Physical Science 2017

Synthesis of copper carboxylate complexes for decarboxylation |  Justin J. Steets, Aaron P. Honeycutt and Jessica M. Hoover 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045 

Decarboxylative coupling reactions are a green way to form C-C, C-N, C-O, C-S, and C-P bonds because the use of carboxylic acids as coupling partners eliminates the need for adding organometallic reagents to the reaction. The decarboxylation of a broad scope of carboxylic acids is made possible by using copper salts. Most transformations however require harsh conditions (up to 210°C) for the decarboxylation to occur. One way to get the reaction to run at lower temperatures and less harsh conditions is to synthesize different complexes with new ligands that enable that kind of reaction. Here, we report a new copper carboxylate complex bearing an electron-rich tripodal ligand. We hypothesize that this ligand will allow for lower temperature decarboxylation by stabilizing the copper aryl or copper alkyl intermediate. This presentation will focus on the synthesis and characterization of the copper carboxylate complexes as well as the preliminary results of the decarboxylation reactions. 

The DARTH laboratory reconnection experiment: scientific aims and diagnostic development |  Andrew J. Jemiolo and Earl E. Scime 

Department of Physics and Astronomy, West Virginia University, Morgantown, WV 26506 

Magnetic reconnection is the breaking of magnetic field lines and the consequent change in magnetic topology. During this process, there is a conversion of magnetic energy to kinetic and thermal energy when field lines of opposite polarity merge. Magnetic reconnection is responsible for several space plasma phenomenon, such as solar flares and coronal mass ejections, the aurorae on earth, and is an important process in thermonuclear fusion experiments. To experimentally test magnetic reconnection in a lab, we are constructing DARTH (Diagnosis of Acceleration, Reconnection, Turbulence, and Heating). A key aspect of DARTH is the extraordinary access for advanced diagnostics, including: laser-induced fluorescence (LIF), which is a non-perturbative method for measuring ion velocity distribution functions, a 300 GHz microwave scattering system for turbulence measurements, and a Thomson scattering diagnostic for electron velocity distribution function measurements. We will present our initial experimental designs and describe the state of the construction of the facility. 

Nickel catalyzed decarboxylative cross coupling reaction by a silver intermediate |  Sierra Ciccone and Jessica Hoover 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506 

Decarboxylative cross coupling reactions are an effective way of producing C-C bonds; therefore, they have broad applications in synthetic and medical chemistry. While copper and palladium catalyzed reactions have been well studied, nickel has recently become a metal of interest for being inexpensive and for its potential to work with a broader range of substrates. In this study, the decarboxylation step and the transmetalation have both been investigated. Thermal, nickel catalyzed, and silver catalyzed decarboxylation reactions were set up. It was observed that the rate of the thermal and nickel catalyzed decarboxylation were much slower than that of the silver catalyzed reaction. This data suggests that silver is responsible for catalyzing the loss of the carboxyl group while nickel has no significant chemistry here. To further investigate the cross coupling, the proposed silver aryl species by which the reaction is thought to proceed was synthesized. It is predicted that the desired product will be produced in yields comparable to that observed under optimized conditions, supporting the proposed mechanism involving the silver aryl intermediate. 

Gas phase kinetics of CH radical reactions with five-membered cyclic molecules |  Connor McCormick, Kacee L. Caster and Fabien Goulay 

C. Eugene Bennett Department of Chemistry, West Virginia University,  Morgantown, WV 26506-6045 

The reactions of CH radicals with unsaturated five-membered ring molecules are believed to proceed via cycloaddition across the double bond to form six-membered rings such as benzene and pyridine. The formation of these molecules is the first ring cyclization toward the formation of polycyclic aromatic hydrocarbons (PAH). PAHs are abundant in combustion environments and are the precursors to soot, an unwanted combustion by product. In these studies, CH radical reactions with five-membered ring molecules are investigated both experimentally and computationally. CH radicals are generated via pulsed laser photolysis (PLP) of bromoform (CHBr3) and are detected by laser-induced fluorescence (LIF). Pseudo-first order kinetics are used to determine the rate of reaction of CH radical with cyclopentadiene. Previous calculations using CBS-QB3 composite method suggest that the expected product of this reaction is benzene. Using Gaussian09 software and CBS-QB3 composite method, the reaction pathway of CH insertion and CH cycloaddition into pyrrole is also investigated with pyridine being the expected product. Further studies will investigate this reaction using the PLP/LIF method. 

Revisiting zirconocene complexes for use as molecular photosensitizers |  Megan Nally, Yu Zhang and Carsten Milsmann 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506 

Transition metal photosensitizers have been a prominent topic due to their importance in photovoltaic cells and photoredox catalysis. Currently available technology relies heavily on the use of precious metals, which limits the potential for large-scale applications due to the low abundance and high cost of the metal precursors. Earth abundant zirconium was chosen as a low-cost alternative to precious metals because cyclopentadienyl zirconium chalcogenolates have been reported to exhibit photoluminescent properties. However, these complexes lack the ability to undergo reversible electrochemical processes, which is a required property for solar energy conversion. Inspired by previous studies, we are trying to develop zirconium complexes with a mixed ligand system of cyclopentadienyl (Cp) and a redox non-innocent ligand, such as catecholate or benzenedithiolate. We hypothesized that the combination of these ligands would result in compounds with favorable optical and electrochemical properties for applications in solar energy conversion or photoredox chemistry. Despite several different synthetic strategies, our attempts to prepare Cp2Zr catecholate were unsuccessful due to uncontrolled pathways leading to complex product mixtures. The synthesis of Cp2Zr benzenedithiolate has proven to be clean and studies of its photophysical and electrochemical properties are currently underway. 

Assessment of the validity of duct tape end matches in forensic comparisons |  Aaron N. Brake, Meghan Prusinowski and Tatiana Trejos 

Forensic and Investigative Science, West Virginia University, Morgantown, WV 26506 

Forensic tape examinations can determine whether or not two items came from the same source. Typically, similarities in the chemical and physical features can provide class characteristics. However, the identification of a fracture match between two (or more) tape pieces has a stronger probative inference as it demonstrates they were once part of the same roll. These conclusions rely on the examiner’s opinion to identify distinctive features across the tape ends, hence the evaluation of the objectivity, validity and accuracy of such conclusions is a critical need. In this study, the occurrence of false positives and false negatives was investigated for 200 hand torn and scissor cut samples, and an approach was developed to qualify and quantify the observed features. Random numbers were assigned to create 1008 blind comparison pairs. The samples were examined independently by two examiners. Five level features were qualified to determine if the pair was a match, non-match or inconclusive. Accuracy of the conclusions was 99.6%, with 0% false positives and 1-2% false negatives depending on the analyst and separation method. 

How temperature affects the weathering of gasoline |  Isaac C. Willis and Glen P. Jackson 

Department of Forensic and Investigative Science and C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6121, USA 

Arson investigations are often influenced by identification of ignitable liquid residues (ILR) in fire debris. ILR analysis is most commonly achieved through headspace extraction, isolating vapors above the sample, followed by gas chromatography mass spectrometry (GC/MS). Previous research has shown that as ILs evaporate, or weather, the most volatile components evaporate first, resulting in a relative increase in concentration of the remaining substances. Recent work has shown that the temperature at which weathering occurs influences relative evaporation rates of different substances, and so, has a major effect on the distribution of weathered residues. This project will expand on the previous findings by evaporating a simplified synthetic mixture of gasoline in a quantitative manner at higher temperatures than has been previously reported. Current findings appear to corroborate the previous results and mathematical model, which show that a residue weathered to a high percent at a high temperature more closely resembles a residue weathered to a somewhat lower percent at room temperature. This contradicts traditional crime laboratory practices of comparing similar percent weathering, achieved at different temperatures. 

Mechanisms of the skunking process of beer introduced to light |  Sydney Giles, Olivia Pavlic, Pedram Tavazohi and James Lewis 

Department of Physics and Astronomy, West Virginia University, Morgantown, WV 26506 

Beer contains alpha acids, with the three most predominant ones being humulone, cohumulone, and adhumulone. During heating when brewing beer, the alpha acids are isomerized, leaving iso-humulone, iso-cohumulone, and iso-adhumulone in their places, with two stereoisomers for each. When exposed to ultraviolet light, each species reacts to form radicals via a Norrish type I alpha cleavage of their acyloin group. Radicals then react with sulfur-containing species in beer to produce 3-methyl-2-butene-1-thiol (MBT), also known as “skunky” thiol, the compound responsible for the undesirable smell and taste of “skunked” beer. Due to little evidence, the exact mechanism is unknown, with two possible pathways for the cleavage of the involved side chain. Using a local-orbit ab-initio tight binding molecular dynamics code, FIREBALL, we seek to simulate the photoreaction of each iso-alpha acid in order to determine the most likely cleavage pathway and the total time the photoreaction takes to occur. Preliminary results suggest that the cleavage of the acyloin group is most probable on the same side of the ketone as the hydroxyl group. 

Mild synthesis of novel boron-based pharmaceutical candidates by copper catalysis with CO 2 |  Natalie R. Ziemer and Brian V. Popp 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045 

For most people, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), such as Ibuprofen (Motrin®) and Naproxen (Aleve®), can be effective; however, for people with chronic pain, NSAIDs can cause gastrointestinal and rental issues if taken for an extended time. Recently the Popp group developed a new way to make the core of an NSAID that also allows the installation of boron. Boron-containing compounds are undeveloped and research in medicinal boron chemistry is promising in drug discovery. The group extracted the protocol to include several novel Bora-NSAIDs such fenoprofen. This was prepared in a two-step synthesis starting with the aldehyde precursor and phosphonium reagent which resulted in a vinyl group. Then, in a single reaction, the product was subjected to a copper catalysis forming new C-C and C-B bonds in perfect regioselectivity. The reactions proceed in good to excellent yields on a half gram scale. Further elaboration of the products were achieved through an electrophilic fluorination of the C-B bond as well as generation of a novel heterocycle salt in good yields. 

Adaptive biasing force simulations of the helix-coil transition of pH (low) insertion peptide |  Emily Ankrom and Blake Mertz 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506 

Developing a mechanism for targeted delivery of therapeutics to cancerous tissues and other sites of inflammation is a major aim of biomedical research. In an acidic environment, pH (low) insertion peptide (pHLIP) is able to bind and insert into cell bilayers to form a stable transmembrane α-helix. The acidity of inflammatory sites allows for pHLIP's binding and insertion properties to be exploited in developing a targeted drug delivery mechanism. The precise conformations of pHLIP in solution, during binding and during insertion must be revealed in order to optimize its ability to perform as a disease targeting agent. Molecular dynamics simulations of pHLIP in solution are employed to understand the energetics of these processes. To deduce the change in Gibbs free energy as pHLIP transitions from an α-helix to a random coil, Adaptive Biasing Force (ABF) simulations were performed. ABF simulations are advantageous because they allow for exploration of the free energy landscape of the coil-to-helix transition on timescales much faster than equilibrium molecular dynamics simulations. This reversible transition is one of the components of a proposed thermodynamic cycle used to characterize the function of pHLIP. Thus, we will be furthering our fundamental understanding of how pHLIP can be optimized for eventual clinical applications. 

Development of nanogel based protein characterization to diagnose and treat disease through bioanalytical separations |  Shannon M. Patberg, Corey Cleavenger, Cassandra Crihfield and Lisa Holland 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045 

Proteins are critical biomarkers that aid in the detection and diagnosis for the treatment of diseases such as cancer. Current methods such as the Western Blot are labor intensive with substantial preparations during each stage that engulf large amounts of time and resources, yielding inaccurate results. Using a newly developed method from the Holland Lab, proteins are easily analyzed within minutes through cost effective capillary electrophoresis methods with precise, rapid analysis. The proteins are sieved, a technique previously applied for DNA analysis. Sieving enables the instrument to separate in a size selective phospholipid nanogel and prevent protein absorption to the capillary wall. Through spiking studies of the dye, the validated method confirms the detection of proteins. The results allow for the compilation of an anionic and cationic protein library that allow for binding analysis with antibodies. These antibody-protein complexes are ultimately the technique that will allow for disease detection 

8-step synthesis of neoprofen a derivative of Ibuprofen |  Perez Youmbi, Paratchata Batsomboon, Alexa Martin, Harvey Fulo and Gregory Dudley 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045 

Neopentylene rings are found in most natural products but are lacking in pharmaceutical product. The focus of this research is to affectively synthesize neoprofen using a faster synthesis process than previous research. Neoprofen is a derivative of Ibuprofen, which is a well-known cyclooxygenase-2 (CO-2) inhibitor with the addition of a neopentylene ring. It was hypothesis that neoprofen would provide different interaction with COX-2 the enzyme responsible for inflammation and pain which would differ from Ibuprofen. The approach taken to synthesize neoprofen is an 8-step synthesis to neoprofen. The preliminary findings showed a percent yield greater than 85% in the first 7-steps of the synthesis. These results are slightly below the anticipated yield which was greater than 95%. The first 7 step worked perfectly with all reaction going to full completion. Overall, at the end of the research, we hope to have develop a faster efficient way to synthesize neopentylene into ibuprofen and eventually into different drugs. 

Lysine location within Alzheimer’s protein sequence reveals correlation to structure and membrane toxicity |  Morgan C. Nyman, Albert W. Pilkington, IV and Justin Legleiter 

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506 

Alzheimer’s disease is caused by the protein beta amyloid. This protein has a sequence that ranges from 40-42 amino acids in length and maintains a U-shaped structure containing beta sheets, a hydrophobic core, and a salt bridge. There are multiple proposed toxic mechanisms beta amyloid expresses to cause the symptoms of Alzheimer’s disease. This study specifically focuses on the mechanism involved with lipid membrane disruption, which causes cell death. Our current hypothesis claims that lysines are significant in the formation of the peptide and overall toxicity due to their specific location within the amino acid sequence of beta amyloid. In order to test their importance, the overall charge of the lysine was altered by incorporating different concentrations of the molecule sulfosuccinimidyl acetate, a process known as acetylation, in solutions with and without lipids. Preliminary results suggest an indirect relationship between the amount of acetylation and beta sheet formation as well as a shift in the lag phase in solutions without lipid. However, in solutions with lipid show only changes in lag phase. 

Progress toward total synthesis of marinoquinolines A-C |  Tanner M. Yawitz , Liberty Embacher , Katharine E. Lambson and Björn C.G. Söderberg  

Department of Chemistry, Saint Francis University, Loretto, PA 15940 and C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506 

The marinoquinoline family of compounds has potential to serve as medicines of the future. The marinoquinolines are a family of alkaloids that were isolated from a marine gliding bacteria, O. kribbensis, off the coast of the Korean peninsula. Preliminary results from the isolated group showed a variety of medicinal properties including antibacterial, anti-cancer, and anti-protozoal applications. The total synthesis of marinoquinolines A-C is being explored, and the proposed pathway includes such as reactions as base-catalyzed cyclizations, reductions, Grignard reactions, and palladium catalyzed cyclizations. Currently, both marinoquinolines A and C have been synthetically prepared; marinoquinoline B, however, has not yet been synthesized. The techniques and methodologies studied are expected to be applied to all three marinoquinoline derivatives, and if successful, all syntheses would feature a palladium-catalyzed reductive cyclization developed in the Söderberg lab as a key transformation. 

Optimization of confocal laser induced fluorescence with comparisons to conventional optics |  Miguel F. Henriquez, Derek S. Thompson, Andrew J. Jemiolo and Earl. E. Scime 

Department of Physics and Astronomy, West Virginia University, Morgantown, WV 26506 

Laser induced fluorescence (LIF) is the workhorse diagnostic for measuring ion and neutral particle velocities and temperatures in a plasma. The conventional method requires multiple intersecting optical access ports that are unavailable in many experiments or in plasmas contained by opaque walls. Confocal LIF, in which the injection and collection paths are concentric, eliminates the need for intersecting optical paths, allowing the diagnostic to be deployed through a single window or into channels with opaque walls. While confocal measurements at short distances are common, it has been a challenge to demonstrate high resolution at the focal lengths needed for many plasma experiments. We report optimized, confocal laser induced fluorescence measurements in a helicon plasma. These optimizations combined aberration mitigating optics with spatial filtering to achieve focal lengths that allow measurements deep within large vacuum vessels. We demonstrate comparable spatial resolution to the conventional method at a focal length of 0.5 m, multiple centimeters longer than previous tests of the diagnostic. The conclusions will compare data from conventional and confocal methods with insights from optical modeling.