The Chemistry Department had an eventful 2011-2012 academic year. We had 28 senior majors this year with an impressive 20 completing senior thesis projects.  We are very pleased to announce a new face to the Chemistry Department.  Dr. Jimmy Blair, a bioorganic chemist, starts his appointment in July 2012.  He will teach Organic Chemistry: Intermediate Level (CHEM 251) in the fall semester and a new course in the spring of 2013, Chemical Biology: Discoveries at the Interface (CHEM 326).  We are delighted that Dr. Blair will begin his academic career as a faculty member in our department.

We are particularly proud of our students and their accomplishments.  Each year, individual students are recognized with departmental awards.  In the class of 2012, the John Sabin Adriance prize went to Christopher Valle for outstanding work throughout his chemistry career.  The James F. Skinner prize was awarded to Cameron Rogers for his distinguished achievement in chemistry and his future promise as a researcher.  The Leverett Mears prize went to Roop Dutta in recognition of both his abilities in chemistry and future in medicine.  Emma Pelegri-O’Day was awarded the American Chemical Society Connecticut Valley Section Award for her sustained scholastic excellence. Matthew Zhou was awarded the American Institute of Chemists Student Award for outstanding scholastic achievement.  Zachary Remillard received the Frank C. Goodrich 1945 Award for demonstrated excellence in chemistry research.  Rachel Patel was the recipient of the ACS Division of Inorganic Chemistry Undergraduate Award in Inorganic Chemistry, and Michelle McRae was awarded the American Chemistry Society Analytical Division Award.  Our newest award, the Skinner Award for Travel to a Professional Meeting, was given to Grace Babula.  Over the course of the academic year, a number of awards were presented to chemistry students for outstanding scholarship.  Grace Kim ’15 and Claire Lidston ’15 received the CRC Awards as the outstanding students in CHEM 151 and CHEM 155, respectively.  Christian Gronbeck ’15 was presented with the Raymond Chang First-Year Chemistry Award for his exceptional work in CHEM 153.  Recognized for their achievement in organic chemistry, Craig Burt ’14 received the Polymer Chemistry Award and Chau Vo ’14 was the recipient of the Harold H. Warren Prize.

This year we continued to participate in the Class of 1960 Scholars Program.  Two distinguished scientists were invited to campus to meet with our students and present a seminar.  Professor Craig Hawker from University of California, Santa Barbara and Professor Geoffrey Hutchison ’99 from the University of Pittsburgh were the 1960 Scholar speakers this year.  Sixteen students were selected by the faculty to be Class of 1960 Scholars during 2012 and to participate in the seminar program which includes: a preliminary meeting of the Scholars with a Chemistry Department faculty member to discuss some of the papers of the seminar speaker, attendance at the seminar/discussion, and an opportunity for further discussion with the seminar speaker at an informal reception or dinner.  The students selected for 2012 are:

Class of 1960 Scholars in Chemistry

During the summer of 2012, approximately 45 Williams College chemistry students were awarded research assistantships to work in the laboratories of departmental faculty.  We gratefully acknowledge support from the American Chemical Society, Bernhard Summer Fellows Program, the College Divisional Research Funding Committee, the J.A. Lowe III ’73 summer research fund, the J. Hodge Markgraf ’52 summer research fund, the National Institutes of Health, the National Science Foundation, Research Corporation, Summer Science Program funds, and the Wege-Markgraf fund.

Associate Professor Dieter Bingemann, with the help of independent study student Jiji Ahn ’12 and research assistants Bryn Falahee ’13 and Chiara Del Piccolo ’14, continued his search for the fundamental reason behind the dramatic slowdown of the motion in glasses at their arresting point. With a newly developed statistical analysis routine they showed that single molecule spectroscopy allows to follow the relaxation at the glass transition in unprecedented detail, individually observing fast and slow domains at the molecular level.

The team found in experiments and molecular dynamics simulations that even though the overall dynamics slows dramatically, the molecules in the material still experience about the same number of very short waits between structural rearrangements. Below the glass transition, however, a very small number of extremely long waiting periods without any rearrangements emerges which is solely responsible for the dramatic effect in the sample. Bingemann presented these results from both the single molecule experiments and computer simulations at the Gordon Conferences “Chemistry and Physics of Liquids” and “Soft Condensed Matter Physics” in August 2011.

Back in the classroom, Bingemann taught Physical Chemistry: Structure and Dynamics (CHEM 361), one of the upper-level physical chemistry courses in the Department, in the fall, using a new project-based approach, which borrows heavily from tutorials, which was favorably received by the students.  In the spring, he taught Instrumental Methods of Analysis (CHEM 364) a hands-on upper level introduction to various state-of-the-art instrumental methods using the same project-based teaching approach. In the same semester, Bingemann also team-taught Introduction to Environmental Science Methods (ENVI 102) with Professor Mea Cook of the Geosciences Department.

Associate Professor Amy Gehring spent her tenth year at Williams returning to her teaching roots and enjoyed working with the same courses that she did in her very first year.  These were all courses in our upper-level biochemistry offerings including Biochemistry I–Structure and Function of Biological Molecules (CHEM 321) in the fall and Enzyme Kinetics and Reaction Mechanisms (CHEM 324) and Topics in Biochemistry and Molecular Biology (BIMO 401) in the spring.  The BIMO 401 course is the capstone for the Biochemistry and Molecular Biology (BIMO) program, and she once again enjoyed lively weekly discussions with the BIMO concentrators in this seminar-style course.  Gehring continued to serve as chair of the BIMO program, with duties that included hosting two exciting seminars by Professor Gökhan Hotamisligil (Harvard School of Public Health) and Professor Lenny Guarente (MIT).

Research continued in the Gehring lab to understand the molecular details of the life cycle of the model antibiotic-producing soil bacterium, Streptomyces coelicolor.  During the summer of 2011, Gehring was joined in this work by Matt Madden ’12, Erin McGonagle ’12, Hetal Ray ’12, Jennifer Rodriguez ’12, Sora Kim ’13, and Jessica Monterrosa Mena ’14.  Erin, Hetal and Jennifer continued during the academic year as thesis students, studying conditions for the overproduction of antibiotics, the role of secreted proteins in the bacterium’s life cycle, and the control of sporulation, respectively.  They were joined in the fall by fellow thesis student, Kenny Murgo ’12, who worked together with Sora over the year to demonstrate the biochemical function of a potential antibiotic biosynthesis regulatory enzyme.  In July, Gehring will attend the Gordon Research Conference on Microbial Stress Response and present a poster detailing Kenny and Sora’s research.  Also participating in research at various times during the academic year were Jessica, Lauren Agoubi ’13, Emily Gao ’13, Sola Haye ’14, Georgiana Salant ’14, and Ashley Kim ’15.  For both the summer and during the academic year as a thesis student, Mike Alcala ’12 pursued a collaborative project with Professor Peacock-Lopez using fluorescence microscopy to visualize oscillations in gene expression in the bacterium E. coli with a minimal 2-gene system; he was joined in this work by Areli Valencia ’14.  With all of these students involved with research, it was definitely a busy and productive year in the lab!  In addition to pursuing her research program, Gehring served as a reviewer for several journals throughout the year including Applied and Environmental Microbiology, FEMS Microbiology Letters, Journal of Bacteriology, and Process Biochemistry.

Christopher Goh spent his AP leave in the laboratory of Geoff Coates in the chemistry department at Cornell University, thanks in part to the generous support of a Hellman Foundation Fellowship. With the help of Skype and occasional trips back to Williams, Goh was also able to oversee the senior thesis of Zac Remillard ’12.  Zac was able to present his thesis work at the National American Chemical Society Conference in San Diego, CA, in March this year, and later at the ACS-Connecticut Valley Undergraduate Symposium.  At the latter, Zac was the recipient of an award for best oral presentation.  The research group also received an ACS-PRF grant to start a new project on developing homogeneous iron catalysts to promote rapid and selective epoxidations of alkenes.  The targeted epoxidation products have potential use as building blocks for new polymeric materials.

Professor Sarah Goh taught Organic Chemistry: Intermediate Level (CHEM 251) in the fall semester.  As part of the Bronfman ventilation renovation over the summer and fall, the laboratory got a facelift, and Michelle McRae ’12 and Matt Zhou ’12 were the first to work in the “new” space. Michelle synthesized polymer micelles displaying mannose sugars and investigated their recognition with sugar-binding receptors.  Matt used controlled radical polymerization techniques to tune the lower critical solution temperature of N-isopropyl acrylamide / N,N-dimethyl acrylamide block copolymers.  Each of these polymer families can be used as a drug delivery vehicle, capitalizing on targeting agents (such as sugars) or manipulating aggregation properties.  Matt and Michelle finished up their calendar year theses during winter study 2012. In the spring, Prof. Goh headed to Ithaca, NY, for a relaxing and reflective sabbatical, returning to Williamstown in time for graduation!  She also served as a reviewer for the National Science Foundation, Molecular Foundry at Lawrence Berkeley National Laboratory, Petroleum Research Fund, Journal of Polymer Science, and Roberts and Company Publishers.

Professor Lawrence J. Kaplan returned from a sabbatical and taught Biophysical Chemistry (CHEM 367) in the fall, Science for Kids (CHEM 11) with Professor Richardson during Winter Study, and Chemistry and Crime (CHEM 113), for the first time since 2005, in the spring semester.

He continues to administer the Center for Workshops in the Chemical Sciences with his colleagues Professors Jerry Smith of Georgia State University, David Collard of Georgia Institute of Technology and Patricia Hill of Millersville University.  Since its founding eleven years ago, the CWCS has received major grants from the National Science Foundation and continues with the current collaborative grants to Williams, Georgia Tech, and Georgia State for $3,908,665 for five years.  As a result of this current NSF grant the CWCS was rebranded the Chemistry Collaborations, Workshops and Communities of Scholars (cCWCS).  The cCWCS sponsors workshops related to the chemical disciplines including Food Chemistry, Chemistry and Art, Environmental Chemistry, Material Science and Nanotechnology, Fundamentals of Proteomics, Biomolecular Crystallography, and Forensic Science.  In addition to offering workshops, the CWCS continues to develop a series of Communities of Scholars.  With the workshops and their alumni serving as the nucleus, the Communities will continue to develop high-quality course content and pedagogy; propagate the use of successful teaching strategies; and provide discussion venues such as online discussion boards and video conferencing.  The website for the Forensic Science Scholars Community, launched in 2010 has been significantly expanded with many more members and more educational resources.

Kaplan taught a weeklong CWCS workshop in forensic science during the summer of 2011 at Williams.  Sixteen participants from colleges and universities as well as community colleges became criminalists for the week.  They processed crime scenes and analyzed evidence such as glass and soil, fibers and fingerprints, drugs and alcohol, blood and bullets, and, of course, DNA.  Ms. Deborah Morandi, Administrative Assistant, and Dr. Tony Truran, Lecturer/Technical Assistant, both in the Chemistry Department, assisted Kaplan in the organization and instruction of the workshop.

Kaplan reviewed numerous papers for the Journal of Chemical Education.

During the past year Professor Lovett continued to serve as Chair of the Bioinformatics, Genomics, and Proteomics Program and Director of the Summer Science Program for Students from backgrounds traditionally underrepresented in the sciences.

Professor Lovett continued his research on the Bacillus subtilis SOS response to DNA damage, which comprises a set of DNA damage-inducible genes (SOS genes) that code for DNA repair and cellular survival functions.  During the past 27 years Lovett and Williams’ students working in his lab have discovered more than 30 SOS genes and characterized their genetic regulation in response to DNA damage.  Based on recent evidence implicating the SOS response in the development of antibiotic resistance in bacteria, research in the Lovett lab has focused on finding SOS response inhibitors. Lovett’s NIH-funded project entitled, “The binding of the LexA protein to the RecA protein nucleoprotein filament,” involves characterizing the molecular details of SOS induction in order to design such inhibitors.  Last year the project was expanded to include searching a library of 14,400 bioactive compounds for SOS response inhibitors using a high-throughput screen developed by Williams students in the summer of 2011.   In the past year Williams students have worked on various aspects of the project during the summer of 2011, during winter study, and during the academic year.  The summer students, working as full time research assistants, included Roop Dutta ’12, Willis Koomson ’14, Andrew Kung ’12, Asvelt Nduwumwami ’13, Emily Niehaus ’12, and Peter Young ’13.  Roop, Andrew, and Emily, along with Clarissa Andre ’12 and Christian Torres ’12 continued as honors thesis students during the academic year. Professor Lovett also supervised winter study as well as work study research students Moses Flash ’15, Tiantian He ’15, Willis Koomson ’14, Jared Nowell ’15, and Amanda Walker ’15.

Last summer, Professor Lovett taught the Chemistry lectures component of the Williams College Summer Science Program.  Together with Professor David Richardson, he also taught in the eighth year of science camp for elementary school students and teachers.

Professor Lovett also served as a reviewer for the Journal of Bacteriology, and as a consultant for the Sherman Fairchild Foundation’s Scientific Equipment Grant Program.

Lee Park’s work on the design of partially fluorinated conjugated compounds for use as organic electronic materials continued this year with the help of a large group of students.  Between summer 2011 and May 2012, the following students helped out in the lab, as summer research assistants, thesis students, or simply by volunteering time in lab: Grace Babula ’12, Chesea Boydstun ’15, Peter Clement ’13, Chris Corbett ’13, Alejandro Gimenez ’13, Dan Gross ’12, Mindy Lee ’12, Cameron Rogers ’12, Joon-Hun Seong ’14, Erica Wu ’13, and Johan Postema, a summer exchange student from the University of Leiden.  Over the year the group has been working on synthesizing and characterizing both polymeric and oligomeric materials, looking at absorption, emission, and self assembly properties of these materials.  We have made good progress and our work for the year culminated in two poster presentations at the National American Chemical Society Conference in San Diego in March; Park took 6 students Grace, Chelsea, Mindy, Dan, Cameron, and Chris to the meeting, and a good time was had by all.  The group for summer 2012 includes Dylan Baker ’15, Chesea Boydstun ’15, Chris Corbett ’13, Alejandro Gimenez ’13, Vera Gould ’14, Joon-Hun Seong ’14, and Felix Sun ’14 – we’re looking forward to a productive summer and next year!

Park taught Inorganic/Organometallic Chemistry (CHEM 335) to a larger than usual group with an enrollment of 23 students and Materials Chemistry (CHEM 336) with 15 students this year.  For the Materials Chemistry course, she offered for the second time the new lab program on nanofabrication strategies.  She also began offering a series of new problem solving sessions for introductory students that we hope will provide students with some fundamental strategies in approaching a range of different kinds of problems that they might encounter in courses and labs.

Park also continues to serve on the Committee on Professional Training for the American Chemical Society, a committee that oversees curricular development at all approved chemistry programs in the country as well as numerous other aspects of the professional training of chemists at all levels.  In addition, she continued her service reviewing proposals for various funding agencies (NSF, Research Corporation, the Petroleum Research Fund, the Keck foundation) as well as manuscripts for various journals.  At Williams she completed her service on the Committee for Appointments and Promotions, and is gearing up to serve as Chair of the Committee on Educational Policy next year.

In 2011-2012 Professor Peacock-López taught Current Topics in Chemistry (CHEM 155) in the fall, and Foundations of Modern Chemical Science (CHEM 256) in the spring.  During January, he taught Spanish for the Health Sciences (CHEM 12).  In collaboration with Professor Amy Gehring, Professor Peacock-López served as co-advisor to Michael Alcala ’12.  Michael was motivated by previous work on repressilator dynamics, considered a relatively simple synthetic transcriptional network in E. coli by developing a two-gene plasmid, which represents the smallest artificial gene network.  Recently, Mimi Lu ’09 and Steve A. Mendoza ’13 analyzed two-gene networks and observed complex dynamics under certain physical conditions.  Based on the theoretical observations, Mr. Alcala has designed and constructed the Minimal 2-Gene Oscillator, a two-gene transcriptional activator-repressor artificial genetic network based on the design of a previous artificial genetic network—the Repressilator (Elowitz, 2000)—that shows oscillatory behavior.  In this case, Mr. Alcala constructed a simpler model by using both a transcriptional repressor gene (tetR-lite) and a transcriptional activator gene (melR-lite), instead of three transcriptional repressor genes, and attempt to show that oscillatory behavior occurs when the half-lives of the gene products are of about the same magnitude as their mRNAs.  Time-lapse fluorescence microscopy experiments monitoring the expression of a GFP variant over time suggests that the network displays oscillatory behavior under certain conditions.

During the academic year, Laura Dos Reis ’12 considered regulated glucose transport to model metabolite concentrations in glycolysis.  In her work, Dos Reis developed and studied a three variable model, where she considered glucose transport and hexokinase inhibition by gluco-6-phosphate.  For the three-variable model, she found complex oscillation including bursting and mixed modes, as well as chaos.

While continuing with his research, Professor Peacock-López, Ms. Gisela Demant, and instructors Mr. Kevin M. Hartmann (Drury High School; 28 students) and Ms. Cheryl Ryan  (Hoosac Valley High School: 21 students) organized and taught chemistry labs at Williams College.  As in previous years, Dr. Tony Truran helped with running the experiments.  These honors chemistry students attended five labs during the year to perform some of the experiments from the Williams introductory chemistry lab program and a newly developed organic synthesis.  The latter experiment was implemented and adapted by Ms. Gisela Demant to include the synthesis of aspirin from salicylic acid and include the characterization of the purity of the product by TLC and melting point determination.  This outreach chemistry effort has now been supported entirely by the National Science Foundation through an RUI grant to professor Peacock-López.

Finally, he has served as reviewer for the National Science Foundation, Mathematical Biosciences, Journal of Chemical Physics, Physica A, and Chaos.

During the 2011-2012 academic year, Professor David Richardson enjoyed a mini-sabbatical in the fall semester, remaining on campus.  Professor Richardson’s research lab remained active throughout the year.  Together with Professor Jay Thoman he supervised the senior honors thesis research of Emma Pelegri-O’Day ’12, which was directed at the development of new methods for the synthesis of deuterofluorocarbons.  He also supervised the efforts of two work-study students, Vanessa Soetanto ’12 and Asvelt Nduwumwami ’14.  Vanessa continued the Richardson lab’s collaboration with Dr. Andria Agusta, of the Indonesian Institute of Biological Sciences, and with Professor Chip Lovett on a project involving the isolation of new antibiotics from medicinally active South East Asian plants.  Asvelt worked on the same project, focusing on APCI-HPLC/MS method development.  In a second collaboration with Professor Jay Thoman he also supervised the summer 2011 research of Ariana Chiapella (MCLA ’13) and Olivia Gannon (Bennington College ’12) directed at measuring PCB levels in sediments and macro-invertebrates from the Hoosic River.  Finally, he also supervised the research of work-study student Zachary MacKenzie ’14 in a collaboration with Professor Luana Maroja of the Biology Department involving cuticular hydrocarbons from crickets.

Professor Richardson continued his supervision and maintenance of the Department’s 500 MHz nuclear magnetic resonance spectrometer and he wrote a user’s manual for the Department’s High Pressure Liquid Chromatography-Mass Spectrometer.  He also served as a reviewer for Steroids, The Journal of Natural Products, Magnetic Resonance in Chemistry, The Journal of Heterocyclic Chemistry, The Journal of Organic Chemistry, and Natural Products Communications, and as a textbook reviewer for Roberts & Co.  He also served on the Science Building Steering Committee at the Massachusetts College of Liberal Arts.

In January 2012, Professor Richardson resumed his teaching responsibilities, teaching Science for Kids (CHEM 11) together with Professor Larry Kaplan.  In the spring semester he taught Organic Chemistry: Introductory Level (CHEM 156) along with one of the course’s laboratory sections.  During July 2011 he taught the chemistry laboratory portion of the Williams College Summer Science Program and, together with Professor Chip Lovett, he hosted the Department’s Summer Science Camp program for local 4^th and 5^th graders.  He also served on the Boards of the New England Tropical Conservatory and the South Williamstown Community Association.

Anne R. Skinner, senior lecturer emerita, attended the 2012 annual meeting of the Paleoanthropology Society and presented her results on a project aimed at dating the changes in the course of the ancient Thames River: “Dating of Submerged Landscapes by Electron Spin Resonance”.  At the 77^th annual meeting of the Society for American Archaeology she discussed “ESR Dating at Grotte de Contrebandiers, Témara, Morocco”.  She is continuing her research on a variety of sites and will present two invited lectures at the upcoming Society of Africanist Archaeology meeting in Toronto.  This summer she will travel to Tanzania on a grant from the Canadian scientific research agency, to study Iron Age rockshelters.

During summer 2011, Nikki Wise ’12 conducted research which involved dating materials from the Kharga Oasis in Egypt.  Nikki then spent the academic year completing her thesis on additional samples from the Dakhleh Oasis in an effort to date a new type of stone tools.

Professor Tom Smith spent his fourteenth year at Williams pursuing his research in organic synthesis and methods development, Asymmetric Methods for the Synthesis of Pyran-Based Anticancer Natural Products, under an NIH Academic Research Enhancement Award (AREA) grant and a Henry Dreyfus Teacher-Scholar Award.  Senior honors student Rachel Patel ’12 worked toward the synthesis of a new marine natural product, enigmazole A.  On leave from the classroom this year, Professor Smith published the results of project on tedanolide C that had been in the works for the past five years.

Jay Thoman taught Concepts of Chemistry: Advanced Section (CHEM 153) in the fall and Physical Chemistry: Thermodynamics (CHEM 366) in the spring.  On campus, he also taught the laboratory component of AP Chemistry for Mount Greylock Regional High School.  With David Richardson, he served as thesis co-advisor to Emma Pelegri-O’Day ’12, who was very successful in developing and extending methods for synthesizing deuterated fluorocarbon molecules from iodofluorocarbon precursors.  Emma demonstrated that the general method developed for iodoperdeutero compounds could be extended in a selective and controlled manner to reactant molecules with hydrogen atoms and also to iodopentafluorobenzene.  Emma also developed local ¹⁹F NMR methods for decoupling ¹H and ¹³C resonances.

In service outside of the college, Thoman served as a reviewer for the Journal of Physical Chemistry and for the Department of Energy.  He continues to serve as Chair of the Review Committee for the Chemistry GRE.

During summer 2011, Thoman worked with Annie Moriondo ’14 and Liam Abbott ’13 to probe the structure and dynamics of hydrofluorocarbon molecules using cavity ringdown laser spectroscopy.  Annie and Liam improved the experimental apparatus and probed the temperature dependence of the CH-stretching overtone spectrum of a series of small gas-phase hydrofluorocarbon molecules.  This project continued during the academic year by work-study student Richard Eiselen ’14.

Additionally during summer 2011, Thoman and Dave Richardson sponsored two students on an ongoing project investigating PCB pollutants in the Hoosic River and its environs.  Olivia Gannon from Bennington College and Arianna Chiapella from MCLA made excellent progress in analysis method development, making a brand new piece of “drying” equipment (obtained by Geosciences Professor Mea Cook) work for our experiment, and making a merely one-year-old piece of equipment work about 3 times faster.  They also collected many crayfish from the Hoosic River, and processed about half of them to quantify the concentration of PCBs.  This work follows the summer 2010 project of Emily Ury ’13 and Alex Lou ’13, who analyzed Hoosic River sediment for PCB concentration, and also collected benthic invertebrates for later analysis.

CHEMISTRY COLLOQUIA

Professor Ronald Christensen, Bowdoin College

“The Long and Short of Polyenes: The Optical Spectroscopy of Linearly Conjugated Systems”

Professor Craig Hawker, University of California-Santa Barbara, Class of 1960 Scholars Program

“Tricking Nature: Generating Complex Nanoscale Patterns Through Bottom-Up Self-Assembly”

Professor Gökhan Hotamisligil, Harvard School of Public Health
Co-sponsored with BIMO and Biology

“Treasure Hunting in Fat to Treat the Plague of Metabolic Diseases”

Professor Geoffrey Hutchison ’99, University of Pittsburgh, Class of 1960 Scholars Program

“Rational Design of Molecular Materials: Molecular Springs, Solar Cells and More”

Professor Kristi Kiick, University of Delaware

“Multivalent Polymers in the Design of Hybrid Biomaterials”

Professor Lee Park, Williams College, Williams Thinking Lecture

“Designing Nanoarchitectures”

Dr. Thomas Pinnavaia, Michigan State University

“Porous Silicates”

Professor Kate Queeney ’92, Smith College

“How Does Your Biofilm Grow”

Dr. Debra Rolison, Naval Research Laboratory
Co-sponsored with Physics and Astronomy

“Integrating the Multifunction Necessary for Electrochemical Power into Energy and Size Scalable Ultraporous Nanoarchitectures”

Professor Jay Thoman, Williams College

“Hodge Markgraf and Jenny Holzer’s 715 Molecules”

Dr. Leo Tsai ’98, Beth Israel Deaconess Medical Center

“An Introduction to Diagnostic Radiology”

OFF-CAMPUS COLLOQUIA

Grace Babula ’12, Chelsea D. Boydstun ’15, Peter L. Clement ’13, Christopher J. Corbett ’13, Alejandro R. Gimenez ’13, Mindy C. Lee ’12, Lee Y. Park

“Optical and Electronic Properties of Discrete Phenylenevinylene-based Oligomers”
243^rd ACS National Meeting & Exposition, San Diego, CA, March 2012

Dieter Bingemann

“Describing Glass Dynamics as a Sequence of Local Relaxation Events”
University of Pennsylvania, January 2012

Dieter Bingemann

“How Individual Structural Rearrangement Events Lead to the Complex Dynamics in Glasses”
University of Wisconsin, May 2012

Daniel Gross ’12, Cameron R. Rogers ’12, Katrina A. Tulla ’11, Erica L. Wu ’13, Lee Y. Park

“Partially Fluorinated Sidechains in Influencing Polymer Film Morphology, Absorption and Fluorescence Behavior”
243^rd ACS National Meeting & Exposition, San Diego, CA, March 2012

Lee Y. Park

“Guiding Morphology Development in Polymer/PCBM Films for Organic Photovoltaic Applications via Surface Patterning and Polymer Design”
Wellesley College, December 2011

Zachary D. Remillard ’12, Sara A. Turner ’11, Emily Gao ’13, Desire T. Gijima ’10, A. Chandrasekaran, Robert D. Pike, Christopher Goh

“Copper Complexes of Tridentate Pyridine-imine and Pyridine-amine Ligands as Catalysts for Atom Transfer Radical Polymerizations”
243^rd ACS National Meeting & Exposition, San Diego, CA, March 2012, INOR-525

Zachary D. Remillard ’12, Sara A. Turner ’11, Emily Gao ’13, Desire T. Gijima ’10, A. Chandrasekaran, Dmitri Royman, Robert D. Pike, Christopher Goh

“Structures and Properties of Copper(I) Complexes of Tridentate Heteroaromatic-imine and Heteroaromatic-amine Ligands”
243^rd ACS National Meeting & Exposition, San Diego, CA, March 2012, INOR-271

POSTGRADUATE PLANS OF CHEMISTRY DEPARTMENT MAJORS

Michael Alcala	Research Assistant, Harvard School of Public Health, then to medical school
Clarissa Andre	Unknown
Grace Babula	Unknown
Oscar Calzada	Research Associate, Boston Children’s Hospital, then to medical school
Roop Dutta	M.D., Tufts University School of Medicine
Daniel Gross	Unknown
Kathryn Kumamoto	Ph.D. in Geology, Stanford University
Andrew Kung	Unknown
Mindy Lee	Economics research, then to graduate school
Natalia Loewen	Work in San Francisco area, then to graduate school
Mathew Madden	Science teacher, Teach For America, Atlanta, GA, then medical school
Erin McGonagle	Luce Fellowship, Angkor Hospital for Children, Cambodia, then to medical school
Michelle McRae	Associate Consultant, Bain & Company, New York, NY
Nari Miller	Graduate school
Kenneth Murgo	Research with an orthopedic surgeon, then to medical school
Emily Niehaus	Clinical research, then to medical school
Rachel Patel	M.D., University of Massachusetts Medical School
Emma Pelegri-O’Day	Fulbright Research Fellowship, Germany
Hetal Ray	Research Assistant, Multiple Sclerosis Research Center of New York
Zachary Remillard	Research Assistant, Reluceo, Inc., Plymouth, MN
Marissa Robertson	Unknown
Jennifer Rodriguez	Work for Basic Health International, El Salvador, then to medical school
Cameron Rogers	Ph.D. in Chemistry, University of California-Berkeley
Christopher Valle	M.D., Feinberg School of Medicine, Northwestern University
Marsha Villarroel	Unknown
Norman Walczak	University of Texas at Austin Law School
Nicole Wise	Work, then to graduate school
Matthew Zhou	Ph.D. in Chemistry, University of California-Berkeley

CHEMISTRY

Dynamic Behavior in Artificial Genetic Networks:
The Minimal 2-Gene Oscillator

Michael Alcala

We have designed and constructed the Minimal 2-Gene Oscillator, a two-gene transcriptional activator-repressor artificial genetic network based on the design of a previous artificial genetic network—the Repressilator (Elowitz, 2000)—that shows oscillatory behavior. We constructed a simpler model by using both a transcriptional repressor gene (tetR-lite) and a transcriptional activator gene (melR-lite), instead of three transcriptional repressor genes, and attempt to show that oscillatory behavior occurs when the half-lives of the gene products are of about the same magnitude as their mRNAs. Time-lapse fluorescence microscopy experiments monitoring the expression of a GFP variant over time suggests that the network displays oscillatory behavior under certain conditions.

Characterizing the Interactions of LexA and RecA in B. subtilis and E. coli Using Cross-Linking Experiments

Clarissa Andre

The bacterial SOS system is an inducible DNA repair system whose activation can lead to antibiotic resistance. Although many of the details of SOS regulation have been characterized, the interactions between the two regulatory proteins RecA and LexA remain unknown. Determining the binding site of RecA on LexA could shed light on the mechanism of these unique protein interactions. Previously, 14 surface amino acids on LexA that are critical for RecA binding have been identified and replaced by cysteine in preparation for crosslinking studies (Bergethon, 2009). The goal of this thesis is to investigate the binding site of RecA on LexA by using the heterobifunctional crosslinker 2-[N2-[N6-(4-Azido-2,3,5,6tetrafluorobenzoyl-6-aminocaproyl)-N6-(6-biotinamidocaproyl)-L-lysinylamido)] ethylmethane-thio-sulfonate (Mts-Atf-LC-Biotin) to covalently attach the B. subtilis LexA mutants to the E. coli RecA protein. We attached the Mts-Atf-LC-Biotin crosslinker to the purified LexA mutants, and added each Mts-Atf-LC-Biotin modified LexA mutant to RecA under UV light. Distinct bands corresponding to the combined molecular weights of LexA and RecA were observed by SDS-PAGE analysis, were excised from the gel, and are ready to be analyzed by mass spectrometry. Furthermore, we prepared cysteine mutants of E. coli LexA for future crosslinking experiments using proteins from the same organism.

Manipulation of the Electronic and Optical Properties of
Phenylenevinylene-Based Oligomers Through Variation in Endcapping Groups

Grace Babula

As global energy consumption continues to grow, research in renewable energy sources becomes increasingly important.  The Park Lab is interested in improving the efficiency of bulk heterojunction organic solar cells by inducing self-assembly within the active layer.  We worked on developing a synthetic route to phenylenevinylene-based oligomers to serve as potential donor and acceptor materials and explored the effects of extending conjugation, altering the terminal groups, and introducing anthracene components on the electronic and optical properties of the oligomers.  A dimeric and trimeric species, along with several other variations, were successfully synthesized and we determined that the identity of the terminal groups has significant effects on the properties of our oligomers.

Investigating LexA-RecA Binding Through Crosslinking Studies

Roop Dutta

The bacterial SOS response is activated by the RecA-mediated autocleavage of the LexA repressor and leads to the subsequent induction of a set of DNA repair and cellular survival genes. This response, characterized by increased DNA repair and mutagenesis, has been hypothesized to be a cause of antibiotic resistance in bacteria. If this is the case, drugs could be developed to inhibit the LexA-RecA interaction to combat antibiotic resistance. However, the specific amino acid interactions between RecA and LexA are not known. The research described here is aimed at identifying these interactions using crosslinking analysis. Previous studies in the Lovett lab have shown that there are 14 surface amino acids conserved between B. subtilis LexA and E. coli LexA that may be critical to LexA-RecA interaction in their respective species. Bergethon (2009) produced 14 B. subtilis LexA mutants in which each of these surface amino acids was mutated to a cysteine. Bruton (2011) attached an Mts-Atf-LC-biotin crosslinker to these unique cysteines, but was unable to crosslink the LexA adduct to E. coli RecA presumably because LexA was cleaved before crosslinking could occur. We added a second mutation, S127A, to each of the 14 LexA mutants in order to inhibit LexA cleavage activity and we show that Mts-Atf-LC-biotin was successfully attached to 10 of these LexA double mutants.  We also provide evidence that the Mts-Atf-biotin-LexA I101C/S127A adduct was crosslinked to E. coli RecA.

Partially Fluorinated Sidechains in Influencing Poly(p-phenylenevinylene) Behavior and Promoting Self-Assembly

Daniel Gross

Development of efficient and robust organic photovoltaic devices would confer several important advances in the way solar energy is harvested. With the ultimate goal of improving organic solar cell efficiency, we are attempting to influence morphology of the light-absorbing “active layer” of these devices. We wish to promote formation of nanoscale features conducive to enhanced photoconversion. Using polyphenylenevinylenes (PPVs) as a model system, and taking advantage of hydrocarbon-fluorocarbon interactions to promote phase segregation, we hope to develop a general strategy for controlling thin-film morphology that can be extended to other active layer materials.

We have prepared a library of PPVs incorporating partially-fluorinated sidechains, made to possess different linear architectures, and these materials have been characterized using range of techniques, for comparison to MDMO-PPV. In particular, we report here on the absorption behavior and the fluorescence quenching behavior of our polymers. Polymer degradation is also discussed.

Developing a High-Throughput Fluorometric Assay
to Screen for SOS System Inhibitors

Andrew Kung

The bacterial SOS system is a DNA repair mechanism whose activation has been strongly linked to the development of antibiotic resistance, a growing problem in the medical field.  Here, we develop a high-throughput assay to screen for inhibitors of the SOS system, exploiting the fluorescence properties of the LexA protein, whose autocleavage in vivo activates the DNA repair mechanism.  The assay was successfully used to find two potential SOS system inhibitors from a library of bioactive compounds: N2-[3,5-di(trifluoromethyl)phenyl]-5-chlorothiophene-2-sulfonamide and ethyl 5-{2-[2-(4-chlorophenyl)-1-cyano-2-oxoethylidene] hydrazino}-3-methylisothiazole-4-carboxylate.  Both compounds exhibit inhibition in fluorescence-based assay as well as SDS-PAGE gel electrophoresis.  Further testing of these two compounds as well as screening more compounds with the assay may lead to better understanding of SOS system regulation, with tremendous potential in pharmaceutical applications.

An Examination of Undecylprodigiosin Production
in Streptomyces coelicolor A3(2)

Erin A. McGonagle

The Streptomyces are a genus of gram positive, soil dwelling actinobacteria with a multicellular lifecycle that are prolific producers of secondary metabolites including antibiotics. Streptomyces coelicolor has been used as a model organism for understanding the molecular pathways that lead to both physiological and morphological development in the genus at large. S. coelicolor produces 5 antibiotics, one of which, undecylprodigiosin, is of particular interest as it has been shown to induce apoptosis in human breast carcinoma cells. The potential pharmaceutical implications of undecylprodigiosin give incentive to understanding and maximizing its biosynthesis in S. coelicolor. Previous studies found that a SCO6673 mutant, which bears a disruption in a phosphopantetheinyl transferase (PPTase)-encoding gene, exhibits a 5-fold increase in undecylprodigiosin production relative to the wild type concomitant with a complete elimination of calcium-dependent antibiotic (CDA) production.

The intent of this current study was to further maximize undecylprodigiosin production in the SCO6673 mutant hyperproducer. The strategy was twofold: maximization via genomic manipulation and maximization via manipulation of the environment. With regard to genomic manipulation, the gene encoding an antibiotic down-regulator wblA was disrupted in both the SCO6673 mutant and wild type (M145) strain backgrounds. While the data quantifying undecylprodigiosin production in the wblA mutants remains preliminary, it suggested that there was no effect of a wblA disruption on antibiotic production in S. coelicolor. In terms of manipulating the environment, wild type and SCO6673 mutant strains were elicited with dead Bacillus subtilis cells. The introduction of B. subtilis to S. coelicolor liquid cultures was found to instigate a statistically significant 5 to 6-fold increase in undecylprodigiosin in both strain backgrounds, the largest increase in undecylprodigiosin production recorded in the SCO6673 mutant to date.

The second intent of this study was to elucidate the molecular mechanism behind the increase in undecylprodigiosin production in the SCO6673 mutant. One approach to this goal involved the comparison of undecylprodigiosin production in a CDA biosynthetic gene mutant and the SCO6673 mutant in order to determine the extent to which CDA elimination influences undecylprodigiosin production. The data indicated that the hyperproduction of undecylprodigiosin in the SCO6673 mutant is not solely due to an influx of metabolic precursors from the disrupted CDA pathway to the undecylprodigiosin pathway. It is therefore likely that the SCO6673 PPTase somehow indirectly affects the regulation of the undecylprodigiosin pathway.

Synthesis of Amphiphilic Glycopolymers for Micellization and Recognition

Michelle M. McRae

The development of self-assembling glycopolymers has the potential to profoundly affect modern medicine due to their ability to serve as inert drug carriers that safely shepherd drugs to malignant cells. This delivery can be targeted by taking advantage of the enhanced permeability and retention (EPR) effect and by functionalizing polymers with sugar moieties to target cell lines that over express particular receptors. With this in mind, amphiphilic diblock copolymers poly(2-(b-D-glucosyloxy)ethyl methacrylate)-co-poly(tert-butyl acrylate) and poly(2-(a-D-mannosyloxy)ethyl methacrylate)-co-poly(tert-butyl acrylate) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization.

The mannose containing glycopolymer, poly(2-(a-D-mannosyloxy)ethyl methacrylate)-co-poly(tert-butyl acrylate), demonstrated self-assembling properties, exhibiting a low critical micelle concentration ranging from 0.00928 mg/mL to 0.00743 mg/mL for pH 3.9 and pH 8.0, respectively. Dynamic light scattering (DLS) confirmed the presence of micelles with an average diameter of 32 nm. Both copolymers were shown to interact with concanavalin A (ConA), an indication that the sugar functionality of these glycopolymers could successfully bind to receptors. Due to this self-assembling nature and receptor recognition abilities, polymers such as these have a promising future in the field of drug delivery.

Potential Role of SCO6672 in Regulation of Antibiotic Production in Streptomyces coelicolor

Kenneth Tyler Murgo

Streptomyces coelicolor is the model organism for the genus Streptomyces, a group of gram positive, filamentous, soil-dwelling bacteria. Streptomyces are known for prolific production of bioactive secondary metabolites, including over two-thirds of the pharmaceutically important antibiotics. These antibiotics are often synthesized by non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS). Phosphopantetheinyl transferasees (PPTases) are essential to antibiotic production in Streptomyces because they post-translationally activate carrier protein domains by catalyzing the attachment of a 4’-phosphopantetheine group (Ppant). This modification occurs on the carrier proteins/domains of the biosynthetic enzymes, thus converting the apo-carrier protein to its activated holo-form. The SCO6673 PPTase is one of three in Streptomyces coelicolor, and it has been shown to be required for calcium-dependent antibiotic  (CDA) biosynthesis.

Immediately upstream and overlapping the SCO6673 PPTase gene is SCO6672; the corresponding SCO6672 protein has a likely metallophosphoesterase domain and is homologous to calcineurin. It was predicted that SCO6672 is a phosphodiesterase that reverses the post-translational modification performed by SCO6673 on the CDA synthetase by hydrolyzing the bond between the Ppant cofactor and the peptidyl carrier protein (PCP) domains and thereby inactivating the CDA synthetase. To test this model, pure CDA holo-PCP2 was incubated with pure SCO6672. As assessed by MALDI-TOF mass spectrometry, the holo-PCP2 was completely converted to the apo-form in the presence of SCO6672. This confirmed that in vitro SCO6672 catalyzes the inactivation of CDA synthetase (reversing the activation by the SCO6673 PPTase) by catalyzing the hydrolysis of the Ppant cofactor.

To test the in vivo effect of SCO6672 on the production of antibiotics including CDA, a number of SCO6672 knockout, complementation and overexpression strains were created. It was expected that overexpression of SCO6672 would result in the inhibition of CDA production because SCO6672 inactivates CDA synthetase, and this was observed. However, contrary to our expectations, the absence of SCO6672 did not increase CDA production. The production of the antibiotic undecylprodigiosin (RED), a potential anti-cancer drug, was also assayed. The absence of SCO6672 did not change the production of RED, but its overexpression resulted in a significant decrease in RED production. This indicates that SCO6672 has a physiological role that is more complex than just inactivating the CDA synthetase.

Efforts Toward the Total Synthesis of Enigmazole A:
Model Studies of C3 Hydroxyl Deoxygenation

Rachel Patel

Enigmazole A is a complex phosphorylated 18-membered macrolide natural product derived from the marine sponge Cinachyrella enigmatica. The molecule has demonstrated potent tumor-supressing qualities, although its biological mechanism of action remains unclear. Enigmazole A has become a target of synthetic exploration for its biological activity as well as its novel architecture. We envision installing asymmetry in the C₁–C₄ dipropionate unit using the powerful Evans β-ketoimide method. The elegance of this synthetic plan lies in its capability to rapidly and selectively install three of the eight stereogenic centers within the entire molecule. However, the β-ketoimide aldol reaction necessitates a superfluous carbonyl or hydroxyl group at the C₃ position. Herein we present research efforts to construct a model system with a sterically crowded C₃ hydroxyl that resembles the actual system, and subsequent tests of the radical Barton-McCombie deoxygenation and its variations as a method to reduce the C₃ hydroxyl.

Methods for the Synthesis of a Family of Deuterofluorocarbons

Emma Pelegri-O’Day

Deuterofluorocarbons are volatile compounds that have utility in spectroscopic studies, both for their high boiling point and manageable computational size. However, many are not commercially available. Previous efforts developed [1] and improved upon [2] a method for synthesizing deuterofluorocarbons from their iodofluorocarbon precursors in high isotopic purity and yield and with relativity low cost. This work reports further optimization of the synthetic method using the previously synthesized deuterofluorocarbon 1,1,1,2,2,3,3,4,4-nonafluoro-4-deuterobutane (1D-nfb). The resulting synthetic conditions are then applied to the synthesis of additional deuterofluorocarbon products, namely 1,1,1,2,2,3,3,4,4-nonafluoro-5,5,6,6,-tetrahydro-6-deuterohexane  (1D-4H-nfh), 1,1,1,2,2,3,3,4,4,5,5-undecafluoro-5-deuteropentane  (1D-pfp) and  1,2,3,4,5-pentafluoro-6-deuterobenzene (1D-pfb). The synthesis of the volatile 1,1,1,2,2,3,3-heptafluoro-3-deuteropropane  (1D-hfp) is also attempted but remains incompletely optimized due to challenges associated with its low reactivity and high boiling point.  Synthetic trials are analyzed by ¹⁹F, ¹³C and ¹H-NMR as well as GC/MS and FTIR spectroscopies to quantitatively assess isotopic purity and conversion. The optimized reaction conditions demonstrate selective conversion to the desired deuterofluorocarbon across a range of iodide substrates and can be applied to related substrates with similarly successful results.

Secreted Proteins and Development in Streptomyces coelicolor

Hetal Ray

Streptomyces are a genus of soil-dwelling, gram-positive bacteria important for their unique developmental complexity and secondary metabolism. Their intricate morphological development is believed to be influenced by extracellular proteins. Through the study of an rsuA mutant of S. coelicolor that fails to produce an aerial mycelium (NY415), several σ^U regulon members were implicated in multiple stages of the organism’s development. Significantly, extracellular protease activity seems to be intimately tied to proper development. Disruption of salO, which encodes a putative protease, induced premature spore germination. Disruption of SCO0732, another putative protease-encoding gene, had a developmental effect on S. coelicolor by not only reducing sporulation but also affecting the viability of its hyphae. Moreover, overexpression of SCO0732 also reduced sporulation; it is thus clear that an optimal expression level of SCO0732 is necessary for proper development of S. coelicolor. In addition to protease-encoding σ^U regulon members, SCO0930, SCO2217, and SCO6650 were implicated in development in this study. Disruption of SCO0930 in the wild type background reduced sporulation while disruption of SCO2217 blocked aerial mycelium formation and led to weaker growth. Also, a SCO6650-rsuA double mutant showed weaker growth and a severely extended delay in actinorhodin secretion as compared to the rsuA single mutant. Lastly, application of concentrated wild type cell-free culture supernatant to rsuA mutant colonies restored their development. STI, an extracellular protease inhibitor, was purified from this concentrate but it did not cause complementation or have an inhibitory effect on the activity of NY415 proteases, including SCO0732 and SalO.

Copper(I) Complexes of Tridentate Pyridine-Imine Ligands and Their Derivatives and Their Use in Atom Transfer Radical Polymerizations

Zachary Remillard

Atom transfer radical polymerization (ATRP) allows control over the molecular weight, composition, and architectures of polymers. The precise functionalization of the polymers through ATRP allows for the creation of polymers that can perform specific functions in a variety of applications. This control is attained through a dynamic equilibrium which keeps the concentration of free radicals low, preventing termination events. Modifications to the catalyst design alter the position of this equilibrium and therefore the efficiency of ATRP. This study explores how modifications to tridentate heteroaromatic-imine and amine ligands complexed with the copper(I) bromide metal precursor affect the efficiency of the ATRP of styrene. We explore characterizations of our complexes including single crystal XRD, NMR, IR, ESI-MS, and cyclic voltammetry. The XRD data show that the copper(I) centers prefer pseudotetrhedral geometries in the solid state. The NMR and IR data show that changes in bonding of ligand occur upon ligation to the metal center. The polymerization data of styrene mediated by these catalysts is presented and discussed with respect to the structural and electrochemical data. We present several complexes which mediate styrene in an ATRP fashion and other complexes which seem to mediate the polymerization of styrene through other processes. Complex C10 bearing a pyridine-amine-amine ligand catalyzes the polymerization of styrene the most efficiently out of the complexes presented, with low PDI values (1.08 – 1.13) and molecular weight data close to the theoretical molecular weights and high polymerization rates. We also present preliminary polymerization data for a complex with a tetradentate pyridine-amine-pyridine-amine ligand C40 which shows promise as an ATRP catalyst and warrants further study.

The Role of whiJ Genes in the Sporulation Pathway of Streptomyces coelicolor A3(2)

Jennifer J. Rodriguez

Sporulation in Streptomyces coelicolor A3(2) involves synchronous septation of filamentous aerial hyphae to produce single-celled unigenomic spores. Studies of the S. coelicolor life cycle have revealed that sporulation requires whi genes whose encoded proteins are believed to interact in an orchestrated manner in a regulatory cascade involved in key checkpoint events, such as chromosome segregation, sporulation septation, and the characteristic grey polyketide spore pigment production. Of the known early whi genes, the whiJ genes are the least well characterized. This thesis focuses on determining the phenotypic effects of mutation of genes in the whiJ locus (whiJB, whiJA, SCO4544) to resolve two competing models for the relationship of genes within the whiJ cluster.

Chater proposed that the 5’-end of whiJA corresponding to the N-terminus of WhiJA, may be sufficient to encode a DNA-binding domain that represses sporulation genes. We found sporulation activity was not compromised in clean deletion mutants of whiJA and whiJAB, as indicated by visual inspection of the grey phenotype and confirmed by phase-contrast and scanning electron microscopy. However, complementation of the clean deletion mutants with the 5’-end of whiJA did not compromise sporulation as the Chater model would predict. Furthermore, whereas the Gehring group had proposed that SCO4544 represses sporulation, overexpression of SCO4544 in the clean deletion whiJAB mutant, as determined, by RT-PCR, suggested that SCO4544 overexpression is not enough to block the sporulation pathway.  Thus, these results did not fully support either the Gehring or Chater models for the function of whiJ. Quantifying expression of other whi genes involved in sporulation could help shed light on the roles of the whiJ cluster genes in regulating sporulation activity.

Morphological Properties of Fluorinated PPV Copolymers for Photovoltaic Applications, Assessed by Atomic Force Microscopy and Carrier Mobility

Cameron Rogers

Although bulk heterojunction (BHJ) organic photovoltaics potentially enjoy several advantages in comparison to extant photovoltaic technology, their use is presently hampered by their low efficiency.  These devices could be made more efficient if the materials that comprise their active layer could be brought to assume a certain well-ordered morphology; to this end, we have synthesized and characterized fluorinated derivatives of one common active layer material, poly(p-phenylenevinylene) (PPV), in hopes of influencing the polymer’s thin-film morphological properties.  The new polymer materials were studied by Atomic Force Microscopy (AFM), as well as by fabricating diodes from them and determining the mobility of charge carriers in those devices.  These data, together with other observations, have led us to conclude that the polymer materials characterized this year had degraded prior to their study, meaning they will need to be resynthesized and studied again before conclusions about their morphological behavior can be drawn.

ESR Dating of Flint Tools in Dakhleh: Bracketing a New Cultural Unit

Nicole Wise

Obtaining accurate ages for prehistoric artifacts is crucial for expanding our knowledge of the development and spread of early human cultures. For groups which predate the use of writing or extensive building, there is little evidence beyond stone tool remnants. Dr. Kleindienst and Dr. Wiseman, in conjunction with the Dakhleh Oasis Project, have recovered a collection of tools which do not seem to fit into any currently accepted lithographic cultural units, and therefore little is known about their age, or when their makers inhabited the oasis. These tools cannot be directly dated. However, as there is evidence that they were deposited near the boundary of two main sedimentary layers in Dakhleh – red silt and green mud – we attempt to pinpoint their age by determining the age of this boundary. In order to do this, we selected one tooth sample collected from green mud (PT74) and one from red silt (PT66c) to be dated using electron spin resonance spectroscopy. We hoped that they would closely bracket the transition. Unfortunately, PT74 showed inconsistent age results, suggesting exposure to non-homogenous levels of radioactive sediment during burial, and was not a useful marker. PT66c gave an age of 116ka, which is consistent with other red silt dates, but did not extend our knowledge of the boundary age. In the future, more green mud samples need to be collected; increased care in obtaining collection site information could help minimize poor results such as PT74 in the future.

Synthesis and Aggregation of PNIPAM-PDMA Copolymers

Matthew N. Zhou

Macromolecules and nanoparticles have been shown to accumulate in tumor tissue via the enhanced permeation and retention (EPR) effect. Techniques for increasing the size of drugs and drug delivery systems are therefore promising given the need for selective chemotherapy agents. In this research, we explored the aggregation behavior of copolymers of poly(N-isopropylacrylamide) (PNIPAM) and poly(N,N-dimethyl acrylamide) (PDMA) synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. PNIPAM exhibited lower critical solution temperature (LCST) behavior: when heated in an aqueous solution, it precipitated out of solution. Copolymerization with PDMA altered LCSTs, allowing us to tune transition temperatures between 27.5 °C with a PNIPAM homopolymer and 35.7 °C with a 74:26 PNIPAM:PDMA ratio. Dynamic light scattering (DLS) experiments revealed a dependence of aggregate sizes on heating rate, sample concentration, and copolymer composition. For instance, 3.5 μg/mL copolymer samples gave particle sizes in the 100-200 nm range using heating rates of 0.5, 1, and 2 °C/min, these sizes are within the optimal literature range for EPR targeting.

Enzyme-polymer conjugates could potentially serve as therapeutic agents, and previous work with peptide-PNIPAM conjugates suggested that conjugation improved aggregate stability upon undergoing LCST transitions. We used carboxylic acid chain transfer agents (CTAs) during polymerization, resulting in functionalized copolymers. Unfortunately, we were unable to successfully bioconjugate copolymers to a model enzyme, trypsin. Future work should therefore aim to synthesize conjugates for LCST analyses, enzyme activity, and cell toxicity studies.

CHEMISTRY

Identification of Intensity Ratio Break Points from Photon Arrival Trajectories in Ratiometric Single Molecule Spectroscopy

Dieter Bingemann and Rachel M. Allen ’08

International Journal of Molecular Sciences, 13, 7445-7465 (2012)

We describe a statistical method to analyze dual-channel photon arrival trajectories from single molecule spectroscopy model-free to identify break points in the intensity ratio. Photons are binned with a short bin size to calculate the logarithm of the intensity ratio for each bin. Stochastic photon counting noise leads to a near-normal distribution of this logarithm and the standard student t-test is used to find statistically significant changes in this quantity. In stochastic simulations we determine the significance threshold for the t-test’s p-value at a given level of confidence. We test the method’s sensitivity and accuracy indicating that the analysis reliably locates break points with significant changes in the intensity ratio with little or no error in realistic trajectories with large numbers of small change points, while still identifying a large fraction of the frequent break points with small intensity changes. Based on these results we present an approach to estimate confidence intervals for the identified break point locations and recommend a bin size to choose for the analysis. The method proves powerful and reliable in the analysis of simulated and actual data of single molecule reorientation in a glassy matrix.

Di-μ-bromido-bis{[N,N-dimethyl-N'-(thiophen-2-ylmethylidene) ethane-1,2-diamine]copper(I)]}

Christopher Goh, Zachary Remillard ’12, Andre P. Martinez ’09,
Amanda C. Keeley, and Jerry P. Jasinski

Acta Crystallographica E., 68, m691-m692 (2012)

Copper complexes of ligands containing hetero-aromatic and amine donor moieties have multiple applications in metal-catalyzed processes. Examples include catalysts for polymerizations and organic transformations, and model complexes in the biomimetic study of copper proteins. Our group has been interested in the use of neutral tridentate hetero-aromatic-amine ligands in metal-mediated atom transfer radical polymerizations (ATRP). Here we report the synthesis and structure of a doubly bromide bridged dinuclear copper(I) complex with the ligand N,N-dimethyl-N‘-(thiophen-2-ylmethylene)ethane-1,2-diamine, [Cu₂Br₂(C­₉H₁₄N₂S)₂]. In the crystal structure of this title compound the molecule resides about a crystallographic inversion center. The coordination sphere around each copper ion has a distorted tetrahedral geometry, with ligation by two bridging bromide ions, an amine N atom and an imine N atom. The thiophene ring is disordered over two sites, with occupancies of 0.719 (3) and 0.281 (3).  Weak C–H – p interactions feature in the crystal packing.

Hammett Correlations of Benzhydrylium Cations

Sarah L. Goh, William H. Parsons ’07, Louisa Hong ’08, and J. Hodge Markgraf (deceased)

Chemical Educator 17, 53-56 (2012)

This laboratory experiment investigates linear free energy relationships between Hammett s⁺ parameters and the ¹H-NMR chemical shifts of substituted benzhydrol reagents. The significance of resonance and field effects on proton shielding can be determined by relating chemical shift data to various forms of Hammett equations. Benzhydrylium cations can be studied as well by ¹³C-NMR spectroscopy.

Complex Dynamics in a Modified Lotka-Volterra Model with Predator Pairing

Syed Kashif Akhtar ’06, Alison B. Peet ’03, and Enrique Peacock-López

Journal of Biological Systems, 20, 87-108 (2012)

In this work we propose an ecological model, which is a modified version of the Bazykin model.  This model of predator–prey interaction emphasizes predator pairing that yields steady state, periodic and extinction stable solutions.  Moreover, we find attractor coexistence between limit cycles, steady states, and the extinction solution, which is always a stable attractor.  We also study this model as a spatially extended system in one and two dimensions and obtain Turing patterns such as stripes and spots as well as the so-called black-eye patterns, and, as in the homogeneous case, the spatial patterns coexist with the homogeneous extinction solution.

Switching Induced Complex Dynamics in an Extended Logistic Map

Erik A. Levinsohn ’12, Steve A. Mendoza ’13, and Enrique Peacock-López

Chaos, Solitons and Fractals, 45, 426-432 (2012)

Switching strategies have been related to the so-called Parrondian games, where the alternation of two losing games yields a winning game.  We can consider two dynamics that, by themselves, yield different simple dynamical behaviors, but when alternated, yield complex trajectories.  In the analysis of the alternate-extended logistic map, we observe a plethora of complex dynamic behaviors, which coexist with a super stable extinction solution.

Self-regulation in a Minimal Model of Chemical Self-replication

Sylvia J. Lou ’09 and Enrique Peacock-López

Journal of Biological Physics, 38, 349-364 (2012)

In biological systems, regulation plays an important role in keeping metabolite concentrations within physiological ranges.  To study the dynamical implications of self-regulation, we consider a functional form used in genetic networks and couple it to a mechanism associated with chemical self-replication.  For the two-variable minimal model, we find that activation can yield chemical toggles similar to those reported for gene repression in E. coli as well as more complex dynamics.

Seasonality as a Parrondian Game

Enrique Peacock-López

Physics Letters A, 375, 3124-3129 (2011)

Switching strategies can be related to the so-called Parrondian games, where the alternation of two losing games yields a winning game.  We consider two dynamics that by themselves yield undesirable behaviors, but when alternated, yield a desirable oscillatory behavior.  In the analysis of the alternate-logistic map, we prove that alternating parameter values yielding extinction with parameter values associated with chaotic dynamics results in periodic trajectories.  Ultimately, we consider a four season logistic model with either migration or immigration.

Stereochemically Versatile Synthesis of the C1—C2 Fragment of Tedanolide C

Thomas E. Smith ’88, Sarah J. Fink ’08, Zebulon G. Levine ’11,
Kerani A. McClelland ’10, Adrian A. Zackheim ’09, and Mary E. Daub ’11

Organic Letters, 14, 1452-1455 (2012)

A flexible synthesis of the C1–C12 fragment of tedanolide C has been accomplished in eight steps from 2-methyl-2,4-pentadienal. Asymmetric hydroformylation of a 1,3-diene allows for the late-stage generation of either C10 epimer with complete catalyst control. Diastereoselective addition of an isobutyryl b-ketoester dianion to an a,b-disubstituted chiral aldehyde sets the C5 stereochemistry while installing the geminal dimethyl unit. Differential protection of a syn-1,3-diol is performed as a highly efficient single-pot operation.