Technical Program Summary
Time
Presentation
Analytical Chemistry 1 (Clapp 304)
3.00 – 3.20 pm
Absolute Determination of Sweat Chloride Using the Same Two Electrodes for
Coulometric Titration and Potentiometric Detection. Kihwan Kim
3.20 – 3.40 pm
Generating Chemical-Based Image Contrast in Hyperspectral Image Analyses. Leanna
N. Ergin
3.40 – 4.00 pm
Simultaneous Determination of Curcumin and its Metabolites in Human Plasma by LCMS/MS for a Phase II Clinical Trial. Sandeep R. Kunati
4.00pm – 4.20pm: Break
Analytical Chemistry 2 (Clapp 304)
4.20 – 4.40 pm
Analysis of Heavy Metal Contamination of Road Dust. Erin Bryant
4.40 – 5.00 pm
Determination of Monosialogangliosides in Human Plasma by a Novel UPLC/MS/MS
Assay Coupled with Chemical Derivatization. Qianyang Huang
5.00 – 5.20 pm
Searching for Biomarkers of Alzheimer’s Disease by Liquid Chromatography Mass
Spectrometry-Based Lipidomics. Chandana Mannem
Analytical Chemistry 3 (Clapp 305)
3.00 – 3.20 pm
Comparison of Different Stationary Phases for Gangliosides Separation. Ashta
Lakshmi Prasad Gobburi
3.20 – 3.40 pm
DNA Films as Peroxynitrite Sensing Interfaces. Heba Salim
3.40 – 4.00 pm
Characterizing Aptamer Binding Affinity to the Ovarian Cancer Biomarker CA125.
Delia Scoville
4.00pm – 4.20pm: Break
Analytical Chemistry 4 (Clapp 305)
4.20 – 4.40 pm
Electrochemical Studies on the Interaction of Peroxynitrite with Synthetic Melanin
Films. Morgan M. Ashcraft
4.40 – 5.00 pm
Characterization of a Human Antimicrobial Protein in Head and Neck Cancer by Mass
Spectrometry-Based Proteomics. Shashank Gorityala
5.00 – 5.20 pm
Demonstrating and Correcting the Systematic Error in Affinity Probe Capillary
Electrophoresis Experiments. Kepler Mears
Biochemistry 1 (Clapp 201)
3.00 – 3.20 pm
Expression and Purification of Human Peptidylarginine Deiminase II (hPADII). Sarah
Krul
3.20 – 3.40 pm
Study of Leucine rich α-2-glycoprotein-1 (LRG-1) Glycosylation and Its Functions.
Qiao-Yun Zheng
3.40 – 4.00 pm
Development of a Model for the Characterization of Cardiac Metabolism in Living
Patients. Alisha House
4.00pm – 4.20pm: Break
1
Technical Program Summary
Time
Presentation
Biochemistry 2 (Clapp 201)
4.20 – 4.40 pm
Profiling Sialylation Status during Monocytes Differentiation. Dan Wang
4.40 – 5.00 pm
Protein Lipidation for Cell Surface Re-engineering via Lipid Fusion Approach.
Mallorie Boron
5.00 – 5.20 pm
Peroxide Induced Specific Protein Modification in HeLa Cells. Abigail Beer
Biochemistry 3 / Bioanalytical Chemistry (Clapp 108)
3.00 – 3.20 pm
Identification of Novel Biomarker for Cardiovascular Disease Risk by Mass
Spectrometry-based Metabolomics. Hassan Alamri
3.20 – 3.40 pm
Exploring the Role of N-Hydroxy Heterocycles in Synthetic Eumelanin Formation.
Samantha Moores
3.40 – 4.00 pm
Pharmacological and Pre-Clinical Testing of 5-NIdR as a New Therapeutic Agent
Against Brain Cancer. Casey Seol Kim
4.00pm – 4.20pm: Break
Organic Chemistry (Clapp 108)
4.20 – 4.20 pm
Toward the Synthesis of Dimethoxyindole-Based Eumelanin Analogs. Jonathan
Quirke
Physical Chemistry 1 (Clapp 405)
3.00 – 3.20 pm
Electrocatalytic Reduction of Selenate on Gold Electrodes in the Presence of Copper
(II). Jonathan R. Strobl
3.20 – 3.40 pm
Early Events in the Absorption of Ultraviolet Light by Pterin Biomolecules. Regina
DiScipio
3.40 – 4.00 pm
Electroreduction of Selenium Oxyanions In The Presence of Methyl Viologen. Qi Han
4.00pm – 4.20pm: Break
Physical Chemistry 2 (Clapp 405)
4.20 – 4.40 pm
Photochemistry of Promising Ancestral RNA Nucleobases. Matthew M. Brister
4.40 – 5.00 pm
Theoretical Aspects of Superoxide Oxidation Kinetics. Nicholas Georgescu
5.00 – 5.20 pm
Transient Absorption Spectroscopy Reveals the Potential Light-Induced Risks
Associated with Incorporating dNaM-d5SICS. Brennan Ashwood
2
Technical Program Summary
Time
Presentation
Materials Chemistry 1 (Millis 123)
3.00 – 3.20 pm
Optimizing the formation of [3]catenates containing 2,6-bis(Nalkylbenzimidazolyl)pyridine. Qiong Wu
3.20 – 3.40 pm
Stimuli-Responsive Liquid Crystalline Elastomer Actuators. Brian Michal
3.40 – 4.00 pm
Integrated Synthetic and Computational Techniques For The Design of
Poly[3]Rotaxanes. Eric P. Bruckner
4.00pm – 4.20pm: Break
Materials Chemistry 2 (Millis 123)
4.20 – 4.40 pm
Structure-Property Studies of Fluorinated Azadipyrromethene Derivatives as n-Type
Acceptors in Organic Photovoltaics. Sandra Pejic
4.40 – 5.00 pm
Biomimetic Dynamic Heat-Stiffening Polymer Nanocomposites. Elvis Cudjoe
5.00 – 5.20 pm
Graphene-Based Materials for Enhanced Performance of Peroxynitrite Sensors.
Haitham Kalil
Inorganic Chemistry (Millis 220 B)
3.00 – 3.20 pm
Investigations into Photolysis Reactions Using Hypervalent Iodine. Andrew Kollar
3.20 – 3.40 pm
Polyoxaphospholes: Polymeric Organophosphorus Materials with Luminescent
Properties. Joshua Gaffen
3.40 – 4.00 pm
Synthesis of Luminescent Gold(III) Cyclometalated Complexes. Amanda N. Sulicz
4.00pm – 4.20pm: Break
Inorganic Chemistry / Chemical Engineering (Millis 220 B)
4.20 – 4.40 pm
Metalloporphyrin with Xanthene (CO2Me) Hangman Molecules. Yishayah Bension
4.40 – 5.00 pm
Electrochemical Micro pH-stat for Point-of-Care Enzyme Assays. Zhehao Zhang
3
4
Support for Awards for Student Presentations at the 2016 MIM
Undergraduate Awards ($350)
- Amalgamated Tuna Company - Dwight Chasar / Lubrizol - Jim Burrington / Lubrizol - Oberlin College, Department of Chemistry and Biochemistry -
Graduate Awards ($400)
- Dwight Chasar / Lubrizol - Cleveland State University, Department of Chemistry - Energizer - Sherwin Williams –
5
6
Abstracts
Analytical Chemistry
7
8
Session: Analytical Chemistry 1 (Clapp 304 / 3.00 – 4.00pm)
1.
ABSOLUTE DETERMINATION OF SWEAT CHLORIDE USING THE SAME TWO
ELECTRODES FOR COULOMETRIC TITRATION AND POTENTIOMETRIC
DETECTION
Kihwan Kim1, Tamas Cserfalvi, Xingyi Tao2, JaeHun Chung1, Sanghyun Kim1, Miklos Gratzl1
1
Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, United States
2
Georgetown University,
Abstract
Elevated sweat chloride is the definitive diagnosis of the presence of Cystic Fibrosis: the most prevalent
genetic disease in the US. This test should be performed as early as possible in newborn's life to prevent
irreversible damage in the lungs, intestines, and pancreas. However an infant of 2 weeks of age cannot
produce 15μL or more sweat for analysis: the required minimum volume for the best currently available
technology. We have developed an approach that makes it possible to sample 2μL of sweat accurately.
This sample after dilution in buffer is coulometrically titrated with silver ions from a silver microelectrode
as the anode. Charge injection is done in pulses between which the detection of free silver ions is
performed using the same silver electrode but in open circuit mode. The platinum counter electrode in the
coulometry pulses becomes the reference electrode in the potentiometry phase. This is possible because a
trace amount of H atoms is generated during coulometry which converts the Pt into a pH-linked reference.
With this arrangement the determination of sweat chloride becomes possible in two-week-old infants. This
technology will help improve morbidity and life expectancy of individuals with cystic fibrosis.
2.
GENERATING CHEMICAL-BASED IMAGE CONTRAST IN HYPERSPECTRAL IMAGE
ANALYSES
Leanna N. Ergin1, John F. Turner II1
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
Abstract
In recent years, hyperspectral imaging has become a routine analytical method due to advances in
technology. A fundamental challenge is the development of processing methods that can rapidly generate
chemical-based image contrast from the large amount of data in the hyperspectral data cube. We have
developed a fully-automated method called reduction of spectral angle space (ROSAS), which is effective
in classifying pixels within the hyperspectral image according to subtle differences is spectral shape.
ROSAS removes the degeneracies caused by angular symmetry, can be done rapidly, requires no training
datasets or a priori information about the dataset, and takes advantage of the full colorspace of modern
RGB displays for visualizing the classified image result. A concise protocol is put forth that will enable
other researchers to utilize this method by following a short, list of steps. The description has been
generalized to work with any number of wavelength dimensions and spectra. In addition, ROSAS image
results from hyperspectral data on both model data and real samples are presented.
9
3.
SIMULTANEOUS DETERMINATION OF CURCUMIN AND ITS METABOLITES IN
HUMAN PLASMA BY LC-MS/MS FOR A PHASE II CLINICAL TRIAL
Sandeep R. Kunati1, Shuming Yang2, Basem M. William3, Yan Xu1,2
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
2
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United
States
3
University Hospitals Seidman Cancer Center, Case Western Reserve University
Abstract
Curcumin, a natural compound derived from turmeric, was shown to disrupt interactions of chronic
lymphocytic leukemia (CLL) cells with microenvironment, and induce apoptosis independent of DNA
damage. The current clinical trial (CASE 5913) investigates pharmacokinetic properties of curcumin in
conjunction with vitamin D for a possible synergistic effect against CLL.
To support the clinical study, we have developed an LC-MS/MS method for simultaneous determination
of curcumin and its metabolites [e.g., curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS)] in
human plasma using a stable heavy isotope of curcumin as internal standard (IS) for curcumin and a stable
heavy isotope of bisphenol-A glucuronide as IS for COG and COS. In this method, the analytes and their
ISs in plasma samples were first prepared by protein precipitation using methanol as solvent, then
separated on a Waters XTerra® MS C18 column (2.1 mm x 50 mm, 3.5 µm) with a mobile phase
containing methanol/10.0 mM ammonium formate by gradient elution profile at a flow rate of 0.250 mL
min-1. Quantitation of curcumin, COG and COS was carried out by negative electrospray ionization
tandem mass spectrometry with multiple-reaction-monitoring (MRM) mode at mass transitions of m/z
367.2 > 148.9, 543.3 > 217.0 and 447.0 > 217.0 for curcumin, COG and COS, respectively.
The method developed has been validated in accordance with the US FDA guidance for bioanalytical
method validation, and successfully applied to the pharmacokinetic study of curcumin in the clinical trial.
10
Session: Analytical Chemistry 2 (Clapp 304 / 4.20 – 5.20pm)
4.
ANALYSIS OF HEAVY METAL CONTAMINATION OF ROAD DUST
Erin Bryant1
1
Bladwin Wallace University, 275 Eastland Rd, Berea, OH 44017, United States
Abstract
Heavy metal concentrations in sediment and soil around the US seem to be increasing from automobiles,
industrialization, agricultural, and other anthropogenic factors. Studying metal concentrations are
important because increased amounts can become harmful to plants, animals, and humans. To successfully
measure and analyze heavy metal concentrations two methods were used to extract the metals from the
soil matrix; EDTA extraction and nitric acid digestion (EPA Method 3050B). The mobile metals in the
road dust are freed by EDTA (ethylenediaminetetraacidic acid) extraction; which is a single step
extraction where EDTA strongly binds to electrostatically bound metal ions regardless of charge. Acid
digest is carried out to obtain the total metal count in the road dust. Not only does it dissolve the mobile
metals, it is also strong enough to dissolve the occluded metals that are strongly bound to the road dust.
The levels of magnesium, manganese, nickel, copper, and iron are analyzed by flame atomic absorption
spectrometry (FAAS).
5.
DETERMINATION OF MONOSIALOGANGLIOSIDES IN HUMAN PLASMA BY A
NOVEL UPLC/MS/MS ASSAY COUPLED WITH CHEMICAL DERIVATIZATION
Qianyang Huang1, Xiang Zhou1*, Danting Liu1, Baozhong Xin2, Karen Cechner2, Heng Wang2, and
Aimin Zhou1*
1
Clinical Chemistry Program, Department of Chemistry, Cleveland State University, 2121 Euclid Avenue
SR 397, Cleveland, OH 44115, United States
2
DDC Clinic, Center for Special Needs Children, 14567 Madison Road, Middlefield, OH 44062, United
States
Abstract
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 being attached to a ceramide portion with variable length and saturation degree on
fatty acid chain. Physiologically, they play critical roles in the regulation of various receptor-mediated cell
signaling pathways and essential cellular events. Disruption in their metabolic pathways has been found to
be implicated in the pathogenesis of numerous neurodegenerative disorders, such as Parkinson disease,
Alzheimer disease, and ganglioside GM3 synthase deficiency (GSD). In order to more comprehensively
understand the disease etiologies, a reliable LC/MS/MS method with enhanced sensitivity is urgently
demanded for relevant biomedical studies.
11
In this work, a novel reverse phase UPLC/MS/MS method for determination of monosialogangliosides,
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 liquid-liquid partition, dried under nitrogen purging, and
derivatized with DMTMM & PAEA. Thereafter, the samples were injected into a Shimadzu Nexera
UHPLC system interfaced to an AB Scix Qtrap 5500 mass spectrometer that operated in ESI positive and
Multiple Reaction Monitoring (MRM) mode to achieve highly sensitive and specific detection.
This method has been applied for plasma measurements of monosialogangliosides in GSD patients for
clinical diagnosis and therapeutic evaluation during the ongoing clinical trial.
6.
SEARCHING FOR BIOMARKERS OF ALZHEIMER’S DISEASE
CHROMATOGRAPHY MASS SPECTROMETRY-BASED LIPIDOMICS
BY
LIQUID
Chandana Mannem1, Satya Girish Avula1, Christine Reece2, Jagan A. Pillai2, Yan Xu1,3*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
2
Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, Ohio 44195, United States
3
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United
States
Abstract
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that affects human brain's nerve
cells and neurons, resulting in loss of memory, thinking and language skills, and behavioral changes. AD
is currently ranked as the 6th leading cause of death in the United States; and recent estimates indicate that
this disease may rank as the 3rd cause of death for older people, just behind heart disease and cancer.
Up to date, there is no single test available for early detection of AD. Clinical diagnosis of AD is often
made at later stages of the disease through neurological exam, mental status test, genetic testing of ApoE4
and ADAD, brain imaging, and proteins in cerebrospinal fluid (CSF). Therefore, biomarkers that can
indicate the presence or absence of AD, or the likelihood of later development of AD are being actively
sought. Lipids are important molecules for brain function. Recent studies revealed that AD is a disease of
lipid disorder. Lipidomic study of plasma samples from AD patients and normal controls may lead to
discovery of lipid biomarkers for early detection of AD.
In this work, the total lipids were first extracted by the Bligh-Dyer method, then, fractionated into three
different groups (e.g., Glycerophospholipids, fatty acids and Glycerolipids) using HyperSep™
aminopropyl solid-phase-extraction cartridges. The fractionated lipid groups were separated by reversephase liquid chromatography with gradient elution and detected by accurate mass quadrupole time-offlight mass spectrometry (QTOF-MS). The acquired data were processed using Agilent MassHunter
Profinder software via retention time and mass alignment, and molecular feature extraction. The extracted
features were subjected to unpaired t-test with p value 0.005 and multiple testing corrections (such as
Bonferroni and Benjamini Hochburg corrections) to eliminate false positives and false negatives, then
12
followed by fold-change calculation using Agilent Mass Profiler Professional (MPP) software for lists of
statistically significant lipid markers which were up- and down-regulated, unique in disease state and
unique in healthy state between the normal controls and AD patients. The significant lists of lipid markers
were annotated by searching against SimLipid® database.
Session: Analytical Chemistry 3 (Clapp 305 / 3.00 – 4.00pm)
7.
COMPARISON
SEPARATION
OF
DIFFERENT
STATIONARY
PHASES
FOR
GANGLIOSIDES
Ashta Lakshmi Prasad Gobburi1, Renliang Zhang2, David J. Anderson1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
2
Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, United States
Abstract
Gangliosides are complex polar sphingolipid molecules made up of a non-polar ceramide head which is a
combination of sphingosine backbone and fatty acid moiety and a polar head consisting of sialic acid
along with glucose, galactose and N-Acetylgalactosamine. The carbon chain length, no. of bonds and
theirs positions in the ceramide moiety and position of the sugars and their number brings a great
heterogeneity among the gangliosides. Thus it is complex to chromatographically separate gangliosides.
A highly sensitive and selective LC-MS/MS method has been developed on phenyl-hexyl column
(Phenomenex, 5µm, 100 × 2.1 mm) and C18 column (Phenomenex, 5µm, 50 × 2.0 mm) to identify and
quantitate gangliosides. A Shimadzu UPLC system with binary pumps was interfaced to turbospray ion
source (AB Sciex QTrap 5500 mass spectrometer). A linear gradient with Methanol was optimized. A
similar method was developed with HILIC column (Imtakt, NH2 column, 50×1 mm, 3U) on Waters
model 2695 with quaternary pumps interfaced to an ESI-triple-QQQ mass spectrometer (Waters
Micromass). A multiple-mobile phase multi-step gradient program has been optimized.
A general chromatographic approach to separate gangliosides based on their polar head was by HILIC
separation. This method is limited as gangliosides with similar ceramide moieties were co-eluted. A
reverse-phase separation based on the ceramide moiety resulted in a partially separated gangliosides with
similar polar heads. In this work, a new LC-MS/MS method was developed with phenyl-hexyl column
and the results are compared with C18 and HILIC columns. A comparison of separation of mono-sialo
ganglioside will be presented.
13
8.
DNA FILMS AS PEROXYNITRITE SENSING INTERFACES
Heba Salim1, Mekki Bayachou1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
Abstract
Peroxynitrite (ONOO−) is a strong oxidizing and nitrating agent, and its formation has been correlated
with many pathological conditions. It is generated in-vivo through the diffusion-controlled reaction
between nitric oxide and superoxide. For example, ONOO− leads to oxidative stress in human leukemia
cells, and in acute and chronic inflammation. Peroxynitrite has been linked to nitration of protein and
DNA as well as to DNA strand breaks. Accumulation of mutations and/or other kinds of DNA damage
represent a carcinogenic risk. The accurate measurement of peroxynitrite concentration has been a
challenge since this analyte is very unstable and reacts with many cellular targets. Development of
analytical techniques capable of rapid and sensitive detection of this fast-reacting and damaging agent is
an important research target to determine the chemical damage by this oxidant at the tissue level and at the
cellular level.
In this work, we develop DNA films as a sensitive sensing platforms to detect and quantify ONOO− DNA
damage. We have used two methods for DNA immobilization on the electrodes surfaces: (1)
electrochemical grafting and (2) layer-by-layer (LBL) deposition methods. In the first method, we
generate carboxylic acid groups on the graphite carbon electrode surface via electrochemical reduction of
trans-4cinnamic acid diazonium tetrafluoroborate, followed by coupling of pre-activated carboxylic
groups with amino terminated oligonucleotide. In the LBL deposition method, we construct films of
alternate layers of positively charged poly(diallyl dimethyl ammonium) and the target DNA as a
negatively charged counterpart on the surface of the graphite electrode. On both platform (grafted oligos
and DNA films), we assess the effect of defined exogenous levels peroxynitrite metabolite on the
electrochemical response of DNA interface. Particularly, for the grafted DNA oligonucleotides we
focused on detecting the differential response of complementary strands versus DNA helices with a single
base mismatch. To this end, we have used chronocoulometry, cyclic voltammetry, and square wave
voltammetry to monitor the effect of the mismatch on the sensitivity of exposure to peroxynitrite through
defined electrocatalytic processes mediated by the grafted oligonucleotides. We will compare and contrast
the response of the two DNA platforms and discuss ways we can use them as sensing tools for
peroxynitrite in biological setting.
14
9.
CHARACTERIZING APTAMER BINDING AFFINITY TO THE OVARIAN CANCER
BIOMARKER CA125
Delia Scoville1, Kepler Mears1, Rebecca Whelan1
1
Department of Chemistry and Biochemistry, Oberlin College, 173 W Lorain St, Oberlin, OH 44074,
United States
Abstract
Aptamers are short oligonucleotide sequences that can bind target molecules with affinities comparable to
antibodies. They are small and hugely versatile, which makes them ideal candidates for developing
detection or therapeutic methods in human diseases like cancer. Ovarian cancer is the most deadly form of
gynecological cancer, and little progress has been made in the last two decades in improving the diagnosis
rate in its early stages. This has the potential to change with the discovery of better detection methods for
the ovarian cancer protein biomarker, CA125. CA125 is FDA-approved as a clinical biomarker and has
recently been shown to track over the course of a woman’s lifetime to her risk of developing ovarian
cancer. The Whelan lab has selected a pool of aptamers candidates via one-pot SELEX, a novel in-vitro
selection method, for potential use in improved early stage ovarian cancer detection. Through a variety of
analytical methods, including fluorescence anisotropy and affinity probe capillary electrophoresis (APCE),
I have further examined the binding between CA125 and its aptamer candidates in an attempt to select the
best aptamer to use in cancer detection.
Session: Analytical Chemistry 4 (Clapp 305 / 4.20 – 5.20pm)
10. ELECTROCHEMICAL STUDIES ON THE INTERACTION OF PEROXYNITRITE WITH
SYNTHETIC MELANIN FILMS
Morgan M. Ashcraft1, Haitham Kalil1, Mekki Bayachou1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
Abstract
Peroxynitrite (PON) is a very reactive nitrogen species. It facilitates both oxidation and nitration reactions.
PON emerged as a major cytotoxic agent, implicated in a host of pathophysiological conditions.
Peroxynitrite, the primary product of the reaction of superoxide ion and nitric oxide, and is relatively a
new member of the nitroxidative array of reactive metabolites. Early reports emphasized the deleterious
physiological reactivity of PON with many cellular targets including DNA, proteins, and lipids in cell
membranes.
Melanin is a natural pigment that has many physiologic functions including neutralizing highly reactive
oxidative species. Tyrosine and its derivative 5,6-dihydroxyindole (DHI) are some precursors of
eumelanin, a black form of melanin that is also photostable.
In this work we examine the chemical interaction between synthesized peroxynitrite and polymerized DHI
films as a model of melanin on electrodes. First we studied the electrochemical characteristics of
15
polymerized 5,6-dihydroxyindole, and then monitored the changes after addition of peroxynitrite. This
part of the work reports mainly on chemical changes within the electropolymerized films of melanin on
the electrode. We also studied the rates of chemical decay of peroxynitrite in the solution in the presence
and absence of melanin films using absorbance spectroscopy. Ultraviolet-visible analysis showed a
dramatic difference between the decomposition rates of peroxynitrite alone and peroxynitrite in the
presence of DHI films.
We will discuss the implication of the changes of the electrochemical signal of DHI films. We will also
compare and contrast the reactivity of peroxynitrite on bare electrodes and on modified electrodes with
DHI films. Finally, we will explore the prospect of using DHI films as a platform for quantitative
detection of peroxynitrite in solutions.
11. CHARACTERIZATION OF A HUMAN ANTIMICROBIAL PROTEIN IN HEAD AND
NECK CANCER BY MASS SPECTROMETRY-BASED PROTEOMICS
Shashank Gorityala1, Ge Jin2,3, Yan Xu1,3,*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, OH
44115, United States
2
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United
States
3
Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University,
Cleveland, OH 44106, United States
Abstract
Oral squamous cell carcinoma (OSCC) comprises approximately 3-5% of all the malignancies in the USA,
corresponding to 10,000 deaths each year. Early detection plays a critical role in cancer diagnosis,
treatment, and patient survival.
Recent studies revealed that human beta defensin-3 (hBD-3), an antimicrobial peptide is overwhelmingly
produced by premalignant cells in carcinoma in situ (CIS) suggesting cross-talk between hBD-3 and
resident stromal cells. Because the expression of hBD-3 in the cancer cell lines and patients are
significantly higher in comparison to those in the normal controls, this peptide is currently being
investigated as a biomarker for screening OSCC using enzyme-linked immunosorbent assay (ELISA) with
body fluids, including saliva samples. Surprisingly, the Western blotting showed that the molecule which
rendered positive ELISA in the cancer patient samples has a much larger molecular mass compared to that
of hBD-3 control. Currently, the cause of the molecular mass increase and chemical structure remain
unknown.
In this work, we used liquid chromatography in conjunction with quadrupole time-of-flight mass
spectrometry (LC-QTOF-MS) to decipher and characterize the synthetic hBD-3 peptide as a prerequisite
for the unknown protein molecule in the disease state. Proteomic analyses on the intact molecule extracted
from patient saliva and its tryptic digest will be performed. Data obtained will be used for deconvolution
and identification of the unknown protein using commercial software and databases. This work is
16
expected to reveal the structural relation of the unknown protein and hBD-3 peptide. The detailed
experimental progress will be discussed in this presentation.
12. DEMONSTRATING AND CORRECTING THE SYSTEMATIC ERROR IN AFFINITY
PROBE CAPILLARY ELECTROPHORESIS EXPERIMENTS
Kepler Mears1, Delia Scoville1, Rebecca Whelan1
1
Oberlin College, 173 W Lorain St, Oberlin, OH 44074, United States
Abstract
Affinity assays form the basis of diagnostic tests and therapeutic approaches, as well as many biochemical
techniques. Affinity Probe Capillary Electrophoresis (APCE) is a powerful technique for performing
affinity assays and determining binding constants of affinity probes. Many commercially available
Capillary Electrophoresis (CE) instruments have a thermoregulated capillary allowing for temperature
control during separation, which is important because many affinity interactions are sensitive to
temperature. In most CE instruments, however, the capillary inlets are not thermoregulated. During CE
separations high voltage creates heat in the capillary inlet that is not actively cooled by the instrument.
Studies have demonstrated that including the capillary inlet in separations promotes dissociation of the
affinity interaction resulting in an artificially lower affinity. While informative, these preliminary studies
were limited to comparison of data only collected using a CE instrument. We seek to further validate the
claim that the capillary inlet creates artificially lower affinity by comparing APCE to an orthogonal
technique, Fluorescence Anisotropy. Using two well characterized thrombin-binding DNA aptamers, a
29mer and 15mer, as a model system we have confirmed that including the capillary inlet during
separation creates an artificially lower affinity. We provide a simple method to account for the capillary
inlet compatible with commercially available CE instruments that provide more reliable measurements of
affinity. This method can be used not only with APCE and related experiments but CE based aptamer
selection as well.
17
18
Abstracts
Biochemistry / Bioanalytical
Chemistry
19
20
Session: Biochemistry 1 (Clapp 201 / 3.00 – 4.00pm)
13. EXPRESSION AND PURIFICATION OF HUMAN PEPTIDYLARGININE DEIMINASE II
(HPADII)
Sarah Krul1, Diana Barko1, Sean Hoehn1, Ricky Surdy1, Nick Ramsey1
1
Bladwin Wallace University, 275 Eastland Rd, Berea, OH 44017, United States
Abstract
Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that catalyze the post-translational
conversion of protein arginine residues to citrulline residues. Characterization of PADs is of significant
interest due to their role in various physiological and pathological processes. Recombinant human PAD II
(hPADII) was studied by transforming the pReceiver B01 vector, containing the hPADII insert, into
BL21*(DE3) E. coli cells. Induction studies were conducted to determine optimum conditions for
overexpression of hPADII. Based on the results, cells were induced overnight with 0.1 mM IPTG at 16 °C.
After harvesting and lysing cells, the his-tagged hPADII was partially purified from the cell lysate using
Ni-NTA affinity chromatography. This was indicated by the intense protein band at 75.5 kDa on the SDSPAGE gel and subsequently confirmed by Western blot analysis. Further optimization of the purification
protocol will lead to greater yield and allow for the kinetic characterization of hPADII.
14. STUDY OF LEUCINE RICH Α-2-GLYCOPROTEIN-1 (LRG-1) GLYCOSYLATION AND
ITS FUNCTIONS
Qiao-Yun Zheng1, Qiaoxia Zheng1, Hao Wang1, Aimin Zhou1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, OH
44115, United States
Abstract
Metastasis is the major cause responsible for cancer-associated mortality, yet it remains one of the most
mysterious aspects of cancer pathogenesis. In the past decades, tremendous efforts have been directed to
elucidate the mechanistic insights of metastasis. In this study, we have recently found that leucine rich α2-glycoprotein-1 (LRG-1), a serum glycoprotein, is highly expressed in most of cancer cells we examined
although its functions are largely unknown. Interestingly, LRG-1 is not glycosylated except excreted into
the medium. To determine if glycosylation is necessary for LRG-1 secretion, we treated the cells with
different glycosylation inhibitors. Our results showed that inhibition of both N- and O-glycosylation on
LRG1 did not prevent its secretion from the cells. Primary function analysis revealed that LRG-1 may
contribute to cell migration. Further investigation of LRG-1 functions is warranted.
21
15. DEVELOPMENT OF A MODEL FOR THE CHARACTERIZATION OF CARDIAC
METABOLISM IN LIVING PATIENTS
Alisha House1, Yana Sandlers1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, OH
44115, United States
Abstract
Cardiomyopathies of all types are inherently difficult to study at the cellular level due to the inability to
sample heart tissue from living patients. We have developed a workflow to characterize cardiac
metabolism and study new therapies for inherited cardiomyopathies in vitro. Our approach is based on a
revolutionary discovery of cell reprogramming methods that allow researchers to obtain human induced
pluripotent stem cells (iPSCs) from adult cells and differentiate these stem cells to donor-specific
cardiomyocytes. The cultured cardiac tissue carries the same genetic mutation as the original donor, thus
allowing us to study the effects of the mutation in question in laboratory settings. The metabolome of
these cells will be characterized with gas chromatography-mass spectrometry (GC-MS) and liquid
chromatography tandem mass spectrometry (LC-MS/MS). Our focus is on organic acids, phospholipids,
amino acids, acylcarnitines, and citric acid cycle intermediates. The metabolome of the disease-specific
cardiomyocytes will be compared to that of the control cardiomyocytes, which will allow us to further
elucidate the biochemical pathways affected by the mutation. To develop our analytical methods for
determining relevant metabolite levels, we have cultured the mouse embryonal carcinoma line p19 cells
and differentiated them into cardiomyocytes using 1% DMSO. We have developed extraction procedures
and mass spectrometry methods to characterize cardiomyocyte metabolites. The optimized assays will be
applied to the iPSC-derived human cardiomyocyte studies.
Session: Biochemistry 2 (Clapp 201 / 4.20 – 5.20pm)
16. PROFILING SIALYLATION STATUS DURING MONOCYTES DIFFERENTIATION
Dan Wang1, Evgeny Ozhegov1, Lin Wang1, Aimin Zhou1, Xue-Long Sun1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, OH
44115, United States
Abstract
Sialic acids (SAs) often exist as the terminal sugars of glycan structures of cell surface glycoproteins and
glycolipids. The level and linkages of cell surface SAs, which are controlled by both sialylation and
desialylation processes and environment cues, can dramatically impact cell properties and represent
different cellular statuses. In this study, we systematically examined the sialylation and desialylation
profiles of THP-1 monocytes after differentiation to M0 macrophages, and polarization to M1 and M2
macrophages by the combination of LC-MS/MS, flow cytometry, and confocal microscopy. Interestingly,
both α2,3- and α2,6-linked SAs on the cell surface were found to be decreased after monocytes were
differentiated to macrophages, which was in accordance with the increased level of free SA in the cell
culture medium and the elevated activity of endogenous Neu1sialidase. Meanwhile, the
22
siaoglycoconjugates inside the cells increased as confirmed by confocal microscopy and the total SA
inside the cells increased as determined by LC-MS/MS. Further, upon polarization, the cell surface
sialylation levels of M1 and M2 macrophages remained the same as M0 macrophages, while a slight
decrease of cellular SAs in the M1 macrophages but increase in the M2 macrophages were confirmed by
LC-MS/MS. 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.
17. PROTEIN LIPIDATION FOR CELL SURFACE RE-ENGINEERING VIA LIPID FUSION
APPROACH
Mallorie Boron1, Pratima Vabbilisetty1, Xue-Long Sun1*
1
Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in
Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115,
United States
Abstract
The cell surface, filled with a variety of different proteins, including receptors, ligand proteins, and
adhesive proteins, is an important platform for the occurrence of many biological processes, such as cell
signaling, cell-cell adhesions, and other extracellular/intracellular communications. This cellular response
can be modified by the artificial presentation of bioactive molecules on the cell surface according to a
process known as cell surface engineering. Hydrophobic anchoring to the cell membrane is an attractive
technique for cell surface engineering as it has several advantages, such as lower cytotoxicity, rapid
modification, and its ability to be applied to a wide variety of different molecules and cells. Practically,
the process of hydrophobic anchoring simply involves mixing the hydrophobic anchors with cells, which
allows for the spontaneous transfer of the anchors from the solution phase to the outer leaflet of the
plasma membrane. In this presentation, we report a protein lipidation approach for effective cell surface
re-engineering with Raw 267.4 cells as model. Briefly, we have developed a fluorescently labeled antigen,
ovalbumin, with a phospholipid anchor that can be delivered to a macrophage via lipid fusion. We aim to
study how the introduction of this antigen alters the cell’s ability to initiate an immune response. This
study suggests the possible use of phospholipid for cell surface re-engineering applications.
18. PEROXIDE INDUCED SPECIFIC PROTEIN MODIFICATION IN HELA CELLS
Abigail Beer1, Yuh-Cherng Chai1*
1
John Carroll University, 1 John Carroll Blvd, University Heights, OH 44118, United States
Abstract
Oxidative stress is known to affect the function of several biological molecules, including proteins, lipids,
and nucleic acids, and also plays a major role in a variety of human diseases. The ability to modify protein
structure and function through oxidative stress is one topic that has been widely studied. In this study, we
focus on protein glutathionylation; the posttranslational modification of protein cysteine residues by the
23
addition of glutathione. We compared the treatment of HeLa cells with oxygen free radical generating
agents, hydrogen peroxide and tert-butyl hydroperoxide, against the treatment of HeLa cells with diamide,
a chemical oxidizing agent. Both oxidizing agents induced many glutathionylated proteins in treated cells
compared to the control cells. More interestingly, in peroxide treated cells there is one prominent protein
around 40 kDa that is not seen in diamide treated cells, which commonly serves as the positive control. To
our knowledge, this is a novel protein because only peroxides induce this protein glutathionylation. Even
though the identity of this protein is currently unknown, it presents an exciting new mechanism for the
study of this specific protein function through oxidative stress.
Session: Biochemistry 3 / Bioanalytical Chemistry (Clapp 108 / 3.00 – 4.00pm)
19. IDENTIFICATION OF NOVEL BIOMARKER FOR CARDIOVASCULAR DISEASE RISK
BY MASS SPECTROMETRY-BASED METABOLOMICS
Hassan Alamri1, Ibrahim Choucair1,2, Nisreen Nimer1,2, Ina Nemet2,3, Tomas Cajka5, Oliver Fiehn5,
Stanley L. Hazen2,3,4, Valentin Gogonea1, 2,3*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115,
United States
Departments of 2Cellular & Molecular Medicine, 3Center for Cardiovascular Diagnostics and Prevention,
4
Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States
5
Department of Molecular and Cellular Biology & Genome Center, University of California, Davis,
California 95616, United States
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. A novel biomarker for early
identification of individuals at risk for future cardiovascular events is still critical to provide new ways to
diagnose disease states and reveal new metabolic pathways connected to CVD pathogenesis. To identify
novel biomarker, we performed non-targeted Gas Chromatography/Mass spectrometry-based (GC-MS)
analysis on subjects at risk for CVD in a semi-quantitative fashion to screen for plasma small-molecule
metabolites that predict risk for CVD. Among these metabolites, several mono-, di-, and tri carboxylic
acids (with/without additional hydroxyl groups) and polyols showed significant potential for prediction of
CVD risk. We are further developing two targeted stable-isotope dilution high performance liquid
chromatography-electrospray ionization-tandem mass spectrometry methods (LC-ESI-MS/MS) for the
quantitation of carboxylic acids and polyols in order to demonstrate their clinical utility by analyzing them
in a cohort study of 2000 subjects.
24
20. EXPLORING THE ROLE OF N-HYDROXY HETEROCYCLES IN SYNTHETIC
EUMELANIN FORMATION
Samantha Moores1, Jason M. Belitsky1*
1
Department of Chemistry and Biochemistry, Oberlin College, 173 W Lorain St, Oberlin, OH 44074
Abstract
Eumelanin is the black to brown form of melanin in humans and is our primary photoprotective agent.
Synthetic analogs of eumelanin have potential applications in a number of fields including water
purification. Small molecule modulators can be used to fine-tune the properties of synthetic eumelanin for
different applications, and also provide information about the biological process of melanin formation. In
the Spring of 2015, the Bioorganic Chemistry lab spent the last few weeks of the semester cataloguing a
series of small molecules and their abilities in promoting or inhibiting L-Dopa aggregation into synthetic
eumelanin. During these preliminary experiments, we found that nitrogen-containing heterocycles with Nhydroxy groups showed promising aggregation results. These compounds are structurally distinct from
aggregation modulators previously investigated in our lab. We are currently running kinetic assays on the
UV-Vis spectrophotometer and the 96-well plate reader to further interrogate the promoting, inhibiting,
and potential catalytic abilities of some of these compounds. This talk will describe our progress toward
understanding the behavior of N-hydroxy heterocycles in synthetic eumelanin polymerizations.
21. PHARMACOLOGICAL AND PRE-CLINICAL TESTING OF 5-NIDR AS A NEW
THERAPEUTIC AGENT AGAINST BRAIN CANCER
Casey Seol Kim1, Jung-Suk Choi1, Dr. Anthony J. Berdis1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115
Abstract
Approximately 4,000 children in the United States are diagnosed annually with a brain tumor. Brain
cancers are the deadliest of all pediatric cancers as they have survival rates of less than 20%. Although
surgery and radiation therapy are widely used to treat adult patients, chemotherapy is the primary
therapeutic option for children. One important chemotherapeutic agent is temozolomide, an alkylating
agent that causes cell death by damaging DNA. In this project, we tested the ability of a specific nonnatural nucleoside developed in our lab, designated 5-NIdR, to increase the efficacy of temozolomide
against brain cancer. Cell-based studies demonstrate that the combination of 5-NIdR and temozolomide
kills more cells compared to treatment with either temozolomide or 5-NIdR used alone. Microscopy
techniques demonstrate that the combination of 5-NIdR and temozolomide causes cell death via apoptosis
rather than necrosis. Animal studies using xenograft mice were performed to evaluate the in vivo efficacy
and safety of this drug combination against brain cancer. Preliminary results indicate that treatment with
5-NIdR does not inhibit the rate of tumor growth. In contrast, treatment with temozolomide slows the rate
of tumor growth by 2-fold but does not cause tumor regression. Striking results are obtained combining 5NIdR with temozolomide as this drug combination causes complete tumor regression within two weeks of
treatment. Collectively, these studies provide pharmacological evidence for combining 5-NIdR and
temozolomide as a possible treatment strategy to effectively treat brain cancers.
25
26
Abstracts
Organic Chemistry
27
28
Session: Organic Chemistry (Clapp 108 / 4.20 – 4.40pm)
22. TOWARD THE SYNTHESIS OF DIMETHOXYINDOLE-BASED EUMELANIN ANALOGS
Jonathan Quirke1, Jeff Levy, Won Hee Ryu, Jason M. Belitsky1*
1
Department of Chemistry and Biochemistry, Oberlin College, 173 W Lorain St, Oberlin, OH 44074
Abstract
Melanins are some of the least understood biopolymers, but they have the potential to have a significant
positive impact, potentially acting as water purification tools and organic semiconductors. Of the three
different kinds of melanin, our lab focuses on eumelanin, the form that gives rise to black and brown
coloration in hair and skin. We are carrying out a series of reactions on functionalized indoles in order to
generate small molecules that function as useful analogs of the biopolymer. Starting from commercially
available dimethoxyindoles, we are investigating iridium-catalyzed borylation and NBS-mediated
bromination, to generate substrates for indole-indole Suzuki-Miyaura coupling reactions. Thus far, we
have been able to synthesize a dimethoxyindole carboxylate ester dimer at roughly 35% yield, and
working to further optimize these reactions. This talk will describe our progress toward well-defined
synthetic eumelanin analogs.
29
30
Abstracts
Physical Chemistry
31
32
Session: Physical Chemistry 1 (Clapp 405 / 3.00 – 4.00pm)
23. ELECTROCATALYTIC REDUCTION OF SELENATE ON GOLD ELECTRODES IN THE
PRESENCE OF COPPER (II)
Jonathan R. Strobl1, Daniel A. Scherson1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Overabundance of selenium species in potable water represents a serious threat to human welfare.
Ingestion of excess selenium has toxic effects, collectively referred to as selenosis. The detection and
removal of soluble selenium from water is therefore necessary to avoid health issues.
Few studies have focused on electrocatalytic reduction of selenate, SeO42- , in aqueous electrolytes. One
such study [1] claims that gold electrodes reduce SeO42- to insoluble selenium at potentials below 0.6 V vs
SHE. Although we could reproduce such observations using commercial selenate salts, no currents
originally attributed to the reduction of SeO42- could be detected once selenite, SeO32-, impurities present
in those chemicals were removed.
Interestingly, however, we have found that purified SeO42- can be reduced on Au electrodes upon addition
of millimolar levels of copper (II) salts to the solution in the so-called Cu underpotential deposition region,
i.e. 0.64 - 0.24 V SHE, to yield a thin copper selenide film. Reduction of selenate can also take place at
lower potentials, alongside formation of bulk Cu deposits. Mechanistic studies of selenate reduction in
these two potential regimes are underway and will be presented at the meeting.
References: [1] Ivandini, T. A.; Einaga, Y. Electrocatalysis. 2013, 4, 367-374.
24. EARLY EVENTS IN THE ABSORPTION OF ULTRAVIOLET LIGHT BY PTERIN
BIOMOLECULES
Regina DiScipio1, Carlos E. Crespo-Hernández1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Pterins are a naturally occurring class of heterocyclic organic compounds found naturally in human bodies.
Recent evidence suggests that pterin derivatives can damage DNA and other biomolecules in skin cells
when exposed to ultraviolet (UV) radiation. Indeed, pterins are known to strongly absorb UV light in the
UVA and UVB regions (290 to 400 nm) of the solar spectrum, leading to the population of long-lived
reactive states and the generation of reactive oxygen species. These characteristics are analogous to those
of photosensitizing compounds used in photodynamic therapy to kill cells. Our group is interested in
delineating the electronic relaxation pathways leading to the postulated photoreactivity of these
compounds in an effort to better understand this chemistry. In particular, I will present recently acquired
results from time-resolved absorption spectroscopy, which has allowed us to characterize the transient
species and associated decay lifetimes of three pterin compounds (pterin, biopterin and neopterin)
33
following electronic excitation at 350 nm. The experimental results are further complemented with density
functional calculations, which allow us to propose electronic relaxation mechanisms that can satisfactorily
explain the reported photoreactivity of these compounds in solution. The potential implications of our
results in the exposure of cells to UVA and UVB light will be briefly discussed.
The authors acknowledge the CAREER program of the National Science Foundation (Grant No. CHE1255084) for financial support.
25. ELECTROREDUCTION OF SELENIUM OXYANIONS IN THE PRESENCE OF METHYL
VIOLOGEN
Qi Han1, Daniel A. Scherson1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
It has been recently claimed [1] that the rates of selenate, SeO42-, electroreduction on glassy carbon
electrodes in neutral and acidic aqueous electrolytes at room temperature can be enhanced by the presence
of methyl viologen in solution, MV2+(aq). This contribution will present evidence that the effects
described in that report are due to the reduction of selenite, SeO32-, a common impurity found in
commercial selenate salts. Our detailed studies have shown that the onset for SeO32- reduction shifts by
more than 0.3 V toward more positive values upon introduction of MV2+(aq) in buffered solutions, which
is also about 0.3 V more positive than the onset of MV2+(aq) solutions devoid of SeO32-. One possible
explanation for this phenomenon may be found in the formation of an adduct between the two reactive
species for which the redox potential would be more positive than for either one of the constituents.
However, no such species was detected in our preliminary measurements involving solution phase NMR
and UV-vis spectroscopies. Additional studies are underway to determine the underlying phenomena
responsible for these electrocatalytic effects.
References: [1] Fumiya, Koshikumo., Wakana Murata., Akiyuki, Ooya; Shin-ichiro, Imabayashi.
Electrochemistry. 81(2013), 350- 352.
34
Session: Physical Chemistry 2 (Clapp 405 / 4.20 – 5.20pm)
26. PHOTOCHEMISTRY OF PROMISING ANCESTRAL RNA NUCLEOBASES
Matthew M. Brister1, Carlos E. Crespo-Hernández1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Ultraviolet light played a key role in the chemistry of organic molecules on early Earth. The energy
associated with the ultraviolet light is high enough to electronically energize, break chemical bonds, and
ionize organic molecules. These effects can degrade biologically-relevant molecules, creating
environmental stress that can impede abiogenesis. Besides, biogenesis also took place long before the
formation of the stratospheric ozone layer, which currently filters out the most dangerous ultraviolet
components of sunlight, and thus under conditions of extremely intense high-energy ultraviolet radiation.
According to the widely accepted RNA World theory, the canonical nucleobases evolved from a complex
mixture of organic molecules on early Earth, the so-called “prebiotic soup”. Hence, it is important to
scrutinize the stability of putative ancestral RNA candidates toward ultraviolet radiation in order to
support their putative prebiotic involvement and, ultimately, to understand the molecular origins of life. In
our laboratory, we use spectroscopic techniques to monitor the electronic relaxation pathways and
molecular integrity of promising ancestral RNA candidates when exposed to ultraviolet radiation. In this
presentation, we will show our most recent and exciting results and will discuss the potential implications
to the molecular evolution of the RNA building blocks.
The authors acknowledge the CAREER program of the National Science Foundation (Grant No. CHE1255084) for financial support.
27. THEORETICAL ASPECTS OF SUPEROXIDE OXIDATION KINETICS
Nicholas Georgescu1, Zhange Feng1, Daniel A. Scherson1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Despite decades of research in oxygen reduction kinetics, a deep, comprehensive mechanistic
understanding of the role of superoxide eludes the field. The chief challenge in analyzing this intermediate
is that it is an extraordinarily short-lived species, and therefore must be created and analyzed within a
short timeframe, and furthermore any experiment studying the rate of reaction must account for this
solution-phase dismutation in the meantime. The rotating ring-disk electrode (RRDE), wherein superoxide
at some concentration is generated on the disk of the electrode, was deployed to analyze superoxide
oxidation by a subsequent reaction on the ring.
35
A correlation between the limiting current on the ring and disk, however, is complicated by the secondorder rate of dismutation. Therefore, in order to infer the quantity of superoxide generated at the disk, the
convective-diffusion equation was implemented, which took into account the rate of dismutation in
correlating the disk and ring currents for various ring kinetic expressions. This presentation will analyze in
depth the nature of these simulations and the kinetic conclusions drawn.
28. TRANSIENT ABSORPTION SPECTROSCOPY REVEALS THE POTENTIAL LIGHTINDUCED RISKS ASSOCIATED WITH INCORPORATING DNAM-D5SICS
Brennan Ashwood1, Marvin Pollum1, Carlos E. Crespo-Hernández1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Expansion of the genetic alphabet has long been a high priority in the field of synthetic biology. Such an
achievement could enable synthesizing unnatural amino acids and proteins, as well as enhance the
capabilities of site-specific labeling. In 2014, in vivo replication of an expanded genetic alphabet was
reported for the first time when E.coli incorporated and replicated successfully the unnatural base pair
dNaM-d5SICS. The question arises as to whether these unnatural bases are as stable to solar radiation as
the natural nucleobases. Using steady-state and time-resolved spectroscopic techniques, we investigated
the photophysical properties of dNaM and d5SICS in phosphate buffer and acetonitrile solution. Our
results demonstrate that dNaM and d5SICS populate long-lived, reactive triplet states in ~30% and near
unity yield, respectively, upon UVA excitation. Furthermore, d5SICS is able to generate singlet oxygen
with a 42% yield upon 355 nm excitation. The implications of these results in the potential phototoxicity
of the unnatural bases to DNA will be discussed.
36
Abstracts
Materials Chemistry
37
38
Session: Materials Chemistry 1 (Millis 123 / 3.00 – 4.00pm)
29. OPTIMIZING THE FORMATION OF
ALKYLBENZIMIDAZOLYL)PYRIDINE
[3]CATENATES
CONTAINING
2,6-BIS(N-
Qiong Wu1, Rudy J. Wojtecki1, Stuart J. Rowan1*
1
The Laboratory for Supramolecular Materials, Case Western Reserve University, 2100 Adelbert Rd,
Cleveland, OH 44106, United States
Abstract
Metal-ligand coordinating is an effective approach toward [2] or [3]catenanes; however, the synthesis of
linear mainchain poly[n]catenanes remains a great challenge due to the difficulty of cyclization after
threading. 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. Two Bip ligand
containing 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 favored. This result might open a door toward the
synthesis of longer mainchain poly[n]catenanes, the progress toward which will also be discussed.
30. STIMULI-RESPONSIVE LIQUID CRYSTALLINE ELASTOMER ACTUATORS
Brian Michal1, Blayne McKenzie, Simcha Felder, Stuart J. Rowan1*
1
The Laboratory for Supramolecular Materials, Case Western Reserve University, 2100 Adelbert Rd,
Cleveland, OH 44106, United States
Abstract
Liquid crystalline elastomer (LCE) materials have been prepared using the metal binding ligand 2,6bisbenzimidazolylpyridine (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 photothermal 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, the
functionality of these materials is extended by incorporation of disulfide bonds which allow the material to
be healable and reprocessable and function as an adhesive.
39
31. INTEGRATED SYNTHETIC AND COMPUTATIONAL TECHNIQUES FOR THE DESIGN
OF POLY[3]ROTAXANES
Eric P. Bruckner1, Michael J.A. Hore, Stuart J. Rowan1*
1
The Laboratory for Supramolecular Materials, Case Western Reserve University, 2100 Adelbert Rd,
Cleveland, OH 44106, United States
Abstract
Rotaxanes are a type of mechanically interlocked molecule, consisting of a molecular “dumbbell”
threaded through a macrocycle, which can be used as a repeat unit to form larger interlocked polymers (i.e.
polyrotaxanes). Due to the complexity of mechanically interlocked molecules, it is difficult to optimize
component geometry by purely synthetic techniques, thereby necessitating the use of an integrated
experimental and computational approach. Herein progress towards the synthesis of a novel doublethreaded poly[3]rotaxane by a metal-templating process with the 2,6-bis(N-alkyl-benzimidazolyl)pyridine
ligand is reported. Design of the poly[3]rotaxane was supplemented by atomistic simulations used to
determine the optimum component geometry to prevent disassembly of the interlocked structure.
Exploratory coarse-grained dissipative particle dynamics (DPD) simulations were used to calculate
viscoelastic properties of the bulk material in order to understand the relationship between component
geometry and material properties.
Session: Materials Chemistry 2 (Millis 123 / 4.20 – 5.20pm)
32. STRUCTURE-PROPERTY STUDIES OF FLUORINATED AZADIPYRROMETHENE
DERIVATIVES AS N-TYPE ACCEPTORS IN ORGANIC PHOTOVOLTAICS
Sandra Pejic1, Forrest Etheridge, Roshan Fernando1, Geneviève Sauvé1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Zinc azadipyrromethene (ADP) chelates are good candidates as electron acceptors for organic
photovoltaics (OPVs) due to their intense light absorption in the visible to near IR regions and high
electron affinity. Previously, we synthesized an ADP-based electron acceptor containing phenylacetylene
arms, Zn(WS3)2, which performed well in OPVs when blended with poly(3-hexylthiophene) (P3HT). In
this work, we added fluorine in various positions to Zn(WS3)2 to further enhance the electron affinity and
study the effect of positioning of the electron withdrawing groups. The fluorinated acceptors were tested
in organic solar cells using P3HT as the electron acceptor. Depending on the position of the fluorines, the
addition of fluorine either increased (for three acceptors) or decreased (for one acceptor) power
conversion efficiencies (PCE) compared to the unfluorinated Zn(WS3)2 acceptor. To understand these
results, we are currently analyzing morphology and charge carrier mobility in blends. The increased
efficiency for three out of the four fluorinated acceptors demonstrate that fluorination is a promising
method to develop better acceptors for OPVs.
40
33. BIOMIMETIC DYNAMIC HEAT-STIFFENING POLYMER NANOCOMPOSITES
Elvis Cudjoe1, Amanda E. Way, Stuart J. Rowan1*
1
The Laboratory for Supramolecular Materials, Case Western Reserve University, 2100 Adelbert Rd,
Cleveland, OH 44106, United States
Abstract
“Smart” materials have attracted a lot of attention in recent years due to their ability to dramatically alter
their mechanical properties, which allow access to a range of responsive materials that exhibit properties
such as shape-memory, actuating and self-healing. Inspired by the soft-stiff transition of the sea cucumber
dermis, we have developed a stimuli responsive material that shows an increase in stiffness upon exposure
to moderately hot water. In this work, we isolated cellulose nanocrystals (CNCs) from sea tunicates,
which were grafted with lower critical solution temperature (LCST) polymers. The polymer grafted CNCs
were incorporated into a matrix, poly (vinyl acetate), and upon exposure to water above the LCST of the
polymer, CNC interactions were switched on leading to the stiffening of the composites. While most
materials are known to soften with heat, these materials offer a unique property, which has the potential as
new biomaterial implants (e.g. craniofacial implants).
34. GRAPHENE-BASED
MATERIALS
PEROXYNITRITE SENSORS
FOR
ENHANCED
PERFORMANCE
OF
Haitham Kalil1, Mekki Bayachou1*
1
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue SR 397, Cleveland, Ohio
44115, United States
Abstract
Peroxynitrite (ONOO−, PON) plays a crucial role in several diseases triggered by oxidative stress. PON is
a strong oxidizing agent produced from the diffusion-controlled reaction between nitric oxide and
superoxide radicals. 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 initiates
radical chain reactions that inflict further chemical damage.
The elevation in PON levels are associated with chronic inflammatory disorders including neurological
and vascular diseases. The accurate quantification of this analyte in biological systems is of great
significance not only to understand the genesis and development of the diseases, but also to assess the
potential therapies and understand the reaction mechanisms.
In this work, we prepare graphene-based materials as potential catalytic interfaces for sensitive
electrochemical determination of PON. We will describe the methods of preparation of metal-decorated
graphene materials. Then, the morphological characterization of these composite materials will be
investigated using scanning electron microscopy (SEM), ultraviolet/visible spectroscopy (UV/Vis), and
energy-dispersive x-ray spectroscopy (EDX). We will discuss the electrochemical profile of PON and
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investigate its electrochemical signature on bare and modified carbon electrodes. The modified
nanostructured-graphene electrodes will be tested as platforms for PON detection and quantification using
voltammetry and dose-response amperometry. In conclusion, we found that the incorporation of
manganese nanoparticles in the graphene-based materials influences the sensitivity of their modified
electrodes towards the quantification of PON.
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Abstracts
Inorganic Chemistry
43
44
Session: Inorganic Chemistry (Millis 220 B / 3.00 – 4.00pm)
35. INVESTIGATIONS INTO PHOTOLYSIS REACTIONS USING HYPERVALENT IODINE
Andrew Kollar1, Bindu Meprathu, John Protasiewicz1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
This talk will focus on the investigation of making aziridines and epoxides through photolysis of
hypervalent
iodine
compounds.
Previously
made
compounds,
2-(tertbutylsulfonyl)tosylaminoiodobenzene and 2-(tert-butylsulfonyl)iodosylbenzene will be examined to make
aziridines and epoxides 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.
36. POLYOXAPHOSPHOLES: POLYMERIC ORGANOPHOSPHORUS MATERIALS WITH
LUMINESCENT PROPERTIES
Joshua Gaffen1, John Protasiewicz1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
Organic π-conjugated materials containing heteroatoms are of interest as each heteroatom has the potential
to alter the material’s electronic and photo-physical properties. The unique nature and stability of the P=C
bond allows for use of phosphorus in such systems, however, previously polymeric systems containing a
P=C bond along the conjugated pathway have proven difficult to synthesize.
Based off of an oxaxphosphole backbone, a family of polymeric compounds has been synthesized using a
variety of novel and known primary phosphines, and a variety of acyl dichlorides with solubilizing
substituents as linkers. The synthetic roadblocks and novel synthesis of these polymeric compounds will
be presented, along with various comparisons with their corresponding small molecule model compounds.
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37. SYNTHESIS OF LUMINESCENT GOLD(III) CYCLOMETALATED COMPLEXES
Amanda N. Sulicz1, Thomas G. Gray1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
The chemistry of cyclometalated gold(III) has been relatively slow to emerge, but recent advances in
catalyst and material design have driven a renewed interest. Reported here are synthetic, structural, and
optical studies of cyclometalated gold(III) aryl complexes. These new complexes show ligand-centered
luminescence that is perturbed by the heavy-atom effect of gold. Traditionally, metal-carbon bond
formation often relied on organometallic complexes of electropositive elements, including lithium and
magnesium. The easily reducible nature of gold(III) often interferes with these conventional reagents, thus
resulting in the use of toxic metals like mercury or thallium. Reported here is the use of palladiumcatalyzed Suzuki-Miyaura coupling to attach aryl ligands to cyclometalated gold(III) chloride complexes,
resulting in a reliable synthesis to both di- and monoarylated species. Several complexes have been
crystallographically characterized. Mixed aryl and alkynyl derivatives are sought. Luminescent derivatives
of a previously published gold(III) chloro precursor, initially reported for catalytic purposes, are being
prepared through boron transmetalation reactions. Alkynyl and aryl products are sought. These
luminescent materials are diamagnetic and will be characterized by multinuclear NMR, absorption and
emission spectroscopies (including time-resolved emission), and by X-ray diffraction crystallography
when possible.
Session: Inorganic Chemistry / Chemical Engineering (Millis 220 B / 4.20 – 5.00pm)
38. METALLOPORPHYRIN WITH XANTHENE (CO2ME) HANGMAN MOLECULES
Yishayah Bension1, Andrew Kollar1, John Protasiewicz1*
1
Department of Chemistry, Case
Cleveland, OH 44106, United States
Western
Reserve
University,
2080
Adelbert
Road
Abstract
The trouble with increasingly complex molecular building blocks is that they require increasingly complex
strategies to functionalize them. One strategy, about forty years old, is remote functionalization. A
particularly promising approach is to attach an arm to a site which can then functionalize another atom
within its reach. Our approach uses the xanthene attached to a metalloporphyrin with two components:
iodosylbenzene and a xanthyl derivative bearing a methyl carboxylate. The four nitrogen molecules at the
center of the porphyrin have been used as a metal atom complexer in this case, iron. This system inspired
by the chlorophyll and hemoglobin structure has been used as an enzyme mimic but also more generally.
The usefulness of the target structure would have many applications such as stereospecific catalysis.
46
Abstracts
Chemical Engineering
47
48
Session: Inorganic Chemistry / Chemical Engineering (Millis 220 B / 4.20 – 5.00pm)
39. ELECTROCHEMICAL MICRO PH-STAT FOR POINT-OF-CARE ENZYME ASSAYS
Zhehao Zhang1, Christian Zorman, Miklos Graztl1*
1
Department of Biomedical Engineering, Case Western Reserve University, 309 Wickenden Building,
10900 Euclid Avenue, Cleveland, OH 44106, United States
Abstract
Enzyme activities in human blood are critical indicators of different clinical conditions. The
electrochemical pH-stat, a unique approach to measure enzyme activities, has been developed in our
laboratory. It is a simple diagnostic device that can cover a wide range of enzymes of clinical importance
using one microfabricated analysis slide. The pH-stat holds two microliters of sample and is composed of
a sample chamber embedded with three electrodes. The enzyme-containing sample is wicked into
chamber via capillary action. Mixing within the chamber is achieved by passive diffusion. The pH sensing
electrode constantly monitors the pH inside the chamber, sending feedback to a software control program,
which then determines the direction and the amount of current to be injected through the working
electrode. The current causes water-splitting and thus can be used to maintain the pH at a desired level
despite the ongoing enzyme reaction. The injected current is directly linked to the rate of substrate
conversion. The proposed device has the potential to be implemented for point-of-care enzyme assays,
significantly accelerating the measurement while lowering the costs.
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