2012 Honors Recipients

Kaitlin Clifford '12

Kaitlin Clifford '12 Title:  The Synthesis of a Sterically Hindered Metallocene Catalyst
Advisor: Richard Broene
Abstract: The ability to isolate a single enantiomer of a catalyst is of critical importance.  For metallocene-based catalysts, the optimal path is to synthesize only the racemic disatereomer rather than the meso, since one enantiomer of the racemic catalyst can then be isolated.  In order to prevent the formation of the meso catalyst diastereomer, steric bulk, in the form of isopropyl groups, was used.  While the desired ligand, bis(diisopropylindenyl)ethane, was formed, it was only obtained in low yield.  Rather than forming the desired ligand, intermediates resulting from a single (rather than double) addition of the tether were synthesized as the major product.  Future work will analyze methods to increase the yield and purity of bis(diisopropylindenyl)ethane.  After the ligand is synthesized and coordinated to the chosen metal, the effects of the isopropyl groups on the geometry of the metallocene catalyst formed will be analyzed.

Chelsea Connon '12

Chelsea Connon '12 Title:  Computational Studies of Selected d6 RuII and IrIII Coordination Compounds
Advisor: Jeffrey Nagle
Abstract:
Coordination compounds of d6 metals, such as IrIII and RuII, have been studied for applications in LEDs, solar energy conversion, photocatalysis, and molecular sensors and switches due to their interesting photochemical properties.  These compounds generally exhibit long excited state lifetimes, high efficiency of phosphorescence due to the strong spin-orbit relativistic effects in 2nd and 3rd row transition metals, and have easily accessible charge-transfer transitions.  Much progress has been made in this area, but chemists continue to search for molecules that will perform more efficiently in these technologies.  Three novel coordination compounds of RuII and IrIII, Ru(phen)2pyrene, Ir(ppz)2pyrene and Ir(ppz)2mepyrene, were studied using a combination of experimental data obtained from collaborators at the University of British Columbia and computational results obtained from ADF.  It was found that Ir(ppz)2pyrene is centered on the pyrene ligand, while the lowest energy excited state of Ru(phen)2pyrene is a LL’CT transition from the pyrene ligand to one of the phenanthroline ligands.  Both the conformation of the molecule and the solvent used were found to affect the absorption spectrum of the molecule.  For Ir(ppz)2pyrene and Ir(ppz)2mepyrene, the conformation was also found to affect the magnitude of the dipole moment.  In general, these results show that in designing molecules for photochemical applications, it is important to consider both the solvent the molecule will be dissolved in and the possibility that the molecule may exist in multiple conformations which differ in their photochemical properties.

Onyinyechi Esonu '12

Onyinyechi Esonu '12 Title:  An Examination of Putative Helicobacter pylori Glycoproteins
Advisor: Danielle Dube
Abstract: 

Pornchai Kaewsapsak '12

Pornchai Kaewsapsak '12 Title:  Synthesis of Phosphine Warheads to Eradicate Pathogenic Helicobacter pylori
Advisor: Danielle Dube
Abstract: 

Heather Kinnear '12

Heather Kinnear '12 Title:  β-Methylamino-L-Alanine Sediment Sorption To Sediments and Minerals
Advisor: Benjamin Gorske
Abstract:
β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid and a neurotoxin produced by many species of nitrogen fixing cyanobacteria. Due to its neurotoxicity, BMAA released from aqueous cyanobacterial blooms may pose as a health hazard. In aquatic systems, transport, transformation, and transfer processes determine the environmental fate of BMAA. To the best of our knowledge, almost no studies to date have evaluated the environmental fate of BMAA. This research focuses on one key BMAA transfer process – BMAA sorption at the solid-water interface. BMAA sorption to sediments and sediment components including calcium-montmorillonite, iron-oxide, and sand was investigated and compared to the previously well-studied histidine due to the similarities in structures and pKa values of BMAA and histidine.

Sorption studies required quantitative analysis of BMAA and histidine, which was attempted via both pre-column derivatization with 9-fluoromethylchloroformate (FMOC) and subsequent analysis via high performance liquid chromatography with fluorescence detection (HPLC-FD), as well as direct analysis with capillary electrophoresis using diode array detection (CE-DAD). Due to our inability, within the time constraints of this study, to develop a method for the preferential formation of single or double derivatives of BMAA with FMOC, reliable standard curves for this method that would have allowed for detection of low BMAA concentrations (10-6 M) could not be established. Therefore, capillary electrophoresis was used for the quantitation of high concentrations (>10-4 M) of BMAA and histidine used for sorption studies.

Sorption studies were performed at initial BMAA and histidine concentrations of 2.5 x 10-3 M. Based on solid-mass normalized parameters BMAA sorbed to the greatest extent onto Ca-montmorillonite, followed by sediment, iron-oxide, and sand, while histidine sorbed to the greatest extent onto sediment, followed by Ca-montmorillonite, iron-oxide, and sand. As sand and iron-oxide displayed less than 10% sorption under our experimental conditions, this data was inferred as insufficient for interpretation and analysis focused on sorption of BMAA and histidine to Ca-montmorillonite and sediment.

The greater extent of BMAA sorption to Ca-montmorillonite as compared to histidine suggested that amino acid speciation and charge, distance between amine and carboxylate moieties, and amino acid orientation on the surface impact extents of sorption. In contrast, the similar extents of BMAA and histidine sorption to sediment suggested either that organic matter may favor histidine sorption or that solution pH differences accounting for more negatively charged surface sites facilitated greater histidine sorption. Based on surface area and cation-exchange capacity normalized parameters, both BMAA and histidine sorbed to sediment to a greater extent than to montmorillonite, highlighting the importance of organic matter receptor sites as more favorable than aluminosilicates for cation-exchange and cation-bridging. BMAA sorption, during and after an algal bloom, is therefore expected to occur to sediments high in aluminosilicates and organic matter, primarily via cation-exchange, cation-bridging, and to a lower extent via surface complexation.

Kathryn Leifheit '12

Kathryn Leifheit '12 Title:  A Systematic Characterization of Thioamide-Aromatic n->π* Interactions in Thiopeptoids
Advisor: Benjamin Gorske
Abstract: Protein-protein interactions between polyproline II (PPII) helices and WW domains have been linked to the pathogeneses of many diseases. Peptoids (N-substituted glycine oligomers) could act as biostable structural analogues of peptide PPII helices, serving as therapeutics or biological probes by interrupting these protein-protein interactions. Thus far, the greatest challenge in peptoid design has been ensuring the discrete folding necessary for tailored protein-ligand binding, a key factor in the design of any potent therapeutic. Strong carbonyl-carbonyl n→π* interactions within the peptoid will stabilize trans-amide conformations, resulting in a secondary structure similar to a PPII helix. In order to strengthen n→π* interactions, we proposed substituting the carbonyl oxygen in peptoids with a more polarizable sulfur atom to create “thiopeptoids.” Further, we expected mixed peptoid-thiopeptoid oligomers to demonstrate stronger thioamide-carbonyl n→π* interactions relative to fully thionated peptoids. To date, no standard protocol for the synthesis of polythiopeptoids has been developed. This project entailed the development of methods for thiopeptoid synthesis, purification, and analysis. We find that our protocol for peptoid trimer thionation yields mono- and di-thionated peptoid-thiopeptoid mixed oligomers along with a variety of byproducts. As a result of this research, the polarities and analytical hallmarks of the mixed oligomers and byproducts are now known, and can be exploited in future thiopeptoid research.

Scott Longwell '12

Scott Longwell '12 Title: Profiliing the subcellular localization of Helicobacter pylori's glycoproteins
Advisor: Danielle Dube
Abstract: The gram-negative bacterium Helicobacter pylori is a prevalent pathogen, infecting the gastric mucosal lining of roughly half the human population. Infection with H. pylori is associated with higher rates of gastritis, ulcers, and gastric cancer. While current antibiotic treatments are generally effective, reports of resistant infections have been on the rise, prompting a search for new molecular targets. Glycoproteins, or proteins modified with glycans (carbohydrates), are one such class of targets. However, little is currently known about H. pylori's glycome. In previous work, metabolic oligosaccharide engineering (MOE) has been used to successfully isolate and characterize H. pylori’s glycoproteins, many of which have been identified as virulence factors. Combining MOE with differential centrifugation and cell lysis has the potential to provide information on glycoprotein localization in addition to identity. Findings thus far have provided evidence that all of H. pylori’s subcellular fractions, including its surface-associated fractions, possess unique glycoprotein profiles and that urease, a virulence factor, is glycosylated. Work has also been done to develop a solid-phase covalent capture-release method of purifying azide-labeled glycoproteins for subsequent identification and structural analysis with mass spectrometry.

Daniel Polasky '12

Daniel Polasky '12 Title: Elucidation of a Putative Enzyme Catalyzed C-Terminal Methylation Reaction in Crustacean Neuropeptides
Advisor: Elizabeth Stemmler
Abstract: Understanding modifications that occur during analysis of neuropeptides is vital to ensuring accurate identification and sequencing of neuropeptides from biological systems. A specific modification reaction of crustacean orcokinin neuropeptides during extractions for mass spectrometry was investigated to determine the nature of the reaction. The reaction was mimicked in a controlled environment using Carboxypeptidase Y and other enzymes in an attempt to replicate the modification observed in crustacean tissue extracts. It was found that the concentration of methanol in solution and solution pH strongly influenced the ability of the various enzymes to truncate and methylate the peptide standards. In addition, orcokinin-like peptides with systematic sequence variations were added to solutions containing enzymes from H. americanus tissue extracts to assess the importance of individual amino acid residues on the reaction. It was found that the putative enzyme responsible exhibits endo-peptidase behavior, and that the glycine and phenylalanine residues immediately before the cleavage site are important to the specificity of the reaction.

Jonathan Ryss '12

Jonathan Ryss '12 Title:  Development of a Peptiod Catalyst for the Enantioselective Trifluoromethylation of ketones
Advisor: Benjamin Gorske
Abstract: The introduction of chiral trifluoromethyl moieties into pharmaceuticals facilitates unique and precise manipulation of drug properties, but current methods for enantioselective trifluoromethylation require catalysts that are difficult to modify and are limited in substrate scope. Peptoids — a type of peptidomimetic foldamer — have been shown to be effective and modular chiral catalyst scaffolds that, when functionalized with an achiral catalytic group, catalyze enantioselective transformations in high yield and enantiomeric excess. The synthesis and reactivity of an N-oxide functionalized monomeric peptoid catalyst for the enantioselective trifluoromethylation of aldehydes is presented. Rigorously dry conditions and inert N2 atmosphere minimized inhibition of the reaction by water and minimized the formation of fluoroform as a byproduct. A crude mixture of two monomeric peptoid catalyst diastereomers successfully catalyzed the trifluoromethylation of benzaldehyde, but the rate of conversion was very low. The low rate of conversion led to the hypothesis that the monomeric peptoid catalyst is too sterically encumbered near the active site. Nevertheless, acetonitrile was shown to be an effective reaction solvent for nucleophilic trifluoromethylation using N-oxide catalysts, which will greatly facilitate the development of future peptoid catalysts.

Samuel Steward '12

Samuel Steward '12
Title:  Identification of Fluorescent impurities in Amphotericin B
Advisor: Elizabeth Stemmler
Abstract:

Katherine Rawden '12

Katherine Rawden '12 Title: Synthesizing a cobalt catalyst to dimerize linear a-Olefins by attaching isocyanide ligands to the cobalt bis-ethene complex.
Advisor: Richard Broene
Abstract: Linear α-olefins (LAOs) are precursors to important consumer goods such as plastics and surfactants. In 2007, the LAO industry was valued at over 2.5 billion dollars with over 3.5 million metric tons produced. Selective dimerization of small chain LAOs by an organometallic catalysts allow for greater control of the chain length of long chain LAOs, resulting in more efficient production of LAOs. In 2005, Broene developed a cobalt catalyst that dimerized 1-hexene into 1-dodecene. However, the catalyst was slow and the major product was branched rather than the desired linear olefin product; this result was attributed to the large size of the supporting ligand. In order to create a catalyst that will successfully generate a specific LAO, various smaller ligands supporting ligands were attached to a catalyst precursor, the cobalt bis-ethene complex, in order to create a catalyst that will favor the desired product. The viability of isocyanides as the supporting ligands was explored in hopes of creating an improved catalyst due to their small cone angles. Synthesis of the improved catalyst was begun through synthesis of the isocyanides and attempted coordination of these isocyanides to the cobalt bis-ethene complex.