2008 Honors Recipients
Title: Purification and Absorption Spectroscopy of Long Polyenes
Advisor: Ron Christensen
Abstract: Optical properties of polyenes with 7, 11, and 13 conjugated double bonds were examined. The polyene samples were synthesized by Richard Schrock's group at MIT using Wittig-like reactions of Mo-bisalkylidene compounds with aldehydes. Matirx assisted laser desorption/ionization mass spectroscopy (MALDI-MS) and high performance liquid chromatography (HPLC) were used to characterize samples, which were found to contain a mixture of shorter polyenes and monitor the stability of the purified samples, which exhibited signs of decomposition one month after purification. Ultraviolet/visible absorbance spectra of the purified polyenes were obtained at 300 K and 77 K. The absorption spectra of the synthetic polyenes were compared with those of natrually occurring polyenes of comparable conjugation lengths to assess how the synthetic samples' optical properties represent those of natural polyene chains. Good correlation was found between the natural and synthetic polyenes, indicating that the synthetic samples are suitable for investigating the electronic states of polyenes with conjugation lengths greater than those found in nature.
Michael Ardolino, '08
Title: Cationic Cobalt Catalysis: Improving upon alpha-olefin dimerization
Advisor: Richard Broene
Abstract: Research has shown that production of alpha-olefins can be improved with the use of geometry specific catalysts. Broene et. al. successfully dimerized 1-hexene into 1-dodecene using catalytic Cp*CoH(P(OMe)3)) slowly and in poor yields. Regioselectivity for the 2,1 insertion product improves with decreasing cone angle of the phosphine ligand. Phosphabenzene has been synthesized as a small cone angle ligand. Work on the synthesis of this ligand and its coupling to the cobalt complex [Cp*Co(ethene)2] is reported.
Jonathan Freedman, '08
Title: New Synthesis of Chromones
Advisor: Richard Broene
Abstract: Novel attempts to synthesize different chromone subclasses using 1-H benzotriazole and salicylic acids are presented. Traditional methods starting with salicylic acids require protection of the phenol group before the carboxylic acid is activated. However, the emergence of the 1-H-benzotriazole methodology allows activation of carboxylic acids in the presence of exposed phenol groups. Thus, a protectionless method of acylation followed by cyclization and dehydration was developed to synthesize chromones. The successful synthesis of 2-methyl-3-acetyl-4-chromones and 2-amino-3-cyano-4-chromones from acetylacetone and malononitrile is reported. Structures are characterized by 1H/13C NMR, FT-IR spectroscopy, and MALDI.
Elizabeth Onderko, '07
Title: Characterization of Peptide Fragmentation Using Energy Resolved SORI-CID
Advisor: Elizabeth Stemmler
Abstract: The fragmentation energies of underivatized and derivatized orcokinin family peptides with the sequences NFDEIDRSGFGF, NFDEIDRSGFGFA, and NFDEIDRSGFGFH were studied using energy-resolved sustained off-resonance irradiation with collision-induced dissociation (SORI-CID) following matrix assisted laser/desorption ionization (MALDI) in a Fourier transform mass spectrometer (FTMS). The peptides were derivatized to form methyl esterified and methyl esterified/acetylated products. Both fixed energy and energy-resolved measurements were taken to elucidate fragmentation pathways. The underivatized peptides undergo Asp-Xxx cleavage, resulting in selective fragmentation. When methyl esterified, this fragmentation is blocked; however; limited fragmentation still results. Upon N-acetylation, the fragmentation becomes much more extensive. The energy-resolved experiements showed that derivatization did not change the energy required for fragmenting methyl esterified vs. methyl esterified/N-acetylated peptides. A mechanism to this fragmentation is proposed, where N-acetylation prevents interactions between the basic N-terminal amine and arginine, allowing the formation of the more productive b-type sequence ions. In a second study, seven peptides containing an N-terminal arginine and C-terminal amino acid of varying basicity were also studied using MALDI-FTMS with SORI-CID. Fixed-energy and energy-resolved measurements were taken to determine possible fragmentation mechanism. The fragmentation efficiency curves of these peptides showed that a significantly lower energy fragmentation pathway is accessible in the presence of the C-terminal basic amino acid. A mechanism for this fragmentation pathway, involving proton transfer to the basic C-terminal residue, is proposed to explain the lower fragmentation energy.
Laura Onderko, '08
Title: Investigating Neuropeptide Processing in Crustaceans using Matrix Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry
Advisor: Elizabeth Stemmler
Abstract: Matrix assisted laser desorption/ionization fourier transform mass spectrometry (MALDI-FTMS) has been used to analyze the midgut of the Jonah crab, Caner borealis, as well as the eyestalk of the American Lobster, Homarus Americanus in an effort to investigate neuropeptide processing. The correlation between feeding status of C. borealis, and ratio of unprocessed Cancer borealis tachykinin-related peptide, G-acid CabTRP, the unprocessed precursor to the biologically active Cancer borealis tachykinin-related peptide, CABTRP, and CabTRP was examined; while a trend suggesting that a higher level of G-acid CabTRP is present in fed animals, no significant difference was found. In addition, a new tissue extraction procedure improved upon prior methods and showed that the ratio of G-acid CabTRP to CabTRP from extracts and direct tisses corresponded. In Homarus americanus, a survey of the eyestalk tissue revealed an interesting peptide at m/z 1270 and subsequent methyl esterificaiton of the extract suggested that although this peak was previously identified in the literature as NFDEIDRSGFA, the peptide might actually be a C-terminally methyl esterified form of Orc[1-11], NFDEIDRSGFG. To further investigate the source and potential processing patterns of these truncated orcokinins, a tissue degradation study was conducted using the crayfish, Procambarus clarkii. The synthetic peptide standards representing a full length orcokinin and truncated orcokinin appear to exhibit similar degradation pathways, however, due to instrument problems, the samples from these studies have yet to be completely analyzed.
Alex Peroff, '08
Title: Atmospheric Studies of Organic Surfaces
Advisor: Laura Voss
Abstract: Aerosols in the atmosphere play a very important role in global climate change. Yet, knowledge about aerosols is very limited. With the growing concerns about global warming and climate change, the need for a greater understanding about the role aerosols play in atmospheric chemistry and radiative forcing is necessary. In this study, self assembled monolagers (SAMs) of alkane thiols on gold surfaces are used to model marine aerosols. SAMs with CH3, OH, COOH, and CH=CH2 functional groups at the terminal position were used. Our research examined changes in SAMs as they were exposed to atmospheric constituents over time, specifically NO2(g) and D2O(I). SAMs were characterized and studied using reflection adsorption infrared spectroscopy (RAIRS).
CH3, OH, COOH, and CH=CH2 terminated SAMs were monitored as they were exposed to atmospheric gases; this resulted in SAM disordering. OH and COOH terminated SAMs tended to be the most stable, while the CH3 and CH=CH2 terminated SAMs showed disorder fastest. Exposure of CH3, OH, CH=CH2 terminated SAMs to NO2(g) not only resulted in overall disordering of the SAM but also resulted in reactions between the NO2(g) and the OH and CH=CH2 terminated SAM. Experiments where OH and CH3 terminated SAMs were dosed in D2O(1) indicate that D2O absorbed onto the surface of both SAMs. An absorption mechanism is yet to be determined.
Elizabeth Richardson, '08
Title: Metabolic Incorporation of Unnatural Azidosugars into Helicobacter pylori
Advisor: Danielle Dube
Abstract: Helicobacter pylori is a gram-negative bacterial pathogen infecting the gastrointestinal tracts of more than half of the world's population (Graham et al.1991). The motility required for H.pylori infection utilizes unipolar sheathed flagella (Goodwin and Armstrong 1990) that are heavily glycosylated with pseudaminic acid (Schirm et al. 2003), a nine-carbon sugar structurally similar to the ubiquitous eukaryotic sugar sialic acid. However, the two sugars share no common pathways or intermediates (Schoenhofen et al. 2003), and pseudaminic acid is found exclusively on a small number of pathogenic bacteria. We are interested in chemically targeting H.pylori based on their exclusive expression of pseudaminic acid, using a technique termed metabolic oligosaccharide engineering (Dube and Bertozzi 2003). We hypothesize that the pseudaminic acid biosynthetic pathway is permissive of unnatural substrates containing azides. To test this hypothesis, we supplemented liquid cultures of H.pylori with peracetylated N-azidoacetylglucosamine (Ac4GlcNAz) and probed for the presence of azides via Staudinger ligation with Phos-FLAG. Western blot analyses of lysates revealed that azides were successfully incorporated into a number of proteins at a 1mM concentration of Ac4GlcNAz. Furthermore, Ac4GlcNAz-treated bacteria display stunted growth and reduced motility compared to their untreated counterparts. These data suggest that treatment of patients with azide-containing sugars might be the first step in a therapeutic strategy to decrease H.pylori infection.
David Soohoo, '08
Title: The Use of a Cobalt (I) Catalyst in the Production of Linear α-olefin Products
Advisor: Richard Broene
Abstract: Methods for the production of linear α-olefin molecules have been investigated because of the wide range of α-olefins' chemical properties. An organometallic cobalt-based catalyst synthesized by Broene et al. catalyzes the dimerization of linear α-olefins. The catalyst developed shows promising results, catalyzing the reaction of 1-hexene to 1-dodecene. A modification of this catalyst is investigated in this research study to determine whether the proposed catalyst will show a greater turnover frequency of the desired product with greater efficiency. Here the first two of the five steps required to synthesize the desired catalyst were successfully performed. 2,3,4,5-tetramethyl-1-(8-quinoyl)-cyclopentadiene was produced in 89.6% yield, but attempts to use this compound to synthesize the cobalt carbonyl intermediate have so far been unsuccessful.