Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2004. / Vita. / Includes bibliographical references. / The chemistry of fluorine, F2, and xenon difluoride, XeF2, with clean Si are nearly indistinguishable. Both species react via the atom abstraction mechanism, whereby a surface dangling bond abstracts a F atom from the incident molecule, scattering the complementary F atom or XeF fragment into the gas phase. However, once all dangling bonds are fluorinated and a coverage of 1 ML F is attained, the chemistry of these two species diverges. Further exposure to F2 results in no increase in F coverage, indicating reactions of F2 with the Si-Si -bonds do not occur. In contrast, further exposure to XeF2 results in additional reaction, cleaving the Si-Si bonds and increasing the coverage beyond 1 ML F. Eventually, sufficient fluorination occurs to effect the desorption of the etch product SiF4. The experiments described in this thesis have been designed to probe the origin of the observed difference in reactivity of F2 and XeF2 with a fluorinated Si surface. Two possible explanations are presented that likely account for the difference in reactivity of F2 and XeF2 with fluorinated Si. The first is the reaction of atomic fluorine, which is produced by the gas phase dissociation of XeF following an abstraction event, with the Si. The second is vibrational excitation of the Si lattice, induced by the initial collisions of XeF2, thereby enabling reaction of the F atoms with the Si-Si bonds. The first chapter describes experiments investigating the chemical dynamics of the reaction of a beam of XeF2 with Si(100). The scattered intensities and the time-of-flight distributions of the reaction products XeF2, XeF, and Xe are measured as a function of coverage and scattering angle, as is the intensity of scattered F atoms. / (cont.) The F atoms arise from the gas phase dissociation of XeF, which results from partitioning of the exothermicity of the abstraction reaction of XeF2 with Si into the internal energy of XeF. The time-of-flight and angular distributions of F and Xe are simulated by applying conservation of momentum, energy, and flux principles to the measured XeF time-of-flight and angular distributions using only two fitting parameters: the average internal energy partitioned to XeF and the allowed range of molecular orientations of XeF as it is scattered from the surface. These parameters are adjusted to reproduce the measured F atom TOF spectra at three scattering angles for the coverage range 0 - 0.22 ML F. The same parameters are then used to predict the Xe atom TOF distributions resulting from the dissociation of XeF. The intensity of the TOF distributions for scattered Xe is scaled such that one Xe atom is produced for each F atom in the simulation. The simulated TOF spectra result from the analysis of 8,085,000 initial XeF trajectories, which are computed at eight coverage ranges. The simulation is found to reproduce the scattered Xe TOF spectra well, including the intensity, with no fitting of the simulated Xe spectra to the data. This excellent agreement corroborates the XeF dissociation as a gas phase event. The dissociation of XeF is the first observed case of a gas phase dissociation resulting from partitioning of exothermicity to a product of a gas-surface reaction. In addition, the simulation indicates that approximately 10% of the F atoms resulting from XeF dissociation are directed back toward the surface ... / by Robert Charles Hefty. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references. / by Jie Julie Wu. / M.S.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1957. / MIT copy bound with: Use of radioactive tracers in following rare earth separations carried out by homogeneous precipitation / John Scott Mudgett. 1957. / Includes bibliographical references. / by Carl Walter Nelson. / B.S.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995. / Includes bibliographical references (leaf 45). / by Raúl Horacio Zambrano. / M.S.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999. / Vita. / Includes bibliographical references (leaves 101-107). / The first part of the thesis describes a novel approach to generate amide cleaving antibodies. Two haptens, O1 and O2, were designed and synthesized to create a hydrophobic pocket for an auxiliary nucleophile as well as elicit complementary basic/acidic side chain residues in the antibody combining binding site. The recently established heterologous immunization protocol was utilized to induce multiple catalytic side chain residues in antibodies. Three antibodies were isolated capable of catalyzing the hydrolysis of propionyl-p-nitroanilide in the presence of phenol, as the nucleophilic cofactor. Further studies with substrate and nucleophile analogs clearly showed that the nucleophilic phenolic hydroxyl group is essential for catalysis, much like amide hydrolysis catalyzed by serine proteases. The second part of the thesis describes the generation of catalytic antibodies capable of removing a protection group for the simultaneous activation of multiple prodrugs. To this end, a protective group was designed which could be attached to any kind of cancer drug, in order to convert a cancer drug into a prodrug. The protective group relies on a [beta]-sulfone elimination process to release the active drug. The corresponding hapten design includes a non-specific element to allow broad substrate tolerance with regard to the drug portion. Two haptens, RI and R2, both structurally similar, but with different functionalities were designed and synthesized. Both haptens include a perfectly placed ammonium residue for a-proton abstraction. The second hapten design, RI, further sought to induce an acidic residue for carbamate leaving group stabilization. A comparison of both haptens showed that leaving group stabilization did not improve antibody performance. Another subject crucial to the prodrug activation project concerns the detection of catalytic activity in hybridoma supematants. A new method called "Capture"-CatELISA was developed, which allowed the efficient screening for catalysis of hundreds of hybridoma supematants in a very short period of time. To this end, a substrate Cl was developed, which upon activation covalently traps catalytic antibodies, and therefore immobilizes them on a solid support. A conventional ELISA-assay was then applied to identify the catalytic clones. / by Roman Fleck. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1994. / Includes bibliographical references (leaves 345-348). / by Squire J. Booker. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995. / Includes bibliographical references. / byt Andrew E. Bennett. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995. / Includes bibliographical references (p. 160-161). / by Christopher Bruce Murray. / Ph.D.

Thesis: Ph. D. in Biological Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Ribonucleotide reductase (RNR) catalyzes the reduction of nucleotides to 2'- deoxynucleotides. The focus of this thesis is the F coli class la RNR, which is comprised of two homodimeric subunits, [alpha]2 and [beta]2, forming an active [alpha]2[beta]2 complex. The [beta]2 subunit harbors the stable diferric-tyrosyl radical cofactor (Y 122*) that reversibly oxidizes the active site cysteine (C₄₃₉) in [alpha]2. This oxidation requires a long-range radical transport (RT) pathway consisting of proton-coupled electron transfer (PCET) events through redox-active aromatic amino acid residues: Y₁₂₂* <--> [W₄₈] <--> Y₃₅₆ in [beta]2 to Y₇₃₁ <--> Y₇₃₀ <--> C₄₃₉ in [alpha]2. Once formed, the transient C₄₃₉* initiates nucleotide reduction. Both the long-range oxidation and the nucleotide reduction chemistries are kinetically masked by rate-limiting protein conformational change(s). To overcome this conformational change, the unnatural amino acid probe 3-aminotyrosine (NH₂Y) has been sitespecifically incorporated at multiple positions (Y₃₅₆, Y₇₃₁, Y₇₃₀) into the RT pathway. Herein, the NH₂Y probe is characterized as pertaining to the previously demonstrated ability for NH₂Y-incorporated RNR (NH₂Y-RNR) to form product. The reduction potential of NH₂Y produces a thermodynamic barrier that RNR cannot overcome. To explain NH₂Y-RNR activity, mass spectrometry was used for relative quantitation of contaminating wt-RNR in the NH₂Y-RNR, lending credence to the fact that the NH₂Y-RNRs are actually inactive. These results provide clarity to the long-standing mystery behind the low activities of the NH₂Y-RNRs. The use of the NH₂Y probe to generate stable radicals on the RT pathway has revealed further remarkable insight, demonstrating a hydrogen bonding network in the [alpha]2 subunit by employing advanced EPR methods on NH₂Y₇₃₀* and NH₂Y₇₃₁*. The evidence for a collinear PCET mechanism is provided with the NH₂Y₇₃₀/Y₇₃₁F and NH₂Y₇₃₁/C₄₃₉A mutants. Mutation of an R₄₁₁ to alanine in [alpha]2 allowed the detection of a "flipped" NH₂Y₇₃₁* conformation using advanced EPR techniques. Herein, photo cross-linked RNR is studied by tandem mass spectrometry (MS/MS). The study of a photo cross-linked [alpha]2[beta]2 complex using a 4-N-maleimido-benzophenone covalently attached to the C-terminal tail of [beta]2 yielded no photo cross-linked peptides. These studies taken together provide additional insight at the [alpha][beta] interface and provide additional tools to study this interaction. / by Wankyu Lee. / Ph. D. in Biological Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references. / An estimated 35% of the human proteome is intrinsically disordered. Disordered proteins play a key role in physiologic and pathologic regulation, recognition, and signaling making protein disorder the subject of increasing investigation. Since disordered samples do not generate x-ray quality crystals and since they have conformations that interconvert faster than the time resolution of NMR or ESR, little is known about their structure or function. By combining isotope-edited two-dimensional infrared spectroscopy (2D IR) with spectral modeling based on molecular dynamics simulations, this work will show that one can measure the residual structure and conformational heterogeneity of a putatively disordered sequence. This methodology was first used to study the structure and dynamics of the tryptophan zipper 2 (TZ2) peptide. The TZ2 peptide is a 12 residue engineered sequence that employs the "tryptophan zipper" motif to stabilize a p-hairpin fold. For this work five isotopologues of TZ2 were synthesized, the p-turn label K8, the midstrand labels T10 and T3T1O, the N-terminal label S1, and the unlabeled peptide UL. Temperature dependent FTIR and 2D IR studies in conjunction with modeling revealed that the TZ2 peptide at low temperatures exists as a folded peptide with a type I' turn and a small previously unobserved subpopulation of a bulged loop structure. Upon heating a fraying of the peptides termini is observed, in addition the population of the type I' turn increases relative to the population of the bulged turn. The TZ2 peptide provided a model hairpin system to test the utility of different forms of analysis and isotope labeling patterns for the subsequent study of disordered hairpin peptides. This methodology was next employed to gain insight into the structure of the elastin-like peptide GVGVPGVG, a prototypical disordered system. For this work nine isotopologues were studied in addition to size dependent variants based on the VPGVG sequence and point mutants variants of the form GVGXPGVG. The conformational ensemble was found to contain a high population of irregular P-turns possessing two peptide hydrogen bonds to the proline C=O (see figure below). Further, it was found that this population grows as a function of 1) side-chain volume for the peptide series GVGXPGVG, where X = Gly, Ala, and Val, and 2) polymer size for the peptide series GVG(VPGVG)a, where n = 1-6 and 251. These findings provide new insight into the molecular origin of the mechanical properties of biopolymers containing XPG turns including collagen (X = Pro), elastin (X = Val), mussel byssus (X = Gly), dragline spider silk (X = Gly), and wheat glutenin (X = Gln).` / by Joshua Lessing. / Ph.D.