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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 2008 Vol. LXXXVI, No. 7 N • AMERI

Monthly Meeting Richards Medal Award Meeting at Harvard Professor Robert G. Bergman

NCW Report National Chemistry Week 2007 Report By Christine Jaworek-Lopes

Leslie Orgel 1927-2007

Summer Research Report By Jiajia Cui and Dean Wilcox 2 The Nucleus March 2008 The Northeastern Section of the American Chemical Society, Inc. Contents Office: Marilou Cashman, 23 Cottage St., Natick, MA 01360. 1-800-872-2054 (Voice or FAX) or 508-653-6329. Announcements 4 e-mail: mcash0953(at)aol.com ______Any Section business may be conducted Norris and Richards Undergraduate Research Scholarships via the business office above. Call for papers: Northeast Student Chemistry Research Conference NESACS Homepage: http://www.NESACS.org Monthly Meeting 5 David Cunningham, Webmaster ______ACS Hotline, Washington, D.C.: 2008 ACS Richards Medal Award Meeting 1-800-227-5558 Awarded to Professor Robert G. Bergman, University of California, Berkeley Officers 2008 Chair: National Chemistry Week 2007 Report 6 Marietta Schwartz ______Chemistry Department, UMASS-Boston By Christine Jaworek-Lopes Boston, MA 02125 617-287-6146; marietta.schwartz(at)umb.edu Leslie Orgel 1927-2007 8 Chair-Elect: ______Dr. E. Joseph Billo Renowned Chemical Evolution Scientist Dies 13 Shattuck Street Natick, MA 01760 5th Annual YCC Career Fair 9 508-653-3074, joseph.billo(at)verizon.net ______Immediate Past Chair: Northeast Student Chemistry Career Fair at Brookline Holiday Inn Mukund Chorghade 14 Carlson Circle, Natick, MA 01360 Summer Research Report 10 508-651-7809 and 308-3891 ______Chorghade(at)comcast.net Nickel Binding Properties of the C-terminal Histidine-rich Sequence of the Secretary: Metallochaperone UreE from Klebsiella aerogenes Michael Singer By Jiajia Cui and Dean E. Wilcox, Department of Chemistry, Dartmouth Col- Sigma-Aldrich 3 Strathmore Rd., Natick, MA 01360 lege, Hanover, NH 508-651-8151X291; msinger(at)sial.com Treasurer: March Historical Events in Chemistry 14 James Piper ______19 Mill Rd., Harvard, MA 01451 By Professor Leopold May, Catholic University of America 978-456-3155, piper28(at)attglobal.net Call for Nominations 15 Auditor: ______Anthony Rosner 2008 ACS Northeast Region Awards Archivist: Myron S. Simon Cover: 20 Somerset Rd. Professor Robert G. Bergman, University of California at Berkeley, Newton, MA 02465; 617-332-5273 2008 Richards Award Winner (Photo courtesy of Professor Bergman) Romysimon(at)mindspring.com Trustees: Deadlines: Joseph A. Lima, Esther A. H. Hopkins, May 2008 Issue: March 11, 2008 Michael E. Strem Summer 2008 Issue: June 16, 2008 Councilors Alternate Councilors Term Ends 12/31/2008 Doris I. Lewis Patrick M. Gordon Morton Z. Hoffman Michael P. Filosa Christine Jaworek-Lopes Lawrence Scott Mary Burgess Liming Shao Donald O. Rickter S.B. Rajur Term Ends 12/31/2009 The Nucleus is published monthly, except June and August by the Northeastern Section of the American Catherine Costello Julia H.Miwa Chemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Text Patricia Mabrouk Alfred Viola Michaeline F. Chen Jerry P. Jasinski must be received by the editor six weeks before the date of issue. Dorothy J. Phillips Eva B. Binnun Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G, Amy Tapper Barney Grubbs Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070 Term Ends 12/31/2010 Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273 Thomas R. Gilbert Timothy B. Frigo Sheila E Rodman, Konarka Techologies Inc., 116 John St. Suite 12, Lowell, MA Pamela Nagafuji Mark Froimowitz 01852 email:srodman(at)konarka.com tel 978-569-1414 Robert Lichter David Cunningham Michael Singer Erik Rozners Board of Publications: Vivian K. Walworth (Chair), Mary Mahaney, David Cunningham 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 Tel: 781-837-0424; FAX: 781-837-1453 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 Councilor of the American Chemical Society Proofreaders: Donald O. Rickter, Myron S. Simon, Vivian K. Walworth, E. Joseph Billo residing within the section area is an ex officio Webmaster: David Cunningham, webmaster(at)nesacs.org member of the Board of Directors. Copyright 2008, Northeastern Section of the American Chemical Society, Inc. The Nucleus March 2008 3 The James Call for Corporate Patrons ($2000+) Abbott Laboratories Flack Norris Papers Lyophilization Service of New England Merck and Theodore Northeast Student Chemistry National ACS Research Conference 2008 Novartis William Pfizer Open to undergraduates, graduates, Sepracor and postdoctoral fellows in all areas of Strem Chemicals Richards chemical research Vertex Pharmaceuticals Saturday, April 19th, 2008 Patrons ($1000-$1999) Undergraduate MIT Astra-Zeneca R&D Boston The Ray and Maria Stata Center IRIX Pharmaceuticals Summer Visit the NESACS YCC website for Millenium Pharmaceuticals more details at www.nsycc.org . Shasun Pharmaceuticals ZINK Imaging Research Abstracts will be accepted on this Ziopharm Oncology, Inc. Scholarships site. There is no registration fee. Students are invited to present a poster Donors ($300-$999) or a 15 minute oral presentation. Cambridge Major Laboratories The Northeastern Section of the Amer- Occidental Petroleum ican Chemical Society (NESACS) Deadlines: Organix Oral presentation: April 8th, 2008 established the and th N PCI Synthesis Theodore William Richards Under- Poster presentations: April 10 , 2008 Royal Society of Chemistry graduate Summer Scholarships to Serono Research Institute honor the memories of Professors Nor- Wyeth Pharmaceuticals ris and Richards by promoting research interactions between undergraduate Eligibility: Applications will be students and faculty. accepted from student/faculty teams at Research awards of $3250 will be colleges and universities within the given for the summer of 2008. The Northeastern Section. The undergrad- New Members student stipend is $2750 for a mini- uate student must be a chemistry, bio- mum commitment of ten weeks of full- chemistry, chemical engineering, or Invitation to attend a meeting time research work. The remaining molecular biology major in good You are cordially invited to attend one $500 of the award can be spent on sup- standing, and have completed at least of our upcoming Section meetings as a plies, travel, and other items relevant two full years of college-level chem- guest of the Section at the social hour to the student project. istry by summer, 2008. and dinner preceding the meeting. Institutions whose student/faculty Application: Application forms are Please call Marilou Cashman at team receives a Norris/Richards available on the NESACS web site at 800-872-2054, 508-653-6329 or: Undergraduate Summer Research http://www.nesacs.org. Completed Mcash(at)aol.com by noon of the first Scholarship are expected to contribute applications are to be submitted no Thursday of the month, letting her toward the support of the faculty mem- N later than April 4, 2008 to the Chair of know that you are a new member. bers and to waive any student fees for the Selection Committee: summer research. Academic credit Professor Edwin Jahngen may be granted to the students at the University of Massachusetts Lowell discretion of the institutions. Chemistry Department, Award winners are required to Room 520, Olney Hall Looking for seminars submit a report (~5-7 double-spaced 1 University Avenue pages including figures, tables, and in the Boston area? Lowell, MA 01854-5047 bibliography) of their summer projects Check out the to the NESACS Education Committee Notification: Applicants will be noti- by November 3, 2008 for publication fied of the results by e-mail on April NESACS Calendar in The Nucleus. They are also required 23, 2008 with written confirmation to N to participate in the Northeast Student follow. www.nesacs.org/seminars Chemistry Research Conference (NSCRC) in April 2009.

4 The Nucleus March 2008 Monthly Meeting Biography Robert G. Bergman was born in The 886th Meeting of the Northeastern Section of the American Chicago, Illinois in 1942. After com- pleting his undergraduate studies in Chemical Society chemistry at Carleton College in 1963, 2008 ACS Richards Medal Award Meeting he received his Ph.D. at the University of Wisconsin in 1966 under the direc- Thursday – March 13, 2008 tion of Jerome A. Berson. Bergman Harvard Faculty Club, spent 1966-67 as a NATO Fellow in 20 Quincy St., Cambridge, MA. ’s laboratories at Columbia, and following that went to 5:30 pm Social Hour the California Institute of Technology 6:15 pm Dinner as a Noyes Research Instructor. He was promoted to assistant professor in 8:15 pm Richards Award Ceremony 1969, associate professor in 1971, and Mallinckrodt Building, Pfizer Lecture Hall - MB23, full professor in 1973. He accepted an 12 Oxford Street, Cambridge, MA. appointment as Professor of Chemistry Professor Marietta Schwartz, NESACS Chair, Presiding at the University of California, Berke- “Theodore William Richards”, Professor Gary R. Weisman, Chair, ley in 1977 and was appointed Gerald Richards Medal Committee E. K. Branch Distinguished Professor Introduction of 2008 Medalist by Professor Peter Vollhardt, Univer- at Berkeley in 2002. sity of California, Berkeley Bergman was trained as an 2008 Richards Medalist - Prof. Robert G. Bergman, Gerald E. K. organic chemist and spent the first part Branch Distinguished Professor, University of California, Berke- of his independent career at Caltech ley, “Selective Organic and Organometallic Transformations investigating the mechanisms of Mediated by Molecular and Supramolecular Environments.” organic reactions. He also developed methods for the generation and study Dinner reservations should be made no later than noon, Thursday, March 6, of unusually reactive molecules, such 2006. Please call or fax Marilou Cashman at 800-872-2054 or e-mail at as 1,3-diradicals and vinyl cations. In Mcash0953(at)aol.com. Please specify vegetarian. Reservations not cancelled at 1972 he discovered the thermal least 24 hours in advance must be paid. Members,$30; Non-members, $35; cyclization of cis-1,5-hexadiyne-3- Retirees, $20; Students, $10. enes to l,4-dehydrobenzene diradicals. THE PUBLIC IS INVITED In the 1980’s this transformation of Anyone who needs special services or transportation, please call Marilou Cash- enediynes was identified as a crucial man a few days in advance so that suitable arrangements can be made. DNA-cleaving reaction in several Free parking in the Broadway St. Garage (3rd level or higher), enter from Cam- antibiotics that bind to nucleic acids, bridge Street via Felton, St. and the enediyne reaction is now often referred to as the “Bergman cycliza- Next Meeting: Esselen Award Meeting, April 17, 2008, Harvard University. tion”. In the mid-1970’s Bergman’s Reception and dinner: 5:30 pm, Harvard Faculty Club; Award Meeting: 8:15 pm, research broadened to include Pfizer Lecture Hall, Mallinckrodt Chemistry Building, 12 Oxford Street, Cam- organometallic chemistry. Since mov- bridge. Dr. John A. Katzenellenbogen, Swanlund Professor of Chemistry, Uni- ing to Berkeley he has made contribu- versity of Illinois Urbana-Champaign: “Estrogens and Estrogen Receptors as a N tions to the synthesis and chemistry of Nexus of Chemistry and Biology in Health and Disease” several types of organotransition metal complexes and to improving our understanding of the mechanisms of their reactions. In this area he has This lecture will discuss several focused on migratory insertion and Abstract approaches to the development of oxidative addition reactions, the chem- selective organic and organometallic continued on page 16 Selective Organic and reactions. Examples will be drawn Organometallic from our group’s efforts to use molecu- bond activation and pericyclic reac- Transformations Mediated by lar and/or supramolecular environ- tions. The lecture will include a focus ments to control the selectivity of on the study of reaction mechanisms to Molecular and Supramolecular organic and organometallic reactions provide a rational approach to reaction N Environments such as hydrolyses, carbon-hydrogen optimization.

The Nucleus March 2008 5 National Chemistry Week 2007 Report

The Northeastern Section Celebrates The Many Faces of Chemistry By Christine Jaworek-Lopes In preparation for National Chemistry visitors to the daylong event enjoyed a with the NESACS NCW events. Week 2007, a volunteer preparation number of hands-on activities. On October 22, 2007, a diverse day was held at Emmanuel College on Hands-on activities included: iso- audience of 225 area high school stu- Saturday, October 13, 2007. More lating iron from Total® cereal, making dents participated in a daylong pro- than 50 individuals attended this event, play putty, studying the chemistry of gram at the Museum of Science- which allowed volunteers to practice different types of nails, making UV Boston high-lighting the variety of the hands-on activities and demonstra- detector bracelets, making marker but- careers impacted by chemistry. This tions in advance of the October cele- terflies, assessing sugar content in program was funded by receipt of a bration. A member of the Boston cereals and beverages, and learning Local Section Innovative Grant, local Children’s Museum staff was on hand how mood lipsticks work. section funds, and a donation from to choose which activities worked best Among the highlights of the day Merck Research Laboratory – Boston. for her audience. were the two lecture demonstrations, The day commenced with the stu- On Sunday, October 21, 2007, the as part of the Phyllis A. Brauner dents participating in an interactive Northeastern Section of the American Memorial lectures, presented by Dr. lecture-demonstration given by Dr. Chemical Society sponsored a National Bassam Shakhashiri, Professor of Bassam Shakhashiri. The students Chemistry Week 2007 Kick-Off Event Chemistry at the University of Wiscon- then had the opportunity to meet and at Museum of Science-Boston (MoS). sin-Madison. These captivating lec- talk at informal conversation stations More than 50 volunteers (from ACS, tures were enjoyed by children and with scientists from a variety of organ- Boston Latin School, the Brauner adults alike. Approximately 300 indi- izations. Each scientist brought a Committee, Emmanuel College, viduals attended these lectures which hands-on activity or demonstration to Malden High School, Merck Research were free with admission to the MoS. encourage conversation. The scientists Laboratories – Boston, Stonehill Col- In addition, Dr. Shakhashiri was pre- that participated in this event were: lege, Suffolk University, Tufts Univer- sented with a Salute to Excellence • Marta Biarnes – a former cosmetic sity) ensured that the more than 1000 Award for his continued involvement chemist from L’Oreal USA, now a member of the MoS staff • Jennifer Chute – Criminalist, Boston Police Department Crime Lab • Raksmey Derival – Program Man- ager, Beyond Benign • Pamela Hatchfield –Head of Objects Conservation, Museum of Fine Arts, Boston • Peter Jepson – Materials Scientist, H.C. Starck • Christian Krahforst – Staff Scientist, Massachusetts Bay’s National Estuary Program • Mimi Leveque – Art Conservator, Peabody Essex Museum • Jacqueline Massua – Forensic Labo- ratory Technician, Boston Police Department Crime Lab • James Waters – Technical Support, Waters Corporation • Bassam Shakhashiri – Professor of Chemistry, University of Wis- consin-Madison The students also had the opportunity to participate in two hands-on activi-

6 The Nucleus March 2008 Chemistry Week Brauner Memorial Lecture Committee. that grows and when the algae grows The theme for NCW 2008 is to be enough to cover all the water it Continued from page 6 “Having a Ball with Chemistry” to be blocks the sun from coming in. When ties related to nutrition and tour the celebrated from October 19-25, 2008. there is no sun that means that the ani- MoS. Finally, students had the option mals and plants that live there can’t of interviewing a scientist and submit- Winning Entry: survive. The nitrogen acts somewhat as ting the interview to the NCW commit- Interviewing a Scientist a shield to the water, but not in a good tee. The winning essay was submitted Christian Krahforst /Chemist way. by Sean Kinnane. By Sean Kinnane Now that all of that is clear, we go In addition, an NCW event was I am taking a class in environmen- back to the sonde process. Now that held at the Boston Children’s Museum tal science presently and I thought it you know what they use the sonde for, on Saturday, October 27, 2007. might be fun to interview the chemist let’s go through the process of how Approximately 1300 individuals par- most closely related to that field, and they take the information that is given ticipated in NCW hands-on activities Mr. Krahforst was just the person that to them from the instrument. The infor- and demonstrations. A particular I needed to see. mation tells you what is in the water favorite at the Boston Children’s Mr. Krahforst had a lot of interest- and whether it is bad or good. When Museum was making marker butter- ing things to say and show. One very scientists know the types of chemicals flies. More than 40 volunteers from interesting thing that he had at his table or types of algae in the water, they can Boston Latin School, Bridgewater was a tool called a sonde. This tool is find or create their own chemicals to State College, Emmanuel College, used to measure the temperature of the help get whatever is bad out of the Gordon College, Merck Research Lab- water, its conditions, including the oxy- water so that the plants and animals oratories- Boston, Simmons College, gen and chlorophyll levels, the water’s that are having trouble living down Suffolk University, and Tufts Univer- conductivity, and the amount of light there have the ability to have a chance sity were available to assist visitors the water has. Once they do all of this to survive. throughout the day. they try to answer their biggest ques- Well, if you’re wondering where Children grades K-12 were able to tion and how to fix their biggest prob- all that nitrogen comes from, here are participate in the national poster com- lem, the nitrogen level. The nitrogen is just a few examples. It comes from petition. Seventeen posters were sub- what is causing all of the algae to places such as storm drains, lawn fer- mitted for the NCW poster spread out over the water. The more tilizers, and pesticides that find their competition. These posters were nitrogen that there is the more algae Continued on page 16 judged by the scientists who partici- pated in the Monday program. The winners from the NESACS were: K-2: Adam Canfield and Jordyn Cooper (joint entry from the Young Scientists Club, Littleton MA); grades 9-12: Marina Kem from Malden High School. Children grades K-12 had the option of participating in a puzzle con- test. The puzzle was designed by Dr. Christopher Morse. Upon solving the criss-cross puzzle, the participants learned they needed to write an essay of fewer than two hundred words, about a Nobel prize winning chemist. The winning essay was submitted by Jeffrey Yu. NESACS received a $3000 Local Section Innovative Grant to defray the cost of the Monday program. Special thanks to all of our volunteers, Boston Children’s Museum, Lynn Baum, Alissa Daniels, Museum of Science Boston, Northeastern Section of the American Chemical Society, David Sittenfeld, Dr. Bassam Shakhashiri, Mariko Taniguchi, and the Phyllis A.

The Nucleus March 2008 7 Salk Chemical Evolution Scientist Leslie Orgel: 1927–2007

Leslie Orgel was well known to arose that could pass on life’s genetic Born in 1927, in London, Eng- NESACS. He was featured in the Janu- blueprint to future generations. land, Leslie Eleazer Orgel earned a ary 2003 Nucleus as the speaker at the He was among the first scientists, bachelor’s degree (1949) and his doc- Monthly Meeting. In addition, his son in the 1960’s, to suggest that RNA, torate (1951) in chemistry from Oxford Robert, is married to the daughter of rather than DNA, was that early University, and accepted research fel- former NESACS Chair, John replicative molecule. He suspected that lowships at California Institute of Neumeyer. an even simpler genetic precursor to Technology and the University of The following was released by the RNA itself must have existed. Chicago in 1954 and 1955, respec- Salk Institute on October 30, 2007. The notion of an “RNA world,” as tively. Orgel then returned to Britain RNA-based life is often called, was and served as assistant director of coincidentally shared by the scientist research at Cambridge’s Theoretical LA JOLLA, CA — Salk scientist who helped discover the structure of Chemistry Department. There he Leslie Orgel, Ph.D., who dedicated DNA – Orgel’s Salk colleague and helped develop ligand field theory, much of his career to the study of how friend, the late Francis Crick. which describes chemical bonding in life began on Earth roughly 4 billion In acknowledging that common metals. Orgel published An Introduc- years ago, died on October 27 from assumptions – such as the belief that tion to Transition-Metal Chemistry: pancreatic cancer. He was 80 years old. DNA is more important than RNA – The Ligand Field Theory in 1961. Orgel, a professor and head of the are often based on lack of evidence, Orgel became a fellow at the Salk Chemical Evolution Laboratory, aimed Crick once jokingly credited Orgel Institute in 1964 and became interested not only to discover the chemical reac- with Orgel’s Second Rule: “Evolution in what distinguishes living organic tions that led to the first life forms on is cleverer than you are.” This state- things from non-living things. He found the primitive Earth, but also to solve ment is now broadly used today as a it intriguing that the proteins found in the mystery of how, during this prebio- general rejoinder to arguments made all of Earth’s life forms are made from logical time, a replicative molecule from ignorance. one set of 20 standard amino acids and that their genetic information is stored in nucleic acids – DNA and RNA – that use the same genetic code. Moreover, RNA uses that information to produce proteins, and proteins, in turn, are needed to help duplicate DNA. But there is a central paradox Orgel and others pointed out: there can be no pro- teins without DNA, and there can be no DNA without proteins. Orgel suggested a way out of this chicken-and-egg conundrum, as did Crick and American microbiologist Carol Woese, each of whom published their ideas independently. They specu- lated that both DNA and proteins could be descendants of RNA. Being more complex and stable, DNA could then have taken over RNA’s role as the guardian of heredity, while RNA took on a more supporting role. Proposing that RNA might have evolved in a way that is consistent with Darwinian selection, Orgel published his thoughts in the 1973 book The Ori- gins of Life: Molecules and Natural Selection.

8 The Nucleus March 2008 Leslie Orgel Continued from page 8 Fifth Annual But more than a decade later, when evidence for an RNA world came with the discovery of an RNA Northeast Student enzyme (ribozymes) that catalyze bio- chemical reactions, Orgel expressed Chemistry Career Fair new doubts. Attempts to form RNA under laboratory conditions that mimic the primordial Earth had been only Thursday, April 24, 2008 marginally successful, largely because 3PM – 7PM ribose (a component of the RNA back- bone) is a sugar that Orgel said may Brookline Holiday Inn not have been stable enough to survive 1200 Beacon Street, Brookline, MA the low oxygen and high radiation con- ditions of the early Earth. Register to participate: Orgel suggested that RNA proba- bly took over from some more primi- ACS Career Services workshops on resume writing and interviewing tive precursor. Accordingly, he and his skills will be performed on-site. Have your resume reviewed. group at Salk studied alternative Job Fair – Meet with representatives from companies in the Northeast genetic backbones that may have pre- about employment opportunities. Hand deliver your resume to com- ceded nucleic acids. They found that a pany scientists and HR representatives. compound known as peptide nucleic acid (PNA), which is much simpler Last Year than RNA, can be copied in the test Over 110 resume submissions tube. Their work demonstrated that the 12 companies recruiting new hires evolution of a more complex, self- replicating molecule from a simpler Come, network with your future colleagues precursor is at least possible. Corporate sponsorship inquiries: 617-304-6474, Lee Johnson. Orgel’s origin-of-life work also had practical applications. During FREE ONLINE REGISTRATION studies in the Chemical Evolution Lab- (Returnable Deposit): Please register at the Northeastern Section oratory, he and his colleagues came Younger Chemists Committee website: www.nsycc.org across a straightforward way to synthe- size cytosine arabinoside (Ara C), a Participating companies and all details will be listed. compound that is one of today’s most commonly used anti-cancer agents. Orgel also enjoyed purely theoret- principal investigators of the NASA- Orgel’s contributions have been ical investigations, and mused about sponsored research and training pro- recognized throughout his career. In how a universal genetic code could gram in exobiology. He also Britain, he was awarded the Harrison have evolved. In 1973, Orgel and Crick participated in NASA’s Viking Mars Prize in 1957 for his work in inorganic put forward the notion that “directed Lander Program as a member of the chemistry, was elected a Fellow of the panspermia” – the seeding of life on Molecular Analysis Team that Royal Society in 1962. In the United other worlds by a guiding intelligence – designed the gas chromatography mass States, he received a Guggenheim Fel- could solve the mystery. In an article in spectrometer instrument. lowship in 1971, the Evans Award the journal Icarus, they said that while In 1998, he chaired the Task from Ohio State University in 1975, it is possible that life reached Earth in Group on Sample Return from Small and the H.C. Urey Medal from the this way, the scientific evidence for this Solar Systems Bodies, and served on International Society for the Study of is so inadequate that no one can say NASA’s astrobiology oversight com- the Origin of Life in 1993. He was anything about the probability. Crick mittee since 1999. Orgel was also part elected a member of the National expanded these ideas in his book “Life of a strategic planning group for the Academy of Sciences in 1990. Itself: Its Origins and Nature.” SETI Institute’s Center for the Study of Leslie Orgel is survived by his Because of his long association Life in the Universe. In addition to his wife, Alice Orgel, M.D., Ph.D., a pedi- with NASA, Orgel would have been work at Salk, Orgel was also an atric allergist, now retired, his two sons one of the first to know if other planets adjunct professor in the Department of Richard and Robert, his daughter N had been so seeded. He was one of five Chemistry and Biochemistry at UCSD. Vivian, and their grandchildren.

The Nucleus March 2008 9 Summer Research Report

Nickel Binding Properties of the C-terminal Histidine-rich Sequence of the Metallochaperone UreE from Klebsiella aerogenes Jiajia Cui and Dean E. Wilcox Department of Chemistry, Dartmouth College, Hanover, NH 03755 Introduction lochaperone that lacks the histidine-rich carboxyl terminus. Bacillus pasteurii UreE Urease is a nickel-containing enzyme found in plants and The best-studied example is , which has a His-Gln-His carboxyl terminus and binds two nickel certain microorganisms, where it catalyzes the hydrolysis of ions per dimer (9). Studies of a truncated form of KaUreE, urea to ammonia and carbon dioxide. This enzyme is impor- H144*UreE, that lacks the 15 carboxy-terminal residues tant in biochemical nitrogen cycles and the uptake of urea 2+ indicate that it binds two Ni ions and retains ~75% of the fertilizer, and has been implicated as a bacterial virulence specific urease-activating activity of wild type KaUreE (10). factor in various human and animal diseases (1). The bacter- This indicates that the 10 C-terminal His residues are not ial urease possesses three structural subunits, designated essential for the delivery of nickel ions to urease. Conse- UreA, UreB, UreC, and contains a bi-nickel active site quently, the histidine-rich carboxyl terminus of KaUreE buried in the UreC subunit (2). Assembly of the functional must play another role in urease activation, possibly tempo- urease metallocenter, however, requires the participation of rary metal storage for UreE. four accessory proteins, designated UreD, UreE, UreF, and Few studies have investigated the thermodynamics of UreG (Figure 1) (3). Deletion of the genes for these proteins metal ions binding to proteins, which is important for under- does not affect urease subunit biosynthesis, and studies have standing the delivery of metal ions by metallochaperones. A shown that UreD, UreF, and UreG stabilize the urease apo recent calorimetric study of metals binding to the truncated (metal-free) protein (4) for nickel insertion by UreE, which H144*UreE confirmed the binding stoichiometry of two is the metallochaperone donor of nickel ions to the UreC 2+ Ni per dimer and reported a condition independent binding subunit (5). 8 constant of 6.3 x 10 (11). Additional measurements on the Figure 1: Crystal wild type KaUreE protein showed that the C-terminal tail of structure of the metal the KaUreE dimer is able to bind 3-4 nickel ions and free K. aerogenes allowed the thermodynamics of this binding to be estimated UreE monomer (8). (11). To further understand the biological role of this histi- dine-rich carboxy-terminal sequence, which is found in many, but not all, UreE proteins, a peptide corresponding to these residues was studied. Isothermal titration calorimetry (ITC), which directly measures the heat generated or consumed in binding reac- tions, was used to determine the thermodynamics of nickel binding to the KaUreE C-terminal peptide. The instrument consists of sample and reference cells that are connected by a thermocouple, and heat that is associated with the titration in the sample cell is determined by detecting and correcting for any temperature difference between the two cells. The experimental parameters, n (stoichiometry), DHITC, and KITC, are determined by fitting the ITC data to an appropri- ate binding model. Further analysis then leads to the condi- The UreE from Klebsiella aerogenes (KaUreE) func- 2+ tion-independent thermodynamics of the binding reaction. tions as an apparent dimer (Mr = 35,000) that binds 5-6 Ni ions per dimer with an experimental K d value of approxi- mately 10 μM, as measured with equilibrium dialysis (5). X-ray absorption and other spectroscopic studies have shown that the Ni2+ ions coordinate to 3-5 histidine residues in a pseudo-octahedral geometry (5, 6). Mutagenesis studies (7) and X-ray crystallography (8) of KaUreE (Figure 2) have implicated several nickel binding sites, including His- 96 at the dimer interface, His-110 and His-112 at the periph- ery of the two subunits, and the histidine-rich carboxyl terminus, which has the sequence HGHHHAHHD- Figure 2: K. aerogenes urease gene cluster, which consists HHAHSH. of three structural genes (UreA, UreB, UreC) and four A number of organisms, however, have a UreE metal- accessory genes (UreD, UreE, UreF, UreG) (5).

10 The Nucleus March 2008 Experimental

NiCl2 was the highest purity chloride salt received from either Fisher or Sigma. Tris (2-amino-2-[hydroxymethyl]- Equation 3. 1,3-propanediol, 99% pure) was obtained from Fisher. Tes (2-[tris(hydroxymethyl)methylamino]-1-ethanesulfonic acid, 99% pure) and EDTA (ethylenediaminetetraacetic acid, 99% pure) were obtained from Sigma. The N-acety- lated 15 residue UreE carboxy-terminal peptide (~85% pure) was obtained from Bio Synthesis Inc., and further purified using reverse phase HPLC (~95% pure). ITC experiments were carried out at 25°C with a MicroCal MCS titration calorimeter. Solutions were buffered with either 100 mM Tris or 50 mM Tes at pH 7.45. Ionic strength was adjusted to 0.1 M using NaCl. Metal analysis by ICP-MS and EDTA titrations was used to deter- mine the concentration of the metal solutions. The concen- Equation 4. tration of UreE peptide solutions was determined by the peptide mass and verified by ITC measurements with Ni2+ tions in Tris and Tes buffers indicate that 0.94 protons are solutions of known concentration. The ITC data were displaced when Ni2+ binds to the peptide at pH 7.45. obtained for Ni2+ titrations into the KaUreE peptide in Tris The analysis to determine the condition-independent or Tes buffered solutions and analogous titrations of the pep- thermodynamics requires certain values. The value of ∆HMB tide into Ni2+ solutions. Four or five data sets were collected for Tris and Tes was determined from the enthalpy of Ni2+ for each type of titration and the average best-fit ITC values titrations of EDTA in these buffers and comparison to the 2+ are reported. known enthalpy of Ni binding to EDTA. The value for KHL et al Analysis was approximated from the results of Grossoehme, , who measured the four His pKa values of the histidine-rich The enthalpies and binding constants obtained from peptide, PHGHGHGHGP, and found them to be 3.44, 5.32, ITC measurements are net values for all reactions in the 6.65, and 7.43 (13). The KaUreE peptide contains 10 histi- sample cell upon addition of titrant. Therefore, care must be dine residues, whose pKa values may be spread over a simi- taken to separate the enthalpy of metal-peptide binding from lar range. Thus, a pKa of 7.45 was used for the proton the enthalpies of metal-buffer interaction, proton displace- 2+ displaced upon Ni binding to the KaUreE peptide. A better ment and subsequent buffer protonation, and other coupled estimate of this pKa value could be obtained from an analy- equilibria. Hess’s law (Equation 1), where M, L, and B cor- sis of a pH titration of the peptide. Finally, values for r, s, respond to metal, ligand, and buffer, respectively, can be Continued on page 12 used to extract the desired ∆HML from other known enthalpy contributions.

Equation 1. Protons are often displaced when metal ions bind to peptides or proteins. In order to calculate the number of dis- 1mM Ni2+ → 50 M tail peptide µ placed protons in a given reaction, ITC data are collected in 100mM Tes (pH 7.45) at least two different buffers at the same pH. Equation 1 can µ = 0.1mM be rearranged to give equation 2.

Equation 2.

Plotting ∆HITC+∆HMB versus ∆HHB for different buffers gives a linear relationship with slope. Finally, given ∆HMB and, condition-independent values for the desired KML and ∆HML can be calculated from equa- tions 3 and 4, respectively (12). Results Experimental ITC measurements of the KaUreE car- boxy-terminal peptide (Figure 3 and 4) indicate that it binds Figure 3: 2+ ITC data for 1mM nickel titration into 50mM histidine- ~1 Ni ion. Analysis of the experimental enthalpy for titra- rich carboxyl terminal peptide in 100mM Tris pH 7.45.

The Nucleus March 2008 11 Summer Scholar ITC data for Ni2+ titrations of this His-rich peptide indi- Continued from page 11 cate that one nickel ion binds to the peptide, displacing approximately one proton from the histidine residues at pH 7.45. Compared to the peptide sequence in the native pro- tein dimer, which binds 3.3 Ni2+ ions, the isolated peptide binds 2.0-2.4 Ni2+ ions per dimer. Thus, more Ni2+ ions bind to these histidine residues in the native KaUreE protein dimer, where X-ray crystallography of H144*UreE indicates that the two C-terminal sequences are held in close proxim- 1mM Ni2+ → 50 M tail peptide µ ity. This is consistent with the storage, or queing, of addi- 50mM Tes (pH 7.45) tional Ni2+ ions by these residues of this metallochaperone µ = 0.1mM protein. The affinity of this peptide for Ni2+ was found to be identical to that estimated for the sequence in the whole pro- tein, with condition-independent log K values of 7.07 and 6.98 (11), respectively, corresponding to DG° values of -9.6 kcal/mol for the isolated peptide and -9.5 kcal/mol for the sequence in the protein. A similar, but slightly lower, Ni2+ affinity (log K = 6.47) was found for another His-rich pep- tide (Table 2), indicating that several histidine residues cre- ate a relatively stable protein binding site for Ni2+ ions. The Ni2+ affinity of the C-terminal sequence is 1-2 orders of magnitude lower than UreE affinity for the two Ni2+ ions that it transfers to apourease, further supporting a storage or Figure 4: ITC data for 1mM nickel titration into 50mM histidine- queing role for this sequence. rich carboxyl terminal peptide in 50mM Tes pH 7.45. These calorimetric measurements have allowed the enthalpy and the entropy of Ni2+ binding to be quantified. and a in equation 4 were calculated to be 0.667, 0, and 2+ The value of DH° for Ni binding to the isolated peptide 0.886, respectively, for the experimental conditions of pH (-22.6 kcal/mol) is significantly more negative than DH° for 7.45 and 100 mM Tris buffer. The average best-fit experi- the same sequence in the native protein (~ -5 kcal/mol). mental values and the corresponding condition-independent 2+ 2+ However, a similarly large negative enthalpy for Ni bind- thermodynamic values for Ni binding to the peptide are ing to another His-rich peptide (Table 2) suggests that summarized in Table 1. molecular interactions in the dimeric KaUreE protein modu- late the enthalpy of Ni2+ binding. On the other hand, the entropy of binding (DS°) of the isolated peptide (-43 cal/mol K) is quite unfavorable, in contrast to the positive value of DS° for the sequence in the native dimeric protein (+15 cal/mol K). As found with the enthalpy, the DS° value for Ni2+ binding to another His-rich peptide (Table 2) is more similar to that of the KaUreE peptide than the same Table 1: Calorimetric values for Ni2+ binding to the C-terminal sequence in the protein. Thus, a more favorable enthalpy KaUreE peptide in Tris or Tes buffers at pH 7.45, and the corre- and a very disfavorable entropy may be hallmarks of metal sponding condition-independent values for the data in Tris buffer. ions binding to isolated peptides. These data also indicate Discussion To further understand the role of the cluster of histidine residues at the carboxyl terminus of UreE from some species, but not others, the Ni2+-binding properties of a pep- tide corresponding to this sequence from Klebsiella aero- genes have been measured with ITC. Analysis of the best-fit experimental values gives the buffer- and pH-independent thermodynamics of this binding. These values for Ni2+ bind- ing to the peptide are compared in Table 2 with analogous values estimated for this sequence when it is part of the Table 2: Thermodynamic values for Ni2+ binding to the KaUreE native KaUreE protein (11) and values determined for a C-terminal peptide, the native KaUreE C-terminal tail sequence peptide that corresponds to a His-rich sequence in the iron- (11) and the peptide corresponding to the His-rich sequence from transport protein IRT1, PHGHGHGHGP (13). IRT1, PHGHGHGHGP (13).

12 The Nucleus March 2008 Summer Scholar Christianson, R. P. Hausinger (1993) B. Devreese, B. Samyn, H. Remaut Purification and Characterization of and J. Van Beeumen (2002) Molecu- Continued from page 12 Klebsiella aerogenes UreE Protein: lar Characterization of Bacillus pas- that this is another example of a phe- a Nickel-binding Protein that Func- teurii UreE, a Metal-binding nomenon known as enthalpy-entropy tions in Urease Metallocenter Chaperone for the Assembly of the compensation, where a very different Assembly, Protein Sci. 2: 1042- Urease Active Site, J. Biol. Inorg. combination of enthalpic and entropic 1052. Chem. 7: 623-631. contributions to binding leads to a sim- 6. G. J. Colpas, T. G. Brayman, J. 10.T. G. Brayman and R. P. Hausinger ilar overall change in free energy and McCracken, M. A. Pressler, G. T. (1996) Purification, Characterization affinity. Babcock, L. J. Ming, C. M. Colan- and Functional Analysis of a Trun- New insight about the thermody- gelo, R. A. Scott, R. P. Hausinger cated Klebsiella aerogenes UreE namics of Ni2+ binding to the histidine- (1998) Spectroscopic Characteriza- Urease Accessory Protein Lacking rich carboxy-terminal sequence of the tion of Metal Binding by Klebsiella the Histidine-rich Carboxyl Termi- Klebsiella aerogenes metalloochaper- aerogenes UreE Urease Accessory nus, J. Bacteriol. 178: 5410-5416. one UreE has been obtained in this Protein, J. Biol. Inorg. Chem. 3: 11. N. E. Grossoehme, S. B. Mulrooney, 150-160. R. P. Hausinger, D. E. Wilcox study of an isolated peptide correspon- 2+ 7. G. J. Colpas, T. G. Brayman, L. J. (2007) Thermodynamics of Ni , ding to this sequence. Differences in 2+ 2+ 2+ Ming, R. P. Hausinger (1999) Identi- Cu and Zn binding to the urease the Ni binding stoichiometry and fication of Metal-binding Residues metallochaperone UreE, Biochem- thermodynamics between the peptide in the Klebsiella aerogenes Urease istry 46: 10506-10516. KaUreE and the sequence in may orig- Nickel Metallochaperone, UreE, 12.N. E. Grossoehme (2007), Dart- inate from interaction between pairs of Biochemistry 38: 4078-4088. mouth College, Ph.D. Thesis. these sequences in the dimeric protein. 8. H. K. Song, S. B. Mulrooney, R. B. 13.N. E. Grossoehme, S. Akilesh, M. L. Thus, future studies will investigate N- Hubert, R. P. Hausinger (2001) Guerinot, D. E. Wilcox (2006) terminal tethered pairs of these pep- Crystal Structure of Klebsiella aero- Metal Binding Thermodynamics of tides to better mimic the dimeric 2+ genes UreE, a Nickel-binding Met- the Histidine-rich Sequence from protein context for their Ni binding allochaperone for Urease Activation, the Iron Transport Protein IRT1 properties. J. Biol. Chem. Arabidopsis thaliana Inorg. 276: 49359-49364. from N , References 9. S. Ciurli, N. Safarov, S. Miletti, A. Chem. 45: 8500-8598. 1. R. P. Hausinger and P. A. Karplus Dikiy, S. K. Christensen, K. Kornet- (2001) Urease, in Handbook of Met- zky, D. A. Bryant, I. Vandenberghe, alloproteins (A. Messerschmidt, R. Huber, T. Poulos, K. Weighardt, Eds) Wiley, Chichester, pp. 866-879. 2. E. Jabri, M. B. Carr, R. P. Hausinger, P. A. Karplus (1995) The Crystal Structure of Urease from Klebsiella aerogenes, Science 268: 998-1004. 3. M. H. Lee, S.B. Mulrooney, M. J. Renner, Y. Markowicz, R. P. Hausinger (1992) Klebsiella aero- genes Urease Gene Cluster: Sequence of ureD and Demonstra- tion that Four Accessory Genes (ureD, ureE, ureF, and ureG) Are Involved in Nickel Metallocenter Biosynthesis, J. Bacteriol. 174: 4324-4330. 4. I. S. Park and R. P. Hausinger (1995) Evidence for the Presence of Urease Apoprotein Complexes Con- taining UreD, UreF and UreG in Cells that are Competent for in vivo Enzyme Activation, J. Bactiol. 177: 1947-1951. 5. M. H. Lee, H. S. Pankratz, S. Wang, R. A. Scott, M. G. Finnegan, M. K. Johnson, J. A. Ippolito, D. W. The Nucleus March 2008 13 March Historical Events In Chemistry by Leopold May The Catholic University of America, Washington, DC

March 1, 1771 March 14, 1854 March 23, 1867 John McLean, first professor of One hundred years ago, Paul Charles L. Parsons, who was born chemistry, at Princeton, estab- Ehrlich and Ilya Ilyich Mechnikov on this date, obtained the federal lished the first laboratory of chem- shared the Nobel Prize in Medi- charter for the ACS,. He helped istry on this day in North America. cine with in recognition of their establish the Petroleum Research March 3, 1709 work on immunity. Ehrlich was a Fund and did research on beryl- researcher in immunity & lium. Andreas S. Marggraf, who was chemotherapy and discovered Sal- born on this date, isolated zinc March 26, 1838 varsan (No. 606) & neosalvarsan. from calamine. He distinguished He improved laboratory staining A. Crum Brown, who devised between potash and soda by flame methods and was born on this day. modern structural formulae in test, found alumina in clay, and 1864, was born on this date. He discovered beet sugar in beetroot. March 16, 1666 formulated rules for substitution in March 5, 1817 Johann Conrad Barchusen, who benzene derivatives named after was born on this date, was a him and did research in the theory The inventor of the first colorime- chemical lecturer at Utrecht Uni- of isomerism and organic com- ter, Jules Duboscq, was born on versity. He did chemical analysis pounds of sulfur. this day. The Duboscq Colorime- using fire and interpreted alchemi- ter was used for visual colorimet- March 27, 1847 cal transmutation as metallic sub- ric quantitative analysis and pH stitution reactions. Otto Wallach, a researcher on measurements. essential oils & terpenes, was born March 18, 1900 March 7,1839 on this date. In 1910, he received Laueren B. Hitchcock, an expert the Nobel Prize in Chemistry in Ludvig Mond, who discovered in chemistry of the environment, recognition of his services to Mond producer gas and nickel was born on this date. organic chemistry and the chemi- carbonyl, was born on this date. cal industry by his pioneering He and John Brunner founded a March 19, 1883 work in the field of alicyclic com- company that later became Impe- One hundred and twenty-five pounds. rial Chemical Industries (ICI). years ago, Walter N. Haworth was March 29, 1883 March 10, 1851 born on this date. He synthesized ascorbic acid (Vitamin C) in 1933 One hundred and fifty years ago, William McMurtie, who was born and did research on sugars and Donald D. Van Slyke was born on on this day, did research on meth- dextran as blood plasma substi- this day. He was a pioneer in clin- ods for converting sewage to fer- N tute. In 1937, he shared the Nobel ical chemistry. tilizer. He served as president of Prize in Chemistry with Paul Kar- the American Chemical Society. rer for vitamin synthesis. March 12, 1824 What’s Yours? March 20, 1908 Gustav R. Kirchhoff, who One hundred years ago, Bausch & DMPK Scientist, invented the spectroscope with Lomb was incorporated as Bausch LC/MS Product Specialist, Robert Bunsen in 1859, was born & Lomb Co., on this day. Mass Spec Operator, on this date. He and Robert Bun- Staff Investigator, March 21, 1817 sen discovered cesium in 1860, Process Chemist, and rubidium in 1861. He discov- George W. Rains, who was a QA Manager, ered that substances which emit chemistry teacher and Confederate radiation absorb the same type of Army chemist, was born on this Synthetic Chemist, radiation when cool (Kirchhoff’s date. Lab Instructor Law). Many local employers post positions The NESACS website on the NESACS job board. Updated frequently • Late-breaking news • position postings Back issues of the Nucleus archived • Career-related Links • Awards and Scholarships Find yours at WWW.NESACS.org www.nesacs.org/jobs

14 The Nucleus March 2008 CALL FOR NOMINATIONS FOR THE 2008 NORTHEAST REGION AWARDS NeRACS

Northeast Region of the American Chemical Society, Inc. Dr. Julianne Smist, Chair Mr. D. Richard Cobb, Vice Chair Dr. Christopher Masi, Secretary Dr. Wayne Jones, Treasurer

THE ACS DIVISION OF CHEMICAL EDUCATION NORTHEAST REGION AWARD FOR EXCELLENCE IN HIGH SCHOOL TEACHING Purpose: To recognize, encourage, and stimulate outstanding teachers of high school chemistry in the Northeast Region. Eligibility: The nominee must be actively engaged in the teaching of chemistry or a chemical science in a high school (grades 9-12) on at least a half-time basis. THE NORTHEAST REGIONAL AWARD FOR EXCELLENCE IN VOLUNTEER SERVICES Purpose: To recognize the volunteer efforts of individuals who have served the Amer- ican Chemical Society by contributing significantly to the goals and objectives of the Society through their Regional Activities. Purpose: The nominee must be a member of the ACS, residing in a Local Section within the Northeast Region, who has made significant contributions to the Section and Region of the ACS.

STANLEY C. ISRAEL REGIONAL AWARD Purpose: Its purpose is to recognize individuals and/or institutions that have advanced diversity in the chemical sciences and significantly stimulated or fostered activities that promote inclusiveness within the region. Purpose: Individuals nominated for the award may come from any professional set- ting: academia, industry, government, or other independent facility. Nominees may also be organizations, including ACS local sections and divisions. The awardees will have increased the participation and leadership of persons from diverse or underrepre- sented minority group(s), persons with disabilities, or women.

Deadline: The deadline for all of these awards is March 31, 2008. For More Information: Contact D. Richard Cobb at Nominating Forms: Available on the NESACS website Presentation of the Awards: At the 2008 Northeast Regional Meeting (NERM) in Burlington, Vermont, June 29–July 2.

The Nucleus March 2008 15 Chemistry Week Biography November Continued from page 7 Continued from page 5 way to our water sources. Once the istry of new dinuclear complexes, the Meeting nitrogen finds its way to the water, the investigation of organometallic com- damage can begin. pounds having metal-oxygen and - It was enjoyable and informative nitrogen bonds (as part of this work he Photos to speak with Mr. Krahforst. I am uncovered one of the earliest examples hopeful that I can use the knowledge of early-transition metal alkyne and by Robert Lichter gained as I continue my Environmental allene hydroamination processes), and Science class. Of all the things he said, the reactions of organotransition metal this particular sentence has stayed with enolates. He is probably best known me from our conversation and it is the for his discovery of the first soluble following quote: organometallic complexes that undergo “As stewards of the environment, we intermolecular insertion of transition must leave something healthy for the metals into the carbon-hydrogen bonds future.” of alkanes and the use of liquefied Thank you Mr. Krahforst!!! noble gas solvents in the study of these A collection of Norris Award Recipients at the reactions, and most recently he has November Meeting. (l-r) A. Truman Schwartz Winning Puzzle Contest Essay been involved in the application of (1997), Mary Virginia Orna (1996), Michael P. Nobel Prize-Winning Chemist Kary C-H activation reactions to problems Doyle (1995), Diane Bunce (2007), John W. Moore (1991), and Morton Z. Hoffman (2005). Mullis in organic synthesis. By Jeffrey Yu Bergman has been the recipient of Kary Mullis was born on Decem- numerous awards: an Alfred P. Sloan ber 28, 1944 in Lenoir, North Carolina. Fellowship (1969), a Camille and He attended high school in South Car- Henry Dreyfus Foundation Teacher- olina where he grew up, and then Scholar Award (1970), the Caltech Stu- moved on to the Georgia Institute of dent Government Award for Technology in Atlanta where he Excellence in Teaching (1978), the acquired a Bachelor of Science Degree ACS Award in Organometallic Chem- istry (1986), an ACS Arthur C. Cope in Chemistry. Seven years later he New NESACS members at the Norris Award earned a Ph.D. from the University of Scholar Award (1987), the E.O. Dinner California, Berkeley in Biochemistry. Lawrence Award in Chemistry (U.S. Kary Mullis is accredited along Department of Energy, 1994), the ACS with Michael Smith of Canada for Arthur C. Cope Award (1996), the developing the Polymerase Chain Edward Leete Award for Teaching and Reaction (PCR) technique. The proce- Research in Organic Chemistry (2001), dure is significant because through the UC Berkeley Department of Chem- PCR, segments of DNA are able to be istry Teaching Award (2002), the ACS amplified. Replicating DNA is a tool James Flack Norris Award in Physical that can be used when there is not Organic Chemistry (2003), and an enough DNA available to be analyzed Award for Excellence in Technology and tested. It helps during medical Transfer from the Lawrence Berkeley Myke Simon, NESACS Archivist and Vivian diagnosis to identify bacteria and National Laboratory (2005). Bergman Walworth, Board of Publications viruses that cause infections; it can is an elected member of the National also be used in genetic testing too. In Academy of Sciences and the Ameri- genetic testing, PCR amplifies a cer- can Academy of Arts and Sciences Society, and Organic Letters. At tain gene which is then sequenced so (both in 1984). In 2007 he was chosen Berkeley he has served as Vice-chair that mutations can be seen. By catch- by the National Academy of Sciences of the Department of Chemistry (1985- ing mutations early on, the disease risk to receive the NAS Award in Chemical 87) and three times as Assistant Dean in patients can be determined and lives Sciences. He has served as a member of the College of Chemistry. He has can be saved. Mullis’ PCR technique of several editorial advisory boards also been elected to serve on the Exec- has advanced the field of Medicine and including those of the Journal of utive Committees of both the Organic allowed further discoveries to be Organic Chemistry, Organometallics, Division (1981-84) and the Inorganic unearthed. His research has improved Chemical Reviews, the International Division (1984) of the ACS, the latter N Journal of Chemical Kinetics, the as chairman of the Organometallic the quality of life of many. N Journal of the American Chemical Subdivision.

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The Nucleus March 2008 19 Harvard, MA 01451 19 Mill Road

Prof. Robert Madix (Stanford University) Mar 19 “Structure Sensitivity of Styrene Epoxidation on Dr. Marina Petrukhina (University at Albany) Silver: Mechanistic Origins” “Fullerene Fragments: Molecular Geometry, Tufts University, Pearson Chemistry Building, Solid State Packing, and Reactivity” Room P-106 Northeastern Univ., 129 Hurtig Hall 4:30 pm 12 noon Prof. Eli Pollak (Weizmann Institute of Science) Mar 20 “The Semiclassical Route to Quantum Dynamics of Systems with many Degrees of Freedom” Jon S. Thorson (University of Wisconsin) MIT, Room 4-237 TBA 4:00 pm Bristol-Myers Squibb Lectures in Organic Mar 5 Synthesis: Jon Thorson, University of Wisconsin MIT, Room 6-120 Dr. David E. Budil (Northeastern University) 4:00 pm “Spin Labeling Studies of Ligand-dependent Prof. Shaul Mukamel (U. of California-Irvine) Structural Changes in the Estrogen Receptor” “Probing Electron and Nuclear Correlations by UMass Dartmouth, Building Group II, Coherent Multidimensional Optical Room 115 Spectroscopy from NMR to X-rays” 4:00 pm MIT, Room 6-321 Mar 10 5:00 pm Mohammad Movassaghi (Massachusetts Mar 24

AMERICAN CHEMICAL Institute of Technology) BUWIC Colloquium U.S. POSTAGE PAID NONPROFIT ORG. NORTHEASTERN Boehringer-Ingelheim Symposium Dr. Jennifer Hollingsworth (Los Alamos TBA SOCIETY SECTION National Laboratory) Harvard Univ., Pfizer Lecture Hall TBA 3:30 pm Boston Univ., Life Science and Engineering Mar 11 Building Auditorium (B01) Prof.Yoshihisa Kobayashi (University of 4:00 PM California, San Diego) Mar 25 “Heterocycles in Natural Product Synthesis” Prof. Christopher Cheatum (University of Iowa) Boston College, Merkert Chemistry Center, “Watching the Protein Mambo: Fast Enzyme Room 130 Dynamics” Calendar 4:00 pm Tufts University, Pearson Chemistry Building, Dr. Fran Ligler (Naval Research Labs) Room P-106 Check the NESACS Homepage “The Array Biosensor and Beyond” 4:30 pm for late additions: Tufts University, Pearson Chemistry Building, Kathryn Steen (Drexel University) http://www.NESACS.org Room P-106 4:30 pm “Patriotism and Patents: The U.S. Synthetic Mar 12 Organic Chemicals Industry in World War I and Note also the Chemistry Department web the 1920s” pages for travel directions and updates. Dr. Heather Carlson (University of Michigan) TBA Univ. New Hampshire, Iddles Room L103 These include: 11:10 am http://chemserv.bc.edu/seminar.html Northeastern Univ., 129 Hurtig Hall http://www.bu.edu/chemistry/events/ 12 noon Prof. Chaitan Kosla (Stanford University) http://www.chem.brandeis.edu/colloquium.shtml Dr. Jason Sello (Brown University) “New Insights into Macrolide Biosynthesis” http://www-chem.harvard.edu/events/ TBA Boston College, Merkert Chemistry Center, http://web.mit.edu/chemistry/ UMass Dartmouth, Building Group II, Room 130 www.chem.neu.edu/web/calendar/index.html Room 115 4:00 pm http://chem.tufts.edu/seminars.html [CHEM.] 4:00 pm Dr. Richard Vachet (University of http://ase.tufts.edu/chemical/seminar.htm Daniel Dubois (Pacific Northwest National Lab) Massachusetts, Amherst) [CHEM. ENGG.] TBA “High Throughput Analysis of Proteins Using http://www.chem.umb.edu/ MIT, Room 6-120 4:00 pm Multiplexed Tandem Mass Spectrometry” www.umassd.edu/cas/chemistry/seminars.cfm Mar 13 New England Society for Applied Spectroscopy www.uml.edu/Dept/Chemistry/speakers.html Meeting http://www.unh.edu/chemistry/seminars.html Prof. Mark Johnson (Yale University) Hampton Inn, Natick MA Mar 3 TBA 7:30 pm — Dinner @6:30 contact Mark Druy Univ. New Hampshire, Iddles Room L103 druy(at)psicorp.com Professor David Cane (Brown University) 11:10 am Mar 26 ‘Polyketide Antibiotic Mar 17 Biosynthesis: Mechanistic and Structural Basis Dr. Carol Korzeniewski (Texas Tech University) of the Programming of Multistep Biosynthetic Prof. Robin Kinnel (Hamilton College) TBA Pathways’ “Adventures and Lessons from Three Decades of Northeastern Univ., 129 Hurtig Hall Boston Univ., Life Science and Engineering Natural Products — Some Finished and 12 noon Building Auditorium (B01) Unfinished Business” Peidong Yang (University of California, 4:00 pm Boston College, Merkert Chemistry Center, Berkeley) Christina D. Smolke (California Institute of Room 130 TBA Technology) 4:00 pm Harvard Univ. Pfizer Lecture Hall TBA Dr. John R. Engen (Northeastern Univ.) 4:00 pm Harvard Univ., Pfizer Lecture Hall TBA Mar 27 4:15 pm Brandeis Univ., Gerstenzang 122 3:45 pm Mar 4 Dr. Fred Walder Prof. Ann Valentine (Yale University) TBA Dr. John L. Marshall (Zink Imaging, Inc.) “Bioinorganic Chemistry of Titanium in UMass Dartmouth, Building Group II, “Zero Ink - Amorphochromic Dyes and Thermal Medicine and the Environment” Room 115 Printing” Boston Univ., Life Science and Engineering 4:00 pm Building Auditorium (B01)4:00 pm Univ. New Hampshire, Iddles Room L103 Prof. Martin Gruebele (University of Illinois at 11:10 am Urbana-Champaign) Continued on page 17