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E N O A E S S S L T A E A C R C I N S M S E E H C C TI N O CA March 2010 Vol. LXXXVIII, No. 7 N • AMERI Monthly Meeting Richards Medal Award Meeting at Harvard Richards Award to Professor Richard N. Zare

Book Review Echoes of Life: What Fossil Molecules Reveal about Earth’s History Reviewed by Mindy Levine

Summer Scholar Report By Rita E. Ciambra, Eva Vennmann, Katherine H. Schiavoni, and Ekaterina Pletneva

My Internship Experiences By Rajeev Chorghade 2 The Nucleus March 2010 The Northeastern Section of the American Chemical Society, Inc. Contents Office: Anna Singer, 12 Corcoran Road, Burlington, MA 01803, 1-800-872-2054 Book Review 4 (Voice or FAX) or 781-272-1966. ______e-mail: [email protected] Echoes of Life: What Fossil Molecules Reveal about Earth’s History Any Section business may be conducted via the business office above. Reviewed by Mindy Levine NESACS Homepage: Monthly Meeting 5 http://www.NESACS.org ______David Cunningham, Webmaster Richards Medal Award Meeting at Harvard ACS Hotline, Washington, D.C.: 1-800-227-5558 Award to Richard N. Zare, Stanford University 13th Weinberg Symposium Report 6 Officers 2010 ______Chair: John McKew Announcements 6,7 Wyeth Research ______200 Cambridge Park Drive Norris and Richards Undergraduate Research Scholarships Cambridge, MA 02140 2010 NESACS Candidates for Election 617-665-5603; jmckew(at)wyeth.com My Internship Experiences 8 Chair-Elect: ______Patrick M. Gordon 1 Brae Circle By Rajeev Chorghade Woburn, MA 01801 Summer Internship Research Report 9 gordonpat(at)emmanuel.edu ______Immediate Past Chair: By Christopher S. Daeffler, Rajeev Chorghade, Dr. E. Joseph Billo Mukund Chorghade, and Robert H. Grubbs 13 Shattuck Street Natick, MA 01760 Summer Scholar Report 10 508-653-3074, joseph.billo(at)verizon.net ______Secretary: Redox Reactivity, Ligand Substitution, and Conformational Michael Singer Changes in Geobacter Heme Protein GSU0935 Sigma-Aldrich By Rita E. Ciambra, Eva Vennmann, Katherine H. Schiavoni, and Ekaterina 3 Strathmore Rd, Natick, MA 01360 508-651-8151 X291, msinger(at)sial.com Pletneva Treasurer: Advances in Chemical Sciences Symposium 13 James Piper ______19 Mill Rd, Harvard, MA 01451 March Historical Events in Chemistry 15 978-456-3155, piper28(at)attglobal.net ______Auditor: By Leopold May, Catholic University of America Anthony Rosner Cover: Archivist: Professor Richard N. Zare of Stanford University. 2010 recipient of the Myron S. Simon 20 Somerset Rd, Newton, MA 02465 Theodore Richards Medal. (Photo courtesy of Linda Cicero, Stanford News Serv- 617-332-5273, romysimon(at)mindspring.com ice) Trustees: Deadlines: Peter C. Meltzer, Esther A. H. Hopkins, May 2010 Issue: March 11, 2010 Michael E. Strem Summer 2010 Issue: June 15, 2010 Councilors Alternate Councilors Term Ends 12/31/2010 Thomas R. Gilbert Timothy B. Frigo Pamela Nagafuji Mark Froimowitz Robert Lichter David Cunnigham Michael Singer Mukund Chorghade The Nucleus is published monthly, except June and August, by the Northeastern Section of the American Term Ends 12/31/2011 Chemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Text Doris I. Lewis C. Jaworek-Lopes must be received by the editor six weeks before the date of issue. Mary Burgess Patrick M. Gordon Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G, Morton Z. Hoffman Lawrence Scott Michael P. Filosa Donald Rickter Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070 Kathi Brown Liming Shao Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273, Term Ends 12/31/2012 Sheila E Rodman, Konarka Technologies, Inc., 116 John St. Suite 12, Lowell, Amy E. Tapper Michaeline F. Chen MA 01852 Email: srodman(at)konarka.com tel 978-569-1414, Catherine E. Costello Jerry P. Jasinski Mindy Levine, 516-697-9688 (c), 617-258-6536(w), mindy.levine(at)gmail.com Patricia A. Mabrouk Gary R. Weisman Assistant Editors: Stefan G. Koenig, Sonia Taktak Dorothy J. Phillips Marietta Schwartz Board of Publications: Vivian K. Walworth (Chair), David Cunningham, Mary Mahaney Ruth Tanner Norton P. Peet Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622 All Chairs of standing Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050, Committees, the editor Email: [email protected]; Tel: 781-837-0424 of THE NUCLEUS, and Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews the Trustees of Section Calendar Coordinator: Sheila Rodman, email: srodman(at)konarka.com Funds are members of the Photographers: Morton Z. Hoffman and James Phillips Board of Directors. Any Proofreaders: Donald O. Rickter, Vivian K. Walworth, Mindy Levine Councilor of the American Chemical Society residing within the section area is an ex officio Webmaster: David Cunningham, webmaster(at)nesacs.org member of the Board of Directors. Copyright 2010, Northeastern Section of the American Chemical Society, Inc. The Nucleus March 2010 3 Book Review Corporate Patrons ($2000+) Abbott Bioresearch Echoes of Life: What Fossil Molecules Reveal about Earth’s Genzyme Lyophilization Service of New England History, Susan Gaines, Geoffrey Eglinton and Jürgen Rullkötter Merck (Oxford University Press, 2009), 376pp., ISBN: 9780195176193, Novartis Institute for Biochemical $35, (hardcover) Research Reviewed by Mindy Levine, Massachusetts Institute of Technology, Schering Corporation Department of Chemistry, Cambridge, MA 02139 Sepracor Serono Reproductive Institute Where does oil come from? How did most part, succeeds in entertaining Vertex Pharmaceuticals ancient cultures preserve mummies? readers while conveying knowledge of Wyeth Pharmaceuticals What is the cause of deadly “red tides” an intriguing and constantly evolving Patrons ($1000-$1999) in oceans? scientific field, that of organic geo- Aptuit The answers to these wildly dis- chemistry. Broad Institute parate questions (and many more) are The book is divided into eleven Creagen Biosciences found in the book Echoes of Life: What chapters: Estate of Wallace Gleekman Fossil Molecules Reveal about Earth’s 1. Molecular Informants: A Chang- Irix Pharmaceuticals History by Susan Gaines, Geoffrey ing Perspective of Organic Chem- PCI Synthesis Eglinton, and Jürgen Rullkötter. The istry Shasun USA book provides an overview of the vari- 2. Looking to the Rocks: Molecular Sirtris Pharmaceuticals ous scientific fields in which “fossil Clues to the Origin of Life Strem Chemicals molecules” can provide key informa- tion and understanding about ancient 3. From the Moon to Mars: The Donors ($300-$999) earth. It is not, however, a rigorous sci- Search for Extraterrestrial Life Cambridge-Major Laboratories entific text; nor is it a text for the non- 4. Black Gold: An Alchemist’s Guide Medicilon Inc scientist. Rather, the book combines to Petroleum Organix anecdotes about the scientists with 5. Deep Sea Mud: Biomarker Clues Peptech Corp actual stories of scientific discovery. to Ancient Climates SAPA-NE The result is a narrative that, for the 6. More Molecules, More Mud, and the Isotopic Dimension: Ancient Environments Revealed 7. Microbiologists (Finally) Climb on Board 8. Weird Molecules, Inconceivable Microbes, and Unlikely Environ- mental Proxies: Marine Ecology Revised 9. Molecular Paleontology and Bio- chemical Evolution 10. Early Life Revisited 11. Thinking Molecularly, Anything Goes Each chapter covers one area in which organic geochemistry has pro- vided an improved scientific under- standing. For example, Chapter 4 investigates how the study of “fossil molecules” has improved our under- standing of the source of petroleum, and how different environmental con- ditions can impact oil production. Chapter 5 discusses fossil molecules that have been discovered in deep-sea continued on page 14

4 The Nucleus March 2010 Monthly Meeting Biography Richard N. Zare is the Marguerite Blake Wilbur Professor in Natural Sci- The 904th Meeting of the Northeastern Section of the American ence at Stanford University with an Chemical Society appointment in the Department of 2010 ACS Richards Medal Award Meeting Chemistry and a courtesy appointment Thursday – March 4, 2010 in the Department of Physics. He is a graduate of Harvard University, where Harvard Faculty Club he received his B.A. degree in chem- 20 Quincy St., Cambridge, MA istry and physics in 1961 and his Ph.D. 5:30 pm Social Hour in chemical physics in 1964. In 1965 he became an assistant professor at the 6:15 pm Dinner Massachusetts Institute of Technology, 8:15 pm Richards Award Ceremony but moved to JILA, University of Col- Mallinckrodt Building, Pfizer Lecture Hall - MB23, orado at Boulder in 1966, where he 12 Oxford Street, Cambridge, MA. remained until 1969 while holding Dr. John McKew, NESACS Chair, Presiding joint appointments in the Department of Chemistry, and the Department of Reflections on Theodore William Richards Physics and Astrophysics. In 1969, he Prof. Roy G. Gordon, Chair, Richards Medal Committee was appointed to a full professorship in Introduction of the 41st Richards Medalist the Department of Chemistry at Professor Mark A. Johnson, Yale University Columbia University, becoming the 2010 Richards Medalist Higgins Professor of Natural Science Prof. Richard N. Zare, Marguerite Blake Wilbur Professor in Natural in 1975. In 1977 he moved to Stanford Science, Stanford University, Palo Alto, CA. “Theodore W. University, where he has been chair of Richards Redux: Determining Isotope Ratios without Mass Spec- their chemistry department since 2004. trometers” He has also been active in public serv- ice, serving on the National Science Dinner reservations should be made no later than noon, Thursday, February 25, Board, the policy-setting body of the 2010. Please call or fax Anna Singer at 800-872-2054 or e-mail at secretary@ National Science Foundation, from nesacs.org. Please specify vegetarian. Reservations not cancelled at least 24 1992 to 1998, the last two years as its hours in advance must be paid. Members,$30; Non-members, $35; Retirees, chair. $20; Students, $10. Zare has made fundamental con- THE PUBLIC IS INVITED tributions to chemical analysis. His Anyone who needs special services or transportation, please call Anna Singer a earliest studies were on the use of laser- few days in advance so that suitable arrangements can be made. Free parking in induced fluorescence (LIF) as a means rd the Broadway St. Garage (3 level or higher), enter from Cambridge Street via to determine molecular structure and Felton, St. as a detection tool for chemical reac- Continued on page 16

weights of more than 20 elements, that all of the radioactive specimens Abstract determined in many cases to five sig- possess a lower atomic weight than nificant figures. Richards thought that ordinary lead, as determined under Theodore W. Richards Redux: the atomic weights of the light ele- identical conditions, the deficiency in Determining Isotope Ratios ments were immutable constants, like one case amounting to as much as 0.75 without Mass Spectrometers the numerical values of e and π but his of a unit.” Since then, different iso- work on lead from different sources, topes, stable and radioactive, have The first American scientist to win the radioactive and non-radioactive, been established to exist for all the ele- Nobel Prize in Chemistry was Profes- helped to confirm the existence of iso- ments. Mass spectrometers have been sor Theodore W. Richards, Harvard topes. To quote from his 1914 Journal used to determine the most precise val- University, who was honored “in of the American Chemical Society arti- ues of isotopic weights, abundances, recognition of his accurate determina- cle,1 “In this paper a description is and ratios, but such devices are large, tions of the atomic weight of a large given of parallel experiments deter- costly, and require operation by number of chemical elements.” mining the equivalent weights of vari- experts. In this lecture, I will describe a Richards’ painstaking, careful investi- ous samples of lead chloride obtained different approach based on isotopic gations led to highly accurate atomic from different sources. It was found Continued on page 16

The Nucleus March 2010 5 The 13th and Announcement th The James Flack Norris and 14 Andrew Theodore William Richards Undergraduate Summer H. Weinberg Research Scholarships Memorial The Northeastern Section of the Amer- Lee Helman, MD at the 13th annual Weinberg ican Chemical Society (NESACS) Memorial Lecture established the James Flack Norris and Lectures Society, and the Dana Farber Cancer Theodore William Richards Under- Institute, the Andrew H. Weinberg graduate Summer Scholarships to Despite decades of research into new Pediatric-Chemotherapy Drug Devel- honor the memories of Professors Nor- drugs to treat cancer, more effort is opment Symposium was established in ris and Richards by promoting research needed to develop targeted therapies 1994. This annual symposium brings interactions between undergraduate for the unique tumors of childhood and together a broad array of physicians, students and faculty. to avoid the toxic side effects of ther- researchers, academicians, and politi- continued on page 7 apy. Most anti-cancer drugs were origi- cal allies with one focus – the develop- nally developed to combat adult ment of new therapies and approaches cancer. Indeed, in the past 50 years, for the treatment of pediatric cancer. treatment strategies for battling child- only 16 new anti-cancer drugs that Last year, thanks to the generosity hood sarcomas. He discussed Ewing’s have been developed to address child- of many individuals and corporations, sarcoma and rhabdomyosarcoma, hood cancer have received FDA the Andrew H. Weinberg Memorial which are driven in part by overactive approval for use in the U.S. Jimmy Fund Walk team raised growth signaling involving the insulin- To help tackle this problem, and over $5,000. This generosity allowed like growth factor receptor (IGFR). with the generous support of family us on April 7th 2009 to welcome our IGFR enables cancer cells to survive and friends, as well as the Medicinal keynote speaker, Lee Helman, M.D, a and avoid cell death. He is testing Chemical Group, the Northeastern world-renowned National Cancer Insti- antibodies that block the receptor in Section of the American Chemical tute scientist who researches new clinical trials. Tumors have shrunk in certain patients, but the responses have been temporary, prompting further research into this approach. On Monday May 24, 2010, inter- nationally renowned scientist and can- cer drug developer, Stephen W. Fesik, Ph.D., of Vanderbilt University Med- ical Center, and formerly of Abbott Laboratories, will deliver this year’s Weinberg Symposium address and meet with Dana- Farber researchers. Details of the lecture will be in the upcoming edition of The Nucleus. Dr. Fesik has published more than 230 papers, trained more than 27 postdoc- toral fellows, has been a reviewer for the NIH Biophysical Chemistry Study Section, and has served as a member of the Editorial Boards of the Journal of Medicinal Chemistry, Journal of Bio- molecular NMR, Biophysical Journal, Molecular Cell, Chemical Biology & Drug Design, ChemMedChem, Molec- ular Cancer Therapeutics, Oncogene, and the Highlights Advisory Panel for Nature Reviews Cancer. continued on page 17

6 The Nucleus March 2010 Announcement Councilor/Alternate (vote for 8) NESACS Dora Carrico-Moniz Continued from page 6 Mukund Chorghade Resea rch awards of $3500 will be Candidates Tim Frigo given for the summer of 2010. The Mark Froimowitz student stipend is $3000 for a mini- Tom Gilbert mum commitment of ten weeks of full- for 2010 Leland L. Johnson Jr. time research work. The remaining Bob Lichter $500 of the award can be spent on sup- Ken Mattes plies, travel, and other items relevant Election Raj Rajur to the student project. From the 2010 Nominating Committee: Mary Schultz Institutions whose student/faculty Joseph Billo (chair), Michaeline Chen, Michael Singer team receives a Norris/Richards Michael P. Filosa, Morton Z. Hoffman, Sofia Su Undergraduate Summer Research Ralph Scannell Al Viola Scholarship are expected to contribute Nominating Committee (vote for 2) toward the support of the faculty mem- Chair-Elect (vote for 1) Ruth Tanner Mukund Chorghade bers and to waive any student fees for Ken Mattes summer research. Academic credit Treasurer (vote for 1) Raeanne Napoleon may be granted to the students at the James Piper Raj Rajur discretion of the institutions. Auditor (vote for 1) Norris Award Committee (vote for 2) Award winners are required to Anthony Rosner submit a report (~5-7 double-spaced Doris Lewis Trustee (vote for 1) pages including figures, tables, and Bob Lichter Esther Hopkins bibliography) of their summer projects Jason Pontrello Martin Idelson to the NESACS Education Committee Mary Schultz by November 1, 2010 for publication Director-at-Large (vote for 2) Petition candidates: “Any group com- in The Nucleus. They are also required John Burke prising 2 percent or more of the mem- to participate in the Northeast Student David Harris bership of the Northeastern Section Chemistry Research Conference Steve Lantos [136 members] may nominate candi- Raeanne Napoleon dates …”. See the NESACS website (NSCRC) in April, 2011. N for details. Eligibility: Applications will be accepted from student/faculty teams at colleges and universities within the Northeastern Section. The undergrad- uate student must be a chemistry, bio- chemistry, chemical engineering, or molecular biology major in good standing, and have completed at least two full years of college-level chem- istry by Summer 2010. Application: Application forms are available on the NESACS web site at http://www.nesacs.org. Completed applications are to be submitted no later than April 2, 2010 to the Chair of the Selection Committee: Professor Edwin Jahngen University of Massachusetts Lowell Chemistry Department, Room 520, Olney Hall 1 University Avenue Lowell, MA 01854-5047 Notification: Applicants will be noti- fied of the results by e-mail on April 23, 2010 with written confirmation to N follow.

The Nucleus March 2010 7 (Chemistry), and Harvard Medical oratories where Lord Thompson dis- My School (Biomedical Sciences). Step- covered the electron, where Wilson ping into these hallowed institutions invented the cloud chamber, where Internship where so much wonderful work was Lord Todd explored the chemistry of done filled me with awe and inspira- nucleic acids, and where Watson and tion. Working with such extraordinar- Crick postulated the structure of DNA Experiences ily distinguished scientists as Steven was a dream come true. I even saw the Ley (Fellow of the Royal Society), famous pub where Watson and Crick By Rajeev Chorghade, Natick High Robert Grubbs (Nobel Laureate), and burst in at lunch and announced “We School, Natick, MA Vikas Sukhatme (Chief Academic have now found the secret of life.” NESACS has benefited from having Officer, Harvard Medical School) were Professor Vikas Sukhatme and countless geniuses and scientists of memorable experiences that have truly colleagues at the Harvard Medical stature from the triad of academia, shaped my scientific acumen, aspira- School introduced me to the magical government and industry. I have been tions and career goals. world of molecular medicine. I learned inspired by works that illustrate the I learned techniques in flow chem- how to run cell enzyme assays to study pride and joy they took in research, istry, synthetic chemistry and biomed- the effects of pharmaceutical drugs on how insatiable scientific curiosity led ical science, respectively. These living cell lines. I felt welcome to them to question the status quo and internships provided me with unique experience the art and science of dis- make groundbreaking discoveries. My opportunities to discuss with distin- covery, ask questions I had, and have scientific hero was the Nobel Laureate guished academicians, post-doctoral the benefit of distinguished scholars Robert Burns Woodward, who when fellows and graduate students their patiently explaining the workings of questioned by a Senator about how his love for science. At Caltech, I met the methodology. I am truly grateful to work would contribute to the defense Professors Robert Grubbs, Peter Der- have experienced the atmosphere of of America, replied that it “would make van, and others who stimulated my these fantastic laboratories and am America a lot more worth defending.” thoughts and encouraged me by dis- especially privileged to have seen them I have a fascination and passion cussing how they were attracted to sci- as a teenager. for learning science and performing ence. Professor Grubbs showed me These experiences led me to col- laboratory experiments. My parents the laboratories where luminaries laborate in establishing a Science Club and high school teachers instilled a Gilbert Lewis, Robert Millikan and at Natick High School. I insisted on love for the natural sciences in me at Linus Pauling had worked. Seeing the taking AP Chemistry, even though it an early age. I love to delve deeper laboratories where all the scientists was not being offered. My teacher, into the scientific rationale of why about whom I had read in my school Kathi Browne, a NESACS Councilor, things work the way they do, am intel- text books was truly a memorable personally mentors me and I am com- lectually curious, ask numerous ques- experience. In Professor Grubbs’ lab, I pleting the course by independent tions, and am the proverbial sponge for participated in projects on chiral reduc- study. the answers. I watch cooking shows tions and also conducted experiments I am thankful for these exciting where chefs experiment with new on olefin metathesis. opportunities; few high school students methods and ingredients to bring out I was honored to work in the labo- have had such a stimulating introduc- exotic flavors. I am fascinated with ratories of Professor Steven Ley and tion to science. I will use these learn- chefs like Heston Blumenthal, who Syrris/Dolomite Industries in Cam- ing experiences to optimize my adds unique scientific flair to the culi- bridge, England. Microfluidics, academic potential, secure an M.D. known as “lab-on-a-chip,” enables and Ph.D and participate in varied nary world by making desserts with N liquid nitrogen! small-scale fluid control and analysis, activities of NESACS. I strive for a career in research and allowing manufacturers to develop medicine, and aspire to secure M.D. smaller, more cost-effective, and pow- and Ph.D. degrees. I am resolved to erful systems. I joined a team that con- conduct research directed at under- ducted proof of concept, development, standing causative and curative factors and trials for a novel plastic microcap- of sports injuries, and exploring novel illary flow disc (MFD) reactor. Steven Q. Exactly, how many awards and options for preventive care and cure. I Ley was extremely gracious and hos- scholarships does NESACS sponsor? wanted to start research early and pitable; his students made me feel embarked on a quest to work in labora- completely at home in their midst. I a) One b) Two c) Many tories that would provide me training was able to appreciate the history of and intellectual stimulation. I was priv- science by visiting the fabled www.nesacs.org/awards ileged to obtain fabulous summer Cavendish laboratories where 29 internships in Cambridge, UK (Phys - Nobel Prizes were won in the early ics), California Institute of Technology part of the last century. Seeing the lab-

8 The Nucleus March 2010 Summer Internship Research Report Christopher S. Daeffler, Rajeev Chorghade, Mukund Chorghade and Robert H. Grubbs Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA

Part 1: lithium aluminum hydride (LiAlH4), a common reducing agent. Similar methodologies are known but not well- The Asymmetric Reduction of Acetophenone i, ii The construction of chiral molecules (those which are developed. In the reaction mixture, (-)-menthol reacts not superimposable over their mirror image, known as an with LiAlH4 to make lithium tri-menthyloxyaluminum enantiomer) is an important problem in modern organic hydride, which then reduces acetophenone to sec-phenethyl chemistry. These are known as asymmetric reactions alcohol. In our experiments, one enantiomer of sec- because they provide unequal amounts of two mirror-image phenethyl alcohol was obtained in 87% enantiomeric excess molecules, which are identical in every other chemical (ee). Decreased temperature lowers the selectivity of the aspect. Most biomolecules are chiral, and many pharmaceu- reaction (Scheme 2) ticals are as well. One good example of this is the com- Future work will focus on the analysis of the other eas- pound L-DOPA, which is used in the treatment of ily available chiral alcohols as chiral auxiliaries, such as (+)- Parkinson’s disease (Scheme 1). In the final steps of its fenchyl alcohol, (-)-borneol and (+)-isopinocampheol. industrial synthesis, one of the precursor compounds is These may offer a variety of steric environments that can be treated with a chiral rhodium catalyst and hydrogen gas. tailored to different substrates. With the development of a This provides one enantiomer almost exclusively. K. Barry reliable set of reaction conditions, we will also test a variety Sharpless, Ryoji Noyori and William Knowles were of prochiral ketones to demonstrate that this technology is awarded the 2001 Nobel Prize in Chemistry for their contri- applicable to a wide variety of structures. butions to the field of “chirally catalyzed reactions,” under- Figure 1: Inexpensive Chiral Alcohols lining the importance of this area. In our project, we sought an inexpensive chiral reagent that could efficiently perform an asymmetric reaction with- out the need for an expensive transition metal catalyst such as the rhodium complex used in the synthesis of L-DOPA. We decided to start our investigations with the reduction of acetophenone to sec-phenethyl alcohol, using a combination Part II: of (-)-menthol, a readily available chiral alcohol, and Polymerization using the olefin metathesis reaction Scheme 1: Synthesis of L-DOPA Scheme 3: Metathesis of dicyclopentadiene

Scheme 2: Yves Chauvin, Richard Schrock, and Robert H. Grubbs, Enantioselective Reduction of Acetophenone the 2005 Nobel Prize Laureates in chemistry, have made olefin metathesis into one of organic chemistry’s most important reaction. Fantastic opportunities were created for producing many new molecules, including pharmaceuticals and polymers. The word metathesis means “change-places.’ In a metathesis reactions double bonds are broken and made between carbon atoms in ways that cause atom groups to change places. This happens with the assistance of special catalyst molecules. continued on page 16 i Yamaguchi, S.; Kabuto, K. Bull. Chem. Soc. Japan 50, 3033 (1977) ii Chandrasekhar, S.; Raghunandan, R. Tetrahedron: Asymmetry 16, 751 (2005)

The Nucleus March 2010 9 Summer Scholar Report Redox Reactivity, Ligand Substitution, and Conformational Changes in a Geobacter Heme Protein GSU0935 Rita E. Ciambra, Eva Vennmann, Katherine H. Schiavoni, and Ekaterina V. Pletneva, Dartmouth College, Hanover, NH 03755 Maintaining a clean environment is a major problem facing Figure 1a-c the world today, and the continuing search for sustainable or alternative energy sources is an active area of scientific research. Geobacter bacteria have shown potential impor- tance in microbial fuel cells, allowing organic compounds to be converted into electricity.1 Additionally, Geobacter species can oxidize petroleum compounds into carbon diox- ide, thus helping to clean up environmentally hazardous petroleum spills. These bacteria have unusually large num- bers of redox metalloproteins, in particular cytochromes with c-type hemes. Studies of redox reactions in these met- alloproteins are important for understanding chemical prin- ciples that govern Geobacter’s ability to remediate contaminated soil and water and to generate electricity. A recently discovered cytochrome GSU0935 from Geobacter sulfurreducens switches its axial ligand H2O to Met60 upon reduction of the heme iron (Figure 1a).2 This change in the metal coordination environment is expected to affect the redox reactivity of the heme and could also require changes in the protein conformation. However, the reasons for ligand substitution in the redox reactions of GSU0935 and other proteins are unclear. We have therefore designed an experimental system to examine reduction and accompanying conformational changes in GSU0935. The reduction is driven by a photoex- citation of a covalently attached Ru(II)-bipyridyl complex (Figure 1b), which creates a strong reducing agent, *Ru2+ . The *Ru2+ species rapidly reduces the heme and the result- ing conformational changes can be followed by kinetic methods (Figure 1c). We have prepared the GSU0935 mutant Gly58Cys and the cysteine-specific reagent 2+ Ru(bipy)2(5-iodoacetamido-1,10-phenanthroline) , Ru(bipy)2phen-IA, and studied the photoinduced reduction in the Ru-bipyridyl-labeled protein. Materials and Methods: Preparation of the Mutant DNA. The construct for the wild-type GSU0935 fused to the ELP purification tag2 served as a template for the mutation Gly58Cys. The mutant ampicillin and 34 mg/mL chloramphenicol. After shaking DNA was prepared with a Quickchange kit from Stratagene for 5 hours at 37°C, the contents of the flask were used to and purified using a QIAprep Spin Miniprep Kit. The muta- inoculate six 2.8 L flasks containing 2XYT media and tion was confirmed by sequencing carried out at the Molec- antibiotics. These cultures were grown overnight at 250 rpm ular Biology & Proteomics Core Facility at Dartmouth and 25°C. When the absorbance at 600nm reached 0.9-1.0, College. the cultures were induced with 50 µM isopropyl-beta-D- Protein Expression. The plasmid encoding the thiogalactopyranoside (IPTG). Incubation was continued GSU0935 mutant (AmpR) was cotransformed into E.coli overnight under the same conditions. SF110 together with the plasmid pEC86 (ChlR) encoding the To harvest the protein, the cultures were centrifuged at proteins responsible for the covalent attachment of the heme 4,000 rpm for 25 minutes at 4°C. The pellet was then resus- group. A single colony from the LB/Amp/Chl plate was pended using a solution of 30% sucrose, 1 mM EDTA, 30 grown in 100 mL of 2XYT media containing 100 mg/mL mM Tris (pH 8.0). The cell suspension was centrifuged at

10 The Nucleus March 2010 4,000 rpm for 20 minutes at 4°C. The resulting pellet was Ru(bipy)2phen-IA in the sample. Guanidine hydrochloride resuspended on ice using a solution of 5 mM MgSO4 and 2 (GuHCl) was necessary to fully elute the protein from the mM sodium phosphate (pH 8.0). The cell suspension was column. The protein was refolded in 10 mM Tris buffer (pH centrifuged at 13,000 rpm for 60 minutes at 4°C. After cen- 8.0) and then applied to a HiTrap Q HP column. Buffer A trifugation, 0.5 mM phenylmethylsulphonyl fluoride was 10 mM Tris (pH 8.0) and buffer B was 10 mM Tris, 1 (PMSF) was added to the supernatant. The Soret peak in the M NaCl (pH 8.0). The labeled protein did not bind to the absorption spectrum at 400 nm indicated the presence of the resin, and unlabeled and aggregated protein eluted as the 0- GSU0935 protein in the sample. 50% gradient of buffer B was applied. Protein Purification. Crystalline NaCl was added to Spectroscopic Measurements. The steady-state the solution of a crude protein to a concentration of 3 M. absorbance and luminescence spectra were measured with The solution became cloudy and was centrifuged at 20,000 Agilent 8453 UV-visible and Horiba Jobin Yvon Fluorolog 3 rpm for 90 minutes at room temperature. The red pellet spectrometers, respectively. The 1H NMR spectra were formed during centrifugation was dissolved in a buffer of 50 measured with a Varian XL-300 NMR spectrometer. Time- mM Tris and 0.5 mM EDTA (pH 8.0). After dissolving, the resolved measurements were obtained using a Continuum solution was centrifuged at 14,000 rpm for 20 minutes at Minilite II Q-switched frequency-doubled Nd:YAG laser as 4°C to remove the insoluble material. The ELP tag was an excitation source, which delivered 5-ns pulses at 532 nm. cleaved overnight at room temperature with rTEV protease. Transient absorbance was measured with a 75 W Xe lamp Gel electrophoresis confirmed the protein cleavage, with the (Oriel, model 66912) as a probe source, with a secondary cleaved protein appearing at 15 kDa and the uncleaved pro- lens focusing the collimated light on a 2-mm aperture. Tran- tein at 55 kDa. sient emission and absorbance were collected perpendicular Two alternative procedures were used to further purify to the excitation beam with a monochromator (Oriel, model the protein on different occasions. The first protocol 77200) placed after the sample. Decay of the *Ru2+ and for- employed a HisTrap and size-exclusion chromatography as mation of the Fe(II) heme were monitored at 620 and 420 previously described.2 The second protocol used ion nm, respectively. Transient signals were measured with a exchange chromatography. The ELP tag and uncleaved pro- Hamamatsu R928 photomultiplier tube. The current was teins were precipitated with 3 M NaCl and the solution was digitized using a Lecroy Wavesurfer 64Xs oscilloscope. For centrifuged at 14,000 rpm for 60 minutes at room tempera- each sample measurement, 500-1000 laser shots were accu- ture. The supernatant was dialyzed overnight in a 4 L buffer mulated and averaged. The traces were fitted using solution of 10 mM Tris, 2 mM DTT (pH 8.0) at 4°C. The SigmaPlot 10.0. next day the protein was collected and the minor precipitate Results and Discussion: was removed by centrifugation at 14,000 rpm for 20 min- A single-cysteine mutant Gly58Cys was designed for utes at 4°C. A HiTrap Q HP column connected to GE Ätka- labeling the GSU0935 cytochrome with the Ru(bipy)2phen- purifier FPLC was used to purify the protein further. Buffer IA reagent (Figure 1b). The estimated short Cys58-to-heme A was 10 mM Tris, 2 mM DTT (pH 8.0) and buffer B was 10 distance of 14 Å2 and good electronic coupling5 have sug- mM Tris, 2 mM DTT, 1 M NaCl (pH 8.0). The protein was gested a possibility of fast rate of the Ru-to-heme electron eluted using a 0-100% gradient of buffer B over 100 min- transfer in this Ru-bipyridyl-labeled derivative. The mutant utes and came out of the column at approximately 30% B. Gly58Cys was expressed and purified four times with an Synthesis of Ru(bipy)2phen-IA. 5-Iodoacetamido- average yield of 0.05 mg pure protein per liter of media. 1,10-phenanthroline (phen-IA) and Ru(bipy)2phen-IA were Although the expression yield was low, adequate amounts synthesized according to the previously published 3 of the protein were purified for labeling and preliminary procedure with the following minor modifications. spectroscopic experiments. Iodoacetyl chloride instead of iodoacetic acid was used in Several techniques for protein purification were the first step of the synthesis. The crude phen-IA product explored. The first steps of purification, to the ELP-tag was ground to a powder and washed in a solution of 5% 2 1 cleavage, were based on a previously published study. Fur- sodium bicarbonate. H NMR spectra confirmed the forma- 4 ther purification of the protein was accomplished using a tion of phen-IA and the final product, Ru(bipy)2phen-IA. new protocol involving ion exchange chromatography. After Protein Labeling. The purified protein was applied purification, spectroscopic properties of the Gly58Cys onto a PD-10 desalting column, equilibrated with 100 mM mutant were examined by absorption spectroscopy. The i NaP (pH 7.4). A ten-fold excess of tris(2-car- absorption spectra of the protein were identical to that of the boxyethyl)phosphine (TCEP) was added to the protein solu- wild-type protein, with the Soret band at 400 nm in the oxi- tion while it was being deoxygenated under nitrogen and dized state and at 418 nm in the reduced state (Figure 2a). stirred constantly. After deoxygenation was complete, a These findings suggest that the environment of the heme 2phen-IA was added. The twenty-fold excess of Ru(bipy) group did not appreciably change upon the mutation. resulting solution was stirred for 5 hours in the dark. The The compound Ru(bipy)2phen-IA was chosen for label- reaction mixture was then dialyzed overnight into 10 mM ing because it can be linked to the protein efficiently through sodium acetate (pH 4.5). The dialyzed protein was injected the cysteine-reactive iodoacetamide handle. This compound onto a HiTrap SP HP column, removing excess continued on page 12

The Nucleus March 2010 11 Summer Scholar Conclusions: We have expressed and purified the new Gly58Cys mutant Continued from page 11 of the heme protein GSU0935. The mutant was labeled with was synthesized according to Scheme 1 to give a final yield the Ru(bipy)2phen-IA reagent and its photoinduced reduc- of 31%.3 The absorption (Figure 2a) and emission spectra of tion was studied. The Ru-bipyridyl labeling changes the 3 Ru(bipy)2phen-IA were in accord with the literature data. heme environment presumably by pushing Met60 to coordi- The lifetime of the deoxygenated sample in a sodium phos- nate to the heme iron already in the ferric state of the pro- phate buffer was 770 ns (Figure 2b), which is slower than tein. 2+ that of the widely studied Ru(bipy)3 . Although the prepared Ru-bipyridyl-labeled derivative Scheme 1 does not undergo H2O-to-Met conformational switching upon reduction, it has allowed us to access the reactivity of the Met-bound heme. This derivative will become an impor- tant reference for direct comparison of the redox reactivity of the Met- and H2O-bound hemes. A mutant lacking methionines in the coordination environment of the heme, Gly58Cys/Met60Ala/Met61Val, also labeled at the position 58, could serve as a model of the H2O-bound heme. Further experiments to analyze conformational changes in the pro- tein can be done with other mutants where labeling sites lie on the opposite side of the heme and away from Met60. These experiments, guided by our findings this summer, will be a direction for future research in the group. Acknowledgements: R.E.C. (University of New Hamp- shire) is the recipient of The Norris-Richards Undergraduate Summer Research Scholarship. E.V. (Hamburg University) thanks the DAAD RISE program for the summer scholar- ship. We also thank Dr. Marianne Schiffer for providing the After the Gly58Cys mutant was labeled with the original GSU0935 plasmid for this work and Dr. Xiaomin Ru(bipy)2phen-IA reagent, it did not bind to the positively- Fang for her help in the initial stages of the project. These charged Q-resin at pH 8.0. This result is consistent with the studies were supported by the ACS Petroleum Research added +2 charge to the protein and contrasts with the unla- Fund (E.V.P.). beled protein which bound to the column. Successful pro- tein labeling was also indicated by a shoulder at 460 nm in References: the absorption spectrum and increase in the absorbance at (1) Richter, H.; McCarthy, K.; Nevin, K. P.; Johnson, J. P.; Rotello, 280 nm (Figure 2a). Interestingly, the Soret band in the V. M.; Lovley, D. R. “Electricity Generation by Geobacter sul- absorption spectrum of ferric Gly58Cys also changed after furreducens Attached to Gold Electrodes” Langmuir 2008, 24, 4376-9. labeling from 400 nm to 410 nm (Figure 2a), an observation (2) Pokkuluri, P. R.; Pessanha, M.; Londer, Y. Y.; Wood, S. J.; consistent with conversion of the high- to low-spin heme Duke, N. E.; Wilton, R.; Catarino, T.; Salgueiro, C. A.; Schif- state. This finding suggests the flexibility of the protein fer, M. “Structures and solution properties of two novel environment surrounding the heme group. We hypothesize periplasmic sensor domains with c-type heme from chemotaxis that in this Ru-bipyridyl-labeled derivative, a Met60 ligand proteins of Geobacter sulfurreducens: Implications for signal replaces H2O already in the ferric protein. The attached transduction” J. Mol. Biol. 2008, 377, 1498-517. ruthenium complex, when covalently bound in close prox- (3) Castellano, F. N.; Dattelbaum, J. D.; Lakowicz, J. R. “Long- imity to the heme (Figure 1b), may push down the surround- lifetime Ru(II) complexes as labeling reagents for sulfhydryl ing loops favoring the Met60 ligation. Future studies will continued on page 16 verify the Met-heme coordination by examining resonance Figure 2 Raman spectra that are sensitive to the heme ligation as well as the 695 nm absorption band that is characteristic of the Met-Fe(III) ligation. Photoinduced reactions in the Ru-bipyridyl-labeled derivative were followed by the decay of the excited state *Ru2+ and by the increase in the absorption of the ferrous heme. The observed very fast reduction of approximately 15 ns (Figure 2b) suggests an efficient electron transfer process6 and is consistent with the Ru(phen)-Cys58-Tyr59- Met60-heme through-bond pathway5 in the Met-bound heme.

12 The Nucleus March 2010 Fourth Annual Advances In Chemical Sciences Symposium sponsored by NESACS and RSC-US

Royal Sonesta Hotel, Cambridge, MA

9:00 a.m. April 9, 2010

This day-long scientific conference will focus on Medicinal Chemistry Organic Synthesis Methodology

Eminent scientists from industry and academia will deliver plenary lectures. Confirmed Lecturers include:

Viresh Rawal, University of Chicago

Daniel Kahne, Harvard University

Sarah O’Connor, MIT

Mark Flanagan, Pfizer

Melissa Ashlock, NHGRI/TRND

Preliminary Announcement The symposium will be followed by a networking reception and vendor exhibition

Symposium registration fee: $ 50.00 or $25 for Students Vendors please contact the Organizing Committee Attendance is Limited – Advanced Registration is REQUIRED Please send your full contact information along with your check for $50 made payable to NESACS to Anna Singer Administrative Secretary, NESACS, 12 Corcoran Road, Burlington, MA 01803 For additional details, including sponsorship and exhibition opportunities contact any of the Organizing Committee:

[email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] Gabriel.Martinez- [email protected] [email protected] [email protected] [email protected] !

The Nucleus March 2010 13 Book Review they’ve got to justify the money to simplistic and condescending. For someone who’s got the whip on their example, when the authors describe the Continued from page 4 back,” Maxwell said, “But in those theory behind mass spectrometry, they sediments, and what such molecules days you did what you wanted and you write, “The mass spectrometer is… indicate about the atmospheric condi- were just desperate to find out some- based on a rather juvenile impulse: the tions on early Earth. thing new. Afterwards, in some cases – best way to see how something is put A key premise of the book is stated and it may have been luck, intuition, it together is to break it apart (page 23).” explicitly in Chapter 9, “that a lot of may have been something else – it led Later in that paragraph, the authors genetic variation, and, presumably, to something. But most of the time you compare mass spectrometry to shatter- evolutionary diversification can occur weren’t aware of that (page 59).” ing a tray of wine glasses, which is an before it is expressed in morphological The authors highlight the some- analogy that may or may not hold true. traits (page 229).” Scientists have his- times-tense relationship between aca- Moreover, the authors are telling a torically studied fossils of ancient demic and industrial chemists. At story of primarily their scientific dis- organisms in their quest to understand annual Gordon Conferences, for exam- covery, of their encounters with other evolution. However, by studying ple, the authors report that academic scientists, of their thoughts and of their ancient molecules and their prevalence chemists willingly shared their re - research. The research of other scien- throughout Earth’s history, one learns search, whereas industrial chemists tists is covered in some detail in the that much about ancient organisms and “would sit quietly in the back, eagerly various chapters, although many of their biochemical pathways is con- soaking up whatever hot new ideas and these other scientists are those whom stantly evolving and changing. Only a information the academics had to offer, the authors know personally through small part of this change is captured while the academics fumed because various scientific conferences. As a successfully in morphological changes they suspected the industry scientists result, the authors may completely that can be detected in actual fossils. of harboring precisely the information ignore research performed by other The book is liberally sprinkled and samples they needed to answer the scientists. with tangential observations about sci- questions at hand (page 81).” In particular, the chapter on mete- entific research. For example, scientist While the book is overall a com- orites, “From the Moon to Mars: The James Maxwell commented on how pelling read, there are a few shortcom- Search for Extraterrestrial Life,” dis- scientific research has changed since ings. First, the attempts to provide the cusses the various amino acids found the 1960s. “Nowadays people have to necessary scientific background to on carbonaceous meteorites such as the focus on what they want to do because non-scientists can verge into the overly continued on page 16

14 The Nucleus March 2010 March Historical Events in Chemistry by Leopold May, The Catholic University of America, Washington, DC March 1, 1910 ide, and oxides of nitrogen. He also March 25, 1863 One hundred years ago, Archer J. P. made the first soda drink. Simon Flexner isolated the common Martin was born. He shared the strain of dysentery bacillus, Shigella March 14, 1935 Nobel Prize in Chemistry with dysenteriae in 1899. He developed Seventy-five years ago, Julius B. Richard L. M. Synge in 1952 for curative serum for cerebrospinal Cohen died on this date. He was a their invention of partition chro- meningitis in 1907. He was born on researcher on the laws of aromatic matography. this date. substitutions and optical activity. He March 3, 1876 was born on May 6, 1859. March 27, 1847 Seventy-five years ago, Gregory P. One hundred years ago in 1910, March 14, 1935 Baxter and C. P. Alter determined Otto Wallach, a researcher on essen- Seventy-five years ago, Arthur the atomic weight of lead, which led tial oils and terpenes, was awarded Hantszch died on this date. He was to estimations of the age of miner- the Nobel Prize in Chemistry in a researcher in electrical conductiv- als. Baxter was born on this date. recognition of his services to organic ity of organic compounds, organic chemistry and the chemical industry March 5, 1893 acids and stereochemistry of nitro- by his pioneer work in the field of Emmett J. Culligan, who founded gen compounds. His birthdate was alicyclic compounds. He was born the world’s largest water treatment March 7, 1857. on this date. organization, as well as discovering March 17, 1803 the concept of water softening, was March 28, 1861 In 1826, Carl Löwig was a discov- born on this date. George C. Pond, a chemistry teacher erer of bromine but, because of and preserver of the Priestley home March 7, 1792 examinations, did not publish a in Pennsylvania, was born on this John F. W. Herschel, inventor of report, thereby allowing A. Balard to date. photography on sensitized paper, receive precedence of discovery. He was born on this day. He introduced was born on this date. March 30, 1920 the terms positive and negative for Daniel E. Koshland, Jr., a researcher March 20, 1735 photography. in the catalytic activity of enzymes Two hundred and seventy-five years and editor of Science, was born on March 8, 1879 ago, Torbern Bergman was born on this date. Otto Hahn discovered protactinium this date. He was a researcher on with Lise Meitner in 1917 and did carbon dioxide, hydrogen sulfide March 31, 1860 research in nuclear fission with Otto and the preparation of artificial min- One hundred and fifty years ago, Strassman. He received the Nobel eral water. Isidor Traube was born on this date. Prize in Chemistry in 1944 for his He founded capillary chemistry and March 21, 1932 discovery of the fission of heavy did research on liquids and critical Walter Gilbert, researcher on the nuclei. He was born on this date. temperature, osmosis, surface ten- determination of deoxyribonucleic sion and colloids (suspensions of March 12, 1900 acid (DNA) base sequences; was nanometer-sized particles). In addi- Seventy-five years ago in 1935, born on this date. In 1980 he shared tion, he designed a viscometer and Frédéric J. Joliot (Joliot-Curie) the Nobel Prize in Chemistry with capillarimeter and in 1891 made the shared the Nobel Prize in Chemistry Paul Berg and Frederick Sanger for first systematic observation of the with his wife Irène Joliot- their contributions concerning the hydrophobic effect. Curie, for production of artificial determination of base sequences in radioisotopes. In 1934, he, H. Hal- nucleic acids. Additional historical events can be ban, and L. W. Kowarski proved found at Dr. May’s website, March 22, 1788 http://faculty.cua.edu/may/Chemistryca experimentally that neutron emis- N sion occurs in nuclear fission. He Pierre J. Pelletier discovered qui- lendar.htm. was born on this date. nine, strychnine, and other alkaloids; with Philip Walter, he obtained March 13, 1733 toluene by distilling pipe resin in Joseph Priestley, who was born on 1836. He was born on this date. this date, was the discoverer of oxy- March 23, 1962 gen, ammonia, hydrochloric acid gas, carbon monoxide, sulfur diox- Neil Bartlett made the first noble gas compound, XePtF6, on this date.

The Nucleus March 2010 15 Biography Book Review Summer Internship

Continued from page 5 Continued from page 14 Continued from page 9 tion products. He went on to use LIF Murchison meteorite, which fell in Professor Grubbs developed an for the detection of mold metabolites 1969. The research of marine chemist air-stable catalyst that has found many (aflatoxins) separated by chromatogra- Professor Jeffrey Bada at the Scripps applications. Metathesis is used daily phy, for detecting and quantitating Institution of Oceanography is high- in the chemical industry, mainly in the analytes separated by capillary electro - lighted. Professor Bada investigated development of new pharmaceuticals phoresis, and for measuring the behav- reports that the amino acids found on and novel advanced plastic materials. ior of single molecules in solutions at the meteorites contained some degree Syntheses using olefin metathesis are: room temperature. He has consistently of L enantiomeric excess (ee), and con- • more efficient (fewer reaction steps, blazed new trails for chemical analysis, cluded that such findings were likely a fewer resources required, less which has resulted in a number of result of terrestrial contamination of wastage), awards including the National Medal the meteorite samples. • simpler to use (stable in air, at nor- of Science in 1983, the Welch Award While this conclusion of Professor mal temperatures and pressures) and in Chemistry in 1999, the Wolf Prize in Bada’s is reported in the book, the • eco-friendly (non-injurious solvents, Chemistry in 2005, and the Priestley book ignores the large body of recent less hazardous waste products). Medal in 2010. He is also recognized research that supports the opposing for his teaching and mentoring, having argument: that the amino acids found Poly(dicyclopentadiene) received the James Flack Norris Award on the Murchison meteorite are extra- Poly(dicyclopentadiene), abbrevi- for Outstanding Achievement in the terrestrial in origin, and that the L ee’s ated poly(DCPD), is an industrial poly- Teaching of Chemistry (2004), the are legitimately extra-terrestrial as mer that is synthesized via ring- George C. Pimentel Award in Chemi- well. For example, Professor Sandra opening metathesis polymerization cal Education (2008), and the Presi- Pizzarello has studied the isotopic (ROMP) by Materia, Inc. The reaction dential Award for Excellence in composition of meteoritic amino acids is catalyzed by a ruthenium catalyst Science, Mathematics, and Engineer- to address this precise question; her developed in the Grubbs research N ing Mentoring (2009). research is not covered. group at the California Institute of It is understood that organic geo- Technology. The polymerization is Abstract chemistry is an exciting and rapidly driven by the high ring strain of the changing field of research, and that monomer, dicyclopentadiene, causing Continued from page 5 one book cannot cover the comprehen- the catalyst to irreversibly open one ring and add a new monomer unit to shifts in the infrared spectra of small sive body of research. However, the the chain. Also present in dicyclopen- molecules. Using the relatively new authors do a disservice to their readers tadiene is a less reactive olefin that absorption technique of cavity ring- by failing to cover both sides of this causes individual polymer chains to down spectroscopy, it is possible to still-unsettled scientific debate. crosslink into a network. This results measure the isotopic ratio of a few In conclusion, this book is struc- in a high-strength material that is used common elements with a precision that tured as a light-hearted narrative in the 2,3 in everything from tractor parts to rivals that of mass spectrometry. field of organic geochemistry. It is baseball bats. I was pleased to make Moreover, a cavity ring-down spec- highly successful in providing an this polymer in the lab and learn the trometer can be constructed that is overview of organic geochemistry for techniques of olefin metathesis and robust, portable, inexpensive, and can the non-specialist, and is recom- N polymerization. run for months without calibration or mended for anyone interested in learn- ing more about this exciting maintenance. This advance opens the N Summer Scholar possibility of much more widespread interdisciplinary field. applications of isotope ratio analysis Continued from page 12 T. G. Spence, and R. N. Zare, “Stable groups” Anal. Biochem. 1998, 255, for understanding the origins and Isotope Ratios Using Cavity Ring- provenances of chemical compounds 165-70. Down Spectroscopy: Determination (4) Ramiro, P.; Garcia-Fresnadillo, D.; — from geological and atmospheric to of 13C/12C for Carbon Dioxide in agricultural and medical samples. Orellana, G. “Synthesis and characteri- Human Breath,” Anal Chem. 74, 2003- sation of N-1,10-phenanthrolin-5- 1. T. W. Richards and M. E. Lembert, 2007 (2002). ylalkylamides and their photosensitising “The Atomic Weight of Lead of 3. R. N. Zare, D. S. Kuramoto, C. Haase, heteroleptic Ru(II) complexs” Tetrahe- Radioactive Origin,” J. Am. Chem. S. M. Tan, E. R. Crosson, and N. M. dron 2005, 61, 9478-9483. Soc. 36, 1329-1344 (1914). R. Saad, “High-Precision Optical (5) Ullmann, G. M., preliminary analysis 13 12 2.E. R. Crosson, K. N. Ricci, B. A. Measurements of C/ C Isotope done with the program Greenpath. Richman, F. C. Chilese, T. G. Owano, Ratios in Organic Compounds at Natu- (6) Gray, H. B.; Winkler, J. R. “Long-range R. A. Provencal, M. W. Todd, J. ral Abundance,” Proc. Natl. Acad.N Sci. electron transfer” Proc. Natl.N Acad. Sci. Glasser, A. A. Kachanov, B. A. Paldus, (USA) 106, 10928-10932 (2009). USA 2005, 102, 3534-9.

16 The Nucleus March 2010 BUSINESS DIRECTORY Weinberg Lectures SERVICES SERVICES

Continued from page 6 The Symposium Committee: Loren D. Walensky, MD, PhD, Dana-Farber Cancer Institute Holcombe Grier, MD, Dana-Farber Cancer Institute Glen Bubley, MD, Beth Israel Deaconess Hospital James S. Weinberg, PhD Sharon Gittens, Dana-Farber Cancer Institute Founding Donors: Affymax Research Institute Amgen BioPhysics Assay Laboratory, Inc. Bristol-Myers Squibb Research Labo- ratories Ciba Pharmaceuticals Division International Union of Operating Engi- neers, Local 4 Lilly Research Laboratories Lotus Development Corporation Pharm-Eco Laboratories Pfizer, Inc. Schering-Plough Research Institute Vertex Pharmaceuticals, Inc. The Dover Church Jon O. Lee N James S. Weinberg Calendar

Continued from page 20 March 30 Prof. Martin Burke (Univ. Illinois) “The Prospect of Molecular Prosthetics: Small Molecules with Protein-Like Functions” Boston College Merkert 130 4:00 pm Prof. Purnendu Dasgupta (Univ. Texas at Arlington) “Perchlorate, Wherefrom, Wherein and Where Do We go From Here? Re-emergence of Iodine Deficiency in the US?” Tufts University Pearson Chemistry Building, Room P-106 4:30 pm Mar 31 Dr. David Lambright,UMASS Medical School, Worcester, “Structural insights into trafficking regulation by GTPases and phosphoinositides”. UMass Dartmouth, Building Group II, Room 115 4:00 pm Notices for The Nucleus Calendar should be sent to:

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The Nucleus March 2010 17 BUSINESS DIRECTORY SERVICES SERVICES SERVICES

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The Nucleus March 2010 19 Harvard, MA 01451 19 Mill Road AMERICAN CHEMICAL U.S. POSTAGE PAID NONPROFIT ORG. NORTHEASTERN SOCIETY SECTION

March 4 March 15 Calendar Dr. Sarah Petty (College of the Holy Cross) Jin Kim Montclare (Polytechnic Institute of Univ. New Hampshire, IddlesL 103 NYU) Check the NESACS home page 11:10 am Host - Prof. Xu for late Calendar additions: March 8 Brandeis, Gerstenzang 122 3:45 pm http://www.NESACS.org Prof. Jonathan Ellman (Univ. California, The Eli Lilly Symposium Yoshito Kishi (Harvard ) Note also the Chemistry Department web Berkeley) “Development and Application of New Metal- TBA pages for travel directions and updates. Harvard, Pfizer Lecture Hall , MB-23 4:00 pm These include: Catalyzed Carbon-Carbon Bond Forming http://chemserv.bc.edu/seminar.html Reactions” March 18 http://www.bu.edu/chemistry/events/ Boston College, Merkert 130 4:00 pm Richmond Sarpong (Univ. California, Berkeley) http://www.chem.brandeis.edu/colloquium.shtml Richard Weiss (Georgetown Univ.) Title: TBA http://www-chem.harvard.edu/events/ Brandeis, Gerstenzang 122 3:45 pm MIT, 6-120 4:00 pm http://web.mit.edu/chemistry/ March 9 March 22 www.chem.neu.edu/web/calendar/index.html http://chem.tufts.edu/seminars.html [CHEM.] Prof. Michael Best (Univ. Tennessee) Phil C. Baran (The Scripps Research Institute) http://ase.tufts.edu/chemical/seminar.htm “Chemical Approaches to the Investigation of TBA [CHEM. ENGG.] Protein-Membrane Binding Interactions using Harvard, Pfizer Lecture Hall , MB-23 4:00 pm http://www.chem.umb.edu/ Synthetic Lipid Probes” Paul Chirik (Columbia Univ.) www.umassd.edu/cas/chemistry/seminars.cfm Boston College, Merkert 130 4:00 pm “Modern Alchemy: Base Metal Catalysis and www.uml.edu/Dept/Chemistry/speakers.html Prof. Jonathan Ellman (Univ. Cal.,Berkeley) Electron Structure” http://www.unh.edu/chemistry/seminars.html Univ. of New Hampshire, Iddles, L103 Brandeis Gerstenzang 122 3:45 pm March 2 11:10 am March 23 March 10 Prof. James Whitten (Univ. Massachusetts, Leon Wong (Univ. of Melbourne) Lowell) Prof. John Caradonna (Boston Univ.) Univ. of New Hampshire, Iddles, L103 “Self-Assembled Monolayers and their Harvard, Pfizer Lecture Hall, MB -23 11:10 am Applications in Nanotechnology and Chemical 4:15 pm March 25 Sensors” Tufts Univ., Pearson Chemistry Building , Dr. Xudong Huang, Harvard Medical Bristol-Myers Squibb Lectures: Room P-106 4:30 pm School/BWH , Andre Charette (Univ. Montreal) “Metal oxide nanoparticle exposure and TBA Barabara Li (Univ. of Melbourne) Alzheimer's disease pathogenesis” TBA Gregory Vite (Bristol-Myers Squibb) UMass Dartmouth, Building Group II, TBA Univ. of New Hampshire, Iddles, L103 Room 115 4:00 pm 11:10 am March 11 MIT, 6-120 4:00 pm Mar 3 W. E. Moerner (Stanford Univ.) Prof. Michael Best (University of Tennessee) TBA Dr. Jane-Jane Chen, Harvard-MIT Division of “Chemical Approaches to the Investigation of MIT, Room 6-120 5:00 pm Health Sciences and Technology (HST), Protein-Membrane Binding Interactions using Prof. Guozhong Cao (Univ. Washington) “Translational Control in Hemoglobin Synthesis Synthetic Lipid Probes” and Erythropoiesis”. “Engineering Nanomaterials and Interfaces for Tufts Univ., Pearson Chemistry Building, Energy Conversion and Storage” UMass Dartmouth, Building Group II, Room P-106 4:30 pm Room 115 Boston College, Merkert 130 4:00 pm 4:00 pm continued on page 17