Program Overview

2:30 pm Registration, Regina Hall, Refreshments served3:00 pm-5:15 pm Technical Sessions (see below)5:15-5:30 pm Adjourn to Administration Building 5:30-6:30 pm Plenary talk, Performing Arts Center, Ground Floor Administration Building 6:30 pm Dinner, Performing Arts Center, Musical arrangements by Sung-Soo Cho,

Doctoral Candidate, Cleveland Institute of Music 7:30 pm Student Awards, Performing Arts Center

Plenary Talk

Venus in a bottle:  Simulating Interactions Between the Crust and Atmosphere of Venus (and Venus-like Exoplanets), Dr. Ralph Harvey, Senior Fellow, NASA Glenn Research Center, Assoc. Professor, Case Western Reserve University

Both historical and current investigations of Venus suggest that atmosphere/rock interactions may play a critical role in the evolution of that planet's atmosphere and crust, particularly in producing or maintaining that planet's thick CO2-rich atmosphere in its current massive greenhouse state. Using GEER (the Glenn Extreme Environment Rig) we are exploring such interactions by creating "Venus in a Bottle"- mixing plausible Venus surface simulants with a high-fidelity recreation of that planet's thick, hot and corrosive atmosphere. These "naturalistic" simulations complement prior and ongoing highly constrained experiments and help us understand the messy and complex nature of Venus' rocks, atmosphere and history.

Technical Sessions (Schedule/Titles, Abstracts) Biochemistry I Regina 019Biochemistry II Regina 024 Biochem/Organometallic/Polymers Regina 025Organic Regina 201Analytical Regina 202Inorganic/Materials/Analytical I Regina 210Inorganic/Materials/Analytical II Regina 211 

American Chemical Society- Cleveland Section would like to thank the faculty, staff, and administration of Notre Dame College for hosting this event. Special thanks to all the organizers,

sponsors, judges, session moderators, and especially our Notre Dame College student ambassadors from NDC Biology Club and NDC Chemistry Club for their assistance.

Biochemistry I, Regina 019 * - Denotes undergraduate presenter ** - Denotes graduate presenter

3:00 pm RNase L is involved in type I diabetes onset, Qiaoyun Zheng**, Chun Zeng, Xin Yi, and Aimin Zhou, Clinical Chemistry Program, Department of Chemistry; Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH

3:20 pm Graphene-Based Composites for Detection and Quantification of Peroxynitrite, Haitham Kalil**, Mekki Bayachou, Department of Chemistry, Cleveland State University, Cleveland, OH

 

3:40 pm Incorporation of Azide Functionality into Recombinant Protein via Recombinant, Enzymatic, and Chemical Approaches for Bio-Orthogonal Modification Lin Wang1**, Rui Jiang1, Lin Wang2 and Xue-Long Sun1. 

1Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation of Health and Disease (GRHD), Cleveland State University, Cleveland, OH2Department of Medicinal Chemistry, China Medical University, Shenyang, Liaoning, China.  

4:00-4:10 pm break

4:10 pm Dissolution of Aggregated Islet Amyloid Polypeptide (IAPP) in Rat Insulinomas Using Novel Beta-Sheet Breakers Melissa Barranger-Mathys, Ph.D. Ursuline College, Department of Chemistry

 

 4:40 pm Profiling Sialylation Status during Monocytes Differentiation, Dan Wang**1, Evgeny Ozhegov2, Aimin Zhou1, Xue-Long Sun1*

1Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio 2Department of Biological, Geological, and Environmental Sciences (BGES), Cleveland State University, Cleveland, Ohio

Biochemistry II, Regina 024 * - Denotes undergraduate presenter ** - Denotes graduate presenter

3:00 pm Lipids Affect Thrombomodulin's Capacity to Generate APC and TAFI, Valentinas Gruzdys**1 and Xue-Long Sun1,2

1Department of Chemistry, Cleveland State University

2 Department of Biomedical Engineering, Cleveland State University

3:20 pm The Role Of Lipid-Free Apolipoprotein A-I Self-Association In The Formation Of High Density Lipoprotein, Celalettin Topbas**1,2, Joseph A. Didonato2,3, Jonathan D. Smith2, Stanley L. Hazen2,3,4, Valentin Gogonea1,2,3

1Department of Chemistry, Cleveland State University, Cleveland, OH2Department Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH3Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH, 4Cardiovascular Medicine Department, Cleveland Clinic, Cleveland, OH

3:40 pm Simultaneous Determination Of Dihydrotestosterone And Its Metabolites In Mouse Sera By Lc-Ms/Ms With Chemical Derivatization, Shashank Gorityala** a, Shuming Yang b, Monica M. Montano c, Yan Xu a,b

aDepartment of Chemistry, Cleveland State University, Cleveland, Ohiob Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OHcDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 

4:00-4:10 pm break

4:10 pm Evaluating The Pro-Mutagenic Replication Of 8-Oxoguanine Anvesh Dasari 1 **, Anthony J Berdis1, 2, 3

1Department of Chemistry, Cleveland State University, Cleveland, OH 2Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 3Red5 Pharmaceuticals, LLC, Cleveland, OH

4:30 pm Role of RNase L in Kidney Norah J Alghamdi**, Qiaoyun Zheng, Danting Liu, and Aimin Zhou, Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH

4:50 pm Determination of Monosialogangliosides in Human Plasma by a Novel UPLC/MS/MS Assay Coupled to Chemical Derivatization, Qianyang Huang**1, Xiang Zhou1, Danting Liu1, Baozhong Xin2, Karen Cechner2, Heng Wang2, and Aimin Zhou1

1Clinical Chemistry Program, Cleveland State University Cleveland, OH2DDC Clinic, Center for Special Needs Children, Middlefield, OHBiochem/Organometallic/Polymers, Regina 025 * - undergraduate presenter ** - graduate presenter

3:00 pm Histidine-Tagged Peptide Binding to Anionic Lipid in Asymmetric Supported Lipid Bilayers, Xiaosi Li** and Adam W. Smith, Department of Chemistry, The University of Akron

3:20 pm Ferreting out homo- and heterodimerization of G-protein coupled receptors (GPCR) via PIE-FCCS William D. Comar** and Adam W. Smith, University of Akron, Akron, OH

 

3:40 pm Stimuli-Responsive Liquid Crystalline Elastomer Actuators, Brian T. Michal**, Blayne M. McKenzie, Simcha E. Felser and Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 

4:00-4:10 pm break

4:10 pm Optimizing the formation of [3]catenates containing 2,6-bis(N-alkylbenzimidazolyl)pyridineQiong Wu**, Rudy J. Wojtecki, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio 

4:30 pm Synthesis of Lead Oxide Carboxylate Single Crystals and Nanostructures, Calvin Gang*,1 Venkata Shiva Mandala,1 Matthias Zeller,2 Catherine M. Oertel1

1Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH2Department of Chemistry, Youngstown State University, Youngstown, OH

 4:50 pm Selective nitrosylation of GAPDH occurs via the S100A8/A9 protein complex: A theoretical investigation, Arlene Praniewicz*1,2 and Valentin Gogonea1,2,3

1Department of Chemistry, Cleveland State University, Cleveland, OH2Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH3Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH

Organic Chemistry , Regina 201 * - undergraduate presenter ** - graduate presenter

3:00 pm Conjugated Organophosphorus Materials, Alexandra Grimm**, Dr. John ProtasiewiczCase Western Reserve University, Dept. of Chemistry, Cleveland, OH

 3:20 pm Synthesis and anti-proliferative activity of N,N’-bis(arylmethyl)imidazolium salts with lipophilic or hydrophilic substituents on the imidazole and benzimidazole rings, Kerri L. Shelton**, Patrick O. Wagers, Michael A. DeBord, Marie Southerland, Matthew J. Panzner, Claire A. Tessier, Wiley J. Youngs, Department of Chemistry, The University of Akron, Akron, OH 

3:40 pm DiPhosphonato Catechol (DPC): From bifunctional electrolytes to conjugated polymersJoshua Gaffen**, Dr. John D. Protasiewicz, Department of Chemistry, Case Western Reserve University, Cleveland, OH 

4:00-4:10 pm break

4:10 pm Ene-Type Cyclization Chemistry from Cyclohexadiene-Tricarbonyliron DerivativesKeith B. Beach**, Anthony J. Pearson. Case Western Reserve University, Department of Chemistry 

 4:30 pm Aziridination via Photolysis Using Hypervalent Iodine, Andrew Kollar**, Bindu Meprathu, John Protasiewicz, Department of Chemistry, Case Western Reserve University, Cleveland, OH

4:50 pm Investigation of Thia-Michael Reversible Addition Towards Dynamic Materials, Katie M. Greenman**, Joy Romulus, Jonathon Onorato, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH

Analytical Chemistry Regina 202 * - Denotes undergraduate presenter ** - Denotes graduate presenter

3:00 pm Lipid Nanodiscs as Potential Carriers of Enzymes: a Light Scattering Study, Ghaith Altawallbeh**1, Chris Verdi1, Christian Gunder2, Kiril A. Streletzky2, Mekki Bayachou1

1 Department of Chemistry, Cleveland State University, OH 2 Department of Physics, Cleveland State University, OH

3:20 pm Qualitative and Semi-Quantitative Analysis of Glycerolipids and Phospholipids in Algae Scenedesmus dimorphus by Shotgun Lipidomics Satya Girish Chandra Avula**1, Joanne Belovich2, Yan Xu1

1Department of Chemistry, Cleveland State University, Cleveland, Ohio 2Department of Chemical Engineering, Cleveland State University, Cleveland, Ohio

3:40 pm Detection of Estrogenic Activity in Water using a Yeast Bioassay Hannah Bowie*, Lisa M. Ponton,Department of Chemistry, Baldwin Wallace University  

4:00-4:10 pm break

4:10 pm Quantifying Hypomethylating Effect of Decitabine in HL60 Cells by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) Sujatha Chilakala**, Yan Xu, Department of Chemistry, Cleveland State University, Cleveland, Ohio

4:30 pm Developing New Schiff Bases for Fluorescent Detection of Aluminum Cation and Their Potential Applications, Lucas McDonald**, Jungfeng Wang, Nick Alexander, Hui Li, Yi PangThe University of Akron, Department of Integrated Bioscience, Department of Chemistry Akron, OH

4:50 pm Determination Of Bardoxolone Methyl By Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS), Chandana Mannem**, Yan Xu* Department of Chemistry, Cleveland State University, Cleveland, Ohio

Inorganic/Materials/Analytical I Regina 210 * undergraduate presenter ** graduate presenter

3:00 pm Chiral Channels in Molecular Co-Crystals: Unexpected Structures that arise from the co-crystallization of 2,4,6-tris(4-X-phenyl)arenes, Ren A. Wiscons1*, Holden W. H. Lai1, Matthias Zeller2, Jesse L. C. Rowsell1

1Department of Chemistry and Biochemistry, Oberlin College, Oberlin, Ohio2Department of Chemistry, Youngstown State University, Youngstown, Ohio

3:20 pm Updated Dielectric Thermal Analysis and Differential Scanning Calorimetry studies led to a unified Polaron Theory of Ionic Conduction of organic and inorganic crystalline materials Alan T. Riga, PhD1,2, Hannah Conway1,

1Notre Dame College, South Euclid, Ohio2Case Western Reserve University, Cleveland Ohio

4:00-4:10 pm break

4:10 pm Computational Techniques for the Design of Mechanically Interlocked Molecules, Eric P. Bruckner*, Katie M. Greenman, Michael J.A. Hore, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio

4:30 pm Excited-State Dynamics as a Benchmark for the Optimization of Small-Molecules for Organic Photovoltaics, Regina DiScipio**, Geneviève Sauvé, and Carlos E. Crespo-HernándezDepartment of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, Ohio

4:50 pm Legal Case study to evaluate product Liability used Forensic Polymer Chemistry measured by FTIR spectroscopy and Differential Scanning Calorimetry, Jacob Kirsh*, Hannah Conway, Alan T Riga, Notre Dame College, South Euclid, Ohio

Inorganic/Materials/Analytical II Regina 211 * undergraduate presenter ** graduate presenter

3:00 pm Enhancing the Phototherapeutic Potential of Sulfur-Substituted DNA and RNA Analogues Marvin Pollum** and Carlos E. Crespo-Hernández, Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, Ohio

3:20 pm A Critical Assessment Of As A Figure Of Merit For Oxygen Reduction Electrocatalysts In Aqueous Electrolytes, Nicholas S. Georgescu**, Adriel J. J. Jebaraj, and Daniel SchersonDepartment of Chemistry, Case Western Reserve University, Cleveland, OH

3:40 pm Effect of Dielectric Properties on Drug Transport Through Shedded Snake Skins Hannah Conway1*, Jacob Kirsh1, Sean Cadden2, Emily Bussis2 , Alan Riga 1,2

1Notre Dame College Ohio, South Euclid Ohio USA2CWRU, Polymer Science and Engineering, Cleveland, Ohio USA

4:00-4:10 pm break

4:10 pm Photophysics of Bacteriochlorin Dyads, Christopher McCleese**a, Zhanqian Yub, Nopondo Esemotob, Arun Mannac, Barry Dunietzc,*, Marcin Ptaszekb,*, Clemens Burdaa,*

a Department of Chemistry Case Western Reserve University, Cleveland, OHb Department of Chemistry University of Maryland Baltimore County, Baltimore, MDc Department of Chemistry Kent State University, Kent, OH

4:30 pm Modeling And Measuring Thermal Properties Of Methylammonium Lead Halide Perovskite, Anton Kovalsky**a, Gage Marekb, Lily Wanga, Jeffrey Dyckb, Clemens Burdaa

a Case Western Reserve University, Department of Chemistry, Cleveland, OHbJohn Carroll University, Department of Physics, Cleveland, OH

Abstracts

Biochemistry I, Regina 019 * - Denotes undergraduate presenter ** - Denotes graduate presenter

3:00 pm RNase L is involved in type I diabetes onset, Qiaoyun Zheng**, Chun Zeng, Xin Yi, and Aimin Zhou, Clinical Chemistry Program, Department of Chemistry; Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH

The cause of type I diabetes continues to be a focus of investigation. Studies have revealed that interferon (IFN)- in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type I diabetes. However, how IFN- contributes to the onset of type I diabetes is obscure. In this study, we found that 2-5A dependent RNase L (RNase L), an IFN--inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type I diabetes. By using RNase L deficient, rat insulin promoter (RIP)-B7.1 transgenic mice which are more vulnerable to environmental harmful factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin (STZ), a drug which can artificially induce type I-like diabetes in experimental animals. Immunohistochemical staining showed that the population of infiltrated CD8+ T-cells was remarkably reduced in the islets of RNase L deficient mice, suggesting that RNase L may contribute to type I diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas in induced conditions. Our findings provide new insight into the molecular mechanism underlying -cells destruction and may suggest novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L.

3:20 pm Graphene-Based Composites for Detection and Quantification of Peroxynitrite, Haitham Kalil**, Mekki Bayachou, Department of Chemistry, Cleveland State University, Cleveland, OH

Recent clinical research indicates that the cytotoxicity role of peroxynitrite (ONOO-) plays an essential role in several cardiovascular dysfunctions and other diseases triggered by oxidative stress. Peroxynitrite (PON) is a strong oxidizing agent produced from the diffusion-controlled reaction between nitric oxide radical (●NO) and superoxide anion-radical (●O2

-). PON attacks vital components inside the body and initiates deleterious effects via direct and indirect interactions. It reacts directly with lipids, DNA, and proteins and indirectly serves as a trigger of radical chain reactions. Some of these reactions yield to cellular dysfunctions that may end up with necrosis or apoptosis of cells.

Previously, we have shown that hemin and hemin-modified graphene can be used as catalytic platforms for electrochemical detection and quantification of peroxynitrite. In this work we prepare metal-decorated graphene-based composite materials as potential catalytic interfaces for sensitive electrochemical determination of PON. We first describe the method of preparation of metal-modified graphene materials. We characterize the hybrid materials using a number of methods including scanning electron microscopy (SEM), atomic force microscopy (AFM), raman, and x-ray photoelectron spectroscopy (XPS). The modified metal-graphene composite is then tested on carbon electrodes for PON detection and quantification using voltammetry and dose-response amperometry. We compare and contrast the performance of the new metal-graphene materials with hemin-only based electrodes as well as bare graphene based electrodes.

3:40 pm Incorporation of Azide Functionality into Recombinant Protein via Recombinant, Enzymatic, and Chemical Approaches for Bio-Orthogonal Modification Lin Wang1**, Rui Jiang1, Lin Wang2 and Xue-Long Sun1. 

1Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation of Health and Disease (GRHD), Cleveland State University, Cleveland, OH2Department of Medicinal Chemistry, China Medical University, Shenyang, Liaoning, China. 

In this study, we systemically investigated four different strategies to introduce azide functionality into recombinant thrombomodulin (TM), site-specifically by recombinant, chemical, and enzymatic methods at either N-terminus or C-terminus for its bio-orthogonal modification application. The first method is to express near C-terminus azido-TM by unnatural amino acid expression. The second method is to incorporate azide molecule into the C-terminus of recombinant TM via sortase-mediated ligation (SML). The third method is to add azide molecule to the N-terminal amine of recombinant TM via amidation chemistry, and the fourth method is to introduce azide to recombinant TM via a tyrosine selective three-component Mannich reaction. The azido-TM derivatives obtained in all four methods were successfully applied for site-specific modification and immobilization of recombinant TM through copper-free click chemistry with upholding their protein C activation activities. In comparison, incorporating azide molecule into the C-terminus of recombinant TM via SML affords highest overall yield since the key protein expression step uses all natural amino acids. Also, single site modification and immobilization facilitate the highest TM activity. Overall, the reported site-specific azide incorporation strategies can be widely used in chemical biology and biomedical research and applications.

4:10 pm Dissolution of Aggregated Islet Amyloid Polypeptide (IAPP) in Rat Insulinomas Using Novel Beta-Sheet Breakers Melissa Barranger-Mathys, Ph.D. Ursuline College, Department of Chemistry

Islet amyloid polypeptide (IAPP), or amylin, is a 37-residue polypeptide that is co-secreted with insulin by pancreatic β-cells. IAPP self-associates, forms cytotoxic fibrils, and aggregates into a β-sheet conformation even at nanomolar concentrations1. This aggregation is the main constituent of pancreatic amyloid, which is observed in patients with Type II Diabetes Mellitus. Inhibition of this fibrillogenesis of may prevent the death of these β-cells. Research suggests that a class of compounds known as β-sheet breakers have the ability to alter the secondary structure of amyloid plaques, making them more soluble and unable to self-associate. Using insulinomas in rat pancreatic β-cells, we tested the ability of our novel five amino acid β-sheet breakers to decrease the aggregation of IAPP. Immunofluorescent FITC tags allowed the visualization of IAPP in the cells with and without β- sheet breaker peptide treatment.

Meng, F. et al. (2007) Biochemistry, 46, 12091- 12099.

4:40 pm Profiling Sialylation Status during Monocytes Differentiation, Dan Wang**1, Evgeny Ozhegov2, Aimin Zhou1, Xue-Long Sun1*

1Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio 2Department of Biological, Geological, and Environmental Sciences (BGES), Cleveland State University, Cleveland, Ohio

Sialic acids (SAs), a family of 9-carbon containing acidic monosaccharides, often terminate the glycan structures of cell surfaces and are involved in many biological functions including early fetal development, cellular recognition and adhesion, and its utilization by microbes. While it is clear that cell surface SAs are highly involved in the immune system, the sialylation status related to individual immune cells and their activation state and functions are still unknown. In this study, we combined a newly developed LC-MS/MS method, along with flow cytometry and confocal microscopy to profile the changing pattern of SAs during THP-1 monocytes differentiation and polarization. After PMA treatment, free SA in the culture medium increased from 4.18±0.01 ng/ml to 11.57±0.78 ng/mL, α-2,3 SAs on the cell surface decreased 35%, and α-2,6 SAs decreased 25%. These results were confirmed by sialidase activity assay, which showed the activity of major sialidase (Neu1) increased by more than a factor of 2. Cellular SAs increased from 718±6 ng/mL to (1.59±0.5)×103 ng/mL. This change was verified by confocal microscopy, which showed the increase of both α-2,3 and α-2,6 SAs inside the cells. Moreover, after M1 and M2 polarization, cellular SA decreased 26% in M1 macrophages and increased 13% in M2 macrophages compared with only PMA treatment. Overall, this study provides for the first time a global investigation of the cellular sialylation status of monocytes and differentiated and polarized macrophages. It has potential significance in understanding the pathology and diagnosis of disorders involving SAs and the immune system.

Biochemistry II, Regina 024

3:00 pm Lipids Affect Thrombomodulin's Capacity to Generate APC and TAFI, Valentinas Gruzdys**1 and Xue-Long Sun1,2

1Department of Chemistry, Cleveland State University

2 Department of Biomedical Engineering, Cleveland State University

Protein C (PC) and thrombin activatable fibrinolysis inhibitor (TAFI) are both activated by the thrombin-thrombomodulin (TM) complex yet have seemingly opposite effects in haemostasis. PC downregulated coagulation while TAFIα maintains already formed clots. There is strong evidence to suggest that PC and TAFI act as competitive inhibitors to one another. Furthermore, it is well known that the activation of protein C by thrombin-TM is greatly affected by phospholipid presence, especially negatively charged phospholipids such as phosphatidylserine which can be exposed during platelet activation. Both APC and TAFI are significant indicators on haemostatic performace. Elevated TAFI antigen levels have been associated with coronary heart disease and other pathologies. We hypothesize that in the presence of different phospholipids, the inhibitory role of PC towards TAFI activation can be significantly altered and result in reduced activation of TAFI in protein C presence. In this work, we determine which lipids have the most significant effect on APC and TAFIα generation. We also determine which lipids result in enhancement of protein C inhibitory role towards TAFI activation.

3:20 pm The Role Of Lipid-Free Apolipoprotein A-I Self-Association In The Formation Of High Density Lipoprotein, Celalettin Topbas**1,2, Joseph A. Didonato2,3, Jonathan D. Smith2, Stanley L. Hazen2,3,4, Valentin Gogonea1,2,3

1Department of Chemistry, Cleveland State University, Cleveland, OH2Department Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH3Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH, 4Cardiovascular Medicine Department, Cleveland Clinic, Cleveland, OH

Apolipoprotein A-I (apoA-I), the main protein constituent of high density lipoprotein (HDL), forms a dimeric antiparallel structure that both confers nascent HDL stability and provides a scaffold for the lipid phase. We performed kinetic analyses of monomeric and oligomeric apoA-I employing both hydrogen-deuterium exchange mass spectrometry (HDX-MS) and functional lipidation assays. At low concentrations lipid-free apoA-I is monomeric based on equilibrium PAGE, dynamic light scattering, and cross-linking studies. Despite this, the protein displays in multiple discrete yet reproducible regions bimodal HDX kinetics indicating the presence of intra-molecular protein – protein interactions (hairpin loops). Kinetic HDX studies further reveal that at higher concentrations, lipid-free apoA-I self-associates and dimerizes through a ten amino acid C-terminus domain (E223-A232). This is suggested by the appearance of new intermolecular interactions surfacing at higher apoA-I concentrations concurrent with the multimeric apoA-I forms. Surprisingly, apoA-I self-association through E223-A232, an equilibrium process, significantly slowed down the rate of apoA-I lipidation. Our studies indicate that HDL genesis starts with lipidation of apoA-I monomers followed by apoA-I dimerization in an antiparallel fashion on the lipid surface.

3:40 pm Simultaneous Determination Of Dihydrotestosterone And Its Metabolites In Mouse Sera By Lc-Ms/Ms With Chemical Derivatization, Shashank Gorityala** a, Shuming Yang b, Monica M. Montano c, Yan Xu a,b

aDepartment of Chemistry, Cleveland State University, Cleveland, Ohiob Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OHcDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH

Prostate cancer is the second leading cause of cancer-related deaths among men. Androgens play a key role in the prostate cancer development, and their elimination and blockade is vital in the disease management. Dihydrotestosterone (DHT) is the key ligand for androgen receptor (AR) in prostate and is locally synthesized from testosterone. In prostate, DHT is predominantly metabolized to 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol). Recent studies show that impaired DHT catabolism is associated with the prostate cancer which signifies the requirement of a sensitive quantitative method for the determination of DHT and its metabolites.

In this work, an LC-MS/MS method has been developed and validated. Steroid-free serum was prepared and used for the preparation of serum calibrators and QCs. DHT and its metabolites along with their respective stable heavy isotope labelled internal standards were first extracted with methyl tert-butyl ether (MTBE) and derivatized with picolinic acid (PA), then the deriviatized analytes were extracted again with MTBE, dried under nitrogen and reconstituted in the mobile phase (80% methanol and 0.2% formic acid in water). Chromatographic separation of the derivatized analytes was achieved isocratically on Xterra C18 column (2.1 x 100 mm) using the mobile phase at a flow rate of 0.25 ml/min. Quantitation was performed using multiple-reaction-monitoring mode with positive electrospray ionization. The mass transitions used were 396 255 for DHT, 399 258 for DHT-d3, 398 257 for 3α-diol, 401 260 for

3α-diol-d3, 503 257 for 3β-diol and 506 260 for 3β-diol-d3. The method has calibration ranges from 0.0500 ng/mL to 50.0 ng/mL for DHT and its two metabolites with acceptable assay precision, accuracy, recovery, and matrix factor. It has been applied to the determination of DHT and its metabolites in a preliminary animal study.

4:10 pm Evaluating The Pro-Mutagenic Replication Of 8-Oxoguanine Anvesh Dasari 1 **, Anthony J Berdis1, 2, 3

1Department of Chemistry, Cleveland State University, Cleveland, OH 2Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 3Red5 Pharmaceuticals, LLC, Cleveland, OH

Oxidative stress produces reactive oxygen species that can damage DNA. The consequences of this can be devastating as the formed DNA lesions are mutagenic and their misreplication cause diseases such as Parkinson’s disease and cancer. 8-oxoguanine (8-OG) is one such lesion that could initiate mutagenesis due to its miscoding nature. Oxidation to the C-8 position of guanine changes its equilibrium from the normal anti conformation to the syn conformation. This simple conformational change results in the misinsertion of dATP opposite the lesion rather than dCTP. To better understand the mutagenic replication of 8-OG, we performed a thorough kinetic analyses for the incorporation of natural and modified nucleotide analogs opposite this miscoding DNA lesion using a high-fidelity DNA polymerase. Mechanistic studies Using modified purines as substrates, our mechanistic work demonstrate that alterations to functional groups associated with hydrogen bonding interactions cause significant decreases in the overall efficiency for their utilization. Surprisingly, the lower efficiencies result from large reductions in the rate constant for insertion rather than from negative effects on nucleotide binding. In fact, all modified nucleotides tested here display higher binding affinities against 8-OG compared to natural nucleotide substrates (dCTP and dATP). These results suggest that substrate binding is influenced by the hydrophobic nature of the incoming nucleotide while the chemistry step is controlled by the formation of correct hydrogen-bonding interactions between the incoming nucleotide and templating nucleobase. Collectively, these studies help explain the pro-mutagenic nature of 8-OG. Future studies are aimed at designing additional nucleotides that can monitor the cellular replication of 8-OG as well to develop inhibitors to block its misreplication.

4:30 pm Role of RNase L in Kidney Norah J Alghamdi**, Qiaoyun Zheng, Danting Liu, and Aimin Zhou, Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH

Renal diseases have been continuing to be a prevalent problem. Current data indicate that 1% of patients admitted to the hospital are diagnosed initially with

acute kidney injury (AKI), while about 2-5% of hospitalized patients develop AKI secondarily. It has been reported that epidermal growth factor (EGF)/EGFR activation contributes to the development and progression of renal diseases such as obstructive nephropathy, diabetic nephropathy, hypertensive nephropathy, and glomerulonephritis through mechanisms involved in induction of tubular atrophy, overproduction of inflammatory factors, and/or promotion of glomerular and vascular injury. In this study, we showed that 2-5A dependent RNase L (RNase L), one of the key enzymes playing an important role in the molecular mechanisms of interferon functions against microbal infection and cell proliferation, mediated EGF/EGFR activation. Interestingly, we found that the kidney size of aged RNase L deficient mice was significantly smaller than that in wild type mice under the same condition. Histological staining revealed that there were remarkably a higher number of vacuoles in the kidney of RNase L deficient mice than that in wild type mice although the biological significance of the observation is largely unknown. Proteomic analyses of urine protein excretion discovered that lack of RNase L exclusively blocked EGF excretion. Further investigation of the molecular mechanism showed that RNase L regulated the shedding of EGF precursor through inhibiting some specific proteases responsible for the event. Our findings provide new insight into the pathogenesis of renal diseases and RNase L may be considered as a target molecule for therapeutic treatment of the diseases.

4:50 pm Determination of Monosialogangliosides in Human Plasma by a Novel UPLC/MS/MS Assay Coupled to Chemical Derivatization, Qianyang Huang**1, Xiang Zhou1, Danting Liu1, Baozhong Xin2, Karen Cechner2, Heng Wang2, and Aimin Zhou1 1Clinical Chemistry Program, Cleveland State University Cleveland, OH 2DDC Clinic, Center for Special Needs Children, Middlefield, OH

Gangliosides are a large subfamily of glycosphingolipids that present abundantly on the plasma membrane of neuronal and glial cells of vertebrates. These molecules are structurally characterized by a distinctive oligosaccharide moiety attached to a ceramide portion with variable length on fatty acid chain. Physiologically, they are believed to play critical roles in the regulation of various receptor-mediated cell signaling pathways and cellular events. Disruptions and disturbances in their metabolic pathways have been found to pathologically facilitate the pathogenesis of numerous neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and ganglioside GM3 synthase deficiency (GSD). Therefore, a reliable LC/MS/MS method with enhanced sensitivity is urgently demanded for relevant biomedical studies.

In this work, a novel reverse phase UPLC/MS/MS method for determination of three monosialoganglioside species, GM1, GM2, and GM3, in human plasma has been developed and validated. This assay employed DMTMM & PAEA chemical derivatization for signal enhancement and D3-labeled monosialogangliosides as internal standards (IS). The analytes and ISs were extracted from plasma using protein precipitation procedure, cleaned up with a mixture of water/methanol/chloroform, dried under nitrogen purging, and derivatized with DMTMM & PAEA under optimized conditions. Thereafter, the samples were injected into a Shimadzu Nexera UHPLC system interfaced to an AB Scix Qtrap 5500 mass spectrometer that operating in ESI positive and Multiple Reaction Monitoring (MRM) mode to achieve highly sensitive and specific detection.

This method has been applied to monitor plasma levels of monosialogangliosides in patients with GSD for clinical diagnosis and therapeutic evaluation during the ongoing clinical trial.

Biochem/Organometallic/Polymers, Regina 025 * - undergraduate presenter ** - graduate presenter

3:00 pm Histidine-Tagged Peptide Binding to Anionic Lipid in Asymmetric Supported Lipid Bilayers, Xiaosi Li** and Adam W. Smith, Department of Chemistry, The University of Akron

Study on the interaction between peptide with lipid plays a critical role in the understanding of various biological processes in plasma membrane. In the supported lipid bilayers(SLBs) model system, anionic lipid phosphatidylinositol biphosphate(PIP2) can interact with protein or peptide that contains the polybasic regions. While , previous research demonstrated that there has some limits to use SLBs to probe peptide dynamics due to the weak binding. Here we present that the Nickel-chelating lipid on the fluid SLBs could selectively interact with histidine-tagged peptide, this specific interaction can siginificant increased the electrostatic interaction between lipid and peptide. After labeling the fluorescent dyes, diffusion and colocalization can be measured by a time-resolved fluorescence spectroscopy called pulsed interleaved excitation fluorescence cross-correlation spectroscopy(PIE-FCCS). The result show us that after lipid-peptide complex formed the lipid lateral mobility is decreased and electrostatic interactions is also influenced by the different concentration of buffer conditions.

3:20 pm Ferreting out homo- and heterodimerization of G-protein coupled receptors (GPCR) via PIE-FCCS William D. Comar** and Adam W. Smith, University of Akron, Akron, OH

Quantifying membrane protein-protein interactions is experimentally challenging, especially in live cells. The complexity of the plasma membrane makes it difficult to rely on observations from reductive model systems. I will present our recent work studying opsin, a prototypical Class A G-protein coupled receptor (GPCR), in live cell membranes. Opsin dimerization has been reported by several groups, but the prevalence and physiological relevance of opsin dimerization remains controversial. To quantify the presence of opsin dimers we have used a time-resolved fluorescence technique called pulsed interleaved excitation fluorescence cross correlation spectroscopy (PIE-FCCS). PIE-FCCS translates fluctuations in fluorescence intensity (arising mainly from diffusion) into information about a protein’s mobility and concentration. By cross-correlating the fluorescence fluctuations in two color channels, PIE-FCCS also quantifies co-localization and co-diffusion with high accuracy (Smith 2012). Our results for individual cell measurements revealed that opsin is predominantly organized into clusters. At low concentrations, we observed that the population of oligomers increased linearly with the square of the individual monomer populations. This evidence suggests a monomer-dimer equilibrium and provides an experimental measurement of the dimerization equilibrium constant. These conclusions were supported by complementary fluorescence methods including fluorescence lifetime and molecular brightness analysis.

Smith. AW; Lipid-protein interactions in biological membranes: A dynamic perspective; Biochimica et Biophsica Acta-Biomembranes 2012, 1818(2):172-177Comar, WD, Schubert, SM, Jastrzebska, B, Palczewski, K, Smith, AW; Time-resolved fluorescence spectroscopy measures clustering and mobility of a G Protein-coupled receptor Opsin in live cell membranes; J. Am. Chem. Soc. 2014, 136:8342-8349

 

3:40 pm Stimuli-Responsive Liquid Crystalline Elastomer Actuators, Brian T. Michal**, Blayne M. McKenzie, Simcha E. Felser and Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH

Liquid crystalline elastomer (LCE) materials have been prepared using the metal binding ligand 2,6-bisbenzimidazolylpyridine (Bip) as a multi-functional monomer. The Bip ligand exhibits thermotropic liquid crystalline properties and has a metal binding site which switches off the liquid crystalline properties of the molecule upon binding a metal ion, thus leading to materials which are both thermo- and metallo- responsive. Incorporation of the Bip ligand in to non-dynamic polymeric networks via thiol-ene chemistry results in a material that can change its shape or actuate in response to heat, light (via a photo-thermal transition of the Bip chromophore) or metal ions. The materials show a high degree of both fixing and recovery in shape memory experiments using either heat or a metal ion as the stimulus. Furthermore, the materials can generate actuation forces in response to heat, light or metal ions. Finally, a structurally dynamic LCE has been produced by incorporating disulfide bonds into the LCE network. This allows for access to monodomain liquid crystalline morphologies which show a much greater actuation response.

 

4:10 pm Optimizing the formation of [3]catenates containing 2,6-bis(N-alkylbenzimidazolyl)pyridineQiong Wu**, Rudy J. Wojtecki, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio

Metal-ligand coordinating is an effective approach toward [2] or [3]catenanes; however, the synthesis of linear mainchain poly[n]catenanes remains a great challange due to the difficulty of cyclization after threading.1 To study the ring-closing efficiency, the 2,6-bis(N-alkyl-benzimidazolyl)pyridine (Bip) ligand was utilized to access mechanically interlocked [3]catenanes via metal-templating.2 Two Bip ligand contating components, namely macrocycles and linear threads, were designed to self-assemble upon the addition of transition metal ions into [3]metallopseudorotaxanes that require a single olefin metathesis ring-closing reaction to yield the [3]catenate. The ring-closing reaction was studied by two-dimensional diffusion-ordered NMR spectroscopy (DOSY). The result showed that the cyclization conversion of the [3]catenates was dependent on two parameters: (1)the preorganization and conformational flexibility of the thread-like component; and (2) the size of the N-alkyl substituents on the Bip in the macrocyclic component.2 Judicious design of both components dramatically improved the cyclization yield, and thus the formation of the [3]catenate was predominantly favoured.2 This result might open a door toward the synthesis of longer mainchain poly[n]catenanes, the progress toward which will also be discussed.

References1) Niu, Z. B.; Gibson, H. W., Chem. Rev. 2009, 109, 6024–6046.2) Wojtecki, R. J.; Wu, Q.; Johnson, J. C.; Ray D. G.; Korley, L. T. J.; Rowan, S. J. Chem. Sci. 2013, 4, 4440–4448.

 

 4:30 pm Synthesis of Lead Oxide Carboxylate Single Crystals and Nanostructures, Calvin Gang*,1 Venkata Shiva Mandala,1 Matthias Zeller,2 Catherine M. Oertel1

1Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH2Department of Chemistry, Youngstown State University, Youngstown, OH

Low-dimensional materials are systems with at least one spatial dimension on the nanoscale. These systems have received attention because of their unique properties that can differ from their bulk counterparts with the same chemical identity. We have synthesized and structurally characterized a series of novel lead carboxylates that are potential starting points for solution processing to prepare low-dimensional materials. When subjected to methods of liquid exfoliation, lead benzoate hydrates with fluorinated and chlorinated ligands have successfully formed low-dimensional wire-shaped nanostructures. Analyses of these materials via powder X-ray diffraction, SEM imaging, and IR spectroscopy suggest that the halogenated lead benzoate hydrate compounds chemically convert to corresponding lead oxide benzoate compounds during the sonication process. The role of solutions processing in the formation of these nanowires offers insight to the properties of an interesting family of lead carboxylate inorganic-organic hybrid compounds as well as opportunities to further develop an understanding of the production of low-dimensional material on the nanoscale via methods of liquid exfoliation.

 4:50 pm Selective nitrosylation of GAPDH occurs via the S100A8/A9 protein complex: A theoretical investigation, Arlene Praniewicz*1,2 and Valentin Gogonea1,2,3

1Department of Chemistry, Cleveland State University, Cleveland, OH2Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH3Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH

Selective nitrosylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) at Cys-247 affects gene regulation through the interferon-gamma (IFN-g) activated inhibitor of translation (GAIT) complex. Oxidized low-density lipoprotein (LDLox) and INF-γ induces assembly of the nitrosylase complex composed of inducible nitric oxide synthase (iNOS), S100A8 and A100A9 proteins. Intracellular GAPDH has been shown to exist as a mixture of monomer, dimer, and tetramer in cell lysate. Because the crystal structure of the S100A8/A9/GAPDH complex is not known, Fox lab at Cleveland Clinic used the ‘‘artificial protease’’ cleavage mapping [Fe(III) (s)-1-(p-bromoacetamidobenzyl) EDTA (FeBABE)] to identify domains of GAPDH (1 and 3) that may interact with S100A8. Within this project, our goal is to produce molecular models for the complex of GAPDH monomer, dimer and tetramer with S100A8/A9 proteins by using protein-protein docking calculations (with the program PatchDock). The molecular models selected for these complexes were further refined with the program FireDock. The candidate molecular models were analyzed by measuring the shortest distance from GAPDH interaction domains (1 and 3) to each of the three FeBABE linking site residues of S100A8, shown by experiment to produce significant cleavage (Ile22, D32, D52). The known cleavage radius (~12Å) and length of FeBABE (~14Å) were used to approximate the maximum distance at which interaction could occur. Proposed models of the S100A8/A9/GAPDH complex presented herein were selected as the best candidates from each category based on this criteria and overall consistency with the FeBABE cleavage experimental data. Our analysis concludes that molecular models of GAPDH tetramer and monomer with S100A8/A9 lead to cleavage patterns that agree with the experimental data.

Organic Chemistry , Regina 201 * - undergraduate presenter ** - graduate presenter

3:00 pm Conjugated Organophosphorus Materials, Alexandra Grimm**, Dr. John ProtasiewiczCase Western Reserve University, Dept. of Chemistry, Cleveland, OH

Phosphorus and carbon have similar electronegativities, making bonds between the two elements relatively non-polar. This unique similarity has led to phosphorus atoms in these bonds being referred to as a “carbon copy”. A variety of compounds have been created exploiting this analogy containing multiply bonded low coordinate phosphorus atoms. Benzoxaphospholes (BOPs) are among these compounds. These BOPs are a class of compound which has a P=C bond within the -conjugated system. Materials that possess P=C bonds have useful photophysical and electroluminescent properties. It is a goal to expand upon these compounds and integrate in polymers, with the P=C bonds as part of the -conjugated system. Materials with such systems promise desirable and unique properties not easily accessible via materials featuring only C=C units for -conjugation. These materials could have applications such as use in organic light emitting diodes, organic solar photovoltaics, and flexible electronics.

3:20 pm Synthesis and anti-proliferative activity of N,N’-bis(arylmethyl)imidazolium salts with lipophilic or hydrophilic substituents on the imidazole and benzimidazole rings, Kerri L. Shelton**, Patrick O. Wagers, Michael A. DeBord, Marie Southerland, Matthew J. Panzner, Claire A. Tessier, Wiley J. Youngs, Department of Chemistry, The University of Akron, Akron, OH

The research area of imidazolium salts is of interest to the scientific community because of their potential as alternative anti-tumor agents to drugs presently used in clinics. Clinically used chemotherapeutics agents, such as cisplatin, are used to treat a variety of cancer types; however, they are also coupled with numerous side effects. N,N’-bis(naphthylmethyl)imidazolium salts have been shown to have anti-proliferative activity comparable to that of cisplatin. However, these highly powerful N,N’-bis(naphthylmethyl)imidazolium salts tend to have inferior aqueous solubility.

In order to develop imidazolium salts with both high anti-proliferative activity and sufficient aqueous solubility, a series of N,N’-bis(arylmethyl)imidazolium salts substituted with a variety of hydrophilic or lipophilic groups on a number of the positions on the imidazole and benzimidazole rings. A series of N,N’-bis(arylmethyl)imidazolium salts are synthesized, characterized and tested against a panel of non-small cell cancer cell lines. Variations of the substituents on the heterocycles’ carbon and nitrogen atoms can impact the lipophilicity and aqueous solubility.

3:40 pm DiPhosphonato Catechol (DPC): From bifunctional electrolytes to conjugated polymers

Joshua Gaffen**, Dr. John D. Protasiewicz, Department of Chemistry, Case Western Reserve University, Cleveland, OH

Originally synthesized as a precursor to aryl diphosphonic acids, but never isolated, tetraethyl-3,6-diphosphonatocatechol (DPC) has been synthesized in two synthetic steps and isolated with an overall yield of 60-70%. This versatile compound was first used in our lab as a chelate in lithium borates and phosphates for use as an electrolytic salt in lithium-ion batteries. These salts demonstrated a strong charring capability which means they could act as a flame retardant barrier in a lithium-ion battery while also acting as the electrolytic salt. This would allow for the addition of a flame retardant to a lithium-ion battery without the need to remove other components, which would reduce the battery capacity. The simple synthesis of DPC also allows permutations to the compound, allowing for the generation of “modified” DPC compounds which target specific properties such as solubility. While keeping the same general synthetic approach, “DPC-like” compounds with changes to both the catechol and the phosphonate moieties have been generated. Additionally DPC can undergo a reduction to generate diphosphinocatechol (DPC-H6). This compound is air stable, despite containing two primary phosphines. DPC-H6 has been utilized in the generation of novel fluorescent phosphaalkenes, and shows potential as a precursor to fluorescent polymeric phosphaalkenes.

4:10 pm Ene-Type Cyclization Chemistry from Cyclohexadiene-Tricarbonyliron DerivativesKeith B. Beach**, Anthony J. Pearson. Case Western Reserve University, Department of Chemistry

Diene-tricarbonyliron chemistry has found great utility in organic synthesis. One area of particular interest utilizes an iron-promoted ene-type reaction to facilitate spirocyclization or tandem double-

cyclization when a pendant alkene or diene is available, respectively. Previously in the Pearson lab, spirocyclizations as well as double-cyclizations have been reported starting from compounds containing a heteroatom (O, S, NPh) within the tethered side chain. The work herein focuses on the preparation of cyclization products containing an all-carbon backbone, such as 1. The intriguing aspect of this fundamental research is that synthesis of potential natural product-derivatives may be achieved, in particular those of the angular triquinane class.

4:30 pm Aziridination via Photolysis Using Hypervalent Iodine, Andrew Kollar**, Bindu Meprathu, John Protasiewicz, Department of Chemistry, Case Western Reserve University, Cleveland, OH

This talk will focus on the investigation of making aziridines through photolysis of hypervalent iodine compounds. A previously made compound, 2-(tert-butylsulfonyl)tosylaminoiodobenzene will be examined to make aziridines from olefins specifically styrene derivatives. Current literature on epoxidation and hydroxylation reactions with hypervalent iodine compounds mention the need for a metal catalyst. Using photolysis the need for a metal can be removed. NMR and GC-MS spectroscopy have been used to characterize new compounds and to analyze these photolysis reactions.

4:50 pm Investigation of Thia-Michael Reversible Addition Towards Dynamic Materials, Katie M. Greenman**, Joy Romulus, Jonathon Onorato, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH

A common synthetic approach to polymeric material design utilizes either covalent bonds or supramolecular interactions to bind long chains together forming a crosslinked network. Both methods, while proven successful in many cases, experience pitfalls that leave critical gaps in their final material properties. Supramolecular interactions generally lack the strength and stability of covalent bonds whereas materials that utilize covalent bonds, as in thermoset plastics, have little to no re-processability once the network has been fixed. This gap between strength and chemical flexibility can be bridged by utilizing dynamic covalent chemistry. In our approach, we construct a ditopic crosslinker with a Michael-acceptor active site that binds reversibly with thiol functional groups. By modifying the chemistry of the crosslinker, mainly the electron-withdrawing capabilities of the end groups, we are able to shift the equilibrium and adjust the kinetics of the reaction which in turn allows us to tailor the reversibility of covalent linkages and program the mechanical properties of the final material. In order to fully understand the differences in dynamic properties between the various Michael-acceptors, an array of kinetic experiments were performed using monotopic analogues to the ditopic crosslinkers. The resulting information is used to understand and explain the unique mechanical properties in the crosslinked films.

Analytical Chemistry Regina 202 * - Denotes undergraduate presenter ** - Denotes graduate presenter

3:00 pm Lipid Nanodiscs as Potential Carriers of Enzymes: a Light Scattering Study, Ghaith Altawallbeh**1, Chris Verdi1, Christian Gunder2, Kiril A. Streletzky2, Mekki Bayachou1

1 Department of Chemistry, Cleveland State University, OH 2 Department of Physics, Cleveland State University, OH

The structure and dynamics of discoidal phospholipid protein complexes (nanodiscs) with and without endothelial nitric oxide synthase (eNOS) were studied with multiangle polarized and depolarized light scattering. Nanodiscs present a mobile system that is similar to enzyme’s native microenvironment which allows to explore the potential effect of membrane phospholipids on the activity of eNOS. Light scattering revealed at least two different size distribution modes for empty nanodiscs, and nanodiscs loaded with eNOSoxy. In both cases, the first mode was diffusive (linear G vs q2 with a small intercept) with apparent RH = 6.4 nm for empty nanodiscs and 6.0 nm for loaded nanodisc, sizes consistent with nanodisc dimensions. The second mode contributed 50% or less and showed non-diffusive behavior which might correspond to coalesced nanodiscs present in solution. Studied concentration dependencies and depolarized scattering measurements on enzyme free and enzyme loaded nanodiscs corroborated these findings. Also, the specific activity of nanodiscs-bound eNOS was found to be significantly lower than the specific activity of free eNOS.

3:20 pm Qualitative and Semi-Quantitative Analysis of Glycerolipids and Phospholipids in Algae Scenedesmus dimorphus by Shotgun Lipidomics Satya Girish Chandra Avula**1, Joanne Belovich2, Yan Xu1

1Department of Chemistry, Cleveland State University, Cleveland, Ohio 2Department of Chemical Engineering, Cleveland State University, Cleveland, Ohio

Microalgae can synthesize, accumulate and store large amounts of lipids (up to 40% of dry biomass) in their cells, which hold an immense potential as a renewable source of oil for biodiesel production. In order to optimize the growing conditions of various algal species in engineered gravity settlers, analytical methods for lipid profiling and quantitation are critically needed. Hence, we set forth a quick and effective infusion-based shotgun lipidomics method for high throughput qualitative and semi-quantitative analyses of lipids from Algae, Scenedesmus dimorphus.In this work, we aim to compare the compositional changes of lipids in algal cells cultivated by two different biofertilizers (Digestate and 3N-BB). For this work, algal dried mass spiked with internal standards was first grounded by mortar and pestle, then extracted by modified Bligh-dyer method and fractionated by amino-propyl solid-phase-extraction cartridge into various lipid classes. Each class of lipids was subjected to an array of multiple precursor and neutral loss scans through direct sample infusion. Lipid identifications were accomplished by LipidView™ software. Our data revealed that there were more than 200 glycerolipids and phospholipids species in Algae, Scenedesmus dimorphus. Semi-quantitative analyses of glycerolipid and phospholipids were achieved using internal standards of representative lipids spiked in the samples. Differential analysis of algal lipid profiles raised by two different biofertilizers was done by MarkerView™ software. Principal component analysis (PCA) and t-test were performed to visualize the compositional changes of lipids in the Algae cells. This method provides a useful way to monitor and optimize lipid growing conditions.

3:40 pm Detection of Estrogenic Activity in Water using a Yeast Bioassay Hannah Bowie*, Lisa M. Ponton,Department of Chemistry, Baldwin Wallace University

Estrogenic compounds are found in excess quantities accumulating in natural water systems, in part due to their ability to pass through unhindered by wastewater treatment plants. A yeast bioassay has been employed to detect estrogens and xenoestrogens that find their way into natural water systems.1 A genetic modification to Saccaromyces cerevisiae provided the strain with an estrogen receptor, similar to what humans and other mammals have in their endocrine systems. The yeast is first allowed to grow with either a stock solution of estrogen, such as 17-β-estradiol, or a sterile-filtered water sample, to give time for estrogens and estrogenic compounds to bind with the modified yeast’s receptor. Once induced, yeast is combined with Z-Buffer substrate containing DTT and ONPG. The yeast lyses and yields a yellow color upon the release of o-nitrophenol due to the reaction of β-galactosidase that forms in the cell and the ONPG. Strength of color development depends on the concentration of cumulative estrogenic activity, which allows concentrations to be quantified via spectroscopy. The work presented here focuses on in-house method development so that we can extend our studies to examine natural waterways and wastewater effluent in the Cleveland area.

1. Balsiger, Heather; de la Torre, Roberto; Lee, Wen-Yee; Cox, Marc. A four- hour yeast bioassay for the direct measure of estrogenic activity in wastewater without sample extraction, concentration, or sterilization. Science of the Total Environment. 2010, 408, 1422-1429.

 

4:10 pm Quantifying Hypomethylating Effect of Decitabine in HL60 Cells by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) Sujatha Chilakala**, Yan Xu, Department of Chemistry, Cleveland State University, Cleveland, Ohio

DNA methylation refers to the addition of a methyl group to the cytosine in the CpG dinucleotide by the DNA methyltransferase. Hypermethylation of DNA leads to transcriptional silencing of numerous tumor suppression genes and is the main cause for many types of cancers including acute myeloid leukemia (AML) and myelodysplatic syndrome. Decitabine (5-aza-2'-deoxycitidine) is a nucleoside analog that induces hypomethylation of DNA. Decitabine incorporates into DNA during S-phase of the cell cycle, irreversibly inhibits DNA methyltansferases, and leads to reactivation of the silenced tumor suppression genes. Although the anticancer property of decitabine has been known for 40 years, the therapeutic dosage and schedules are still under clinical investigation. For instance, recent studies show that the low-dose drug regimen with low cytotoxicity was more desirable and efficacious than the high-dose ones. To study the hypomethylating effect of low-dose decitabine, we have developed an ultrasensitive LC-MS/MS method for quantitative assessment of the amounts of decitabine, cytidine, 5-methylcytidine released from cellular DNA by a multi-enzyme digestion. In this method, enzyme digestion reaction was optimized for releasing all deoxynucleosides; stable heavy isotope of 2-deoxycytidine was used as internal standard; chromatographic separation was carried out on reverse-phase C18 column; and analytes of interest were quantified by mass spectrometry operated under the multiple-reaction-monitoring mode. The linear calibration ranges and limits of quantitation for the analytes were established. The method developed has been successfully applied to the measurement of decitabine released from HL60 cellular DNA after low-dose decitabine treatment at various time points.

4:30 pm Developing New Schiff Bases for Fluorescent Detection of Aluminum Cation and Their Potential Applications, Lucas McDonald**, Jungfeng Wang, Nick Alexander, Hui Li, Yi PangThe University of Akron, Department of Integrated Bioscience, Department of Chemistry Akron, OH

As the most abundant metal in the Earth’s crust, aluminum is widely used in various products including food storage, automobiles, and fireworks. Aluminum (III) cation is known to react with various biological tissues, more specifically neural tissue. Excessive aluminum has been shown to be toxic to human, which has been shown to have possible connections to Alzheimer’s and Parkinson’s disease along with a variety of other neural and vascular diseases. A series of fluorescent sensors have been developed to study their optical response to Al3+ ion. The response mechanism of the fluorescent sensors has been examined by using a wide range of spectroscopic methods, which include 1H NMR, single X-ray diffraction crystallography, dynamic light scattering, UV-vis, variable temperature fluorescence spectroscopy, and fluorescent microscopy. The developed sensors were tested in zebrafish embryos of varying ages (24 to 72 hpf), and the models revealed that, after 1.5 hours of exposure to Al3+, the aluminum ions were concentrating in the brain, heart, and in superficial areas of the yolk sack. These results show that the aluminum sensors could have potential applications for studying the possible biological impacts of Al3+ in animal models.

4:50 pm Determination Of Bardoxolone Methyl By Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS), Chandana Mannem**, Yan Xu* Department of Chemistry, Cleveland State University, Cleveland, Ohio

Bardoxolone methyl [2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me] is a semi-synthetic triterpenoid with high anti-inflammatory activity, which currently under clinical trials for the treatment of cancer and chronic kidney disease in type 2 diabetes patients.

In this work, we have developed a rapid and highly sensitive method for quantitation of CDDO-Me in human urine matrix using positive electrospray ionization UPLC-MS/MS. In this method, CDDO-Me and internal standard (CDDO-TFEA) were first extracted from the human urine using methyl tert-butyl ether (MTBE). Chromatographic separation was carried out isocratically on Kinetex C18 column (2.1 × 50 mm, 1.7 µm) using a mobile phase containing 80% acetonitrile and 20% 10 mM ammonium formate with 0.2% formic acid at a flow rate of 0.5 mL/min. Quantitation was accomplished by tandem mass spectrometry using multiple-reaction-monitoring mode with mass transitions of m/z 506.4→446.4 for CDDO-Me and m/z 573.4→ 446.4 for the IS. This method has a lower limit of quantitation (LLOQ) of 0.500 ng/mL and a linear calibration range up to 100 ng/mL in human urine. It has been validated according to the industry guidance for bioanalytical method.

Inorganic/Materials/Analytical I Regina 210 * undergraduate presenter ** graduate presenter

3:00 pm Chiral Channels in Molecular Co-Crystals: Unexpected Structures that arise from the co-crystallization of 2,4,6-tris(4-X-phenyl)arenes, Ren A. Wiscons1*, Holden W. H. Lai1, Matthias Zeller2, Jesse L. C. Rowsell1

1Department of Chemistry and Biochemistry, Oberlin College, Oberlin, Ohio2Department of Chemistry, Youngstown State University, Youngstown, Ohio

Diffraction of 2,4,6-tris(4-methylphenyl)pyridine and 2,4,6-tris(4-methylphenyl)pyrylium co-crystals revealed a pseudohexagonal columnar structure assembled from π-stacked helices that enclose channels containing disordered tetrafluoroborate counterions and solvent molecules. PXRD investigations suggest modification of the crystal structure as a result of interactions between the co-crystal and monovalent anions, indicating a possibility of ion exchange properties. The co-crystal structure is not shared with either of the end-members’ crystal structures, though all three structures exhibit disorder, aperiodicity, and complex twinning patterns. To gain a better understanding of the unique structural properties that arise from co-crystallization, our group has synthesized the 2,4,6-tris(4-halophenyl)arenes and studied the subtleties of aromaticity, steric constraints, and halogen interactions on packing motifs. Preliminary results suggest the possibility of modifying solvent accessible volume in the tetrafluoroborate channels through ion exchange.

3:20 pm Updated Dielectric Thermal Analysis and Differential Scanning Calorimetry studies led to a unified Polaron Theory of Ionic Conduction of organic and inorganic crystalline materials Alan T. Riga, PhD1,2, Hannah Conway1,

1Notre Dame College, South Euclid, Ohio2Case Western Reserve University, Cleveland Ohio

Coauthors: Professor Ieda Santos (Paraiba, Brasil), Dr. D. Mantheni (Americhem, USA), Dr. P. Mahashwearn (Americhem, USA), R. Munigeti (Ricerca, Painesville, OH, USA) and Professor Kenneth Alexander (University of Toledo, OH, USA)

Unique variations in AC electrical conductivity and permittivity of organic (solid state mobility) or inorganic (electrochemical metal oxide dissolution) solids, were measured with respect to dielectric, temperature, time and frequency and the resulting behavior has led to a unified theory of polaron conduction, the "ion hopping model". A wide range of organic solids were examined and include pharmaceuticals, polymers, amino acids and carbohydrates.

Experimental results clearly show novel dielectric behavior of a linear increase in a log polar ionic conductivity vs. temperature in the pre-melt (solid state) and melt transition regions with correlation coefficients of >0.990. We have differentiated the solids which show the polar conductivity and permittivity (capacitance) variations in the pre-melt from those with low conductivity in the liquid state only, i.e. the latter non polar wax and polyethylene. The effect of various experimental factors, e.g. moisture and purity, on the results were evaluated and found not contributing to the ionic conductivity of the chemicals studied. Correlating calorimetric and dielectric analysis gave us a better understanding of solid state properties. Calorimetric analysis was employed to assure that the observed variations in the solid state conductivity were not due to impurities in the sample. ASTM E698, the DSC purity method, verified the chemical purity at >99.97 mole %.

Activation energies were calculated based on the Arrhenius behavior, log conductivity vs. reciprocal temperature (1/K) and identified the polar conduction mode in the solid state. As the different chemicals were heat/cool cycled they become more quantitatively amorphous with decreasing activation energy and an increasing amorphous content and polar conduction.

Entrepreneurial recommendations based on the new conduction properties will be explored and include enhanced chemical reaction (Mallard reaction) and effective drug delivery through pig skin and rabbit eye sclera.

4:10 pm Computational Techniques for the Design of Mechanically Interlocked Molecules, Eric P. Bruckner*, Katie M. Greenman, Michael J.A. Hore, Stuart J. Rowan, Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio

The synthesis of rotaxanes and polyrotaxanes requires optimization of the different molecular components. Consisting of a molecular axle-like component threaded through a macrocycle and end-capped with a bulky stopper group, rotaxanes are a type of mechanically interlocked molecule. In order to prevent component disassembly, the size of the stopper group relative to the macrocycle must be optimized to prevent chain dethreading while still allowing for high mobility of the interlocked molecules. Using computational techniques (e.g. molecular mechanics and semi-empirical quantum mechanics), the optimal size for a stopper group was determined for a [3]rotaxane with two axles threaded through one ring. Building upon these atomistic studies, coarse-grained dissipative particle dynamics (DPD) simulations were used to predict the relationship between a singular [3]rotaxane and the bulk rheological properties of a corresponding poly[3]rotaxane. Modifications to individual components, such as macrocycle size and thread length, were made to investigate the resulting effect on the rheological properties of these materials. Further understanding of the structure-property relationships within mechanically interlocked polymers will guide the synthesis and allow for the design of the next generation of these interesting materials.

4:30 pm Excited-State Dynamics as a Benchmark for the Optimization of Small-Molecules for Organic Photovoltaics, Regina DiScipio**, Geneviève Sauvé, and Carlos E. Crespo-HernándezDepartment of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, Ohio

The utility of a prospective donor or acceptor molecule for photoelectric applications is difficult to predict a priori. This hinders productive synthetic exploration and necessitates lengthy device optimization procedures for reasonable estimation of said molecule’s applicability. Using femtosecond broadband transient absorption spectroscopy, supported by time-dependent density functional theory computations and steady-state-absorption and emission spectroscopies, we have characterized a family of perspective optoelectronic compounds, in an effort to predict their relative performance in organic photovoltaic devices from information accrued from excited-state dynamics and photophysical properties.A series of tetraphenylazadipyrromethene (ADP) complexes chelated with three different metal centers was investigated. We have determined that the chelating metal has little effect on the ground state properties of this family. However their excited state dynamics are strongly modulated by the metal. Specifically, the zinc-chelated ADP complex remains in the excited state tenfold longer than the cobalt or nickel complexes. We assert that this is key photophysical property that should make the zinc complex outperform the other two complexes in photovoltaic applications. This hypothesis is supported by preliminary power conversion efficiency results in devices.

4:50 pm Legal Case study to evaluate product Liability used Forensic Polymer Chemistry measured by FTIR spectroscopy and Differential Scanning Calorimetry, Jacob Kirsh*, Hannah Conway, Alan T Riga, Notre Dame College, South Euclid, Ohio

Forensic Case studies were developed to train students to solve product liability problems using laboratory analytical tools. A fast food restaurant sold a cola beverage dispensed from their machine. A person imbibed the drink and later discovered that shards of a material, that appeared to be a plastic, were in the drink. Course of legal action was to use non-destructive testing by Microscopic analysis and Infrared Spectroscopy as well as a modified test by Differential Scanning Calorimetry. Non-destructive testing of the solids in the drink was measured by macrophotography and Infrared Spectroscopy to determine the size and nature of the solid debris in the drink. Next to confirm the nature of the solid debris the sample was scanned by Differential Scanning Calorimetry to identify an amorphous plastic glass transition temperature or crystalline plastic melting temperature and heat of fusion. The FTIR spectrum of the debris matched the polypropylene IR standard and the DSC of polypropylene with a melting temperature of 155-160oC.

Within a reasonable degree of scientific and engineering certainty and clear and convincing evidence the plastic debris imbibed by your client was polypropylene (PP) tubing fragments. PP is commonly used in transferring fluids. Within a reasonable degree of scientific and engineering certainty the plastic delivery tubing or excess debris fractured due to a defective design or erroneously placed in the restaurant’s cola cup and the PP plastic debris caused the injury to your client.

Inorganic/Materials/Analytical II Regina 211 * undergraduate presenter ** graduate presenter

3:00 pm Enhancing the Phototherapeutic Potential of Sulfur-Substituted DNA and RNA Analogues Marvin Pollum** and Carlos E. Crespo-Hernández, Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, Ohio

Thio-analogues of the nucleobases, wherein a carbonyl oxygen is replaced by a sulfur atom, have recently been demonstrated as effective photosensitizers for the light-activated treatment of various cancers and skin diseases. Following the absorption of light, these thiobase derivatives populate long-lived, highly-reactive triplet states that are able to efficiently generate reactive oxygen species. When this photosensitization occurs inside of malignant cells, the resulting oxidative stress ultimately leads to cell death. A major drawback of the currently used thiobase photosensitizers is their absorption cutoff in the mid-UVA region of the spectrum (~365 nm). These relatively short wavelengths are unable to deeply penetrate tissues and can be absorbed by other biomolecules, thus reducing the phototherapeutic efficacy. Our group has recently focused its efforts towards understanding the structure-photoreactivity properties of several thiobase derivatives, seeking to maximize their prospective use in phototherapeutic applications. I will show how the site and degree of sulfur substitution impact the absorption spectra, the rates and yields of triplet state population, and the singlet oxygen yields of these thiobases. Significantly, we have found that doubling sulfur substitution increases the photoreactivity, while simultaneously shifting the absorption spectrum into the near-visible region (~395 nm) where light is able to penetrate more than 110% deeper into tissues. These results lay the foundation for greater selectivity and deeper tissue treatment in phototherapies based on sulfur-substituted nucleobase analogues.

The authors acknowledge the CAREER program of the National Science Foundation (Grant No. CHE-1255084) for financial support.

SCHEME I

3:20 pm A Critical Assessment Of As A Figure Of Merit For Oxygen Reduction Electrocatalysts In Aqueous Electrolytes, Nicholas S. Georgescu**, Adriel J. J. Jebaraj, and Daniel SchersonDepartment of Chemistry, Case Western Reserve University, Cleveland, OH

The rotating ring-disk electrode, RRDE, is particularly suited for gaining insight into the kinetics and mechanism of the oxygen reduction reaction, ORR, in aqueous electrolytes. In particular it allows the amount of solution phase peroxide, H2O2(aq), produced at the disk to be detected quantitatively at the ring polarized at a potential positive enough for its oxidation to proceed under diffusion limited conditions. Under conditions in which the disk is not active for the reduction of H2O2(aq), i.e. I3 = 0 in Scheme I, the fraction of the disk current that generates

H2O2(aq), denoted as , may be shown to become independent of the rotation rate of the electrode, . If, on the other hand, the disk is active for the reduction of H2O2(aq), a plot of the ring over the disk current vs ω-1/2 would be expected to yield a straight line with a non-zero slope and an intercept proportional to the rate of H2O2(aq) reduction on the disk. On this basis, no reliable conclusions regarding the relative activities of electrocatalysts can be made based on measurements performed at a single rotation rate. Illustrations of this formalism will be provided using data collected in this and other laboratories.

3:40 pm Effect of Dielectric Properties on Drug Transport Through Shedded Snake Skins Hannah Conway1*, Jacob Kirsh1, Sean Cadden2, Emily Bussis2 , Alan Riga 1,2

1Notre Dame College Ohio, South Euclid Ohio USA2CWRU, Polymer Science and Engineering, Cleveland, Ohio USA

Unique variations in AC ionic conduction of drug solids on polymeric shed snake skins were evaluated by scanning temperature Dielectric Thermal Analysis (TA Instrument #2970). The polar conduction properties were studied with respect to Permittivity (dipole content), temperature, time and frequency. A range of drugs, based on melting temperature, affixed to shed snake skin as Lidocaine HCl and Caffeine as well as Sulfamerazine was examined for this study. Experimental results clearly show novel dielectric behavior of linear increase in a log ionic conductivity or permittivity (capacitance or dipole constant) vs. temperature. The results follow the “Unified theory of Polar Conduction for organic and inorganic chemicals” derived by Riga (USA) and Santos (Brazil) 2012-2014 in the Premelt (solid state) transition temperature region. Dielectric Analysis was used to study the cause of this variation in polar solids which yielded a measure of the behavior. Activation energies were calculated based on Arrhenius attributes to better understand the solid state properties. As the different drugs were heat cool cycled they were more amorphous as evidenced by the decreasing Activation Energy for charge transfer or ionic conduction and a decrease in Permittivity (e’)-time response (Run1/Run2 on shed snake skin: 300 to 16 e’ for 5% caffeine; 700 to 1 e’ 0.1% for Lidocaine.HCl and 6 million to 1000 e’ 0.02% for Sulfamerazine at 30 minutes) with an definitive increase in amorphous content. All three drugs passed the shed snake skin with Sulfamerazine>Lidocaine>Caffeine. The remaining crystalline phase was measured to 5 to 0.1%.

4:10 pm Photophysics of Bacteriochlorin Dyads, Christopher McCleese**a, Zhanqian Yub, Nopondo Esemotob, Arun Mannac, Barry Dunietzc,*, Marcin Ptaszekb,*, Clemens Burdaa,*

a Department of Chemistry Case Western Reserve University, Cleveland, OHb Department of Chemistry University of Maryland Baltimore County, Baltimore, MDc Department of Chemistry Kent State University, Kent, OH

Bacteriochlorin is the macrocyclic structure that makes up the reaction center of bacteriochlorophyll, the photosynthetic pigment in bacteria. These macrocycles are of interest because of their applications in fields such as energy conversion and fluorescent probes. Here we use fs-transient absorption spectroscopy and time resolved photoluminescence measurements to study the photodynamic process between directly linked and phenylene bridged bacteriochlorins. We find that the dynamic processes between these linked bacteriochlorins are highly dependent on the distance and conformation between the two macrocycles when dissolved in polar solvent. We find that with increasing distance between the bacteriochlorins that the rates of charge transfer becomes slower.

4:30 pm Modeling And Measuring Thermal Properties Of Methylammonium Lead Halide Perovskite, Anton Kovalsky**a, Gage Marekb, Lily Wanga, Jeffrey Dyckb, Clemens Burdaa

a Case Western Reserve University, Department of Chemistry, Cleveland, OHbJohn Carroll University, Department of Physics, Cleveland, OH

Organic-inorganic hybrid perovskites have attracted much attention because of their unique photoelectric properties for potential uses in photovoltaic solar cell. In real application, the effect of operating temperature on the output efficiency should not been neglected, as increasing temperature results in decreasing efficiency, due to structural degradation and photovoltage reduction. Thus, it is crucial to dissipate the thermal energy to avoid this. Presented herein is temperature dependent lattice thermal conductivity data on polycrystalline methylamine lead iodide, CH3NH3PbI3. For comparison, we present data on PbI2, which is both a precursor in the synthesis of the CH3NH3PbI3 and an eventual degradation product. The experimental data are well fit to a model describing phonon scattering in this material. The model both supports the only previous report on thermal behavior of hybrid perovskite and also points the way toward further exploration of thermal management in related perovskite materials and devices thereof, whose function and stability are dependent on the counter ion’s effect on the unit cell.