Massachusetts Institute of Technology. Dept. of Chemistry. Thesis. 1969. Ph.D. / Vita. / Bibliography: leaves 177-179. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / 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 (p. 119-133). / Density functional theory (DFT) is a computationally efficient formalism for studying electronic structure and dynamics. In this work, we develop DFT-based excited-state methods to study electron transport, Rydberg excited states and to characterize diabatic electronic configurations and couplings. We simulate electron transport in a molecular wire using real-time time-dependent density functional theory in order to study the conduction of the wire. We also use constrained density functional theory to obtain diabatic states and diabatic couplings, and use these excited-state properties in a configuration-interaction method that treats both dynamic and static correlation. Lastly, we use eDFT, an excited-state self-consistent-field method, to determine the energies of excited Rydberg atomic states. / by Chiao-Lun Cheng. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999. / Vita. / Includes bibliographical references. / by Tao Ke. / Ph.D.

Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2014. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 44-48). / The proposed research is a study and application of Stochastic analysis- Random Matrix Theory(RMT) to fast calculate the transport properties of large static systems with relatively large disorder in mesoscopic size. As a major topic of Random Matrix Theory(RMT), free convolution managed to approximate the distribution of eigenvalues in an Anderson Model.So the next step is trying to expand RMT to approximate other quantities, such as transmission probability, conductivity and etc. Due to the eigenvectors' shifts, RMT works well only for small disorder. System with larger disorder requires to take in account of the changes in eigenvectors directly or through other approximations of the eigenvectors. / by Wanqin Xie. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Vita. / Includes bibliographical references. / Studies directed toward the synthesis of the A-ring portion of glycinoeclepin A are described. The enantioselective synthesis of key diketone intermediate 128 in four steps from 2,2-dimethyl-1,3-cyclohexanedione (5) has been accomplished via the acid-catalyzed intramolecular Michael cyclization of an enone generated in situ from 132. In the course of these studies, a new method for the preparation of the highly reactive a-alkynyl acroleins was developed. Several methods for the further elaborations of diketone 128 to the key enyne intermediate 95 were investigated and the best route developed to date involves the conversion of the methyl ketone to a vinyl triflate (177) followed by Sonogashira coupling. In addition, the conversion of diketone 128 to the vinyl halide 258 via a Shapiro strategy was achieved and model studies were carried out on the synthesis of vinylallene by coupling cuprate derivatives of this intermediate with propargyl alcohol derivatives. / by Charnsak Thongsornkleeb. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. / Vita. / Includes bibliographical references. / (cont.) affords the two fluorophores, such that excitation of the coumarin at 445 nm and measurement of the emission at 488 nm affords information of the amount of sensor present, while excitation of the fluorescein at 505 nm and measurement of the emission at 535 nm indicates the amount of sensor in the zinc(II)-bound form. This system has been characterized and applied to the study of exogenous zinc(II) fluxes in HeLa cells. Chapter 4: Unimolecular Two-Fluorophore Ratiometric Zn²⁺ Sensing Systems. Dichlorofluorescein compounds covalently bound to zinc(II)-insensitive reporter fluorophores via a rigid cyclohexyl linker have been prepared and characterized. Based on favorable photophysical properties, a Zinpyr-1 species covalently bound to coumarin 343 has been prepared and shown to afford a ratiometric response to excess zinc(II). Chapter 5: ZPI Synthons for Functionalization of Biological Targets. Installation of a functional group prior to Mannich reaction is impractical in many cases. This chapter describes the preparation of reactive ZP1 synthons for direct functionalization of biological targets containing an amine or azide, and reports applications to the synthesis of ZPI conjugates. Appendix 1: Synthetic Approaches to Other Isomerically Pure Functionalizable Fluorophores. Crystallization approaches have been applied to separate fluorescein 5- and 6-sulfonic acid, and subsequent generation of the sulfonyl chlorides is discussed. A dibromofluoran approach to isomerically pure rhodamine carboxylates is based on a similar separation. Basic hydrolysis of the previously described 2',7'-dichlorofluorescein ... / Chapter 1: The Development and Use of Fluorescent Sensors in the Imaging of Physiological Zinc(II): A Review This chapter presents an overview of fluorescent techniques used to image chelatable zinc(II) in vivo. Many intensity-based sensors take advantage of photoinduced electron transfer quenching pathways. Peptide- and protein-based sensors offer excellent selectivity but are poorly suited to intracellular applications. Recently, ratiometric sensors in which the zinc(II) binding event interrupts or alters conjugation within the fluorophore have been described. Chapter 2: Carboxylate-Functionalized Zinpyr-1 Sensors: Synthesis, Characterization, and In Vivo Staining Patterns. A class of Zinpyr-1 sensors containing a carboxylic acid or ester at the 5- or 6-position of the fluorescein has been prepared. These sensors offer decreased background fluorescence and enhanced fluorescence response compared to the parent Zinpyr-1. The acid-functionalized sensors bear a negative charge at physiological pH, rendering them cell-impermeable. The esterified sensors are cell-permeable, but are hydrolyzed in vivo by intracellular esterases, affording a clear delineation of zinc(II)-containing damaged neurons in mechanically-injured or seizure-induced rats, rather than the punctate staining pattern obtained with Zinpyr-1. Chapter 3: Esterase-Dependent Two-Fluorophore Ratiometric Sensing of Zinc(II). This chapter describes a new approach to ratiometric sensing in which a zinc(II)-sensitive fluorescein fluorophore based on Zinpyr-1 is functionalized with a zinc(lI)-insensitive coumarin fluorophore via a flexible ester linker. The flexible linker enables intramolecular quenching of the two fluorophores. Esterase hydrolysis of the linker / by Carolyn C. Woodroofe. / Ph.D.

Thesis: Ph. D. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2017. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references (pages 129-136). / This thesis focused on designing, characterizing and understanding the electronic or ionic behavior of electron- or ion-conducting metal-organic frameworks (MOFs). Chapter 1 gives a general introduction for electron- or ion-conducting MOFs, including a review of the reported materials exhibiting such behavior. Chapter 2 describes new MOFs designed using through-space charge transport strategies, as introduced in Chapter 1. Chapter 2 discusses four isostructural materials of general formula M2(TTFTB) (M = Mn, Co, Zn, and Cd), which exhibit infinite helical TTF stacks and reveal a correlation between the shortest intermolecular S ... S interaction among neighboring TTF cores and their single crystal conductivity. These results are the first demonstration of tuning intrinsic electrical conductivity of a MOF and provide a systematic blueprint for the design of throughspace charge transporting MOFs. Chapter 3 details the study of ligand-directed topologies in the material Mg₂H₆(H₃O)(TTFTB) 3 (MIT-25), obtained from H₄TTFTB, a ligand with a high propensity toward [pi]-stacking. Because understanding intermolecular [pi]-stacking interactions is important for designing through-space charge transport materials, we studied the significance of how the organic secondary building unit (SBU), which is energetically competitive with the formation of common inorganic SBUs, can also define MOF topology. Chapters 4 and 5 demonstrate examples of MOFs as ionic conductors. In Chapter 4, the proton conductivity of MIT-25 is studied. Owing to its large proton content and compositionally integral hydronium ion, MIT-25 exhibits an strongly hydrophilic environment that facilitates proton conduction. Lastly, Chapter 5 reports a Cu(II)-azolate MOF (MIT-20) with cylindrical pores, which undergoes a reversible single crystal-to-single crystal transition between neutral and anionic phases upon reaction with stoichiometric amounts of halide or pseudohalide salts. By utilizing this transformation, halide/pseudohalide anions are bound to the metal centers and become stationary, while the cations move freely within the one-dimensional pores, giving rise to single-ion Li+, Na+, or Mg²+ solid electrolytes. / by Sarah Sunah Park. / Ph. D. in Inorganic Chemistry

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Includes bibliographical references (leaf 26). / by Neme O. Nnolim. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009. / Vita. / Includes bibliographical references. / Light scattering spectroscopy has emerged as a valuable diagnostic tool for cancer diagnoses in the past ten years. The interaction of light with cellular structures brings out information about morphological changes accompanying malignancy at early stages. The virtue of this technique is to extract key morphological information such as size distribution of nucleus and submicron-sized particles with minimal data acquisition and model-based data analysis. This enables wide area screening and onsite analysis, critical to the clinical applications. The extracted information, however, strongly depends on the selection of the specific model of the cell/tissue scattering and on constraints from prior knowledge about the sample, leaving the validity of the information questionable. The main focus of this thesis work is to validate various models of cell/tissue scattering used in light scattering spectroscopy. Conventional intensity-based light scattering spectroscopy, which records intensity distribution at the angular plane, was set up to measure angular and wavelength distribution of scattered light in cell monolayers, cell suspensions and rat esophagus tissues for both forward and backward scattering. Morphological information was extracted from cell models such as the cell model based on Mie theory and the power-law model. At the same time, field-based microscopy was used to measure 3D refractive index distributions of single live cells and to provide intensity-based light scattering spectroscopy with a more realistic optical model of a cell. / (cont.) From the index tomogram, the contribution of individual organelles and cellular components to the light scattering was determined without the need for modeling. Indeed, field-based microscopy was used as a validation tool for the various models and assumptions used in the intensity-based approach. Two types of scattering behavior had been previously reported for a visible range of wavelengths and an angular range of forward-to-backscattering in cells and tissues: an oscillatory behavior of scattering intensity in angle near exact forward and exact backward scatterings associated with cell body or nuclei, and smooth power-like behavior in wavelength for all scattering angles except near forward scattering. This study addresses two key questions related to the two types of behavior mentioned above: feasibility of extracting nuclear size distribution from oscillatory behavior, and extracting cellular parameter(s) characterizing smooth power law decay. To answer the first question, we performed a light scattering study with a single cell using field-based microscopy. Relative contributions to forward scattering of the cell border, the nucleus and other sub-cellular structures were established for the HT29 cell. Nuclear scattering is found to be small compared to the cell border scattering and sensitive to scattering by other sub-cellular structures. In agreement with single cell results, the cell border signal dominates forward scattering in cell suspensions of HeLa cells. This was confirmed by modeling with Mie theory and by index-matching the cell-media interface. / (cont.) Cell border signal was not observed in backscattering from cell suspensions, even with the use of large particle signal enhancement methods. Thus, the nuclear signal is estimated to be a few orders of magnitude below the current system sensitivity level and mixed with other scatterers' signals. The main scattering feature is a smooth power law in scattering wavelength. The exponent characterizing smooth power law decay, can separate normal and pre-cancerous tissues within the same tissue type, such as rat esophagus tissue. The range of power law exponents observed in the rat tissue experiments overlaps with the range of power law exponents extracted from HeLa, HT29 and T84 monolayers. Therefore, the power law exponent does not have enough dynamic range to separate independent samples with quite different morphology. In conjunction with the last statement, the power law behavior is explained by three different morphological base sets: the Mie model, describing cell as a collection of spheres, the Fourier model, in which cell is described as combination of periodic structures with a continuous range of spatial frequencies, and a fractal model, in which index fluctuations inside the cell are described by von Karman correlation function. Although all three models can explain the power law behavior, the Fourier model is the most feasible one, because, unlike the other models, no assumptions are made about structure of the sample. / by Maxim M. Kalashnikov. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / Site-specific labeling using E coli biotin ligase (BirA) and its 15-amino acid "acceptor peptide" (AP) has been applied to study the function of various cellular proteins. In order to extend the capabilities of biotin ligase-based labeling, we engineered key elements of the labeling platform. First we characterized a novel peptide substrate (called "yeast acceptor peptide" (yAP)) for yeast biotin ligase (yBL) that had been evolved by phage display. Assays performed in vitro and on the yeast surface showed that the yBL/yAP pair was orthogonal to the BirA/AP pair, allowing two-color labeling of different proteins on cells with differently-colored probes. Second, to improve the kinetic efficiency of yAP, we developed a novel selection scheme based on yeast display. Model selections demonstrated up to 1000-fold enrichment, and three rounds of selection on a randomized peptide library were performed. Third, we attempted to improve the kinetic efficiency of BirA through evolution by in vitro compartmentalization (IVC). Because the original IVC protocol based on bead-linked DNA had many technical problems, we developed a novel bead-less IVC protocol. An enrichment factor of 25 was obtained in a model selection. Due to the single-turnover nature of the selection, however, this scheme was not able to enrich highly active catalysts over moderately active ones. In separate work, we turned our attention to the streptavidin-biotin pair. Again using bead-less IVC, we performed a selection for streptavidin mutants that could bind a ketone analog of biotin with high affinity. / (cont.) Two rounds of selection were performed but characterization of enriched clones was not completed. Finally, we helped to discover a mutant ligase that could catalyze attachment of a fluorinated aryl azide photocrosslinker to proteins fused to a 17-amino acid peptide tag. The aryl azide probe was tested and shown to be accepted by a W37V mutant of E coli lipoic acid ligase (LplA). / by Yoon-Aa Choi. / Ph.D.