Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Includes bibliographical references. / Quenching of the fluorescence of buried tryptophans (Trps) is an important reporter of protein conformation. Human [gamma]D-crystallin (H[gamma]D-Crys) and human [gamma]S-crystallin (H[gamma]S-Crys) are both very stable eye lens protein that must remain soluble and folded throughout the human lifetime. Aggregation of non-native or covalently damaged H[gamma]D-Crys or H[gamma]S-Crys is associated with the prevalent eye disease mature-onset cataract. Both H[gamma]D-Crys and H[gamma]S-Crys have two homologous [beta]-sheet domains, each containing a pair of highly conserved buried tryptophans (see Fig. 1). The overall fluorescence of the Trps is quenched in the native state of H[gamma]D-Crys N-terminal domain C-terminal domain and H[gamma]S-Crys. In crystallin proteins, these Trps will Tr56 be absorbing UV radiation that reaches the lens. The dispersal of the excited state energy is likely to be H[gamma]siological relevant for the lens crystallins. Trp42 Steady-state and time-resolved fluorescence measurements combined with H[gamma]brid quantum Figure 1: The crystal structure of wild- mechanical-molecular mechanical (QM-MM) type H[gamma]D-Crys depicted in ribbon simulations revealed the quenching mechanism of representation showing the four H[gamma]D-Crys. From fluorescence of triple Trp to Phe intrinsic tryptophans in spacefill, mutants, the homologous pair Trp68 and Trpl56 are Trp42 and Trp68 in the N-terminal domain and Trpl30 and Trp156 in the found to be extremely quenched, with quantum C-terminal domain (Protein Data Bank yields close to 0.01, and with very short lifetimes, Code: 1HKO). T-0. 1ns. In contrast, the homologous pair Trp42 and Trpl30 are moderately fluorescent, with quantum yields of 0.13 and 0.17, respectively, and with longer lifetimes, T-3ns. In an attempt to identify quenching and/or electrostatically perturbing residues, a set of 17 candidate amino acids around Trp68 and Trp156 were substituted with neutral or H[gamma]drophobic residues. / (cont.) None of these mutants showed significant changes in the fluorescence intensity compared to their own background. H[gamma]brid quantum mechanical-molecular mechanical (QM-MM) simulations were carried out by Prof. Patrik R. Callis at Montana State University. Computations with the four different excited Trps as electron donors strongly indicate that electron transfer rates to the amide backbone of Trp68 and Trp156 are extremely fast relative to those for Trp42 and Trpl30. This is in agreement with the quantum yields I measured experimentally and consistent with the absence of a quenching sidechain. Efficient electron transfer to the backbone is possible for Trp68 and Trp156 because of the net favorable location of several charged residues and the orientation of nearby waters, which collectively stabilize electron transfer electrostatically. The fluorescence emission spectra of single and double Trp to Phe mutants provide strong evidence for energy transfer from Trp42 to Trp68 in the N-terminal domain and from Trp130 to Trp156 in the C-terminal domain. In the presence of the energy acceptor (Trp68 or Trp156), the lifetime of the energy donor (Trp42 or Trpl30) decreased from ~3ns to ~Ins. The intradomain energy transfer efficiency is 56% in the N-terminal domain and is 71% in the C-terminal domain. The experimental values of energy transfer efficiency are in good agreement with those calculated theoretically. Time-resolved fluorescence anisotropy measurements with the single-Trp containing proteins, Trp42-only and Trpl30-only, indicate that the protein rotates as a rigid body and no segmental motion is detected. The absence of a time-dependent red shift in the time-resolved emission spectra of Trpl30 proves that its local environment is very rigid. / (cont.) A combination of energy transfer with electron transfer results in short excited-state lifetimes of all Trps, which, together with the high rigidity of the protein matrix around Trps, could protect H[gamma]D-Crys from excited-state reactions causing permanent covalent damage. Similar experimental and computational studies indicate that the quenching of the Trp fluorescence in H[gamma]S-Crys is also caused by fast electron transfer and intradomain Förster resonance energy transfer. The electrostatically enabled excited state quenching by electron transfer to the backbone amide is highly conserved in other [beta], [gamma]-crystallins despite the absence of precise sequence homology. This striking conservation, together with the observation of Tallmadge and Borkman [Tallmadge and Borkman, 1990] that the conserved quenched Trps in bovine [gamma]B-crystallin were protected from photolysis relative to the more fluorescent Trps, strongly suggests that the quenching is an evolved property of the protein fold that allows it to absorb ultraviolet light while suffering minimal photodamage. / by Jiejin Chen. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / Vita. / Includes bibliographical references. / Conjugated polymers exhibit useful and interesting electrical and optical properties. We exploit the wandering excitons produced after photoexcitation for chemosensory applications. By sampling many sites in a polymer film, the excitation has a greater chance to encounter an analyte, such as 2,4,6 trinitrotoluene (TNT), electrostatically poised to induce non-radiative decay. The result is attenuation of the fluorescence signal characteristic of these bright polymers. Because energy migration is responsible for the amplification of sensory response, we sought to augment this migration by integrating chromophores with long-lived excited states into the polymer backbone. The first chromophore we targeted, triphenylene, has a symmetrically-forbidden ground state transition, resulting in a long excited state lifetime. Chapter 2 describes the synthetic incorporation of triphenylene into conjugated polymer backbones, and Chapter 3 details the spectroscopic interrogation of these materials. We demonstrate that lifetime extension is universal to all triphenylene-containing polymers. The longer excited state lifetimes are then correlated with increased energy migration through polarization spectroscopy. In Chapter 4, we extend this paradigm for elongating energy migration in conjugated polymers to several other systems. Unique polymers with symmetric, aromatic chromophores are investigated. These materials allow us to look more rigorously at the variations of effective conjugation pathways and their implications before and after chromophore cyclization. The novel dibenzo[g,p]chrysene, triphenylene and thiophene-based systems afforded us a more complete understanding of the interplay of rigidification, symmetrization, lifetime, and energy migration in conjugated polymers. / (cont.) In the final chapter, we exploit another excited state process in conjugated polymers, stimulated emission, to provide additional amplification of sensory response. We demonstrate that lasing action in optically-pumped conjugated polymer thin film structures can be inhibited by exposure of samples to trace amounts of electron deficient aromatic analytes such as TNT. Analyte exposure introduces non-radiative pathways in the polymer, increasing the lasing threshold. Because lasing is a non-linear phenomenon, it provided two orders of magnitude greater sensitivity to TNT. In combination, we hope that the developments described in this thesis will serve to improve current dernining teclmology in the near future. / by Aimee Rose. / Ph.D.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / The research presented in this dissertation is aimed at the development of novel methodologies for carbon-heteroatom cross-coupling reactions catalyzed by late-transition metals. Both palladium and copper are central to the field of transition metal-catalysis and are integral to the catalyst systems developed as part of our continual advancement in cross-coupling reactions. The first part of this thesis focuses on the use of palladium catalysts to form carbon-sulfur bonds directed towards aryl sulfonamide synthesis. The second part of the thesis describes the recent development in the copper(!) hydride mediated formation of carbon-nitrogen bonds via hydroamination of olefins. Part I. Chapter 1. Palladium-Catalyzed Chlorosulfonylation of Arylboronic Acids Using a biaryl phosphine ligand platform, the first palladium-catalyzed cross-coupling reaction of phenyl chlorosulfate with arylboronic acids was achieved. In this context, the arylsulfonyl chloride products serve as useful precursors to a variety of sulfonyl functional groups, such as aryl sulfonamides, aryl sulfones, and arenesulfonate esters. In particular, this method allows for the preparation of a number of arylsulfonyl chlorides that are not accessible via electrophilic aromatic substitution pathways and under mild reaction conditions. Additionally, this methodology points to an unprecedented selectivity for the phenylchlorosulfate electrophiles used in the cross-coupling reactions. Part II. Chapter 2. Enantio- and Regioselective Copper-Catalyzed Hydroamination of Styrenes and the Extension of the Methodology towards Anti-Markovnikov Hydroamination of Terminal Aliphatic Alkenes The development of a copper-mediated strategy towards the hydroamination of styrene derivatives is reported. In this system, the reaction proceeds regioselectively and enantioselectively to generate [alpha]-branched amines. The system can transform a wide variety of substituted styrenes, including trans-, cis-, and [beta]-disubstituted styrenes. In addition, our extension to copper-catalyzed hydroamination reactions of unactivated aliphatic olefins is reported. Using terminal aliphatic alkenes, the copper-catalyzed hydroamination reactions proceed with anti-Markovnikov regioselectivity. Preliminary results point to the application of this methodology towards [beta]-chiral amine synthesis via the hydroamination of I, 1-disubstituted alkenes. Chapter 3. [alpha]-Aminosilane Synthesis via Copper-Catalyzed Hydroamination of Vinylsilanes The copper-catalyzed hydroamination of vinylsilanes is described. This regioselective reaction generates a-chiral aminosilanes in high yields and enantioselectivities. The method is compatible with differentially substituted vinylsilanes and allows access to many valuable chiral organosilicon compounds. Chapter 4. Synthesis of [gamma]-Chiral Amines via Copper-Catalyzed Hydroamination of 3,3- Disubstituted Allylic Alcohols and 3,3-Disubstituted Allylic Benzoates An investigation into the copper-catalyzed hydroamination of allylic alcohols and allylic benzoates is reported. The reaction proceeds via a [beta]-alkoxy elimination, setting a stereogenic center at the 3-postion to generate [gamma]-chiral amine products. The reaction is more efficient using allylic benzoates. This method is completely regioselective and is applicable to aliphatic allylic benzoates as well as aromatic allylic benzoates. Additionally, we demonstrated that this strategy is applicable towards an allylic epoxide substrate to generate [delta]-chiral amine. / by Nootaree Niljianskul. / Ph. D. in Organic Chemistry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003. / 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. / Chapter 1. Introduction: Electron Transfer in Biological Systems In many biological processes, including oxidative phosphorylation and photosynthesis, electron transfer reactions play vital roles. Electrons must be transported at catalytically relevant rates and with specificity to prevent indiscriminate electron transfer that would quickly bring cells to equilibrium. To meet these requirements, biological systems employ a panoply of organic and inorganic redox centers, most of which are sequestered within proteins. In addition to protecting a cofactor from undesirable reactions, the surrounding protein environment tunes its redox properties and mediates specific contacts with other molecules. This brief overview describes the types of redox centers used in biology, the application of electron transfer theory to physiological systems, the kinetic complexity introduced by interprotein interactions, and general mechanisms for regulating biological electron transfer. Chapter 2. Expression and Site-Directed Mutagenesis of the Reductase Component of Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath) ... Chapter 3. Expression and Characterization of Ferredoxin and Flavin Adenine Dinucleotide-Binding Domains of the Reductase Component of Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath) ... Chapter 4. Intermolecular Electron Transfer Reactions in Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath): A Role for Hysteresis in Protein Function. / (cont.) Chapter 5. Domain Engineering of the Reductase Component of Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath) ... Chapter 6. Expression in Escherichia coli of the Hydroxylase Component of Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath) / by Jessica L. Blazyk. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. / Vita. / Includes bibliographical references. / This dissertation details the synthesis and characterization of materials that consist of molecules with unusual shapes. We have pursued this goal into the regimes of both small molecules (liquid crystals) and polymeric materials. In both cases, the ultimate goal is the creation of materials that display unique properties that arise due to molecular organizations and/or interactions driven by the underlying shape of the molecules or subunits. Chapter One is an introduction to the study of liquid crystals and their phases. Chapter Two and Three both describe the synthesis and characterization of bent-core tetracatenar liquid crystals. The focus in Chapter Two is on the effects that changing the bend angle and/or lateral dipole have upon the phase behavior of these compounds. We found that the thiophene-based mesogens with the largest lateral dipoles display the most stable liquid crystalline phases. We believe that this effect is due to the formation of antiparallel dimers within the phases of these compounds. Chapter Three describes the synthesis and phase behavior of thiophene-based liquid crystals with desymmetrized cores. Reduction of the symmetry had the effect of either broadening or narrowing the resulting phases, depending on the types of endgroups attached to the molecular core. Chapter Four details the synthesis and phase-behavior of triphenylene-based dione liquid crystals. These molecules are roughly half-discs in terms of molecular shape, and yet were found to form columnar mesophases typical of discotic liquid crystals. Chapter Five describes our efforts investigating a number of extended thiophene-based aromatic systems which are roughly discotic, display columnar / (cont.) liquid crystal phases and/or interesting structures from an electronic standpoint. Chapter Six describes our initial steps toward establishing a new paradigm for the design of high-strength polymers through the incorporation of iptycene moieties. Our preliminary studies suggest that iptycenes can improve the properties of polymers significantly by increasing the entanglement between polymer chains. Chapter Seven describes our efforts toward using ring-opening metathesis polymerization to create liquid crystalline polymers in which the mesogenic units are tightly associated with the polymer backbones. / by Alexander John Paraskos. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Low-temperature fuel cells (FCs) are highly efficient and environmentally friendly energy conversion devices that have been in the spotlight of many energy research efforts in the past few decades. However, FC commercialization is limited by several difficulties, one including the 60 % cell voltage loss caused by the sluggish oxygen reduction reaction (ORR) at the cathode despite the use of the active Pt nanoparticles (NPs) supported on high surface area carbon as the catalyst. In addition, the voltage loss due to the anode reaction kinetics in alkaline FCs (AFCs) remains unknown to the FC society, unlike for the proton exchange membrane fuel cell (PEMFC) case, where the loss due to the anode reaction has been well understood. Moreover, the high surface area carbon used for supporting nanoparticle catalysts is also known to corrode during the FC operation, degrading the cell performance over time. To offer a guideline to develop potential solutions to the above issues, this thesis seeks to explore and develop the fundamental understandings of both the cathode and the anode reaction kinetics for low temperature FCs of both PEMFCs and AFCs, and to demonstrate a new type of catalyst support that is resistant to corrosion. On the cathode side (the ORR), how the size of the Pt nanoparticle catalyst affect the performance is still under debate. By investigating the ORR on Pt NPs at different sizes and coupling the results to the spectroscopic information, we seek to explore the fundamentals behind the size effect on the ORR activities. We found that below 5 nm, particle size does not play a big role in the catalytic activity. However, the instability of Pt NPs in acidic environment, under simulated operation conditions of a PEMFC, is found to strongly depend on the particle sizes, which is proposed to be due to the Gibbs- Thomson effect. The findings of the particle size effect on the ORR activities and instability suggest that a trade off between smaller NP catalysts, which gives a benefit of a larger mass activity, can suffer from fast degradation. Therefore, a proper NP size that balances between high mass activity and stability would be the best for FC applications according to our study. On the anode side (the HOR), we found that the reaction kinetics in acid solution on Pt is solely limited by the diffusion of the reactant, and therefore, within the experimental uncertainty, the reaction rate of the HOR in acid is not measurable with conventional rotating disk electrode setup. However, once the same testing configuration is applied to the alkaline solution, the HOR kinetics on Pt electrode are found to be limited by the reaction kinetics, which is in contrast to the case in acid. From this finding, the anodic overpotential loss in AFCs/AMFCs is projected for the first time and is found to be 1/3 of the ORR loss. This thesis thus highlights the need for development of highly efficient HOR catalysts in alkaline in order to make AFCs/AMFCs more efficient. Carbon corrosion represents one of the biggest effects that contribute to the performance degradation in FCs. In this work, multi-walled carbon nanotubes (MWCNTs) supported Pt NPs as a novel corrosion-resistant electrocatalyst support for the ORR is proposed as a solution. The Pt/MWCNTs were synthesized through the electrostatic interaction between the Pt precursor and the functionalized MWCNTs, followed by chemical reduction in H2 at elevated temperatures. Our Pt/MWCNTs catalysts exhibit an enhanced durability after an anodic potential holding, which simulates a typical FC environment during the carbon corrosion. The ORR activity of Pt/MWCNTs is also in agreement with that of the commercial Pt/C. The results indicate that MWCNTs have great potential to serve as a novel carbon-support material with high stability without affecting the Pt catalytic activity. / by Wenchao Sheng. / Ph.D.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Reactions in which halogen on a beta carbon atom is internally displaced by nitrogen are well known and have been studied in the past. Most of the work has been done where nitrogen was in the form of an amine. No work had been previously carried out where nitrogen was in the form of a sulfonamide. The preparation of various B-halo substituted benzenesulfonamides and the investigation of the kinetics of ring closure of a select few of these compounds forms the main body of this thesis. The synthesis of the B-halobenzenesulfonamides was carried out in several ways. In some cases, allylamine was treated with benzenesulfonyl chloride and subsequently brominated. By a series of cyclizations with alkali and ring ruptures with the appropriate halogen acid, the 1,3-dihalo-2-benzenesulfonamidopropanes were prepared. For some compounds the B-haloamine was readily purchased and was combined directly with benzenesulfonyl chloride. In one case, propylenimine was reacted with benzenesulfonyl chloride and the imine ring was ruptured with the appropriate halogen acid. Some of the compounds had been prepared previously and were reported in the literature. Where new compounds were prepared, their structures were proven by analysis for carbon, hydrogen, nitrogen and halogen and also by analysis of the infrared spectra of the compounds. / 2031-01-01

In recent years, metals based antitumor complexes have played an important role in chemotherapy. In this study, two new metal complexes - dioxovandium LVO2 and dichloroiron LFeCl2-have been synthesized. The dioxovanadium complex LVO2 is formed from the reaction between the ligand HL and VO(acac)2 in 1:1 molar ratio, while the dichloroiron complex was prepared from the reaction between ligand HL with FeCl2 in 1:2 molar ratio. Both new complexes have been characterized by FT -IR and UV -Vis. The IR spectrum revealed the absorption band changes between the complexes and their ligand, and UV -Vis show d-d transitions for the iron complex and LMCT for the vanadium complex. Molecular structures of the two complexes have been determined by X-ray crystallography. The central metals (both vanadium and iron) have adopted distorted trigonal bipyramidal configurations. The ligand serves as tridentate providing two nitrogen and one oxygen atoms for coordination. The complexes with vanadium and iron central atoms have shown promising results in preclinical testing and have already been evaluated for enhancement of the anti-proliferative activity on PC3. All three compounds HL, LVO2, and LFeCh displayed high cytotoxicity toward prostate cancer cell line.

Polymeric nanocomposites of poly(ethylene oxide) (PEO) and silica nanoparticle (Si02) were prepared by solution blending using dichloromethane. The goal of the study was to understand the effect of the silica nanoparticle on the morphology of poly(ethylene oxide) and the ability of the poly(ethylene oxide) to disperse the nanoparticle within the matrix. The study focused on the dispersion of the silica nanoparticle (20 run) as filler into poly(ethylene oxide) of molecular weights 8K and 20K. The nanocomposite products were powders.The products were characterized by Fourier Transform Infrared Spectroscopy, X-ray Diffraction, solid-state nuclear magnetic resonance spectroscopy (13C T1prelaxation rates), scanning electron microscopy and differential scanning calorimetry. Differential scanning calorimetry analysis results of the nanocomposites show thermal properties that are different from the individual components. The results show that the crystallinity is slightly reduced on increasing the Si02 nanoparticle loading. Increasing the SiO2 nanoparticles causes an increase in the Tt p relaxation rate of the PEO 8K suggesting effective dispersion of the nanoparticles within the matrix.Overall, the results suggest that the PEO 8K is better at dispersing the nanoparticles within the matrix compared with the PEO 20K.

Surgery has been a popular method for the treatment of cancers, in particular solid tumours; but the surgical margins for cancerous tissues are often indistinct and in most cases, the poor identification of residual cancer tissues can result in re-excision. Therefore, near infrared (NIR) fluorescence-guided surgery (FGS) is being developed as a real time intra-operative imaging technique to assist surgeons by improving the accuracy and precision of the removal of tumours. However, current FDA approved fluorophores suffer from poor chemical stability, limited water-solubility, and lack selectivity toward neoplastic tissue, limiting their clinical application. These current challenges have led to the development of new and improved fluorophores capable of absorbing and emitting light at NIR wavelengths, negating autofluorescence and improving deeper light transmission. Throughout this project, a series of BODIPYs, aza-BODIPYs and bacteriochlorins were synthesised and developed for bioimaging applications. Despite many of them showing interesting fluorescence properties, the investigation suggested aza-BODIPYs were the most promising red / NIR fluorophores (λem 600-700 nm) due to their excellent photostability. Methods have been developed to incorporate functionalities suitable for bioconjugation. Different bioconjugation strategies have been explored to covalently conjugate the NIR fluorophores to a clinically relevant protein, peptide and antibody under mild conditions. The viability of aza-BODIPY conjugates against biological targets were investigated and a range of other novel targeted NIR fluorophores were successfully developed. In vitro fluorescence imaging was subsequently carried out to demonstrate the enhanced selectivity of the targeting NIR fluorophores toward overexpressed receptors on various cancer cells lines. This project has demonstrated the potential of aza-BODIPY in biological imaging and developed targeted NIR fluorophores. Further biological evaluation is progressing with the eventual aim of developing a pre-clinical model for NIR FGS in oncology.