulated Raman scattering (ISRS) method to generate and probe polaritons with arbitrary wavevectors is developed. A novel method to generate phonon-polaritons with high amplitudes via focusing is also presented. The motivation for this work is ultimately the generation of lattice oscillations with high amplitude that will permit exploration of the potential energy surface of collective vibrational motion beyond its linear regime. Femtosecond laser machining has been used to fabricate microstructures in lithium niobate and lithium tantalate. Phonon-polaritons propagation has been extensively characterized in a number of functional elements, including waveguides, resonators, and various diffractive, reflective, and focusing elements. The experimental results are supplemented by two-dimensional finite-difference time-domain simulations of polariton generation and propagation in arbitrary two-dimensional patterned structures. The phonon-polaritons studied have THz frequencies and propagate at lightlike speeds. The motivation for this research is the development of a versatile terahertz spectroscopy platform, in which phonon-polaritons are used as a source of THz radiation. Furthermore, these fabricated microstructures can serve as the basic building blocks of an intergrated platform in a single crystal where phonon-polaritons are used for ultrafast signal processing. / by Nikolay Staykov Stoyanov. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2008. / Includes bibliographical references (p. 133-151). / Carbonaceous aerosols are among the most prevalent yet least understood constituents of the atmosphere, particularly in urban environments. We have performed analyses of field samples and laboratory studies to probe the physico-chemical properties of soot and organic aerosols in a complimentary approach to obtain information essential for understanding their atmospheric evolution and environmental effects. Samples of particulate matter < 2.5 pm in diameter (PM2.5) were collected from the Mexico City Metropolitan Area (MCMA) for both bulk compositional analysis and single particle characterization. Approximately 50% of the non-volatile component of PM2.5 was found to consist of carbonaceous material, including both soot and organics. Other major components included sulfates, soil/dust and heavy metals indicative of industrial emissions. Single particle analysis confirmed the prevalence of soot particles; our evidence suggests they quickly became internally mixed with sulfates and other inorganic compounds in a day or less through extensive processing during their atmospheric residence times. In the second half of our approach, a Quartz Crystal Microbalance - Chemical Ionization Mass Spectrometry (QCM-CIMS) system was developed to probe the OH-initiated oxidation of organic and soot thin films as atmospheric aerosol surrogates. Mass loss (volatilization) from the films was observed upon exposure to OH radicals in the presence of 02 at 295 K and 100 Torr. The loss rate was found to be linearly dependent on OH and independent of 02 concentrations over the range 02 _1012 to 2.1018 molec/cm3. A relatively slower mass loss rate in the presence of NOx suggests simultaneous formation of alkyl nitrate compounds potentially important in polluted urban environments. Experimental data were used to extract the rate constants of individual steps within the context of a previously proposed oxidation mechanism. / Volatilization was observed in 15% relative humidity at a rate slower than under dry conditions, suggesting water adsorption to the surface. Initially hydrophobic alkane surfaces became noticeably hydrophilic as a result of oxidation. Although the oxidized surfaces did not exhibit measurable water uptake, water contact angle measurements show increased hydrophilicity, suggesting formation of polar (oxygen-containing) organic functional groups. / by Kirsten S. Johnson. / Ph.D.

Massachusetts Institute of Technology. Dept. of Chemistry. Thesis. 1969. Ph.D. / Vita. / Bibliography: leaves 179-184. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Vita. / Includes bibliographical references. / The application of recently developed stereoselective nickel-catalyzed reductive coupling reactions of alkynes and aldehydes to the synthesis of complex natural product targets was explored. The "B-Type" amphidinolides were selected as ideal targets owing to their molecular complexity and the paucity of synthetically viable means for their total construction. The diastereoselective nickel-catalyzed reductive coupling of simple aryl-substituted alkynes and a-oxyaldehydes was developed and applied to the construction of the C15-C26 region of amphidinolide H3. ... Alternatively, the nickel-catalyzed reductive coupling reaction of 1,3-enynes and aldehydes was found to be a very effective way of installing the congested 1,3-diene moiety common to all members of this class of natural products. This methodology was further examined as a fragment coupling strategy for the syntheses of amphidinolides G3 and H4. This allowed for a highly convergent and functional group tolerant assembly of these ... molecules and, to date, stands as the most complicated setting for the application of the catalytic reductive coupling reaction. / by Chudi O. Ndubaku. / Ph.D.