Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009. / Vita. / Includes bibliographical references. / N-linked glycosylation is a ubiquitous form of protein modification whereby a preassembled oligosaccharide is covalently attached the asparagine side chain of an acceptor protein. This process involves numerous enzymes, produces a diverse set of oligosaccharide structures, and results in a variety of structural and functional effects on the glycoprotein. Research discussed in this dissertation applies synthetic organic chemistry to probe this important biological system. To study the effects of N-linked glycosylation on protein folding, a semi-synthetic strategy was developed to access a set of model proteins that were homogeneously glycosylated at several sites of interest. The folding kinetics of this set of glycoproteins were then characterized using stopped-flow fluorescence spectroscopy, which revealed that the presence of the glycan show discrete effects on both the rate of protein folding and unfolding, and that the overall effect is highly specific to the local primary and secondary structure of the glycosylation site. The gram-negative bacterium Campylobacterjejuni was recently discovered to contain a general N-linked glycosylation system with a defined glycan structure and tractable enzymes for heterologous expression including a single subunit oligosaccharyltransferase. To probe the bacterial N-linked glycosylation machinery, a chemo-enzymatic synthesis for each of the glycan intermediates within this pathway was developed, which are impractical to obtain from the host organism. Importantly, chemo-enzymatic allowed for the incorporation of structural modifications for binding-specificity assays and radiolabels for accurate quantification. Access to these substrates allowed us to define the minimum glycosylation consensus sequence for the oligosaccharyltransferase as well as the polyisoprenol specificity of three representative enzymes within the pathway. / by Mark M. Chen. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1993. / Includes bibliographical references (leaves 200-202). / by David Youngjin Son. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Vita. / Includes bibliographical references. / Chapter 1. Modeling Carboxylate-Rich Diiron Sites of Dioxygen-Dependent Non-Heme Enzymes Carboxylate-bridged diiron centers are employed in a variety of biological systems to activate dioxygen for substrate oxidation, and small molecule models have been synthesized to mimic this chemistry outside of the natural systems. In this introductory chapter a brief overview of terphenyl-based carboxylate systems is given and progress toward achieving structural, spectroscopic, and functional models of the protein active sites is reviewed. Chapter 2. Synthesis and Reactivity of Carboxylate-Bridged Diiron(II) Complexes with Primary Alkyl Amine Ligands The synthesis and crystallographic characterization of a series of diiron(II) complexes with sterically hindered terphenyl carboxylate ligands and alkyl amine donors are presented. The compounds ... , where ... 2,6-di(p-tolyl)benzoate, and [...] (L= NH₂(CH₂)₃SMe (4); NH₂(CH₂)₃CCH (5)), where ... is 2,6-di(3,5- dimethylphenyl)benzoate, were prepared as small molecule mimics of the catalytic sites of carboxylate-bridged non-heme diiron enzymes. / (cont.) The compounds with the ... carboxylate form tetrabridged structures, but those containing the more sterically demanding ... ligand have only two bridging ligands. The ancillary nitrogen ligands in these carboxylate-rich complexes incorporate potential substrates for the reactive metal centers. Their oxygenation chemistry was studied by product analysis of the organic fragments following decomposition. Compound 1 reacts with dioxygen to afford PhCHO in [approx.] 30% yield, attributed to oxidative dealkylation of the pendant benzyl group. Compound 3 decomposes by established bimolecular pathways upon exposure to dioxygen at low temperatures. When the ... carboxylate is replaced by the ... ligand, as in 5, this behavior no longer occurs. Instead the six- coordinate iron(III) complex with one bidentate and two monodentate carboxylate ligands, [...] (6), was isolated from the reaction mixture following the oxidation of 5. / (cont.) Chapter 3. C-H Activation with Benzyl- and Ethyl- Substituted Pyridine Ligands in Carboxylate-Bridged Diiron(II) Complexes with Dioxygen In this study benzyl and ethyl groups were appended to pyridine and aniline ancillary ligands in diiron(II) complexes of the type [...], where ... is the sterically hindered 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh, respectively). These crystallographically characterized compounds were prepared as models for the diiron(II) center in the hydroxylase component of soluble methane monooxygenase (MMOH). Use of 2- benzylpyridine (2-Bnpy) afforded doubly-bridged [...] (1) and [...] (4), whereas tetra-bridged [...] (3) resulted when 4-benzylpyridine (4-Bnpy) was employed. Similarly, 2-(4-chloro- benzyl)pyridine (2-(4-ClBn)py) and 2-benzylaniline (2-Bnan) were employed as N-donor ligands to prepare [...] (2) and [...](5). Placement of the substituent on the pyridine ring had no effect on the geometry of the diiron(II) compounds isolated when 2-, 3-, or 4-ethylpyridine (2-, 3-, or 4-Etpy) was introduced as the ancillary nitrogen ligand. The isolated [...] (6), [...] (7), [...] (8), and [...] (9) complexes all contain doubly-bridged metal centers. / (cont.) The oxygenation of compounds 1 - 9 was studied by product analysis of the organic fragments following decomposition. Hydrocarbon fragment oxidation occurred for compounds in which the substrate moiety is in close proximity to the diiron center. The extent of oxidation depended on the exact makeup of the ligand set. Chapter 4. A Thermally Sensitive Intermediate Generated in the Reaction of [...] with Dioxygen In this chapter the reaction of [...] (la) with dioxygen at low temperature to form the 02-sensitive intermediate (lb) was investigated. Various spectroscopic methods including UV-visible, resonance Raman (rR), electron paramagnetic resonance (EPR), and M6ssbauer were applied to study the mechanism and the intermediates involved. Chapter 5. Synthesis and Reactivity Studies of Carboxylate-Bridged Diiron(II) Compounds with Dangling Sulfur-Containing Substrates Functional models of the carboxylate-bridged diiron active site in soluble methane monooxygenase are described in which potential substrates are introduced as substituents on bound pyridine ligands. / (cont.) Thiol, sulfide, and sulfoxide moieties tethered to pyridine were allowed to react with the prefabricated diiron(II) complex [...], where ... is a sterically hindered 2,6-di(p-tolyl)benzoate. The resulting diiron(II) complexes were characterized crystallographically. Triply- and doubly-bridged compounds [...] (1), [...] (2), and [...] (3) resulted when 2-phenylthiopyridine (2-PhSpy), 2-methylthio- pyridine (2-MeSpy) and 2-pyridylmethylsulfoxide (2-MeS(O)py), respectively, were employed. Use of 2-mercaptopyridine (2-HSpy) afforded the mononuclear complex [...] (4a). The dioxygen reactivity of these iron(II) complexes was investigated. A dioxygen-dependent intermediate (4b) formed upon exposure of 4a to 0₂, the electronic structure of which was probed by various spectroscopic methods. Exposure of 1 - 3 to dioxygen revealed both sulfide and sulfoxide oxidation. Chapter 6. Effect of Substrate Position in Diphenylphosphinopyridine Ligands on Geometry and Reactivity of Diiron(II) Carboxylate-Bridged Compounds In this chapter the exploration of carboxylate-bridged diiron(II) compounds containing phosphino-derivatized pyridine ligands to mimic aspects of chemistry at the active site of soluble methane monooxygenase (sMMO) is presented. / (cont.) 2-, 3-, or 4-Diphenylphosphino moieties incorporated into a pyridine ligand (2-, 3-, or 4-Ph₂Ppy) were allowed to react with the preassembled diiron(II) complex [...], where ... is a sterically hindered 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh). Triply-, doubly-, and tetrabridged compounds [...] (1), [...] (2), [...] (3), [...] (4) resulted and were characterized crystallographically. Exposure of 1 - 4 to dioxygen revealed both stoichiometric and catalytic phosphine oxidation. Oxidation of 4 in CH₂C1₂ affords [...] (6), which contains the biologically relevant [Fe₂([mu]-OH)₂([mu]-O₂CR)] ³⁺ core. This reaction is sensitive to the choice of carboxylate ligands, however, since the p-tolyl analog 1 yielded a hexanuclear species, 5, upon oxidation. / by Emily Carrig Carson. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1992. / Vita. / Includes bibliographical references. / by John Anthony Thomas. / Ph.D.

Thesis: Ph. D. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references. / In the field of coordination chemistry, there are many standard organic ligand designs that are optimized for their ease of synthesis as well as established and favorable properties. Nevertheless, there is still room to add new ligand classes to the toolbox for specific applications. This thesis focuses on expansion of the types of ligands available for (1) metallic nanomaterial surface modification and (2) metal-ligand driven supramolecular assembly. (1) Surface ligands are typically used for surface passivation, imparting new properties such as solubility, or introducing a functional handle for further modification. The different demands in many diverse fields such as catalysis, electronics, and biomedicine necessitate that ligands interact strongly with surfaces and are structurally versatile. Herein, we advance N-heterocyclic carbenes (NHCs) as a new class of surface ligands to complement other established classes such as thiols, carboxylic acids, phosphines, ammonium salts, and phosphine oxides. Our studies have focused on ligand design for gold nanoparticles (NPs) and nanorods (NRs) in aqueous media. Using a polyethylene glycol (PEG)-conjugated NHC strategy, we demonstrate the first example of water-soluble NHC-stabilized Au-NPs. We then develop a bidendate NHC-thiol to modify gold NRs for photothermal therapy. (2) We examine the interface between amorphous polymers and crystalline metal organic frameworks (MOFs) in an emerging class of materials called polyMOFs. PolyMOFs use polymer ligands as their building blocks, opening the door to new material properties. In our work, we have developed a strategy for the synthesis of addressable, unimolecular polyMOF-forming oligomers using iterative-exponential growth, which has allowed us to study unique structure-property relationships of polyMOFs. Furthermore, we have developed pre- and post- synthetic modification strategies for polyMOF based materials. / by Michelle MacLeod. / Ph. D. in Inorganic Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1989. / On t.p. "[beta]" is the Greek letter. Vita. / Includes bibliographical references (leaves 168-176). / by Michelle Anne Jane Palmer. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Chapter 1 describes the synthesis of tert-butylimido alkylidene complexes for molybdenum and tungsten. A dimer species [chemical formula] served as a bisimido precursor. After alkylation with Grignard reagent, alkylidene formation is accomplished using pyridinium chloride. [chemical formula] crystallizes as a dimer [chemical formula] with a loss of pyridine for each W center. For the case of molybdenum, addition of pentafluorophenol to the diimido dialkyl precursor affords [chemical formula]. Dipyrrolide complexes for both Mo and W are synthesized and isolated as a 2,2'-bipyridine adduct. Addition of a sterically encumbered terphenol along with ZnCl₂(dioxane) affords monoalkoxide pyrrolide (MAP) complexes [chemical formula]. Chapter 2 investigates Z-selective ring-opening metathesis polymerization (ROMP) of 3- substituted cyclooctenes (3-RCOEs) by Mo and W MAP catalysts. [chemical formula], [chemical formula], and [chemical formula] all produced >98% [chemical formula]. The key in forming high molecular weight polymer instead of cyclic oligomer species was to run the reaction neat. Surprisingly, the fastest initiator was [chemical formula] among all three MAP species. Polymerization proceeds via a propagating species in which the R group is of C2 position of the propagating chain, giving HT polymers with high regioselectivity. Chapter 3 describes the synthesis and reactivity of compounds containing a tert-butylimido ligand. Chelating alkylidenes can be synthesized either by alkylidene exchange or by traditional routes in forming alkylidene complexes from diimido dialkyl species. A W MAP complex containing a chelating alkylidene can be synthesized and its reactivity is comparable to that of neopentylidene analogue in 1-octene homocoupling. Complexes with a chelating diolate ligand [chemical formula] and [chemical formula] were synthesized. However, attempts to remove the pyridine ligand induced C-H activation of one tertbutyl group on Biphen ligand to form alkyl complexes. Chapter 4 presents the synthesis of high sequence-regular alternating trans-AB copolymers by ROMP initiated by [chemical formula]. Monomers employed were 2,3-dicarbomethoxy-7-isopropylidenenorbomadiene (B), [chemical formula] (B'), cyclooctene (A), and cycloheptene (A'). All four combinations afford structures containing a high degree of monomer alternation. Evidence suggests a catalytic cycle proceeding through a syn alkylidene arising from insertion of B (syn-MB) reacting with A to form an anti alkylidene (anti-MA) and a trans-AB linkage. A MAP complex [chemical formula] [chemical formula] was also found to form trans-poly[A-alt-B'] with >90% alternating dyad sequences. Variations on imido and alkoxide ligands were surveyed as well as both A and B type monomers. / by Hyangsoo Jeong. / Ph. D.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Mechanistic studies on the palladium catalyzed C-N bond-forming reaction were carried out to generate a more complete understanding of the catalytic cycle. To understand this reaction, several kinetic studies employing simple aryl halide and amine coupling partners were performed to elucidate unknown reaction pathways. Chapter 1. The resting state for the palladium catalyzed cross-coupling of various diarylamines and aryl halides is found to be the diphenylamido complex. Kinetic studies of the catalytic reaction are used to generate an Eyring plot. Hammett studies were performed for both the aryl halide and diarylamine coupling partners. The rates of reductive elimination for catalysts based on the biaryl ligands XPhos, CyJohnPhos, CPhos, BrettPhos, RuPhos, and SPhos were evaluated. Analogues of SPhos demonstrated that electron-donation of the lower aryl group is key to the stability of the amido complex in accordance with theoretical calculations. The methoxy substituent at the C3 position is demonstrated to retard the overall rate of reductive elimination for a RuPhos-BrettPhos hybrid ligand. These studies demonstrate that reductive elimination is likely not a problematic step for C-N cross-couplings. Chapter 2. Kinetic experiments demonstrated an inverse dependence on the concentration of both amine and aryl halide coupling partners. These observations are demonstrated to be valid for several amine classes, aryl halides, and biaryl ligands. Some work is done to demonstrate mechanistic overlap with other bidentate ligands. Based on these studies, a simplified reaction network for oxidative addition is proposed which reproduces key features of the experimental system. / by Pedro Luis Arrechea. / Ph. D. in Organic Chemistry

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002. / Vita. / Includes bibliographical references. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / The microscopic chemical mechanisms of heterogeneous reactions involving HC on crystalline ice and nitric acid trihydrate (NAT) are of fundamental interest to physical chemists, because such reactions yield "active" chlorine compounds that are readily photolyzed to yield radicals responsible for the annual destruction of polar stratospheric ozone. Using molecular-orbital and density-functional-based computational methods that are extensively validated, partial dissociation of HCl is shown to be kinetically rapid and thermodynamically favorable on an extended ice Ih surface model with two dangling OH groups in close proximity to adsorbed HCl at a binding site on the surface. Additionally, surface disordering of this ice model is observed at polar stratospheric temperatures when HCl is adsorbed at this site. The partial dissociation of HCl on/atop ice will compete with other proposed mechanisms only if the local density of surface dangling OH groups is high. This alternative mechanism of chlorine activation is not important on NAT, based on the theoretical study of HCl interacting with various low index NAT faces. This is due to the fact that the NAT (001) face (which may be the most prevalent in the polar stratosphere) possesses a low surface density of dangling OH groups. In addition, other selected defect-free low-index NAT faces do not have their dangling OH groups situated favorably for effective partial solvation of HCl. The efficiency of aluminum oxide particulate, which is emitted by solid rocket motors (SRMs), as a catalyst for "activating" chlorine involved in the less dramatic, but still consequential, / (cont.) depletion of ozone at mid-latitudes in the lower stratosphere is also of interest. The pseudo-first-order rate constants for the heterogeneous reaction of ClONO2 + HCl on laboratory a-alumina and actual SRM emissions are measured experimentally using a narrow-bore capillary tube interfaced to a chemical ionization mass spectrometer under reactant partial pressure and temperature conditions typically encountered in the mid-latitude lower stratosphere. Preliminary results indicate that the rate constants are the same. It is likely that the global atmospheric models that employ a reaction probability of 0.02 for ClONO2 + HCl previously measured on laboratory [alpha]-alumina do not need to be revised. / bt Yves André Mantz. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007. / Vita. / Includes bibliographical references. / This thesis presents work towards the development of a new catalytic C-C bond forming reaction. Alkynes and olefins insert into [(IPr)CuH]2 (IPr = N,N-bis-(2,6-diisopropylphenyl)-1,3-imidazol-2-ylidene) to give copper vinyl and copper alkyl complexes. These copper complexes insert CO2 into the Cu-C bond to form copper acrylate and copper carboxylate complexes. Acrylic and carboxylic acids can be isolated by hydrolysis. A catalytic cycle based on (IPr)copper(I) was developed. Alkynes undergo reductive carboxylation to give acrylic acids in moderate yields. Unexpected interactions between several components of the catalytic system led to a number of side reaction, most importantly between [(IPr)CuH]2 and the product silyl acrylate. The use of silylcarbonate salts to desylilate the product enhanced yield. In addition, silylcarbonates can also serve as a source of CO2. / by Gergely Sirokman. / Ph.D.