American Chemical Society Cleveland Section

MEETING-IN-MINIATURE

PROGRAM

Oberlin College March 21, 2012

PROGRAM OVERVIEW

1

2:00 p.m. Registration, Commons, Science Center

3:00-5:00 p.m. Technical Sessions, Science Center

Analytical Chemistry Room A154 Page 7

Biochemistry Craig Lecture Hall Page 11

Inorganic and Materials Chemistry Room A155 Page 15

Organic Chemistry Room A254 Page 18

Physical and Biophysical Chemistry Room A255 Page 21

5:15-6:15 p.m. Plenary Address, Professor Sibrina N. Collins, Craig Lecture Hall

6:15-6:40 p.m. Social, Commons, Science Center

6:40 p.m. Dinner, followed by awards presentation, Commons, Science Center

JUDGES SESSION CHAIRS

Mekki Bayachou, Cleveland State University Peter Chivers, Oberlin College Jeff Mathys, Emerald Materials

Mike Nichols, John Carroll University Ken Street, NASA-GRC

Manish Mehta, Oberlin College Drew Meyer, Oberlin College

David Orosz, Notre Dame College Tony Pearson, Case Western Reserve Univ.

Sarah Preston, Ursuline College

The Cleveland Section of the ACS extends a special thanks to the following persons and organizations for their support for the 2012 Meeting In Miniature

Amalgamated Tuna Dwight Chasar

Department of Chemistry, Cleveland State University Energizer Corporation Lubrizol Corporation

Lily Ng

Elected Officers of the Cleveland Section of the American Chemical Society

Chair Kathleen Wollyung, Perkin Elmer Chair-Elect Donald Jaworske, NASA-GRC Treasurer John Moran, Notre Dame College Secretary Anna Bowman, Northeastern University Program Chair for 2012 Meeting-in-Miniature Catherine Oertel, Oberlin College !

TECHNICAL SESSIONS

2

* Denotes undergraduate student presenter ** Denotes graduate student presenter Analytical Chemistry Session, Room A154, Science Center Drew Meyer, Chair 3:00 p.m. Lipid Profiling in Algal Species, Scenedesmus dimorphus by Mass Spectrometry Satya Girish Avula1, ** Joanne Belovich2, Yan Xu1 1Department of Chemistry, Cleveland State University; 2Department of Chemical Engineering, Cleveland State University 3:15 p.m. Improved enzyme loading in layer-by-layer thin films of nitric oxide synthase and polyethylenimine; effect of pH on enzyme immobilization and activity Bhagya Gunasekera,** Mekki Bayachou Department of Chemistry, Cleveland State University 2399 Euclid Avenue Cleveland OH 44115 3:30 p.m. On-line Electrochemical Mass Spectrometry under Forced Convection Imre Treufeld,** Adriel Jacob Jebaraj, Jing Xu, Denis Martins de Godoi, Daniel Scherson Ernest B. Yeager Center for Electrochemical Sciences and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106-7078 3:45 p.m. Mass Spectroscopy: A Central Technology for Protein Analysis Sujatha Chilakala,** Yan Xu Department of Chemistry, Cleveland State University 4:00 p.m. Determination of Polymer Sequences and Architectures by Mass and Tandem Mass Spectrometry Aleer M. Yol1,** Jonathan E. Janoski2, Roderic P. Quirk2, Chrys Wesdemiotis1, 2 1Department of Chemistry and 2Department of Polymer Science, The University of Akron, Akron, OH 4:15 p.m. Determination of Triapine, a Potent Ribonucleotide Reductase Inhibitor, in Human Plasma by LC-MS/MS Ye Feng1,** and Yan Xu1,2 1Cleveland State University, Cleveland, OH; 2Case Comprehensive Cancer Center, Cleveland, OH Biochemistry Session, Craig Lecture Hall, Science Center David Orosz, Chair 3:00 p.m. The B Domain of Factor V: A Natural Hemostatic Regulator Joesph R. Wiencek1,** Jamila Hirbawi2, Mahesheema Na,1 Michael Kalafatis1,2,3 1Chemistry, Cleveland State University, Cleveland, OH., 2Molecular Cardiology, Cleveland Clinic, Cleveland, OH; 3Biological,Geological and Environmental Sciences, Cleveland State University 3:15 p.m. Site-specific Lipidation of Recombinant Thrombomodulin Lin Wang,** Rui Jiang, Jacob Weingart, Xue-long Sun Department of Chemistry, Cleveland State University 3:30 p.m. Controlling Recruitment of Transcriptional Complexes with Small Molecules Aaron Van Dyke1, Jonas Hjfeldt,3 Anna Mapp1,2 1 Department of Chemistry, 2Department of Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA; 3 Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark

TECHNICAL SESSIONS

3

3:45 p.m. Activity Analyses of Selective Sulfonamide Tubulin Inhibitors in African Trypanosomiasis Rati Lama1,** Bin Su1,2 1Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA; 2Center for Gene Regulation in Health and Disease, College of Sciences & Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, 4:00 p.m. Lectin Mimetics for Glyco-Capturing, Glycomics and Glycoproteomics Applications Poornima Pinnamaneni,** Satya Nandana Narla, Xue-Long Sun Cleveland State University, Cleveland, OH 44115 4:15 p.m. Cleavage at Arg1018 during Thrombin-Mediated Activation of Coagulation Factor V Is Dispensable Mahesheema Na1,** Joesph R Wiencek1, Jamila Hirbawi2, Michael Kalafatis1, 2, 3, 4 1Dept. of Chemistry, Cleveland State University, Cleveland, OH; 2Molecular Cardiology, Cleveland Clinic, Cleveland, OH; 3Molecular Cardiology, The Cleveland Clinic, Cleveland; 4Biological,Geological and Environmental Sciences, Cleveland State University 4:30 p.m. Synthesis and Evaluation of 5-Indole Acetic Acid Derivatives as Potential Chemotherapeutic Agents for Colon Cancer Snigdha Chennamaneni,** Bin Su Department of Chemistry, Cleveland State University 4:45 p.m. Oriented Immobilized Sialyloligo-Macroligand and Its Protein Binding Specificity Satya Nandana Narla,** Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115 Inorganic and Materials Chemistry Session, Room A155, Science Center

Sarah Preston, Chair 3:00 p.m. Synthesis and Photophysical Properties of Air-stable Benzoxaphospholes Shanshan Wu,** John D. Protasiewicz Department of Chemistry, Case Western Reserve University 3:15 p.m. Stereocontrolled Intramolecular Iron-mediated Diene/Olefin Cyclization Sheng Zhang,** Anthony J. Pearson Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 3:30 p.m. Phosphorus Containing Derivatives of Polyaniline David K. Hildebrandt,* Michael Rectenwald, John Protasiewicz Department of Chemistry, Case Western Reserve University, Cleveland, OH 3:45 p.m. DFT/QTAIM Analysis of Carbon Monoxide Chemisorption to Nickel(111) and Bimetallic Ni3X, Ni2X2 (X=Pd, Cu, Ag, Au) Clusters Peter C. Psarras,** David W. Ball Department of Chemistry, Cleveland State University, Cleveland, Ohio, 44115 4:00 p.m. Self-Doped Conjugated Polymers Containing Phosphorus Michael F. Rectenwald,** John D. Protasiewicz Department of Chemistry, Case Western Reserve University

TECHNICAL SESSIONS

4

4:15 p.m. Ion-Exchange Synthesis of Niobium and Tantalum Complex Oxides Liv R. Dedon,* Joshua T. Greenfield, Catherine M. Oertel Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 4:30 p.m. Bicyclic-borate Synthesis for Use in Lithium Ion Batteries Ryan Kowalski,* John Protasiewicz Department of Chemistry, Case Western Reserve University 4:45 p.m. Synthesis and Characterizations of Phosphorus-Containing Conjugated Materials Feng L. Laughlin,** Marlena P. Washington, Vittal B. Gudimetla, John D. Protasiewicz Chemistry Department, Case Western Reserve University Organic Chemistry Session, Room A254, Science Center Tony Pearson, Chair 3:00 p.m. Synthesis of Azidoethyl Sialylglycoside for Sialyl Glyco-macroligand Fabrication Jayasri Kakarla,** Jacob J. Weingart, Xue-Long Sun Department of Chemistry, Cleveland State University 3:15 p.m. Amine-catalyzed Nazarov cyclizations: A Computational Investigation Laura Ros,* Albert Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 3:30 p.m. Amine-Catalyzed Nazarov Cyclizations: Experimental Studies Joseph Hamilton,* Nathaniel Kadunce, Laura Rios, Albert Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin OH, 44074 3:45 p.m. Synthesis of Hexatriene-3-d1 for Use in High-Resolution Molecular Spectroscopy Yihui Chen,* Henrik Ehrhardt, William Gautier, Norman C. Craig, Albert R. Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 4:00 p.m. Alteration of Carbocyclic Core Skeleton of Bryonolic Acid - Employing DOS Strategy Vasily A. Ignatenko,** Gregory P. Tochtrop Department of Chemistry, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106 4:15 p.m. Synthesis of a Chiral Ionic Liquid Derived from (S)-Phenylalanine Christopher Barton,* Raymond J. Shively Department of Chemistry, Baldwin Wallace College 4:30 p.m. Development of N-Prolinylanthranilamide Pseudopeptides for Asymmetric Aldol Reactions Santanu Panda,** Anthony J. Pearson Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 4:45 p.m. Adventures in Haloorganic Chemistry: Synthesis of Selectively Deuterated 1,4-Difluorobutadiene Yuhua Lu,* Herman van Besien, Norman C. Craig Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074

TECHNICAL SESSIONS

5

Physical and Biophysical Chemistry Session, Room A255, Science Center Manish Mehta, Chair

3:00 p.m. Small Angle Neutron Scattering Study of the Structure of High Density Lipoprotein Celalettin Topbas 1,2,** Xavier Lee2, Stanley L. Hazen2,3,4, Valentin Gogonea1,2,3 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115; Departments of 2Cell Biology, 3Center for Cardiovascular Diagnostics and Prevention, and 4Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 3:15 p.m. The Structure of IKK/NEMO and its Role in the Assembly of the IkB Kinase Complex Carolina Parada 1,* Dmitriy Parshakov 1, Camelia Baleanu Gogonea1, Valentin Gogonea1,2 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 441154; 2Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 3:30 p.m. Gas Phase Oxidation Kinetics For Atmospheric Relevant Epoxied Intermediates Adam Darer,* Matthew J. Elrod Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074. 3:45 p.m. Immobilized Cell Membrane Mimetic System for Functional Analysis of Membrane Protein Valentinas Gruzdys,** Yong Ma, Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115 4:00 p.m. Solid-State NMR Study of Porous Dipeptides Benjamin Altheimer,* Manish Mehta Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 4:15 p.m. Molecular Modeling of LCAT, a Plasma Enzyme Involved in Reverse Cholesterol Transport Christopher Pechura1,* Valentin Gogonea1,2 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115; 2Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 4:30 p.m. Study of the Oligomerization Kinetics and Equilibria of 2-Methyl Glyceric Acid Adam W. Birdsall,* Cassandra A. Zentner, Matthew J. Elrod Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074. 4:45 p.m. Glyco-Functionalization of Liposomes and Their Stability Study Pratima Vabbilisetty,** Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115

PLENARY SESSION

6

African American Contributions to the Chemical Sciences

5:15 6:15 p.m., Craig Lecture Hall

Sibrina N. Collins Department of Chemistry, The College of Wooster, Wooster, Ohio

Why should we be concerned about minority contributions to the chemical sciences? By the year 2050, over 50% of the U.S. population will be underrepresented minorities. Thus, the STEM (science, technology, engineering, and mathematics) workforce must be truly reflective of these changing demographics. This presentation will discuss the scientific contributions of many African American chemists, including Saint Elmo Brady, the first African American to earn a PhD in chemistry; Marie Maynard Daly, the first African American woman to earn a PhD in chemistry; and Thomas Nelson Baker, Jr., a graduate of Oberlin College and presumably the first African American to earn a PhD in chemistry from The Ohio State University. Sibrina N. Collins is an assistant professor in the department of chemistry at the College of Wooster. She received her B.A. in chemistry from Wayne State University in 1994. She went on to The Ohio State University and received an M.S. in 1996 and a Ph.D. in 2000, both in inorganic chemistry. She was a postdoctoral researcher at Louisiana State University. Professor Collins professional experience prior to joining the Wooster faculty combined her interests in teaching and broadening participation in chemistry. She has served as editor of the Minority Scientists Network (MiSciNet), a publication of the American Association for the Advancement of Science in Washington, DC; NSF ROA Fellow at Furman University; visiting researcher in the Department of Chemistry at the University of Cincinnati; assistant professor at Claflin University in Orangeburg, SC; visiting assistant professor in the Department of Chemistry at The Ohio State University; and Director of Graduate Diversity Recruiting (STEM) at the University of Washington in Seattle. Professor Collins research interests include crystal engineering of metal-organic frameworks, nanoporous materials; inorganic photochemistry; inorganic synthesis; and the history of chemical sciences.

ANALYTICAL CHEMISTRY SESSION

7

3:00 p.m. Lipid Profiling in Algal Species, Scenedesmus dimorphus by Mass Spectrometry Satya Girish Avula1, ** Joanne Belovich2, Yan Xu1 1Department of Chemistry, Cleveland State University 2Department of Chemical Engineering, Cleveland State University As concern grows over the supply of fossil fuels (i.e., petroleum, natural gas, and coal, etc.), other sources of energy are being sought. Biodiesel from microalgae has been one of the frontiers. While the percentages of proteins, carbohydrates, and lipids vary from species to species, some algal species can store up to 40% of lipids of their dry masses. It is these lipids that can be extracted and converted to biofuels. In general, biological lipids can be divided into: fatty acids, neutral lipids (glycerolipids), polar lipids (glycerophospholipids, sphingolipids) and non-acyl lipids (saccharolipids, polyketides, sterol lipids, and prenol lipids). The aim of the study was to profile lipid classes present in the algal species Scenedesmus dimorphus under different growing conditions to understand the biochemistry of algae for maximizing lipid productivity. In this work, all lipid classes were first extracted from algae dry mass by Bligh-Dyer method, and then fractionated into individual classes by NH2 propyl cartridge with various solvents. Fatty acids and monoglyceride classes were qualitatively identified by both gas chromatography ion-trap mass spectrometry (GC-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). The GC-MS data showed that C-16 and C-18 fatty acids are the building blocks of the Neutral lipids, and the ESI-MS/MS data revealed that the acyl chain constituents involving the C-16 and C-18 fatty acids form the monoglycerides. Further, quantification of the identified lipids can be achieved by either or both mass spectrometric techniques. 3:15 p.m. Improved enzyme loading in layer-by-layer thin films of nitric oxide synthase and polyethylenimine; effect of pH on enzyme immobilization and activity Bhagya Gunasekera** and Mekki Bayachou Department of Chemistry, Cleveland State University 2399 Euclid Avenue Cleveland OH 44115 Layer-by-layer multi-component protein-polyelectrolyte films provide the opportunity to build nanometer-thick coatings with functional components such as enzymes. The possibility to include active enzymes in thin coatings enables the fabrication of coatings that are not only biocompatible but also are able to impart biological function to the surface. In this project, we investigate the layer-by-layer (LBL) adsorption of nitric oxide synthase (NOS) as the functional component and polyethylenimine (PEI) as the matrix on model surfaces. Our research has previously established that these films, when exposed to the ingredients of the NOS reaction, release fluxes of nitric oxide (NO). Since nitric oxide is a molecule proven to counteract platelet aggregation and the thrombosis cascade, our proposed NOS-containing functional films are expected to be good candidates as coatings for blood-contacting implants and other medical devices such as stents and catheters. At pH 7, polyethylenimine carries a net positive charge in solution versus a net negative charge carried by the NOS protein. In this work we examined if the pH of the protein medium, which affects the net surface charge on the protein in solution, can modulate the amount of NOS protein that can be adsorbed onto a PEI-coated surface. To this end, we used buffered NOS solutions and PEI solutions adjusted to desired pHs to investigate the charge-driven layer-by-layer adsorption. We used, Atomic Force Microscopy (AFM) to characterize the morphology of the outermost NOS layer. We also used the catalytic electro-reduction of nitric oxide by NOS in the films as a handle to monitor the integrity of the immobilized NOS enzymes under the various conditions. In terms of enzymatic function, we measured the cumulative NO release from the various films using the Griess assay. After a 72-hour window, we used chemical and physical means to recover the immobilized protein layers which we then quantified using Bradford assay. AFM imaging of the outermost NOS layer shows the enzyme in varying cluster densities representing the NOS layers on films incubated at pH 7 and pH 8.6. Griess assay results show an initial burst of NO through the first 12

ANALYTICAL CHEMISTRY SESSION

8

hours followed by a decline and then stable NO release up to 72 hours. Our data show that NO flux peaks through 4-8 hours. The NO flux values range from an average of 1.8mol.mm-2 for discs incubated with protein at pH 7 to 4mol.mm-2 for discs incubated with protein at pH 8.6. Overall, our results show that the pH of the NOS protein solution modulates the amount of NOS proteins ultimately immobilized in the LBL NOS-PEI film. We will discuss the implication of this finding in the optimization of NOS-based nanofilms as potential antithrombotic coatings. 3:30 p.m. On-line Electrochemical Mass Spectrometry under Forced Convection Imre Treufeld,** Adriel Jacob Jebaraj, Jing Xu, Denis Martins de Godoi, Daniel Scherson Ernest B. Yeager Center for Electrochemical Sciences and Department of Chemistry Case Western Reserve University, Cleveland, OH 44106-7078 The coupling of electrochemistry and mass spectrometry has played a key role in helping unveil the mechanisms of electron transfer reactions with relevance to a growing number of fundamental and applied processes. Ingenious approaches have been devised to detect gaseous products generated directly or indirectly by heterogeneous redox reactions. This study introduces a novel arrangement that combines the well-defined hydrodynamics of the flow associated with liquid emerging from a tube nozzle impinging on the surface of a disk electrode surrounded by a gas permeable coplanar ring. Gases produced by the redox reaction flow radially along the surface of the assembly (Fig. 1) and permeate through the Teflon membrane into a tube leading to a mass spectrometer setup. Figure 2 displays electrochemical (A) and mass spectrometric data (B) of hydrazine (N2H4) oxidation at various concentrations. As reported in the literature, N2H4 undergoes oxidation on Au yielding N2 as the only gaseous product. The shape of the current-voltage curves (Fig. 2A) recorded with the electrolyte solution flowing and the N2 mass signals (Fig. 2B) closely resemble each other. Excellent linear fits were observed for the limiting currents as well as the MS signals, as a function of N2H4 concentration. Theoretical aspects of this geometry are now underway to explain the data quantitatively.

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Fig. 1. Illustration of the MS probe with the impinging flow of electrolyte against the Au electrode and its subsequent spreading along the surface. Fig. 2 (A) Current-voltage curves in different concentrations of N2H4. Inset: limiting current density vs concentration. (B) The associated mass signal for N2. Inset: mass signal vs

concentration.

ANALYTICAL CHEMISTRY SESSION

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3:45 p.m. Mass Spectroscopy: A Central Technology for Protein Analysis Sujatha Chilakala** and Yan Xu Department of Chemistry, Cleveland State University Quadrupole time-of-flight (Q-TOF) mass spectrometry is a powerful analytical technique for protein research and for study of macromolecules. With its high sensitivity and specificity, Q-TOP mass spectrometry has been used for identification and quantification of proteins and nucleic acids, as well as for characterization of protein-ligand complex, enzyme-inhibitor interaction and reaction mechanism. In this work, we demonstrated the use of Q-TOF mass spectrometer for protein identification and characterization using intact bovine serum albumin (BSA) and in-solution digested BSA by both external and internal calibrations with rennin, and Protein Pilot software for bioinformatics. The methodology established was applied to the studies of enzyme inhibition in certain novel antibiotics. 4:00 p.m. Determination of Polymer Sequences and Architectures by Mass and Tandem Mass Spectrometry Aleer M. Yol1,** Jonathan E. Janoski2, Roderic P. Quirk2, Chrys Wesdemiotis1, 2 1Department of Chemistry and 2Department of Polymer Science, The University of Akron, Akron, OH The development of soft ionization techniques, such as matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), has significantly facilitated the mass spectrometry (MS) characterization of synthetic polymers. These soft ionization methods minimize the fragmentation of large molecules, thereby permitting their observation without fragmentation. Similarly, the time-of- flight (TOF) mass analyzer, which can be coupled to MALDI and ESI, has allowed the detection of large ionized molecules, because of its unlimited mass range. In this project, MALDI-TOF/TOF mass spectrometry has been utilized to characterize functionalized homopolymers and copolymers. For homopolymers, the monomer unit and combined end groups can usually be identified from the m/z ratios observed in the mass spectrum. The characterization of copolymers presents additional challenges, arising from complexities in their structure, composition, and molecular weight distribution. Now, single-stage MS may not provide the information needed to determine all structural features of the copolymer. My project evaluates the characterization of new synthetic copolymers by combined MS and tandem mass spectrometry (MS/MS) techniques. The goal is to develop mass spectrometry based protocols that provide information about comonomer composition, individual end groups, and copolymer sequence and /or architecture. 4:15 p.m. Determination of Triapine, a Potent Ribonucleotide Reductase Inhibitor, in Human Plasma by LC-MS/MS Ye Feng1** and Yan Xu1,2 1Cleveland State University, Cleveland, OH; 2Case Comprehensive Cancer Center, Cleveland, OH Triapine (also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or 3-AP) is a novel anticancer drug, belonging to the family of drugs referred to as ribonucleotide reductase (RR) inhibitor. It can remove ferric ion from the catalytic di-iron-tyrosyl radical center of RR, inhibits de novo synthesis of deoxyribonucleotides, and impairs the required ratio of DNA to cell mass during cell division and DNA repair. Preclinical study showed that triapine significantly decreased RR activity and enhanced radiation-mediated cytotoxicity in cervical and colon cancer cells by impairing DNA repair process that rely on the production of deoxyribonucleotides, thereby sensitized the radiation therapy of human cancers. These preliminary findings warrant further clinical study of this compound.

ANALYTICAL CHEMISTRY SESSION

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In this work, we have developed and validated a sensitive and specific LCMS/MS method for direct determination of triapine in human plasma using 2-[(3-fluoro-2-pyridinyl)methylene]-hydrazinecarbothioamide (NSC# 266749) as the internal standard (IS). Plasma samples were prepared by deproteinization with acetonitrile. Tripaine and the IS were separated on a Waters Xbridge Shield RP 18 column (3.5 m; 2.1 50 mm) using 25.0% methanol and 75.0% ammonium bicarbonate buffer (10 mM, pH 8.5) (v/v) as mobile phase. The column eluate was monitored by the positive turbo-ion-spray tandem mass spectrometry, and quantitation was carried out by multiple-reaction-monitoring (MRM) mode. The method developed had a linear calibration range of 0.25050.0 ng/mL with correlation coefficient of 0.999 in human plasma, and the lower limit of quantitation (LLOQ) at 0.250 ng/mL. The recovery of triapine and the IS normalized matrix effect in human plasma ranged 101104% and 1.031.06, respectively. The accuracy expressed as percent error (%RE) and precision expressed as coefficient of variation (%CV) were 15% and 15%, respectively. This is the first validated LC-MS/MS method for the determination of triapine in human plasma. It has been successfully applied to the measurement of triapine in human blood samples.

BIOCHEMISTRY SESSION

11

3:00 p.m. The B Domain of Factor V: A Natural Hemostatic Regulator Joesph R. Wiencek1,** Jamila Hirbawi2, Mahesheema Na1, and Michael Kalafatis1,2,3 1Chemistry, Cleveland State University, Cleveland, OH., 2Molecular Cardiology, Cleveland Clinic, Cleveland, OH., 3Biological,Geological and Environmental Sciences, Cleveland State University Coagulation factor V is synthesized as a multidomain (A1-A2-B-A3-C1-C2) procofactor with nominal procoagulant activity. A highly basic region of amino acids in the B-domain of factor V suggests a potential sheathing of either the heavy or light chain fXa interface sites. We investigated the role of amino acid region 1000-1008 that contains seven basic amino acid residues. To ascertain the role of this region our laboratory has generated a recombinant mutant fV molecule with all activation cleavage sites (R709/R1018/R1545) mutated to glutamine (fVQ3), a mutant fV molecule with region 1000-1008 deleted (fVB8), and a mutant fV molecule containing the same deletion with all activation cleavage sites changed to glutamine (fVB8/Q3). The recombinant molecules along with wild type fV (fVWT) were transiently expressed in COS7L cells, purified to homogeneity, and assessed for their capability to bind fXa within prothrombinase prior (fV) and after incubation with thrombin (fVa). The data showed that fVQ3 and fVaQ3 were unable to interact with fXa. In contrast, the Kd values for fVB8 (0.9 nM), fVaB8 (0.4 nM), fVB8/Q3 (0.7 nM) and fVaB8/Q3 (0.5 nM), were similar to the affinity of fVaWT for fXa (0.22 nM). Two-stage clotting assays revealed that while fVaQ3 was practically devoid of clotting activity, the mutant molecules fVaB8, and fVaB8/Q3 had clotting activities comparable to fVaWT. Thus, unactivated fVB8/Q3 has an affinity for fXa that is similar to the affinity of fVaWT for the enzyme. In addition, fVB8/Q3 that cannot be cleaved and activated by thrombin or activated during the course of the clotting assay has similar clotting activity as fVaWT (~3110 U/mg). These data strongly suggest that amino acid region 1000-1008 of fV contains a regulatory sequence protecting the organisms from spontaneous binding of the procofactor to fXa and unnecessary prothrombinase complex formation which will result in catastrophic physiological consequences. 3:15 p.m. Site-specific Lipidation of Recombinant Thrombomodulin Lin Wang,** Rui Jiang, Jacob Weingart and Xue-long Sun Department of Chemistry, Cleveland State University We report an enzymatic site-specific lipidation of recombinant thrombomodulin (TM) via sortase A (SrtA) mediated ligation (SML). TM is a cofactor for protein C activation with thrombin, and thus a crucial regulator in protein C pathway and coagulation cascade. TM contains 6x epidermal growth factor (EGF)like structures, in which the forth to sixth EGF-like region (TM456) is responsible and the minimum functional domain for the activity of Protein C activation. SrtA is a transpeptidase from S. aureus which recognizes and cleaves LPXTG motif on the target protein, and then catalyzes the linkage of the target protein with the compound containing glycine. Truncated TM456 derivative with a C-terminal LPETG motif was expressed in E. coli and purified by Nickel Affinity Chromatography. Glycine-DSPE was synthesized and conjugated with TM456 derivative by SML. Glycine-DSPE was successfully added to the C-terminal of TM456 by SDS-PAGE confirmation. This site-specific covalent modification leads to molecules being arranged in a definitively ordered fashion and facilitating the preservation of the proteins biological activity.

BIOCHEMISTRY SESSION

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3:30 p.m. Controlling recruitment of transcriptional complexes with small molecules Aaron Van Dyke1, Jonas Hjfeldt,3 and Anna Mapp1,2, 1 Department of Chemistry, 2Department of Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA, 3 Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark Nuclear receptors (NRs), such as glucocorticoid receptor (GR), are ligand-inducible transcription factors that regulate gene expression by recruiting protein complexes to DNA. NRs are important therapeutics targets which, historically, have been modulated by small molecules that allosterically recruit cofactors. Alternatively, bifunctional small molecules that can directly control cofactor recruitment would provide excellent tools to study and treat disease. As a proof of principle, bifunctional molecules were used to recruit a potent transcriptional activator to GR. A histone deacetylase (HDAC) inhibitor will then be used to recruit corepressor complexes to GR. Chromatin immunoprecipitation (ChIP) is used to study the recruitment of these proteins to DNA. 3:45 p.m. Activity Analyses of Selective Sulfonamide Tubulin Inhibitors in African Trypanosomiasis Rati Lama1** and Bin Su1,2 1Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA 2Center for Gene Regulation in Health and Disease, College of Sciences & Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, Human African Trypanosomiasis, also known as sleeping sickness is endemic vector-borne parasitic disease transmitted by tse-tse fly that threatens over 60 million people in 36 countries of sub-Saharan regions of Africa. Current drug treatments available exhibit drawbacks in their methods of administration and their ineffectiveness in treating the disease when it reaches latter stages. A class of sulfonamide tubulin inhibitors developed as anti-cancer agents showed inhibitory action on the growth of Trypanosoma brucei, a parasitic protozoan that causes African trypanosomiasis. Sulfonamides are Non-steroidal anti-inflammatory drugs (NSAIDs) that are potent in the treatment of this disease. Sulfonamides act by tubulin inhibition mechanism and show anti-cancer activity by binding to colchicine domain. Selective sulfonamide derivatives were evaluated in determining their selectivity against T. brucei to human breast cancer cell growth. A co-relational study was conducted on the potential of the sulfonamide analogs for inhibiting parasitic cell growth, breast cancer cell apoptosis and their effect on normal mammalian fibroblast cells. Several sulfonamide analogs showed excellent selectivity to the parasite. The difference in the colchicine binding domains between T. brucei and mammalian cells demonstrated the selectivity of the compounds for the parasitic cell growth inhibition. The study provides basis for new drug development approach to treat sleeping sickness.

BIOCHEMISTRY SESSION

13

4:00 p.m. Lectin Mimetics for Glyco-Capturing, Glycomics and Glycoproteomics Applications Poornima Pinnamaneni,** Satya Nandana Narla and Xue-Long Sun Cleveland State University, Cleveland, OH 44115 Cell surface carbohydrates existing as glycoproteins and glycolipids represent the first information about the cell with the outside world and are closely involved in various biological processes such as cell communication, and the molecular orientation and cell targeting. However, the mechanisms of most of the processes at the molecular level are still unclear. It is therefore very important to develop specific carbohydrate-binding molecules for a fast, efficient, sensitive and accurate analysis of complex carbohydrates structures and functions. In addition, certain carbohydrate-binding molecules can be used in medical applications such as biomarkers for diseases diagnosis and targeted drug delivery applications. In this presentation, we report design and synthesis a lectin mimetics based on bovine serum albumin (BSA)-boronic acid (BA) conjugates. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized BSA-BA conjugates by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto malimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by Alizarin Red displacement assay. These lectin mimetics will provide an important tool for glycomics and glycoproteomics research and applications. 4:15 p.m. Cleavage at Arg1018 during Thrombin-Mediated Activation of Coagulation Factor V Is Dispensable Mahesheema Na1,** Joesph R Wiencek1, Jamila Hirbawi2 and Michael Kalafatis1, 2, 3, 4 1Dept. of Chemistry, Cleveland State University, Cleveland, OH; 2Molecular Cardiology, Cleveland Clinic, Cleveland, OH; 3Molecular Cardiology, The Cleveland Clinic, Cleveland; 4Biological,Geological and Environmental Sciences, Cleveland State University Blood clotting results in the proteolytic conversion of prothrombin (Pro) to thrombin which in turn will produce the fibrin clot. The proteolytic conversion of Pro to thrombin is catalyzed by the prothrombinase complex which is composed of the enzyme, factor Xa (FXa), the cofactor, factor Va (FVa), assembled on a membrane surface in the presence of divalent metal ions. Factor V (FV), is a multidomain protein (A1-A2-B-A3-C1-C2) with nominal procoagulant activity and is activated by thrombin to FVa through three sequential proteolytic cleavages at Arg709, Arg1018 and Arg1545. To determine the importance of the cleavage site at Arg1018 for procofactor activation and the function of amino acid region 1000-1008 during proteolysis, several other recombinant molecules were generated. FVRQR is a FV molecule with the mutation Arg1018Gln, and FV1000-1008 is a mutant FV molecule with region 1000-1008 deleted. We have also generated FV1000-1008/RQR and FV1000-1008/QRQ. Two-stage clotting assays revealed that FVaRQR and FVa1000-1008/RQR have similar clotting activities as FVaWT , whereas FVaQRQ, FVa1000-1008/QRQ are impaired in their clotting activities. Kinetic analyses demonstrated that FVaRQR and FVa1000-1008/RQR have similar affinity for FXa as FVa WT while FVaQRQ and FVa1000-1008/QRQ were impaired in their interaction with factor Xa. The kcat values for prothrombinase assembled with FVaRQR and FVa1000-1008/RQR were similar to the kcat obtained with prothrombinase assembled with FVa WT, while prothrombinase assembled with FVaQRQ and FVa1000-1008/QRQ had 2-fold and 7-fold reduced catalytic efficiency respectively, when compared to the kcat values obtained with prothrombinase assembled with FVaWT. Overall, the data demonstrate that cleavage at both Arg709 and Arg1545 are a prerequisite for expression of optimum cofactor activity. Our data also suggests that cleavage at Arg1018 is redundant for cofactor activity. The role of cleavage at this site by thrombin during procofactor activation remains to be determined.

BIOCHEMISTRY SESSION

14

4:30 p.m. Synthesis and Evaluation of 5-Indole acetic acid derivatives as potential Chemotherapeutic Agents for Colon Cancer Snigdha Chennamaneni** and Bin Su Department of Chemistry, Cleveland State University The quest for new chemotherapeutics for the treatment of diseases such as cancer is a continuing challenge to both synthetic and biological chemists. Our strategy utilizes Non-steroidal anti-inflammatory drug (NSAID), 5-Indole acetic acid (Indomethacin) as lead compound, for further development. NSAIDs have been widely reported to display strong efficacy for cancer chemoprevention, although their mechanism of action is poorly understood. The well-documented effects of NSAIDs include inhibition of tumor cell proliferation and induction of apoptosis, but their effect on tumor cell invasion has not been well studied. A new series of 5-Indole acetic acid derivatives were investigated for their anti-cancer activity. 5-Indole acetic acid derivatives were chemically synthesized and evaluated by invitro MTT assay and IC50 cytotoxicity determined. The results showed that one of the derivatives, Compound 21, N-(3-(dimethyl amino) ethyl)-2-(5-methoxy-2-methyl-1-(3, 4, 5-trimethoxybenzoyl)-1H-indol-3-yl) acetamide, was most active against HT 29 cell line with an IC50 of 2.710.75m. More importantly in conjugation with structural and docking studies, this compound provides an insight into the molecular determinants that govern the ligand binding in Tubulin polymer. In summary, our results show that compound 21 is a new 5-indole acetic acid derivative with potent anti-cancer activity. Compound 21 inhibits the tubulin polymerization, a novel target for chemotherapeutic drugs and is worthy of further investigation as a potent chemotherapeutic agent for treating colon cancer. 4:45 p.m. Oriented Immobilized Sialyloligo-Macroligand and Its Protein Binding Specificity Satya Nandana Narla** and Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115 We report a chemoenzymatic synthesis of chain-end functionalized sialyllactose-containing glycopolymers with different linkages and their oriented immobilization for glycoarray and SPR-based glyco-biosensor applications. Specifically, O-cyanate chain-end functionalized sialyllactose-containing glycopolymers were synthesized by enzymatically a2,3- and a2,6-sialylation of terminal galactose of lactose-containing glycopolymers that was synthesized by cyanoxyl-mediated free radical polymerization. 1H NMR showed almost quantitative a2,3- and a2,6-sialylation. The O-cyanate chain-end functionalized sialyllactose-containing glycopolymers were printed onto amine-functionalized glass slides via isourea bond formation for glycoarray formation. The specific protein binding activity of the arrays were confirmed with a2,3- and a2,6-sialyl specific binding lectins together with inhibition assays. Further, immobilizing O-cyanate chain-end functionalized sialyllactose-containing glycopolymers onto amine-modified SPR chip via isourea bond formation afforded SPR-based glyco-biosensor, which showed specific binding activity for lectins and influenza viral hemagglutinins (HA). These sialyloligo-macroligand derived glycoarray and SPR-based glyco-biosensor are closely to mimic 3D nature presentation of sialyloligosaccharides and will provide important high-throughput tools for virus diagnosis and potential anti-viral drug candidates screening applications.

INORGANIC CHEMISTRY SESSION

15

3:00 p.m. Synthesis and Photophysical Properties of Air-stable Benzoxaphospholes Shanshan Wu** and John D. Protasiewicz Department of Chemistry, Case Western Reserve University Low-coordinated organophosphorus compounds featuring P=C units have got intensive study in recent years due to their unique optoelectronic properties. Benzoxaphospholes (BOPs) is a class of heterocycles which a benzene ring fused to a phosphorus and oxygen containing five membered ring which shown remarkable luminescent properties. In order to improve its stability, bulky groups are introduced into BOP. In this work, bulky substituted BOPs are prepared. Their air-stability and photophysical properties are characterized. 3:15 p.m. Stereocontrolled Intramolecular Iron-mediated Diene/Olefin Cyclization Sheng Zhang** and Anthony J. Pearson Department of Chemistry, Case Western Reserve University, Cleveland, Ohio44106 A tricarbonyliron moiety [Fe(CO)3] coordinated with dienes has been widely used in organic synthesis.1 Pearson and Zettler developed a stereocontrolled intramolecular iron-mediated diene/olefin cyclocoupling reaction, which forms spirolactones spirothiolactones and spirolactams under thermal or photothermal conditions.2 We recently examined thermal condition spirocyclization using vinylethers as substrates to afford a functionalized side chain (figure 2). With R1 as a methoxy substituent, the demetalation and hydrolysis afforded one single product. Further progress on this topic will be reported in this presentation.

Figure 1 Spirocyclization and demetalation of vinylether substrates 1) Knlker, H. Chem. Soc. Rev., 1999, 28, 151157. 2) Pearson, A. J.; Zettler, M. W J. Am. Chem. Soc. 1989, 111, 3908-3918.

INORGANIC CHEMISTRY SESSION

16

3:30 p.m. Phosphorus Containing Derivatives of Polyaniline David K. Hildebrandt,* Michael Rectenwald, and John Protasiewicz Department of Chemistry, Case Western Reserve University, Cleveland, OH Advanced materials are needed for new industrial products in which many of these desired materials are polymers. Polyaniline has been long known to conduct electricity when in an acid solution and from this it was discovered that it the ability to tune its conductivity based on the amount of doping. Here, polyaniline and phosphorus-containing derivatives were synthesized and compared to a previously made polymer through de-alkylation. Specifically, diethyl phenylphosphoramidate was polymerized and attempts at polymerizing diethyl (2-aminophenyl)phosphonate were made. Polymers were characterized by NMR and IR. 3:45 p.m. DFT/QTAIM Analysis of Carbon Monoxide Chemisorption to Nickel(111) and Bimetallic Ni3X, Ni2X2 (X=Pd, Cu, Ag, Au) Clusters Peter C. Psarras,** and David W. Ball Department of Chemistry, Cleveland State University, Cleveland, Ohio, 44115 Density functional theory calculations combined with the quantum theory of Atoms in Molecules were used to examine the effect of various promoted nickel four-atom clusters on the surface-carbon and carbon-oxygen bond. All systems were optimized at the B3PW91/LANL2DZ level of approximation in Gaussian 09. Calculations of the carbonyl-surface binding energy, bond lengths, frequencies, and bond dissociation energies of the carbonyl bond were performed. The results show that trends in binding and dissociation energies cannot be ascribed to any one ensemble or ligand effect. QTAIM analysis of the bond critical point (BCP) between carbon and oxygen shows a migration toward carbon as the carbonyl was removed from the surface, though no connection between rate of BCP migration and carbonyl activation could be established. Molecular graphs obtained from the gradient vector fields combined with the bifurcation mechanism of structural change reveal greater structural stability for certain clusters. This may provide valuable insight into the nature of promoter effect on activation. Finally, quadratic synchronous transit guided optimizations were performed to search for a proposed transition structure for the H2-mediated dissociation of oxygen. A comparison of methods, with and without QTAIM assistance, is discussed. 4:00 p.m. Self-Doped Conjugated Polymers Containing Phosphorus Michael F. Rectenwald** and John D. Protasiewicz Department of Chemistry, Case Western Reserve University Self-doped polymers with phosphonic acid functional groups were synthesized using oxidative chemical and electrochemical polymerization techniques. The resulting polymers were progressively neutralized by NaOH, resulting in several water soluble polymers. Copolymers containing varying amounts of phosphoric acid functional groups have also been prepared.

INORGANIC CHEMISTRY SESSION

17

4:15 p.m. Ion-Exchange Synthesis of Niobium and Tantalum Complex Oxides Liv R. Dedon,* Joshua T. Greenfield, and Catherine M. Oertel Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 Complex niobium and tantalum pyrochlore oxides are of interest as photocatalysts for processes including splitting of water to produce hydrogen fuel. Pyrochlore oxides have the general formula A2B2O7 or A2B2O6O', and both the A and B cations influence the electronic structure and optical properties of the oxide. The structure is made up of interpenetrating B2O6 and A2O' nets. Weakly bound A cations in the A2O' net can be selectively exchanged without disrupting the robustly bound B2O6 net. Starting from hydrothermally prepared K1.27Nb2(O,OH)61.2H2O and K1.26Ta2(O,OH)61.3H2O, we have used mild ion exchange reactions to prepare new pyrochlore phases with A-site Na+, Sn2+, and Ag+. Rietveld refinement of synchrotron powder X-ray diffraction data has elucidated the structural adjustments that occur when K+ is replaced with Na+. A decrease in the optical band gap results when Sn2+ replaces K+. The tin-exchanged niobium oxide has a band gap in the visible range, the first requirement for use in solar water-splitting. 4:30 p.m. Bicyclic-borate synthesis for use in lithium ion batteries. Ryan Kowalski* and John Protasiewicz Department of Chemistry, Case Western Reserve University Bicyclic-borate complexes have been synthesized for use as an alternative anion for lithium ion batteries in hopes that they will provide insight into more flame retardant types of ions, or FRIons. This synthesis has been done through azeotropic distillations and solvent-free methods utilizing boronic acids. The current bicyclic compounds being produced were inspired by creating derivatives of lithium bis(oxalato) borate, also known as LiBOB. 4:45 p.m. Synthesis and Characterizations of Phosphorus-Containing Conjugated Materials Feng L. Laughlin,** Marlena P. Washington, Vittal B. Gudimetla, John D. Protasiewicz Chemistry Department, Case Western Reserve University Phosphorus-containing fluorescent conjugated materials, benzoxaphospholes (BOP), benzobisoxaphospholes (BBOPs), naphthoxaphospholes (NOPs) and naphthobisoxaphospholes (NBOPs) were synthesized. They were characterized by 1H, 31P and 13C NMR spectroscopy and elemental analyses or HRMS. Most of compounds were characterized in UV-vis absorption spectroscopy, fluorescence spectroscopy and cyclic voltammetry (CV); selected compounds were characterized by single-crystal X-ray diffraction.

ORGANIC CHEMISTRY SESSION

18

3:00 p.m. Synthesis of Azidoethyl Sialylglycoside for Sialyl Glyco-macroligand Fabrication Jayasri Kakarla,** Jacob J. Weingart, Xue-Long Sun Department of Chemistry, Cleveland State University Sialic acids, a family of 9-carbon containing acidic monosaccharides, often terminate oligosaccharide structures of cell surface glycoproteins and glycolipids and are involved in many biological recognition processes such as cell-cell signal recognition, adhesion to ligands, antibodies, enzymes and microbes. The importance of sialic acid in these processes, especially with respect to human disease states, has led to increased interest in the synthesis of natural and modified sialic acids both as probes of sialic acid-recognizing proteins, and as potential glycopharmaceuticals. We report here the synthesis and characterization of azidoethyl glycoside of sialic acid as key compound for sialyl glyco-macroligand fabrication applications, which facilitates strong binding affinity through multivalent interactions with the sialic acid-binding proteins. The azidoethyl sialylglycoside can be used for modification of polymer, liposome, nanoparticle, and immobilized lipid membrane directly via click chemistry or Staudinger ligation or by converting to amine derivative.

3:15 p.m. Amine-catalyzed Nazarov cyclizations: A Computational Investigation Laura Ros* and Albert Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 Nazarov cyclization of cross-conjugated dienones provides a useful synthetic tool for the preparation of substituted cyclopentenones. The traditional catalysts for this reaction are strong Bronsted or Lewis acids (e.g. H3PO4, AlCl3). This presentation will detail B3LYP computational studies of an amine-catalyzed variant of the Nazarov cyclization. Activation energies of dienone substrates using different amine catalysts were computed in order to determine the feasibility of the cyclization. 3:30 p.m. Amine-Catalyzed Nazarov Cyclizations: Experimental Studies Joseph Hamilton,* Nathaniel Kadunce, Laura Rios, and Albert Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin OH, 44074 The Nazarov cyclization is an important synthetic tool used in converting divinyl ketones to corresponding cyclopentenones. The Matlin lab has been interested in developing an amine-catalyzed variant to the acid-catalyzed (Lewis and Bronsted) Nazarov Cyclization. Following the lead of MacMillan, we first examined pyrrolidine-based catalysts and found them to be ineffective. However, we have discovered that hydroxylamine successfully catalyzes the cyclization. Several examples will be presented.

ORGANIC CHEMISTRY SESSION

19

3:45 p.m. Synthesis of Hexatriene-3-d1 for Use in High-Resolution Molecular Spectroscopy Yihui Chen,* Henrik Ehrhardt, William Gautier, Norman C. Craig, and Albert R. Matlin Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 To determine accurate equilibrium structures of the cis and trans isomers of hexatriene, variants of hexatriene having selective isotopic substitution are needed. These substances are investigated with high-resolution microwave or infrared spectroscopy to determine rotational constants. Remaining to be made for the hexatriene project is the 3,4-d2 or the 3-d1 species. Our first efforts focused on the 3,4-d2 species with maleic anhydride-2,3-d2 as the starting material. This approach failed. A new, successful approach begins with the oxidation of 1,5-hexadien-3-ol to 1,5-hexadien-2-one. This ketone is reduced with lithium aluminum deuteride to 1,5-hexadien-3-ol-3-d1, which is dehydrated by distillation over phosphorus pentoxide. The close-boiling isomers of hexatriene-3-d1 are separated by gas chromatography. 4:00 p.m. Alteration of Carbocyclic Core Skeleton of Bryonolic Acid - Employing DOS Strategy Vasily A. Ignatenko** and Gregory P. Tochtrop Department of Chemistry, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106 Chronic inflammation is an important factor in the severity and progression of cancer. Many triterpenoids are known to have anti-inflammatory properties and thus can serve as cancer chemopreventive agents. Triterpenoids such as oleanolic acid and bryonolic acid are natural products that resemble steroids in their biogenesis by cyclization of squalene. Synthetic oleanane triterpenoids have already been shown to be potent in the treatment and prevention of cancer. Moreover, a medicinal chemistry approach led to the discovery of CDDO, a derivative of oleanolic acid that may be the strongest known inhibitor of the de novo synthesis of iNOS and COX-2. Our approach for expanding repertoire of synthetic triterpenoids utilizes diversity oriented synthesis strategy with bryonolic acid serving as a starting material to generate a library of molecules with diverse unnatural triterpenoid scaffolds. The overall carbocyclic skeleton of bryonolic acid is very similar to oleanolic acid, but of critical importance is that it contains the unsaturated B/C -ring fusion that allowed us to employ oxidative cleavage/aldol addition strategy to generate skeletal diversity. The main challenge with bryonolic acid is that it is not commercially available and we are currently isolating this molecule from Curcubita pepo L. (zucchini) sprouts. 4:15 p.m. Synthesis of a Chiral Ionic Liquid derived from (S)-Phenylalanine Christopher Barton* and Raymond J. Shively Department of Chemistry, Baldwin Wallace College The primary of goal of our research was to induce stereoselectivity in typically non-stereoselective catalytic reactions by using a chiral ionic liquid solvent. Towards that end, a new chiral ionic liquid, (S)-3-(2-((tert-butoxycarbonyl)amino)-3-phenylpropyl)-1-methylimidazol-3-ium methanesulfonate was synthesized in four steps from (S)-phenylalanine. Through multiple attempts, an effective route has been found in order to synthesize this new compound. In the process two other new compounds have been synthesized, (S)-tert-butyl(1-hydroxy-3-phenylpropan-2-yl)carbamate, and (S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropylmethanesulfonate. The compounds have been characterized by IR, 1H NMR, 13C NMR and GC-MS (when possible). Further research will be conducted to remove the tBOC protecting group and to determine the effectiveness of this chiral compound as a solvent for the methyltrioxorhenium catalyzed epoxidation of alkenes.

ORGANIC CHEMISTRY SESSION

20

4:30 p.m. Development of N-prolinylanthranilamide pseudopeptides for asymmetric aldol reactions Santanu Panda** and Anthony J. Pearson Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 Organocatalysis is currently one of the most rapidly growing areas of organic synthesis research, and one entire recent issue of Chemical Reviews was devoted to this topic.1 We recently reported the use of N-prolinylanthranilic acids,2 which are very effective catalysts for aldol reactions of cyclic ketones with aromatic aldehydes, in most cases, giving >95% ee. However, for aldol reactions of acetone those catalysts were marginally better than proline itself (80% vs 75% ee). Consequently, we examined modifications of this system in which the anthranilic carboxyl terminus is modified by attaching an additional amino acid to create a pseudotripeptide. We anticipated that such a structure would show a preferred conformation that results from intramolecular hydrogen bonding as shown figure 1a. Proline anthranilamide-based pseudopeptides were shown to be effective organocatalysts for enantioselective direct aldol reactions of a selection of aldehydes with various ketones with excellent yield, enantioselectivity up to 99% and anti to syn diastereoselectivity up to 25:1(figure 1b).3 Also we are able to do the formal synthesis of few natural products, which have significant biological activity.

Figure 1. (a) Chem3D structure of the catalyst, (b) Different aldol reaction using catalyst. 1) List, B., Ed. Chem. Rev. 2007, 107(12), 5413-5883. 2) Pearson, A. J.; Panda, S. Tetrahedron 2011, 67, 3969. 3) Pearson, A. J.; Panda, S. Org. Lett. 2011, 13, 5548-5551. 4:45 p.m. Adventures in Haloorganic Chemistry: Synthesis of Selectively Deuterated 1,4-Difluorobutadiene Yuhua Lu,* Herman van Besien, and Norman C. Craig Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 Deuterium isotopologues of 1,4-difluorobutadiene are needed for high-resolution infrared spectroscopy. Analysis of the detailed rotational structure in these spectra will contribute to the determination of equilibrium structures, accurate to 0.001 . The basic method for selective deuterium substitution is an assembly strategy, in which fluoroethylene-1-d1 and 1-fluoro-2-iodoethylene are linked photochemically. The resulting 1,4-difluoro-4-iodobutene-4-d1 is dehydroiodinated with base to give a mixture of the isomers of 1,4-difluorobutadiene-1-d1. 1-Fluoro-2-iodoethylene is prepared from 1-fluoro-2-bromoethylene. The synthesis of 1-fluoroethylene-1-d1 begins with bromoethylene. The trans,trans isomer of 1,4-difluorobutadiene,which is the least favored isomer, is isolated by gas chromatography after iodine-promoted equilibration of the isomers.

R1 R2

OOOH

R R

OH O

NH

O

HO O

R

upto 91% ee85% yield

upto 99% eedr 25:178% yield

upto 84% ee97% ee 62% yield(af ter recrystallization)

R1=R2= CH3R1, R2= -(CH2)5 -R1=R2= CH3

CH3

NH

O NH

O

HN CO2H

DMSO, TFA, H2O

4 C

PHYSICAL AND BIOPHYSICAL CHEMISTRY SESSION

21

3:00 p.m. Small angle neutron scattering study of the structure of high density lipoprotein Celalettin Topbas1,2,** Xavier Lee2, Stanley L. Hazen2,3,4, Valentin Gogonea1,2,3 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115; Departments of 2Cell Biology, 3Center for Cardiovascular Diagnostics and Prevention, and 4Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 The high-density lipoprotein (HDL), the carrier of good cholesterol, transports cholesterol from periphery cells to liver for catabolism, a process termed reverse cholesterol transport (RCT). HDL particles are complexes of amphipathic proteins (e.g. apoA1) with various lipids (phospholipids, cholesterol, cholesterol ester, and triglycerides). We used small angle neutron scattering with contrast variation and the isotopic labeling of the protein (apoA1) to determine the low resolution structure of the protein and lipid components of nascent HDL reconstituted with dimyristoyl phosphatidyl choline (DMPC). The scattering data indicate that apoA1 conformation in this particle is open, contorted, and out of plane, while the shape of the lipid phase is an oblate ellipsoid that fits well within the protein shape. This overall architecture of HDL may be suited for changing lipid cargo content by stochastic expansion of apoA1 domains hinged by proline residues. 3:15 p.m. The structure of IKK/NEMO and its Role in the Assembly of the IkB Kinase Complex Carolina Parada1,* Dmitriy Parshakov 1, Camelia Baleanu Gogonea1, Valentin Gogonea1,2 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 441154; 2Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 The role of NF-kB transcription factors in human inflammation and disease makes them targets for therapeutics. IKK/NEMO is a critical component of the assembly of the high molecular weight IkB kinase (IKK) complex, an important player in the NF-kB transcription pathway. This complex is composed of two protein kinases, IKK- and IKK-, and IKK/NEMO protein. It is believed that the activation of IKK/NEMO requires a drastic change in its conformation. We investigate the hypothesis that IKK/NEMO oligomerizes as a compact trimer in order to expose its binding domain to the IKK-/IKK- complex. This assumption is based on previous results obtained by small angle neutron scattering (SANS). To accomplish our goal, we are studying both the full length IKK/NEMO (419 amino acids) and a C-terminus truncated form (125 amino acids). We are expressing the two proteins using cDNA prepared in our lab, and in the next stage of the project we will use the proteins to perform SANS analyses and crystallography studies. The SANS results will be used in conjunction with the published crystal structure of the N-terminus of IKK/NEMO to build a molecular model for the full length IKK/NEMO. The model will be further used to predict the mutual interactions between IKK/NEMO monomers within the trimer, and with IKK-/IKK- within the IKK complex

PHYSICAL AND BIOPHYSICAL CHEMISTRY SESSION

22

3:30 p.m. Gas Phase Oxidation Kinetics For Atmospheric Relevant Epoxied Intermediates Adam Darer* and Matthew J. Elrod Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074. Isoprene, 2-methyl-1,3 butadiene, is the most abundant non-methane hydrocarbon present in the atmosphere. This volatile alkene, which is produced mainly by trees, undergoes gas phase oxidation reactions to form epoxide intermediates. Isoprene epoxide intermediates may undergo further oxidation by OH radicals to form peroxy species. These oxidation steps of isoprene are related to the production of tropospheric ozone and secondary organic aerosol (SOA) formation, and thus linked to air pollution and global climate change. OH radical initiated oxidation reaction rates for isoprene epoxide species have not previously been measured. The specific goal of the project is the measurement of the rate constants for the reaction of atmospherically relevant isoprene epoxide intermediates with OH radicals using Turbulent Flow Chemical Ionization Mass Spectrometry. 3:45 p.m. Immobilized Cell Membrane Mimetic System for Functional Analysis of Membrane Protein Valentinas Gruzdys,** Yong Ma and Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115 Membrane biomolecules play an important role in every living cell. One of the most significant groups, membrane proteins, play key roles in cells function, such as cell-cell interaction, signal transduction, and nutrient transport. Despite their importance and abundance, there are significant knowledge gaps about their structure and function. Their amphiphilic nature means that their structure and binding properties are difficult to measure. In addition, the presence of negatively charged carbohydrate and phospholipid groups in close proximity to some transmembrane proteins in cells has been shown to affect their binding behavior, but is difficult to replicate in vitro. Such environment, containing a lipid bilayer with specific surface biomolecules would mimick cellular surfaces and allow for transmembrane protein studies that reflect the in vivo interactions. In this work, fabrication of a cell-surface mimicking tethered lipid bilayer on a gold surface is demonstrated. The assembly process attempts to replicate cellular environment where transmembrane and membrane-bound molecules can interact. The gold surface represents a suitable environment to monitor the reactions through Surface Plasmon Resonance (SPR). The presented approach provides several significant benefits. SPR allows for label-free, real-time kinetic studies, requiring relatively small amounts of sample. The central copper-free click conjugation approach allows for versatile functionalization of the lipid surface with a wide array of molecules, carrying a free azido group. The overall tethered lipid bilayer (tBL) fabrication consists of three parts: functionalization of the gold surface with azide; introduction of an anchor lipid, separated by a hydrophilic polyethylene glycol linker from the gold surface; introduction of a transmembrane protein in liposomal form resulting in the bilayer formation. The presented approach allows for a density and lipid composition controlled fabrication of a tBL, allowing for introduction of a variety of functional groups onto the surface for a wide array of studies. The use of SPR measurements allows for sensitive detection and analysis of the bilayer itself and the interactions that take place on the surface. In addition, the use of biocompatible polymers and conjugation allows for a possible application of this analysis technique with living cells.

PHYSICAL AND BIOPHYSICAL CHEMISTRY SESSION

23

4:00 p.m. Solid-State NMR Study of Porous Dipeptides Benjamin Altheimer* and Manish Mehta Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074 Some peptides crystallize into structures with extended 1-dimensional pores that can accommodate a variety of small guest molecules including some organic solvents and gases. These may be useful for gas storage and separation. Designing and utilizing these materials and others like them for these purposes requires a better understanding of the interactions between the pore walls and guest. The interactions between the guest and the pore walls are affected by the size and shape of the pore. The pore can also shift in size and shape to better accommodate the guest by conformation shifts in the pore wall and the interior structural framework of the crystal. In the first part of this project, we explore the utility of solid-state nuclear magnetic resonance in studying the effects of adding guest molecules to the pores on the structure of the dipeptide Ala-Val. Ala-Val is one of seven dipeptides that form an isostructural series. These peptides, with hydrophobic side chains ranging in size from alanine to isoleucine, crystallize into structures with very similar conformations and the same hydrogen bonding patterns. Given the variations in side chain size, the similarities in these structures are unusual and only made possible by the presence of the pore into which the additional atoms can fit. In the second part of this project, we use this set of seven similar dipeptides to study the relationship between structure and NMR chemical shift. 4:15 p.m. Molecular modeling of LCAT, a plasma enzyme involved in reverse cholesterol transport Christopher Pechura1* and Valentin Gogonea1,2 1Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115; 2Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 Lecithin cholesterol acyltransferase (LCAT) is a plasma enzyme that remodels nascent high density lipoprotein (HDL) into a mature formed called spherical HDL. The impeding of this critical step in reverse cholesterol transport (RCT, that the transport of excess cholesterol from periphery cells to liver for catabolism), leads to atherosclerosis. Our goal is to use computational chemistry and molecular modeling tools to build molecular models for LCAT and its complex with nascent HDL. The molecular models are constructed from low resolution structures of LCAT and LCAT-HDL complex obtained by small angle neutron scattering (SANS) with contrast variation. Ultimately, we combine various experimental data (SANS data, hydrogen-deuterium exchange tandem mass spectrometry, other biochemical data) with computational techniques (bioinformatics, molecular modeling, SANS modeling, protein-protein docking, molecular dynamics simulation) to produce a molecular model for LCAT and its complex with nascent HDL. The model will be used in future work to map the amino acid residues from LCAT and the protein component of nascent HDL (apoA1) involved in the mutual interaction, and to identify LCAT residues interacting with the lipid phase of nascent HDL.

PHYSICAL AND BIOPHYSICAL CHEMISTRY SESSION

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4:30 p.m. Study of the Oligomerization Kinetics and Equilibria of 2-Methyl Glyceric Acid Adam W. Birdsall,* Cassandra A. Zentner, and Matthew J. Elrod Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074. Recent environmental chamber studies have demonstrated that multi-step oxidation products of isoprene contribute significantly to secondary organic aerosol (SOA) formation in the atmosphere. In particular, 2-methyl glyceric acid (2-MG) is postulated to be an important source of SOA via oligomerization reactions (forming polyesters). However, the conditions that might promote efficient, atmospherically relevant SOA formation from 2-MG, such as acid concentration and water content, are not well understood. In order to better determine the parameters that lead to efficient oligomerization of this species, 2-MG has been separately synthesized, and oligomerization kinetic and equilibrium measurements have been performed using an NMR-based analytical technique. 4:45 p.m. Glyco-Functionalization of Liposomes and Their Stability Study Pratima Vabbilisetty** and Xue-Long Sun Department of Chemistry, Cleveland State University, Cleveland, OH 44115 Self-assembled lipid bi-layers such as liposomes have been widely used as biomimetic models of cell membranes and as drug/gene delivery carrier systems. Liposome encapsulation technique has been demonstrated to enhance their compatibility with the biological milieu in vitro and in vivo. Cell surface carbohydrates have specific interactions with proteins, which play an important role in various biological recognition processes such as fertilization, embryogenesis, metastasis, inflammations and hostpathogen adhesion. Therefore, carbohydrate molecules serve as attractive molecules for surface modification of liposomes with purpose for tissues specific and biocompatibility. In this report, glyco-functionalized liposome systems were prepared by the thin-film hydration and extrusion process followed by chemically selective glyco-functionalization of liposomes via Staudinger ligation. The structural characteristics and stability of the glyco-functionalized liposomes were confirmed by DLS and fluorescence spectroscopy. Particularly, anchor lipid effects on the stability of glyco-functionalized liposomes was investigated by using two different anchor lipids namely (Cholesterol-PEG2000-TP) and (DSPE-PEG2000-TP) monitored via the fluorescence leakage assay.