Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1994. / Includes bibliographical references. / by Qing Feng. / Ph.D.

Thesis: S.M. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2014. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / In order to overcome side effects and drug resistance associated with conventional Pt(II) drugs, our lab has developed novel platinum complexes. One of the new platinum complexes developed in our lab is the monofunctional platinum anti-cancer compound phenanthriplatin. We have found that by binding to sulfur complexes, phenanthriplatin undergoes changes in its kinetic and cytotoxic properties. Sulfur adducts of phenanthriplatin were synthesized to study the complex roles sulfur compounds serve in the cellular action of the monofunctional compound. In addition, we have examined how Pt(IV) chemistry can be successfully applied to increase the efficacy of Pt(II) compounds. We conjugated hydrophobic chains to trans-[Pt(NH₃)₂Cl₂] (TDDP) through isocyanate couplings and successfully transformed TDDP into an active compound. We demonstrated that Pt(IV) chemistry can be applied to transform even inactive trans compounds into active complexes that can potentially be used in chemotherapy. Finally, we examined the anticancer properties of the dinuclear osmium(VI) nitrido complex [NBu₄]₂[(OsNCl₄)₂(pyz)]. We studied its cellular activity in the hope of discovering interesting and unexpected properties. We found that the compound has moderate cytotoxicity and leads to DNA damage and apoptosis. / by Hyunsuk Yoo. / S.M. in Inorganic Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Vita. / Includes bibliographical references. / Quantum dot-based fluorescent probes were synthesized and applied to biological imaging in two distinct size regimes: (1) 100-1000 nm and (2) < 10 nm in diameter. The larger diameter range was accessed by doping CdSe/ZnS or CdS/ZnS quantum dots (QDs) into shells grown on the surfaces of pre-formed sub-micron SiO2 microspheres. The smaller diameter range was accessed with two different materials: very small InAs/ZnSe QDs and CdSe/ZnS QDs, each water solubilized with small molecule ligands chosen for their ability not only to stabilize QDs in water but also to minimize the total hydrodynamic size of the QD-ligand conjugates. Indium arsenide QDs were synthesized because nanocrystals of this material can be tuned to fluoresce in the near infrared (NIR) portion of the electromagnetic spectrum, especially in the 700-900 nm window where many tissues in the body absorb and scatter minimally, while maintaining core sizes of 2 nm or less. The QD-containing microspheres were used to image tumor vasculature in living animals, and to generate maps of size-dependent extravasation. With subcutaneously delivered nAs/ZnSe QDs, multiple lymph node mapping was demonstrated in vivo for the first time with nanocrystals. When administered intravenously, < 10 nm QDs escaped from the vasculature, or were efficiently cleared from circulation by the kidney. Both of these behaviors, previously unreported, mark key milestones in the realization of an ideal fluorescent QD probe for imaging specific compartments in vivo. Also presented in this thesis is the growth of single-crystalline cobalt nanorods through the oriented attachment of spherical cobalt nanocrystal monomers. / (cont.) When administered intravenously, < 10 nm QDs escaped from the vasculature, or were efficiently cleared from circulation by the kidney. Both of these behaviors, previously unreported, mark key milestones in the realization of an ideal fluorescent QD probe for imaging specific compartments in vivo. Also presented in this thesis is the growth of single-crystalline cobalt nanorods through the oriented attachment of spherical cobalt nanocrystal monomers. / by John P. Zimmer. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references. / Quantum dots (QD) are unique materials in which their optical properties are decoupled from their solution properties via the tunability of surface ligands. The primary focus of this thesis is the design and synthesis of new ligand coatings to render QDs water soluble, pushing the boundaries of QD applications in biology both in-vivo and in-vitro. On the in-vivo front, ultrasmall QDs (-5 nm hydrodynamic diameter) were synthesized via the use of Cysteine as a zwitterionic ligand coating to generate the smallest biocompatible QDs known to date, allowing for the first time collection of quantitative in-vivo renal clearance data of inorganic nanoparticles in a mouse as a model for design of future clearable nanoparticle in-vivo probes and drug delivery vehicles. On the in-vitro front, a suite of multifunctional ligands were synthesized to produce QDs that exhibit low non-specific binding to cells, small hydrodynamic diameter (HD), tunable surface charge, high quantum yield, and good solution stability across a wide pH range. These ligands feature dihydrolipoic acid for tight binding to the QD surface, a short poly(ethylene glycol) (PEG) spacer for water solubility and biocompatibility, and an amine or carboxylate terminus for covalent derivatization. We successfully demonstrated covalent attachment of energy acceptor dyes to enable sensing applications via Forster Resonance Energy Transfer (FRET), and attachment of proteins to enable high-affinity cell labeling and single particle tracking. In addition, QDs solubilized with these ligands could be derivatized via metal-affinity driven conjugation chemistry with polyhistidine-tagged proteins, which facilitated the purification of monovalent QDs for the first time via gel electrophoresis. Further improvement on ligand stability focused on addressing the problem of thiol oxidation, and a new class of multifunctional polymer ligands were developed featuring multiple imidazole moieties for multidentate interactions with the QD surface. The polymers are synthesized via reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization to produce molecular weight controlled monodisperse random copolymers from three types of monomers that feature imidazole groups for QD binding, polyethylene glycol (PEG) groups for water solubilization, and either primary amines or biotin groups for derivatization. / by Wenhao Liu. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002. / Vita. / Includes bibliographical references. / Proton-coupled electron transfer (PCET) is the basic mechanism for bioenergetic conversion. Consummate examples include water oxidation in photosynthesis and oxygen reduction in respiration. Despite the importance of PCET in such catalytic bond-making and bond-breaking reactions, the underlying mechanisms of coupled proton and electron transport in these processes is not well understood. To address mechanistic issues surrounding the role of PCET in catalytic chemical transformations, we have begun characterizing PCET events at a molecular level in a broad spectrum of small-molecule activation reactions for the first time. Two distinct structural scaffolds have been elaborated to study the PCET chemistry of 0-0 bond forming and cleaving reactions. The first consists of platforms containing two redox sites linked face-to-face by a rigid xanthene (DPX) or dibenzofuran (DPD) spacer - Pacman porphyrins. A comparative structural study demonstrates that DPD has the unprecedented ability to open and close its binding pocket by a vertical distance of over 4 A upon substrate binding, providing the first direct observation of the Pacman effect in a single cofacial platform. Moreover, efficient oxygen-activation chemistry is preserved when such cofacial motifs exhibit a large range of vertical motion; for example, dicobalt(II) complexes of both DPX and DPD are effective electrocatalysts for the direct four- electron reduction of oxygen to water despite their ca. 4 A difference in metal-metal distances. / (cont.) The second scaffold consists of acid-base and redox functionalities affixed to a xanthene (HPX) or dibenzofuran (HPD) scaffold - Hangman porphyrins. HPX selectively encapsulates water between its acid-base and redox sites by hydrogen bonding, affording a minimalist model for the cytochrome P450 heme water channel assemblies. Comparative reactivity studies for the catalase-like disproportionation of hydrogen peroxide and the epoxidation of olefins by HPX and HPD platforms bearing acid and ester pendants reveal that the introduction of a proton-transfer network properly oriented to a redox-active platform can orchestrate catalytic 0-0 bond activation. For the catalase and epoxidation reaction types, a marked reactivity enhancement is observed for the xanthene-bridged platform with a pendant carboxylic acid, establishing that this approach can yield superior catalysts to analogs that do not control both proton and electron currencies. / by Christopher J. Chang. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998. / Vita. / Includes bibliographical references. / Although complexes derived from anionic borabenzenes (boratabenzenes) had been used for a long time, little was known about their neutral counterparts, mostly because an easy synthetic entry to them was not available. A facile three-step synthesis that allows the preparation of large quantities of neutral borabenzenes in three days, from commercially available starting materials is described in Chapter 2. In Chapter 3 it is shown that neutral borabenzenes can be converted into anionic boratabenzenes, thereby providing a versatile new synthesis of this family of compounds. The solid state structures of these complexes are described. The developments in Chapters 2 and 3 allowed us to continue on to studies of both borabenzene and boratabenzene complexes. Chapter 4 deals with the complexation of borabenzenes and boratabenzenes to some common transition metal fragments, mostly Cr(CO)3 and [Rh(olefin) 2 ]+ , as well as structural studies thereof. We also discuss the interconversion between borabenzene- and boratabenzene-metal complexes. Chapter 5 deals with the chemistry of the parent 1-H-boratabenzene. We discuss its synthesis, structure (in the solid state and in solution), and reactivity. In this chapter it is shown that the B-H is hydridic, and that the ring can form R-complexes with transition metals. The electron-donating ability of 1-H-boratabenzene is shown to lie somewhere between that of benzene and of Cp. Chapter 6 is concerned with the chemistry of diphenylphosphidoboratabenzene. This molecule is unique among boratabenzenes in that it prefers to bind main group electrophiles and transition metals through its boron substituent. Solid state structural studies establish that it has the same steric bulk as triphenylphosphine. Comparative studies of its transition metal complexes show that it is considerably more electron-donating than triphenylphosphine. / by Diego Andrés Hoic. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1992. / Includes bibliographical references. / by David Michael Jonas. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1912. / MIT copy bound with: Analysis of gas blacks / Frank D. Bishop -- Identification of certain coal tar dyes used in coloring foods / Hattie D. F. Haub -- A rapid volumetric method for tan analysis / M. W. Hedden -- A study of the so-called false equilibrium between selenium and hydrogen / Walter H. J. Taylor -- An investigation of methods recently proposed for the determination of tin in canned food products / E. B. Wettengel. / by Kenneth H. Barnard. / B.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Vita. / Includes bibliographical references. / Purine biosynthesis has been used as a paradigm for the study of metabolism of unstable molecules. Both phosphoribosylamine (PRA) and N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) have estimated half-lives in vivo of seconds. In order to avoid metabolite decomposition, one strategy cells could employ is channeling-the direct transfer of a metabolite between enzyme active sites without diffusion into the bulk media. While kinetic evidence for channeling of PRA has been reported between phosphoribosylpyrophosphate amidotransferase (PurF) and glycinamide ribonucleotide synthetase (PurD), no evidence for a PurF:PurD complex has been found. In an effort to detect this complex, stopped-flow fluorescence spectroscopy was used to detect changes in PurF fluorescence that may result from interaction with PurD. Critical to the success of these experiments was incorporation of tryptophan analogs (4-fluorotryptophan and 7-azatryptophan) into the proteins in order to increase signal specificity for PurF. No evidence for a PurF:PurD interaction was found under any of the conditions tested. The implication of this finding is discussed with regard to the PurF:PurD channeling model. Like all amidotransferase enzymes (ATs), channeling of NH3 between glutaminase and AT active sites has been implicated in the formylglycinamide ribonucleotide amidotransferase (FGAR-AT). / (cont.) In B. subtilis, the FGAR-AT is composed of three proteins: PurS, PurQ, and small PurL. The first characterization of the B. subtilis FGAR-AT complex was carried out, and it was determined that a complex between the three proteins can only be isolated in the presence of Mg2+-ADP and glutamine. By analogy to the Salmonella FGAR-AT, ADP is believed to be acting as a structural cofactor, while formation of a PurQ-glutamine complex is essential for assembly of the FGAR-AT. Subsequent biophysical studies have indicated that the physiologically relevant form of the FGAR-AT complex contains 2 PurS, 1 PurQ, and 1 small PurL. Further studies on PurQ have identified residues important for catalysis and complex formation, while insight into the small PurL active site has been obtained by studies on the T. maritima enzyme. The FGAR-AT complex provides a new system in purine biosynthesis to study metabolite transfer among weakly interacting proteins. / by Aaron A. Hoskins. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1960. / Vita. / Includes bibliographical references (leaves 102-103). / by James E. Davis. / Ph.D.