As a means of reducing the dependence on fossil fuels, generation of hydrogen (H₂) has been proposed as a route for storing energy in a chemical bond. To access this energy, H₂ can be combusted with oxygen or used in a fuel to release the energy stored in the chemical bond, while generating water as the byproduct. To generate the hydrogen necessary to fuel a hydrogen economy, an energy efficient and stable catalyst needs to be designed. The work presented in this thesis describes the investigation of a catalytic mimic inspired by the [FeFe]-hydrogenase enzyme. The design of this and similar mimics have been pursued as the active site of the enzyme is composed of readily available and abundant elements, and has a turnover rate of 6000-9000 molecules of H₂ s⁻¹. The catalyst in this work was studied via cyclic voltammetry and density functional theory calculations to determine the catalytic activity as well as a mechanism for H₂ production of the complex. The complex 2,5-bis-(2',2"-thiophen-2-yl)-thiophene-µ-3,4-dithiolato)diiron hexacarbonyl, 1, was prepared and found to catalyze the production of molecular hydrogen in CH₂Cl₂, however the overpotential for catalysis was not determined as the standard potential of acetic acid in CH₂Cl₂ is not known. Comparison of the catalytic potentials of terthiophene-cat to µ-(1,2-benzenedithiolato)diiron hexacarbonyl, 2, and µ-(3,4-thiophenedithiolato)diiron hexacarbonyl, 3, in CH₂Cl₂ showed that 1 had a less negative potential (0.14 V and 0.16 V, respectively) for the catalytic reduction of protons to H₂. Electrochemical investigations combined with density functional theory (DFT) indicated that 1 has an ECEC mechanism for the reduction of protons, where E is an electrochemical step and C is a chemical process. The proposed mechanism for 1 is similar to that of 2 and 3, with 1 catalyzing the production of H₂ using acetic acid at a less negative potential than 2 and 3.

Unnatural amino acid derived fragments are present in a multitude of pharmaceuticals and biologically relevant molecules including complex peptides. Current preparative methods focus almost entirely on the enantioselective synthesis of the α-amino acid and rely on traditional condensative amide bond formation for peptide synthesis. Herein we report the development and application of a two-step protocol for the synthesis of unnatural α-alkyl α-amino amides, featuring enantioselective aza-Henry additions that feed directly into Umpolung Amide Synthesis (UmAS). The first and second enantioselective additions of bromonitromethane to N-Boc alkyl imines are reported. In the first, a known cinchona alkaloid-derived phase-transfer catalyst was leveraged to provide β-amino-α-bromonitroalkanes in high enantiopurity. The second method employs a bifunctional bis(amidine) catalyst to obtain the same β-amino-α-bromonitroalkanes with increased scope (access to both enantiomers) and in improved yield. In a separate study, mechanistic insight led to the development of UmAS utilizing N-iodosuccinimide (NIS) as a substoichiometric promoter, providing access to α-amino amides as a single diastereomer using fully enantioselective and catalytic methods. This two-step peptide synthesis protocol was applied to the synthesis of a fluorinated analogue of the natural product feglymycin, a tridecapeptide featuring nine arylglycine residues. Additionally, a protocol for the one-pot oxidative amidation of primary nitroalkanes was developed.

This masters thesis discusses developments of novel organic methodologies utilizing oxyallyl cationic systems in the pursuit of highly functionalized molecular scaffolds. Chapter 1 focuses on the discovery of the oxyallyl cation intermediate, and examines reported transformations. Detailed optimization and substrate studies following exploitation of a protected 2-oxyallyl cation for nucleophilc capture comprises the information in both Chapter 2 and Chapter 3. Chapter 4 extends methodologies performed by my colleagues and establishes a tandem process using 2-silyloxypentadienyl cations to furnish complex structures. In this report, reaction design and optimization are chronicled, followed by exploration into the reactivity, mechanism, and scope of the developed reactions.

A one-pot and straightforward synthesis, which results in the formation of imidazo[1,5-a]pyridines, has been intensely investigated. This methodology has been applied to 2,2'-pyridil, α- pyridoin and 2-benzoylpyridne ketone systems respectively. Treatment of 2,2'-pyridiI, α -pyridoin or 2-benzoylpyridine with aromatic aldehydes, and ammonium acetate in the presence of hot acetic acid has been shown to give 1-(2-Pyridoyl)-3-phenylimidazolesand 1,3-di-phenylimidazo[1,5-a]pyridines in good to excellent yields. These reactions were carried out without the use of metal catalysts, which is a commonly used methodology for imidazo[1,5-a]pyridine synthesis. A new and efficient synthesis of 1,3-diaryl-[1,5-a]imidazopyridines has also been developed based on the reaction of 2-benzoylpyiridne with aldehydes in the presence of ammonium acetate and hot acetic acid Aldehydes applicable to this reaction include aryl aldehydes, heteroaromatic aldehydes, salicylaldehydes.

Glass is a hard, amorphous, and transparent or translucent substance, and it is examined in forensic science to place a person or object at a scene or with a victim when a crime is committed. Due to its brittle nature when combined with some force, glass is often broken, and is then submitted as a type of trace evidence to a crime laboratory in cases such as hit and runs, breaking and enterings, and homicides. Broken glass is most often obtained from bottles, windows, doors, and automobiles, and can easily be found on the street. Previous published research has examined known samples of glass and compared these samples with their known categories or types of glass. In this current research, a population study was conducted based on the collection and analysis of broken glass with unknown origins in Boston, MA. Glass samples (n=100) were collected from the streets and sidewalks around Boston neighborhoods, and an analytical scheme, constructed by the Boston Police Department Crime Laboratory (Boston, MA, USA), was utilized for every sample. This analytical scheme included physical characteristics, such as color, transparency, thickness, curvature and the observance of UV fluorescence. Further instrumental analysis was performed using the Glass Refractive Index Measurement system (GRIM3®) for the measurement of refractive index and the Scanning Electron Microscope and Energy Dispersive Spectroscopy (SEM/EDS) for elemental composition of each sample. Refractive index varies with glass depending on the manufacturing process and its added components and is defined as the ratio of the speed of light in a vacuum to the speed of light in the substance. Using an SEM/EDS it was possible to qualitatively determine the elemental components in each unknown glass sample. Using this analytical scheme, it may be possible to distinguish every unknown sample of glass from each other using differences in physical, optical, and elemental characteristics. This study showed the differences observed in a population of glass within the city of Boston, which ultimately could help with better statistics for testimony when asked about the significance of determining an inclusion or exclusion with casework samples.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019 / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 191-215). / Metal-organic frameworks (MOFs) have established themselves as some of the most versatile materials available, with applications ranging from gas sorption to separation to sensing to catalysis. With a large abundance of structural motifs published to date, research efforts have shifted towards further framework elaboration via post-synthetic modification (PSM), a method to alter the chemical structure of preformed MOFs. The secondary building units (SBUs) of MOFs, which are commonly small inorganic clusters, have been particularly interesting targets for this synthetic approach. The aim of this thesis is to further our understanding of how metal cations interact with these inorganic nodes. Additionally, the node functionalization approach is used to synthesize novel catalysts for the olefin metathesis reaction. In Chapter 1, the reader is introduced to post-synthetic modification of MOFs with a focus on early transition metal species. A review of pertinent literature is presented. Chapter 2 describes how a desire to challenge the limits of the well-precedented cation exchange process led to a serendipitous discovery of a long-sought binding mode in the iconic MOF-5 system using NbCl₄(THF)₂ as a precursor of niobium. In Chapter 3, attention shifts from fundamental studies to the development of new catalysts for olefin metathesis, a process that to (late has been not been extensively studied in MOFs. After a short introduction about the traditional olefin metathesis catalysis, the prospect of using the inorganic nodes of MOFs as supports akin to the classical platforms used in heterogeneous catalysis is explored. Chapter 4 expands the concepts developed in the previous chapter to rhenium oxide-based olefin metathesis, which is unique compared to catalysis using molybdenum and tungsten oxide systems. / by Maciej Damian Korzyński. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Chemistry

Tetrahydroxanthones are a large class of natural products that contain a partially reduced xanthone moiety. These compounds exist in both monomeric and dimeric forms in nature. A concise retro-biomimetic synthetic approach to monomeric tetrahydroxanthone natural products has been developed. The key transformation involves vinylogous addition of siloxyfurans to benzopyryliums to access chromone lactone precursors which is followed by late-stage Dieckmann cyclization to the tetrahydroxanthone core. Application of this methodology led to efficient syntheses of blennolides B, C, and its stereoisomer epi-blennolide C. Synthetic efforts towards dimeric tetrahydroxanthones, including 2,2'-biaryl dimer secalonic acid D, have been pursued as well. We developed an efficient kinetic resolution using homobenzotetramisole (HBTM) catalysis to obtain enantiopure tetrahydroxanthones. The development of a mild, copper-mediated dimerization of stannyl tetrahydroxanthones also allowed access to enantiopure 2,2'-linked dimeric tetrahydroxanthones including secalonic acids A and D. After successful syntheses of secalonic acids A and D, we also applied the methodologies developed towards a synthesis of the axially chiral dimer rugulotrosin A. An enantiopure monomer was prepared in gram-scale by applying our previously developed methodology. The atropselective synthesis of rugulotrosin A was achieved via a one-pot Sukuzi dimerization with chiral palladium precatalyst. A rationale for point-to-axial chirality transfer observed in the key dimerization step has been developed. This key transformation led to the successful 7-step syntheses of rugulotrosin A, its enantiomer, and the atropisomer. Finally, we further exploited the kinetic resolution using homobenzotetramisole catalysts which successfully led to a unified strategy for syntheses of both the 2,4'-linked and 4',4'-linked secalonic acid derivatives. The isomerization properties of 2,2'-linked, 2,4'-linked, and 4,4'-linked secalonic acids was also studied in an effort to understand the "shapeshifting" properties of the dimeric tetrahydroxanthone family.

M.Sc., Faculty of Science, University of the Witwatersrand, 2011 / In the initial, methodological part of this MSc project we intended to expand upon and improve various aspects of the ultrasound accelerated, iodine catalyzed, conjugate addition reaction of amines with 1,4-naphthoquinones first reported by Ji and co-workers in Synthetic Communications (2008, 38, 1201-1211). In recent times, the synthesis of 2-amino-1,4-naphthoquinones has become a heated area of research as a direct consequence of their multitude of diverse pharmaceutical activities; including anticancer, antimalarial, antifungal and trypanocidal properties. Sonochemical transformations, reactions accelerated by ultrasound irradiation, have attracted considerable attention of late due to the shorter reaction durations, higher yields and milder reaction conditions associated with these processes. Additionally, as a result of its unique catalytic properties, iodine has been extensively exploited in diverse, atom-economical and accelerated organic reactions to afford the corresponding products in excellent yields with high selectivity. With these considerations in mind a combinative library of eleven 2-amino-1,4-naphthoquinones with promising anticancer activity were successfully constructed in moderate to exceptional yields, with greatly reduced reaction times, 60 - 90 minutes, using the environmentally friendly, protic solvent ethanol.

This dissertation describes the characterization of the magnetic and electrical properties of a unique class of transition metal complexes known as single-molecule magnets (SMMs). The experimental work of this dissertation is focused on the SMMs [(C6H15N3)6Fe8O2(OH)12]Br7(H2O)Br •8H2O (Fe8Br8), K6[V15As6O42(H2O)] • 8H2O (V15), as well as the analogous cluster compounds [NH(C2H5)3]4[V84.5+V44+As8O40(H2O)]•H2O (V12) and [(C6H15N3)4Fe4O(OH)5]I7 • 2.5 H2O (Fe4). SMMs are transition metal cluster complexes that exhibit single-molecule hysteresis and quantum tunneling of the magnetization (QTM). Fe8Br8 is one of the best characterized SMMs with its ground state spin S = 10, while V15 exhibits SMM behavior with a spin of S = ½. The foci of our investigations were the single-spin model in Fe8Br8, the basic electrical properties of V15 and V12, and the synthesis and characterization of the analogous cluster compound Fe4. Chapter 2 describes the characterization (magnetic parameters and energetic location) of the S = 9 excited state in Fe8Br8 by high field electron paramagnetic resonance, while Chapter 3 focuses on the measurement of the unpaired electron density distribution in Fe8Br8 as determined by 81Br solid state NMR. Both of these chapters bring into question the validity of the currently accepted single-spin model for Fe8Br8. Chapter 4 details the dielectric relaxation properties of V15 as determined by an ac impedance method. The semiconductive behavior of both V15 and V12 is described in Chapter 5, along with its comparison to optical absorption measurements, while the synthesis and magnetic characterization of the new cluster compound Fe4 is described in Chapter 6. The summary and main conclusions are presented in Chapter 7. The results presented herein should make a significant contribution to the fundamental understanding of the mechanism of quantum tunneling in Fe8Br8 and the basic electrical properties of SMMs for their potential use in future applications. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Fall Semester, 2004. / Date of Defense: July 12, 2004. / Electrical Transport, Magnetic Resonance, Single Molecule Magnets, Excited States / Includes bibliographical references. / Naresh Dalal, Professor Directing Dissertation; Stephan von Molnár, Outside Committee Member; Kenneth Goldsby, Committee Member; Oliver Steinbock, Committee Member.

Prostate cancer is the most prevalent cancer diagnosed among men in the United States. The major green tea polyphenol epigallocatechin-3 gallate (EGCG) has been shown to exert remarkable preventive effects against various types of cancer including prostate cancer. Recent human clinical study proved that EGCG can prevent progression of high grade prostatic intraepithelial neoplasia (PIN) to prostate cancer. Cellular studies show that EGCG exhibits antiproliferative and apoptotic effects in androgen-responsive LNCaP and androgen-unresponsive DU145, PC3 prostate cancer cell lines. Previously, we have established a new type of prostate cancer line, androgen repressed carcinoma of prostate (ARCaP). ARCaP cells are highly invasive and metastatic and this cell line showed unique response to androgen since the hormone repressed the proliferation. In this study, we show that androgen-repressed ARCaP prostate cancer cell line, which represents more advanced and aggressive type of prostate cancer, is resistant to EGCG treatment. In Western blot analyses, EGCG treated ARCaP cell line showed increase in phosphorylation of NF-κB and decrease in activation of p38 MAPK and Bax/Bcl-2 ratio. The levels of p21/CIP1/WAF1, cyclin-dependent kinases (CDKs) 2, 4, 6, activated forms of Akt and c-Jun NH2-terminal protein kinase (JNK) remain unchanged in EGCG treated ARCaP cells whereas decrease in active Akt, active JNK, and CDKs 2, 4, 6, and increased level of p21/CIP1/WAF1 were observed in LNCaP cells upon EGCG treatment. Moreover, EGCG treatment confers stronger adherence to types I, II, IV collagen extracellular matrix proteins on ARCaP cells. On the contrary, LNCaP cells lost the adhesion significantly to all extracellular matrix proteins tested, including collagens, fibronectin, laminin, vitronectin, and tenascin. Most importantly, ARCaP cells formed more colonies on soft agar in our anchorage-independent assay when treated with EGCG whereas the colony forming ability of LNCaP cells was totally abolished under the same condition. This study suggests that the use of tea catechin EGCG as anticancer agent may not be effective for treating patients with androgen repressed subtype of prostate cancer. This is the first study of apoptosis in ARCaP cell line. The GeneChip microarray analysis revealed several genes that were differentially expressed when treated with EGCG. Among those, matrix metalloproteinases (MMPs) 1 and 3 were significantly up regulated in LNCaP cells upon EGCG treatment. Both RNA transcription and protein secretion/activation of these MMPs were observed by GeneChip assay, reverse transcription-polymerase chain reaction (RT-PCR) and by enzyme linked immunosorbent assay (ELISA) which can detect proMMP1 and total MMP3 in cell culture media. This feature is very unique in that (1) the MMPs are generally known to be involved in tumor invasion and metastasis not the cell death, and (2) the other EGCG sensitive prostate cancer cell lines, DU145 and PC3, did not display such characteristics. EGCG did not affect the expression of these MMPs in ARCaP cells also. Using GeneChip analysis, we found several genes whose expressions were oppositely regulated in LNCaP and ARCaP cells upon EGCG treatment. These include early growth response -1 (EGR1), growth arrest and DNA damage inducible gene 45 (GADD45). The expression level of EGR1 and GADD45 were decreased in ARCaP cells but the level was increased in LNCaP cells after EGCG treatment. These results suggest that the proapoptotic EGR1 and GADD45 may play a role in EGCG induced apoptosis in LNCaP cells and thus may explain, at least in part, the resistance of ARCaP cells against such apoptotic stimuli. The role of these proteins in EGCG induced apoptosis is not known. The decreased level of topoisomerase II in EGCG treated LNCaP cells is also exciting. Topoisomerases are necessary in DNA replication and thus for survival of the organism. Since only LNCaP cells, but not ARCaP cells, displayed reduced expression of topoisomerase II during EGCG induced apoptosis and since ARCaP cells underwent apoptosis when treated with topoisomerase inhibitor etoposide, the function of this enzyme might be involved in life or death decision of ARCaP and LNCaP cells. Elucidating the molecular effects of these proteins and the mechanisms of how these proteins function in ARCaP and LNCaP cell lines would help understanding the prostate cancer and may help with future design of cancer chemopreventive and chemotherapeutic agents. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Summer Semester, 2006. / Date of Defense: May 12, 2006. / Apoptosis, Tea, Catechin, Prostate, Cancer / Includes bibliographical references. / Qing-Xiang Amy Sang, Professor Directing Dissertation; Thomas C.S. Keller III, Outside Committee Member; Joseph B. Schlenoff, Committee Member; Hong Li, Committee Member.