1

Willard H. Dow Laboratories

The University of Michigan

930 N. University Ave Ann Arbor, MI 48109

Vaughan Symposium

Book of Abstracts

August 18, 2010

• Sponsored by:

Dow Chemical

University of Michigan Department of Chemistry

Chemistry Graduate Student Council

Keynote Speakers:

Cliff Gerwick Dow Agrosciences

Marcey Waters University of North Carolina, Chapel Hill

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Table of Contents

Schedule of Events 3

About the Vaughan Symposium 4

Keynote speaker Cliff Gerwick’s abstract 5

Keynote speaker Marcey Waters’ abstract 5

Student speaker abstracts 6

Poster Abstracts

- Analytical 9

- Chemical Biology 14

- Inorganic 24

- Materials 35

- Organic 44

- Physical 52

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Schedule of Events

Vaughan Symposium Schedule 2010

Check-in begins at 7:45 AM

Morning Session 1 – Chemistry 1210

7:45-8:30 Breakfast, Session 1 poster setup

8:30-8:40 Welcoming Remarks

8:40-9:20 Dow Chemical Keynote Speaker, Dr. Cliff Gerwick, Dow Senior Scientist

9:20-9:45 Jeffery Raymond (Physical) – Advisor : Prof. Theodore Goodson III

9:45-10:10 Hasnain Malik (Organic) – Advisor : Prof. John Montgomery

10:10-10:35 Xin Liu (ChemBio) – Advisor : Prof. Carol Fierke

Morning Session 2 - Lower & Upper Atrium

10:45-12:00 Poster Session 1 (Poster #’s 1-47)

12:00-1:00 Lunch, Take down Session 1 posters and Session 2 poster setup

Afternoon Session 1 – Chemistry 1210

1:00-1:25 Tim Berto (Inorganic) – Advisor : Prof. Nicolai Lehnert

1:25-1:50 Kira Landenberger (Materials) – Advisor : Prof. Adam Matzger

1:50-2:15 Kevin Hartman (Analytical) – Advisor : Prof. Ayyalusamy Ramamoorthy

Afternoon Session 2 – Lower & Upper Atrium

2:25-3:50 Poster Session 2 (Poster #’s 48-95)

3:50-4:00 Take down Session 2 posters

Afternoon Session 3 – Chemistry 1210

4:00-5:00 Vaughan Keynote Speaker, Prof. Marcey Waters, UNC, Chapel Hill

5:00-5:30 Closing Remarks/Awards

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The Vaughan Symposium was designed by Michigan graduate students as a venue in which

to share exciting research taking place within the department. Originally named PECRUM,

the first symposium was held in 2003. Through participants presenting their work to the

department as a whole, students foster collaborations, inspire new avenues of research, and

nurture a growing sense of community within the department. The symposium has become an

annual tradition within Michigan's Department of Chemistry. The symposium is student

organized, and members of the student organizing committee are listed below:

Chair: Alana Canfield

Chair-elect: Elaina Zverina Yash Adhia

Jing Chen Ming Fang

Deidra Gerlach Joseph Jankolovits

Aireal Jenkins Erica Lanni

Sharon Neufeldt Heidi Pedini

Shana Santos Sunny Yau

Faculty Advisors: Nicolai Lehnert, Anne McNeil

At the 2010 Vaughan Symposium, awards will be distributed to graduate students who

give the highest quality talks and posters. Presentations will be judged on ….

The following awards will be distributed:

One oral presentation first prize $1000 travel award

Two oral presentation $500 travel awards

Twenty poster $400 travel awards.

The Vaughan Symposium is named in honor of Victor Clarence Vaughan (1851-1929), one

of the first students to graduate from University of Michigan with a Ph.D. in Chemistry.

Vaughan graduated in 1876, and his dissertation is entitled “Quantitative Separation of

Arsenic From Each of The Metals Precipitated by Hydrogen-Sulphide in Acid Solution.”

Vaughan also earned an M.D. from Michigan in 1878 and later served as dean of the

Medical School from 1891-1921. Vaughan additionally taught physiological and

pathological chemistry, hygiene, bacteriology, and therapeutics at Michigan, among other

subjects, and served as the president of the American Medical Association from 1914-1915.

About the Vaughan Symposium

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DHT: A New Family of Herbicide Tolerance Traits

Cliff Gerwick, Discovery Ag-Chemistry leader at Dow AgroSciences

LLC, 9330 Zionsville Road, Indianapolis, IN 46268

The availability of glyphosate resistant crops in the Americas offered a number of

advantages to growers over existing weed control technologies including simplicity and

efficacy. The rapid and widespread adoption of this technology, however, is resulting in weed

shifts and weed resistance to glyphosate. Anticipating this problem and seeking to identify

technology to extend the utility of the glyphosate herbicide tolerant (HT) system, we pursued

the discovery and development of a new family of HT traits based on a-ketoglutarate-dependent

dioxygenase metabolism of

other proven, broad-

spectrum herbicides. DHT1

-corn, DHT2-soybeans, and

DHT2-cotton will be

deployed with other key

traits, including traits for

insect resistance and traits

conferring tolerance to other

commercially available

herbicides.

Problems of Molecular and Biomolecular Recognition

Marcey Waters, University of North Carolina, Chapel Hill

Research in the Waters group focuses on the connection between molecular structure

and biological function, specifically with regard to protein folding and biomolecular

recognition. To this end, we utilize structured peptides to investigate the role of perturbations in

molecular structure, including posttranslational modifications (PTMs) such as glycosylation,

acylation, and methylation, on folding and function. In addition, we use dynamic combinatorial

chemistry to develop molecular receptors for PTMs with the goal of both gaining funda-mental

understanding of the molecular recognition and developing new tools for identification of

PTMs. These topics will be discussed.

Keynote Speaker Abstracts

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Student Speaker Abstracts Synthetic Light-Harvesting Mimics: Relating ultrafast energy delocalization

to nonlinear optoelectronic enhancement.

Jeffery Raymond, Physical, Class of 2006, Goodson Group

Porphyrin dyads and dimers, the building blocks of several natural light harvesting systems, have shown

much promise in elucidating the manor by which energy transfer contributes to enhanced optoelectronic

properties. These studies have been particu-

larly focused on applications such as bio-

mimetic photovoltaics, remote sensing and

nonlinear optics. In the realm of two-photon

absorption, higher order assemblies of por-

phyrin building blocks have shown enhance-

ment factors as high as two orders of magni-

tude. We will discuss several studies in

which the ultrafast excited state behavior

illuminates the causes, both energetic and

architectural, of this marked increase in

nonlinear optical behavior. We will also

point towards how these associations might

be harnessed for device applications.

A General Strategy for Regiocontrol in Nickel-Catalyzed Reductive Cou-

plings of Aldehydes and Alkynes

Hasnain A. Malik, Organic, Class of 2005, Montgomery Group

An approach for catalyst-controlled regioselectivity in aldehyde−alkyne reductive couplings has been

developed where either regiochemical outcome may be selected for a broad range of couplings. This

method is the first requiring no substrate biases or directing effects to influence regioselectivity. The

complementary use of small cyclopropenylidene carbene ligands or highly hindered N-heterocyclic car-

bene ligands allows for either regiochemical outcome with unbiased internal alkynes, aromatic internal

alkynes, conjugated enynes, or terminal alkynes. Further experiments are underway to achieve both re-

gio- and enantioselectivity via similar catalyst-control strategies.

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A Fluorescence Polarization Assay for Screening Inhibitors against Bacterial

RNase P

Xin Liu, Chembio, Class of 2007, Fierke Group

Due to the continued emergence of drug-resistant bacteria, there is an urgent need for new antibiotic tar-

gets and treatments. Ribonuclease P (RNase P) is an enzyme that catalyzes the maturation of the 5‟ ter-

mini of precursor-tRNAs. Bacterial RNase P is an attractive potential antibacterial target because it is

essential for cell survival and has distinct structural differences from its eukaryotic counterpart. We have

developed a fluorescence polarization (FP) assay using pre-tRNA labeled with a fluorophore at the

5‟end to screen for inhibitors of bacterial RNase P. This FP assay was amenable to both kinetic studies

and endpoint measurements. This assay was used to measure inhibition of B. subtilis RNase P by neo-

mycin B (IC50 = 20 ± 2 µM) and kanamycin B (IC50 = 78 ± 11 µM). Furthermore, a primary screen of

a 266 compound library in a 96-well plate format

was carried out. This assay provides a Z‟ factor of

0.8 and is rapid, cost-effective and robust. We are

optimizing the assay in 384-well microplate format

and will perform high-throughput screening of lar-

ger small molecule and natural product compound

libraries. The high-throughput methodology for

screening of RNase P inhibitors will allow both a

test of hypothesis that RNase P is a viable drug tar-

get and investigation of molecular recognition of

inhibitors by this enzyme.

Sophisticated Tetraphenylporphyrin Derivatives for the Modeling of the Di-

nuclear Active Site of Bacterial Nitric Oxide Reductase

Tim Berto, Inorganic, Class of 2007, Lehnert Group

Bacterial nitric oxide reductase (NorBC) is a protein which contains a combined ferrous heme/non-heme

active site where the heme shows axial histidine coordination trans to NO. Due to the exceptionally

strong sigma trans effect of NO, model complexes must employ covalently attached N-donor ligands in

order to remain 6-coordinate. Our results indicate that the use of slightly electron poor porphyrin centers

along with bulky benzylimidazole tethers facilitate a relatively strong Fe-N-donor interaction in the 6-

coordinate NO complex. A crystal structure of the corresponding zinc complex was obtained. These

tethered systems can be used to mimic the heme component of NorBC. The non-heme iron site of

NorBC can be modeled using ferrous complexes of substituted tris(2-pyridalmethyl)amine or di-2-

picolyl amine derivatives. A recent crystal structure of NorBC shows these systems accurately model

the protein‟s non-heme iron site. Covalent linkage of the heme and non-heme components yields a sys-

tem in which two iron centers are in close proximity to one another. Interactions between the heme and

non-heme iron nitro-

syls can then be used

to examine the mecha-

nism of NO reduction

in NorBC as well as

the influence of the

axial histidine on NO

reactivity.

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Energetic Cocrystals

Kira Landenberger, Materials, Class of 2008, Matzger Group

Traditionally, the development of new energetic materials, including explosives, propellants and pyro-

technics, has focused primarily on the synthesis of new compounds and/or the discovery of polymorphs

with the most attractive properties. This is a time-intensive process and, due to the stringent require-

ments for practical energetic materials, new energetics are seldom fielded. Here we present a unique

approach to alter the properties of existing energetic materials through cocrystallization. Cocrystalliza-

tion utilizes non-covalent interactions to form a regular solid-state arrangement from two or more neu-

tral molecular components. The structure and properties of seventeen new cocrystals of the benchmark

energetic material 2,4,6-trinitrotoluene (TNT) will be presented as will progress on cocrystallization of

cyclotetranitromethylenetetranitramine (HMX). A detailed study of the cocrystals formed thus far re-

veals an alteration of key properties including density, packing coefficient, melting point and decompo-

sition temperature. Cocrystallization provides the opportunity to tune properties of existing energetics to

create superior materials. The donor acceptor π-π interaction represents a reliable supramolecular syn-

thon for the formation of

cocrystals with aromatic en-

ergetic materials such as of

TNT whereas the cocrystals

of HMX appear to lack spe-

cific structure-directing in-

teractions.

Role of Zinc in Human Islet Amyloid Polypeptide Aggregation

Kevin Hartman, Analytical, Class of 2007, Ramamoorthy Group

Human Islet Amyloid Polypeptide (hIAPP) is a highly amyloidogenic protein found in islet cells of patients with

type II diabetes. Because hIAPP is highly toxic to beta-cells under certain conditions, it has been proposed that

hIAPP is linked to the loss of beta-cells and insulin secretion in type II diabetics. One of the interesting questions

surrounding this peptide is how the toxic and aggregation prone hIAPP peptide can be maintained in a safe state at

the high concentrations found in the secretory granule where is stored. We show here through a combination of

NMR, ITC, CD, and Thioflavin T fluorescence that zinc, which is found at millimolar concentrations in the secre-

tory granule, binds to hIAPP with a Kd of approximately 100 nM

and inhibits hIAPP amyloid fibrillogenesis in the micromolar

range. NMR spectroscopy shows that zinc interacts with hIAPP

through coordination to His18 and a probable cation – pi stacking

interaction with Phe15. ITC binding experiments with the rat vari-

ant of IAPP, which lacks His18, indicated an additional binding

site with approximately 1 mM affinity. The lower affinity binding

site was localized to Arg11 by NMR. The binding of zinc also al-

ters the structure of hIAPP, rigidifying the N-terminal region of the

protein in a near-helical conformation stabilizing the non-amyloid

form of the peptide. The inhibition of the aggregated and toxic

forms of hIAPP by zinc provides a possible mechanism between

the recent discovery of linkage between deleterious mutations in

the SLC30A8 zinc transporter, which transports zinc into the secre-

tory granule, and type II diabetes. granule, and type II diabetes.

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1: A novel method for high spatial and temporal resolution monitoring of

neurotransmitters in the brain using segmented flow and low-flow push-pull

perfusion

Thomas Slaney, Class of 2007, Kennedy Group

A new method to achieve both high spatial and temporal resolution monitoring of neurotransmitters in the brain

was developed. By using low-flow push-pull perfusion sampling probes, smaller than 0.02 square millimeter spa-

tial resolution was demonstrated. Brain extracellular fluid was collected as 6 nL plugs at 50 nL/min in an oil car-

rier phase to prevent diffusion, which has limited this method to 45 s resolution in previous studies. High-

throughput analysis of femtomole quantities of the neurotransmitter glutamate was achieved using a novel device

to add 3 nL of a fluorescent enzyme reagent to each plug. Concentration changes could be observed with 7 s reso-

lution, limited by the frequency of generated plugs. Average basal glutamate in the striatum was 0.8 ± 0.2 µM (N

= 7 rats). High potassium (70 mM) physiological saline buffer was microinjected next to the probe to stimulate

neurotransmitter release. Glutamate responses had a maxima of 5.9 ± 1.1 µM for the first injection (N = 5 rats),

and 3.5 ± 0.2 µM for subsequent injections (N = 13 injections, 5 rats). Future work will utilize enzyme assays for

GABA and choline/acetylcholine analysis, and a mi-

crofluidic chip for capillary electrophoresis of samples

for analysis of other neurotransmitters. Better than 1 s

resolution should be possible in future by generating

smaller, higher frequency plugs. This method should

augment the in vivo neurochemistry toolbox, allowing

small brain nuclei to be observed with high spatiotem-

poral resolution without the analytical challenges of

electrochemical sensors.

2: Membrane orientation of the Gβγ-GRK2 complex

Andrew Boughton, Class of 2004, Chen Group

G-proteins and G-protein coupled receptors (GPCR) are involved in a host of cellular signaling proc-

esses. It has been proposed that successful phosphorylation and inhibition of activated GPCRs by G-

protein coupled receptor kinase 2 (GRK2) requires that the kinase be recruited to the membrane by Gβγ

subunits in a specific orientation, but direct experimental evidence for this orientation has not been ob-

served. Using SFG and a new computational software package that we have designed, we have studied

formation of the Gβγ-GRK2 complex directly at a model cell membrane interface, without the use of

exogenous labels. We first successfully demonstrated that the complex could be formed at the membrane

via serial addition of subunits, and then analyzed molecular orientation using multiple constraints. Possi-

ble orientations of the Gβγ-GRK2 complex have been quantified. Surprisingly, measurements of mo-

lecular orientation indicate that the orientation of the Gβγ -GRK2 complex at the lipid interface is domi-

nated by the anchoring group of Gβγ, with minimal membrane binding by basic residues present along

the GRK2 surface. Our results may suggest that Gβγ -GRK2 binding to GPCRs occurs in a two-stage

model, in which the final orientation of the complex for receptor phosphorylation requires interactions

with lipids and the GPCR. In addition to providing basic structural insights, we demonstrate that SFG

can be used to study the formation of large protein complexes in a stepwise fashion. The SFG methods

and software package for data analysis will greatly facilitate the future study of other multi-subunit pro-

tein complexes in situ using vibrational spectroscopy.

Analytical Poster Abstracts

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4: Electron Induced Dissociation (EID) of Singly Protonated Glycans

Di Gao, Class of 2008, Hakansson Group

Cross-ring cleavages are crucial for structural characterization of branched glycans. Electron capture

dissociation (ECD) and electron detachment dissociation (EDD) can yield extensive glycosidic and cross

-ring fragments in carbohydrate MS/MS but require multiply charged precursor ions. Electron induced

dissociation (EID) involves irradiation of singly charged cations or anions to generate vibrational and

electronic excitation and has been shown to yield complementary fragmentation patterns compared to

collision induced dissociation (CID). Here, for the first time, EID is applied to singly protonated gly-

cans.

Lacto-N-difucohexaose I (LNDFH I), lacto-N-fucopentaose (LNFP I), lacto-N-hexaose (LNH) were la-

beled with 9-aminofluorene (9FL) (Sigma-Aldrich). Mass spectra were recorded on a 7 Tesla Q-FT-ICR

mass spectrometer (Bruker Daltonics). EID was performed inside the ICR cell with a cathode bias volt-

age of -17-22 V for 0.3-0.5 s while CID was performed in the collision cell. Mass spectra were summed

over 64 scans for EID and 32 scans for CID.

Our data show that EID provides complementary information about glycan structure compared to CID,

including enhanced Y-, Z-, B-, C-type glycosidic cleavages, X-type cross-ring cleavages, and internal

fragments. 1,5X-type cleavages are more common than other X-type product ions in EID, similar to high

-energy CID. This observation may further indicate similarity between the mechanism of EID and that

of high-energy CID. Fucose-migration fragments are much less abundant in EID compared to CID. EID

of tagged glycans produces more fragments than that of untagged glycans. The presence of 9-

aminofluorene may facilitate electronic excitation in EID.

5: Spectroscopic Studies of E. coli Flavorubredoxin Nitric Oxide Reductase

Josh Skodack, Class of 2005, Lehnert Group

E. coli Flavorubredoxin Nitric Oxide Reductase (FNOR) is a unique two-domain protein that catalyzes

the reduction of nitric oxide. The protein structure consists of three domains; a metallo-beta-lactamase

domain that contains the non-heme diiron active site, a flavodoxin like domain which contains a FMN

moiety, and a rubredoxin domain that is important for reducing the FMN. The catalytically active dimer

form of the protein resides in a "head-to-tail" arrangement where the diiron site of a monomer is reduced

by the FMN cofactor from a separate monomer. The reduced ferrous non-heme diiron active site is able

to bind two molecules of NO prior to reduction by the FMN moiety. EPR, Stopped-flow and conven-

tional UV-Vis absorption spectroscopy, and MCD spectroscopy have been utilized to elucidate the

mechanism of nitric oxide reduction. We hypothesize that the FMN reduces the central diiron dinitrosyl

intermediate directly by one electron reduction to activate the bound nitric oxide. Thus we believe that

the FMN cofactor plays a crucial role in the catalytic mechanism of FNOR.

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6: Surface Enhanced Raman Spectroscopy Platforms for Studying Chemical

Processes at Nanostructured Semiconductor Interfaces

Junsi Gu, Class of 2009, Maldonado Group

Nanostructured semiconductors are the key functional elements in emerging microelectronics, solar cells

and chemical sensors. The chemistry of their interfaces strongly controls their capacity to function in

these applications. This presentation will highlight data that describes a methodology for studying

chemical processes at nanostructured semiconductors. Ultra-thin films of group IV and II-VI semicon-

ductors were electrodeposited onto Au nanoparticle films exhibiting a strong surface enhanced Raman

spectroscopy (SERS) amplification. These platforms augmented the Raman signatures for the vibronic

processes at the surfaces of the ultra-thin semiconductor films. Real time SERS measurements were con-

ducted to provide insight on the electrodeposition processes of Ge, CdSe, and CdTe and to confirm the

crystallinity of the semiconductor films as prepared. Preliminary data on the surface functionalization of

the Cd-based films will be presented. We show that the adsorption of cysteamine onto CdSe can be

monitored in-situ in aqueous solution at room temperature. Separately, data will be shown for Ge ultra-

thin films that illustrate their integrity, crystallinity, and reactivity. These data provide the groundwork

for studying the chemistry of nanostructured semiconductor optoelectronic materials.

48: Volatile Organic Compound Determinations by Multi-Transducer Micro-

Sensor Arrays

Kee Scholten, Class of 2009, Zellers Group

The need for in situ determinations of volatile organic compounds (VOC) in applications such as envi-

ronmental monitoring, biomedical diagnostics, and homeland security continues to drive the develop-

ment of microfabricated sensor arrays composed of elements operating on different transduction mecha-

nisms that respond to different analyte properties. Toward that end, we are exploring three different mi-

crofabricated sensing technologies: chemiresistors employing temperature modulated tin-oxide

nanowire ensembles (NW-CR), chemiresistors employing thiolate-monolayer-protected gold nanoparti-

cle films (MPN-CR), and optofluidic ring resonators (µOFRR) employing polymeric or MPN coatings.

A primary focus is on testing performed with the first two sensor types. In the NW-CRs, mats of NWs

bridge an electrode gap on a micro-hotplate; temperature dependent VOC oxidation produces changes in

conductivity. MPN-CRs consist of thin sorptive MPN films deposited over interdigital electrodes; VOC

sorption leads to swelling-induced changes in tunneling current. Two NW-CRs operated a different tem-

peratures were tested alongside four different MPN-CRs upon exposure to three VOCs. The response

data were combined to create “virtual” arrays; Monte Carlo simulations coupled with principal compo-

nents regression analysis of virtual arrays of 2-4 sensors reveal that the diversity of responses of these

two sensor technologies is comparable. The NW-CRs proved more sensitive but less stable and repro-

ducible. Complementing this work, we have embarked on the design and fabrication of a novel µOFRR

that integrates a polymer- or MPN-coated optical resonator into a microfluidic channel that should pro-

vide yet another element of a multi-transducer array for VOC determinations. The µOFRR design and

microfabrication techniques being employed are described.

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49: Development of a Hofmeister Series Analogue for Gas-phase Protein

Complexes: Evidence from Ion Mobility-Mass Spectrometry

Linjie Han, Class of 2009, Brandon Ruotolo Group

The application of ion mobility mass spectrometry (IM-MS) in structural biology requires that the struc-

ture of electrospray-generated ions of biomolecules to be conserved. However, in the case of proteins

and protein complexes, the extent of „dehydration‟ is often challenging to control leading to difficulties

in downstream structural assignments. In preliminary experiments, we have generated stabilized protein

complex ions by replacing bulk solvent contacts with stabilizing counter-ions. Now, we have extended

this „salt shell‟ concept to include both stabilizing and destabilizing salts bound to large multi-protein

complexes. Here, we quantify the stabilizing or de-stabilizing influence of a range of counter ions on gas

-phase protein structure – analogous to the Hofmeister series in solution, for applications in gas-phase

structural biology

50: Negative Ion Electron Capture Dissociation (niECD): a Novel Technique

for Characterizaton of Acidic Peptides

Ning Wang, Class of 2009, Kristina Hakansson Group

Electron capture dissociation (ECD) is one of the most significant developments in tandem mass spec-

trometry for structural characterization of proteins, peptides and other biomolecules. In ECD, low en-

ergy electrons (<1 eV) are captured by multiply positively charged ions, resulting in a charge-reduced

radical intermediate that undergoes structurally informative fragmentation, including retention of post-

translational modification (PTMs). The main drawback of ECD, however, is that it requires multiply

positively charged precursor ions, possibly precluding analysis of acidic molecules such as phospho- and

sulfopeptides that ionize poorly in positive ion mode.

We employed electron irradiation (10-20 s) towards negatively charged peptides ([M - nH]n-) and found

that peptide anions can capture electrons within a narrow energy range (6-7 eV), leading to charge-

increased radical species ([M - nH](n+1)-•), and inducing extensive backbone fragmentation analogous to

that observed in positive ion mode ECD. We refer to this new tandem mass spectrometry technique as

negative ion electron capture dissociation (niECD). One possible mechanism for niECD is the presence

of zwitterionic structures in the gas phase and capture of electrons by positively charged sites. We have

explored the effects of acetylating primary amines, dephosphorylation in both solution and gas phase as

well as comparing peptides with and without a sulfate group. All these experiments support the zwit-

terion hypothesis. Compared to conventional collision induced dissociation, niECD provides higher se-

quence coverage and more extensive backbone fragments while retaining labile PTMs. For this reason,

niECD holds great promise for PTM localization and for de novo sequencing.

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51: Capillary Liquid Chromatography Tandem Mass Spectrometry for High

Sensitivity Metabolomic Analysis

Peng Song, Class of 2007, Kennedy Group

Liquid chromatography coupled with mass spectrometry is a powerful technique in the fast developing

field of metabolomics. Capillary liquid chromatography was explored for its ability to work with micro-

scale samples. Fused silica capillary packed with hydrophilic interaction (HILIC) stationary phase was

interfaced with triple quadrupole mass spectrometer for high sensitivity analysis of polar ionic small

molecules in biological matrices. Improvement in sensitivity was achieved by less chromatographic dilu-

tion of nanoscale liquid chromatography and preconcentration of relatively large injection volume.

Preconcentration was made possible by good retention in HILIC mode of chromatography and use of

trapping column. System was fully automated by the adaption of commercial instrumentation. Good

throughput (30 to 50 runs per day) was achieved. Capillary LC-MS methods for a select group of posi-

tively and negatively charged analytes were developed and validated. This technique was used to detect

concentration changes of glycolysis and TCA cycle metabolites extracted from islets of Langerhans and

neurotransmitters from rat brain microdialysate under different conditions. 20 to 30 analytes were usu-

ally monitored in each run using multiple reactions monitoring on the triple quadrupole mass spectrome-

ter. Limit of detection range from 100 fmole to 50 pmole with median value around 5 pmole. Average

standard deviation is around 7% with n= 3. This technique demonstrated high sensitivity, robustness and

versatility for the analysis of small polar molecules in limited biological samples.

52: A Critical Evaluation of Charge Manipulation Strategies Coupled to

Nano-Electrospray Ion Mobility-Mass Spectrometry

Russell Bornschein, Class of 2009, Ruotolo Group

Recent evidence has highlighted the utility of ion mobility-mass spectrometry (IM-MS) in conjunction

with nano-electrospray ionization (nESI) for applications in structural biology. Many of these reports

have also indicated that the overall charge of the ions observed can have a significant effect on the infor-

mation content of the IM-MS dataset obtained. For example, protein complex ions of decreased charge

state have been shown to exhibit more compact conformations and, when activated, can release subunits

that are also compact. Conversely, highly-charged protein assemblies dissociate asymmetrically, and

under high-energy activation conditions can also release sequence-informative fragment ions. The util-

ity associated with charge manipulation is clear and here, we critically evaluate a number of charge re-

duction approaches adapted for IM-MS analysis of protein complexes. For our work, we have chosen to

classify multiple charge reduction approaches in terms of three main figures of merit: 1) charge reduc-

tion efficiency 2) charge state „tuneability‟ and 3) resulting gas-phase ion structure. Our primary goal is

to generate an optimized charge reduction method for the study and analysis of large protein complexes

using IM-MS, an endeavor that requires high performance from all three criteria described above. Our

proof-of-principle work has included multiple experiments aimed at optimizing charge reduction in such

a way to take advantage of both highly charged and lowly charged ions using the same sample. This

presentation will focus on our most recent results in this area, and will present an expansive comparison

between charge reduction methods and their application to IM-MS of protein complexes.

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53: Development of Ion Mobility-Mass Spectrometry as a High-throughput Approach for Structural Genomics

Yueyang Zhong, Class of 2008, Ruotolo Lab Group

Individual proteins associate together to act as the molecular machinery of cells. One of the chief bottle-

necks in the acquisition of IM-MS data for protein complexes is the time-consuming identification of

optimal sample solution parameters that disrupt efficiently and provide all of the relevant information to

form a topology model for a multi-protein complex.

Here, we employ an extensive screen of solution conditions for protein complexes in order to derive a

set of best-practices and basic rules for selecting appropriate solution conditions for IM-MS analysis and

protein topology generation. Screens are performed as a series of two-dimensional surveys of solution

parameters (i.e., organic content and ionic strength) so as to be compatible with robotic sampling of a 96

-well plate.

Preliminary data for the avidin homotetramer indicates the combination of organic solvents and ionic

strength to be a rather efficient means in generating solution phase dissociation for this complex. In-

creasing both acetonitrile and DMSO percentage led to enhanced disruption of the tetramer. Ionic

strength seems to work as a “disruption pattern shifter”, which facilitates the conversion from dimer to

monomer. We generated a range models for the avidin tetramer based on the momomer, dimer and

tetramer CCS data obtained. Good agreement was achieved relative to the subunit-overlaps observed in

the crystal structure in some models. Concanavalin A and alcohol dehydrogenase were also tested, both

presented informative disruption. Ultimately, automated screens will be performed to identify optimized

conditions for targeted experimental objectives in a higher-throughput manner.

7: Substrate Activity Screening Methodology for the Discovery of Substrate-

Competitive Kinase Inhibitors

Meghan Breen, Class of 2008, Soellner Group

Meghan E. Breen, Sonali Kurup, and Matthew B. Soellner

The malfunction and/or overexpression of protein tyrosine kinases (PTKs) has been linked to over 400 human dis-

eases including cancer, diabetes, and autoimmune diseases. Although all currently approved therapeutics targeting

PTKs are ATP-competitive inhibitors, we believe that substrate-competitive inhibition of PTKs offers several im-

portant benefits over ATP-competitive inhibition. However, the discovery of substrate-competitive kinase inhibi-

tors using traditional high throughput screening methods has been relatively unsuccessful as it rarely yields hits

that bind outside of the ATP pocket. A recently reported method called substrate activity screening (SAS) utilizes

a fragment-based screening approach that tests for weak binding substrates of an enzyme. These substrates can

then be optimized to give compounds with high affinity for the target, and finally the reactive moiety is replaced

with a pharmacophore to give tight binding inhibitors. We have applied a SAS approach to the discovery of sub-

strate-competitive kinase inhibitors. A library of 50 aromatic alcohols was screened and 7-quinolinol was identi-

fied as a substrate for the PTK Src. Replacement of the reactive hydroxyl group with substituted phenyl pharma-

cophores identified via an inhibitor

peptide library has yielded low micro-

molar inhibitors with mixed inhibition

modes. Work to further optimize the

quinoline scaffold and phenyl pharma-

cophore for substrate-competitive, ATP

-noncompetitive inhibition is ongoing.

Chemical Biology Poster Abstracts

15

8: Development of Bifunctional Small Molecules that Target Metal-Amyloid-

Species

Joseph J. Braymer, Class of 2008, Lim Group

One of the most devastating diseases affecting millions of Americans today is Alzheimer‟s disease

(AD). In the metal-amyloid- (a) hypothesis of AD, various aggregation states of the a peptide asso-

ciated with metal ions (Fe, Cu and Zn) are implicated in the progression of the disease. Metal ions have

been shown to facilitate a aggregation and produce reactive oxygen species (ROS) that may lead to the

neurotoxicity observed in AD patient‟s brains. The roles of metal-associated a species though have

remained uncertain and controversial. In order to understand the functions of metal-a species, tradi-

tional metal chelators have been used to study the effect of metal on a aggregation events. Although

effective in vitro, metal chelation alone has not provided sufficient therapeutic value and understanding

into the disease. To improve this approach, a rational-structure-based design strategy has been taken to

develop new bifunctional small molecules that can target both the a peptide and metal ions. A series of

bifunctional stilbene derivatives

that can modulate metal-a aggre-

gation and neurotoxicity have

been developed. The potential of

our small molecules as chemical

probes for understanding metal-

abeta chemistry and biology in

AD will be discussed.

9: Building toward the substrate pocket: A potential route for achieving se-

lectivity in kinase inhibition.

Kristoffer Brandvold, Class of 2008, Soellner Group

Aberrant tyrosine kinase activity is associated with a variety of disease states, which has made regula-

tion of these enzymes medicinally relevant. All current FDA-approved kinase inhibitors act through

ATP-competition, and are often poorly selective due to interactions with highly conserved residues

within the nucleotide-binding domain. Conversely, identification of other interactions in the catalytic

domain outside of the ATP pocket (ie. substrate-peptide or phosphate-binding domains) may offer a

mode of selective inhibition. The study to be presented involves rationally adding elements onto ATP-

competitive inhibitors to extend

away from the ATP-binding domain

in order to discover interactions with

other regions of the enzyme. Design-

ing small-molecule inhibitors that

exploit the interactions discovered

through this study may provide a

means for selective regulation of ty-

rosine kinase activity.

16

10: Identification of Small Molecule Substrate-Competitive Kinase Inhibitors

Shana Santos, Class of 2008, Soellner Group

Shana M. Santos, Sonali Kurup, Meghan Breen, and Matthew B. Soellner

Protein tyrosine kinases (PTKs) have been implicated in diseases including cancer,

inflammation, and diabetes. Currently, the approved therapeutics targeting PTKs

are ATP-competitive inhibitors. Although these compounds are extremely potent,

the ATP pockets of protein kinases share a high sequence homology and therefore,

selectivity is difficult to achieve. PTKs are known to utilize short tyrosine contain-

ing peptides as substrates in vitro. We believe that substrate-competitive inhibition

of PTKs can offer advantages over ATP-competitive inhibition. However, peptidic

inhibitors are subject to poor bioavailability. Thus, we aim to develop small mole-

cule substrate-competitive PTK inhibitors. We found the peptide Ac-AIBiPhAA-

NH2 is an inhibitor for c-Src (Ki = 700 μM) and c-Abl (Ki = 200 μM). This pep-

tidic scaffold was subjected to a series of truncations, leading to a small molecule

inhibitor, upon which SAR studies are ongoing. Information gleaned from this

study will be applied to the development of optimal small molecule substrate-

competitive kinase inhibitors.

11: Investigating the catalytic mechanism of the yeast palmitoyltransferase

Akr1p

Xiaomu Guan, Class of 2006, Carol Fierke Group

Protein palmitoylation is a widespread posttranslational modification in which cysteine thiols on a sub-

strate protein are modified with a palmitoyl group. Defining the active site and catalytic mechanism of

palmitoyltransferases responsible for this modification represents a key step towards understanding its

biological significance. Akr1p, one of the first identified protein palmitoyltransferases, is an 86 kDa

yeast integral membrane protein. Mutagenesis studies of Akr1p suggest that a conserved DHYC cysteine

-rich domain (CRD) serves as a potential active site, potentially involving a two-step mechanism where

the palmitoyl group is transferred from palmitoyl-CoA to Akr1p, and finally from Akr1p to the substrate

protein. The covalent intermediate has been detected using radioactive assays. Further mutagenesis

study of all cysteine residues in Akr1p indicates that other cysteine residues may also be palmitoylated.

We are using mass spectrometry to confirm the covalent modifications of these cysteines and therefore

elucidate the

me c h a n i s m

of Akr1p.

17

12: Super-resolution fluorescence microscopy of nucleic acid nanostructures

Alexander Johnson-Buck, Class of 2007, Walter Group

“Spiders” are synthetic molecular walkers consisting of a streptavidin body and four biotinylated DNA

legs. By virtue of the endonucleolytic activity of their deoxyribozyme legs, these primitive molecular

robots can move in a programmed fashion by recognizing and cleaving chimeric oligonucleotide sub-

strates assembled on nanostructured landscapes. Although their programmable behavior has been ob-

served by atomic force microscopy (AFM) and single-particle fluorescence tracking [1], the dynamic

interactions between spiders and their immediate environment have not yet been resolved. Super-

resolution fluorescence imaging techniques such as stochastic optical reconstruction microscopy

(STORM) [2] combine the non-invasiveness and dynamic imaging capability of fluorescence micros-

copy with resolution approaching that of AFM, and may yield more detailed insight into how substrate

cleavage influences subsequent movement of spiders on their landscapes. Upon optimization of acquisi-

tion conditions, STORM experiments have yielded promising images of DNA origami landscapes, in-

cluding a track of spider substrate. Current efforts are directed at optimizing spider activity on fluores-

cently-labeled landscapes, followed by STORM imaging of individual spider-origami complexes to re-

solve their local interactions.

1. Lund, K., Manzo, A., Dabby, N., Michelotti, N., Johnson-Buck, A., Nangreave, J., Taylor, S.,

Pei, R., Stojanovic, M., Walter, N., Winfree, E., Yan, H. (2010) Molecular robots guided by prescriptive

landscapes. Nature 465: 206-210.

2. Zhuang, X. (2009) Nano-imaging with STORM. Nature Photonics 3(7): 365-367.

13: Using Fluorine Nuclear Magnetic Resonance To Probe the Interaction of

Membrane-Active Peptides with the Lipid Bilayer

Benjamin Buer, Class of 2007, Marsh Group

A variety of biologically active peptides exert their function through direct interactions with the lipid

membrane of the cell. These surface interactions are generally transient and highly dynamic, making

them hard to study. Here we have examined the feasibility of using solution phase 19F nuclear magnetic

resonance (NMR) to study peptide−membrane interactions. Using the antimicrobial peptide MSI-78 as a

model system, we demonstrate that peptide binding to either small unilamellar vesicles (SUVs) or bi-

celles can readily be detected by simple one-dimensional 19F NMR experiments with peptides labeled

with L-4,4,4-trifluoroethylglycine. The 19F chemical shift associated with the peptide−membrane com-

plex is sensitive both to the position of the trifluoromethyl reporter group (whether in the hydrophobic

face or positively charged face of the amphipathic peptide) and to the curvature of the lipid bilayer

(whether the peptide is bound to SUVs or bicelles). 19F spin echo experiments using the

Carr−Purcell−Meiboom−Gill pulse sequence were used to measure the transverse relaxation (T2) of the

nucleus and thereby examine the local mobility of the MSI-78 analogues bound to bicelles. These results

are in accord with structural models of MSI-78 bound to lipids and point to the feasibility of using fluo-

rine-labeled peptides to monitor peptide−membrane interactions in living cells.

18

14: Mechanistic Studies on Aldehyde Decarbonylase - Towards the Next Gen-

eration of Biofuels

Debasis Das, Class of 2008, Marsh Group

Long chain hydrocarbons are important components of plant‟s epicuticular waxes which protect leaves

and stems from dehydration. Fatty aldehydes are decarbonylated by aldehyde decarbonylase to produce

hydrocarbon and CO. This enzyme has not yet been characterized and its mechanism is not known. Our

primary aim is to over express this protein in E. coli and S. cerevisiae, purify and study its substrate

specificity and mechanism. Since aldehyde decarbonylase is an integral membrane protein, our current

approach involves expression of this protein with different fusion partners. A long term goal of this pro-

ject is to incorporate these enzymes in engineered pathways to develop a new generation of biofuels.

15: Simulated Protein-Ligand Docking and Free Energy Calculations of Am-

phipathic Small Molecules in KIX Domain of CREB Binding Protein

Jessica Gagnon, Class of 2009, Brooks Group

Transcriptional activators are essential for recruitment of transcription machinery, and transcrip-

tion regulation, leading to cellular responses like apoptosis, proliferation or inflammatory re-

sponse. Improper regulation of these activators can lead to many cancers and inflammatory diseases.

Development of potent and specific small molecules that could function as artificial transcriptional acti-

vators could lead to further understanding of the mechanism behind these processes as well as potential

therapeutic agents. A collaborative approach between the Brooks and Mapp labs at the University of

Michigan aims to further develop these artificial transcriptional activators. Small molecules with

improved potency were predicted using rational drug design and simulated protein­ligand dock-

ing, and current docking methodology was further validated.

19

54: Development of Multifunctional Small Molecules as Chemical Tools and

Potential Therapeutics for Alzheimer's Disease

Jung-Suk Choi, Postdoctoral Researcher, Lim Group

Alzheimer‟s disease (AD) is a severe neurodegenerative disease in which many genetic and environ-

mental factors are involved. The hallmarks of this disease are the accumulation of neurofibrillary tangles

and amyloid-β (Aβ) plaques. Aβ peptides, generated through sequential proteolytic cleavage of amyloid

precursor protein (APP), aggregate to form amyloid plaques in AD. Metal ions such as Cu(II) and Zn(II)

have been implicated as contributors to their formation and deposition. In addition, redox-active Cu(II)

is implicated in the generation of reactive oxygen species (ROS), leading to an increase in oxidative

stress, which is one proposed neuropathological pathway of AD. Herein, the design strategy, synthesis,

characterization, and reactivity of a new series of bifunctional compounds will be presented. We have

shown that our rationally designed small molecules are capable of modulating metal-induced Aβ aggre-

gation and neurotoxicity in vitro and in living cells, which demonstrates the potential development of

small molecules as chemical tools for understanding the role of metal ions associated with amyloid spe-

cies in biological systems.

55: Multiscale structural dynamics of the preQ1 riboswitch from single-

molecule fluorescence microscopy, NMR spectroscopy, and molecular dy-

namics simulations reveal ligand-dependent conformational docking

Krishna Chaitanya Suddala, Class of 2008, Walter Group

The preQ1 riboswitch regulates the expression of genes involved in the biosynthesis and transport of pre

-queuosine1 (preQ1, also 7-aminomethyl-7-deazaguanine), the precursor to queuosine, a modified nu-

cleobase essential for translational fidelity. It is the smallest known naturally occurring riboswitch, re-

quiring just 34 nucleotides for ligand recognition and has a very high affinity for its ligand preQ1 (Kd ~

50 nM). Ligand binding causes a conformational change in the aptamer domain leading to premature

transcription termination. The preQ1 riboswitch presents an interesting case of a very small RNA ap-

tamer displaying high affinity for its ligand and is a good model system for investigating the structural

dynamics of riboswitches due to its simple structure. Recent studies using X-ray crystallography and

solution-state NMR have shown that the aptamer forms a pseudoknot upon ligand binding. The mecha-

nism of this conformational 'switch', its kinetics, and the resulting refolding of the downstream expres-

sion platform remain poorly understood. We use a combination of single-molecule fluorescence reso-

nance energy transfer (FRET), solution-state NMR spectroscopy, and molecular dynamics (MD) simula-

tions to study the conformational dynamics and folding kinetics of the B. subtilis preQ1 riboswitch,

which are crucial for its function. We have investigated the docking kinetics of the adenine-rich tail into

stem-loop P1-L1, the main step towards transcription termination, in both the presence and absence of

the ligand. A picture emerges in which the riboswitch appears poised to rapidly switch conformation in

response to ligand recognition to be able to impact the downstream activity of RNA polymerase while

still in proximity.

20

56: Structural Studies of the Hepatitis Delta Virus (HDV) and Human HDV-

like Ribozymes

Kamali Sripathi, Class of 2008, Walter Group

Kamali Sripathi1, Caitlin Marlatt2, Pavel Banáš3,4, Jiří Šponer3,4, Michal Otyepka3,4, and Nils Walter5

Hepatitis delta virus (HDV) is the only known human pathogen to contain a catalytic RNA motif

(ribozyme) in its genome. Several other HDV-like ribozymes have been recently discovered in a variety

of organisms, the most notable of these being the human CPEB3 ribozyme. A thorough understanding of

the ribozymal cleavage mechanism and structure-function relationships would lay an ideal foundation

for development of therapeutic agents. However, the details of this reaction are not fully known. We are

using molecular dynamics simulations to study both the C75 mechanism in the HDV ribozyme, as well

as the link between global and local conformational changes in the HDV and CPEB3 ribozymes. We

have completed several unrestrained and restrained simulations to determine if the catalytic C75 of the

genomic HDV ribozyme acts as a general acid or a general base during the phosphotransesterification

reaction. Simulations have been conducted with restraints to constrain the C75(N3H+)-U-1(O5‟) hydro-

gen bond; however, the bond would not hold when these restraints were released. We have also been

conducting simulations using cis- and trans-acting HDV and CPEB3 ribozymes. Experimental results

show that trans-acting HDV ribozyme constructs have about a 30-fold slower catalytic rate than do cis-

acting constructs. We believe that our second set of simulations will elucidate how cleaving a bond to

generate the trans-acting construct results in the slower cleavage rate. Studying the local conformational

changes and hydrogen bonding patterns within the CPEB3 catalytic core may also provide further in-

sight into the HDV catalytic mechanism.

57: Catch & Release: Viral RNA Silencing Suppressor Competes with hDicer

& Impairs RISC Assembly by Reversibly Binding siRNA

Vishalakshi Krishnan, Class of 2007, Walter Group

RNA interference (RNAi) is a conserved gene regulatory mechanism employed by higher eukaryotes to

avert emergent viruses and retrotransposons. During viral infection, the RNase III-type endonuclease

Dicer cleaves viral double-stranded RNA into small interfering RNAs (siRNAs), 21-24 nucleotides in

length, and helps load them into the RNA-induced silencing complex (RISC) to guide cleavage of com-

plementary viral RNA. As a countermeasure, many viruses have evolved viral RNA silencing suppressor

(RSS) proteins that tightly, and presumably quantitatively, bind siRNAs to thwart RNAi-mediated deg-

radation. Here we report fluorescence quenching and electrophoretic mobility shift assays that probe

siRNA binding by the dimeric RSS p19 from Carnation Italian Ringspot Virus (CIRV), as well as by

Dicer and RISC assembly complexes. We find that the siRNA:p19 interaction is readily reversible, char--1s-1) and marked dissociation (koff = 0.062 ± 0.002 s-1).

We also observe that p19 efficiently competes with recombinant human Dicer and inhibits formation of

RISC-related assembly complexes found in human cell extract. Computational modeling based on these

results provides evidence for the formation of a ternary complex between siRNA, p19, and Dicer. An

expanded model of RNA silencing suppression predicts the surprising benefit that the observed multiple

turnover by p19 affords the virus in its fight against the RNAi response of the host cell. Our predictive

model is expected to be relevant for the development of p19 as a silencing suppressor in viral gene ther-

apy.

21

58: Structural modeling analysis guides mechanistic studies of D-arabinose 5-

phosphate isomerase

Mou-Chi Cheng, Postdoctoral Researcher, Woodard Group

D-arabinose 5-phosphate isomerase (API) enzymes catalyze the 1,2-keto/aldol interconversion between

D-ribulose 5-phosphate (Ru5P) and D-arabinose 5-phosphate (A5P). A5P is a unique intermediate in the

pathway providing 3-deoxy-D-manno-octulosonate (KDO). KDO, essential to the highly conserved in-

ner lipopolysaccharide (LPS) core of the outer membrane of most Gram-negative bacteria, connects the

O-antigen, a repetitive glycan polymer determining antigenic specificity, to the outer membrane im-

planted lipid A responsible for much of the toxicity. In E. coli three genes (yrbH, kpsF, gutQ) encode

APIs (KdsD, KpsF, GutQ) each having unique intracellular purposes. KdsD is the principal API provid-

ing A5P. Based on homology modeling analysis of the sugar isomerase (SIS) domain of KdsD,

mutagenesis studies show that conserved histidine 193 behaves not only as the general acid polarizing

the carbonyl group, but also maintains the orientation of the activated substrate which is deprotonated by

another conserved residue, glutamate 85, forming an enediol intermediate. Subsequently, glutamate 85

readily reprotonates the intermediate at the other end of the double bond and generates the product. A5P

presents primarily in the furanose form with less than 1% in the acyclic and hydrate forms which are

insufficient to directly provide linear substrate. Conserved residue lysine 59 is responsible for the

anomerase activity opening the furanose ring and supplying adequate linear A5P.

59: Monitoring pre-mRNA and Spliceosome Dynamics in Real-Time using

Single-Molecule Fluorescence Microscopy

Ramya Krishnan, Class of 2008, Walter Group

The spliceosome is a large ribonucleoprotein (RNP) complex that contains a total of 5 small nuclear

RNAs (snRNAs) and over 100 different proteins. Biochemical and genetic characterization has revealed

the dynamic nature of this complex machinery in terms of its conformational rearrangements and

changes in composition. Studied for over 30 years, the architectural complexity of the spliceosome is

often dominated by the myriad of protein-protein and protein-RNA interactions. By contrast, suitable

tools have been lacking to observe the dynamic conformational flexibility of the pre-mRNA substrate,

which the spliceosome exploits throughout the splicing reaction. Using single-molecule fluorescence

resonance energy transfer (smFRET), we have devised a unique approach to observe the real-time dy-

namics of the pre-mRNA during yeast spliceosome assembly and catalysis in vitro. Using fluorescent

labels on the exons and/or introns of the short yeast pre-mRNA Ubc4, we are able to measure the ATP-

and splicing-signal dependent conformational transition kinetics for individual pre-mRNA molecules. In

addition, we have developed strategies for fluorescently labeling the U2, U5 and U6 snRNAs and sev-

eral protein factors known to be at the catalytic core of the spliceosome. smFRET studies upon the de-

pletion and reintroduction of these snRNAs and splicing factors reveal pre-mRNA dynamics in relation

to specific steps of catalysis.

22

60: Engineering Metal Binding Sites in Designed Three-Helix Bundles using

„Bottom up Approach‟: Expression and Characterization of a Triple-Cys De-

rivative Capable of Binding Metals

Saumen Chakraborty, Class of 2006, Pecoraro Group

Metalloproteins catalyze some of the most important processes in nature. Designing novel metallopro-

teins is a challenging and complex task to the scientific community. Once succeeded, the de novo metal-

loproteins resulting from a „bottom-up‟ approach can provide significant insight into the structure and

function of the native metalloproteins which is often difficult to fathom owing to the complexity of the

natural proteins. So far we have directed our efforts towards designing metalloproteins capable of bind-

ing metals such as CdII, HgII and PbII within a three-stranded α-helical coiled coil framework. Herein we

describe design, expression and characterization of a de novo metalloprotein α3DIV, containing an anti-

parallel three-helix bundle motif. It is an energy minimized derivative of α3D where a metal-binding site

containing three cysteine residues was engineered at an open end of the bundle to allow easy access of

metals. α3DIV is ~97% folded at pH 8.0 and shows chemical shift dispersion in NOESY spectrum char-

acteristic of native proteins. It has a free energy of unfolding of 2.6 kcal mole-1 which is almost half than

the WT α3D. We have characterized α3DIV bound to metals CdII, HgII and PbII using various spectro-

scopic techniques and the properties are similar to what has been observed for the three-stranded coiled

coil constructs. Our successful design of this triple-Cys mutant now opens the door to designing metallo-

proteins containing asymmetric metal binding ligands at the first coordination sphere and introducing

secondary shell interactions such as hydrogen bonding which can potentially be useful for making func-

tional metalloproteins.

61: Cyclic Peptides as Tyrosine Kinase Inhibitors

Sameer Phadke, Class of 2009, Soellner Group

Non-receptor tyrosine kinases play a crucial role in cellular signal transduction by the phosphorylation

of certain tyrosine residues of intracellular proteins. The overexpression or dysregulation of tyrosine

kinases such as c-Src and c-Abl, have been implicated in tumorigenesis and cancer progression. Inhibi-

tion of these enzymes provides a promising therapeutic target against various cancers. Our study aims at

targeting the peptide substrate binding pocket of c-Src and c-Abl using cyclic peptides as inhibitors. In-

hibition of the peptide substrate binding pocket, as opposed to the highly conserved ATP binding pocket,

offers the potential for high specificity for Src or Abl over other tyrosine kinases. While linear peptides

and peptidomimetics have been used as inhibitors of the substrate binding pocket, they have at best

achieved micromolar potency and typically lack cell permeability. Our use of cyclic peptide analogs as

inhibitors offers an advantage over linear peptides in that they are conformationally constrained due to

lactamization thus allowing for a better fit within the substrate binding pocket due to a favorable en-

tropic bias for binding. These cyclic peptides can further be modified into highly potent and specific

small molecule inhibitors of tyrosine kinases.

23

62: Single molecule FRET applied to the hepatitis delta virus genomic ri-

bozyme

Wendy Tay, Class of 2009, Walter Group

Wendy Tay, Alex Johnson-Buck, Kamali Sripathi, Chamaree de Silva, Nils G. Walter

The hepatitis delta virus (HDV) ribozyme catalyzes a self-cleavage reaction that is important for the re-

production of HDV. HDV contains two related ribozymes, the genomic ribozyme and the antigenomic

ribozyme, that have similar global folds. Single molecule Förster resonance energy transfer (FRET)

studies have been used to probe the global structural dynamics of the genomic ribozyme. In doing this,

a variety of constructs have been made. Some of these constructs vary the position of the donor and ac-

ceptor fluorophores. Other constructs are used to compare the cis-acting and trans-acting ribozymes.

There are also constructs containing key mutations, such as at U-1. Previous biochemical studies have

shown that replacing U-1 with any other nucleotide significantly decreases the catalytic rate, possibly

due to disruption of a highly kinked structure that positions the scissile phosphate in the active site [1].

Thus, it is likely that there are differences in global structure and dynamics between these mutants. So

far, only a few constructs have shown a dynamic FRET behavior and there are not yet clear differences

in comparing the structure and dynamics for the various constructs. However, further studies on these

issues may lead to better understanding how fluorophore labeling schemes and mutations, among other

factors, can affect the structure and activity of the HDV ribozyme.

1. Sefcikova, J., Krasovska, M.V., Sponer, J., and Walter, N.G. (2007). The genomic HDV ribozyme util-

izes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis. Nucleic Acids Res. 35: 1933-

1946.

63: Metal Oxide Synthesis Toward Z-scheme Approaches to Water Splitting

Photocatalysis

Joseph Yourey, Class of 2009, Bartlett Group

Conversion of solar energy to chemical fuels such as hydrogen using semiconductor photoelectrolysis

has the potential to supply clean renewable energy as the global energy demand increases. Research has

focused on development of photoelectrodes for water splitting through a two photosystem Z-scheme like

process in which the redox half reactions of water splitting are physically separated. Higher quantum

yields are achievable by dividing the two half reactions because a wider range of visible light can be

utilized and, by employing a highly reversible redox couple, this process can be made catalytic at zero

applied bias.

Our research focuses on divalent metal tungstates synthesized from electrodeposition onto transparent

conducting substrates, which gives as a well-defined film thickness. In addition, we have prepared a

solid solution of Ti1-xMnxO (x = 0.05) synthesized by a sol-gel process. These photoanodes oxidize

water and use an Fe3+/2+ redox shuttle in conjunction with electrodeposited Cu2O as the photocathode.

We have characterized the photoelectrochemistry of our anodes and observe generated short-circuit cur-

rent (50 μA/cm2) at zero bias using potassium ferricyanide(II) as the sacrificial electron donor. The

photocathode, a stable electrodeposited Cu2O film, has generated short-circuit cathodic current (10 μA/

cm2) using potassium ferricyanide(III) as a sacrificial acceptor. The Z-scheme chemistry is followed by

monitoring oxygen production using a fluorescence probe as well as monitoring changes in Fe2+/3+ con-

centration by electronic absorption.

24

16: Advances in Development of Homogenous Catalysts for Oxidative Oli-

gomerization of Methane

Matthew Remy, Class of 2005, Sanford Group

A variety of palladium and platinum model systems have been studied for their stoichiometric activity in

ethane generation from methyl-substituted complexes. One electron oxidants efficiently promoted this

desired methyl coupling, and ligand optimization in these model systems has generated fundamentally

new and exciting chemistry at palladium and platinum.

17: Synthesis and characterization of tetrathiafulvalene complexes for charge

-transfer in photocatalysis

Emily Nelson, Class of 2009, Bartlett Group

Tetrathiafulvalene (TTF) is a non aromatic 14 π-electron molecule that can undergo two successive re-

versible oxidations, making it an excellent ligand to support charge transfer between redox centers. We

have prepared TTF-dithiolene ligands with various electron withdrawing and donating substituents (-

SEtS, -SMe, -H, and –Br) attached to molybdenum- and vanadium oxo centers. We have characterized

our compound using X-ray crystallography, cyclic voltammetry, UV-Vis absorption spectroscopy, IR

spectroscopy and spectroelectrochemistry. We find that as the substituent is varied, the metal-oxo stretch

shifts, suggesting the substituent has an effect on the electronics of the metal center. Next, we are syn-

thesizing a bis-Ru(II)bipyridyl complex analogous to the Creutz-Taube ion in order to study valence

localization/delocalization , and hope to use the knowledge from the above compounds for the develop-

ment of dimetallic complexes to deliver 2 photoinduced electron equivalents for hydrogen production

from water photolysis.

Inorganic Poster Abstracts

25

18: Cationic Pt and Pd Complexes for C-H Bond Functionalization

Marion H. Emmert, Postdoctoral Researcher, Sanford Group

The understanding of C-H activation reactivity that will allow the development of reagents capable of

selective transformations of C-H bonds into more functionalized molecules has been called the “Holy

Grail” of C-H activation research. The concept of cationic ligands for Pt and Pd to enhance the stability

and activity of these catalysts in C-H activation reactions will be presented. The application of these iso-

lable analogues of Periana‟s Catalytica system for the development of Pd catalyzed C-O bond forming

reactions will be discussed.

19: Solvent Dependent Formation of a Ln3+[12-Metallacrown-4]2 Sandwich

Compound and its Inclusion Complex with a Larger Metallacrown

Joseph Jankolovits, Class of 2007, Pecoraro Group

Joseph Jankolovits, Jeff W. Kampf, Vincent L. Pecoraro

Metallacrowns are high nuclearity inorganic analogues of crown ethers that draw interest for their mag-

netic and spectroscopic properties, structural diversity, and molecular recognition behavior. Two novel

Zn2+ metallacrowns are presented that encapsulate a central lanthanide (Ln3+) ion. The first compound

contains two bowl-shaped [12-MC-4] units sandwiching an 8-coordinate La3+. The second compound is

the inclusion complex of the aforementioned Ln3+[12-MC-4]2 bound in a [24-MC-8] central cavity. ESI-

MS reveals substantial complex stability, with no lanthanide exchange occurring at room temperature.

The self-assembly of the molecules is highly solvent dependent. The species can be selectively synthe-

sized through solvent choice and interconvert in opposing solvents. ESI-MS reveals solvent and lantha-

nide considerations also provide routes to novel, highly sought MC species such as Ln3+[15-MC-5] and

Ln3+[12-MC-4] complexes. Implications of these complexes for luminescence and molecular recognition

applications are considered.

26

20: Ferric Porphyrin Nitrosyls as Synthetic Models of Fungal P450 Nitric

Oxide Reductase (P450nor)

Lauren Goodrich, Class of 2007, Lehnert Group

Nitric oxide (NO), a mammalian signaling molecule, is responsible for nerve signal transduction, blood

pressure control, and immune response. Unfortunately, overproduction of NO in the blood stream due

to a bacterial infection can lead to septic shock and organ degradation, both of which can be fatal. Thus,

the need to develop a method by which to detoxify NO from biological systems is of critical importance.

Cytochrome P450nor, a NO reductase, represents one way to achieve this detoxification. P450nor plays

a vital role in the fungal denitrification of Fusarium oxysporum by catalyzing the reduction of NO to

N2O through a two electron reduction of the initially formed ferric heme nitrosyl by NADH. However,

little is known about the interaction of nitric oxide (NO) with ferric heme thiolates such as cytochrome

P450nor. In order to fully elucidate the mechanism of this enzyme, stable ferric heme nitrosyl model

complexes are necessary. Unfortunately these suffer greatly from the instability of the Fe-S bond, espe-

cially in the presence of NO, and in their ability to perform two electron reductions. To this end, a series

of ferric heme nitrosyl complexes have been synthesized employing various porphyrin macrocycles and

thiolate ligands. This has allowed us to determine the key characteristics required to form these highly

unstable ferric nitrosyls. In conjunction with density functional theory calculations, we have now been

able to gain detailed insight into the

electronic structures and spectro-

scopic properties of these species as

a function of the axial ligand donor

strength.

21: Functional Urease Biomimics Incorporating Secondary Coordination-

Sphere Interactions

Cameron Moore, Class of 2010, Szymczak Group

The demand for energy-efficient chemical transformations has become vital due to increasing world population

and industrialization. Ammonia, which is required to produce the nitrogen-based fertilizer used to sustain the

planet, is traditionally formed by means of the Haber-Bosch process. This process accounts for 1-2% of the world-

wide energy consumption annually. Fixed nitrogen, in the form of ammonia, is converted to essential amino acids

by plants and are eventually consumed and excreted by humans and livestock in the form of urea. The disposal of

urea into waste systems gives rise to a unique chemical recycling opportunity to potentially reclaim fixed nitrogen.

The metalloenzyme urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide with an impressive rate

enhancement over the spontaneous elimination reaction.

While the mechanism of this transformation is still somewhat

debated, it is widely accepted that the secondary coordination

sphere around the dinuclear nickel active site of the enzyme

plays a vital role in catalytic activity. As such, we are inter-

ested in secondary coordination sphere interactions, namely

hydrogen-bond accepting groups, within hydrolysis catalysts

for the ultimate goal of catalyzing the hydrolysis of urea to

ammonia and carbon dioxide. Specifically, we aim to develop

mono- and bimetallic classes of hydrolysis catalysts that

mimic the hydrogen-bond framework required to activate urea

toward hydrolysis. Such a conversion represents an energy-

efficient chemical recycling strategy of fixed nitrogen to pos-

sibly alleviate the demand for the energy-intensive Haber-

Bosch process.

27

22: Determining the Solution Structure of Apo- and Metallated-α3DIV Pep-

tides

Jefferson Plegaria, Class of 2009, Pecoraro Group

De novo protein design is widely used for understanding protein structure and function. By mimicking the thiol-

rich metal binding sites of proteins found in bacteria, capable of detoxifying heavy metals, we have developed pep-

tides with three cysteine residues that bind to heavy metals such as lead, mercury, and cadmium. We are now fo-

cused on incorporating metals capable of catalysis or redox reactions, which require an asymmetric (different

amino acids) binding site. Our current model utilizes the TRI family peptide to form three-stranded-parallel coiled

coils. Although this has provided further insight into heavy metal coordination, due to its symmetric metal binding

site, it fails to mimic complex asymmetric metal-binding systems commonly found in nature. To overcome the

limitations of the coiled-coil peptides, we have adapted the α3D model developed by DeGrado et al. α3D is a sin-

gle polypeptide chain, containing 73 amino acids, that

folds into a three-stranded bundle. Our construct, α3DIV

(L18CL28CL67C), contains three cysteine residues and,

from spectroscopic studies, coordinates with Hg2+ and

Cd3+. Furthermore, NMR data demonstrates different

binding modes, which are pH dependent, of mercury

bound to α3DIV. Establishing the solution structure of

apo- and metallated-α3DIV will allow us to design and

incorporate asymmetry, leading to α3D constructs with

catalytic or redox functions in the metal binding site.

Thus far we have started the solution structure determi-

nation by obtaining COSY, TOSCSY and NOESY spec-

tra of apo-α3DIV and Hg2+-α3DIV at pH 5.8.

23: Sp3 versus sp2 Carbon-X Bond Formation from High Oxidation State

Palladium

Joy Racowski, Class of 2006, Sanford Group

Carbon-heteroatom bond-forming reductive elimination from transient PdIV intermediates has been pro-

posed as the product-release step of a variety of important Pd-catalyzed transformations. Over the past

25 years, a variety of PdIV model complexes have been synthesized in order to study reductive elimina-

tion reactions at PdIV centers. For the first time, a system has been developed to explore sp3 versus sp2

C-X bond formation from isolated PdIV complexes. To begin this series of inquiry, a PdII species was

synthesized with a cyclometaled sp3-sp2 ligand and t-butyl bipyridine. This complex was then subjected

to oxidation by PhI(Cl)2, PhI(O2CX)2 or 1-fluoro-2,4,6-trimethylpyrdinum triflate. The reactivity of

these complexes was studied in detail along with the reactivity of various cationic PdIV species in the

presence of external nucleophiles. In these studies, it was discovered that C-X bond formation occurred

from the external X- source. Additionally, from this study the only example of sp3 C-F reductive elimi-

nation from PdIV emerged.

28

24: A Mixed 3d-4f 14-Metallacrown-5 Complex that Displays Slow Magnetic

Relaxation through Geometric Control of Magnetoanisotropy

Thaddeus T. Boron, III, Class of 2007, Pecoraro Group

Single-molecule magnets promise to deliver large amounts of storage capacity in small spaces, serve as quantum

computers, and act as magnetic refrigerants. The properties of single-molecule magnets depend on both the spin

and magnetoanisotropy of the molecule. Many published single-molecule magnets have extremely large spin val-

ues but suffer from extremely low effective energy barriers due to low amounts of magnetoanisotropy. To solve

this problem, we have attempted to increase the magnetoanisotropy through geometrically controlled metalla-

crowns. We describe the synthesis and magnetic properties of a unique mixed 3d-4f 14-metallacrown-5 complex.

This is the first metallacrown family to feature μ-O and μ-OH bridges as well as to incorporate a Ln(III) into the

ring. By systematically substituting the lanthanides in the metallacrown, we can probe if the magnetic properties

are due to the ring Mn(III) ions alone or both the Ln(III) and Mn(III) ions. We can also observe how the choice of

Ln(III) affects magnetoanisotropy and total spin, and ultimately the molecule‟s magnetic properties. AC SQUID

magnetometry of the Tb, Dy, and Ho derivatives reveal slow-magnetic relaxation, a hallmark property of single-

molecule magnets. For the Dy structure, an

effective energy barrier Ueff of 16.7 K and a

relaxation time of 4.9 x 10-8 s was calcu-

lated. This is the second highest energy bar-

rier reported for a mixed Mn/Ln single-

molecule magnet. Due to the relatively small

total spin, this behavior most likely results

from a large magnetoanisotropy, which is

controlled through geometric constraints.

25: Discriminating Between the Formation of Mn2IV(2-OHsalpn)2(OH)+ and

MnIVMnV=O(2-OHsalpn)2+ to Understand High Valent Intermediates in Pho-

tosynthetic Water Oxidation

Fangting Yu, Class of 2009, Pecoraro Group

We are interested in clarifying the mechanism of photosynthetic water oxidation. Binuclear manganese complexes

containing polydentate Schiff-base ligands have been used to model the structure and reactivity of the manganese

cluster in photosystem II. We proposed that the evolution of oxygen involves a MnV=O species being attacked by a

nucleophilic hydroxide bound to CaII. Unfortunately, there are no multinuclear model compounds to test this hy-

pothesis as all structurally characterized MnV=O species are mononuclear. The Mn2(2-OHsalpn)2 system poten-

tially provides access to binuclear MnV=O complexes. Previous work in our group suggested that the oxidation of

MnIIIMnIV(2-OHsalpn)2+ produces Mn2IV(2-OHsalpn)2(OH)+ in-

stead of the desired MnIVMnV=O(2-OHsalpn)2+. However, it is

possible that the MnIVMnV=O species was initially generated, but

then rapidly converted to Mn2IV complex. I will present the use of

2-methyl-1-phenyl-prop-2-yl hydroperoxide (MPPH) to probe the

mechanism of Mn-catalyzed oxygen-oxygen bond cleavage. If

the O-O bond undergoes heterolytic cleavage, yielding the

MnIVMnV=O, only 2-methyl-1-phenyl-prop-2-yl alcohol will be

produced; if homolytic cleavage occurs to form Mn2IVOH, a radi-

cal species will be generated that undergoes rapid β-scission pro-

ducing a series of small molecules(e.g. benzaldehyde, toluene,

etc.). GC-MS evidence indicates that O-O bond undergoes homo-

lytic cleavage, producing Mn2IV(2-OHsalpn)2(OH)+, which is

consistent with the previously reported result.

29

26: De novo Design of a Metalloenzyme; a Structural and a Catalytic Site

within a Three-Stranded Coiled Coil

Melissa Zastrow, Class of 2008, Pecoraro Group

Melissa L. Zastrow, Anna F. A. Peacock, Jeanne A. Stuckey*, and Vincent L. Pecoraro

Over one third of all proteins require a metal for their structure or function. De novo protein design is an

effective approach for understanding and mimicking metal coordination environments in biological sys-

tems. Our approach has been to assess whether a single peptide aggregate could be stabilized using one

metal binding site and have its catalytic function at a separate site. We chose to exploit the groups previ-

ous work on heavy metal binding to thiolate rich sites to achieve the structural center. Highly stable con-

structs can be obtained using the high affinity metal-sulfur bonds formed. To achieve a catalytic center,

we incorporated single histidine binding sites into our standard TRI peptide series (Ac-G(LKALEEK)4G

-NH2) to model metal environments such as the ZnN3O center in carbonic anhydrase. The crystal struc-

ture of CoilSerL9PenL23H satisfies our objective with Hg(II) in a stabilizing sulfur site (HgS3) and Zn

(II) in an N3O-type site. Competition assays have yielded apparent Zn(II) binding constants in the low

micromolar range to His3 sites in our peptides. Assessment of initial rates and apparent Zn(II) binding

constants for peptides lacking the structural site indi-

cate that Hg(II) confers stability to the designed pro-

tein. Further, saturation kinetic studies using p-

nitrophenyl acetate as a substrate for HgSZnN

(TRIL9CL23H)3 have yielded kcat up to 2.4 min-1 for

hydrolysis at pH 9.5, making this the most efficient

model system for ZnN3O hydrolases.

64: Investigation into the Photolabilization of Ruthenium Nitrosyl Complexes

Anna Merkle, Class of 2006, Lehnert Group

Nitric oxide (NO), a highly reactive diatomic radical, can readily oxidize and nitrosylate DNA to cause

cell death. Delivery of NO to DNA in order to activate programmed cell death is an active field of re-

search. One potential method of delivering NO to cancer cells is the photolabilization of the Ru-NO

bond in water soluble ruthenium nitrosyl complexes. In order to investigate the photolabilization of NO

in aqueous medium, a series of ruthenium nitrosyl complexes have been explored. Two multidentate

ligands, ethylenediaminetetraacetic acid and tris[(2-pyridyl)methyl]amine, were used to compare their

photolability. Interestingly, utilizing a variety of synthetic routes to obtain the desired ruthenium nitro-

syl complexes produced different binding modes of these ligands to the ruthenium center, which caused

unexpected changes in the solubility and photolability of the ruthenium nitrosyls. Direct comparison of

a range of ligand binding modes will allow for a better understanding of the co-ligand properties re-

quired to obtain a water soluble, photolabile ruthenium nitrosyl complex with high quantum yields suit-

able for use in cancer treatment. Here, studies concerning the synthesis and photolability of both water

soluble and water insoluble ligands will be presented.

30

65: Catalyst Controlled Selectivity for C-H Arylation

Amanda Hickman, Class of 2007, Sanford Group

Aryl-aryl bonds are ubiquitous in organic molecules. While these linkages are most commonly formed

by cross-coupling between two prefunctionalized arenes, there has been tremendous recent progress in

the development of transition-metal catalyzed C–H arylation reactions. A major challenge for these reac-

tions is to achieve site selective C–H functionalization of the arene/heteroarene starting material. Com-

mon strategies to address this challenge include: substrates that possess a directing group, substrates

containing a tethered (intramolecular) coupling partner, and substrates (for example, indoles, pyrroles,

thiophenes) that contain highly activated C–H sites. However, all of these strategies rely on substrate

control, which inherently restricts the scope of the reactions. In this work, we report the development of

modular, diimine-based Pd catalysts for the direct arylation of naphthalene. By tuning the steric and

electronic parameters for the diimine ligand, we have identified catalysts that provide outstanding (>50 :

1) selectivity for arylation at the 1-position of naphthalene. Preliminary mechanistic studies implicate an

unusual mechanism in which naphthalene metalation occurs at a high oxidation state Pd center.

66: Oxidative Interception of Heck Intermediates

Andrew Satterfield, Postdoctoral Researcher, Sanford Group

This poster describes the development of palladium-catalyzed reactions to accomplish 1,1 and 1,2 di-

functionalization of α-olefins through the interception of Heck intermediates. The 1,1 and 1,2 arylhalo-

genation (halogen = Cl or Br) of alkenes was achieved with good yields and selectivities that could be

controlled by changing reaction conditions and/or the halogenating reagent. The use of hypervalent io-

dine reagents resulted in the 1,1 arylacetoxylation of alkenes in good yields with excellent selectivities.

In addition, conditions were found to promote an intramolecular reaction that formed heterocyclic prod-

ucts.

31

67: Synthesis and Electrochemistry of Mixed Metal Oxide Spinel Phases for

Lithium-ion Battery Cathodes

Brendan Clifford, Class of 2009, Bartlett Group

Lithium ion secondary batteries have gained much attention due mainly to higher possible energy densi-

ties than the NiMH and lead acid batteries. Among the various positive electrode materials investigated

for Li-ion batteries, spinel LiMn2O4, is one of the most important cathode materials. LiMn2O4 has be-

come an attractive material due to its low cost, low toxicity, low internal resistance, and high theoretical

capacity of 293 mAh∙g-1. Lithium can be electrochemically extracted at ~4 V to yield Li1-xMn2O4, or

inserted at ~3 V producing Li1-xMn2O4. However, severe capacity fade occurs in the 3 V region due to a

cubic to tetragonal phase transition attributed by Jahn-Teller distortion of Mn3+ at the end of discharge.

This issue can be suppressed by replacing Mn with other transition metal elements such as cobalt. Our

group has developed a hydrothermal synthesis to prepare LiCoxMn2-xO4 (x = 0.05 – 0.20). Commercially

available CoCl2∙6H2O and KMnO4 were dissolved in aqueous solutions of lithium hydroxide. Acetone

was utilized as the organic reducing agent for KMnO4. The cubic spinel phase can be isolated after short

reaction times (~5 h) at low temperatures of 180 oC. Samples prepared hydrothermally possess the cu-

bic spinel structure with particle sizes < 100 nm, as evidenced from XRD and SEM. Cyclic voltam-

metry shows a reversible redox process with E1/2 of ~2.9 V. Galvanostatic cycling of a cell composed of

LiCo0.20Mn1.80O4 between 3.45 and 2.0 V demonstrates an initial discharge capacity of 80 mAh∙g-1 with

only ~11% capacity fade after 15 cycles.

68: Naturally Occurring Small Molecule Modulators of Metal-Mediated Aβ

Pathways

Alaina S. DeToma, Class of 2009, Lim Group

Alzheimer‟s disease (AD) is rapidly becoming one of the most serious health conditions among the eld-

erly due to the loss of cognitive functions associated with neuronal cell death. The amyloid-β (Aβ) pep-

tides, which can aggregate from monomers into higher order structures such as fibrils, have been cited as

an underlying cause into the progression of the disease. The peptides are also known to bind to metal

ions such as Fe, Cu and Zn. The redox cycling of Fe and Cu bound to Aβ may cause oxidative stress

leading to neurodegeneration. The role of metal ions in AD pathogenesis is still controversial, thus small

molecules that can directly target the metal ions surrounded by Aβ are desired as potentially useful as

chemical tools for studying metal-Aβ species. Naturally occurring polyphenolic compounds, such as

flavonoids, are attractive candidates for this goal due to their known anti-amyloidogenic and metal che-

lation properties; however, the effect of these compounds on metal-Aβ species has not been investigated.

The flavonol myricetin is capable of modulating Cu(II)- and Zn(II)-induced Aβ aggregation pathways

and neurotoxicity in vitro, which suggests the importance of this structural framework for reactivity.

Thus, further development of bifunctional small molecules based on the flavonol structure may be a

promising approach to understand metal-Aβ species and their role in AD.

32

69: Elucidating the rold of the hydrogen bonding network in ferric cyto-

chrome P450cam and corresponding mutants using magnetic circular dichro-

ism spectroscopy

Grace Galinato, Postdoctoral Researcher, Lehnert Group

Cytochrome P450 nitric oxide reductase catalyzes the reduction of NO to N2O. This enzyme is part of a

huge family of Cyt P450 enzymes that contain heme b ligated to a trans cysteine, stabilized by a H-

bonding network composed of L358, G359 and Q360 (in Cyt P450cam), known as the “cys pocket” that

influences NO and O2 activation. To investigate the Fe-S(Cys) interaction in resting ferric Cyt P450, low

temperature magnetic circular dichroism spectroscopy was performed on wild-type Cyt P450cam, mu-

tants Q360P (pure ferric high-spin), L358P, where the cys pocket has been altered by substituting amino

acids involved in the hydrogen bonding network to a non-hydrogen bonding amino acid; and Y96W, a

mutant that is pure ferric low-spin. Analysis of the electronic spectra of Q360P and Y96W therefore

proves critical in deconvoluting the MCD spectrum of WT P450cam. Gaussian deconvolution on the

MCD spectrum of Q360P reveals fourteen electronic transitions between 15200-31050 cm-1. The polari-

zations (in-plane or out-of-plane), oscillator strengths, and TD-DFT calculations were used to assigned

the electronic transitions. A broad, prominent band at 28570 cm-1 shows overlaying saturation isotherms

with ~40% out-of-plane (z) polarization. This is assigned to a S to Fe CT transition. For wt, Q360P and

L358P, this band occurs at 28724, 28570, and 28620 cm-1. The small shift of this feature indicates that

the role of the „cys‟ pocket is for stabilization of the thiolate against external reactants (NO, O2), and

proper positioning of cysteine for coordination to the iron center.

70: Binding of an Iron Sulfur Cubane Cluster to a Metalloporphyrin via

Functionalized Ligands

Deidra Gerlach, Class of 2007, Lehnert/Coucouvanis Groups

One route to synthesizing functional model complexes for the active site of sulfite and nitrite reductase,

functionalized iron sulfur cubane clusters have been attained. In contrast, a multitude of [Fe4S4(SR)4]2-

cubane clusters have been presented in the literature focusing on mimicking naturally occurring ferre-

doxins and investigating the electronic properties of the cluster when varying the bound ligands. Here,

the focus is to obtain cubane clusters featuring ligands that bind to a second metal system to form a

bridge between the two redox active metal moieties. Thus, para-thiopyridines have been utilized where

the thiol is bound to the iron sulfur cubane leaving the pyridine lone pair to coordinate to zinc or iron

macrocycles. Evidence of binding between the ligated cluster and metalloporphyrins is found in shifts to

lower energy of the Soret band in the absorption spectrum and shifts to lower ppm in 1H-NMR. Prelimi-

nary results featuring evidence of electronic coupling as observed using cyclovoltammetry are in pro-

gress. Previous difficulties of binding tetra-ligated clusters to metallated macrocylces has led to the re-

cent use of site-differentiated cubane clusters which give stability to the clusters and reduce the probabil-

ity of the formation of extended lattices. Initial use of these site-differentiated cubane clusters demon-

strate binding occurring analogous to previous binding investigations with the tetra-ligated cubane clus-

ters. These are the preliminary synthetic steps towards biologically inspired complexes capable of multi-

ple electron reductions exhibited by the inspirational enzymes.

33

71: Novel Rh/Ir complexes for C-H activation

Brannon Gary, Class of 2006, Sanford Group

Developing catalysts for efficient and mild conversion of C–H bonds into directly functionalized prod-

ucts containing C–Cl, C–Br, C–O, and C–N bonds has the potential to dramatically increase the effi-

ciency of many chemical and industrial processes. Previous chemistry in this field based upon Pd(II) and

Pt(II), has suffered from the use of toxic and harsh/expensive oxidants along with difficulty in the funda-

mental C–H activation step. Using a set of standard catalytic conditions for H/D exchange, multiple

ligand scaffolds have been investigated with Rh/Ir complexes for activity in the fundamental C–H acti-

vation step. New catalysts have been developed for H/D exchange which show comparable and even

enhanced reactivity to other Group 9 based systems in the literature. Reactivity and selectivity data will

be presented to highlight and contrast these newly developed systems.

72: A thermodynamic study of Pb(II) binding to de novo designed peptides:

Implications for Understanding the Molecular Basis of Lead Toxicity

Kosh P. Neupane, Postdoctoral Researcher, Pecoraro Group

Lead is a ubiqutious environmental pollutant but the exact mechanism of lead toxicity is poorly under-

stood. The peptide models we have utilized here provide a close architectural match with the active site

of aminolevulinic acid dehydratase (ALAD), an enzyme required in the second step of heme biosynthe-

sis. ALAD contains Zn2+ coordinated with three cysteine thiolates and one exogeneous water molecule

in a pseudo-tetrahedral coordination geometry. Poisoned with lead, Zn2+ is removed from the ALAD

active site and substituted by Pb2+ in a trigonal pyramidal geometry. Previous spectroscopic studies from

our lab showed that Pb2+ binding to designed peptides in a PbS3 environment was very similar to the Pb-

poisoned ALAD active site. Now we have utilized Pb-207 NMR spectroscopy to detect the coordination

environment of Pb2+ in the peptide models. In addition to detecting Pb2+ in this environment, we were

able to show the selectivity of Pb2+ in a peptide that has two binding sites with similar first coordination

spheres but a different second sphere coordination environment. This result provides experimental con-

firmation of the importance of the lone pair for the selectivity of Pb2+ for sulfur sites in proteins such as

ALAD and the metalloregulatory protein PbrR691. We hope that 207Pb NMR may now be useful to iden-

tify and characterize proteins associated with Pb toxicity.

34

73: Various Germylenes and Stannylenes Utilized for C-H Activation

Ahleah Rohr, Class of 2006, Wolfe/Banaszak Holl Groups

Previous work in the Banaszak Holl lab has shown the utility of main group metals in C-H activation

reactions, more specifically silylenes, germylenes, and stannylenes. Germylenes for C-H activation con-

tinues to be of great interest because of their substantially lower toxicity as compared to tin analogues

and their superior functional group tolerance as compared to silicon analogues. We have been exploring

the utility of Cp^GeR (Cp^ = functionalized Cp) systems for C-H activation since both the Cp^ and R

groups can be conveniently varied in terms of steric and electronic effects. Initial studies include C-H

activation of different ethers, alkanes and amines with Cp*GeCH(TMS)2, a stable germylene previously

synthesized by Jutzi et al. The latest C-H activations demonstrating regioselection with stannylene will

also be presented.

74: Optical Properties of Visible Light Harvesting Transition Metal Oxide

Thin Films

Tanya Breault, Class of 2008, Bartlett Group

The requirements of photocatalytic water splitting include the absorption of photons to form electron-

hole pairs, charge separation and migration to surface reaction sites, and construction of surface reaction

sites for hydrogen and oxygen evolution. Following the discovery of photoinduced splitting of water on

titanium dioxide electrodes forty years ago; extensive research has led to the breakthroughs of many

semiconductor materials that can be used for solar energy to chemical fuel conversion, although no ma-

terials meet the needed efficiencies, costs, and stabilities for a realistic, deployable system. We have

primarily focused on synthesizing complex transition metal oxide thin films via the sol-gel process for

use as photoanodes. We have prepared 500 nm thick SrTi1-xMnxO3 (x = 0.1, 0.2, 0.3) films and observe

maximum absorbance at λ = 350 nm. These doped films also exhibit an additional absorption band at

650 nm. For SrTi0.8Mn0.2O3, linear sweep voltammetry shows an onset potential at about 1.2 V vs RHE

at pH 13 using a 150W Xe lamp filtered by an AM1.5 filter. Furthermore, 50 μA of photocurrent is ob-

served at 1.4 V vs RHE. As we aim to improve the optical properties of our films, targeting the optimal

film thickness for maximum photon absorption and minimum bulk recombination is an important aspect

to investigate for photocatalytic materials.

35

27: Evidence for Ligand-Dependent Mechanistic Changes in Nickel-

Catalyzed Chain-Growth Polymerizations

Erica Lanni, Class of 2006, McNeil Group

Conjugated polymers comprise many of the materials utilized in exciting applications such as photovoltaics and

chemical sensors. Recent work suggests that some conjugated polymers can be synthesized in a chain-growth fash-

ion using a Ni-catalyzed Kumada cross-coupling. To guide strategies for improving the synthetic method, our

group aims to elucidate the polymerization mechanism by performing rate and structural studies on the reaction

and its organometallic intermediates. We have found that the rate-determining step of the polymerization is de-

pendent on the nature of the phosphine ligand, but independent of monomer structure. Moreover, when transmetal-

lation is rate-determining, the addition of LiCl is found to influence the reactivity of the monomer. Structural and

reactivity studies on complexes modeling the hypothesized Ni π-aryl and oxidative addition intermediates were

also performed. This work pro-

vides a foundation for future

investigations on the mechanis-

tic influences of additional

monomers, catalysts, and addi-

tives. Due to the strong influ-

ence of the phosphine, our work

also suggests that the method

maybe improved through ra-

tional ligand design.

28: Comparing Molecular Gelators and Nongelators Based on Solubilities

and Solid-State Interactions

Jing Chen, Class of 2007, McNeil Group

Molecular gels have shown a myriad of applications in chemical sensing, bio-responsive materials, re-

generative medicine and environment remediation. Due to the fact that gelation ability is highly sensitive

to subtle structural modifications, designing gelators for each individual application still remains a major

challenge. Therefore, a thorough understanding of the relationship between structure and gelation ability

is necessary to advance this field. Herein, we present a systematic study of structure-property relation-

ships for 19 pyridine-derivatives (8 gelators and 11 non-gelators) via spectroscopic, microscopic and

crystallographic techniques. We concluded that gelators and non-gelators were not distinguishable by

room temperature solubility, and that the presence (or absence) of one-dimensional intermolecular inter-

actions did not correlate with gelation ability. Excitingly, we discovered that the majority of gelators had

higher dissolution enthalpies and entropies than the majority of non-gelators, indicating stronger inter-

molecular interactions and more order in gelators. Finally, a moderate correlation between gelator struc-

ture and gel properties

was revealed. Overall,

these data present a

complex structure-

property relationship

in gelation.

Material Poster Abstracts

36

29: The Effect of Non-enzymatic Glycation to Bone Collagen Nanomorphol-

ogy

Ming Fang, Class of 2008, Banaszak Holl Group

Type I Collagen is the most common protein in mammals; it provides structural scaffolding and me-

chanical ductility to a variety of tissues including bone, tendon, skin, and artery wall. In these native tis-

sues, collagens cross-link and self assemble to form fibrils with a characteristic D-periodic gap/overlap

spacing pattern. While normal cross-links contributed by lysyl oxidase can provide tissues optimal me-

chanical stability and toughness, another type of cross-linking - called non-enzymatic glycation (NEG) -

occurs between collagen and glucose in vivo to form so called advanced glycation end-product (AGE)

with devastating effect to the tissues. AGE accumulates rapidly with aging and diabetic mellitus, and

studies have shown that AGE causes increase in stiffness and brittleness in bone tissues in diabetic pa-

tients. In this study we hypothesize that NEG reinforces collagen crosslinks and changes D-spacings.

Ovine cortical bone samples were incubated in buffered solution with D-ribose to introduce cross-links

and subsequently imaged with

atomic force microscopy. Control

experiments were done in the same

condition without D-ribose. Colla-

gen D-spacings were analyzed and

compared between control and

NEG group, the effect of NEG to

collagen nanomorphology has

shown interesting results.

30: Structure-Property Relationships among Aryl Trihydroxyborate Gelators

Cheryl Moy, Class of 2007, McNeil Group

Aryl boronic acids are important reagents in Suzuki-Miyaura cross-coupling reactions. Although a base

is needed to form the reactive species, an alternative reagent - aryl trihydroxyborates - eliminates the

need for a base. These salts are proposed to be the reactive intermediates in the transmetallation step of

SM reactions. In studying these salts to develop aqueous-free reaction conditions we found that they gel

aromatic solvents. This poster will highlight the unique structure-property relationships observed among

these aryl trihydroxyborate salts. For example, the critical gel concentration (cgc) shows an unusual de-

pendence on side-chain length; this trend has yet to be seen in any other class of gelators. In addition, the

previously unknown sensitivity of these reagents to heat and light will be reported.

37

31: The Design and Modification of Cryoloops for Protein Crystallization

and Capture

Ross Putman, Class of 2009, Matzger Group

Protein single crystal growth and harvesting remains one of the most difficult tasks in structural biology.

Fewer than 5% of all total cloned proteins have been crystallized and have ultimately produced solvable

single crystal X-ray diffraction data sets. First introduced in 1990, thin loops used to mount crystals pro-

vide a new way to harvest protein crystals that leads to increased diffraction quality and decreased mo-

saicity. By eliminating the need to actively capture protein crystals from mother liquor, it may be possi-

ble to improve the success rate of crystal collection. Utilizing polymer induced heteronuclation (PIHn)

in the media of cryoloops, we have grown single crystals suitable for diffraction directly on the

cryoloops themselves. PIHn has proven successful in increasing crystal size and quality as well as to

identify different phases of proteins and small molecules. Well-known proteins such as lysozyme, con-

canavalin A, and bovine liver catalse have been chosen as model systems.

32: Two-photon absorbing GFP-type chromophores: Synthetic design and

spectroscopic characterization

Travis Clark, Class of 2007, Goodson Group

Efforts have been made toward the design and synthesis of two-photon active green fluorescent protein-

type chromophores having absorption and fluorescence maxima in the visible (400-600 nm) region with

strong two-photon absorption in the 600-900 nm region. Preliminary synthetic investigations directed

toward a modified version of a ZsYellow chromophore have resulted in a generalized approach for chro-

mophore synthesis, allowing for flexibility in the incorporation of functional groups such as donor-

acceptor substituents and for additional groups to provide extended conjugation. Steady-state spectros-

copy, fluorescence quantum yields, excited-state dynamics, and the two-photon absorption cross-

sections of the synthesized chromophores have been extensively investigated. These molecules show

promise as biological markers for application in the study of conformation changes and aggregation of

amyloid peptides, known to play an important role in many neurodegenerative diseases.

38

33: Enhancing molecular gelation using functionalized polymers

Yash J. Adhia, Class of 2008, Anne J. McNeil Group

Molecules that form gels are promising candidates for applications such as tissue regeneration, cleaning

oil-spills and chemical sensing. However, the sensitivity of such stimuli-responsive gelation depends on

the minimum concentration of the molecules required to form a gel (cgc). This poster will highlight our

recent efforts towards enhancing the gelation ability of a class of molecular gelators using polymer-

based additives. Our results indicate 1 forms gels with altered microstructures exhibiting a significantly

lower cgc in the presence of certain functionalized polymers. Herein we present our studies to under-

stand the interaction between different polymeric additives with 1 and other related molecular gelators at

the macroscopic (cgc, rheology),

microscopic (hot-stage optical mi-

croscopy) and molecular level (X-

ray diffraction). These studies will

help us to understand the role of

the gelator and the polymer struc-

ture in modulating molecular gela-

tion, and in focusing the efforts for

selecting an appropriate additive to

facilitate molecular gelation at

lower concentrations.

34: Synthesis and Characterization of Microporous Coordination Polymers

for Carbon Dioxide Capture

Austin Kizzie, Class of 2007, Matzger Group

Amine-scrubbing is a well-established process for capturing carbon dioxide from flue gas, but is also

energy intensive and costly. An adsorption-based process that relies on microporous coordination poly-

mers (MCPs) may offer a more cost-effective route to carbon sequestration. MCPs of the M/DOBDC

series (where DOBDC is 2,5-dioxido-1,4-benzenedicarboxylate, and M is Mg, Co, Ni, and Zn) have pre-

viously been shown to have significant capacities for carbon dioxide at low partial pressures, with Mg/

DOBDC displaying 23.4 wt% carbon dioxide uptake at 0.1 atm. However, previous studies have only

focused on static carbon dioxide sorption measurements or breakthrough experiments with simple nitro-

gen/carbon dioxide mixtures. Here we present the effect of water, a critical component of flue gas, on

the carbon dioxide capacities of members of the M/DOBDC series by comparing post regeneration ca-

pacities after nitrogen/carbon dioxide/water breakthroughs with capacities from the pristine materials.

These data underline some of the challenges associated with using physisorptive materials for capturing

carbon dioxide from flue gas.

39

35: ULTRA-FAST SPECTROSCOPY OF SILSESQUIOXANE DERIVA-

TIVES

Jin Zhang, Class of 2007, Goodson Group

Molecular components assembled in a well-defined three dimensional geometry potentially lead to novel

electronic, optical and nonlinear optical properties. Among nonlinear optical properties, two-photon ab-

sorption (TPA, a third order optical nonlinearity) has received tremendous research attention in recent

years because of their applications in different areas of science. It has also been shown that when the

chromophores are decorated on silver nanoparticle, there is a strong electronic coupling between the

chromophores and thereby enhancing the nonlinear optical properties[2]. However when the chromo-

phores are adsorbed on a nanoparticle it is difficult to judge the orientation and geometry of chromo-

phore on the nanoparticle. If the chromophores are covalently attached to a known three dimensional

geometry, it is easy to understand the influence of the molecular orientation as well as charge transfer

character on the two-photon absorption properties. To this effect, we have investigated the two-photon

absorption properties of the donor-acceptor derivatives of diphenyl stilbene attached three dimensionally

to a silsesquioxane backbone. The sets of materials are fully conjugated. Investigation of the UV-Vis,

emission and two-photon absorption properties of the R‟-vinylStilbeneSiO1.5]8 compounds especially

where R‟ = NH2 reveals exceptional red shifts (120 nm), CT behavior and excellent two photon absorp-

tion properties that may suggest that the silica core serves the role of electron acceptor in the system.

75: Utilizing chain-growth polymerizations for synthesis of gradient thio-

phene copolymers

Jonas R Locke, Class of 2007, McNeil Group

A chain-growth copolymerization based on Kumada cross-coupling of 3-hexylthiophene and 3-

(hexyloxy)methylthiophene monomers has been developed to generate new conjugated copolymers.

This copolymerization has been applied to the development of new gradient copolymers wherein the

monomer composition changes continuously along the polymer chain. A series of copolymers with vary-

ing compositional sequence were prepared via batch and semi-batch methods. Relative rate studies were

undertaken to determine the first reactivity ratios for thiophene copolymerizations and found little differ-

ence in reactivity. Thin-film spectroscopic studies indicate that gradient copolymers display unique ag-

gregation behavior in the solid state. These new materials offer the ability to tune the solid-state proper-

ties of polythiophenes for use in polymer electronic devices. Control over the polymer physical proper-

ties will enable improvements in device efficiency and longevity.

40

76: Stimuli-Responsive Gelation Triggered by Mercury

Kelsey King, Class of 2009, McNeil Group

Molecular gels are a class of materials formed by the self-assembly of small molecules to exhibit solid-

like behavior, but are largely comprised of a liquid. Details of what causes a molecule to form a gel and

the exact mechanism of gelation remain elusive. It is largely believed that 1D intermolecular interac-

tions in the solid state, such as pi-pi stacking or hydrogen bonding, are a key feature. It was hypothe-

sized that identification of crystal structures with evidence of 1D molecular packing motifs could help to

make the search for new gelators more efficient. Indeed, a novel stimuli-responsive gelator was discov-

ered by first examining crystal structures for 1D intermolecular interactions involving Hg and pi-

systems. This poster presents subsequent derivatives of the resulting Hg complex to find potential struc-

ture-gelation trends.. These results will theoretically provide further insight into the process of gelation

and help to determine what molecules will be gelators.

77: Vapor Discrimination with Resistive Films of Gold-Thiolate Nanoparti-

cles Doped with Metallophthalocyanines

Lindsay K. Amos, Class of 2009, Zellers Group

Monitoring of explosives, including nitroaromatics and peroxides, is of critical importance to counter-

terrosim efforts. Chemiresistor (CR) arrays incorporating sorptive films of thiolate-monolayer-protected

gold nanoparticles (MPNs), alone or doped with a small amount of metallophthalocyanines (MPc), are

being explored for this application. These arrays are being designed for use as detectors in a microfabri-

cated gas chromatograph (µGC) for distinguishing the following explosive marker compounds from

background interferences: 2,4- and 2,6-dinitrotoluene (DNT) and dimethyldinitrobutane (DMNB). The

synthesis, thin-film deposition, and testing of MPNs and MPN-MPc composites as CR sensor interfaces

for these targets is described. This presentation will focus on preliminary results obtained with Fe-Pc-

doped diphenylacetylene-MPN films at room temperature, which show highly unusual and potentially

useful selectivities toward a series of test vapors; resistance increases are observed for some analyte va-

pors while resistance decreases are observed for others. It is clear that charge transfer interactions with

the Fe-Pc modulate the influence of vapor sorption on the tunneling current passing through the MPN

network. The findings are being rationalized using known models of conduction through nanoparticle

films, wherein the film conductance is portrayed as a function of the Au-Au intercore separation and the

tunneling activation energy which, in turn, are functions of the properties of specific analyte (e.g., vapor

pressure, density, dielectric constant, polarizability), the MPN ligands (e.g., intercalation, dielectric con-

stant, rigidity, polarizability), and the analyte-ligand interactions (e.g., partition coefficient, swelling ef-

ficiency).

41

78: Isolation and Characterization of Unique PAMAM Dendrimer Species

and Conjugates

Mallory van Dongen-Sohmer, Class of 2009, Banaszak-Holl Group

Starburst poly(amidoamine) (PAMAM) dendrimers are capable of polyvalent interactions that make

them ideal for applications in targeted therapeutics, sensing, and detection. Since their introduction

dendrimers have been considered to be relatively monodisperse, almost macromolecular as opposed to

polymer in nature. However, structural disparity can be and is detected in both native dendrimers species

and subsequent multivalent conjugates. Such variations in composition affect the efficiency and

stoichiometry of further modification and application. Presently, common defects are acknowledged but

little has been done to isolate and fully characterize the various species present in commercial den-

drimers. Here, semi-preparitive high-performance liquid chromatography has been used to fractionate

generation 5 PAMAM dendrimer into its various components which were characterized by additional

methods (analytical preparative HPLC, NMR, MALDI-TOF-MS, GPC). Additionally, semi-prep HPLC

was used to isolate various precisely defined PAMAM conjugates from heterogeneous mixtures.

79: Cellular Defense Mechanisms Affecting Transgene Expression

Rahul Rattan, Class of 2007, Banaszak Holl Group

Gene therapy is a promising platform for treating many life-threatening diseases with a long-lasting pre-

ventive and therapeutic outcome. Success of gene delivery for medical application requires a safe, selec-

tive, and efficient vector system. Presently, gene therapy vector systems can be divided into two main

classes; viral and non-viral based vector systems. Each class of vector systems has their own advantages

and disadvantages. The main drawback of using a more versatile non-viral polymer systems is its lack of

transgene expression. There have been many hypotheses for the reason behind inefficiency of polymer

systems. Some of these hypotheses include a lack of proper uptake mechanism for polyplex (polymer +

transgene) inside the cell and nuclease activation leading to transgene degradation. In this study, the

transgene degradation pattern or transgene topology will be directly studied among various polymeric

systems having different transgene expression. This study will give us insight into whether higher ex-

pression by some polymer-based systems is due to a certain transgene topology inside the cell, a de-

crease in cellular nuclease activation, or both. The goal is to use this information to help design high ex-

pression polymeric based gene delivery systems.

42

80: Wet Chemical Functionalization of Gallium- Based III/V Semiconductors

Sabrina Peczonczyk, Class of 2009, Maldonado Group

A new wet chemical synthetic methodology for the surface functionalization of gallium- based III/V

semiconductors has been developed to gain control over the interfacial properties of these materials. GaP

(111A), GaAs(111A) and GaN particles have been chemically modified via a two-step chlorination and

alkylation sequence, using Grignard reagents. The resulting surfaces have been characterized by X-ray

photoelectron spectroscopy, Fourier Transform infrared grazing angle attenuated total reflection spec-

troscopy, and sessile contact angle measurements. The electrochemical properties of these materials

have also been probed via Hg-contact measurements. This method is the first to chemically modify Ga-

based III/V semiconductors without the use of thiol chemistry, or a high vacuum system. These types of

materials have broad potential applications in the fields of sensing, electronics and specifically photo-

electrochemistry for solar conversion.

81: Understanding the ligand effects on Ni-catalyzed polymerization

Se Ryeon Lee, Class of 2009, McNeil Group

Organic π-conjugated polymers are studied as a substitute for the present technology in many applica-

tions, including light-emitting diodes and solar cells. Their advantageous characteristics include syn-

thetically tunable properties, ability to be processed in solution, and low material cost. In 2004, chain-

growth syntheses were first reported for Ni-catalyzed poly(3-hexylthiophene). Chain-growth polymeri-

zations provide more control over polymer formation compared to previous step-growth polymeriza-

tions. However, the conditions to synthesize Ni-catalyzed polymers have shown to vary greatly based on

the monomer, ligand, and additive. Our work focuses on understanding the ligand effects in the polym-

erization to develop a universal system. Specifically, we have been studying initiation and propagation

rate of the polymerization of poly(2,5-bis(hexyloxy)phenylene) with ligands of different electron-

donating ability. Using a homogeneous Ni-catalyst has allowed us to determine k1 (transmetallation)

and k2 (reductive elimination) during initiation and to compare these rates with k2 during propagation.

These results will provide the information needed to tune the catalyst to promote faster initiation and

result in narrower molecular weight distribution.

43

82: Gallium phosphide and silicon nanowires for solar energy conversion

Wen Wen, Class of 2009, Maldonado Group

To function efficiently, existing commercial solar cells require expensive, high purity materials that in-

hibit economic scalability of the technology. Semiconductor nanowires (NWs) with a high aspect ratio

provide a means of circumventing the need for prohibitively expensive materals. In this work, data are

presented for the preparation and utilization of gallium phosphide (GaP) and silicon (Si) NWs. These

materials were grown using a custom-built vapor-liquid-solid (VLS) chemical vapor deposition (CVD)

system. GaP NWs utilized a solid source for their growth on (100) GaP substrates. The as-prepared

materials were studied for their activity as photoelectrodes in non-aqueous regenerative photoelectro-

chemical cells. Two separate methods to dope the GaP NWs either more n-type or p-type were investi-

gated. By annealing in a N-rich environment, the materials exhibit a high incorporation of nitrogen into

the crystalline lattice of GaP NWs. By annealing in Zn-rich gas, the GaP NWs exhibit increased p-type

character. Si NWs were obtained using direct liquid injection (DLI) of two silane precursors, diphenyl-

silane or tris(trimethylsylil)silane on (100) Si substrates in a reducing hydrogen (H2) atmosphere. As

deposited films of NWs exhibited carbon (C) as well as Si in the EDS and Raman spectrum. The crys-

tallinity of the materials was strongly dependent on the growth conditions. Characterization of the NWs

through scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission elec-

tron microscopy (TEM), spectral response and current-voltage (I-V) characteristics are presented.

83: Hydrothermal synthesis or treatment of transition metal oxides as Li-ion

batteries‟ cathodes

Xiaoguang Hao, Class of 2009, Bartlett Group

Lithium ion batteries (LIBs) have been applied as portable power sources for the last two decades. The

most widely-used cathode material is lithium cobalt oxide, LiCoO2, which was commercialized by

SONY in 1990. The key structural feature of LiCoO2 is its layered structure, which affords high charge-

carrier mobility in the alkali intercalation compounds. For mass production, high temperature (~ 900 ºC)

solid-state sintering is typically employed, but this limits the ability to control particle size and morphol-

ogy. In this project, sealed bomb hydrothermal methods at much lower temperatures (180 ºC) are con-

sidered. Readily available, soluble precursors such as alkalki hydroxides and hydrogen peroxide are

employed in the reactions. We have developed a “freezing” method for this reaction, leading to a better

control of the autogeneous reaction pressure. The electrochemically active high-temperature phase of

LiCoO2 (HT-LiCoO2) has been achieved, with a 120 mAh/g discharge capacity having a stable plateau

in the voltage range 3 -4.2 V.

As a potential substitute for LiCoO2, vanadium (V) oxide is treated hydrothermally to prepare nano

wires or nano belts of V2O5. High specific capacity value (close to 300 mAh/g in the voltage range 1-4

V, is achieved without apparent fading during the first 10 charge/discharge cycles. Although there are

several crystallographic phase changes during cycling , the ability to intercalate lithium, as well as so-

dium and magnesium makes this a promising material for cathode exploration.

44

3: Palladium-Catalyzed Carboetherification for the Synthesis of Ben-

zopyrans

Amanda Ward, Class of 2007, Wolfe Group

Benzopyrans are found in a wide variety of natural products and are considered privileged substructures

in organic synthesis. Despite the prevalence of benzopyrans in biologically active compounds, few

methodologies can construct the benzopyran core and append a variety of different functional groups to

the 1‟ position. Additionally, a method that is amenable for the synthesis of analogs and benzoypyran

libraries would be of great utility. Thus, we sought to extend our palladium-catalyzed carboetherification

methodology towards the synthesis of benzopyrans.3 Preliminary results indicated that a variety of aryl

or alkenyl halides could be coupled with 2-(but-3-enyl)phenol and 2-(3-methylbut-3-enyl)phenol to af-

ford substituted benzopyrans. However, in order to apply our methodology toward the synthesis of natu-

ral products, asymmetric reaction conditions must be developed. SHIP, a spirobiindane phosphite cata-

lyst, has shown excellent enantioselectivity in the carboetherification reaction; however, the desired

product was obtained in low yield. Thus, the objective of current research is to develop a novel spirobi-

indane catalyst that can produce benzopyrans in good yield and excellent enantioselectivity. 1. Kiem, P.V.; Dang, N.H.; Bao, H.V; Huong, H.T.; Minh, C.M.; Huong, L.M.; Lee, J. J.; Kim, Y. H. Arch

Pharm Res 2005, 28, 1131–1134.

2. Levai, A.; Timar, T.; Sebok, P.; Eszenyi, T. Heterocycles 2000, 53, 1193–1203.

3. Hay, M. Wolfe, J. J. Org. Chem. 2005, 70, 3099–3107.

36: Pd-Catalyzed Carboamination of Oxazolidin-2-ones: A Stereoselective

Route to trans-2,5-Disubstituted Pyrrolidines

Georgia Lemen, Class of 2006, Wolfe Group

Previous carboamination methodology developed in the Wolfe group allowed for the synthesis of 2,5-cis

-disubstituted pyrrolidines. However, while this core is found in some natural products, others, such as

the broussonetine alkaloids, contain a 2,5-trans-disubstituted pyrrolidine. Thus, accessing the 2,5-trans

diastereomer is desirable. By transition state analysis, it was hypothesized that tethering the substituent

at the 2-position with the nitrogen in the pentenylamine substrate should afford a fused 2,5-trans-

pyrrolidine. 4-(but-3-enyl)oxazolidin-2-one derivatives were synthesized from amino acid precursors

and subjected to palladium catalysis. This strategy successfully afforded the desired pyrrolidine product

in >20:1 dr after cleavage of the cyclic carbamate linker between the nitrogen and hydroxyalkyl substitu-

ent. The transformations were most effective with slightly electron deficient to electron rich aryl bro-

mides.

Organic Poster Abstracts

45

37: Facile preparation of protected benzylic and heteroarylmethyl amines via

room temperature Curtius rearrangement

Matt Leathen, Class of 2005, Wolfe Group

A step-wise, room temperature procedure for acyl azide formation and the subsequent Curtius rearrange-

ment of phenyl and heteroaryl acetic acids is described. We have developed a protocol for room tem-

perature Curtius rearrangement in MeOH or CHCl3 that provides an improvement over standard condi-

tions, avoiding the use of additives or heat. This room temperature optimization of the Curtius rearrange-

ment prevents the formation of side products often observed with benzylic acids, allowing access to a

variety of benzylic and heteroarylmethyl amines.

38: Oxidative Interception of Wacker Intermediates

Sharon Neufeldt, Class of 2007, Sanford Group

Nucleopalladation of an olefin is typically followed by ß-hydride elimination to afford a Wacker-type

monofunctionalized olefin. Less commonly, the Pd-alkyl Wacker intermediates can be oxidatively in-

tercepted to yield valuable vicinally difunctionalized products. However, selective methods to accom-

plish this transformation are relatively rare and suffer from limited reagent scope and lack of stereocon-

trol. Our strategy toward this olefin difunctionalization is to employ a directing group proximal to the

target olefin in order to faciliate regioselective functionalization, help inhibit competitive ß-hydride

elimination, and allow a means of achieving stereocontrol. Efforts toward the development of a selec-

tive method for ligand-directed olefin dioxygenation via a high-oxidation-state Pd intermediate will be

presented, with a focus on achieving stereoselectivity. Oxime-ether-directed olefin dicarboxylation has

been accomplished with extremely high cis diastereoselectivity. Furthermore, a marked preference for a

given absolute stereochemistry is demonstrated when non-racemic chiral oxime auxiliaries are em-

ployed. The oxime E/Z isomers are configurationally stable under the reaction conditions, and the con-

figuration of the oxime is shown to have an important effect on the selectivity of the reaction.

46

39: Development of Nickel Catalyzed Intermolecular Enoate-Alkyne [3+2]

Cycloadditions

Aireal Jenkins, Class of 2007, Montgomery Group

A new method to access cyclopentenone [3+2] cycloaddition products using α,β-unsaturated enoates and

alkynes in the presence of a nickel catalyst has been found. This methodology is complementary to our

previous [3+2] cycloaddition methodology which utilizes enals, instead of enoates, and produces

cyclopentenol products. These reactions are thought to proceed through a nickelacycle O-enolate which

reacts with an acidic hydrogen or a hydrocarbon electrophile followed by insertion of the vinyl nickel

species into the carbonyl to form the carbocycle. This reaction also shows potential for developing the

[3+2] cycloaddition three-component coupling methodology. These alkylative cycloaddition products

were previously only accessible using stoichiometric equivalents of nickel, and all attempts to make the

reaction catalytic were unsuccessful. We have so far demonstrated that [3+2] reductive cycloaddition

products are easily accessible and [3+2] alkylative products are accessible using aldehydes as electro-

philes. Optimization of the [3+2] reductive cycloaddition methodology is nearly complete, and the reac-

tion has been found to tolerate a variety of functionality and substitution patterns on the enoate and al-

kyne. Future developments of this methodology will involve completion of the [3+2] reductive cycload-

dition optimization and development and optimization of the [3+2] alkylative cycloaddition methodol-

ogy

40: Development of a palladium-catalyzed arylfunctionalization of alkenes

Asako Kubota, Class of 2007, Sanford Group

Palladium-catalyzed difunctionalization of olefins using aryltin reagents and a halogenated oxidant (Cl

and Br) has been shown to yield arylhalogenated products. A wider variety of arylfunctionalization is

plausible to achieve by using a combination of other transmetalating reagents and different oxidants.

This poster will present our effort to expand and develop the methodology for arylfunctionlization of

olefins with increased choices of oxidants.

47

41: Electrophilic Boron Reagents for C-H Bond Functionalization

Aleksandrs Prokofjevs, Class of 2006, Vedejs Group

The main focus of our research is the transition metal-free functionalization of unactivated aromatic and

aliphatic C-H bonds using boron cations. High electrophilicity of the boron reagents is the key for

achieving the desired reactivity. This methodology allowed us to prepare organoboron compounds, that

cannot be accessed by the conventional means.

42: The Application Nickel-Catalyzed Reductive Couplings towards

Heterocycle Synthesis

Ben Thompson, Class of 2006, Montgomery Group

Five-membered heterocycles such as pyrroles, thiophenes, and furans are found in many bioactive com-

pounds, making their synthesis an important aim in organic chemistry. There are many ways to make

the different substitution patterns of these heterocycles, however, one popular method is the cyclization

of 1,4-dicarbonyl compounds. 1,4-Dicarbonyl compounds are available from multiple methods such as

the Stetter reaction. Many of these methods have some scope limitations and often focus on only a few

substitution patterns of these molecules. Recently, our group reported two reductive coupling reactions

that can produce γ,δ-unsaturated carbonyl compounds, which upon oxidative cleavage of the alkene por-

tion, furnish 1,4-dicarbonyls. This technique allows access to many different substitution patterns of

heterocycles via Paal-Knorr-type cyclizations that are not commonly available, such as the 2,3 and 2,4

substitutions . This work shows the application of this methodology to the synthesis of pyrroles, thio-

phenes and furans.

48

43: Pd-Catalyzed Synthesis of 1,4-Benzodiazepines

Joshua Neukom, Class of 2006, Wolfe Group

The benzodiazepine moiety has a rich history in medicinal chemistry dating back to the 1950s and the

serendipitous discovery of the blockbuster drug diazepam (Valium). Although several synthetic routes

for the synthesis of benzodiazepines exist, none are suited for the facile preparation of 2-arylmethyl-1,4-

benzodiazepines, which are a relatively unexploited variation on the parent benzodiazepine scaffold. Our

Pd-catalyzed carboamination approach to generate these compounds has the following advantages: (1)

substrates are readily available in a short sequence from inexpensive methyl anthranilate ($0.08/gram);

(2) the reactions proceed with good to excellent yields (60-94%) and complete diastereoselectivity for

the cis-2,3-disubstituted products (>20:1 dr); (3) concomitant formation of the C–N bond as well as a C–

C bond allows for the preparation of numerous analogs suitable for structure-activity studies. Currently,

1,4-benzodiazepine and 1,4-benzodiazepin-5-one products have been submitted to the National Institutes

of Health Molecular Library Small Molecule Repository (NIH-MLSMR) for biological assays. Addi-

tionally, chiral ligands are being employed to develop an asymmetric variant of this reaction. An initial

screen of chiral ligands has provided up to 66% enantioenriched product. Work is ongoing in develop-

ment of chiral ligands to increase the enantioselectivity of these reactions.

84: Pd-catalyzed ligand directed alkenylation of sp3 C–C bonds us-

ing O2 as the terminal oxidant.

Kara J. Stowers, Class of 2006, Sanford Group

Directed sp3 bond formation is demonstrated between primary methyl groups and terminal alkenes with

dioxygen as the oxidant. This is a benchmark example of the use of substoichiometric polyoxometalates

in the presence of dioxygen for sp3 bond funcationalization. Rapid Michael addition of the directing

group can be reversed to obtain further derivations of the formed C–C double bond such as hydrogena-

tion, oxidative Heck, and conjugate additions. These reaction conditions are amenable to a variety of

electron poor and electron rich pyridines. The results of this investigation advance the scope and accessi-

bility of sp3 C–C functionalization to include bond formations using terminal olefins as starting materi-

als.

49

85: Advances in Conjugate Addition Reactions via Nickel-Catalyzed Cou-

pling

Wei Li, Class of 2006, Montgomery Group

Conjugate addition reactions have been a benchmark in preparing ɣ,δ-unsaturated carbonyl compounds,

which are useful intermediates in synthesis of natural products and complex molecules. Traditionally,

additions of cuprate reagents to enones have been the standard for conjugate addition reactions. More

recently, hydrometallation of alkynes and alkenes have been used as a way to circumvent the limitation

in functional group tolerance by the cuprate preparation route. However, the use of stoichiometric or-

ganometallic reagents has remained a major hurdle to the synthetic utility of this reaction. To alleviate

the heavy use of transition metals, couplings of unsaturated π-components using catalytic amount of

transition metals have been introduced in terms of advancing the synthetic utility of the conjugate addi-

tion reactions.

86: Aryl- CF3 Bond-Forming Reductive Elimination from Pd(IV)-CF3 Com-

plexes

Nicholas Ball, Class of 2005, Sanford Group

Direct carbon–trifluoromethyl reductive elimination proceeding through a Pd(0)/Pd(II) transformation

has proven to be extremely challenging. Alternatively, C–CF3 bond formation could be better promoted

through a Pd(II)/Pd(IV) pathway. Key to the proposed mechanism is the existence of a Pd(IV) interme-

diate which undergoes subsequent C–CF3 bond reductive elimination. This presentation will discuss oxi-

datively induced Ar−CF3 bond-forming reductive elimination from new Pd(II) complexes of general

structure (L–L)Pd(II)(Ar)(CF3). The electrophilic fluorinating reagent N-fluoro-2,4,6-

trimethylpyridinium triflate promotes these reactions in good to excellent yields. Three palladium(IV)

intermediates have been isolated, characterized, and demonstrated to undergo high yielding Ar−CF3 cou-

pling upon thermolysis. Additionally, kinetic studies will focus on elucidating the mechanistic details of

reductive elimination from Pd(IV). This work provides an attractive conceptual framework for the de-

velopment of Pd(II)/(IV)-catalyzed arene trifluoromethylation reactions.

50

87: Nickel and Palladium Catalyzed Perfluoroaklyation of Arenes

Rebecca Loy, Postdoctoral Researcher, Melanie Sanford Group

The installation of fluorine changes the biological, physical and chemical properties of molecule and has

great utility for material science, pharmaceuticals and agrochemicals. This poster describes the develop-

ment of both a palladium and nickel catalyzed perfluoroalkylation of arenes. A wide variety of per-

fluoralkylated arenes can be obtained in good yield and regioselectivity

88: Synthesis of Unnatural Substrates for PikC Oxidation Studies

Solymar Negretti, Class of 2008, Montgomery Group

Macrolides are a special class of polyketide natural products with antibiotic activity which are produced

as secondary metabolites from Actinomycete bacteria. PikC, a cytochrome P450 monooxygenase from

the organism Streptomyces venezuelae, is responsible for catalyzing the last hydroxylation step in the

synthesis of macrolide antibiotics methymycin, neomethymycin and pikromycin. The PikC catalyzed

hydroxylation exemplifies one of the most challenging reactions for synthetic organic chemists: regio-

and stereoselective oxidation of unactivated C-H bonds. Also PikC exhibits greater substrate tolerance

than most known P450‟s involved in macrolide hydroxylation and it has been employed for the moder-

ately regioselective hydroxylation of several desosamine linked carbocyclic rings, proving PikC to be

capable of oxidizing unnatural substrates and its potential as a bio-catalyst. However, achieving high

levels of regioselectivity and stereoselectivity for unnatural substrate hydroxylation has been challeng-

ing. To improve the usefulness of PikC oxidation as a synthetic tool substrates containing more structur-

ally complex aglycone that more closely resemble the endogenous substrate, and substrates containing

modifications in the sugar are being evaluated.

51

89: Progress towards Peroxide-based Explosives Detection via Gelation

Phillip Stratton, Undergraduate Researcher, McNeil Group

Practical applications of functionalized organic gels are expanding into areas such as tissue engineering,

pollutant detection and capture, biosensing, and drug delivery. In this work, we present our efforts to-

wards a gelation-based sensor for detecting an explosive, triacetone triperoxide (TATP). Using a gelator

for detecting TATP is a simple, efficient and effective way to positively identify the presence of this non

-nitrogenous explosive. Several catalysts were investigated for oxidizing dihydropyridine to pyridine

using di-tert butyl peroxide as a simulant for TATP. The reactions with hydrogen peroxide exhibited

much greater yields (about 60% to 100% for a given catalyst) than when tert-butyl peroxide was em-

ployed (about 30% to 55%). These results can be considered a good foundation for further investigation

into catalysts that will utilize TATP under mild conditions.

90: Regioselectivity in Pd-catalyzed oxidative aryl coupling

Tom Lyons, Class of 2005, Sanford Group

Palladium catalyzed oxidative coupling reactions allow for regioselective aryl-aryl bond construction

without the aid of prefunctionalized starting materials. Previous work by our group has shown such re-

actions can be achieved through two discrete C-H activation steps whose selectivities are controlled by

proximity to a ligand (first C-H activation) as well as by the steric environment around the arene C-H

bond (second C-H activation). Recent mechanistic studies show that regioselectivity in this system is

greatly impacted by both sterics and electronics on the metal center as well as the relative concentration

of added benzoquinone ligand. These studies have revealed a new reaction pathway leading to a reversal

in the predominant regioisomeric product. Further studies exploring the nature of this selectivity are

described in this poster.

52

91: Oxidation of Catalytically Relevant Pd Dimer with “CF3+”: Formation

and Reactivity of a Monomeric Pd(IV) Aquo Complex

Yingda Ye, Class of 2008, Sanford Group

The oxidation of [(bzq)Pd(OAc)]2 with “CF3+” reagents in wet AcOH to afford monomeric PdIV aquo

complex (bzq)Pd(CF3)(OAc)2(OH2) is demonstrated. This high oxidation state Pd complex undergoes

competing C–CF3 and C–OR reductive elimination reactions, and the product ratio is highly dependent

on the solvent and the presence of Lewis acidic/basic additives. These studies provide potentially valu-

able insights regarding the speciation, nuclearity, and reactivity of Pd intermediates in catalytic C–H

functionalization.

44: On the conditions for enhanced transport through molecular junctions

based on metal centers ligated by pairs of pyridazino-derived ligands

Bei Ding, Class of 2009, Chen Group

Transport properties of a Ni complex ligated by pairs of bi-pyridazino derivatives are considered. This

complex provides the opportunity to avoid perpendicular alignment of the ligand pi planes. We study the

effects of pi bonding and of intramolecular hydrogen bonding between the ligands as mediated by the

metal center on electron transport. The complicated effect of the electronic structure level provides

guidelines to design a molecular

bridge that is based on metal

complexation with effective

electronic transport.

Physical Poster Abstracts

53

45: Electron Transfer Studies in Functionalized Silsesquioxane Complexes

using Novel Time-dependent Density Functionals

Heidi Phillips, Class of 2009, Dunietz/Geva Group

The application of nano-devices in light harvesting and storage is a major focus in solar energy research.

There is interest in identifying molecular systems that possess charge transfer properties such as those of

a chromophore semiconductor interface. Recently, large red-shifts in the emission spectra of the silses-

quioxane nano-cube upon functionalization with chromophores coupled to the corners suggest photo

induced charge transfer which is associated with cube-mediated 3D conjugation.

In order to understand the charge transfer process, ab

initio electronic structure calculations (DFT/TDDFT) can be

used to obtain the excited state energies. However, the limi-

tations of DFT/TDDFT in describing charge transfer systems

are well known and can be corrected by use of range-

separated hybrid functionals.

In this study, the effect of cube-chromophore cou-

pling on the excited state energies and electronic couplings

between ground and excited charge-localized states were

compared for the B3LYP hybrid functional and the BNL

range-separated hybrid functional. The cube was functional-

ized with vinyl groups, which served as a model, and stilbene

groups, which had been measured experimentally.

46: Bright Lights and Bad Bugs: A Single-Molecule Fluorescence Study of

Pathogenicity in Live Vibrio cholerae Cells

Beth Haas, Class of 2009, Biteen Lab Group

Beth L. Haas, Mou-Chi Cheng, Jyl S. Matson, Victor J. DiRita, Julie S. Biteen

No matter the quality of an optical microscope, the wave nature of light limits the resolution of its im-

ages to approximately 300 nm. Single-molecule fluorescence imaging and superresolution techniques

such as (f)PALM and STORM can overcome this diffraction limit barrier, allowing localization preci-

sion as good as a few nanometers. . Here we investigate the regulatory pathway controlling pathogenic-

ity in cells of live Vibrio cholerae, the bacteria responsible for the pandemic human disease cholera. In

particular, we examine the membrane-localized DNA transcription activator, TcpP, by labeling its perip-

lasmic domain with the fluorescent proteins Dendra or mCherry. This is the first step toward visualizing

the dynamics, colocalization pat-

terns, and diffusion characteris-

tics of the regulatory proteins

and the genes they control. This

work aims to expand the scope

of single molecule imaging

methods as well as to provide

valuable insight into the patho-

genicity of an organism that

threatens public health.

54

47: Solvent effects on the dynamics of hexatriene isomerization reaction: A

Molecular Dynamics Simulation Study

Surma Talapatra, Class of 2009, Geva Group

The ring opening reaction of 1,3-cyclohexadiene (CHD) is important because it is analogous to the reaction of 7-

dehydrocholesterol to form pre-vitamin-D. Previous experiments on the multistep reaction reveal that the ring

opening of CHD is followed by isomerization of cis-1,3,5-hexatriene (Zt-HT) from cis (cZt-HT) to trans (tZt-HT)

conformer. Detailed studies on this last step reveal that the rate constants of isomerization in different alcohols and

alkanes do not follow the inverse viscosity dependence predicted by Kramers theory.

We have investigated the isomerization reaction using molecular dynamics simulations to develop a molecular

level explanation for this interesting trend of reaction rates in alcohols and alkanes. Using a number of alcohols

(methanol, ethanol, propanol, butanol) and alkanes (cyclohexane, n-hexane, n-heptane, cycloheptane) as solvents,

the isomerization reaction rate constant was calculated at various temperatures ranging from 280K to 320K. The

rate constant was measured using the reactive flux correlation function and transition state theory. In order to ex-

plain the results seen, thermodynamic properties of the reac-

tion were calculated, including changes in free energy, en-

tropy and enthalpy as the cZt-HT goes to the transition state.

Primary results reveal that the rate of isomerization in alco-

hols is indeed slower than in alkanes. The entropy changes

indicate that the faster reaction rates in alkanes can be attrib-

uted to structural difference brought about by the fact that the

alcohol solvents form protic liquids with a relatively rigid

hydrogen-bonded network, while alkane solvents form aprotic

liquids so that solvent molecules can access the close vicinity

of the solute.

92: Real-Time Super-Resolution Tracking of Single Deoxyribozyme Based

Molecular Robots

Anthony J Manzo, Postdoctoral Researcher, Walter Group

The probing and characterization of the behavior of individual nucleic acid based molecular robots is

presented, using real-time single-particle tracking with super-resolution total internal reflection fluores-

cence microscopy (TIRFM). Nucleic acid based molecular assemblies, called “spiders”, implemented as

robots with multiple deoxyribozyme sensor-actuator legs traverse and cleave two-dimensional land-

scapes of surface bound oligonucleotide substrates. We analyze the movement of spiders to determine

the characteristics of their random walk on various substrates and at the product/substrate interface. The

experimental approach demonstrated here should allow for control over the cybernetic properties of spi-

ders, resulting in the integration and synthesis of complex robotic behaviors at the nanoscale based on

DNA and RNA nanotechnology.

55

93: Entangled Two-Photon Absorption and Excited Fluorescence with Or-

ganic Chromophores

Alica Guzman, Class of 2009, Goodson Group

Organic conjugated nonlinear optical (NLO) macromolecules have been shown to successfully absorb

and detect entangled photons generated by the process of spontaneous parametric down-conversion

(SPDC). Entangled photon pairs produced by SPDC are used in our laboratory to investigate entangled

two-photon absorption (ETPA) at extremely low excitation flux in these materials. This presentation

shows the results of an investigation of 2D annulene systems, which are seen to have impressive classi-

cal two-photon cross-sections displaying enhancement with the number of chromophores. We explore

the influence of the spatial entangled states of the photon pairs on the ETPA process. ETPA is observed

for emission patterns which exhibit overlap, but not for patterns which exhibit a non-overlapping, or spa-

tially distinguishable, emission pattern. Furthermore, the amount of absorption is observed to depend on

the degree of overlap of the photons in cases of overlap. Absorption of entangled photons by organic

chromophores can thus be „tuned,‟ selectively enhanced or limited through variation of the degree of

overlap of the photons. Also shown are the preliminary results of Entangled Two-Photon Excited Fluo-

rescence (ETPEF) with a conjugated dendrimer. This is the first experimental result showing ETPEF,

obtained in our laboratory by utilizing a novel optical cavity design for collection of the fluorescence.

94: Investigating anaerobic gut microbes using single-molecule-based super-

resolution fluorescence microscopy

Ben Coupland, Class of 2008, Biteen Group

Bacteriodes thetaiotaomecran (B. theta) is an anaerobic microbe which catabolizes complex carbohy-

drates that the human gastrointestinal tract cannot digest, accounting for about 10% of our daily calorie

intake. We are studying the starch utilization system (Sus) of B. Theta, a collection of proteins responsi-

ble for catabolism of complex carbohydrates. We are working toward using single-molecule-based super

-resolution fluorescence microscopy to fully visualize the procession of a marked carbohydrate through

the starch utilization system and the components involved in this trajectory. Imaging protein and carbo-

hydrate localization events in live cells in this obligate anaerobe requires the development of methodolo-

gies conductive to the requirement of ultralow oxygen concentrations.

Here, we explore physical and chemical methods of increasing the anaerobicity of sample conditions,

while investigating fluorescent labels other than fluorescent proteins, the majority of which fail to fold

correctly in the absence of oxygen. We have begun to explore the viability of the fluorescein derivative

FlAsH, which binds tetracystein tags, as a labeling scheme for single molecule fluorescence microscopy

with the goal of using FlAsH to label the surface protein SusD. In addition, we will test the viability of

Halo tags in an anaerobic environment, with the intention of using them to tag other proteins in the

starch utilization system if they perform correctly.

56

95: Energy Transfer in Model Light Harvesting Systems

Jessica Donehue, Class of 2009, Goodson Group

The linear and nonlinear optical properties of two sets of organic molecules known to have optical and

structural properties similar to those in naturally occurring light harvesting complexes, porphyrin macro-

cycles and thiophene macrocycles, have been investigated. In our study of the porphyrin macrocyles,

we have probed a series of carbazole-bridged bisporphyrin self-assembly arrays using steady-state ab-

sorption, emission and femtosecond transient absorption spectroscopy to study how excited-state energy

relaxation takes place in the macrocycle, compared to its monomeric unit. Pump-probe experiments

were performed using excitation wavelengths of 465 nm and 650 nm, targeted for selective excitation

into the B-band and Q-band, respectively. Our studies have shown an ultrafast component in the self-

assembled structure which can be associated with energy transfer. In our study of the thiophene macro-

cycles, we have systematically investigated the size dependence of their optical properties using three-

photon echo peak shift experiments. Our studies have shown that initial peak shift increases with in-

creased ring size, suggesting a decrease of coupling of the chromophore to the bath environment.

Through the use of ultra-fast optical measurements, this work has provided insight for understanding the

structural properties that dictate efficient energy transfer in model light harvesting systems.