Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Solid-state nuclear magnetic resonance (SSNMR) is a powerful technique to study the structure, dynamics and interactions of bio-macromolecules. This thesis mainly focuses on the characterization of the architecture and loosening of primary plant cell walls and the interactions between membrane and peptides. Plant cell wall is a complex system mainly comprising three types of insoluble polysaccharides: cellulose, hemicellulose and pectin. The spatial arrangement of these macromolecules has been largely elusive due to the lack of high-resolution and sitespecific characterization techniques. Here, we introduce SSNMR to investigate the interactions of macromolecules in ¹³C-labeled plant primary cell walls with minimal treatment. Our multidimensional ¹³C spectra show intense cellulose-pectin correlations, suggesting subnanometer contacts between these polymers. The cellulose-pectin interaction is found to be an inherent feature of primary cell walls because it is independent of the hydration history and is caused by site-specific interactions instead of molecular crowding. By measuring water to polysaccharide spin diffusion in intact and sequentially digested walls, we are able to examine the three-dimensional structure of cell walls. Our results suggest a single network model, where cellulose microfibrils make physical contacts with both pectin and hemicellulose. We also investigated how this network was unlocked by expansin, a wall-loosening protein. Using differential isotopic labeling and dynamic nuclear polarization, we determined the binding sites of 0.2 mg expansin in cell walls. Cellulose microfibrils with entrapped hemicellulose were found to be the targets of expansins, thus shedding light on the mechanisms of wall elongation and plant growth. These results have deepened our understanding of plant cell walls, a smart material with both high mechanical strength and extensibility. In addition, we also developed new approaches to investigate the interactions between membranes and peptides. By measuring heteronuclear correlation spectra and proton relaxation times, we determined the localization of the Influenza M2 peptide in distinctly curved membrane domains. Using a rigid-solid heteronuclear correlation experiment, we were able to determine the depth of insertion of dynamically invisible peptides in gel-phase membranes. These studies provide new strategies to study the functionally relevant membrane-curvature induction by proteins and the partitioning and insertion of proteins into lipid membranes. / by Tuo Wang. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Includes bibliographical references. / To date, the most successful conducting polymer actuators are based on polypyrrole, which operates through incorporating and expelling counterions and solvent molecules to balance the charges generated by electrochemical stimuli (swelling mechanism). Although significant progress has been made, there still exists a need for developing new materials that would overcome the intrinsic limitations in the swelling mechanism, such as slow diffusion rate, limited expansion volume, etc. Our group has contributed this area with a different approach -- lecular mechanisms, which utilize a dimensional change of a single polymer chain. We propose two types of molecular mechanisms: contracting and expanding. We proposed earlier a calix[4]arenebased molecular actuator for the contracting mechanism, in which p-dimer formation was proposed as a driving force. In this dissertation, we first confirm by model studies that p-dimer formation can indeed be a driving force for the calix[4]arene-based system. We propose another molecular hinge, binaphthol moiety, for the contracting model. The syntheses of polymers with binaphthols and their characterization, including signatures of oligothiophene interactions, are described. Due to its chirality, we examined the possibilities of the binaphthol polymer as a chiral amine sensor. To create actuators that make use of the expanding model, we propose new conjugated seven-membered ring systems with heteroatoms (thiepin with sulfur and azepine with nitrogen) and their syntheses and characterization will be described. Inspired by the fact that sulfoxide has very low extrusion barrier in the related system, we applied the thiepin molecules to create a peroxide sensor. / (cont.) In addition, during the investigation of phenol functional groups in conducting polymers, we found interesting properties that strategic positioning of phenol groups can render a conjugation-broken meta-linked system just as conductive as a fully conjugated para-linked isomeric system. / by Changsik Song. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007. / Vita. / Includes bibliographical references. / Chapter 1 describes the development of an asymmetric nucleophile-catalyzed [2+2] cycloaddition of ketenes with aldehydes. This is the first report of a catalytic enantioselective synthesis of trisubstituted [beta]-lactones. Two enantioselective phosphine-catalyzed [3+2] cycloadditions of allenoates are detailed in Chapter 2. A method for the asymmetric synthesis of cyclopentenes via a [3+2] cycloaddition of allenoates with enones is first discussed. This is followed by a report of our efforts to extend this [3+2] methodology to imine electrophiles. We conclude, in Chapter 3, with an account of the development of a novel phosphine-catalyzed synthesis of bicyclo[3.3.0]octanones and bicyclo[4.3.0]nonanones. Preliminary results for an enantioselective variant of this method are also disclosed. / by Jonathan E. Wilson. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Vita. / Includes bibliographical references. / I. The Development of a General Strategy Towards Dimeric Hexahydropyrroloindole Alkaloids. A Concise Total Synthesis of (+)-Chimonanthine, (+)-Folicanthine and (-)Calycanthine. An efficient and convergent strategy for the synthesis of dimeric hexahydropyrroloindole alkaloids is described. The simultaneous formation of the vicinal quaternary stereocenters using a reductive dimerization reaction provides gram-scale access to an optically active key intermediate employed in the synthesis of (+)-chimonanthine, (+)-folicanthine, and (-)calycanthine. II. The Development of a General Strategy Towards Dimeric Hexahydropyrroloindole Alkaloids. A Concise Total Synthesis of (+)-WIN 64821, (-)-Ditryptophenaline and (-)-1'(2-Phenylethylene)-ditryptophenaline. The concise enantioselective total synthesis of (+)-WIN 64821 and (-)-ditryptophenaline in six and seven steps, respectively, from commercially available amino acid derivatives is described. The gram-scale synthesis of key intermediates and simultaneous introduction of the vicinal quaternary stereocenters provides a highly effective and preparative synthesis of these natural alkaloids. Additionally, the synthesis and structural confirmation of the natural alkaloid (-)-1 '-(2-phenylethylene)-ditryptophenaline is described. III. N-Heterocyclic Carbene-Alcohol Hydrogen Bonds. Studies and Application in the Amidation of Unactivated Esters. A single-step and catalytic amidation of unactivated esters with amino alcohols is described. Treatment of equimolar quantities of amino alcohols and unactivated esters with N,Nbismestiylimidazolylidene (5 mol%) affords the desired amides in high yield under mild reaction conditions. / (cont.) The compatibility of the present methodology with a wide range of functional groups, heterocycles, and optically active substrates in addition to both aromatic and aliphatic esters is noteworthy. Preliminary data regarding an unprecedented hydrogen-bonded carbene-alcohol complex is reported. Further investigation of this hydrogen bond revealed steric and electronic influences on the nature of this bond, cumulating in discovery of a practical metal free method for the stabilization and storage of these nitrogen heterocyclic carbenes. Also described is a method for the synthesis of optically active imidazo-[1,5-a]-pyridinium salts as precursors to optically active nitrogen heterocyclic carbenes. / by Michael Anthony Schmidt. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008. / Vita. / Includes bibliographical references. / The effect of relative humidity (RH) on OH uptake by surfaces of tropospheric importance was investigated. Due to diffusion limitation conditions, experiments were performed with parallel reactors packed with beads and using a surface dilution technique. A virtual cylindrical reactor approximation was developed to further quantify and confirm the reaction probability of OH for the surfaces of interest. While OH exposure of hydrophobic organic surfaces (paraffin wax, pyrene, and methane soot) did not result in measurable change in their relative hydrophilic properties, the presence of water vapor enhanced the OH reactivity on a hydrophilic organic surface (glutaric acid). The RH effect on OH uptake by sea salt and its components was dependent on the nature of the cations. Redistribution of surface ions under humid environments caused changes in pH on the inorganic surfaces, thereby influencing the rate-determining step in the reaction mechanism of heterogeneous OH uptake. This segregation effect explains why the RH effect on OH uptake by sea salt is determined by MgCl2 rather than NaC1. Experimental evidence suggests that adsorbed water on the surfaces of SiO2 and A1203 is responsible for enhancement in OH reactivity with mineral dust surfaces under high humidity conditions. Mass spectra of the gas-phase species produced from the heterogeneous reaction of OH with NaCl were obtained in order to characterize the reaction products and the kinetic mechanism. Evidence for gas-phase HC1, supplemented with kinetics modeling and experiments on heterogeneous 03 reactivity strongly suggest that C12, sole product of the heterogeneous reaction, transforms to HCI in the presence of H radicals. / (cont.) The C12 yields per OH collision were determined to be 0.020 and 0.022 at 0% and 6% of RH, respectively. Enhancement in C12 production was observed under wet conditions, consistent with a measured chlorine deficit on the NaCl surface. Two alternate reaction mechanisms are proposed to describe the heterogeneous OH uptake by NaC1. / by Jong-Ho Park. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1931. / Vita. / Includes bibliographical references (leaves 79-91). / by Paul Hamilton Doleman. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / MIT Science Library copy: 2 v. set, in leaves. / Also issued in leaves, 2 v. set. Vita. / Includes bibliographical references. / I. Enantioselective Nickel-Catalyzed Reductive Couplings of Alkynes and Aldehydes Allylic alcohol synthesis via a nickel-catalyzed reductive coupling reaction of alkylsubstituted alkynes and aldehydes was studied for ligand effects with respect to the regioselectivity and enantioselectivity of the coupling process. A class of P-chiral, ferrocenyl phosphines was designed, synthesized, and evaluated for efficacy. Ultimately, these phosphines were found to be the most effective chiral ligands for coupling reactions of this class of alkynes, providing (E)-allylic alcohols in up to 67% ee and 85:15 regioselectivity. ... II. Total Syntheses of Amphidinolides T and T4 via Catalytic, Stereoselective Reductive Macrocyclizations Total syntheses of amphidinolides T and T4 were achieved using two nickelcatalyzed reductive coupling reactions of alkynes, with an epoxide in one case (intermolecular) and with an aldehyde in another (intramolecular). The latter was used to effect a macrocyclization, form a C-C bond and install a stereogenic center with >10:1 selectivity in both natural product syntheses. Alternative approaches in which intermolecular alkyne-aldehyde reductive coupling reactions would serve to join key fragments were investigated and are also discussed; it was found that macrocyclization was superior in several respects (diastereoselectivity, yield, and length of syntheses). Alkyneepoxide couplings were instrumental in the construction of key fragments corresponding to approximately half of the molecule of both natural products. In one case (T4 series), the alkyne-epoxide coupling exhibited very high site selectivity in a coupling of a diyne. / (cont.) A model for the stereoselectivity observed in the macrocyclizations is also proposed. ... amphidinolide T1 amphidinolide T4 * site of catalytic, stereoselective macrocyclization / by Elizabeth A. Colby Davie. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2007. / 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. / Time-resolved optical spectroscopy has been employed for mechanistic studies in model systems designed to undergo photo-induced proton-coupled electron transfer (PCET) and oxygen atom transfer (OAT) reactions, both of which are important to energy conversion chemistry (Chapter I). The effect of coupling proton transfer (PT) to electron transfer (ET) depends on their spatial configuration, thus model PCET systems must control both. Noncovalent amidinium-carboxylate PT interfaces are used assemble an electron D/A pairs (D = donor, A = acceptor), establishing uni-directional ET and PT coordinates. A highly conjugated porphyrin-amidinium derivative bears optical signatures that report on the structure of PT interfaces formed upon association with carboxylate acceptors (Chapter II). PT is supported within the interface and the mediating proton's position is sensitive to the peripheral electronic structure. Transient absorption (TA) spectroscopy is applied to a related porphyrin D---[H+]---A assembly, where ---[H+]--- = amidinecarboxylic acid (Chapter III). Specific probe wavelengths are targeted in order to amplify the optical signatures of PCET over those of competing quenching mechanisms. / (cont.) The observed PCET rates are strongly attenuated compared with comparable covalentlybridged analogues, indicating that the PT interface reduces electronic coupling. Temperature-isotope dependence of the PCET rates reveals an unusual inverse isotope effect at low temperature, which is interpreted in a model of vibrationally-assisted PCET (chapter IV). Hangman porphyrin dyads have been developed to study bi-directional PCET in relation to oxygen activation. ET and PT coordinates are orthogonalized at fixed distances about a FeIII-OH center (Chapters V and VI). TA spectroscopy and electronic structure calculations reveal that the structural reorganization attendant to metal-centered PCET imposes a severe kinetic cost and alternative quenching pathways prevail. Finally, TA spectroscopy has been used to elucidate the mechanism of photocatalytic OAT for bridged diiron [mu]-oxo bisporphyrins (Chapter VII). The [mu]-oxo bond is photo-cleaved to generate a terminal iron(IV) oxo, which undergoes OAT to nucleophilic substrates. OAT rates are maximized when the bridge actively splays the porphyrin subunits apart to present the oxo before reclamping can occur. / by Justin M. Hodgkiss. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references. / by Bashir O. Dabbousi. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references. / physicochemical properties in comparison to their linear counterparts. Here we detail a method for a divergent macrocyclization of unprotected peptides by crosslinking two cysteine residues with bis-palladium organometallic reagents. These synthetic intermediates are prepared in a single step from commercially available aryl bis-halides. Two bioactive linear peptides with cysteine residues at i, i + 4 and i, i + 7 positions, respectively, were cyclised to introduce a diverse array of aryl and bi-aryl linkers. These two series of macrocyclic peptides displayed similar linker-dependent lipophilicity, phospholipid affinity, and unique volume of distributions. Additionally, one of the bioactive peptides showed target binding affinity that was predominantly affected by the length of the linker. Collectively, this divergent strategy allowed rapid and convenient access to various aryl linkers, enabling the systematic evaluation of the effect of appending unit on the medicinal properties of macrocyclic peptides. Chapter 2: We report the use of a sulfonated biarylphosphine ligand (sSPhos) to promote the chemoselective modification of cysteine containing proteins and peptides with palladium reagents in aqueous medium. The use of sSPhos allowed for the isolation of several air-stable and water-soluble mono- and bis-palladium reagents, which were used in an improved protocol for the rapid S-arylation of cysteines under benign and physiologically relevant conditions. The cosolvent-free aqueous conditions were applied to the conjugation of a variety of biomolecules with affinity tags, heterocycles, fluorophores, and functional handles. Additionally, bispalladium reagents were used to perform macrocyclization of peptides bearing two cysteine residues. Chapter 3: The synthesis of palladium oxidative addition complexes of unprotected peptides is described. Incorporation of 4-halophenylalanine into a peptide during solid phase peptide synthesis allows for subsequent oxidative addition at this position of the unprotected peptide upon treatment with a palladium precursor and suitable ligand. The resulting palladium-peptide complexes are solid, storable, water-soluble, and easily purified via high-performance liquid chromatography. These complexes react rapidly with thiols at low micromolar concentrations in an aqueous buffer, offering an efficient method for bioconjugation. Using this strategy, peptides can be rapidly functionalized with small molecules to prepare modified aryl thioether sidechains. Additionally, peptide-peptide and peptide-protein ligations are demonstrated under dilute aqueous conditions. / by Anthony J. Rojas. / Ph. D.