Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1988. / Includes bibliographical references. / by John David Beckerle. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2004. / Vita. / Includes bibliographical references. / Because Lewis acids are very versatile mediators of a variety of stereoselective organic transformations, a great deal of effort has been devoted toward the development of chiral Lewis acids. This thesis describes the design, synthesis, and applications of 1,2-azaborolyl complexes as a novel family of planar-chiral Lewis acids that can perform a wide range of stereoselective transformations. The 1,2-azaborolyl ligand is a five-membered B-N bearing heterocycle that is isoelectronic and isostructural with the ubiquitous cyclopentadienyl ligand. In Part I of this dissertation, the feasibility of using boron-substituted 1,2-azaborolyls as tunable cyclopentadienyl surrogates is established. Thus, X-ray structural and spectroscopic studies demonstrate that 1,2-azaborolyls can serve as six-electron [pi]-ligands to a variety of transition metals and that the electronic nature of the boron substituent can modulate the properties of the resulting complexes. Building on the foundations of 1,2-azaborolyl ligand chemistry described in Part I, we establish in Part II that 1,2-azaborolyl complexes bearing good leaving groups on boron can serve indeed as planar-chiral Lewis acids. As a result, we have successfully synthesized a number of enantiomerically pure planar-chiral Lewis acids, and we show through structural and stereochemical correlation studies that these Lewis acids can activate substrates such as aldehydes and imines toward stereoselective nucleophilic attack in a predictable fashion. Specifically, we have investigated planar-chiral Lewis acid mediated nucleophilic attack of Grignard reagents to imines and Lewis acid mediated Mukaiyama aldol reaction of aldehydes with silyl ketene acetals. / (cont.) Our studies indicate that unfavorable peri-interactions between the imine substrate and the Lewis acid may be the conformation-controlling element for nucleophilic additions to imines. On the other hand, detailed mechanistic studies of the Mukaiyama aldol reaction suggest a reaction pathway involving an intermediate with a coplanar aldehyde-Lewis acid conformation. These studies demonstrate the broad scope and the high efficiency with which the chiral information is transferred from the planar-chiral Lewis acid to its substrates. Consequently, the turnover step (regeneration of the active Lewis acid) represents the last hurdle to be addressed for achieving asymmetric Lewis acid catalysis. Part III of this thesis describes miscellaneous applications that have been discovered during the course of the development of 1,2-azaborolyl-based planar-chiral Lewis acids. In Chapter 7, we present a surprisingly mild and versatile method for palladium-catalyzed Suzuki cross-couplings of aryl chlorides in the presence of a triarylphosphine. With this catalytic system, both sterically demanding and electronically deactivated aryl chlorides can be efficiently coupled with a range of boronic acids in good yields, and coupling of activated aryl chlorides can be accomplished at room temperature. In Chapter 8, we report the synthesis and characterization of novel 1,2-azaborines and their potential as benzene surrogates. / by Shih-Yuan Liu. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009. / Includes bibliographical references. / Isobenzofuran, a member of the benzo[c]heterocycles, is an extremely reactive molecule with unusual electronic properties. In this thesis we investigate the integration of isobenzofuran subunits into conjugated optical materials. We discuss the properties of isobenzofuran, its role in organic chemistry, and the synthesis of isobenzofuran containing materials in the context of the other well known benzo[c]heterocycle, isothianaphthene. Isothianaphthene has been used in conducting polymers and organic fluorophores as a proquinoid unit, and we posit that isobenzofuran, due to its intrinsic instability, would display greater proquinoid character. To study this effect, we developed a synthetic route to integrate isobenzofuran into near-infrared donor-acceptor type fluorophores. These dyes, the IBF-NIADs, exhibit red-shifted absorption and emission over corresponding isothianaphthene containing dyes, thus highlighting the effective proquinoid nature of isobenzofuran. With the fundamentals of the IBF-NIAD dyes developed, we then expanded the series into a library of fluorophores for near-infrared fluorescence imaging application. Due to low absorption, autofluorescence, and scattering in the near-infrared region, near-infrared fluorescence imaging has the potential to provide non-invasive diagnostic techniques. In particular, our interest lay in imaging P-amyloid plaques, a hallmark pathology of Alzheimer's disease. / (cont.) We tailored our dye series by modifying the conjugated backbone and the electron-donating group in order to optimize their photophysical properties, minimize their aggregation in aqueous solution, and maximize their optical response on binding to P-amyloid fibrils. Through these efforts we developed several fluorophores that exhibit large bathochromic shifts on binding, with concomitant increases in fluorescence intensity and lifetime, and absorption and emission spectra that extend well into the near-infrared. With the Backskai group at MGH, we found that most of these dyes stain P-amyloid plaques in transgenic APP/PS 1 mouse brain tissue, and efforts are underway to test their in vivo imaging potential. Finally, we present our initial synthetic work in integrating isobenzofuran into donor-acceptor-donor oligomers for nonlinear optical applications. / by Scott Thomas Meek. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references. / CHAPTER1 A general introduction to olefin metathesis is given. Highlights include a detailed discussion of group VI imido alkylidene catalysts. CHAPTER 2 Several bispyrrolide species Mo(NAr)(CHCMe 2Ph)(pyr)2 (Ar = 2,6-i-Pr2C6H3, pyr = 2,3,4,5- tetramethylpyrrolide, 2,5-diisopropylpyrrolide, or 2,5-diphenylpyrrolide) have been synthesized and characterized. X-ray structural studies of these species display one r 1-pyrrolide ring and one 5-p1y rrolide ring. Monohexafluoro-t-butoxide pyrrolide (MAP) species can be prepared, either through addition of one equiv of Me(CF 3)2COH to a bispyrrolide or through reactions between the lithium pyrrolide and the bishexafluoro-t-butoxide. Trimethylphosphine adducts of MAP hexafluoro-t-butoxide species, Mo(NAr)(CHCMe 2Ph)(pyr)[OC(CF 3)2Me](PMe3), have been prepared. An X-ray structural study of one of these phosphine adducts was found to have PMe3 bound approximately trans to the pyrrolide. This adduct serves as a model for the structure of the initial olefin adduct in olefin metathesis. CHAPTER 3 The two diastereomers of Mo(NAr)(CHCMe2Ph)(2,5-dimethylpyrrolide)(OBitet) ((SMRJ)-1 and (RMR])-1, respectively, where OBitet is an enantiomerically pure (R) phenoxide and Ar = 2,6- diisopropylphenyl), form adducts with PMe3. One of these ((RmR)-1(PMe3)) has been isolated. An X-ray structure reveals that PMe3 has added trans to the pyrrolide; it is a model for where an olefin would attack the metal. Trimethylphosphine will catalyze slow interconversion of (SMRI)- 1 and (RMRJ)-1 via formation of weak PMe3 adducts, which undergo a series of Berry pseudorotations or (equivalent) turnstile rearrangements. The interconversion of diastereomers in the presence of trimethylphosphine was investigated by a variety of kinetic studies, variable temperature NMR spectroscopic studies, and labeling studies. CHAPTER 4 Addition of ethylene to Mo(NAr)(CHCMe 2Ph)(OBitet)(2,5-Me2Pyr) led to the trigonal bipyramidal metallacyclobutane complex, Mo(NAr)(C 3H6)(OBitet)(2,5-Me 2Pyr), in which the imido and aryloxide ligands occupy axial positions. NMR studies of Mo(NAr)(C 3H6)(OBitet)(2,5-Me 2Pyr) showed that the metallacyclobutane - species is in equilibrium with ethylene/methylidene intermediates before losing ethylene to yield the respective methylidene complexes. Detailed NMR studies of Mo(NAr)(C3H6)(OBitet)(Me 2Pyr) were carried out and compared with previous studies of W(NAr)(C 3H6)(OBitet)(Me 2Pyr). .It could be shown that Mo(NAr)(C 3H6)(OBitet)(Me 2Pyr) forms an ethylene/methylidene intermediate at 20 0C at a rate that is 4500 times faster than the rate at which W(NAr)(C 3H6)(OBitet)(Me 2Pyr) forms an ethylene/methylidene intermediate. It is proposed that the stability of methylidene complexes coupled with their high reactivity account for the high efficiency of many olefin metathesis processes that employ MonoAryloxidePyrrolide (MAP) catalysts. CHAPTER 5 MonoAryloxide-Pyrrolide (MAP) olefin metathesis catalysts of molybdenum that contain a chiral bitetralin-based aryloxide ligand are efficient for ethenolysis of methyl oleate, cyclooctene, and cyclopentene. Ethenolysis of 5000 equivalents of methyl oleate produced 1- decene (1D) and methyl-9-decenoate (M9D) with a selectivity of >99%, yields up to 95%, and a TON (turnover number) of 4750 in 15 hours. Tungstacyclobutane catalysts gave yields approximately half those of molybdenum catalysts, either at room temperature or at 50 0C, although selectivity was still >99%. Ethenolysis of 30000 equiv of cyclooctene to 1,9-decadiene could be carried out with a TON of 22500 at 20 atm (75% yield), while ethenolysis of 10000 equiv of cyclopentene to 1,6-heptadiene could be carried out with a TON of 5800 at 20 atm (58% yield). Some MonoAryloxide-Pyrrolide (MAP) olefin metathesis catalysts of molybdenum that are Z selective for the homocoupling of terminal olefins can be employed for the selective ethenolysis of Z internal olefins in the presence of E internal olefins in minutes at 22 0C. Therefore it is possible to take an E:Z mixture to a pure E product by selectively destroying the Z component and removing the resulting low molecular weight ethenolysis products. Exclusively E olefins can be obtained from terminal olefins in a two step process: the first step consists of a nonselective homocoupling to give approximately a 4:1 E:Z; while the second step consists of Zselective ethenolysis of the olefinic mixture to generate pure E-olefin. Several functional groups can be tolerated, such as ethers and esters. CHAPTER 6 3,5-Dimethylphenylimido complexes of tungsten can be prepared using procedures analogous to those employed for other tungsten catalysts, as can bispyrrolide species, and MonoAryloxide- Pyrrolide (MAP) species. X-ray structural studies of metallacylcobutane MAP species show them to have the expected TBP geometry with the imido and aryloxide ligands in apical positions. Homocoupling of 1-hexene, 1-octene, and methyl-10-undecenoate are achieved in 45- 89% yield and a Z-selectivity of >99% with W(NAr")(C 3H6)(pyr)(OHIPT) (Ar" = 3,5-Me 2C6H3; HIPT = 2,6-(2,4,6-(i-Pr) 3C6H2)2C6H3) as a catalyst. Homocoupling of terminal olefins in the presence of E olefins elsewhere in the molecule was achieved with excellent selectivity. CHAPTER 7 A monotriflate species, Mo(NAd)(CHCMe 2Ph)(OHIPT)(OTt) (Ad = 1-Adamantyl), is obtained by salt metathesis of bistriflate species and one equivalent of lithium alkoxide. Addition of PMe3 to the monotriflate species led to the formation of a phosphine adduct. An X-ray structural study revealed a square pyramidal coordination environment, with the alkylidene in the apical position and the phophine trans to the triflate ligand. The triflate can be exchanged with a variety of anionic ligands, such as 2-Mespyrrolide and t-butoxide. These species have been characterized by X-ray crystallography and they reveal the expected tetrahedral geometry. CHAPTER 8 Exposure of diethylether solution of Mo(NAr)(CHCMe 2Ph)(Me2Pyr)(OSiPh3) (1) to one atmosphere of ethylene for one hour led to the formation of the ethylene complex Mo(NAr)(CH 2CH 2)(Me 2Pyr)(OSiPh 3) (2). Addition of one equivalent of triphenylsilanol to a solution of 2 gives Mo(NAr)(CH 2CH2)(OSiPh 3)2 (3) readily. Mo(NAr)(CHCMe 2Ph)(OTf)2(dme) reacts slowly with ethylene (60 psi) in toluene at 80 'C to give cis and trans isomers of Mo(NAr)(CH 2CH 2)(OTf)2(dme) (4a) in the ratio of -2(cis):1. Addition of lithium 2,5- dimethylpyrrolide to 4a under 1 atm of ethylene produces Mo(NAr)(CH 2CH 2)(h-Me2Pyr)(h 5- Me2Pyr) (5). Neat styrene reacts with 2 and 3 to generate the styrene complexes, Mo(NAr)(CH 2CHPh)(Me2Pyr)(OSiPh 3) (6) and Mo(NAr)(CH 2CHPh)(OSiPh3)2 (7), respectively. Similarly, the trans-3-hexene complex, Mo(NAr)(trans-3-hexene)(OSiPh 3)2 (8a), can be prepared from 3 and neat trans-3-hexene. When 3 is exposed to 1 atm of ethylene, the molybdacyclopentane species, Mo(NAr)(C 4Hs)(OSiPh3)2 (9), is generated. X-ray structural studies were carried out on 2, 5, 7, 8a, and 9. All evidence suggests that alkene exchange at the Mo(IV) center is facile, followed by cis,trans isomerization and isomerization via double bond migration. In addition, trace amounts of alkylidene complexes are formed that result in slow metathesis reactions of free olefins to give (e.g.) a distribution of all possible linear olefins from an initial olefin and its double bond isomers. APPENDIX A Monopyrrolide monothiolate species of type Mo(NAr)(CHR)(2,5-Me 2NC4H2)(SR') (Ar = 2,6-i- Pr2C6H3; R = CMe3, CMe2Ph; R'= 2,6-Me 2C6H3, C6F5) have been synthesized by protonolysis of Mo(NAr)(CHR)(2,5-Me 2NC4H2)2 with one equivalent of R'SH. Addition of one equiv of 2,6- Me2C6H3SH to Mo(NAr)(CHCMe 2Ph)[OC(CF3)2Me] 2 led to the formation of Mo(NAr)(CHCMe 2Ph)(2,6-Me2C6H3S)[OCMe(CF 3)2] (3) in good yield. Using the same method, Mo(NAr)(CHCMe 3)(SCMe 3)[OC(CF 3)2Me] (4) was synthesized. A ligand scrambling effect was observed by 1H NMR spectroscopy leading to the formation of bisalkoxide and bisthiolate species. The bisalkoxide species, Mo(NAr)(CHCMe 2Ph)(OBitet) 2, was synthesized by salt metathesis of Mo(NAr)(CHCMe 2Ph)(OTf) 2(dme) and two equivalents of BitetONa. An X-ray structural study of this compound shows an anti configuration of the alkylidene. / by Smaranda Constanţa Marinescu. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998. / Includes bibliographical references (p. 373-381) and index. / In this thesis, I describe work done to understand the band edge exciton fine structure of CdSe quantum dots (QDs). These QDs or nanocrystallites are the result of recent synthetic efforts in the Bawendi group to produce nearly monodisperse nanocrystalline materials. The QDs are roughly spherical in shape and range in size from 10 to 50 A in radius. A number of optical experiments have been conducted on the material to understand its optical properties, particularly, the absorption and luminescence. However, several longstanding questions remain. Among them is the origin of the material's band edge luminescence. The emission is unusual because it displays long ([mu]s) lifetimes and exhibits a characteristic, size dependent, Stokes shift. As a consequence, many past studies have implicated the surface as the origin of the emission. In this respect, the surface localization of photogenerated carriers qualitatively explains both the long lifetimes and redshift of the luminescence. Recent theoretical and experimental studies, however, have suggested that the emission arises from an intrinsic core state analogous to a triplet state in small molecules. We describe the theoretical modeling of the QD electronic structure in.eluding the effects of shape, crystal field and the electron-hole exchange interaction. When all symmetry breaking effects are considered, we predict the presence of five fine structure states underlying the hand edge exciton rather than an eightfold degenerate exciton ground state. Following this, we intentionally modify the surface of the nanocrystallites to see the effect this has on the luminescence. Our results suggest that, to a large extent, the surface plays little role in the energetics of the emission. For QDs passivated with different organic and inorganic ligands we find little or no change in values of the "resonant" and "non-resonant" Stokes shift. This strongly supports the above mentioned fine structure model. Subsequent chapters take the proposed theory a step further, using it to explain the unusual behavior of the nanocrystallites subjected to an external magnetic field. The last two chapters pose the question of what happens when the QDs are intentionally doped with a paramagnetic impurity such as manganese? We expected that spin interactions between host and dopant will result in interesting optical phenomena such as the activation of dark excitons as well as shifts in fine structure energies due to an exchange induced mixing of states. / by Masaru Kenneth Kuno. / Ph.D.

Massachusetts Institute of Technology. Dept. of Chemistry. Thesis. 1965. Ph.D. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. / Vita. / Includes bibliographical references. / This thesis presents the synthesis, structure and reactivity of two-coordinate Group 11 metal complexes, supported by N-heterocyclic carbene (NHC) ligands. The NHC ligand was found to stabilize monomeric, terminal fluoride complexes of copper, silver and gold, the last representing the first isolable gold(I) fluoride. These complexes were shown to be reactive synthons for new metal complexes. The ability of the NHC ligand to support unusual coordination environments for these metals inspired us to explore the chemistry of copper(I) bonded to various main group elements, leading to the development of new catalytic reactions. The first well-characterized copper(I) boryl complex was synthesized and shown to react with a variety of unsaturated organic substrates. This complex reacts rapidly with CO2 to form CO and a copper(I) borate complex. The boryl complex may be regenerated by treatment of the borate complex with the bis(pinacolato)diboron, (pin)B-B(pin), giving the stable byproduct (pin)B-O-B(pin). The use of a copper(I) alkoxide precatalyst and stoichiometric diboron reagent results in catalytic reduction of CO2, with high turnover numbers (1000 per Cu) and frequencies (100 per Cu in 1 hour) depending on supporting ligand and reaction conditions. / (cont.) Carbon dioxide also inserts into the Cu-Si bond of a copper silyl complex. The resulting complex evolves CO to give a copper siloxide complex. Mesitaldehyde inserts cleanly and selectively into the Cu-B bond of (NHC)CuB(pin), to form a B-O and a copper-carbon bond. This complex reacts with bis(pinacolato)diboron to regenerate (NHC)CuB(pin) and produce an aldehyde diboration product, in which a diboron reagent has been added across the C=O bond of mesitaldehyde. A copper boryl complex with a smaller NHC supporting ligand proved to be a much more effective diboration catalyst and a wide range of aldehydes react cleanly with bis(pinacolato)diboron. The insertion of alkenes into an (NHC)copper(I) boryl affords isolable -boroalkyl complexes in high yields; competition experiments using substituted styrenes show that electron-donating substituents slow the reaction. Although the insertion products are stable at ambient temperature, a P-hydride elimination/reinsertion sequence affords a rearranged a-boroalkyl complex on heating. / by David S. Laitar. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1997. / Includes bibliographical references. / by Melissa Hirsch Kuchma. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / The intracellular delivery of biomolecules into mammalian cells is a major challenge due to the plasma membrane, which acts as a barrier between the extracellular environment and intracellular components. Recently, a non-toxic delivery platform derived from anthrax lethal toxin has been developed to overcome this challenge for the delivery of biomolecules into the cytosol of mammalian cells. The PA/LFN delivery platform has been used to deliver over 30 known biomolecules of diverse sequences, structures, and functionalities. Collectively, these translocation studies have helped to elucidate the translocation mechanism and to probe intracellular biological processes. In this thesis, the PA/LFN delivery platform was used to analyze the delivery of assorted biomolecules through the PA pore. A facile, modular ligation strategy using sortase A was developed for the conjugation of biomolecules to LFN. The biomolecules for this analysis included antibody mimic proteins with defined sizes and secondary structures, mirror image peptides and proteins, polypeptides containing non-canonical amino acids or small molecule drugs, and cyclic peptides. Our translocation analyses have led to guidelines for translocation as well as insight into design parameters for the efficient delivery of new cargos. The PA/LFN delivery platform has also been used to translocate bioactive cargos for the disruption of intracellular protein-protein interactions (PPI). The translocation efficiency and bioactivity of a tandem monobody to Bcr-Abl, an affibody to hRaf- 1, and a mirror image peptide to MDM2 were analyzed. Efficient translocation and disruption of the intended PPI in each case indicated that the delivery platform could be used to deliver bioactive cargos into cells for therapeutic utility. As an application of this technology, the PA/LFN delivery platform was employed to analyze the intracellular stability of mixed chirality proteins. One major factor that governs a protein's stability is the N-end rule, which states that the N-terminal residue of a protein impacts its intracellular stability through the ubiquitin (Ub)/proteasome system. Utilizing the PA/LFN delivery platform, the stability of proteins containing one N-terminal D-amino acid was analyzed. In contrast to N-terminal L-amino acids, each N-terminal D-amino acid abrogates protein degradation by the N-end rule pathway. / by Amy Ellen Rabideau. / Ph. D.

Thesis: Ph. D. in Physical Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Solid-state nuclear magnetic resonance (ssNMR) spectroscopy is an essential tool for elucidating the structure, dynamics, and function of biomolecules. ssNMR is capable of studying membrane proteins in near-native lipid bilayers and is thus preferred over other biophysical techniques for characterizing the structure and dynamics of membrane proteins. This thesis primarily focuses on the study of the following membrane proteins: 1) the N-terminal ectodomain and C-terminal cytoplasmic domain of influenza A virus M2 and 2) HIV-1 glycoprotein gp4l membrane-proximal external region and transmembrane domain (MPER-TMD) in a near native membrane environment. The cytoplasmic domain of M2 is necessary for membrane scission and virus shedding. The M2(22-71) construct shows random-coil chemical shifts, large motional amplitudes, and a membrane surface-bound location with close proximity to water, indicating the post-amphipathic helix (AH) cytoplasmic domain is a dynamic random coil near the membrane surface. The influenza M2 ectodomain contains highly conserved epitopes but its structure is largely unknown. The M2(1-49) construct containing both the ectodomain and transmembrane domain exhibits an entirely unstructured ectodomain with a motional gradient in which the motion is slower for residues near the TM domain, which attributed to the formation of a tighter helical bundle in the presence of drug that should cause the more tightened C-terminal ectodomain, thereby slowing its local motions. HIV-1 virus gp4l is directly involved in virus-cell membrane fusion. However, the structural topologies of the gp4l MPER-TMD are still controversial and the biologically-relevant intrinsic conformational state of MPER has not yet been determined. In order to obtain near native structural information of gp4l, we have studied gp41 (665-704) and found a primarily a-helical conformation, membrane-anchored trimeric TMD and water-exposed membrane surface-bound MPER. Intra- and intermolecular distances measured using ¹⁹C-¹⁹F REDOR and ¹⁹F-¹⁹F CODEX revealed that MPER-TMD has a significant kink between MPER and TMD, which has aided a deeper understanding of the HIV virus entry mechanism and the design of vaccines. / by Byungsu Kwon. / Ph. D. in Physical Chemistry