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Younger Chemist Committee Presents 15th Annual American Chemical Society Poster Session Abstracts March 31, 2015 University of the Sciences Bobby Morgan Arena (ARC) The 15th Annual Younger Chemist Committee Poster Session has been made possible by: YCC Poster Session Committee Renee Harris – Temple University Catherine Jarinko-‐ University of the Sciences Ogan Kumova – Drexel University College of Medicine Christine McInnis – Dow Chemicals Ivona Sasimovich – Drexel University Thomas Umile – Gwynedd Mercy University Lauren Weinrich – American Water Karen Wendling—Chestnut Hill College The committee would like to thank: The University of the Sciences for venue and equipment. USciences undergraduate ACS chapter for their help. www.PhillyYcc.org design by Patrick O’Gorman ACS Philadelphia section Administrator Libby Harper. The abstracts in this book have been provided by the presenter and have not been edited by the committee. HIGH SCHOOL Students High School 1 Novel Chemistries in the Synthesis of Next Generation Antimalarials Jimmy Olsen, Other Authors? LaSalle College High School, University of Pennsylvania In the past few decades, there has been an increase in malaria parasites that have developed resistance to common antimalarial agents. Therefore, novel antimalarial agents have become an increasingly important area of study in recent times. The problem of this project is ?using novel nickel catalyst chemistry, can I synthesize and purify novel antimalarial compounds that are analogs of the Walter Reed molecule?? I hypothesize that by using nickel catalyst chemistry and other processes, I will be able to synthesize analogues of WR-‐965 that can be tested against various strains of malaria. The first step taken was to develop a collaboration with the Professor Percec Laboratory at the University of Pennsylvania, where the synthesis was performed, and with Dr. Dennis Kyle at the University of Southern Florida, where the antimalarial testing will be performed. A six-‐step synthesis was planned, with the last two steps varying depending on the target analogue. Aqueous workups and silica gel columns were done after each step to purify the reaction, as well as N.M.R. studies to confirm product production and purity. The synthesis is currently ongoing, and the compounds will be tested at USF against wild-‐type and resistant strains of malaria. In conclusion, a synthetic procedure was initiated and is currently ongoing for analogues of WR-‐965. Potential errors include synthetic mistakes, especially impurities. Finally, I hope to continue to synthesize analogues over the summer to test against malaria. High School 2 Effective methods for high yield protein production of LarC Betsy Vivar, Adetoun Adeniji-‐Adele, John W. Tomsho Camden Academy Charter High School, University of the Sciences in Phildelphia, Univeristy of the Sciences in Philadelphia Lasso peptides are a class of naturally occurring peptides that can act as antimicrobial and antiviral agents. Lasso peptides are of interest due to their lasso shape which makes them less susceptible to enzymatic degradation. Lariatin A is a lasso peptide with activity against tuberculosis. Lariatin A is produced by five genes and each gene serves a unique purpose in the production of the peptide. larC is the largest of the lariatin A genes and it is thought to help in the process of cyclizing the peptide onto its backbone. Efficient production of lariatin A requires that all the processing enzymes are synthesized to a maximum without causing toxicity in the cell. This project examined the best way to produce the maximum amount of LarC protein. Three different media (LB, 2xYT and SOC) and various IPTG concentrations were used to identify the best conditions to produce the most amount of LarC. larC was transformed into BL21(DE3), then the cells were grown in different media and protein production was then induced using IPTG. The extracted proteins were run on a protein gel and visualized using Coomassie blue stain. Densitometric analysis was performed on the expected protein band and values compared between the different media and concentrations of IPTG. The hypothesis was that the best protein production would be seen using the most enriched media and at the highest concentration of IPTG. The 2xYT is like placing the bacteria on a high protein diet while the SOC is like placing the bacteria on a high carbohydrate diet. Preliminary data show that neither the increased protein nor increased carbohydrate regimen resulted in increased protein production. Also, the highest IPTG concentration did not result in the greatest protein production. My results indicate that LB at lower concentrations of IPTG was the best for producing the most amount of LarC protein. High School 3 Using Surface Sampling to Determine what is on Hamburger Meat David A. Serrano , Madeline A. Fenner, Charles N. McEwen Camden Academy Charter High School, University of the Sciences in Philadelphia Beef burgers play a large role in the diets of many Americans. Americans, on average eat three hamburgers per week. Hamburgers are made of beef which are full of dietary fats. Fats add flavor to foods but they also provide essential fatty acids and aid in the absorption of fat soluble vitamins A, D, E, and K. In addition, fats are a concentrated source of energy that provides up to 9 calories per gram compared to proteins and carbohydrates provide 4 calories every gram. In my research project, I investigated what was on the surface of hamburgers from various fast food franchises (McDonald?s, Wendy?s, Burger King). Mass Spectrometry was used to determine content of each of the franchise hamburgers. It identified the type and amount of chemicals present on an analyte (hamburgers) by measuring the abundance of gas phase ions. Samples were ionized by employing two atmospheric ionization techniques: ASAP and MAI. ASAP-‐
atmospheric solids analysis probe ionizes samples using corona discharge. MAI-‐
matrix assisted ionization is part of a family of ionization techniques that uses the heat of capillary to ionize samples. Results show that each of the burgers contained an abundance of fatty acids. Specifically, 3-‐Pyridylcarbinol Ester which is a derivative of gamma-‐Linolenic acid was found consistently in all of the samples for the ASAP Ionization method. McDonald?s burgers had both Caprylic and Capric Acid. Other fatty acids found consistently in all the ASAP data sets are Myristic, Stearic, Oleic, and Palmitic Acids. MAI ionized different fatty acids than ASAP. UNDERGRADUATE
Undergraduate 4 Determining the Amount of Caffeine and Theobromine In Dark Chocolates from Unique Sources in Africa Brenda Ho, Karen S. Wendling Chestnut Hill College This poster describes the extraction of caffeine and theobromine from four chocolate bars. These methylxanthines were then detected using High Performance Liquid Chromatography (HPLC) with UV-‐VIS detection (270nm). This study of interest due to the fact that chocolate bars do not usually state their caffeine and theobromine content. The four chocolate bars purchased contained cocoa from beans originating in differenct countries: Sao Thome, Ghana, Madagascar, and Tanzania. An internal standard (7-‐(?-‐hydroxyethyl)theophylline) was added to each melted chocolate sample which allows for the percent recovery of the methylxanthines to be determined. Initially, the fat was wax were extracted from the chocolates using petroleum ether. The two methylxanthines were then extracted into a water solution using acid and base properties. Results from the internal standard show a consistent ~60% recovery of the methylxanthines from the chocolates. The levels of theobromine deteremined from all the chocolates were statistically similar (90% confidence). However, the caffeine level in the Madagascar chocolate was significantly higher compared to the caffeine levels of the other chocolate samples; this was confirmed by an additional analysis of another chocolate bar variety from Madagascar. Undergraduate 5 Molecular Interactions of Dibucaine with Biological Membranes Oleg Davydovich, Nicholas Chen, Ara Abramyan, Zhiwei Liu, Preston Moore Department of Chemistry & Biochemistry, University of the Sciences Design and development of new pharmaceutics and therapeutics is an increasingly necessary and complex process. Researchers are constantly striving to improve medicine by employing various techniques such as in a traditional laboratory setting or through modeling, typically the use of a computer simulation program. By applying such a program, the investigator can directly observe drug interactions, its movements and dynamics (i. e., what it binds to, how it interacts with certain compounds, and other various critical details are difficult to observe or study). In this work an ampipathic drug known as dibucaine, a local anesthetic, is studied. It consists of a hydrophobic component, allowing the drug to traverse through the hydrophobic tails of the lipid membrane, and a hydrophilic component, responsible for its mode of action. We applied computational methods to determine the atomic-‐
level interactions between dibucaine and the lipid bilayer and the free energy profile (?G of binding) of the pathway by which the drug traverses through the membrane. The free energy (?G) was found to be -‐6.4 kJ/mol and can then directly be compared to the experimentally observed binding constants. Thus, this study will facilitate researchers' understanding of the mechanisms of drug-‐membrane interactions, which will help in the rational design of new therapeutic entities with higher efficiency as well as lower toxicity.
Undergraduate 6 Regenerated Tri-‐component Lignocellulose Bio-‐Films Using Ionic Liquids Ashley Lewis , Johua C. Waters, Joseph Hess, John Stanton, Darrel Cowan, David Salas-‐de la Cruz Rutgers University-‐Camden In making regenerated biofilms, cellulose has been used in the past both for its effectiveness and its abundance as a renewable resource. However, in the natural world, cellulose interacts with other components, such as lignin and hemicelluloses, to form the structural and morphological features of plants. The physico-‐chemical property of all lignocelluloses components (i.e lignin cellulose and hemicellulose) into bio-‐films has yet to be fully explored. Understanding the structure-‐property interactions amongst these components can give knowledge for producing biofilms from the regeneration of all three natural components, which would create more efficient properties for energy production and for biomedical applications, such as the generation of scaffolding for organs. The purpose of this investigation was to compare the structure-‐property relationship of regenerated films with varying proportions of lignin, hemicellulose and cellulose using 1-‐allyl-‐3-‐methylimidazolium chloride ionic liquid. ATR-‐FTIR, SEM, TGA, and AFM were used to study whether modifications to the films properties as a function on the proportion of the components. The results displayed that the addition of lignin and hemicellulose to the cellulose films resulted in an increase in ionic liquid concentration within regions of the films. The FTIR spectral analysis provided evidence of such interaction. It showed a higher similarity between 1-‐allyl-‐3-‐methylimidazolium chloride and the regenerated film when the concentration of lignin increased with a constant level of cellulose in the fingerprint region. Similarly, the SEM also depicted traces of morphological changes related to ionic liquid in the films and the TGA results displayed a similar trend with higher decomposition temperature for higher lignin and cellulose films. These results provide possible evidence of ionic entrapment with regions of this polymer blend. The increased entrapment of 1-‐allyl-‐
3-‐methylimidazolium chloride ionic species in the regenerated lignocellulose films suggests that the high content of lignin and cellulose have strong bonding interactions during regeneration, illustrating that successful biofilm production is contingent on the appropriate proportions of lignocelluloses components and the ionic liquid. Undergraduate 7 An Analysis of Carbendazim Found in Organic vs. Conventional Orange Juices Elizabeth Kowal, Amanda Vogel, Chris Bianca, Karen Wendling Chestnut Hill College, JRF America The goal of this research was to compare the concentration of the fungicide carbendazim (MBC) in three organic and three non-‐organic (conventional) orange juices. Acetonitrile was added to the juice, followed by a citrate buffer as a liquid-‐
liquid extraction. A portion of the acetonitrile layer was subjected to a Quecher cleanup (dispersive Solid Phase Extraction). The final supernatant was mixed with water prior to analysis using liquid chromatography-‐triple quadrupole mass spectrometry (LC-‐MS/MS) in Multiple Reaction Monitoring (MRM) mode. The results indicated that any MBC contamination was less than the limit of detection for all organic and conventional orange juices. Thus there was no significant difference between this particular fungicide found in either organic or conventional orange juices.
Undergraduate 8 Para-‐Photocycloaddition of 2-‐Pyridone to Substituted Benzenes Michal Glogowski, Darius Vrubliauskas Depertment of Chemistry, Temple University Ultraviolet mediated formation of complex ring structures from aromatic substrates has been long known dating back to the case of anthracene [4? + 4?] photocycloaddition. Since the initial observation, the ability of various tethered arenes (benzene, naphthalene, anthracene) to undergo such forward and reverse reactions has been investigated in the context of synthetic applications as well as those of photonic devices, optical switches, lithographic patterning, and imaging processes. Dr. Sieburth’s group has previously demonstrated that tethered pyridone substrates are also capable of singlet mediated intramolecular formation of biplanamers. Since these para-‐ photocycloadducts contain eight-‐membered carbocyclic rings, they can potentially be utilized as intermediates en route to a variety of otherwise synthetically challenging natural products. We hypothesize that a correlation can be established between substituted benzene-‐pyridone substrates and their reactivity and selectivity for various photocycloaddition products.
Undergraduate 9 Using “POGIL” as an Effective Teaching and Learning Strategy for General Chemistry Devin Morse Dr. Daniel King In today’s exponentially expanding world knowledge it has become our responsibility to ensure that students are prepared them for the increasingly competitive global market by equipping with the knowledge and higher-‐order thinking skills necessary to be lifelong learners. The attempt of Process Oriented Guided Inquiry Learning is to bring a student-‐centered teaching strategy to classrooms. This strategy uses guided inquiry activities to develop processing skills and focus on subjects? core concepts which encourage a deeper understanding of course materials. This study focuses on 25 first year students enrolled in a General Chemistry II. Throughout the duration of this course the students covered a multitude of topics some of which had corresponding POGIL activities and quizzes. 3 exams were also administered, which included material covered with and without POGIL. The performance on POGIL and non-‐POGIL topics of each student was anonymously collected and analyzed to find trends in students’ learning. Undergraduate 10 Studies on The Acid Catalyzed Rearrangement of Cyclic Sulfonanilides to Sulfones Susan Jones, Katherine Harrigan, James R. McKee, Murray Zanger University of the Sciences In our laboratories we have previously observed that sulfonamides can be rearranged to amino sulfones in the presence of strong acids, such as triflic acid. We were curious to see if the same reaction would take place if the amide were part of ring (sultam). Accordingly, 6-‐methyl-‐6H-‐dibenzo[c,e][1,2]thiazine-‐5,5-‐dioxide was prepared. Rearrangement of this compound would provide a novel amino benzothiophene dioxide, generating a new synthesis of a class of compounds that have shown strong anti-‐plasmodium activity. These new agents will be particularly beneficial to immunodeficient individuals, particularly those suffering with HIV. Undergraduate 11 Molecular Simulations Predict Conformational Pre-‐Organization in Cyclic RGD Peptides Amanda Wakefield, Vincent Voelz, P.h.D. Temple University Department of Chemistry To test the ability of molecular simulations to accurately predict the solution-‐state conformational properties of peptidomimetics, we examined a test set of 18 cyclic RGD peptides selected from the literature, including the anti-‐cancer drug candidate cilengitide, whose favorable binding affinity to integrin has been ascribed to its pre-‐
organization in solution. For each design, we performed all-‐atom replica-‐exchange molecular dynamics (REMD) simulations over several microseconds, and compared the results to extensive published NMR data. We find excellent agreement with experimental NOE distance restraints, suggesting that molecular simulation can be a useful tool for the computational design of pre-‐organized solution-‐state structure. Moreover, our analysis of conformational populations estimates that, despite the potential for increased flexibility due to backbone amide isomerizaton, N-‐
methylation provides about 0.5 kcal/mol of reduced conformational entropy to cyclic RGD peptides. The combination of pre-‐organization and binding-‐site compatibility explains the strong binding affinity of cilengitide to integrin.
Undergraduate 12 THE ROLE OF PV WORK ON LIMITING THE SOLUBILITIES OF THE HIGHER HOMOLOGS OF THE DIACIDS, PLUS INTERPRETATIONS ON “SALTING IN” AND “SALTING OUT” EFFECTS. Daniel Kogan, Dr. Robert Przeslawski Temple University The excess molar volumes of the diacids, C2-‐C5, were obtained in distilled water at 298.15 K. A linear trend was obtained in comparing each acid with its number of methylene groups, (-‐CH2-‐)n. This molar volume was found to be 22.5 cm3 mole-‐1 of ?CH2-‐. The molar volumes of the solid diacids also have a linear increase when compared to the number of ?CH2-‐ groups. The difference between the solid and solution molar volumes show the molar volume of the ?CH2-‐ group increases by 7.88 cm3 mole-‐1. When converted to P?V work an energy of 7980 J mole-‐1 resulted. Since diacid enthapies of solution are also linear, the enthalpies were compared against the number of methylene groups. The result yielded 8869 J mole-‐1 of CH2-‐ indicating that the insolubilities of the higher homologs were due principally to loss of energy of dissolving due to energy expended as PV work. In addition it was found that, salting out substances such as NaCl increased the excess molar volumes. This is greater energy expended as PV work which lowers solubility, showing that the two processes are enthalpy driven . Undergraduate 13 Oxidative Cleavage of Pyrolytic Lignin using Transition Metal Catalysts Amy Lai, Dr. Nathan M. West USDA Agricultural Research Service Lignin is the second most abundant natural polymer, found as part of the lignocellulosic biomass of plant cell walls. Its native structure consists of rich and diverse aromatic compounds, which makes lignin a potential source for renewable chemicals and fuels. Fast pyrolysis of switchgrass can produces crude pyrolysis oil that contains high molecular weight lignin. We report here the catalytic cleavage of pyrolytic lignin into smaller monomers with homogeneous transition metal compounds. We have investigated a variety of manganese, copper, vanadium, and iron complexes for their ability to reduce the molecular weight of lignin samples and produce volatile aromatic products. We have also investigated how different degradation conditions, such as solvents, temperatures and additives, affected the yield and products. Comparison to lignin model compounds provides insight into the reaction mechanisms.
Undergraduate 14 Palladium Nanoparticle-‐Catalyzed Carbon-‐Carbon Coupling Reaction: The Influence of Stabilizers and UV Irradiation. Zachery Custer, Nicholas Fales, Joon-‐Seo Park Department of Chemistry, Eastern University, St. Davids, PA 19087-‐3696 The Suzuki-‐Miyaura carbon-‐carbon coupling reaction has useful applications in the production of pharmaceuticals, natural products, polymers, and organic materials. Catalyzing the reaction with palladium nanoparticles has been of interest due to their recyclability, high surface area to volume ratio, and low degree of toxicity when compared with molecular palladium or conventional heterogeneous catalysts. This study investigated the stability and the catalytic activity of palladium nanoparticles surrounded by four different stabilizers. It sought to investigate the percent yields and kinetics of the Suzuki-‐Miyaura reaction at room temperature, with heating under reflux, and under UV irradiation. The reaction progress was monitored by gas chromatography and the coupling product was confirmed using GC-‐MS, NMR, and IR. The stability and catalytic activity of palladium nanoparticles were greatly influenced by the nature of stabilizers. Under the established optimum condition, the percent yield of the coupling reaction was over 99%. The results can be applied to develop an improved strategy for carbon-‐carbon coupling based on green chemistry through source reduction and pollution prevention. Undergraduate 15 The Effects of Synthesized and Surface-‐Modified Gold Nanoparticles on Daphnia Diana Perry, Karin Mattsson, Tommy Cedervall, Karin S. Akerfeldt Department of Chemistry, Haverford College, Haverford, PA 19041, Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden, Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden, Department of Chemistry, Haverford College, Haverford, PA 19041 Gold nanoparticles (AuNPs) are increasingly used in various technologies, diagnostic procedures, and therapies. While these particles are becoming more commonplace, their impact on the environment and the health of organisms is still not fully understood. Our goals with this study were to (1) synthesize particles of specific size and minimal size range, (2) modify them covalently with different groups, and (3) study their impact on the health of Daphnia. To achieve these goals, various existing synthetic protocols were tested in which the chemical reduction of HAuCl4 by citrate was found to be most reproducible. These AuNPs were then surface-‐modified with chemicals of specific charge or with different proteins containing at least one cysteine. Each set of AuNPs was tested on Daphnia magna and monitored over time to observe effects on health and longevity. Each set of particles (neutral, positively-‐charged, negatively-‐charged, and protein conjugated) was found to display little effect at low concentrations. At higher concentrations, the positively charged AuNPs showed the greatest impact on the Daphnia. Undergraduate 16 Crystallization Studies of Calmodulin Binding Targets Abigail Healy, Jennifer Willemsen, Katrina Nayak, Janina Sprenger, Roger Rowlett, Birgitta Frohm, Sara Linse, KarinÊ_kerfeldt Haverford College, Lunds Universitet, Colgate University *contributed equally to this project Department of Chemistry, Haverford College, Haverford, PA 19041, US.| Department of Biochemistry and Structural Biology, Lund Department of Chemistry, Colgate University, Hamilton, NY 13346, US. In a recent scientific study, 70 new calmodulin (CaM) binding targets have been identified in human brain. For this research project, peptides corresponding to the CaM binding portion of a number of these targets, including, LAT1, RPS2, STIM1, CaMkv, and Rab11b, have been synthesized and purified. The ultimate aim is to obtain an understanding of how CaM can regulate so many targets with such selectivity. Toward this goal we are collecting target binding data as well as structures of a range of peptides and proteins in complex with CaM using x-‐ray crystallography. The peptides described in this work have been synthesized using Fmoc solid peptide synthesis. This past summer, we optimized the crystallization conditions for a specific subset of these complexes. Diffraction data were obtained for CaM:LAT1 at the Max Lab synchrotron facility in Lund, Sweden. The data obtained was then refined at Colgate University, NY, employing the software, Refmac5, to furnish a crystal structure with a resolution of 2.1 _ and an R-‐factor of 25%. We will also present preliminary binding data of the LAT1 sequence bound to CaM, determined to be in the uM range, as obtained by isothermal titration calorimetry (ITC).
Undergraduate 17 Characterization of Lignocellulosic Biomass Fractionation Joshua Waters, David Salas-‐De La Cruz Rutgers University Department of Plant Biology and Pathology Lignocellulosic biomass is one of the most abundant energy-‐rich resources on the planet; however its full potential as a source for materials and biofuels remains hindered by high fractionation and pretreatment costs. Lignocellulose is a composite of cellulose, hemicellulose, and lignin that confers stability and rigidity to plant cell walls. The structural complexity that provides utility in cell walls hinders the fractionation of lignocellulose into its component resources. To understand the structural-‐thermal stability of lignocellulosic biomass various plant species were subjected to chemical treatments followed by thermal gravimetric analysis. Samples were treated with 0.2M and 0.6M acetone, ethanol, or chloroform to remove extractives such as waxes, or 10%, 25%, 50%, and 72% sulfuric acid to remove lignin and hemicellulose. Treatment with small organics resulted in increased thermal stability, with increases in the temperatures required for onset of decomposition, and maximum degradation, along with increased weight% loss. Sulfuric acid treatment, on the other hand, significantly decreased temperatures for onset of decomposition and isolated distinct decomposition events, due to delignification and removal of hemicellulose.
Undergraduate 18 The Synthesis of New Precursors to Pentacyclo[4.3.0.02,4.03,8.05,7]non-‐4-‐ene Dr. Mark Forman, April Savarese, Casey Adams, Rachel Troxel, Stephanie Schallenhammer, DJ Walz Saint Joseph's University We have previously shown that pentacyclo[4.3.0.02,4.03,8.05,7]non-‐4-‐ene may be generated via dehalogenation of 4,5-‐diiodopentacyclo[4.3.0.02,4.03,8.05,7]nonane alkyllithiums. The pyramidalized alkene product of this reaction may be trapped as its Diels-‐Alder adduct with diphenylisobenzofuran and other conjugated dienes. More recently, we have been investigating new methods for the synthesis of 4,5-‐
diiodopentacyclo[4.3.0.02,4.03,8.05,7]nonane as well alternative approaches toward pentacyclo[4.3.0.02,4.03,8.05,7]non-‐4-‐ene, and we will report our progress in this area.
Undergraduate 19 A Study in Semenogelin I Hydrogel Kinetics of Aggregation Beatrice Ary, Connie Friedman€, Matthew Rohn€, Birgitta Frohm, Luigi Gentile, Ulf Olsson, Sara Linse| and KarinÊ_kerfeldt Department of Chemistry, Haverford College, Haverford, PA 19041, US.; | Department of Biochemistry and Structural Biology, Lund University, S-‐22100 Lund, Sweden.; Department of Physical Chemistry 1, Lund University, 2-‐22100 Lund, Sweden. In earlier investigations, we have shown that a peptide sequence, Sg I 38-‐48, derived the protein human semenogelin I forms a hydrogel. In this work, we describe approaches to examine the kinetics of aggregation of both the Sg I 38-‐48 sequence and an extended sequence, Sg I 37-‐49. The kinetics experiments are based on using the chromophore Thioflavin T. When bound to extended ?-‐sheet fibrils the intensity of Thioflavin T fluorescence increases dramatically and this can be used to monitor fibril formation of the Sg I sequences. Fibril formation has been shown earlier by CD and IR spectroscopy to consist of extended b-‐sheets. In the kinetics experiments, the peptide is first isolated as a monomer employing gel filtration under acidic conditions when it does not form a fibril. The pH is then adjusted to pH 8 to trigger aggregation and the kinetics are monitored using a plate reader, with an excitation wavelength of 440 nm and monitoring the fluorescence emission at 480 nm. We have studied the effect of concentration, pH, and salt on the kinetics of aggregation. We have also carried out disc centrifugation studies in order to determine the size and homogeneity of the aggregates formed. The next step will be to fit our data to a mechanism. For this purpose we are using Global Fitter. We have also carried out rheology experiments in order to characterize the behavior of the Sg I 38-‐48 sequence, which have confirmed that this peptide forms a hydrogel. Undergraduate 20 Simulations of MDM2 and its complex with p53 yield insight into force field accuracy and conformational dynamics. George A Pantelopulos, Vincent A Voelz Institute for Computational Molecular Science The p53-‐MDM2 complex is both a major target for drug development and a valuable model system for computational predictions of protein and peptidomimetic binding. To investigate the accuracy of molecular simulations of MDM2 and its complex with p53, we performed a number of long (200 ns to 1 µs) explicit-‐solvent simulations using a range of force fields. We systematically compared nine popular force fields (AMBER ff03, ff12sb, ff14sb, ff99sb, ff99sb-‐ildn, ff99sb-‐ildn-‐nmr, ff99sb-‐ildn-‐phi, CHARMM22*, and CHARMM36) against experimental chemical shift data, and found similarly accurate results, with newer potentials CHARMM22* and ff14sb performing slightly better. Although the experimentally-‐determined apoÂ structure has closed binding cleft, simulations in all force fields suggest the apo state of MDM2 is highly flexible, and able to sample holo-‐like conformations, consistent with a conformational selection model. Initial structuring of the MDM2 lid region, known to competitively bind the binding cleft, is also observed in long simulations. Taken together, these results show molecular simulations can accurately sample conformations relevant for ligand binding. We expect this study to inform future computational work on folding and binding of MDM2 ligands.
Undergraduate 21 Expansion of the electrophile scope in the transition metal-‐catalyzed coupling of Corey-‐Seebach umpolung reagents Emily McKinstry, Summer Baker Dockery , Jason Schmink Haverford College, Bryn Mawr College The transition metal-‐catalyzed cross-‐coupling of aryl electrophiles (i.e. Br, Cl, OTf) with substituted Corey-‐Seebach umpolung reagents is described. Recently we disclosed the first examples of palladium-‐catalyzed cross-‐couplings of 2-‐aryl-‐1,3-‐
dithianes with aryl bromides. Wanting to increase the utility of the transformation, we now report the first use of aryl triflates as alternative electrophiles. Critical to expanding electrophile scope was the modification of our catalyst system. We found that the use of the third generation biphenyl Buchwald catalyst system engaged previously unreactive aryl triflates. The expanding reaction scope, our group's current mechanistic understanding, and future goals are presented. Undergraduate 22 Electronic and Structural Relationships in the Anomeric Effect William Bell , Whelton A. Miller III Lincoln University The anomeric effect describes the propensity for a substituent attached adjacent to the heteroatom in a heterocycle, to orient in an axial position rather than the less sterically hindered equatorial position. The exact method by which this stabilization occurs is still a point of controversy. The goal of this study is to understand the intramolecular electrostatic forces and its relationship with geometry. We employed Density Functional Theory (DFT) to analyze the energy differences between structural isomers of six-‐atom heterocycles (tetrahydropyran, tetrahydrothiopyran, and piperdine) starting in either a chair or boat position, in order to investigate these structures and add clarity to this argument. Undergraduate 23 Free-‐standing MXene/Metal Oxide Composite Paper as a Flexible Anode for Li-‐
ion Batteries Michelle Torelli, Mengqiang Zhao, Yury Gogotsi Drexel Nanotechnology Institute Two-‐dimensional (2D) materials, such as graphene, are attractive candidates for energy storage devices due to their large areas of electrochemically-‐active surfaces. Recently, MXenes, a new family of 2D carbides discovered at Drexel University in 2011, have shown promise for electrodes in Lithium-‐ion batteries and supercapacitors. The goal of this study was to determine if a combination of MXenes, which have high metallic conductivity but moderate capacity, and oxides with high lithium storage capacity but poor conductivity may result in improved performance. Flexible and free-‐standing sandwich-‐like MXene/metal oxide papers were fabricated by vacuum filtration method. In these composites, the 1-‐nm thin flakes of Ti3C2-‐MXene provide superior conductivity, ensure mechanical integrity and flexibility, as well as some Li-‐ion storage capacity; the metal oxide (Co3O4) nanosheets serve as spacers between MXene flakes to improve the accessibility of electrolyte ions and provide additional capacity. The synergetic effect of the two materials leads to much improved performance compared to pure MXene or cobalt oxide. The sandwich-‐like MXene/Co3O4 paper electrodes containing alternation layers of carbide and oxide achieved a high reversible capacity of ~1200 mAh/g at 0.1C (10-‐hrs discharge), 4 times higher than commercial graphite anodes. This paper electrode also exhibited excellent rate performance and superior cycling stability. A highly stable capacitance around 500 mAh/g was retained for >1000 cycles at 1C rate (1-‐hr charge/discharge). This work provides a simple, scalable, and effective strategy for the fabrication of advanced electrode materials that can be used in wearable or structural electrochemical energy storage and conversion systems. Undergraduate 24 First examples of Pd-‐catalyzed cross-‐coupling of 2-‐aryl-‐1,3-‐dithianes Summer Baker Dockrey, Dr. Jason Schmink Bryn Mawr College The palladium-‐catalyzed cross-‐coupling of aryl electrophiles with substituted Corey-‐ Seebach umpolung reagents is described. For decades, the anions of 1,3-‐dithianes have been used as polarity-‐reversed nucleophiles, reacting with, for example, aldehydes, ketones, and primary and secondary alkyl halides. Recently, we disclosed the first examples using 1,3-‐dithianes as transmetalation reagents. To date we have used this new strategy to synthesize medically relevant motifs, including diaryl ketones and diarylmethanes. Throughout our investigations, we have unearthed some unexpected, mechanistically interesting variations on our initial findings when employing various surrogates for 1,3-‐dithianes. The expanding reaction scope, our group's current mechanistic understanding, and the current future goals are presented.
Undergraduate 25 Computational Signal, Image and 3D Analysis of Small Drug Molecule interactions with Anaplastic Lymphoma Kinase (ALK) Mutations Chance Barrett, Jehnae Linkins, Carl Richardson, William Bell, Vesna Zeljkovic, Whelton Miller, Uzoma "James" Chikwem Lincoln University For many years treatment of advanced or metastatic Non-‐Small-‐Cell Lung Cancer (NSCLC) and Neuroblastoma has utilized many chemotherapy regimens for patient care. This has offered up a host of possibly new molecularly targeted therapies. ALK inhibitors, in particular crizotinib, target abnormal kinase activity. However, due to several point mutations, for example ALK (L1196M) and ALK (C1156Y), some patients have developed crizotinib resistance. Therefore, a number of second-‐
generation ALK inhibitors are needed against both wild-‐type and mutated resistance ALK. Identifying theses principle interactions for rational drug design is critical to design of these second-‐generation compounds. One method is the use of shape similarity comparison methods, as well as identifying other similar aspects e.g. electrostatic potential. We hope to develop an alternative method using signal and imaging processing techniques to identify similar aspects of potentially active compounds, in particular their shape and orientation in the binding pocket. The goal of this study is to not only to understand the relationship between the various ALK mutations, their structure and function in the ligand protein interaction, but to recognize a potential pattern based on developed mathematical model using signal and image processing tools with the aim to understand those interactions.
Undergraduate 26 Shear Thickening Fluids for Extra-‐Vehicular Activity(EVA) Space Suit Application Jehnae Linkins, Norman J. Wagner Lincoln University, University of Delaware Astronauts and spaceships are frequently vulnerable to exposures such as micrometeorite and orbital debris (MMOD). Incisions and nicks of the EVA space suits retrofitted with shear thickening fluids (STFs) have been proved to offer exceptional defense against ballistic and puncture threats. It has been recommended to use the STF nanocomposites to expand the protection for the astronauts, space suits, MMOD shielding for the spaceships from tools or sharp edges, and abrasion from space dust. The STF moves like a liquid until an object strikes or agitates it forcefully; then it hardens in a few milliseconds. If there is a sudden impact of energy overwhelms the repulsive forces between particles, forming masses called Hydro clusters. When the energy stops the particles repel each other again and the solid substances become a liquid again. The fluid is a colloid that is made up of tiny particles suspended in a liquid. The particles repel each other slightly, so they float easily through the liquid without clumping together or settling at the bottom. Undergraduate 27 Photosensitization of Singlet Oxygen by Ruthenium(II) Polypyridyl Complexes for DNA Photocleavage Stephanie Yang, Kai Wang, Benjamin R. Williams, Sharon J.N. Burgmayer Bryn Mawr College Ruthenium polypyridyl complexes can intercalate double stranded DNA, inhibiting DNA replication and cell proliferation. These complexes can also photochemically induce DNA cleavage by damaging the genetic material of cells. These abilities affirm their potential use as antitumor agents, especially in the field of photodynamic therapy. In this study we report the photocleavage ability of a variety of ruthenium(II) pteridinyl complexes with varied substituents on the third bidentate ligand. Only complexes with a cleaved terminal pteridine ring (ring-‐open), for example, [Ru(bpy)2L-‐aap]2+ exhibit DNA photocleavage. Compounds were incubated with plasmid DNA for 2 hours and photocleavage ability was assessed using gel electrophoresis. The mechanism used to cleave DNA involves the photosensitization of singlet oxygen, as determined from experiments with reactive oxygen species inhibitors. Singlet oxygen quantum yields were obtained through spectroscopic studies conducted with the fluorescent probe 1,3-‐
diphenylisobenzofuran. Undergraduate 28 Photosensitization of Singlet Oxygen by Ruthenium(II) Polypyridyl Complexes for DNA Photocleavage Stephanie Yang, Kai Wang, Sharon J.N. Burgmayer, Benjamin R. Williams Bryn Mawr College Due to cisplatin?s popularity as an anticancer drug, researchers are becoming more and more interested in utilizing transition metal complexes as antitumor agents. One class of these compounds, ruthenium polypyridyl complexes, can intercalate double stranded DNA, inhibiting DNA replication and cell proliferation. These complexes can also photochemically induce DNA cleavage, damaging the genetic material of cells and inducing cell death. In the Burgmayer lab, we have synthesized a family of ruthenium(II) pteridinyl complexes with varied substituents on the third bidentate ligand. Only complexes with a cleaved terminal pteridine ring (ring-‐open) exhibit DNA photocleavage. Compounds were incubated with plasmid DNA for 2 hours and photocleavage ability was assessed using gel electrophoresis. The singlet oxygen sensitizing mechanism behind photocleavage was determined from experiments with reactive oxygen species inhibitors and anaerobic conditions. Singlet oxygen quantum yields of compounds were obtained through spectroscopic studies conducted with the fluorescent probe 1,3-‐diphenylisobenzofuran. GRADUATE POST-‐DOC
Graduate/Post Doc 29 Study of Use of Collagen Nanofibrils to Recover Ethanol Fuel Produced During the Fermentation of Biomass and Organic Waste. Snehanjani Shivakumar, AnnMarie Foglio, Gennaro Maffia Manhattan College The biggest impediment to the utilization of fermentation based alcohols such as ethanol and butanol as fuel is the cost of recovering the alcohols as the neat product. Water from fermentation must be removed conventionally with distillation and then additional means required to break the azeotrope. Collagen nanofibrils have the potential to replace this whole process. Collagen dispersions can be made biphasic. Additionally molecules such as ethanol will distribute unevenly between the two phases. This, therefore becomes the basis of a novel separation technology requiring only minimal energy. Collagen nanofibrils recovered via a patented process (US 660829) from waste bovine corium. When applied to aqueous ethanol streams, the collagen preferentially retains ethanol and rejects water. The entire process has minimal energy requirements. Large energy consumption and high capital expenditure has been the single most impediment to the use of ethanol as a fuel on a global basis.
Graduate/Post Doc 30 A Single Stereodynamic Center Modulates the Rate of Self-‐Assembly in a Biomolecular System Yitao Zhang, Roy M. Malamakal, David M. Chenoweth University of Pennsylvania Chirality is a property of asymmetry important to both chemical and biological systems. The simplest form of molecular chirality is a carbon atom with four different substituents arranged in a tetrahedral form. Understanding how molecular systems respond to perturbations in their chiral building blocks can provide insight into diverse areas, such as biomolecular self-‐assembly, drug design, and protein folding. While no previous report show the influence of replacing an asymmetric carton atom with a stereodynamic atom in a biomolecular system, we show a single C to N mutation in a triple-‐helical collagen model peptide leads to a higher order structure with similar thermal unfolding but dramatically different kinetic refolding behavior. Our results show how biopolymers of life would behave if one of their chirality center is not configurationally stable, and highlight the importance of chiral centers as pre-‐organizing elements for biomolecular assembly and functioning.
Graduate/Post Doc 31 Probing Influenza NS1A dimerization with the intention of discovering therapeutic targets David Rushmore, Daniel Olea, Salma Sheik, Melissa Neavear, Zachary Moorefield, Dr. John Tomsho Chemistry and Biochemistry Department University of the Sciences in Philadelphia The rapid evolution of viral resistance to modern medical treatments is a major public health concern. To combat resistant organisms, it is necessary to identify novel targets and active molecules. The influenza A virus is one infectious agent that builds resistance to new medicines annually. A potential target for treatment of influenza infections is Non-‐Structural protein 1 from strain A (NS1A). NS1A has important roles in the viral life cycle and is a main contributing factor to the pathogenicity of an influenza infection. The functions of NS1A are to suppress the cell innate immune response and interferon production, accomplished by the ED, and to regulate viral gene expression and replication, through RBD activity. NS1A is composed of two domains, the N-‐terminal RNA binding domain (RBD) and C-‐
terminal effector domain (ED), that are connected by a short and variable linker region. The activity of NS1A is dependent on protein-‐protein interactions, with either itself (homodimerization) or host cell proteins (heterodimerization). Currently there are limited druggable interactions known to involve NS1A or any molecules that target those interactions. Hypothesis: This research aims to develop novel inhibitors of NS1A dimerization with the intent of producing new drugs or drug leads and to further elucidate the interactions between NS1A and its individual domains. Aim 1: Investigate and characterize the dimerization of full length NS1A and its individual domains in a reverse two hybrid system (RTHS), Aim 2: Screen cyclic peptides libraries for inhibition of NS1A dimerization Aim 3: Elucidate binding coefficients of full length NS1A, individual domains, and any inhibitors by use of surface plasmid resonance or other quantitative analytical techniques. Graduate/Post Doc 32 Computational Study of Domain Registration of Lipid Rafts Nicolas Chen, Dr. Preston B. Moore University of the Sciences, Department of Chemistry and Biochemistry Lipid rafts are microdomains that contain lipids, cholesterol, and proteins. These self-‐assemblies are critical to membrane signaling and flux controlling across the membrane. Lipid rafts are used to study the penetration of virus since these microdomains could provide specific interaction upon viral entries. Lipid rafts are too small to be able to visualized directly using light diffraction method since the size of these microdomains are range from 10-‐200nm. Experiments have used synthetic diblock copolymers as model for lipid rafts to investigate raft registration. Synthetic polymers provide major advantage over phospholipid membrane such as being stable for months. In addition to experiments, molecular dynamics simulations could show detail interaction of raft registration in smaller time scale. We are studying raft registration using computational method. In detail, the formation of these microdomains are investigated. LAMMPS Molecular Dynamics Simulator is used in this project to calculate the dynamics of systems contain poly(acrylic acid)-‐(1,4)-‐polybutadiene (PAA-‐PBA) diblock copolymer as the constituent of a lipid bilayer. We show that simulations of diblock copolymers form rafts and that these structures do indeed register as in biological and model lipid systems. The goal of this project is to reveal the molecular driving force for raft formation and registration. With molecular understanding of the interaction, we could utilize and/or modify the function of these lipid rafts as platforms, possible preventing unwanted cellular interactions.
Graduate/Post Doc 33 Synthesis and characterization of a new ruthenium-‐based photolinker used to cage morpholinos Teresa Rapp, Julianne Griepenburg, Ivan Dmochowski Department of Chemistry, University of Pennsylvania Ruthenium polypyridyl complexes have been known to be photo-‐active for over 60 years. Over the years, chemists have noticed that in certain complexes, ligands are exchanged rapidly upon irradiation with light into the MLCT band, but this property has not been exploited until the past decade. Here, we apply this property of ruthenium bisbipyridine complexes for use as a photolinker, a molecule capable of linking two spatially distant parts of a macromolecule (such as a protein or a section of DNA) together, deactivating a previously active state. Upon irradiation, one ligand is exchanged with water, releasing the macromolecule back to its original, active form. In its first application, we generated a ruthenium-‐based photolinker containing two terminal alkyne groups, which were then ?clicked? to two ends of a morpholino using a Huisgen 3+2 Cu-‐mediated cycloaddition. This effectively deactivated the morpholino until irradiated in vivo. This light-‐mediated reaction at the ruthenium center was characterized in this work by 1H NMR, UV-‐Vis spectroscopy, and electrochemistry, and in vivo studies were performed using zebrafish (Danio rerio) to show its efficacy.
Graduate/Post Doc 34 Mechanism of Diastereoselective Encapsulation by Arylamide Foldamers: a Computational Investigation Marianne Wujcik, Dr. Ara Abramyan , Dr. Zhiwei Liu, Dr. Vojislava Pophristic Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, Philadelphia, PA 19104 Arylamide foldamers are synthetic polymers consisting of alternating aromatic and peptide units that fold into stable secondary structures in solution. They have a variety of applications in biochemistry, medicine, and material science. One promising application uses arylamide helices to encapsulate ligands and isolate them from the environment and has potential application in drug delivery. Recently Huc et al. synthesized foldamer capsules that diastereoselectively encapsulates tartaric acid and other small chiral molecules. Their studies have shown that the left handed helix prefers to bind the L-‐tartaric acid however, the mechanism is unknown. Using molecular dynamics (MD) simulations, we are investigating the stereoselective encapsulation of tartaric acid by examining the structure, interactions, and dynamics of the capsule/tartaric acid systems. The knowledge gained from this study will aid in the rational design of foldamer capsules. Graduate/Post Doc 35 ?Refine restraints first-‐modeling next? approach to improve trans-‐membrane protein modeling Rajan Chaudhari, Andrew Heim, Zhijun Li Department of Chemistry & Biochemistry, University of the Sciences, Philadelphia, PA 19104 G protein-‐coupled receptors (GPCRs) are the top ranked drug targets in pharmaceutical industry because of their ability to induce wide variety of cellular responses. Therefore, structural information of such drug targets plays important role in accelerating drug discovery process. Results from GPCR DOCK competitions indicate that homology modeling of GPCRs based on low sequence identity is still a major challenge. To tackle this problem, we developed ?refined restraints first -‐ modeling next? approach that extracts unique distance restraints from multiple templates and incorporates them into homology modeling process. This method was applied to improve modeling of human beta 2 adrenergic receptor based on low sequence identity templates of bovin rhodopsin (1u19) and human protease-‐
activated receptor 1 (3vw7). Results show improvement over standard single-‐
template and multiple-‐template methods in terms of generating low RMSD models. Our method is easy to implement and can be applied to all alpha helical trans-‐
membrane proteins. Graduate/Post Doc 36 Complex Columnar Self-‐Organization of Dendronized Core-‐Derivatized Naphthalene and Perylene Bisimide Electron-‐Acceptors Benjamin E. Partridge, Pawaret Leowanawat, Hao-‐Jan Sun, Mihai Peterca, Yu-‐Chun Wu, Emad Aqad, Mohammad R. Imam, Robert Graf, Hans W. Spiess, Xiangbing Zeng, Goran Ungar, Chain-‐Shu Hsu, Paul A. Heiney, Virgil Percec Department of Chemistry, University of Pennsylvania, Philadelphia, USA, Department of Physics and Astronomy, University of Pennsylvania, USA, Max-‐Planck Institute for Polymer Research, Mainz, Germany, Department of Materials Science and Engineering, University of Sheffield, UK, Department of Applied Chemistry, National Chiao Tung University, Taiwan Supramolecular assemblies of naphthalene bisimides (NBI) and perylene bisimides (PBI) have found utility in a diverse range of applications: as industrial pigments, as biological membrane mimics, and as n-‐type semiconductors of use in organic electronics, among others. However, the molecular arrangement of PBIs and NBIs in these assemblies is often poorly understood. Furthermore, the use of NBI and PBI derivatives in organic electronics is hampered by several issues, including sensitivity to air and moisture and inaccessibly high melting temperatures. Here we report the synthesis of a range of NBI and PBI molecules functionalized with electron-‐withdrawing moieties at their core and with self-‐assembling dendrons at their termini. These molecules self-‐organize into a variety of columnar 2D and 3D phases which were investigated by a rigorous structural analysis methodology including variable rate differential scanning calorimetry, fiber and powder X-‐ray diffraction and solid state NMR studies. This analysis elaborated several concepts for the self-‐organization of NBI and PBI derivatives, which will find utility in supramolecular chemistry, materials science and organic electronics.
Graduate/Post Doc 37 HIGH-‐THROUGHPUT SCREENING OF NATURAL PRODUCT EXTRACTS FOR INHIBITORS SELECTIVE TO MYCOBACTERIAL PROTEASOMES Amber Gunderwala, John Porter Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, Department of Biological Sciences, University of the Sciences in Philadelphia Tuberculosis, caused by the pathogen Mycobacterium tuberculosis (Mtb), causes 1.3 million deaths annually. Mtb is successful in establishing latent infections in humans due to its ability to resist eradication by the immune system. The mycobacterial proteasome plays an important role in the defense mechanism of Mtb. We have investigated fluorescence and luminescence assays as potential screening methods to determine their respective robustness and repeatability for use in screening natural product extracts as Mtb proteasome inhibitors. The goal of this project is to develop and validate the luminescence assay as a novel method to screen proteasome inhibitors. We have also characterized the enzyme-‐inhibitor interaction using Epoxomicin, a known proteasome inhibitor. This will help in characterizing inhibitors obtained from the screening. The luminescence and fluorescence assays have been used to screen a small set of plant test extracts. The fluorescence assay is subject to interference by the natural fluorescence of compounds in many of the extracts; the luminescence approach is free of this interference. Luminescence is the more suitable assay for screening natural product extracts for proteasomal activities. Graduate/Post Doc 38 Structure Property Relationships of Carbohydrates-‐Protein Composite Films John Stanton, Ashley Lewis, Joshua C. Waters, Darrel Cowan, Xiao Hu, David Salas-‐De La Cruz Department of Chemistry, Rutgers Camden University, Camden, NJ, USA, Department of Biology, Rutgers Camden University, Camden, NJ, USA , Department of Physics and Astronomy, Department of Biomedical and Translational Sciences, Rowan University, Glassboro, NJ 08028, USA Biomass polymeric films can be used in a number of different ways, especially in the medical field and energy sector. Using carbohydrates and proteins as biomaterials for 3D printing will lead to the fabrication of artificial tissues, organs, and coating for implants in the future. In this study, Ionic Liquid (IL) is used to dissolve the polymer blend and make the biofilms composite. IL as a solvent is reusable, making it cost effective. Here, cellulose represents the carbohydrate material component and Mori silk represents the protein material component in the composite. The 1-‐Allyl-‐3-‐
methylimidazolium chloride (AMIMCl) is used as the IL solvent to form a 10% silk-‐
cellulose IL solution. Final films with different ratios of silk contents, ranging from 10% to 90%, in the composite film were evaluated. The results showed complete dissolution of the cellulose and protein materials into the ionic liquids. Upon coagulation and drying, the carbohydrate-‐based films were evaluated by FTIR, SEM, DSC and TGA. The FTIR results provided evidence of homogenous blending of the two materials. The peaks of silk protein beta-‐sheet crystalline shifted to a higher band, which indicates a change in the morphological structure from a crystalline structure to an amorphous structure due to the addition of cellulose. Furthermore, FTIR data also demonstrated that the functionalized groups of ionic liquid have connected with the blended structure during the mixing process. SEM data confirmed that the surface topology of the blends changed gradually with the change in the Mori silk content. The data also provided evidence of possible topological changes from an amorphous arrangement to a cylindrical-‐type formation at a lower content of silk (~30%-‐50%). It is seen that at 70% of silk, the surface remains amorphous, but as it goes towards 50%, a more uniformed cylindrical formation can be observed. This is critical as it provides possible evidence of intermolecular structural interactions between silk and cellulose at different mixing ratios. The possible structural changes were also observed as the decomposition temperature changed as a function of silk percentage. The TGA results showed a reduction of the decomposition temperature as compared to pure microcrystalline cellulose and silk films. This indicated that the heat transfer coefficient increased as the percent silk decreased. The different results provided evidence of a possible path to control the structure-‐property relations of carbohydrate-‐protein films. In the near future, we will determine if this stable structure in carbohydrate-‐protein composites is a crucial variable in controlling material properties that will result in optimal strategy for 3D printing using these composite materials.
Graduate/Post Doc 39 Transition metal catalyzed lignin oxidative cleavage Michael Fortin, Courtney, Vander Pyl, Joey Harmon, Amy Lai, Jeremy Schmoyer University of the Sciences, United States Department of Agriculture The application of novel catalytic design is necessary to extent the usefulness of lignin in biorefinery applications for generating energy and useful chemicals. We are isolating and studying the altered structure of the pyrolytic lignins introduced by the first step of converting switchgrass (Panicum virgatum) into bio-‐oil and thoroughly characterized. We are developing oxidation catalysts based on Mn, Fe, and Cu to cleave these oligomers into monomers. The inspiration comes from bacterial and fungal metalloenzymes which contain these metals and can actually breakdown lignin. A variety of schiff base ligand fragments have been employed to optimize the cleavage reaction. Substituted arenes, such as vanillin and guaiacol derivatives can be formed from the pyrolytic lignins. The effect of coreagents, such as TEMPO + linoleic acid, on the oxidation reactions will be reported.
Graduate/Post Doc 40 Molybdenum Pyranopterin Dithiolene Complexes: Synthetic Models for Pyran Cyclization in the Molybdenum Cofactor Douglas Gisewhite, Benjamin Williams, Sharon Burgmayer Bryn Mawr College The molybdenum cofactor, Moco, is found in all living organisms, excluding Saccharomyces cerevisiae, and participates in global nitrogen, carbon, and sulfur cycles. There is a conserved pterin dithiolene ligand which coordinates molybdenum (Mo) in the cofactor of mononuclear enzymes. Crystal structures of several bacterial molybdoenzymes suggest the pterin dithiolene ligand can exist in both a tricyclic and a bicyclic state. Interconversion of the two states has been thought to play a role in the catalytic mechanism of Moco. Therefore, understanding the pyran cyclization and scission, a type of ring-‐chain tautomerism, is an important aspect of study to understand its role in catalysis. Here, we report the synthesis and characterization of two Moco model complexes with the formula [TEA][Tp*Mo(X)pterin-‐CR2OH-‐dithiolene] where TEA is tetraethylammonium, Tp* is tris(3,5-‐dimethylpyrazolyl)hydroborate, Mo is in either the Mo(IV) or Mo(V) oxidation state, X is either sulfur or oxygen, and R is either methyl or ethyl. 1H and 13C NMR experiments indicate the hydroxyl group undergoes reversible intramolecular cyclization producing a pyran ring, which is dependent on solvent dielectric constant. Cyclization of the pyran ring is favored as solvent polarity increases.
Graduate/Post Doc 41 Understanding selectivity of Na+/K+ -‐ATPase for Na+ and K+ ions by computational approach Asghar Razavi, Lucie Delemotte, Vincenzo Carnevale, Vincent Voelz Temple University Na+/K+-‐ATPase (NKA) is a membrane protein that transports Na+ ions out of cell and brings K+ ions inside the cell against their concentration gradient. High selectivity of NKA for Na+ or K+ can be explained either by different affinity of binding sites or by kinetic barriers before reaching the ions to the binding sites or both. Understanding the exact location of binding sites is the first step in determining roots of selectivity in NKA. Molecular dynamics (MD) simulations with intrinsic atomic resolutions can be very useful to determine exact location of binding sites. We used MD metadynamics simulations as a first step towards achieving this goal and we show that the exact location of binding sites depends on protonation state of the binding residues. We also show that the thermodynamic affinity is highly controlled by protonation state of the binding residues and the same binding residues have different protonation state in sodium or potassium occluded states. Furthermore, free energy perturbation (FEP) calculations confirm importance of binding sites affinity in selectivity of the NKA. We also use FEP calculations to investigate the importance of cooperative binding in Na or K states. Graduate/Post Doc 42 Synthesis of Non-‐Hydrolyzable C-‐di-‐GMP Analogs Madison Fletcher, Kyle Knouse, Alex Koval, Claire Burns-‐Lynch Temple University Recently, the role of signaling molecules in bacteria, specifically c-‐di-‐GMP and c-‐di-‐
AMP has become increasingly important to the scientific community. Although found in very low concentrations within bacteria, they play a distinct and vital role in many cellular processes. One pathway regulated by c-‐di-‐GMP of significant importance to both the scientific and general community is that of biofilm formation. The regulation of bacterial biofilms is concentration dependent, with a certain threshold needed to both begin formation as well as for its degradation. However, while parts of the pathway have been elucidated, much of it has not been due to the lack of amenable probes for in vivo studies. Current analogs used for the investigation of this pathway have featured modifications to the phosphate linkage in attempts to make it less hydrolyzable, however, to date these analogs have not been water soluble, limiting them to in vitro investigations only. We propose that by replacing the phosphate linkage entirely we can increase water solubility and to date have pursued a total synthesis of five compounds with varied linkages as well as structural modifications to the sugar backbone. The total synthesis of these compounds are reported. Graduate/Post Doc 43 Total Synthesis of ( ? )-‐Leucoridine A and ( ? )-‐Leucoridine C Praveen Kokkonda, Keaon Brown, Shivaiah Vaddypally, Michael J. Zdilla, Rodrigo B. Andrade Department of Chemistry, Temple University We report the first asymmetric total synthesis of Strychnos-‐Strychnos type bisindole alkaloids, (?)-‐leucoridine A and (?)-‐leucoridine C, complex Strychnos-‐
Strychnos type of bisindole alkaloids isolated from the stem-‐bark extract of leuconotis griffithii in 2010. Key steps involve a late-‐stage trifluoroacetic acid mediated one-‐pot elimination/dimerization sequence of natural product (?)-‐1, 2-‐
dehydrogeissoschizoline, hydrochloric acid mediated hydrolytic cleavage of N-‐1-‐C-‐2 linkage in (?)-‐leucoridine A to (?)-‐leucoridine C, Pb(OAc)4 mediated oxidation of indoline to indolenine, and our previously reported one-‐pot method to prepare the ABCE tetracycle.
Graduate/Post Doc 44 Progress towards Determining the Binding Site of Alstolucine Natural Products to ABCC10 Christiana N. Teijaro, Surendrachary Munagala, Ekaterina V. Malofeeva, Elizabeth Hopper-‐Borge, Rodrigo B. Andrade Temple University, Fox Chase Cancer Center ATP-‐Binding Cassette (ABC) efflux pumps and their over expression plays an important role in multidrug resistant cancers. Inhibition of these proteins and attendant resensitization to chemotherapeutic agents present a promising strategy for the treatment of cancer. In collaboration with Elizabeth Hopper-‐Borge at Fox Chase Cancer Center we have synthesized and tested alstolucine natural products and found that alstolucine B and F inhibit ABCC10 ATPase activity at 12.5 ?M without modulating P-‐gp function. Furthermore, we found that alstolucine B and F resensitized ABCC10-‐transfected cell lines to paciltaxel at 10 ?M. Recently, we have synthesized photo labeled analogs of alstolucines B and in due course hope to elucidate their binding site to ABCC10.
Graduate/Post Doc 45 Contributions of Reactive Oxygen Species (ROS) from Nrf2 Activators to Nrf2/ARE Activation Bradly Bauman, Nicholas Janigian, Zachary Kemmerer, Aimee Eggler Villanova University The transcription factor Nrf2 is a promising target for therapies treating chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Increasing interest in this target is due in part to its activation by bioactive compounds from edible, plant-‐based sources, known as phytochemicals. Upon activation, Nrf2 is responsible for the upregulation of a variety of detoxification and cytoprotective proteins. However, activation by these compounds, broadly classed as Nrf2 activators, is not entirely understood. Controversy exists over the role reactive oxygen species (ROS) play in the activation of Nrf2 by various small molecules. Typical Nrf2 activation by a given compound occurs via an electrophilic moiety modifying reactive cysteines within Keap1, the repressor protein of Nrf2. This modification allows Nrf2 to accumulate and bind to the antioxidant response element (ARE) within target genes. Our research suggests that chemicals capable of both being electrophiles and generating ROS may not only work via electrophilic modification of Keap1, but that the ROS may act in a synergistic manner to enhance Nrf2/ARE activation. Graduate/Post Doc 46 Boronic Acid Analogs of Anti-‐HIV Therapies Sarah J. Burke, James M. Gamrat, John W. Tomsho University of the Sciences Boronic acids and their derivatives have recently emerged as biologically interesting moieties, with increased attention in their use as pharmaceutical agents. To date the FDA has approved two drugs containing boron atoms: Velcade¨, a peptidyl boronic acid treatment for multiple myeloma, and KerydinTM, an oxaborole-‐containing antifungal. The purpose of this work is to provide further insight into boronic acids as a medicinally relevant functional group, specifically as phosphate isosteres. To this end, we created a library of boronic acid analogs of nucleoside monophosphates and phosphonates for examination as antiviral agents. These analogs were synthesized through substitution reactions between nucleobases and boron-‐
containing alkyl halides, which were initially difficult to obtain. We therefore developed comparatively high yielding syntheses (65-‐92%) of potassium haloalkyltrifluoroborate salt electrophiles through hydroboration of commercially available haloalkenes with dichloroborane (prepared in situ from triethylsilane and boron trichloride), followed by treatment of the crude hydroboration products with potassium hydrogen difluoride. A hexaethyldisiloxane byproduct that hinders the isolation of boronic acids and esters was identified and easily removed in this procedure. Additional synthesis of a borono-‐tenofovir analog is currently underway, and soon biological evaluation of these compounds will be undertaken.
Graduate/Post Doc 47 Synthesis and Evaluation of Boronic Acid Analogues of Inhibitors of the Non-‐
mevalonate Isoprenoid Synthesis Pathway James M. Gamrat, Sarah J. Burke, Dylan Tomares, John W. Tomsho* University of the Sciences in Philadelphia With the increase in resistance of pathogens to common anti-‐infective agents, there is an urgent need to develop new classes of therapeutic molecules and discover new mechanisms of action to overcome this resistance. The non-‐mevalonate isoprenoid synthesis pathway (MEP pathway) is essential to the survival of a series of pathogens including Plasmodium falciparum and Mycobacterium tuberculosis. This pathway has emerged as an attractive therapeutic target for drug design since it is not present in the human body. A phosphonate-‐containing natural product, fosmidomycin, is the most potent inhibitor of the MEP pathway to date. Historically, the phosphonate moiety has been used to mimic the phosphate fragment of the natural substrates. The highly charged nature of this moiety hinders absorption and leads to poor pharmacokinetic properties thus fosmidomycin has found limited utility as a therapeutic agent. In an effort to overcome these issues, our work investigates the use of boronic acids as phosphate and phosphonate isosteres. Here we report the synthesis of a series of fosmidomycin analogues that will be assayed for inhibition of 1-‐deoxy-‐D-‐xylulose-‐5-‐phosphate reductoisomerase (IspC), of second step of the MEP pathway. Graduate/Post Doc 48 Synthesis of Dithioethers: Tandem Ring Opening and Cross-‐Coupling of Benzylic Dithianes Nissa Abidi, Jason R. Schmink Bryn Mawr College The tandem base-‐catalyzed elimination/ring-‐opening of 2-‐benzyl-‐1,3-‐dithianes with subsequent cross-‐coupling of the thiolate with a range of aryl bromides. A simple Pd(OAc)2/Xantphos system is employed and has a wide range in compatibility towards functional groups as well as heterocycles. The reaction proceeds stereoselectively favoring the E-‐alkene, in high yields. This transformation affords a previously undisclosed motif of a propyl-‐linked (E)-‐S-‐styryl/S-‐aryl dithioether
INDEX Poster # Last Name First Name Title 48 Abidi Nissa Synthesis of Dithioethers: Tandem Ring Opening and Cross-‐Coupling of Benzylic Dithianes 19 Ary Beatrice A Study in Semenogelin I Hydrogel Kinetics of Aggregation 24 Baker Dockrey Summer First examples of Pd-‐catalyzed cross-‐coupling of 2-‐aryl-‐1,3-‐dithianes 25 Barrett Chance Computational Signal, Image and 3D Analysis of Small Drug Molecule interactions with Anaplastic Lymphoma Kinase (ALK) Mutations 45 Bauman Bradly Contributions of Reactive Oxygen Species (ROS) from Nrf2 Activators to Nrf2/ARE Activation 46 Burke Sarah Boronic Acid Analogs of Anti-‐HIV Therapies 35 Chaudhari Rajan Refine restraints first-‐modeling next? approach to improve trans-‐membrane protein modeling 32 Chen Nicolas Computational Study of Domain Registration of Lipid Rafts 14 Custer Zachery Palladium Nanoparticle-‐Catalyzed Carbon-‐Carbon Coupling Reaction: The Influence of Stabilizers and UV Irradiation. 5 Davydovich Oleg Molecular Interactions of Dibucaine with Biological Membranes 42 Fletcher Madison Synthesis of Non-‐Hydrolyzable C-‐di-‐GMP Analogs 39 Fortin Michael Transition metal catalyzed lignin oxidative cleavage 47 Gamrat James 40 Gisewhite Douglas 8 Glogowski Michal Para-‐Photocycloaddition of 2-‐Pyridone to Substituted Benzenes 37 Gunderwala Amber HIGH-‐THROUGHPUT SCREENING OF NATURAL PRODUCT EXTRACTS FOR INHIBITORS SELECTIVE TO MYCOBACTERIAL PROTEASOMES 16 Healy Abigail Crystallization Studies of Calmodulin Binding Targets 4 Ho Brenda Determining the Amount of Caffeine and Theobromine In Dark Chocolates from Unique Sources in Africa 10 Jones Susan Studies on The Acid Catalyzed Rearrangement of Cyclic Sulfonanilides to Sulfones 12 Kogan Daniel The Role Of PV Work On Limiting The Solubilities Of The Higher Homologs of the Diacids, Plus Interpretations On "Salting In" And "Salting Out" Effects. 43 Kokkonda Praveen Total Synthesis of ( )-‐Leucoridine A and ( )-‐Leucoridine C 7 Kowal Elizabeth An Analysis of Carbendazim Found in Organic vs. Conventional Orange Juices 13 Lai Amy Oxidative Cleavage of Pyrolytic Lignin using Transition Metal Catalysts 6 Lewis Ashley Regenerated Tri-‐component Lignocellulose Bio-‐Films Using Ionic Liquids Synthesis and Evaluation of Boronic Acid Analogues of Inhibitors of the Non-‐mevalonate Isoprenoid Synthesis Pathway Molybdenum Pyranopterin Dithiolene Complexes: Synthetic Models for Pyran Cyclization in the Molybdenum Cofactor Poster # Last Name First Name Title 26 Linkins Jehnae Shear Thickening Fluids for Extra-‐Vehicular Activity(EVA) Space Suit Application 21 McKinstry Emily Expansion of the electrophile scope in the transition metal-‐catalyzed coupling of Corey-‐
Seebach umpolung reagents 22 Miller Whelton Electronic and Structural Relationships in the Anomeric Effect 9 Morse Devin Using "POGIL" as an Effective Teaching and Learning Strategy for General Chemistry 1 Olsen Jimmy Novel Chemistries in the Synthesis of Next Generation Antimalarials 20 Pantelopulos George 36 Partridge Benjamin 15 Perry Diana The Effects of Synthesized and Surface-‐Modified Gold Nanoparticles on Daphnia 33 Rapp Teresa Synthesis and characterization of a new ruthenium-‐based photolinker used to cage morpholinos 41 Razavi Asghar Understanding selectivity of Na+/K+ -‐ATPase for Na+ and K+ ions by computational approach 31 Rushmore David Probing Influenza NS1A dimerization with the intention of discovering therapeutic targets 18 Savarese April The Synthesis of New Precursors to Pentacyclo[4.3.0.02,4.03,8.05,7]non-‐4-‐ene 3 Serrano David Using Surface Sampling to Determine what is on Hamburger Meat 29 Shivakumar Snehanjani Study of Use of Collagen Nanofibrils to Recover Ethanol Fuel Produced During the Fermentation of Biomass and Organic Waste. 38 Stanton John Structure Property Relationships of Carbohydrates-‐Protein Composite Films 44 Teijaro Christiana Progress towards Determining the Binding Site of Alstolucine Natural Products to ABCC10 23 Torelli Michelle Free-‐standing MXene/Metal Oxide Composite Paper as a Flexible Anode for Li-‐ion Batteries 2 Vivar Betsy Effective methods for high yield protein production of LarC 11 Wakefield Amanda Molecular Simulations Predict Conformational Pre-‐Organization in Cyclic RGD Peptides 17 Waters Joshua Characterization of Lignocellulosic Biomass Fractionation 34 Wujcik Marianne 28 Yang Stephanie 30 Zhang Yitao Simulations of MDM2 and its complex with p53 yield insight into force field accuracy and conformational dynamics. Complex Columnar Self-‐Organization of Dendronized Core-‐Derivatized Naphthalene and Perylene Bisimide Electron-‐Acceptors Mechanism of Diastereoselective Encapsulation by Arylamide Foldamers: a Computational Investigation Photosensitization of Singlet Oxygen by Ruthenium(II) Polypyridyl Complexes for DNA Photocleavage A Single Stereodynamic Center Modulates the Rate of Self-‐Assembly in a Biomolecular System