JULIA EVE BECK

jbeck3@nd.edu | 1234 Notre Dame Ave Notre Dame, IN 46556 | 765-366-6195 Education University of Notre Dame - Notre Dame, IN Anticipated May 2017 Ph.D. Biochemistry, Department of Chemistry and Biochemistry Advisor: Dr. Francis Castellino Dissertation Topic: Study of Components in the Human Fibrinolytic System: Platelet Activation in Traumatic Brain Injury and Plasminogen Activation in Bacterial Infection DePauw University – Greencastle, IN May 2011 B.A. Biochemistry IUPUI Wells Center/Riley Hospital – Indianapolis, IN March 2007 Molecular Medicine in Action Program Professional Skills

Technical: Polymerase Chain Reaction Restriction digest and ligation Site directed mutagenesis Cellular transformation and transfection

Protein expression and purification Fast protein liquid chromatography Binding and activity assays Analytical Ultracentrifugation Surface Plasmon Resonance

Computational: Serial cloner Prism Chimera

Molprobity SedFit SedNTerp

Research Experience University of Notre Dame – Notre Dame, IN June 2013 - Present Graduate Research Assistant, Dept. of Chemistry and Biochemistry Advisor: Dr. Francis Castellino

• Express human and bacterial proteins with various expression systems including E. coli, S2 Drosophila cells, and Pichia pastoris.

• Study protein interaction using surface plasmon resonance, analytical ultracentrifugation, and activation assays.

University of Notre Dame – Notre Dame, IN Aug. 2011 - June 2013 Graduate Research Assistant, Dept. of Chemistry and Biochemistry Advisors: Dr. Francis Castellino, Dr. Victoria Ploplis, and Ms. Deborah Donahue

• Developed model to study platelet dysfunction in brain injured rats. • Analyzed blood coagulation parameters using thromboelastogram, hemostasis analyzer, and

complete blood count.

University of South Alabama – Mobile, AL May 2010 - July 2011 Undergraduate Research Assistant, Dept. of Pharmacology Advisors: Dr. June Ayling and Dr. Luai Hasoun

• Developed a method to extract and quantify folate from human skin using methanol precipitation and High-Performance Liquid Chromatography.

• Summer internship under auspices of National Science Foundation Research Experiences for Undergraduates (NSF-REU) program entitled “Structure and Function of Proteins”.

DePauw University – Greencastle, IN Jan. 2010 - May 2011 Undergraduate Research Assistant, Dept. of Chemistry and Biochemistry Advisor: Dr. Jeff Hansen

• Performed organic synthesis and analyzed results using spectroscopy. DePauw University – Greencastle, IN Jan. 2008 - May 2009 Undergraduate Research Assistant, Dept. Chemistry and Biochemistry Advisor: Dr. Dan Gurnon

• Performed a range of lab techniques, including PCR, DNA purification, gel analysis, DNA sequencing, restriction digests, protein expression trials, and troubleshooting.

DePauw University – Greencastle, IN Aug. 2007 - Dec. 2007 Undergraduate Research Assistant, Geology Department Advisor: Dr. Tim Cope

• Studied the correlation between mountain range and basin areas to determine petroleum deposits.

Wabash College – Crawfordsville, IN May 2007 - July 2007 Summer Research Student Advisor: Dr. Becky Sparks-Thissen and Dr. Ann Taylor

• Performed a range of lab techniques, including PCR, plating, protein expression and purification under the guidance of Dr. Ann Taylor.

• Studied effect of household chemicals on the growth and inhibition of a range of common bacterial strains.

Professional Experience University of Notre Dame – Notre Dame, IN June 2016 - present Keck Center Focus Group Meeting Leader

• Leader duties include planning, organizing, managing, and recording results of weekly meetings.

XVth International Workshop: Sep. 2015 Molecular and Cellular Biology of Plasminogen Activation – Rome, Italy Session Co-chair

• Co-chair duties included managing session of workshop. Publications

1. Butera D, Wind T, Lay AJ, Beck J, Castellino FJ, Hogg PJ. Characterization of a reduced form of plasma plasminogen as the precursor for angiostatin formation. J. Biol Chem. (2014) 289 (5): 2992-3000.

2. Donahue DL, Beck J, Fritz B, Davis P, Sandoval-Cooper MJ, Thomas SG, Yount RA, Walsh M, Ploplis VA, Castellino FJ. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans. J. Neurotrauma. (2014) 31 (4): 404-10.

Selected Presentations

1. Beck, Julia, Victoria A. Ploplis, Francis J. Castellino (September 25, 2015) “The Role of Lysine Binding Sites (LBS) within the Kringle Domains of Plasminogen in PAM Binding”, XVth International Workshop: Molecular and Cellular Biologyof Plasminogen Activation, Rome, Italy

2. Beck, Julia, Deborah Donahue, Victoria A. Ploplis, Francis J. Castellino (June11, 2013) “Platelet Dysfunction in a Rodent Model of Traumatic Brain Injury”, 18th Biochemistry Retreat, Department of Chemistry and Biochemistry, University of Notre Dame

3. Beck, Julia June Ayling, Luai Hasoun (July 30, 2010) “The Role of Skin Pigmentation

in the Protection of Enzyme Cofactors”, NSF-REU program on “Structure and Function of Proteins”, University of South Alabama

Grants & Fellowships Graduate Student Union Conference Presentation Grant July 2015 University of Notre Dame Graduate Assistant in Areas of National Need Fellow Jan. 2014 - present University of Notre Dame, Dept. of Chemistry and Biochemistry Science Research Fellow Aug. 2007 - May 2011 DePauw University Honors & Awards Outstanding Poster Award for Graduate Students Sept. 2015 XVth International Workshop: Molecular and Cellular Biology of Plasminogen Activation Dept. of Chemistry and Biochemistry Travel Award July 2015 University of Notre Dame Old Gold Honors Award Aug. 2007 - May 2011 DePauw University Professional Memberships American Association for the Advancement of Science Jan. 2014 - present Phi Lambda Upsilon, National Chemistry Honorary Fraternity May 2011 Phi Alpha Theta, National History Honor Society May 2011

ResearchSummaryI am graduate student at the University of Notre Dame under the tutelage of Dr.FrancisCastellino,Directorof theW.M.KeckCenter forTransgeneResearch. OurresearchattheKeckCenterisfocusedonthehumanfibrinolyticsystemandhowitrelatestotraumaticbraininjury,stroke,andinfection.Myfirstresearchexperienceunder the guidance of Dr. Castellino involved developing a rodent model oftraumatic brain injury. This work resulted in a publication in the Journal ofNeurotrauma.Ourfindingshavedirectlyimpactedhowdoctorstreatpatientswhohavesufferedatraumaticbraininjury.BasedonourworkattheKeckCenterandincollaborationwithMemorialSouthBendHospital,doctorshavechangedhowtheyadministerkeyfluids likefreshfrozenplasmaandplatelets,whichhaveleadtoanimproved prognosis for the patient. My currentwork is focused on studying theinteractionof thehumanproteinplasminogenandavirulence factor foundonthesurface of Group A Streptoccocus called PAM. Previous studies have shown acorrelationbetween the interactionofplasminogenandPAMandvirulenceof thebacteria. Recently I had the opportunity to present my work at the XVthInternationalWorkshop:MolecularandCellularBiologyofPlasminogenActivationin Rome, Italy. The aim of this work is to better understand this importantinteractionbetweenplasminogenandPAMandhowitrelatestovirulence.Myworkat theKeckCenter alignswith oneofmy core values,which is to use research tounderstandandalleviatethosesufferingfrommedicalailments.

NEIL T BERKEL 20 Longshot Dr. • Troy, IL 62294 • (618) 558-1133 • nberkel@nd.edu

EDUCATION

UNIVERSITY OF NOTRE DAME Notre Dame, IN Master of Science, Physical Chemistry Expected January 2017 GPA: 3.648/4.000

MCKENDREE UNIVERSITY Lebanon, IL Bachelor of Science, Chemistry May 2015 Minors: Biochemistry & Mathematics GPA: 3.985/4.000 Summa Cum Laude Recipient of Outstanding Senior Chemistry (2015) and Outstanding Junior Chemistry Student (2014)

RESEARCH EXPERIENCE

UNIVERSITY OF NOTRE DAME Notre Dame, IN Graduate Research/Teaching Assistant August 2015 – Present

• Developed methodology for computational screening of ferrocene-type ligands in asymmetric catalysis • Collaborated with a large pharmaceutical company to implement method in process chemistry workflow • Applied both quantum mechanical and classical force field methods • Refined computer skills when working with in-house python code • Instructed 15+ students in several organic laboratory courses and ensured laboratory safety

MCKENDREE UNIVERSITY Lebanon, IL Undergraduate Research Assistant January 2014 – May 2015

• Developed methodology for prediction of relative product yields in electrophilic addition reactions • Modeled kinetics and thermodynamics of mentioned reactions • Solved problems and applied creativity by designing original work

PROFESSIONAL EXPERIENCE

SIGMA-ALDRICH St. Louis, MO Summer Intern, Quality Control May 2014 – August 2014

• Replaced product that was used in QC assays to ensure continued sales of 10.5 million dollars per year • Updated operating procedures to implement the new product under quality guidelines

LEADERSHIP & SERVICE

VARSITY TENNIS McKendree University August 2013 – May 2015

• Committed 20+ hours weekly as a student-athlete in practices, work-out sessions, and competition Lewis & Clark Community College August 2011 – May 2013

• Co-Captain and MVP for 2012 - 2013 season • Led team to best finish in school history: 8th Place at the 2013 National Tournament

MISSION TRIPS East St. Louis, IL – High Poverty Area March 2015

• Helped distribute food for the needy and assisted with 8th grade math and science courses Washington, IL – Tornado Stricken Area March 2014

• Cleaned local houses that were destroyed from tornado

TECHNICAL SKILLS Chemistry Skills: Proficient: IR, UV-VIS, Karl Fischer, Western Blots, Electrophoresis

Basic: NMR, HPLC, ELISA Computer Skills: Proficient: Python, UNIX, Gaussian, Schrödinger, Mathematica Basic: SQL, R

Neil Berkel 20 Longshot Dr., Troy, IL 62294 nberkel@nd.edu · (618) 558-1133

Research Summary

(1) University of Notre Dame – Enantioselectivity of Ferrocene-Based Ligands The enantioselectivity of reactions are predicted to aid experimental chemists’ work. The group creates a

large virtual library to point synthetic chemists in the right direction, potentially saving months of time spent in the lab. This is done using a method called Quantum Guided Molecular Mechanics (Q2MM). This is a series of Python scripts that take quantum mechanical (QM) data, i.e. bonds, angles, dihedral angles, frequencies, energies, etc., and automatically fit a molecular mechanics (MM) force field to reproduce the QM data. Because MM is ~104 times faster than QM, this can then be used for the screening of ligands in enantioselective catalysis. Figure 3 shows an example of how well the geometries are reproduced.

One type of reaction that the group has focused on is the hydrogenation of enamides (Figure 1). The problem posed to me was to create a subset of force field parameters to define transition states for the reaction catalyzed by ferrocene-type ligands. Specifically, there were no parameters for ferrocene-based ligands (Figure 2), which are widely used in enantioselective catalysis. The previously developed parameters work for the same reaction, but are defined at the reaction center, leaving out ferrocene. My goal was to combine these two separate subsets to not only get them to work together, but also to predict enantioselectivity.

Before combining the force field parameters for ferrocene with the rhodium parameters, this ferrocene

subset was tested on a variety of ferrocene-based diastereomers. The point of this step is to prove that the ferrocene parameters can predict energy differences accurately. Overall, the data has shown a consistent trend. When combining with the rhodium subset, the enantioselectivity could be estimated showing positive initial results. Through my project, the group was able to gain a better understanding of how to successfully predict the enantioselectivity of ferrocene-based ligands in asymmetric catalysis.

Figure 1: Rhodium-catalyzed hydrogenation of enamides

Figure 2: Example ferrocene ligand – Josiphos Figure 3: Orange – QM geometries. Blue – MM geometries.

(2) McKendree University – Relative Yields of Electrophilic Addition Reactions

The electrophilic addition to conjugated systems was studied to predict product yields. I studied the reaction of HBr and 1,3-butadiene (Figure 4). By breaking down its mechanism, I could understand the theory and calculations behind the project. The interesting part of the research was tackling the issue of predicting the kinetic and thermodynamic controlled products.

By computationally generating a reaction energy profile plot (Figure 5), the reaction could be further

broken down. Based on the activation energies, there is a subtle difference that would ultimately determine which product would be created. The kinetically controlled product is mostly generated at the start of the reaction and at low temperatures. Conversely, the thermodynamically controlled product is typically created after some time and at high temperatures. My goal for this project was to predict the relative percent yields of the products at any given temperature.

The resulting percent yields that were predicted from the research project show positive trends in agreement with the experimental data. As the temperature increased, the more thermodynamically stable product became predominant. Through this independent research project, I was able to solve different problems and overcome them to develop positive results.

(3) Sigma-Aldrich – Reproducing Kodak Supernatant

During my internship with Sigma-Aldrich, a formerly purchased supernatant from Kodak was reproduced due to the fact that it was discontinued at Kodak. The supernatant is used in many assays and is important for the company’s sales. The total amount of sales from the products involved average to about 10.5 million dollars per year.

Over the course of the internship, the lysate was successfully reproduced. The Western Blot assay in Figure 6 shows that one single protein band binds with the antibody when it is spiked. The robust lysate created ensures that the multimillion dollar product line will continue without interruption in the future.

Figure 4: Electrophilic addition of HBr and 1,3-butadiene

Figure 5: Overall reaction energy profile plot

Figure 6: Western Blot showing the crude E. coli lysate tested next to the Kodak

supernatant

Chia-Fu Chang

321 McCourtney Hall, University of Notre

Dame, Notre Dame, IN 46556

Phone: (574)-383-8288

E-mail: cchang5@nd.edu

EDUCATION AND RESEARCH EXPERIENCE

Graduate Research Assistant June 2012 – Present

University of Notre Dame (USA)

Research Advisor: Prof. Richard E. Taylor

Ph.D. Expected Graduation: May 2017 GPA: 3.83/4.0

Thesis title: The Development of Synthetic Methodologies for the preparation Polyketide Natural

Products: Lyngbyaloside C and Ambruticin J, F, and S.

Project I: Total Synthesis and Structural Reassignment of Lyngbyaloside C

Project II: Project II: Biomimetic Total Synthesis of Ambruticin F and S from Ambruticin J via tandem reactions epoxidation/cyclization

Research Assistant Dec. 2010-June 2012

National Tsing Hua University (Taiwan)

Advisors: Prof. Chun-Cheng Lin, Yean-Jang Lee

Research Projects:

Project I: Co-op Research-Drug Synthesis Core Project-V: Synthesis of Heterocyclic Aromatic Compounds As Potential Candidate for Medicine.

Project II: National Science Council Project: Synthesis of Nitrogen-Contained Polycyclic Natural Alkaloids and Polypetides as Anticancer and Anti-HIV Agents.

M.Sc. May 2007-June 2009

National Changhua University of Education (Taiwan)

Advisor: Yean-Jang Lee

Graduation: June 2009 GPA: 4.0/4.0

Research Topic: Total Synthesis of Maleic and Succinic Acid Natural Product Derivatives, Morusin, and Synthetic Investigation Toward Cyclosexipyridine.

HONORS AND AWARDS

Selected to present research work, ACS Division of Organic Chemistry Graduate Research Symposium, Bryn Mawr College (2016)

Thesis Award, Annual Meeting Taiwan Chemical Society (2009, December)

Fellow of Phi-Tao-Phi Scholastic Honor Society Fund, Taiwan (2009)

Masters Scholarship, Ministry of Education, Taiwan (2008, October)

CONFERENCE PRESENTATIONS (SELECTED)

Chia-Fu Chang, Richard E. Taylor, “Synthetic Progress Toward Lyngbyaloside C and Ambruticins”, 17th, 16th, 15th and 17th 17th Biannual Eli Lilly Grantee Symposium, Indianapolis, IN, 2012, 2014 and 2016.

Chia-Fu Chang, Richard E. Taylor, “The Applications of Our Methodologies in Total Synthesis of Polyketide Natural Products: Lynbyaloside C and ambruticins”, Graduate Research Symposium (Organic Division of Chemistry, ACS), Bryn Mawr College PA, July 28-31 2016, Poster presentation.

Chia-Fu Chang, Richard E. Taylor, “Application of Ether Transfer Reaction in Total Synthesis of Lyngbyaloside C”, 98th Canadian Chemistry Conference and Exhibition, Ottawa, June 13-17 2015, Oral presentation.

Chia-Fu Chang, Richard E. Taylor, “The First Total Synthesis and Structural Reassignment of Lyngbyaloside C”, 44th National Organic Chemistry Symposium, University of Maryland, June 28-July 2 2015. Poster presentation.

PUBLICATIONS

1. Chang, C. F.; Stefan, E.; Taylor, R. E. “Total Synthesis and Structural Reassignment of Lyngbyaloside C Highlighted by Intermolecular Ketene Esterification” Chem. Eur. J. 2015, 21, 10681.

2. Lee, Y. J., Tsau, W. S., Chang, C. F., Chuang, S. K. “Total Synthesis of Moscatilines and Wedelolactones as Potential Inhibitors of Anti-Metastic Agents in MDA-MB-231 Cells” Biophys. J. 2011, 100, 216.

3. Thangaraj, S.; Tsao, W. S.; Luo, Y. W.; Lee, Y. J.; Chang, C. F.; Lin C. C.; Uang, B. J.; Yu, C. C.; Guh, J. H.; Teng, C. M. “Total synthesis of moniliformediquinone and calanquinone A as potent inhibitors for breast cancer” Tetrahedron, 2011, 67, 6166

4. Tseng, T. H.; Chuang, S. K.; Hu, C. C.; Chang, C. F.; Huang, Y. C.; Lin, C. W.; Lee, Y. J. “The synthesis of morusin as a potent antitumor agent” Tetrahedron, 2010, 66, 1335. (First order for synthetic work)

5. Chang, C. F.; Huang, Y. C.; Huang, C.Y.; Lee, Y. J. “Total synthesis of (±)-armepavines and (±)-nuciferines from (2-nitroethenyl)benzene derivatives” Synthetic Communications, 2009, 3452.

6. Lee, Y. J., Chang, C. F., Lin, C. W., Tseng, T. H. “The First Total Synthesis of Morusin and Himanimide D as Arachidonate 5-lipoxygenase Inhibitor in Automated Docking” Biophys. J. 2009, 96, 86.

7. Yang, L. Y.; Chang, C. F.; Huang, Y. C.; Lee, Y. J.; Hu, C. C.; Tseng, T. H. “The first total synthesis of kynapcin-24 by palladium catalysis” Synthesis, 2009, 1175.

8. Chang, C. F.; Yang, L. Y.; Chang, S. W.; Fang, Y. T.; Lee, Y. J. “Total synthesis of demethylwelolactone and wedelolactone by Cu-mediate/Pd(0)-catalysis and oxidative-cyclization” Tetrahedron, 2008, 64, 3661.

9. Chang, C. F.; Lai, Z. C.; Lee, Y. J. “Total synthesis of (±)-camphorataimides and (±)-himanimides by NaBH4/Ni(OAc)2 or Zn/AcOH stereoselective reduction” Tetrahedron, 2008, 64, 4347.

Our lab has been focused on the identification and synthe-

sis of natural products with potential biological activities

that address current human health issues. The development

of new synthetic and biosynthetic methodologies continues

to play a crucial role in accessing compounds of interest,

while studying their underlying mechanism of action. With

this in mind, the goal of my research project is to develop

synthetic methods in the total synthesis of two unique

polyketide natural products. The first project focused on

the total synthesis of lyngbyaloside C by exploiting our

ether transfer protocol previously developed in our lab.

The second project relies on Taylor’s cyclopropanation

that targets the family of ambruticins. To date, I have suc-

cessfully completed the the total synthesis of lyngbyaloside

C as well as ambruticin J, which serve as a biosynthetic

putative intermediate to ambruticin F and S.

Project I: Total Synthesis and Structural Re-

assignment of Lyngbyaloside C

Lyngbyaloside C 1, a polyketide isolated from lyngbya

bouilloni, has recently grabbed the attention of the synthet-

ic community due to its structural moieties and interesting

biological activity (Figure 1). The structural features in-

clude a 14-membered glycosylated macrolide embedded

with a 2,6-cis tetrahydropyran (THP) and diene appendage.

Particularly, the unique tertiary ester moiety poses a signif-

icant synthetic challenge, which is currently tackled via a

ketene esterification. However, the competing ketene

polymerization significantly decreases the overall efficacy

of current methodologies.1 In addition, despite previous

synthetic efforts there is no general pathway towards the

(E,Z) diene side chain. Since lyngbyaloside C, occurs natu-

rally in both isomers, (E,Z) and (E,E), it was chosen as our

target. In addition, due to the fact that lyngbyaloside C

hasn’t been made previous, the total synthesis can confirm

its absolute structure.

Our retrosynthetic plan features a ring closing metathesis

(RCM) and an intermolecular ketene esterification between

a ketene precursor 3 and tertiary alcohol 4a to furnish the

macrolactone (Figure 1). We envisioned a β-ketothioester

3 as a ketene precursor that would circumvent thermal ke-

tene polymerization.2 The 1,3-syn-diol of 4a could be in-

stalled via regioselective ether transfer methodology.

Synthesis of 3 commenced from a Mukaiyama aldol reac-

tion3 followed by Sharpless kinetic resolution to provide

the enantiomeric rich (S)-allyl alcohol (Scheme 1). Meth-

anolysis followed by subsequent intramolecular hydride

delivery afforded the 1,3-anti diol, which was protected

with TES. Subsequently, the ester was converted to 3 via

reduction and Büchner–Curtius–Schlotterbeck reaction.

Synthesis of 4a started from Leighton’s crotylation of a

readily accessible aldehyde 11 to afford 13, which was then

elaborated into 14 by protection and Wittig olefination

(Scheme 2). Application of our ether transfer conditions

gave the 1,3-syn diol monoether 15 in good diastereoselec-

tiviy (10:1) without ICl addition to monosubstituted olefin.

After three facile functional group manipulations, 16 can be

prepared, which is then opened by the corresponding cu-

prate reagent generated in situ to yield 4a.

Figure 1 Retrosynthetic analysis of lyngbyaloside C

Scheme 1 Synthesis of β-keto-thioester 3

Scheme 2 Synthesis of tertiary alcohol 4a

With both coupling partners in hand, our efforts turned to

constructing the macrocyclic skeleton of the natural prod-

uct (Scheme 3). Under optimized conditions, the one-pot

scalable intermolecular ketene esterification was carried

out to furnish the tertiary ester and THP moieties in good

yield. The formation of 18 was achieved after two protec-

tions. The ensuing RCM advanced smoothly using Hov-

eyda-Grubb 2nd

generation catalyst in the presence of ben-

zoquinone (BQ), followed by regioselective hydrogenation

using Raney nickel to provide 19. Due to acidic sensitivity

of molecule, I decided to install the diene bromide using

cross-metathesis (CM) followed by Wittig reactions to pre-

vent the formation of double elimination product 24. Ac-

cordingly, primary alcohol 19 was eliminated under Grieco

conditions followed by removal of PMB. The critical gly-

cosylation proceeded in quantitative yield with 81% desired

β isomer using La(OTf)3 as a catalyst, which successfully

suppressed epimerization on C2’ on sugar moiety. Extension

of terminal alkene via CM and Menche’s optimized Wittig

reaction effectively elaborate the 23 as a mixture of Z/E

isomers. Lastly, global deprotection gave the nominal

lyngbyaloside C 1a as a mixture of Z/E isomers. Serendipi-

tously, I found that the mixture of isomers can be converted

to the pure Z 1a via DDQ-promoted selective decomposi-

tion. This methodology could potentially be used in the

preparation of Z vinyl or diene halide,2 which is currently

under investigation in our lab.

Scheme 3 Total synthesis of nominal lyngbyaloside C

Surprisingly, the appreciable discrepancies in both NMR

and specific optical rotations between our synthesized

compound and natural lyngbyaloside C required us to in-

vestigate its structural assignment. Consequently, two dia-

stereomers were made (Scheme 4). The synthesis of the

two corresponding tertiary alcohol 4b and 4c features a

Crimmin’s Ti-mediated asymmetric aldol reaction4 from a

fully functionalized aldehyde 25. Upon a comparison of

NMR data, 1b have similar irregularities with the nominal

structure 1a. In contrast, the characterization data for 1c

matched those of the natural product, concluding the abso-

lute configuration of lyngbyaloside C is ambiguously reas-

signed as structure 1c.

Scheme 4 Total synthesis of two diastereomers

Project II: Biomimetic Total Synthesis of Am-

bruticin F and S from Ambruticin J via tan-

dem reactions epoxidation/cyclization

The ambruticins are, a series of cyclopropane containing

polyketides produced by myxobacteria Polyangium cellu-

losum and Sporangium cellulosum. These molecules exhib-

it potent antifungal activity through the disruption of osmo-

regulatory systems. Their structures feature a congested

poly-olefinic skeleton, with an embedded trisubstituted

cyclopropane and two THP moieties. The ambruticins natu-

rally became synthetic targets due to their intriguing struc-

tures and potent antifungal activity. The biosynthetic path-

way proposed by Reeves et al.5 inspired us to develop a

biomimic synthetic route toward ambruticin F and am-

bruticin S. The route includes a tandem reaction sequence,

epoxidation/cyclization from the putative biosynthetic in-

termediate ambruticin J 2 and its C5 epimer respectively.

This synthetic tactic involves two main challenges. One is

the instability of ambruticin J under acidic condition, and

the other is the stereo-and-regio chemistry control of

expoxidation. In order to address these issues, we needed to

develop a scalable synthetic route toward ambruticin J. Our

synthetic plan focused on the assembly of three fragments

via Suzuki-Miyaura cross coupling and Julia-Kocienski

olefination (Figure 2).

The synthesis of sulfone 5, is depicted in Scheme 5. It

commenced with the preparation of benzyl ether 26 via

modification of Hanessian’s protocol.6 25 was converted to

Weinreb amide 27 via three steps functional manipulation,

which was then subjected to nucleophilic substitution to

afford ketone 28. The challenging (E)-trisubstituted olefin

29 then was installed via Comins’ triflation and Fürster’s

Iron-catalyzed cross coupling. Subsequently, the requisite

sulfone 5 was furnished via a known route.

Synthesis of 6 and 7 was described in Scheme 6. To pre-

pare pinacol borate ester 6, we applied our own cyclopro-

pantion methodology to synthesize the trisubstituted cyclo-

propane 31. The required homoallyl alcohol 30 was pre-

pared using Hall’s double-allylation,7 as single E isomer in

high yield with high enantiomeric purity. The resultant

terminal alkene was then elaborated smoothly into pinacol

borate 6 via Ohira-Bestmann rearrangement and hydrobo-

ration catalysed by Schwartz reagent. For the synthesis of

the vinyl iodide 7, a convergent pathway was implemented

with anionic dithiane chemistry.

Figure 2 Retrosynthetic analysis of ambruticin J 2

Scheme 5 Synthesis of requisite sulfone 5

With the three required fragments in hand, they were

assembled expeditiously via thallium-accelerated Suzuki

coupling and modified Julia-Koscienski reactions to cast

the linear structure. After global deprotection, the corre-

sponding triol 32 was converted to ambruticin J 2 via the

lactone intermediate 33 (Scheme 7).

Scheme 6 Synthesis of fragment 6 and 7

Scheme 7 Accomplishment of total synthesis of ambruticin

J 2

Summary

We accomplished a structural reassignment of lyngbyalo-

side C, and the total synthesis of the nominal structure and

two diastereomers. This scalable and robust synthetic route

features the formation of a tertiary ester and the THP moie-

ty via a one-pot intramolecular ketene esterification. In

addition, we applied a regioselective ether transfer reaction

in the synthesis of the tertiary alcohol and developed a

practical method in synthesizing the Z halo-diene. In the

second project, we developed a robust and convergent syn-

thetic route toward ambruticin J, which is highlighted a

convergent synthetic plan using Suzuki-Miyaura cross cou-

pling and Julia-Koscienski olefination. Finally, we were

able to scale up the trisubstituted cyclopropane using Hall’s

double allylation and our cyclopropanation methodology.

REFERENCES

(1) Chang, C. F., Stefan, E., Taylor, R. E. Chem. Eur. J. 2015, 21, 10681. (2) Booth, P. M., Fox, C. M. J., Ley, S. V., J. Chem. Soc. Perkin Trans. 1

1987, 121.

(3) Koh, M. J., Nguyen, T. T., Zhang, H., Schrock, R. R., Hoveyda, Amir,

Nature, 2016, 531, 459.

(4) Crimmins, M. T., Chaudhary, K. Org. Lett. 2000, 2, 775.

(5) Julien, B., Tian, Z-Q., Reid, R., Reeves, C. D. Chem. Biol. 2006, 13, 1677.

(6) Hanessian, S., Focken, T., Mi, S., Oza, R., Chen, B., Ritson, D.,

Beaudegnies, R. J. Org. Chem., 2010, 75, 5601. (7) Peng, F., Hall, D. G. J. Am. Chem. Soc., 2007, 129, 3070.

JeremyA.Eberle

384StepanHall 574.631.2861UniversityofNotreDame 812.786.7077NotreDame,IN46556 jeberle@nd.eduObjectives

• Chemistseekinganopportunityasaninorganic/organometallicchemisttoutilizemysyntheticandmanagementskills

EducationPh.D.inInorganicChemistry,UniversityofNotreDame,NotreDame,IN 2017

• GPA3.778/4.0B.S.inChemistry,IndianaUniversity-Southeast,NewAlbany,IN December2011

• GPA3.712/4.0

ResearchExperiencePh.D.Candidate,UniversityofNotreDame 2012-present

• Advisor:KennethHenderson,PhDo Synthesizedandcharacterized20+mono-anddinuclearorganometallic

moleculesonmgandgscalesforuseascatalystsinthecopolymerizationofcarbondioxideandepoxidestoformpolycarbonates.Requiredseveralmultistepsyntheses.

o Reactionsincludemetalations,saltmetatheses,condensations,oxidations,reductions,polymerizationcatalysis,andsolvothermalsyntheses.

o Managedandmentored2undergraduatestudentsand8visitingresearchersVisitingResearcher,UniversitätHeidelberg,Heidelberg,Germany Summer2015

• Advisor:MarkusEnders,PhDo Designed3newtetradentateligandsbasedonphosphinimino/phosphorane

moietiesforformingdinuclearmetalcomplexes.o Preparedmagnesium,zinc,andchromium(III)metalcomplexes.o Investigatedthetrimerizationofethyleneusingachromium(III)metalcomplex

UndergraduateResearcher,IndianaUniversity-Southeast • Advisor:ElaineHaub,PhD Fall2011–July2012

o SynthesisofcatalystsforuseinformationofBisphenolA-freepolycarbonates§ Synthesizedligandsforpreparingdinuclearzinccomplexestobeusedas

catalystsintheformationofBPA-freepolycarbonates.• Advisor:VictorWaingeh,PhD Summer2010–Spring2012

o ComputationalstudiesofquinolinederivativesbindingtoglycolyticenzymesinPlasmodiumfalciparumandHomosapiens

§ Investigatedprotein-ligandinteractionsbetweenglycolyticenzymesandquinoline-derivedanti-malarialdrugstoelucidatepossiblebindingsites,affinities,andthermodynamicsofbinding.

JeremyA.Eberle

Page2

SkillsandTechniques• ExperimentalTechniques:InertatmospheremanipulationutilizingSchlenkandglovebox

techniques• InstrumentExperienceandAnalysisTechniques:Multinuclear1Dand2DNuclear

MagneticResonance(NMR)spectroscopy,SingleCrystalandPowderX-rayDiffraction,massspectrometry,thermogravimetricanalysis,gaschromatography,gaschromatography-massspectrometry,infrared/UV-Visspectroscopy

• ComputerSkillsandSoftwareexperience:NMRspecificsoftware(ACD-NMRprocessor,Topspin),Crystallographyspecificsoftware(Mercury,Olex2,Platon,ShelXle,Shelxtl),Gaussian09,MicrosoftOffice(Word,Excel,PowerPoint)

AwardsandRecognition

• RudolphS.BotteiGraduateStudentTeachingAward March2015• OutstandingGraduateStudentTeachingAward March2013• OutstandingChemistryGraduateofIndianaUniversitySoutheast April2012

ProfessionalAffiliationsAmericanChemicalSociety August2011–presentLeadershipandCommunityServiceExperiencesLabSafetyCommittee,UniversityofNotreDame September2015–present

• Graduatestudentrepresentativeondepartmentallabsafetycommittee• Promotedsafelabpracticesandcompliancethroughstandardoperatingprocedures

OutreachCoordinator,ChemistryGraduateStudentOrganization February2016–present• OrganizeddepartmentalinauguralRelayforLifefundraiserteam• Expandedoutreachopportunitiesavailabletochemistrygraduatestudentswithinthe

NotreDameandSouthBendcommunitiesMentor,ParadigmShiftatND June2016–present

• MentoredmiddleandhighschoolstudentsinexploringSTEMtopics• Developedactivelearningtoolstobeusedinscienceoutreachinitiativestoimprove

scienceliteracyOrganizer,YouBetheChemistChallenge–St.JosephCounty,IN February2016–present

• JudgedSpring2016competitionwith32participants(5th-8thgrade)• CoordinatedwithChemicalEducationFoundation,DowChemicals,andlocalmiddle

schoolstoorganizeSpring2017localchallengeeventfornationwidecompetition• Organizedanddeployedgraduatestudentmentorstotutorandpreparestudentswith

challengestudymaterialPublications

• Oneopen-accessjournalarticleandninepresentations

JeremyA.EberleResearchStatement

Theuseofcarbondioxide(CO2)asaC1chemicalfeedstockhasgarneredmuchattention

inrecenttimes.1-5Notonlyisitnon-toxicandrelativelyinexpensive,itisalsoaproblematicgreenhousegas.In2012alone,globalemissionsofCO2fromfuelcombustionreached32Gt.6However,asCO2isoneofthemostthermodynamicallystableformsofcarbon,4thereisaneedtodevelopcatalyststhatareeffectiveatactivatingchemicaltransformations.Indeed,ithasbeendemonstratedthatCO2canbetransformedintocarbonmonoxide,methane,methanol,formate,carbonates,andureasusinghomogeneousorheterogeneouscatalyticsystems.7OfinteresttousisutilizingCO2toformpolymers,suchaspolycarbonates.Byreactingepoxides,suchaspropyleneoxide(PO)orcyclohexeneoxide(CHO),inthepresenceofacatalystunderaCO2atmosphere,theformationofthreeproductscanresult:polycarbonates,polyethers,andcycliccarbonatesasshowninScheme1.Inindustrialsettings,mostpolycarbonatesareformedfromcostlyandnon-renewablepetrochemicals.ByutilizingCO2,especiallyfromacarboncaptureandutilization(CCU)process,thecostofproductionwoulddecrease,awasteproductwouldbeconvertedtosomethingofvalue,andtheprocesswouldbe“greener”overall.Althoughtherehasbeensignificantimprovementsincatalystdesign,theyarenotyetindustriallyviable.Thus,thereisinterestinthedevelopmentofviablecatalystscapableofperformingwithhighactivityandselectivityundermildreactionconditions(i.e.1atmCO2,<100°C).

Scheme1.GeneralreactionofepoxideswithCO2.Formedproductsarepolycarbonate,polyether,andcycliccarbonate.

Thefocusofmyworkhasbeentodesign,synthesize,andtestnovelcatalyststoselectivelyandefficientlypreparepolycabonatesunderatlowpressuresofCO2(1atm).Buildingonourknowledgeofthereactionmechanism,wedesignedandtestedaseriesofligandframeworksincludingheteroscorpionates,salens,andRobsonmacrocyles.Thisallowsustoinvestigatetheeffectsmetalatomidentity(Mg,Zn,Al),metalcomplexgeometry(tetrahedral,octahedral,mono-ordinuclear),andanionicinitiator(halide,alkoxide,carboxylate,amide)oncatalyticactivity.

Informationgatheredfromthesestudiesledustodevelopanewligandfamilythat

featurestwo(phosphinimino/phosphorano)methanemoietiesconnectedbyaphenylenebridge(Scheme2).Theouterphosphoranearmscanbemodifiedwithawidevarietyofdonoratoms(O,S,N,Se,etc.)toproviderichcoordinationchemistrytoawiderangeofmetalcenters.Moreover,theligandcanactasaneutraluptoatetraanionic“carbene-like”donor,andhasthepotentialtoreadilygenerateflexiblebimetalliccomplexes.

RR

O CO2

RR

OO

O

ncatalyst RR

O

n

OO

R

O

+ +

R

JeremyA.Eberle–ResearchStatement Page2

Scheme2.Generalstructureofanewlydevelopedclassoftetradentateligand,H4NPPY.

References1 G.W.Coates,J.Chem.Soc.,DaltonTrans.,2002,467–475.2 D.J.Darensbourg,Chem.Rev.,2007,107,2388–2410.3 C.K.WilliamsandM.A.Hillmyer,PolymerRev.,2008,48,1–10.4 M.R.Kember,A.BuchardandC.K.Williams,Chem.Commun.,2011,47,141–163.5 X.-B.LuandD.J.Darensbourg,Chem.Soc.Rev.,2012,41,1462–1484.6 IEA,InternationalEnergyAgency,2014,1–136.7 T.Sakakura,J.-C.ChoiandH.Yasuda,Chem.Rev.,2007,107,2365–2387.

N NP

R RP

R R

P PY

RRYR

R

H4NPPY

rgraff@nd.edu

https://www.linkedin.com/in/robert-graff-19bab810b

PROFESSIONAL SUMMARY

►Experienced synthetic organic/polymer chemist with expertise controlled radical polymerization, emulsion

polymerization, analytical techniques and polymer structure-property relationships (>5 years).

►Industrial experience in the paints and coatings industry (1 year).

►A team-oriented leader and self-starter with excellent interpersonal and oral/written communication skills

(co-authored twelve research articles working with interdisciplinary research teams, three awarded

presentations and a proven record of mentoring and oral teaching experience).

►Passion for troubleshooting complex problems.

EDUCATION

Ph.D. Polymer Chemistry - University Of Notre Dame May 2017

Dissertation title: Regulating the Synthesis of Nanostructured Polymers by Atom Transfer Radical

Polymerization in Microemulsion.

Bachelor of Science in Chemistry- Grand Valley State University May 2012

PROFESSIONAL EXPERIENCE

Graduate Research Assistant August 2012 - Current

University Of Notre Dame Advisor: Professor Haifeng Gao

►Leveraged expertise in synthetic chemistry, design of experiments, effective communication and

collaboration with researchers resulting in twelve peer-reviewed journal articles and one book chapter.

►Initiated projects having clear objectives and approach, to improve polymer characterization accuracy,

resulting new methods to more completely characterize complex polymers.

► Exploited modern techniques in polymer and organic chemistry, utilizing materials including monomers,

synthetic polymers, dendrimers, initiators and additives and the methodologies of ATRP, RAFT, click

chemistry, encapsulation, and drug delivery to achieve target research goals and publish work.

►Applied skills in polymer synthesis, method development, and independent creative thinking to advance a

technique for better controlling the structure of branched polymers resulting in three published articles.

►Utilized strategic project management, through prioritization of tasks, to outline and reassess project goals,

maintain tight deadlines and drive project completion resulting in a consistent publication record.

Graduate Teaching Assistant

University Of Notre Dame

August 2012 - Current

►Independently led organic chemistry lecture, recitation, laboratory, review and office hour sessions.

►Utilized effective teaching methods, open and helpful communication and enthusiasm for the subject

material to achieve consistent top reviews from students and professors.

►Granted Kaneb Outstanding Teaching Assistant Award for excellence in teaching.

Quality Intern Sherwin-Williams Paint Co.

May 2011- July 2012

►Conducted statistical process capability studies of product fillers increasing efficiency & cost savings.

►Effectively communicated with team members across all levels in order to drive projects to completion.

LEADERSHIP AND SERVICE

►Mentored (high school, undergraduate, and junior graduate students) on research projects encompassing

organic/polymer synthesis, purification, and characterization.

► Invited by previous professors at Grand Valley State University to present academic research, mentor

current undergraduate students, recruit for Notre Dame and discuss potential career pathways.

TECHNICAL SKILLS

►Polymer synthesis and characterization: FRP, ATRP, RAFT, Click Polymerization

►Small molecule/monomer synthesis and characterization

►Emulsion formulation and polymerization: Emulsion, Miniemulsion, Microemulsion

►Instrumentation: SEC, SEC-MALS, DLS, NMR, FT-IR, LC-MS, ESI-MS, GC-MS, GC-FID, UV-VIS

►Repair and maintenance: HPLC-SEC, GC, Small Lab Equipment

231-740-7502

707 Travers Circle, Mishawaka, IN 46545

Robert William Graff

Robert William Graff rgraff@nd.edu

231-740-7502

Mishawaka, IN 46545

707 Travers Circle

Synthesis, characterization and applications of branched polymers

My research has targeted the synthesis, characterization and application of branched polymers with

highly controlled structures. Branched polymers show a number of interesting properties resulting from

their globular architecture including core-shell structure and tunable size, as well as excellent flow and

processing properties at high molecular weight. This globular structure also leads to a high concentration

of reactive end-groups which facilitates the customization of properties for a wide range of applications.

These polymers, with properly incorporated functionalities, have attracted the commercial use as

specialty additives in coatings, resins, and other advanced applications such as carriers for catalytic

species and nanomedicines.

Synthesis of branched polymers with highly controlled structures using confined space

My peers and I developed two synthetic strategies to produce nanostructured branched polymers with

highly controlled structures. The first strategy, which I led, utilized a confined nanospace via a

microemulsion. This inhibited inter-polymer coupling reactions that normally led to an uncontrolled

structure. By inhibiting these

reactions, the resulting nanostructured

polymers had controllable molecular

weights and narrow molecular weight

distributions while in a single pot

reaction, which was previously not

possible. Further investigation of this

method has shown it to be effective

over a broad range of compositions,

sizes and molecular weights. In

addition to leading the synthetic work,

I also developed a robust strategy to

accurately characterize these complex

polymers via a combination of light

scattering, chromatography and

nuclear magnetic resonance

experiments. My early work on this

characterization method remains our

research group’s primary strategy for the characterization of complex branched polymers.

Resulting publications: Macromolecules 48 (7), 2118-2126, Polymer Chemistry 6 (37), 6739-6745

Synthesis of branched polymers with low polydispersity via living chain growth mechanism

The second strategy my peers and I have developed relies on a much different approach and utilized a

different type of chemistry. This route made use of copper catalyzed azide-alkyne click reactions

100 1000 10000 100000 1000000

0.0

0.5

1.0

Molecular Weight

Solution polymerization

broad molecular weight

distribution

Microemulsion polymerization

narrow molecular

weight distribution

Mw/Mn = 9.3

Mw/Mn = 1.3

Scheme 1. Comparison of the molecular weight distribution of

hyperbranched polymers synthesized in conventional solution

polymerization versus a confined space.

between multi-function monomers to form highly branched polymers. The breakthrough of this work

came from two key insights: that each reaction required a copper catalyst and that the polymer could act

as a ligand. Because the polymer could bind the catalyst, it localized on the growing polymers and only

allowed reactions to occur between polymer and monomer, thus transforming the polymerization

mechanism to a living chain growth. This resulted in the inhibition of monomer to monomer reactions,

exclusively allowing polymer to monomer reactions which led to a highly controlled polymer structure.

My role in this work was primarily on the characterization efforts, which allowed me to utilize my

previous project’s expertise. The precise characterization of the polymerization’s kinetics and final

polymer structure allowed us to elucidate the complex mechanism underlying the polymerization.

Resulting publications: Angewandte Chemie 127 (26), 7741-7745, Journal of Polymer Science Part A:

Polymer Chemistry 53 (2), 239-248, Macromolecules 49 (3), 760-766, Macromolecules 49 (15), 5342-

5349, Polymer Chemistry 7 (35), 5512-5517

Study of the applications and properties of branched polymers

Although this summary has primarily focused on the synthetic breakthroughs of our research, we have

also made significant efforts on exploring the applications and properties of the materials generated.

These efforts include exploring their usage in catalysis, drug delivery, water-oil separation and studying

their properties from glass transition temperatures to degradability and active molecule encapsulation.

This success was not only due to my personal research efforts but also the development of good working

relationships and effective collaborations, which allowed me to contribute on a wide range of projects.

This research has resulted in twelve peer-reviewed journal articles, and has improved on previous efforts

to easily synthesize and characterize branched polymers with controlled structures and furthered the

understanding of their potential applications and properties.

Resulting publications: Polymer 72, 361-367, ACS applied materials & interfaces 7 (8), 4969-4978,

Macromolecules 49 (12), 4416-4422, Macromolecular rapid communications 36 (23), 2076-2082,

Chemical Communications 51 (93), 16710-16713

Scheme 2. Synthesis of hyperbranched polymers with low polydispersity and a high degree of branching

by chain-growth CuAAC polymerization.

Eric Carl Hansen ericchansen@gmail.com · ehansen3@nd.edu · (616) 970-4216

www.nd.edu/~ehansen3 330 West Colfax Ave www.github.com/ericchansen Apartment 214 www.linkedin.com/in/ericcarlhansen South Bend, IN 46601

PROFESSIONAL SUMMARY Computational chemist with expertise in molecular mechanics and quantum mechanics methods used

to study reaction mechanisms and asymmetric catalysis. Designed and developed software from to optimize force fields to model advanced potential energy

surfaces and transition states. Significant experience in teaching as well as dedication to improving teaching technique. Team-oriented self-starter and group leader with excellent interpersonal and oral/written

communication skills. Passion for developing and collaborating on software for scientific research and data analysis.

EDUCATION Ph.D. Computational Chemistry · University of Notre Dame Expected May 2017 Development of Quantum Guided Molecular Mechanics (Q2MM), a tool for optimizing force fields for advanced potential energy surfaces and reaction specific transition state force fields (TSFF), and applying TSFFs to screen ligands for asymmetric catalysis Bachelor of Science in Chemistry · Grand Valley State University Frederick Meijer Honors College

May 2012

PROFESSIONAL EXPERIENCE Graduate Research Assistant August 2012 – Current University of Notre Dame Advisor: Olaf Wiest Utilized experience in computational organic chemistry to study reaction mechanisms and rapidly

predict ligands for efficient asymmetric catalysis. Developed software for the optimization of molecular mechanics parameters using quantum

mechanically derived data. Center for Research Computing Award for Computational Sciences and Visualization for

development and use of software for parallel computing. Graduate Teaching Assistant August 2012 – Current University of Notre Dame Independently led classes in general chemistry, including office hours and review sessions, as well

as labs in analytical chemistry. Completed several workshops for improving teaching skills and was awarded the Kaneb Center

Striving for Excellence in Teaching Certificate (2016), Outstanding Graduate Student Teaching Award (2014) and Graduate Assistance in Areas of National Need (GAANN) Teaching Fellow (2014 – present).

LEADERSHIP AND SERVICE Webmaster (2016 – present), mentor (2013 – present) and member (2013 – present) of the Chemistry

Graduate Student Organization, a group advocating professional development and departmental service.

Vice president (2016 – present), treasurer (2015) and board member (2014) of the AIDS Ministries / AIDS Assist of Northern Indiana, a non-profit organization that provides services to those affected by HIV/AIDS (www.aidsministries.org).

Recruiting and mentoring undergraduates at Grand Valley State University. TECHNICAL SKILLS

Chemistry skills: Reaction mechanisms, physical chemistry, statistical and quantum mechanics General languages: Python, Fortran, Git, SQL, R, HTML Chemistry software: Gaussian, Schrödinger, Jaguar, MacroModel, Amber, Tinker

Eric Hansen ehansen3@nd.edu (616) 970-4216

330 West Colfax Ave Apartment 214

South Bend, IN 46601

Designing ligands for asymmetric catalysis Experimentally screening ligands for asymmetric catalysis can be costly, and typically requires specialized high-throughput machinery and hours of a bench chemist’s time to operate the equipment. Furthermore, the discovery of an efficient ligand is commonly the result of a trial-and-error process, which leaves us with little understanding of why certain ligands perform better than others. The primary focus of my graduate work has been designing and developing the Quantum to Molecular Mechanics (Q2MM) method, which can be used to computationally predict the performance of ligands in asymmetric catalysis, while simultaneously providing an atomistic view of how they achieve their selectivity, solving the problems mentioned above.

Q2MM methodology and application to predicting enantioselectivity To predict the ligands that impart the best selectivity, we use Q2MM to develop a reaction specific transition state force field (TSFF). Upon identifying the stereoselecting step in the mechanism, typically through a combination of experimental and computational efforts, we calculate high level ab initio reference data for a model of the corresponding transition state (TS). The data is then used to parameterize a TSFF following the outline shown in Scheme 1. Unique to our method, we represent the quantum mechanical (QM) TS as an energetic minimum on the FF potential energy surface. This allows us to use our TSFFs with standard molecular mechanics (MM) engines to sample extensively around the TS, which is critical for making accurate predictions. We can then predict the selectivity by comparing the Boltzmann distributions of the two diastereomeric TSs leading to opposite enantiomer products. Generation of the reference data and subsequent optimization of the TSFF is the most time consuming process in the Q2MM method. However, with the TSFF in hand, it can rapidly be applied to predict the selectivity of thousands of ligands for a variety of substrates within hours, making it an extremely effective tool for rapid reaction optimization.

Development of Q2MM I designed and developed the Q2MM Python library from the ground up, and I have also made it open source and publicly available on my GitHub, www.github.com/ericchansen/q2mm. The library contains all the tools necessary to produce a TSFF from ab initio calculations. Reference data can be loaded into Q2MM directly from the output of Gaussian or Jaguar, but it is also possible to use other sources of reference data, e.g. experimental measurements, by using a standardized input format. Q2MM optimizes MacroModel FFs, but work to directly interface with Amber is nearing completion. The software that I developed has gained widespread use throughout the Wiest laboratory at Notre Dame, as well as with several other labs across the globe, namely the pharmaceutical company AstraZeneca, who applies Q2MM in their own ligand screening process. I train and mentor these groups in the usage of Q2MM and continue to guide the way for future developments.

Scheme 1. Flowchart for the iterative optimization of a Q2MM FF.

Q2MM as a tool for mechanistic studies Unidirectional catalyst that imparts alternating chirality

Q2MM TSFFs can also be used to study reactions mechanisms that traditional QM methods cannot access due to the size and flexibility of the system of interest. Cyclic oligopeptides consisting of only a few amino acids are challenging to synthesize. However, they can be formed using turn-inducing amino acids, such as dehydro-phenylalanine and then hydrogenated post cyclization to form the desired product. Vy Dong’s experimental group at the University of California-Irvine observed that the anti-product is formed almost exclusively, as shown in Scheme 2. In collaboration with their group, we used Q2MM to gain a better understanding of the underlying mechanism and quantitatively predict the alternating pattern observed in the resulting product distribution.

Le, D.; Hansen, E.; Wiest, O.; Dong, V. Unidirectional Rh Catalyzed Hydrogenation of Cyclic Oligo-Dehydropeptides. In preparation.

Diverse applications of Q2MM

NNR3

[Pd]

R2R1 R2

Nu

R1

Palladium-mediated allylation

O2OsO

ON*

Osmium tetroxide catalyzed asymmetric dihydroxylation of alkenes

ROOC NH

OR

[Rh+]

H2

ROOC NH

OR

Rhodium catalyzed hydrogenation of enamides

R R

O*

R R

OH

H2

Ruthenium catalyzed hydrogenation of ketones

RuH

H NP

NPOH

HO

Scheme 3. Subset of the reactions studied using the Q2MM methodology. The Q2MM method has been applied to a wide variety of reactions, such as palladium-mediated allylation, osmium tetroxide catalyzed asymmetric dihydroxylation of alkenes, ruthenium catalyzed hydrogenation of ketones and palladium-catalyzed C-C coupling between unsaturated halides and activated alkenes in the presence of bases. Currently, it is being used to parameterize TSFFs for palladium allyl aminations, an iridium catalyzed hydrogenation of imines and the palladium catalyzed redox relay Heck arylation. Q2MM has also been used to parameterize ground state FFs for systems with complicated potential energy surfaces, such as sulfonamides, and it is currently being applied to optimize a FF for ferrocene, which will allow us to expand our current ligand library used for screening. We are also applying Q2MM to study enzymes, in this case the mechanism behind the action of HMG-CoA reductase. Hansen, E.; Rosales, A.; Tutkowski, B.; Norrby, P.-O.; Wiest, O. Prediction of Stereochemistry using Q2MM. Acc. Chem. Res., 2016, 49, 996 – 1005. Hansen, E.; Limé, E.; Norrby, P.-O.; Wiest, O. Anomeric Effects in Sulfamides. J. Phys. Chem. A, 2016, 120, 3677 – 3682.

cat. [Rh(I)]

HNNH

HNNHNH

O

OO

O

Ph

Ph Ph

Ph

O

HNNH

HNNHNH

O

OO

O

Ph

Ph Ph

Ph

O

Ph2P PPh2

HNNH

HNNHNH

O

OO

OPh

Ph Ph

Ph

O

Experimental > 20 : 1Predicted 65 :1

Scheme 2. The rhodium catalyst moves around the oligopeptide unidirectionally and imparts alternating chirality at each forming stereogenic center. Our Q2MM TSFF was used to extensively sample the diastereomeric TSs and quantitatively predict the preference for the experimentally observed anti-product, as well as provide an atomistic view of the reaction, which cannot be obtained using pure experiments.

Jacob B. Hoffman 211 Radiation Laboratory • South Bend, Indiana 46556 • (419)-961-5818 • jhoffm10@nd.edu

SUMMARY OF QUALIFCATIONS

Laboratory and Technical Skills: During my graduate studies I mastered the synthesis of semiconductor nanoparticles, assembly of nanomaterials in the solid state, steady state and time resolved spectroscopy techniques, and construction of liquid junction and solid state photovoltaics. I was also responsible for the maintenance of laboratory instrumentation including a femtosecond transient absorption system, steady state spectroscopy equipment, and nanoparticle synthesis setups.

Leadership and Communication: I served as the laboratory safety officer where I managed the implementation of a new departmental safety program within the research building, maintained laboratory cleanliness, and documented safety training. Additionally, I mentored and trained several undergraduate and masters students resulting in publications. I honed my communication skills through attending several national and international research conferences and presenting my research through oral and poster presentations.

EDUCATION

University of Notre Dame Notre Dame, IN Ph.D., Physical Chemistry Expected May 2017 Thesis Title: Utilizing Energy and Charge Carrier Transfer in Nanostructure Assemblies.

Heidelberg University Tiffin, OH B.S., Chemistry and Mathematics May, 2012 Academic honors: Honors diploma, Magna Cum Laude Topic: Computation of Electron Hole Recombination Probability in Quantum Dots.

RESEARCH EXPERIENCE

University of Notre Dame Notre Dame, IN

Ph.D. Candidate, Department of Chemistry and Biochemistry

Investigated energy transfer mechanisms in quantum dot–dye assemblies discovering alternative strategies for light harvesting.

Examined energy transfer interactions in quantum dot solids illustrating the importance of surface chemistry in energy transfer cascades.

Developed a new method for perovskite deposition through nanoparticle annealing and constructed solid state photovoltaics using CsPbBr3 and CsPbI3 perovskites.

SELECTED PUBLICATIONS (2/5) • PRESENTATIONS (1/6)

Hoffman, J.B.; Schleper, A. L.; Kamat, P. V. Transformation of Sintered CsPbBr3 Nanocrystals to Cubic CsPbI3 and Gradient CsPbBrxI3-x through Halide Exchange. J. Am. Chem. Soc. 2016, 138 (27), 8603–8611

Hoffman, J.B.; Choi, H.; Kamat, P.V. Size Dependent Energy Transfer Pathways in CdSe Quantum Dot-Squaraine Light Harvesting Assemblies: Förster versus Dexter. J. Phys. Chem. C., 2014, 116(32), 18453-18461

Hoffman, J.B; Kamat, P.V. Transformation of CsPbBr3 to Cubic CsPbI3 and Gradient CsPbBrxI3-x through Halide Exchange. 2nd International Conference on Perovskite Solar Cells and Optoelectronics, September 28th, 2016. (contributed talk)

TECHNICAL SKILLS

Nanoparticle Synthesis and Surface Chemistry: colloidal semiconductor quantum dots, perovskite quantum dots, organic surface modification, solid state deposition Time Resolved and Steady State Spectroscopy: UV-visible absorbance (in situ heating), photoluminescence (solution and solid state), emission lifetime, nanosecond flash photolysis, femtosecond transient absorption, X-ray photoelectron spectroscopy (XPS), X-ray diffraction spectroscopy (XRD) Solar cell assembly and characterization: mesoporous TiO2 film deposition, perovskite deposition, spin and drop casting, metal evaporation, photovoltaic testing and characterization Other: scanning electron microscopy (SEM), glove box, profilometry, thin layer chromatography (TLC), electrophoretic deposition (EPD)

PROFESSIONAL ACTIVITIES

Computer Skills: Mathematica, Origin Pro, Adobe Illustrator and Photoshop, Microsoft Office, Java Professional Affiliations: American Chemical Society Honors and Awards: Eilers Graduate Student Fellowship for Energy Related Research (University of Notre Dame, 2016), National Science Foundation Research Experience for Undergraduates (2011) Student activities: Peer reviewer for ACS journals, Research Experience for High School Teachers Mentor, University of Notre Dame science fair judge, Siemens Competition students laboratory tour guide

Jacob Hoffman – Research Summary

Effective coupling and ordered assembly of nanomaterials is beneficial for tailoring the design of both next generation photovoltaics and light emitting diodes (LEDs). There are two main avenues to accomplish this task, charge transfer and energy transfer.1,2 Charge transfer requires close proximity of the interacting materials and energetically favorable conditions between the potential donor and acceptor.3–5 In energy transfer, excitation is transferred from an excited state donor to a ground state acceptor, usually through dipole-dipole coupling called resonance energy transfer (RET).2,6–8 My research has focused on studying energy and charge transfer in two promising materials, semiconductor quantum dots (QDs) and cesium based perovskites. QDs are nanoscale semiconductor particles that possess highly variable optical properties that change with nanoparticle size.1,3 These changes are due to the quantum confinement effect, which occurs when nanoparticle dimensions approach the Bohr-exciton radius.9 My research involving QDs focused on the utilization of CdSe QDs as an energy transfer donor in two circumstances. First, energy transfer mechanisms between CdSe QDs and a near infrared squaraine dye used to link QDs to TiO2 were investigated as a function of QD size.10 Surprisingly, the observed energy transfer increased as size decreased. The unexpected increase in energy transfer was attributed to Dexter energy transfer (DET), an alternative energy transfer mechanism based on simultaneous electron exchange. This discovery could be utilized in dye-QD couples to expand the spectral range of light harvesting in dye sensitized solar cells.2,6 Second, the effects of CdSe QD surface chemistry on RET were investigated in CdSe QD films. The results illustrated the need to consider how deposition methods impact QD surface chemistry when considering QDs as energy transfer donors. Lead halide perovskites are a family of materials that have rapidly gained research interest as a light harvester, due to possessing many favorable properties for charge transport.11–13 In my research, I developed a new method for the deposition of cesium bromide based perovskites through thermal annealing of CsPbBr3 nanoparticles.14 Such films were readily shown to participate in Br- to I- halide exchange, allowing low temperature formation of cubic CsPbI3. Additionally, halide exchange provided a route to produce gradient structure CsPbBrxI3-x hybrids. These films exhibited ultrafast hole transfer from Br- rich to I- rich film regions, a property that can enhance charge carrier separation in CsPbX3 (X= Br-,I-) photovoltaics.

References

(1) Kamat, P. V. J. Phys. Chem. C 2008, 112 (48), 18737–18753. (2) Rogach, A. L.; Klar, T. A.; Lupton, J. M.; Meijerink, A.; Feldmann, J. J. Mater. Chem. 2009, 19 (9), 1208–1221. (3) Carey, G. H.; Abdelhady, A. L.; Ning, Z.; Thon, S. M.; Bakr, O. M.; Sargent, E. H. Chem. Rev. 2015, 115 (23), 12732–12763. (4) Tvrdy, K.; Frantsuzov, P. A.; Kamat, P. V. Proc. Natl. Acad. Sci. U. S. A. 2011, 108 (1), 29–34. (5) Hines, D. A.; Forrest, R. P.; Corcelli, S. a.; Kamat, P. V. J. Phys. Chem. B 2015, 119 (24), 7439–7446. (6) Turro, N. J.; Ramamurthy, V.; Scaiano, J. C. Modern Molecular Photochemistry of Organic Molecules, 1st ed.; University Science Books,

2010. (7) Lakowicz, J. R. In Principles of Fluorescence Spectroscopy; Springer US: Boston, MA, 2006. (8) Förster, T. Ann. der Phys. 1948, 4a, 55–75. (9) Alivisatos, A. P. J. Phys. Chem. 1996, 3654 (95), 13226–13239. (10) Hoffman, J. B.; Choi, H.; Kamat, P. V. J. Phys. Chem. C 2014, 118 (32), 18453−18461. (11) Manser, J. S.; Christians, J. A.; Kamat, P. V. Chem. Rev. 2016, DOI:10.1021/acs.chemrev.6b00136. (12) Xing, G.; Mathews, N.; Sun, S.; Lim, S. S.; Lam, Y. M.; Grätzel, M.; Mhaisalkar, S.; Sum, T. C. Science 2013, 342 (6156), 344–347. (13) Brenner, T. M.; Egger, D. A.; Kronik, L.; Hodes, G.; Cahen, D. Nat. Rev. Mater. 2016, 1 (1), 15007. (14) Hoffman, J.; Schleper, A. L.; Kamat, P. V. J. Am. Chem. Soc. 2016, 138 (27), 8603–8611.

Paul Johns

251 Nieuwland Science Hall, Notre Dame, IN 46556–5670 • (574) 222–5251 • pjohns@alumni.nd.edu

PROFESSIONAL SUMMARY • Physical chemist with 4 years of experience in nanoscience, plasmonics, Raman, spectroscopy, and computer

simulation using COMSOL Multiphysics, Python, and MATLAB • Expertise in ultrafast pump-probe spectroscopy and finite element method calculations focused on surface

plasmon polariton propagation in nanostructures • Published 2 first author and 2 co-author publications in high-impact journals

EDUCATION UNIVERSITY OF NOTRE DAME Notre Dame, IN Ph.D. Candidate, Physical Chemistry Anticipated on or before May 2017

• Dissertation: Surface Plasmon Propagation in Gold Nanostructures Advisor: Dr. Gregory V. Hartland SAINT FRANCIS UNIVERSITY Loretto, PA Bachelor of Science in Chemistry, minors in Mathematics and Physics May 2007

• Graduated Magna Cum Laude, Honors Program Graduate • Thesis: Quantum Mechanical/Molecular Mechanical Simulations of the Fluorescence Quenching of H-Type

Homodimers of Fluorescein and Tetramethyl Rhodamine Advisor: Dr. Pedro L. Muíño

EXPERIENCE UNIVERSITY OF NOTRE DAME Notre Dame, IN Doctoral Researcher, Physical Chemistry September 2007–May 2008; January 2013–Present

• Developed procedures to model surface plasmon propagation in nanostructures in two-dimensional and three-dimensional models

• Designed and setup a pump/probe transient absorption spectroscopy system • Taught Physical Chemistry II as the primary instructor, resulting in student reviews in the top decile of the

university; TA for Analytical Chemistry, Chemistry Across the Periodic Table, and Chemical Principles • Trained other graduate students in the use of laboratory equipment • Wrote programs in LabVIEW, Igor Pro, MATLAB, Python, and Java to automate data acquisition and

processing SAINT FRANCIS UNIVERSITY Loretto, PA Visiting Laboratory Instructor August 2011–May 2012

• Developed laboratory experiments for the General Chemistry Laboratory • Taught Physical Chemistry I Laboratory, Organic Chemistry I & II Laboratory, and General Chemistry

Laboratory to a total of 69 students, resulting in positive student reviews CHEMIMAGE, CORP. Johnstown, PA Applications Scientist Intern May 2004–July 2005

• Validated CI Print Macroscopic Chemical Imaging System™ for detection of latent and patent fingerprints • Assisted in developing a Raman chemical database for identification purposes which was incorporated into

the Falcon Molecular Chemical Imaging System™ database

TECHNICAL SKILLS Pump/probe spectroscopy, transient absorption spectroscopy, class 100 cleanroom training, Airco FC-1800 electron-beam evaporator for metal deposition, lasers, oscilloscopes, photodetectors, instrument maintenance, general optics, plasmonics, finite element modeling, COMSOL Multiphysics, LabVIEW, MATLAB, Mathematica, Igor Pro, OriginPro, Python, Java, Microsoft Office

SELECTED AWARDS AND HONORS Graduate Assistance in Areas of National Need (GAANN) Teaching Fellow, University of Notre Dame, 2014–

Present Advanced Teaching Scholar, Kaneb Center for Teaching and Learning, University of Notre Dame, 2015 Barry M. Goldwater Scholar, Barry M. Goldwater Scholarship and Excellence in Education Program, 2006

PROFESSIONAL ORGANIZATIONS SPIE—The International Society for Optical Engineering, Graduate Student Member 2015–Present American Chemical Society, Graduate Student Member 2005–Present American Association for the Advancement of Science, Graduate Student Member 2007–Present

P. Johns, 1/2

RESEARCH SUMMARY FOR PAUL JOHNS

Nanoscience is a widely researched area of science that is quickly growing in popularity. One of the areas that has interested me is the use of surface plasmon polaritons in nanostructures as waveguides. Surface plasmon polaritons are collective oscillations of free electrons that occur between a noble metal surface (most commonly gold or silver) and a dielectric. These oscillations propagate down the length of a nanostructure until they are damped away. Nanostructures with sufficiently long propagation lengths and minimal damping can be used as waveguides. Nanoscale waveguides can be used for nanocircuitry, logic functions, sensors, and other uses. My research has focused on how plasmon propagation is affected by defects either in the nanostructure or in the supporting substrate. Many studies involving plasmon propagation have neglected the effects of the underlying substrate, however, taking this into account, provides a more realistic depiction of plasmon propagation. I have studied these effects through femtosecond pump-probe spectroscopy combined with finite element method (FEM) calculations from COMSOL Multiphysics. It can also be difficult to control the shapes and characteristics of the plasmon modes. My research suggests ways of controlling the modes to yield desirable characteristics.

NANOBAR SUBSTRATE DEFECTS In my research, a pump-probe spectroscopy technique was used to image the surface plasmon polariton

propagation through gold nanobars (nanowires with rectangular cross-sections) on a substrate when defects were present either in the substrate or in the nanobar itself. In this technique, the pump laser launches the plasmon mode, and the probe laser is used to interrogate the sample for the intensity of the mode. The probe laser is raster scanned over an area larger than the nanobar to create an image of the plasmon propagation. This image provides information on the intensity of the mode and therefore the propagation length of the mode, but does not provide information on which mode(s) is excited or how each mode is affected by defects. To overcome this difficulty, information on the modes was obtained through FEM calculations.

FEM calculations were performed using COMSOL Multiphysics to solve numerically for solutions to the electric wave equation around the nanobars to determine the propagating mode shapes and to visualize how the modes are affected by defects. This is done by performing a mode analysis at the face of the nanobar to determine the supported plasmon modes. The desired mode is selected and used as the excitation for a three-dimensional calculation. There are two primary modes that propagate in these structures: bound and leaky. The bound mode propagates primarily at the glass/gold interface and the leaky mode propagates primarily at the air/gold interface. To visualize the modes, the norm of the electric field is plotted.

When investigating substrate defects, gold nanobars were suspended over trenches cut into a glass substrate. Experiments showed two scenarios when measuring the characteristic propagation length before the trench and after the trench: either the characteristic propagation lengths were the same on either side of the trench, or the propagation length was shorter on the far side of the trench. Initially, this seemed problematic since it was expected that the same effects would be observed for all wires. The calculations showed that in the experiments both the bound and leaky modes were excited by the pump laser. At the cut, the bound mode no longer had a medium to propagate through, so the bound mode dissipated. The leaky mode converted in the area over the trench to a mode that surrounded the nanobar. The leaky mode was then

reconstituted on the other side of the trench. In the experiments, when measuring the far side of the trench, the leaky mode was always the one being measured. On the near side of the trench, either the leaky or the bound mode could be measured depending on which one has the longer characteristic propagation length. This is possible since the specific geometry has a significant impact on which mode has the longer propagation length. The fields and transformations are shown pictorially in Figure 1.

DEFECTS IN NANOBARS Defects can not only occur in the substrate but also in the nanostructures themselves. To investigate these

kind of defects and how the plasmon modes are affected, gold nanobars on a substrate were cut using FIB milling and then interrogated with the pump-probe spectroscopy technique. The experiments showed a large decrease in intensity of the plasmon as it propagated through the cut. This is evident in the lower left panel of Figure 2.

Figure 1. The supported propagating plasmon modes in a nanobar suspended over a trench. Bound and leaky modes are present on the excitation side. The bound mode is lost over the trench. The leaky mode is transformed over the trench and reconstituted on the far side.

P. Johns, 2/2

Both the bound and leaky modes were simulated and the propagation through the gap was studied. Larger losses were sustained at small gap sizes due to the excitation of localized surface plasmon resonance associated with the gap. The right side of Figure 2 shows the FEM calculated bound mode with an excited resonance at the gap in the nanobar. Experimentally, the cuts are not perfectly straight, but are wider at the top of the bars than at the bottom due to limitations of the FIB milling. Because of the gap discrepancy between the top and the bottom of the nanobar, the leaky mode does not have as much of the gold nanostructure supporting its propagation. This causes the leaky mode to be more heavily damped than the bound mode.

To summarize this work, combining the experiments and the computations for these two types of defects, I have demonstrated the loss of modes and mode conversions, which suggests a method to control which modes propagate through nanostructures. This work has resulted in two publications: the nanobars suspended over trenches was published in Nanoscale1 and the cut nanobars was published in ACS Nano2. The information from this project could be used in designing better waveguides or in controlling the propagating plasmonic modes of current waveguides.

FUNDAMENTAL PROPERTIES OF PLASMONICS During the previous two studies, some fundamental properties of plasmonics were observed that have not

been elucidated in the literature. I am currently investigating the localization of the plasmon mode and how that localization contributes to radiative losses and heating losses sustained by the plasmon. Plasmons propagating in nanowires with small diameters tend to have shorter propagation lengths than those that propagate in nanowires with larger diameters. This is due to two factors: plasmon energy localization inside the nanowire compared to outside the nanowire and the ability of the leaky mode to couple into the substrate. Noble metals intrinsically damp plasmons due to having an imaginary component to their refractive indices. Surrounding media, whether air, water, oil, or glass, typically do not have an imaginary component to their refractive indices and so contribute less to the overall damping. Using FEM calculations, I have shown that for the bound mode, the ratio of energy localized inside a nanowire to energy localized external to the nanowire is higher with small diameter wires than with large diameter wires. Since a larger portion of the energy is localized inside the nanowire, the damping sustained is greater resulting in a shorter propagation length.

The leaky mode has an additional loss mechanism. This mode primarily propagates at the gold/air interface. However, it can also couple to the supporting substrate depending on the size of the nanowire. At small sizes, the leaky mode nearly completely surrounds the nanowire, and is able to couple into modes that are supported by the glass substrate. This can be seen in Figure 3 for the nanowire with a width of 250 nm as the two tails coming off of the nanostructure. This propagation of the leaky mode through away from the nanowire causes a greater damping than a

mode that is propagating through along the nanowire. As the width increases, the leaky mode is distanced further from the glass substrate, resulting in a weaker coupling to the substrate, and an increased propagation length. This can be seen above for the nanowires with widths of 550 nm and 2000 nm. These results are in preparation for publication.

In summary, my research has focused on the use of ultrafast spectroscopy and finite element method modeling of gold nanostructures to understand the oscillation and propagation of free electrons in those structures in the form of propagating plasmon modes. This has led to a better understanding of ways to control the propagating modes in nanostructures and potential loss mechanisms that need to be considered when designing plasmonic devices.

1. Johns, P.; Yu, K.; Devadas, M. S.; Li, Z.; Major, T. A.; Hartland, G. V., Effect of Substrate Discontinuities on the Propagating Surface Plasmon Polariton Modes in Gold Nanobars. Nanoscale 2014, 6, 14289-96. 2. Johns, P.; Yu, K.; Devadas, M. S.; Hartland, G. V., Role of Resonances in the Transmission of Surface Plasmon Polaritons between Nanostructures. ACS Nano 2016, 10, 3375-81.

Figure 2. SEM image of a cut nanobar (left top). Experimental plasmon intensity with excitation from the left (left bottom), loss in intensity is observed at each cut. FEM calculation of the bound mode as it propagates through a cut in the nanobar (right).

Figure 3. Coupling of the leaky mode to the substrate is observed for small sized wires (like 250 nm) but is not evident for large sized wires (like 2000 nm).

KAYLA M. LEWIS (574) 904-0869 klewis9@nd.edu www.linkedin.com/in/kayla-m-lewis

QUALIFICIATIONS

Independent chemist with 5 years of experience synthesizing organometallic geminal dianionic compounds

Organometallic chemist with background in s-block metals and air and moisture sensitive compounds

Multidisciplinary research experience with experience in inorganic, organic, and analytical environments.

Skills: Inert atmosphere, Schlenk techniques, NMR spectroscopy, organic synthesis, chromatography EDUCATION UNIVERSITY OF NOTRE DAME Notre Dame, IN

Ph.D., Inorganic Chemistry Anticipated May 2017 Thesis topic: Synthesis and characterization of geminal dianionic compounds with s-block metals

AQUINAS COLLEGE Grand Rapids, MI B.S., Chemistry and Mathematics May 2012 magna cum laude Senior project: Development of Paper Analytical Devices for the detection of isoniazid in tuberculosis medication

RESEARCH EXPERIENCE UNIVERSITY OF NOTRE DAME Notre Dame, IN Graduate Research Assistant September 2012-Present

Characterized over ten organometallic ions by NMR spectroscopy and quench reactions, showing how the formation of geminal dianions could be manipulated based on bulk, metal counterions, and functional group

Synthesized two novel ligands based on sulfur and phosphorus to study the effects of steric bulk and functional groups on the formation of geminal dianionic compounds

Mentored an undergraduate researcher for 1.5 years by advising details of a subproject and teaching laboratory techniques

STOCKHOLM UNIVERSITY Stockholm, Sweden Visiting Researcher May 2015-September 2015

Explored the reactivity of the Knölker complex for the racemization of alcohols in Dynamic Kinetic Resolution reactions

Developed and screened a variety of reaction conditions that resulted in full racemization of alcohol in less than half an hour

INTERNSHIP AND LEADERSHIP ROLES PERRIGO COMPANY Allegan, MI Analytical R&D Intern May 2011-September 2011

Tested the predictions of LC Simulator software on the HPLC methods of common pharmaceuticals to determine the potential use for the company

Demonstrated that the software could shorten method times by half with better resolution, saving both time and resources

SOCIETY OF SCHMITT FELLOWS Secretary and Social Committee Chair September 2012-May 2015

Organized fund raising, social, and professional events for Schmitt Fellows to attend

Recorded membership and meeting minutes and prepared documents to communicate the officers’ actions to Society members

Tracked membership and evaluated applications for the Schmitt Fellowship Travel Fund IMPACT LECTURE: STUDENT INVITED SEMINARS Inorganic Division Organizer January 2014-January 2016

Administered nomination and votes to the students of my division for speaker selection Invited respected members of the chemistry community to speak Scheduled meetings between students and the speaker and hosted throughout the visit

HONORS Arthur J. Schmitt Leadership Fellowship 2012-present Albertus Magnus Fellowship 2013-present TECHNICAL SKILLS Computer Skills: Microsoft Office, ChemDraw, NMR analysis software (MestReNova, Topspin, ACD/Labs), Crystallographic data analysis software (Olex 2, publCIF)

Geminal dianions are useful synthons in both organic and inorganic chemistry. They have been used since the 1970s for a multitude of transformations,1 but to date only a few have been fully characterized. In turn, this has limited their application due to issues with reproducibility and predictability. The lack of understanding of the highly reactive group I and II geminal dianions led our group to study this class of potentially useful compounds.

Previously, bis(phenylsulfonyl)methane has been used to synthesize mono and dianions (Figure 1).2 However , solubility problems preclude full identification. Our focus was to investigate increasing the solubility of this class of dianion by studying the effects of the metal cations, the steric bulk of the ligand, and the presence of additional donor ligands. A series of approaches and characterization techniques were employed in order to gain an understanding of these systems. This included in situ NMR monitoring, X-ray crystallography, and quenching studies followed by GC analyses.

These studies led to the design and synthesis of a series of functionalized sufonyl ligands (Figure 2). These ligands demonstrated increased solubility as desired.

S S

O O OOS SO O OO

S S

O O OO

A second avenue of study was then developed. Specifically, a critical question that has not been addressed in a systematic manner is the nature of the stabilizing groups required to enable the formation of germinal dianions. Some of the compounds that have been studied have attributed negative hyperconjugation, electrostatic effects, or metal interactions as the primary factor for stability.3 However, the reports differ, and individual stabilizing groups have not been evaluated against each other.

We developed a library of ligands that include one known stabilizing group and another that has generally been considered as not stabilizing (Figure 3). This allowed us to compare different stabilizing groups by comparing reactions under the same conditions by NMR spectroscopy and quenching reactions. We were also able to compare the difference between the electronic effects of phenyl groups and the steric effects of tert-butyl groups.

Ph PPh

S

R Ph PPh

O

R

Ph P

Ph

N

R

TMS

Si R

R = Ph or tBu

S ROO

Ph

S RNO

Ph

R'

1. Marek, I.; Normant, J.-F. Chem. Rev. 1996, 96, 3241–3267. 2. MacDougall, D.; Kennedy, A.; Noll, B.; Henderson, K. Dalton T 2005, 0, 2084–2091. 3. a) Chen, J.-H.; Guo, J.; Li, Y.; So, C.-W. Organometallics 2009,28, 4617. b) Orzechowski, L.; Jansen, G.; Harder,

S. J. Am. Chem. Soc. 2006, 128, 14676. C) Hull, K. L.; Charmichael, I.; Null, B. C.; Henderson, K. W. Chem. Eur. J. 2008, 14, 3939.

Figure 1. Dilithio bis(phenylsulfonyl)methandiide

Figure 2. Ligands with additional steric bulk.

Figure 3. Ligand library used to investigate the roles of individual stabilizing groups.

NICOLE M. SCHIAVONE 1220-2B Jersey Circle, Mishawaka, IN 46544 • (845) 596-3740 • schiavonen1@gmail.com

EDUCATION University of Notre Dame Notre Dame, IN, USA PhD Candidate, Analytical Chemistry Expected: April 2017

Advisor: Dr. Norman J. Dovichi Research: Capillary zone electrophoresis (CZE) coupled to electrospray ionization-mass spectrometry (ESI-MS) for metabolomics

La Salle University Philadelphia, PA, USA B.S., Chemistry and Biochemistry May 2012

Magna cum laude Advisor: Dr. Michael Prushan Research: Synthesis and characterization of metal-oxime ligand complexes

RESEARCH EXPERIENCE University of Notre Dame Notre Dame, IN, USA Graduate Student Research Assistant 2012 – present

• Developed a high-speed CZE-MS method for a complex amino acid mixture • Expanded our CZE-ESI-MS system to accommodate negative mode ionization MS • Investigated the C57BL/6J metabolome in normal vs. breast cancer tumor tissue via CZE-MS • Studied the Xenopus laevis metabolome via CZE-MS analysis

La Salle University Philadelphia, PA, USA Undergraduate Researcher 2010 – 2012

• Synthesized nickel (II) and copper (II) oxime ligand complexes • Characterized metal-ligand complexes via GC-MS, 1H NMR and magnetic susceptibility

PROFESSIONAL EXPERIENCE Pacific Northwest National Laboratory Richland, WA, USA Intern, National Security Internship Program July 2015 – September 2015

• Constructed and implemented a database using FileMaker Pro 14 Advanced • Gained basic knowledge of secondary ion MS (SIMS) and thermal ionization MS (TIMS) • Learned the operating procedures of CAMECA IMS 4f and IMS 1280-HR instruments for SIMS • Completed Radiological Worker II Training

University of Notre Dame Notre Dame, IN, USA Co-inventor, Provisional Patent (62,274,097) December 31, 2015

“Capillary Electrophoresis Coupled to Negative Mode ESI-MS.” AWARDS AND HONORS

• Association for Women in Science-Notre Dame, National Membership Award, 2016 • California Separation Science Society (CASSS), Student Travel Grant, 2014 and 2016 • Harper Cancer Research Institute, Research Like a Champion Award, 2015 • American Chemical Society, Philadelphia Chapter Award, 2012 • Chemistry and Biochemistry Department Award, La Salle University, 2012

RELEVANT SKILLS AND EXPERIENCE Experimental

• Constructed electrokinetically pumped, nano-spray sheath flow interface for CZE-ESI-MS • Designed, performed, and evaluated CZE-ESI-MS metabolomic analyses • Prepared coated fused-silica capillaries for CZE-MS of complex proteome digests • Executed protein precipitation, digestion, and sample preparation for LC-MS and CZE-MS • Performed lipid and small molecule extractions from tissue specimens for CZE-MS

Instrumentation • Operated and maintained mass spectrometers including Q-Exactive HF, Orbitrap Velos, and LTQ

XL (Thermo Scientific), micrOTOF-QII (Bruker), IMS 4f (CAMECA) • Operated and maintained Alliance HPLC system (Waters)

Computer skills: Microsoft Office, MATLAB, FileMaker Pro 14 Advanced PROFESSIONAL ACTIVIES AND MEMBERSHIPS Student/Leadership Activities:

• Graduate Student Union – Chemistry Department Representative – 2016-present o Served on the Professional Development Committee

• Chemistry Graduate Student Organization – Representative – 2015-present o Liaised between chemistry graduate students and department management o Organized recruitment and orientation activities for incoming graduate students

Mentoring Activities: • Association for Women in Science STEM Mentor Program, 2015-present

o Mentored and advised three undergraduate STEM students • Undergraduate Researcher Mentor, 2013-present

o Trained student to build CZE-ESI-MS interface and conduct unassisted experiments o Edited the student’s fellowship applications and poster presentations

American Society for Mass Spectrometry – Short Course Certificates: • Bioinformatics for Protein Identification (2016), High-resolution MS (2015), Metabolomics

(2014) Professional Memberships: AWIS (2015-present), CASSS (2014-present) Cross Country and Track, Division I, La Salle University, 2008-2012 TEACHING EXPERIENCE University of Notre Dame Notre Dame, IN, USA Teaching Assistant, Department of Chemistry and Biochemistry 2012-2013

• Oversaw general chemistry lab (~60 students) and thermodynamics recitation (~40 students) PUBLICATIONS AND SELECTED POSTER PRESENTATIONS

• Schiavone NM, Sarver SA, Sun L, Wojcik R, Dovichi NJ. High speed capillary zone electrophoresis-mass spectrometry via an electrokinetically pumped sheath flow interface for rapid analysis of amino acids and a protein digest. J. Chrom B. 991 (2015) 53-58.

• Sarver SA, Schiavone NM, Arceo J, Peuchen E, Zhang ZB, Sun L, Dovichi NJ. Capillary Electrophoresis Coupled to Negative Mode Electrospray Ionization-Mass Spectrometry Using an Electrokinetically-Pumped Nanospray Interface with Primary Amines Grafted to the Interior a Glass Emitter. Talanta (2016) Under review.

• Schiavone NM, Arceo J, Boley DB, Peuchen, E, Dovichi NJ. “Capillary zone electrophoresis-electrospray ionization-mass spectrometry for Xenopus laevis metabolomics analysis.”

o American Society for Mass Spectrometry Annual Conference, 2016, San Antonio TX. o CASSS, CE in the Biotech and Pharma Industries, 2016, San Diego, CA.

• Schiavone NM, Sarver SA, Gartner C, Wojick R, Dovichi NJ. “High-speed capillary electrophoresis coupled with electrospray ionization-mass spectrometry for metabolite analysis.”

o Pittcon Conference & Expo, March 2014, Chicago, IL.

Research Summary

My thesis research entails applying our lab’s electrokinetically pumped, sheath-flow interface to couple capillary zone electrophoresis (CZE) to electrospray ionization-mass spectrometry (ESI-MS) for metabolomic analyses.

First, I developed high-speed CZE separations of complex amino acid mixtures and resolved the structural isomers, leucine and isoleucine. Next, I optimized my sample preparation and CZE-ESI-MS system to analyze complex metabolomics samples. I first profiled metabolite extracts from two different tissue specimens: healthy breast tissue and breast tumor tissue. I generated unique metabolite profiles and high-quality fragmentation data for each sample. I am working to confirm identifications through migration time matching, database searching and comparison against standard compounds.

Currently, I am using my CZE-ESI-MS platform to profile the Xenopus laevis metabolome. Xenopus laevis is a well-studied model of early embryogenesis and I am building metabolite profiles from 4 stages of early development. By generating accurate mass measurements and high-quality tandem mass spectra in positive ionization mode, I aim to confidently identify metabolites present in each development stage and correlate them with a biological pathway.

Finally, I have expanded our CZE-ESI-MS system to operate in negative ionization mode. I aim to identify metabolites that display preferential ionization for either positive or negative mode and improve our coverage of the Xenopus laevis metabolome. Nicole Schiavone Ph.D. Candidate, Dovichi Research Group Department of Chemistry and Biochemistry University of Notre Dame Notre Dame, IN schiavonen1@gmail.com 845-596-3740

Xiaofeng Wang 433 White Oak Drive Mishawaka, IN 46556 574.485.8033 xwang26@nd.edu www.linkedin.com/in/xwang26

PROFESSIONAL SUMMARY

Organic/polymer chemist with over 5 years of experience on polymeric materials development, environmental

friendly media polymerization, polymer analytical techniques and structure-property relationships.

Independent researcher and valuable team player with excellent time management, pressure handling, and

interpersonal skills.

Led three research projects, participated in four collaborating projects with interdisciplinary research teams and

authored 15 publications in high-impact journals.

EDUCATION

University of Notre Dame Notre Dame, IN

Ph.D. in Polymer Chemistry May 2017

East China University of Science and Technology Shanghai, China

Master of Engineering in Polymer Materials March 2012

Qingdao University Qingdao, China

Bachelor of Engineering in Polymer Materials, Graduate with Honors June 2009

PROFESSIONAL EXPERIENCE

University of Notre Dame Notre Dame, IN

Research Assistant, Department of Chemistry and Biochemistry Aug. 2012 - Present

Pioneered and expanded three high-impact research projects in both fundamental study and material

development resulting in fourteen peer-reviewed journal papers.

Developed two original methods that achieved one-pot synthesis of hyperbranched polymers with high

molecular weights, low polydispersity and tunable degree of branching.

Applied knowledge in polymer chemistry, skills in material engineering, and creative thinking to achieve

micron-sized oil contaminant separation from water with recyclable nanoparticles.

Advanced star-shaped polymeric materials with controlled radical polymerization and emulsion polymerization;

collaborated with interdisciplinary teams and realized applications of star-shaped polymeric materials in drug

delivery and lithium battery performance improvement.

Henkel Shanghai, China

Intern, Research & Development Jan. 2011- May 2011

Worked closely with my supervisor for hair coloration product formulation and registration.

Optimized hair coloration product standards and documented technical reports.

Recruited and organized volunteers for new product testing.

University of Notre Dame Notre Dame, IN

Teaching Assistant, Department of Chemistry and Biochemistry Aug. 2012 - May 2015

Taught pre-lab lectures, demonstrated organic lab techniques, and maintained safe procedures for undergraduate

organic chemistry laboratory course.

Worked with students in a variety of formats to ensure understanding of topics and complex issues.

Evonik Shanghai, China

Intern, Environmental Health and Safety (EHS) Mar. 2012 - Jun. 2012

Worked with EHS staff to generate and update MSDS for Evonik chemical products.

TECHNICAL SKILLS & PROFESSIONAL ACTIVITIES

Small molecules and functional monomers synthesis and characterization Polymerization: ATRP, RAFT, CuAAC click polymerization, and emulsion formulation/polymerization

Instrumentation: GPC (RI and MALLS), TEM, SEM, NMR, FT-IR, DLS, GC, DSC, TGA

Honors & Awards: 1st Place in Student Research Presentation Competition, GLCACS 20th Annual Conference (2016)

Outstanding Graduate Award, Provincial Department of Personnel, Shandong Province, China (2009) Leadership Activities: Diversity Leader, Chemistry Graduate Student Organization of Notre Dame (2016) Lab Safety Manager, Gao Lab of University of Notre Dame (2013 - present)

1

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e %

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Increase in polymer size

28 26 24 22 20 18

Low PDI at high vinyl conversion

Elution Volume

(61.9%) 1 min.

(86.6%) 5 min.

(95.9%) 10 min.

(98.1%) 20 min.

(99.9%) 60 min.

Brij 98HB

~ 100% vinyl

conversion

Key: one polymer molecule per latex

Scheme 1. Application of confined space in

regulating hyperbranched polymer structure

with polymerization of AB* inimer.

Research Summary

Xiaofeng Wang

574.485.8033 xwang26@nd.edu 433 White Oak Drive Mishawaka, IN 46556

Development and Applications of Nano-structured Polymeric Materials

My research has focused on the new polymerization methods development, characterization, and

application of nano-structured polymers. These nano-structured polymers represent intriguing types of

nanostructured materials that can be used as specialty addictive in catalysis, molecular electronics,

lubricants, adhesives, as well as nanomedicines. These emerging markets generated new directions in

fundamental and applied polymer research to design macromolecules with controlled chemical

compositions, molecular weights and distributions, site-specific functionalities and architectures, which

represent a robust multidisciplinary area, i.e., macromolecular engineering.

Synthesis of hyperbranched polymers with controlled structures via controlled radical

polymerization and confined nanospace

My initial focus was on the synthesis of hyperbranched polymers with well-defined structures and

molecular weight. The current challenge in the synthesis of hyperbranched polymers introduces random

bi-molecular side reactions and results in poorly defined polymer structure, which significantly limits

their property and applications. In this aspect, I contributed unique ideas and developed three highly

original methods with my peers that can achieve one-pot synthesis of hyperbranched polymers with high

molecular weighs, low polydispersity and tunable degree of branching.

The first approach applies atom transfer radical polymerization (ATRP) in confined nanospace, e.g.,

micelles, to regulate the structure of hyperbranched polymers. A microemulsion system was applied to

segregate the polymerization so that the monomers

inside each discrete locus can react/polymerize

completely, while there is no inter-micelle reaction.

Systematic study of this innovative method by

varying several experimental parameters

demonstrates the robustness of the techniques to

produce an array of polymers with tuned

functionalities, high molecular weight and low

polydispersity. The concept of polymerization in

confined space could be further expanded for a one-

pot synthesis of hyperbranched polymers with

layered structures via sequential monomer additions

in situ. This new method development represents as

intriguing direction that can be broadly applied in the

construction of any branched polymer structures.

Resulting publications: Macromolecules 48 (7),

2118-2126, Polymer Chemistry 6 (37), 6739-6745,

Chemical Communications 51 (93), 16710-16713,

Macromolecular rapid communications 36 (23),

2076-2082

2

Scheme 3. Polymerization of transmer using

RAFT with PEG-azo thermal initiator and

concurrent ATRP/RAFT without thermal initiator

9 12 15 18 21 24 27

180 min

50 min

20 min

10 min

Elution volume (mL)

5 min

Scheme 2. Synthesis of hyperbranched polymers

with low polydispersity and high degree of

branching by chain-growth CuAAC polymerization

The second method I contributed to develop is even more interesting, which is a seminal work to achieve

one-pot chain-growth polymerization of ABm (m≥2) monomers using copper-catalyzed click

polymerization. I worked with postdoc Dr. Yi Shi

and other students for the first time applied the

feature that triazole groups in polymer complex

Cu to successfully concentrate all Cu catalyst into

polymers at very low monomer conversion. The

confined Cu into polymer selectively favor the

monomer-polymer reactions over monomer-

monomer reactions and results in a chain-growth

polymerization that exhibits liner increase of

molecular weight versus conversion and clean

chain extension in multiple batched of monomer

addition. It is amazing to see how powerful this

new method being capable for one-pot synthesis

of hyperbranched polymers with over a million

molecular weight as well as very low

polydispersity < 1.05.

Resulting publications: Angewandte Chemie 127

(26), 7741-7745, Macromolecules 49 (3), 760-

766, Macromolecules 49 (12), 4416-4422,

Macromolecules 49 (15), 5342-5349, Polymer

Chemistry 7 (35), 5512-5517

To further expand the hyperbranched polymer development techniques for diversified applications which

require wide range of functionalities, I explored the application of polymerizable chain transfer agent, i.e.,

transmer, in reparation of hyperbranched polymers. Traditional RAFT polymerization of transmers was

only able to produce hyperbranched polymers with relatively low molecular weights due to the presence

of external thermal initiator which has limited

radical generation lifetime. This places a challenge

for regulating the molecular weight and

polydispersity via the application of confined

nanospace. A new strategy was explored that used

copper catalyst to activate the alkyl trithiocarbonate

to generate radicals without the use of thermal

initiator. This new initiation system eliminated the

presence of primary radicals and ensured radical

termination reactions only happening between

propagating radicals, resulting in the production of

hyperbranched polymers with very high molecular

weight. High molecular weight and narrow

polydispersity could be achieved when

microemulsion was applied.

Resulting publication: Macromolecules, 2016, 49

(17), 6471–6479

3

Scheme 4. Application of pH-responsive magnetic

nanoparticles as recyclable stabilizers for oil-water

separation.

Application of nanostructured polymers

With the advanced polymerization methods development and polymer structure control, the

macromolecular engineering to tailor certain application becomes implementable. Several successful

applications were either completed or undergoing with significant efforts from interdisciplinary

collaborations. These efforts include exploring their applications in oil-water separation, fine particle

separation, drug delivery, catalysis, and lithium battery performance improvement. Besides my own

research contribution, the tremendous efforts from my collaborators allowed me to expand my research

and helped to realize the application of lab synthesized materials in real world. Out of the major four

material-related projects, one was led and independently completed by myself which is the development

of recyclable pH-responsive magnetic nanoparticles for oil-water separation. This research was

targeting on efficient separation of oil from produced water streams which represents an important

process in petroleum industry. Hybrid magnetic nanoparticles (MNPs) with well-defined core-shell

structure, pH-tunable interfacial activity and

strong magnetic responsiveness were

developed as recyclable stabilizers for oil-

water separation. The magnetic core allowed

rapid separation of the micron-sized oil

droplets from emulsions under external

magnetic field, while the pH-responsive

polymer shell offered the hybrid MNPs

tunable interfacial activity to form and break

Pickering emulsion reversibly for recyclable

use of the hybrid MNPs. Multiple

characterization techniques including

microscopy and movies were utilized to

prove efficient separation of diesel droplets

from water and the recyclability of the hybrid

MNPs.

For the other three projects, all of them are related to the synthesis and application of star-shaped

polymers with various composites. These projects include the preparation of honeycomb film for fine

particles separation, hyperstar polymer development for combinatorial therapy for triple negative breast

cancer, and hierarchically branched polymer structure to simultaneously improve the conductivity and

mechanical integrity of solid polymer electrolytes. The complex polymer structures were designed and

synthesized by me and my collaborators fulfilled the property test. Effective communication and

collaborations allowed the success of these projects.

Resulting publications: Polymer 2015 72, 361-367, Chemical Communications 51 (93), 16710-1671,

Macromolecular rapid communications 35 (2), 221-227