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Monthly Meeting Richards Medal to Stephen J. Lippard
Meeting Report What Is Different about Fluorocarbons? by David M. Lemal
Summer Scholar Report Toward a Small-Molecule Activated Protein Splicing System
Book Review Having Faith, an ecologist’s journey to motherhood by Sandra Steingraber 2 The Nucleus March 2002 The Northeastern Section of the American Monthly Meeting ______5 Chemical Society, Inc. Office: Marilou Cashman, 23 Cottage St., Richards Medal to Stephen J. Lippard ( M.I.T.): Three Avenues in Bioinorganic Natick, MA 01760. 1-800-872-2054 Chemistry: Cisplatin, Methane Monooxygenase, and Metalloneurochemistry (Voice or FAX) or 508-653-6329. e-mail: [email protected] Any Section business may be conducted Who Was Theodore William Richards?______6 via the business office above. NESACS Homepage: Pictures on pp. 24-25 http://www.NESACS.org Frank R. Gorga, Webmaster Meeting Report 8 Washington, D.C. ACS Hotline: ______1-800-227-5558 January 2002 Meeting Address:What Is Different About Fluorocarbons? Officers 2002 By David M. Lemal Chair: Morton Z. Hoffman Chemistry Department, Boston University ACS Short Course______13 Boston, MA 02215-2507; 617-353-2494 [email protected] Interpretation of Mass Spectra, May 2 and 3, 2002 Chair-Elect: John L. Neumeyer Section Business ______14 Harvard Medical School/McLean Hospital 115 Mill St., Belmont, MA 02478; Candidates for 2003, Board of Directors Meeting of December 6, 2001 617-855-3388 [email protected] Immediate Past Chair: Summer Research Report 16 Timothy B. Frigo ______Advanced Magnetics, Inc. Toward a Small-Molecule Activated Protein Splicing System, 61 Mooney St., Cambridge, MA 02138 617-497-2070x3007 [email protected] by Ravi V. Shah, Joshua M. Finkelstein, and Gregory L. Verdine (Harvard) Secretary: Michael Singer Book Review ______22 Sigma RBI 3 Strathmore Rd. Having Faith, an Ecologist’s Journey to Motherhood, by Sandra Steingraber; Natick, MA 01760-2447 reviewed by Dennis Sardella 508-651-8151x291 [email protected] Treasurer: Puzzle Column ______23 James Piper Simmons College, 300 The Fenway Solution to the February Puzzle: p. 21 Boston, MA 02115, 617-521-2722 [email protected] Cover: Stephen J. Lippard in the Saddle Auditor: Anthony Rosner Archivist: Deadlines: May 2002 issue: March 14, 2002 Myron Simon 20 Somerset Rd. Summer Issue: June 28, 2002 (National Meeting Issue) Newton, MA 02465; 617-332-5273 [email protected] Trustees: Michael E. Strem, Joseph A. Lima, Esther A.H. Hopkins Councilors: Alternate Councilors: Term Ends 12/31/2002 Term Ends 12/31/2002 The Nucleus is distributed to the members of the Northeastern Section of the American Chemical Mary T. Burgess Michael J. Dube Society, to the secretaries of the Local Sections, and to editors of all local A.C.S. Section publications. Michaeline F. Chen Jean Fuller-Stanley Forms close for advertising on the 1st of the month of the preceding issue. Text must be received by the Doris I. Lewis Patrick M. Gordon editor six weeks before the date of issue. Julia H. Miwa John L. Neumeyer Editor: Arno Heyn, 21 Alexander Rd., Newton, MA 02461, Term Ends 12/31/2003 Term Ends 12/31/2003 Catherine E. Costello Wallace J. Gleekman Tel: 617-969-5712, FAX: 617-527-2032; e-mail: [email protected] William Klemperer Arno H.A. Heyn Associate Editor: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273 Dorothy J. Phillips Howard R. Mayne Board of Publications: Patrick M. Gordon (Chair), Frank R. Gorga, Marietta H. Schwartz, E. Joseph Barbara G. Wood Alfred Viola Billo (Consultant) Term Ends 12/31/2004 Term Ends 12/31/2004 Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Thomas R. Gilbert Timothy B. Frigo Tel: 978-456-8622 Patricia H. Hamm Morton Z. Hoffman Michael J. Hearn Truman S. Light Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050, Arlene W. Light Donald O. Rickter Tel: 781-837-0424; FAX: 781-837-8792 Contributing Editors: Mukund Chorghade, Patricia Hamm, Features; Edward Atkinson, History of All Chairs of standing Chemistry; Maryann Solstad, Health; Dennis Sardella, Book Reviews; Marietta H. Committees, the editor Schwartz, Software Reviews; E. Joseph Billo, Puzzles. of THE NUCLEUS, and the Trustees of Section Calendar Coordinator: Donald O. Rickter, e-mail: [email protected] Funds are members of the Proofreaders: E. Joseph Billo, Donald O. Rickter, M.S. Simon Board of Directors. Any Webpage: Webmaster: Frank R. Gorga, [email protected] Councilor of the American Chemical Society Asst. Webmasters:Terry Brush, [email protected] residing within the section area is an ex officio Kurt Heinselman, [email protected] member of the Board of Directors. Copyright 2002, Northeastern Section of the American Chemical Society, Inc. The Nucleus March 2002 3 Biography Corporate Patrons Alfa Aesar, a Johnson Matthey Com- Stephen J. Lippard is series “Progress in pany the Arthur Amos Inorganic Chem- Hoechst Marion Roussel Co. Noyes Professor of istry” from Volume Pharm-Eco Laboratories, Inc. Chemistry and Head 11 to 40, w as an Physical Sciences, Inc. of the Chemistry Associate Editor of Polaroid Corporation Department at the the journal Inorganic Strem Chemicals, Inc. Massachusetts Insti- Chemistry, is now an Corporate Sponsors tute of Technology. Associate Editor of Aerodyne Research, Inc. He was born in Pitts- the Journal of the AstraZeneca R&D burgh, Pennsylvania American Chemical Borregaard Synthesis, Inc. and educated in the Society, was a Bristol-Myers Squibb Pittsburgh public Founding member of Cambridge Isotope Labs schools. He studied at the Editorial Advi- Consulting Resources Corporation Haverford College sory Board for Dike, Bronstein, Roberts & (B.A., magna cum Chemical Research Cushman, LLP laude, 1962) and the Stephen J. Lippard (Photo by Bachrach) in Toxicology, and Houghton Chemical Corp. Massachusetts Insti- serves or has served JEOL, USA, Inc. tute of Technology (Ph.D, 1965). After on the editorial boards of Accounts of MassTrace, Inc. a postdoctoral year at MIT during Chemical Research, Anticancer Drug New England Biolabs 1965-66 he joined the f aculty of Design, Bioorganic & Medicinal Organix, Inc. Columbia University as an Assistant Chemistry, Bioorganic & Medicinal Pfizer, Inc. Professor of Chemistry, being pro- Chemistry Letters, ChemBioChem, Research Biochemicals Int’l moted to Associate Professor with Chemical and Engineering News, Zymark Corporation tenure in 1969 and to Professor in Chemical Research and Technology, 1972. In January of 1983 he moved to Chemistry & Biology, Inorganic Chem- MIT. He has taken sabbatical leaves at istry, Inorganic Chemistry Concepts, the University of Göteborg in Sweden, Inorganica Chimica Acta, Journal of New the MRC Laboratory of Molecular Biological Inorganic Chemistry, Jour- Biology in Cambridge, England, the nal of Inorganic Biochemistry, and Anorganisch-Chemisches Institut der Topics in Biological Inorganic Chem- Members Technischen Universität München, istry. He is the author or co-author of Includes members relocated to the Garching, Federal Republic of Ger- over 550 publications in the fields of Northeastern Section many, and the University of California, inorganic and coordination chemistry, Invitation to attend a Section San Diego. organometallic chemistry, and biologi- meeting Professor Lippard has held fellow- cal chemistry. You are cordially invited to attend one ships from the Woodrow Wilson Foun- He has co-authored a book with of our upcoming Section meetings as dation, the National Science Jeremy Berg entitled “Principles of guest of the Section at the Social hour Foundation, The Alfred P. Sloan Foun- Bioinorganic Chemistry.” He holds and Dinner Meeting. dation, The Camille and Henry Drey- several US. and foreign patents. He has fus Foundation, the Guggenheim chaired several symposia at American Please call Marilou Cashman at Foundation, and the John E. Fogarty Chemical Society national meetings, 800-872-2054, 508-653-6329, or: International Center. was Alternate Councilor for the Divi- [email protected] by noon of the He is a member of the American sion of Inorganic Chemistry, was first Thursday of the month, to accept this invitation, letting her know that Chemical Society, The Royal Chairman of the Bioinorganic Subdivi- Society of Chemistry, The American sion, and Chairman of the Inorganic you are a new member. Crystallographic Association, The Bio- Division. He has given over 50 named physical Society. He was elected to lectureships at universities both in this ration, Johnson Matthey Co., Procept, Phi Beta Kappa (junior year), Sigma country and abroad, served as a panel Smith Kline & Beckman, Suntech and Xi, and the American Society of Bio- member of the Medicinal Chemistry John Wiley & Sons, Inc. He is cur- logical Chemists, and a Fellow of Study Section B and BMT Study Sec- rently Chairman of the Scientific Advi- the American Association for the tion of the National Institutes of sory Board of N AXCOR He was Advancement of Science. Health, and has been a consultant for Chairman of the 1985 Gordon He was editor of the well-known Engelhard Corporation, Exxon Corpo- continued on page 6
4 The Nucleus March 2002 Section News Monthly Meeting January Section Meeting speaker David The 832nd Meeting of the Northeastern Section of the American M. Lemal, as announced earlier, will Chemical Society be receiving the 2002 ACS Award for Richards Medal Award Meeting Creative Work in Fluorine Chemistry at the Orlando Meeting. There is an Thursday, March 14, 2002 extensive write-up about his work in Harvard University C&ENews 2002, Jan. 21, 54. Harvard Faculty Club, 20 Quincy St., Cambridge, MA The following students will be 5:30 pm Social Hour; a table of Career Services Literature and Aids will be receiving Fellowships of the Organic available Division, ACS (name of the mentor 6:30 pm Dinner and institution in parentheses): David J. Guerin (Scott J. Miller, 8:15 pm Award Meeting, Mallinckrodt Building, 12 Oxford St., Pfizer Boston College) Lecture Hall (MB23, ground floor) Rebecca T. Ruck (Eric N. Jacobsen, Dr. Morton Z. Hoffman, NESACS Chair, presiding Harvard Univ.) Reflections on T.W. Richards-Dr. Patricia A Mabrouk, Jennifer V. Schaus (James S. Panek, Chair, Richards Medal Award Committee Boston Univ.) Introduction of the Award Recipient-Dr. Daniel G. Nocera, Mass. Our congratulation and best wishes to Institute of Technology these Award/Fellowship recipients. Presentation of the Medal to Prof. Stephen J. Lippard, Mass. Insti- tute of Technology-Dr. Morton Z. Hoffman ment for ovarian cancer, currently Three Avenues in Bioinorganic Chemistry: Cisplatin, Methane undergoing a phase I clinical trial in Monoxygenase, and Metalloneurochemistry-Dr. Stephen J. Lippard, Boston. Mass. Institute of Technology Metal ions are also key compo- Dinner reservations should be made no later than noon, March 7, 2002. Please nents of enzymes. In methanotrophic call or f ax Marilou Cashman at (800) 872-2054 or e-mail at bacteria, which use methane as their [email protected]. Reservations not cancelled at least 24 hours in sole source of carbon and energy, a advance must be paid. Members, $30.00; Non-members, $35.00; Retirees, hydroxylase enzyme (MMOH) hous- $20.00; Students, $ 8.00. ing a carboxylate-bridged non-heme THE PUBLIC IS INVITED. diiron unit activates dioxygen for the Anyone who needs special services or transportation, please call Marilou selective conversion of methane into Cashman a few days in advance so that suitable arrangements can be made. methanol. This remarkable reaction Free Parking: in the Broadway St. Garage (3rd level or higher), enter from proceeds in a stepwise fashion, the Cambridge St. via Felton St. details of which have been delineated Next Meeting: April 18, 2002, Gustavus J. Esselen Award to Dr. Ronald Bres- through structural studies of the low, Columbia University. 5:30 Reception and Dinner, Harvard Faculty Club; enzyme and its partner proteins 8:15 Award Meeting, Pfizer Lecture Hall, Mallinckrodt Building, 12 Oxford St. required for activity, mechanistic stud- Dr. Breslow: ”Chemistry Lessons from Biology and Vice-versa” ies of intermediates, and experimental and theoretical analyses of the C-H bond activation step. The transition a leading cause of death of young state involves a bound radical that Abstract males. This and related platinum anti- evolves products through both con- cancer drugs kill cancer cells through a certed insertion and recoil /rebound Three Avenues in Bioinorganic multifactorial mechanism. The first steps. Analogs of the active site have Chemistry step is activation to facilitate DNA been synthesized that afford insight The interface between inorganic and binding. Structures of the major plat- into the structures and chemistry of biological chemistry is broad and ex- inum-DNA adduct reveal distortions of MMOH. panding. Metal ions are extensively the double helix that trigger the inter- Neurochemistry is similarly applied in diagnostic and therapeutic action of proteins involved in gene replete with inorganic ions essential for medicine. The simple coordination activation. Inhibition of the key cellular function. New fluorescent sensors for compound cis-diamminedichloroplat- processes of transcription and zinc and nitric oxide ha ve been inum(II), also known as cis-platin, has nucleotide excision repair ensues. The obtained that have the potential to map contributed significantly to the man- discovery of a means of applying this neural networks in the hippocampus, agement of testicular cancer, formerly information has afforded a new treat- the center of learning and memory.
The Nucleus March 2002 5 Biography Who was Theodore Continued from page 4 Research Conference on Inorganic Chemistry and was Chair of the 1996 William Richards? Gordon Research Conference on Met- by M.S. Simon als in Biology. Adapted from The NUCLEUS, 1996 (3) 4 ff His awards include the Henry J. Albert Award of the International Pre- cious Metals Institute for his work on The presentation of the Theodore sors in chemistry. The Northeastern platinum metals and their interactions William Richards Medal to Stephen J. Section has many great chemists, but with nucleic acids, the American Lippard this month recognizes ‘con- the earliest of the internationally Chemical Society Award in Inorganic spicuous achievement in the advance- renowned was Theodore William Chemistry sponsored by Monsanto ment of chemistry’, and we can take Richards. His Nobel Prize in Chem- Company, the Remsen Award spon- pride not only in the choice this year, istry, awarded in 1914, was the first sored by the Maryland Section of the but also in the many distinguished given an American chemist. American Chemical Society , the chemists who have won this honor in He was born in Germantown in Alexander van Humboldt Senior US. past years. [See the listing in THE 1868, was educated at home by his Scientist Award, the John C. Bailar, Jr. NUCLEUS, 1998 (2) 24]. But as we mother, a poet, and his father a marine Medal of the University of Illinois, the honor Prof. Lippard, we are also hon- artist. He became interested in science American Chemical Society Award for oring the memory of Richards himself. at the age of six when he was shown Distinguished Service in Inorganic Who was this. man? the rings of Saturn through a four inch Chemistry sponsored by Mallinckrodt The first award of what, at that telescope by Professor Josiah Parsons Company, the William H. Nichols time; was known as the Theodore Cooke, Jr. of Harvard while the family medal sponsored by the New York Sec- William Richards Gold Medal (the was at Newport, R.I. At ten he was tion of the American Chemical Society, medal is still gold, with a silv er replica making Pharaoh’s Serpents with mer- the Frontiers in Biological Chemistry for informal display) was made to curic thiocyanate and coloring flames Award from the Max Planck Institut Arthur Amos Noyes in 1932. The Sec- with various salts.. He obtained money für Strahlenchemie, honorary D. Sc. tion Chairman, William Ryan, intro- to set up a chemistry laboratory when degrees from Haverford College and duced the occasion with the following he was 13 by printing on a hand press, Texas A&M University, an Honorary quotation by Henry Watterson: copywriting, and selling an edition of Membership in the Italian Chemical A mound of earth a little higher graded his mother’s sonnets. He was allowed Society, and Scientific Membership in Perhaps upon a stone a c hiselled to attend chemistry lectures at the Uni- the Max-Planck-Gesellschaft. He has name, versity of Pennsylvania, and at 14 been elected to the American Academy A daub of printer’s ink soon blurred entered and studied chemistry at of Arts and Sciences, the National and faded Haverford. He received the Bachelor of Academy of Sciences, and the Institute And then — oblivion. That — that is Science at 17. He went to Harvard to of Medicine. fame. study under Cooke and received a Professor Lippard’s research activ- Ryan went to point out that Wat- Bachelor of Arts and, at 20, after a year ities span the fields of inorganic, bio- terson, as an observer in national poli- of very difficult research in which he logical chemistry, and neurochemistry. tics, had developed a cynical attitude demonstrated exceptional experimental Included are mechanistic studies of toward self-seeking politicians, and skills in determining the atomic weight platinum anticancer drugs, the synthe- Ryan contrasts the impermanence of ratio of oxygen to hydrogen in water, sis of dimetallic complexes as models reputation of such with the seekers of earned the Ph.D. degree. A year in for non-heme iron enzymes and metal- truth for truth’s sake for whom true Europe on a Harvard fellowship gave lohydrolases, structural and mechanis- fame is imperishable. With reference to him the opportunity of studying analyt- tic investigations of methane Richards he said, “True fame ... lives ical techniques at Göttingen and visit- monooxygenase, and novel sensors for on, not merely to perpetuate the name ing important laboratories in Germany, neurotransmitters. of the individual and his accomplish- France, England, and Switzerland. He ments, but rather to inspire and encour- returned to Harvard in 1889 as an age others who are serving similar assistant and remained there for the ends.” rest of his years. When Cooke died, in But in our age, when only “fifteen 1892, Richards, already an assistant minutes” of fame are allowed, it professor, was sent to Ostwald at behooves us to keep alive the names Leipzig and Nernst at Göttingen to pre- and accomplishments of our predeces- pare himself to become the instructor
6 The Nucleus March 2002 Who Was TWR? the mantle on his own shoulders. A tion (with G.S. Forbes and L.J. Hen- modest man, only after searching dili- derson) of an adiabatic calorimeter led Continued from page 6 gently for his own possible errors to studies of specific heats of acids, would he conclude that the Stas work bases and salts, heats of solution and in physical chemistry. His rise to full had to be superseded. dilution, heats of neutralization and the professorship at Harvard in 1901 came He was guided to success by “his thermochemistry of organic com- quickly, when Göttingen attempted to ability to foresee all sources of error pounds. recruit him. and possible calamities which the aver- His laboratory attracted students His early work centered one what age investigator would have over- from many other countries to learn the at the time was one of the major sci- looked completely”, reported his methods of the Harvard school. His entific problems, that of determining son-in-law, James B. Conant. ability to devise methods which could exact atomic weights. He explained his Richards put it thus, “Every sub- give superb results in the hands of stu- choice, “not merely because I felt more stance must be assumed to be impure, dents led to volumes of published competent in that direction than in an y every reaction must be assumed to be research. The list of his students other, but also because atomic weights incomplete, every method of measure- includes many of the most capable seemed to be one of the primal myster- ment must be assumed to contain some physical chemists of the first half of ies of the universe. They are values constant error, until proof to the con- the twentieth century. which no man by taking thought can trary can be obtained. As little as possi- At his death in 1928 the North- change. They seem to be independent ble must be taken for granted.” eastern Section appealed for funds to of place and time. They are silent wit- It is illuminating to consider that set up a memorial and, with ‘gratifying nesses of the very beginnings of the much of his work was conducted in response’, raised a sum of ten thousand universe, and the half-hidden, half-dis- Boylston Hall, where his laboratory dollars in a few months. The Theodore closed symmetry of the periodic sys- had been a stockroom, where the iron William Richards Gold Medal was tem of the elements only enhances sashes of the fume hood rained rust, designed by Cyrus Dallin, a distin- one’s curiosity about them. Moreover, and a flood on the floor above caused guished sculptor and friend of among the many properties possessed the ceiling to collapse on him; where Richards. A more complete account of by an element, the atomic weight fumes from elsewhere in the building the career of Richards may be found in seems one of the most definite and pre- could ruin his experiments. Finally, the a lecture delivered by Sir Harold Hart- cise. Hence in trying to satisfy a desire Wolcott Gibbs Memorial Laboratory, a ley and recorded in the Journal of the which had as its object the discovery of gift of Dr. Morris Loeb, was built in Chemical Society (London), 1930, more knowledge concerning the funda- 1912 and Richards had the facilities his 1930-1968, from which much of this mental nature of thing’s, one naturally work deserved. article was taken. Other sources assigns to the atomic weights an The concentration on atomic include the Encyclopedia Britannica important place.” weights suggests that Richards was and The NUCLEUS. The Scientific In the following years Richards solely an analytical chemist. Indeed, he Work of Theodore William Richards is and his students (if we include inde- was a superb analytical experimental- the title of a Ph.D. dissertation by Shel- pendent work of Baxter and ist, but his work in other areas of phys- don J. Kopperl, U. Wisconsin, Madi- Hönigschmid, who had been trained ical chemistry formed an important son, 1970, 333-359. by him) determined the atomic weight part of the total picture. His work (For pictures of T.W. Richards see of 55 of the 92 known elements, in began at the period when physical p. 24 and 25) many cases in parts per ten thousand, chemistry was aborning; van’t Hoff, in some, parts per hundred thousand. Arrhenius, Ostwald, Nernst were the All of the elements whose atomic new names and the Zeitschrlft für weights were the basis for determining Physikalische Chemie was founded in the atomic weights of other elements 1887. Richards’ first student in physi- were determined. His work on lead cal chemistry was G.N. Lewis, to Have you looked from uranium and from non-radioac- whom he assigned the study of the tive sources advanced acceptance of electrochemistry and thermochemistry at the NESACS the theory of isotopes, the only of amalgam cells. Richards rejected the conclusive evidence until the develop- belief of that day that atoms were website? ment of the mass spectrograph. incompressible, developed evidence He was always respectful to those that atomic volumes change, and, on whose shoulders he was standing, according to Lewis, very nearly dis- J.J. Berzelius and J.S. Stas, pioneers in covered the third law of thermodynam- WWW.NESACS.org atomic weight determination, but when ics in his studies of the relationship of his superior methods showed that the changes in free energy and total energy Stas values had to be revised, he took accompanying a reaction. His inven-
The Nucleus March 2002 7 Call For Papers Meeting Report What Is Different About Fluorocarbons? Northeast Student Chemistry An address delivered at the January 10, 2002 meeting of Research Conference 2002 the Northeastern Section by David M. Lemal, Dartmouth College Open to undergraduates, graduates, and postdoctoral fellows in all areas of chemical research Of all the elements in the Periodic Table, only fluorine can fully replace the hydrogens in virtually every kind of Saturday, April 27, 2002 organic molecule.1 The properties and chemical reactivity Boston University, Science Building of the resulting fluorocarbons and fluorocarbon derivatives are dramatically different from those of the parent com- Visit the NESACS YCC website at pounds. From the inert, uniquely slippery polymer Teflon® http://people.bu.edu/nsycc for details. to the liquids that carry oxygen in blood substitutes and Abstracts will be accepted on this site. There is no breathing liquids, perfluorinated substances enjoy an abun- registration fee. dance of uses, for many of which they are without equal. Fluorinated drugs and agrochemicals are also very impor- Students are invited to present a poster or a 15 minute oral tant, but these compounds generally contain at most a few presentation. fluorines. The account that follows is focused on fundamen- Deadlines: tal aspects of fluorocarbon chemistry, with emphasis on the Oral presentations: April 5, 2002 relationship between perfluorinated compounds and their Poster presentations: April 12, 2002 hydrocarbon counterparts. Contrasts between these classes of compounds are traceable principally to three key differences between hydro- gen and fluorine. The great disparity in electronegativity is of central importance, and fluorine’s ~20% greater van der Undergraduate Research Poster Waals radius and bond length to carbon give rise to large Session steric effects in highly fluorinated molecules. In addition, lone pairs give fluorine π donor ability that hydrogen lacks. th 224 National Meeting of the American Chemical Society The remarkable volatility and low refractive indices of Boston, Massachusetts, August 18–22, 2002 fluorocarbons are attributable to fluorine’s status as the most The ACS invites undergraduate students to submit abstracts electronegative element, for its tightly bound electrons resist of their research papers for presentation at the Under gradu- polarization. The consequently weak London forces ate Research Poster Session, which will be part of the pro- between fluorocarbons are largely responsible for their gram for undergraduates at this national meeting. peculiar solubility properties. Immiscibility of fluorocarbon Abstracts must be submitted electronically: liquids with many other solvents forms the basis for fluo- rous biphase technology,2 which facilitates the separation of • Go to the meeting web site: reaction mixtures.
8 The Nucleus March 2002 Meeting Report can assume in fluorocarbons, as the reaction is driven by relief of nonbonded repulsion in the benzene. Continued from page 8
Electron withdrawal by fluorine tends to lower in energy all of the molecular orbitals in a fluorocarbon, but the effect is much greater on σ-type than on π-type orbitals because of the compensating π donor effect of the fluorine lone pairs (the “perfluoro effect”7). Whereas the first ioniza- tion potentials (π) of ethylene and tetrafluoroethylene are Ketones are strongly destabilized by fluorine substitu- virtually identical, the second (σ) differ by more than 3 eV. tion because of electron withdrawal from an already elec- Another manifestation of the perfluoro effect is found in the tron-deficient carbonyl carbon. In contrast to typical enols, perfluoroenols are strikingly stable kinetically, resisting hexafluorobenzene radical anion (3), wherein the half-filled 14 8 ketonization even in the presence of powerful acids. In LUMO is a σ* instead of a π* orbital. 15 Perfluoroalkyl substituents markedly stabilize strained some cases they are thermodynamically stable as well. carbon skeletons (the “perfluoroalkyl effect”9), making pos- Heptafluorocyclopentenol (9) is a case in point, as K enol for its formation from the cyclopentanone 8 is ~130 even in car- sible the isolation and study of ring systems whose parent -8 bon tetrachloride (cf. cyclopentanone itself, Kenol = 1.1 x 10 molecules are unknown or extremely unstable. Steric pro- 16 tection is responsible in part for the effect, but strengthening in H2O ). Equilibrium constants for enolization of 2 H-per- of skeletal C-C bonds is apparently also significant. As an fluoroketones are far higher in Lewis basic solvents such as example, Dewar thiophene (4) has been observed only in ether, THF and acetonitrile than in carbon tetrachloride cryogenic matrices,10 but perfluorotetramethyl Dewar thio- because of the powerful hydrogen bond donor ability of per- phene (5) has a half-life for aromatization of 5.1 hours at fluoroenols. 160 oC.11 Isomerization of hexamethyl Dewar benzene (6) to the benzene is highly e xothermic (∆H = ca. -57 kcal/mol12), yet at 400 oC perfluorohexaethylbenzene is transformed in good yield into its Dewar isomer 7.13 This amazing reversal illustrates the importance that steric effects Continued on page 10
The Nucleus March 2002 9 Meeting Report cleanly to the strained bicyclo[2.1.1]hexane 13,23 a reaction that proceeds completely in the opposite direction with the Continued from page 9 parent hydrocarbons.24 Cope rearrangement of perfluoro- 25 The strain energy of hexafluorocyclopropane is greater 1,5-dienes takes place via biradical transition states, not 26 than twice that of the parent hydrocarbon (~70 vs. 27.6 concertedly as with hydrocarbon dienes, again in large part kcal/mol).17 The large amount of s character in the exo- because of fluorine’s preference for p-rich carbon orbitals. cyclic carbon orbitals results in especially strong bonds to hydrogen, thus lowering the energy of cyclopropane, but electronegative fluorine atoms prefer bonding to carbon orbitals with more p character (Bent ’s Rule18). Destabiliza- tion of 3-membered rings by fluorine is e vident in the con- trasting behavior of quadricyclane (10) and its perfluoro counterpart. The hydrocarbon has a half-life of 4 hours at In contrast to cyclopropanes, fluorine substitution sig- 154 oC for ring opening to norbornadiene, 19 but octafluoro- nificantly stabilizes cyclobutanes, presumably because it quadricyclane (11) rearranges to a tricy- reduces repulsion between nonbonded carbons by diminish- 27 cloheptene at temperatures just above ing electron density in the center of the ring. This helps to 0oC.20 Incidentally, the 19F NMR spec- explain why the highly strained and reactive alkene 14 is 28 trum of octafluoroquadricyclane spans stable at elevated temperatures while the parent hydrocar- o 29 more than 100 ppm, thus illustrating the bon dimerizes or polymerizes rapidly below 0 C, and why 30 great dispersion available in fluorine [2.2.2]propellane 15 ring opens a great deal slower at NMR that enhances its value as a struc- room temperature than the only previously isolated deriva- 31 tural tool.21 tive of this very strained ring system (16). Other evidence for fluorine’s preference for sp3 over sp2 hybridization at carbon includes the much greater heat of polymerization of tetrafluoroethylene as compared with eth- ylene: ∆H = -37.2 vs –22.7 kcal/mol.22 It is apparent as well in the thermal cyclization of perfluorodienes and –trienes. For example, decafluorohexa-1,5-diene (12) rearranges
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10 The Nucleus March 2002 Meeting Report Continued from page 10 Nominations Whereas the fragile central bond of 16 is cleaved elec- Henry A. Hill Award for Outstanding Service to trophilically in an instant by bromine at –70 oC, 15 is stable the Northeastern Section even to sulfuric acid in acetonitrile at room temperature. Nominations for the Henry A. Hill Award for Outstanding The electron withdrawal by fluorine that makes 15 stoutly Service to the Northeastern Section are invited. Nomina- resistant to electrophilic attack renders it v ery susceptible to tions should be sent by August 8, 2002 to the Administra- attack by nucleophiles, for all of the halide ions clea ve its tive Secretary, NESACS, Marilou Cashman, 23 Cottage St., 32 central bond under gentle conditions. Natick, MA 01760. A resume of professional activities and We hope the above catalog of contrasts, though hardly description of the nominee’s service to the Northeastern complete, serves to highlight the special nature of fluorocar- Section should be included. The Award is to be presented at bons and their derivatives, and to help the reader understand the October meeting of the Section. why they continue to fascinate the researchers who study Michael J. Dube, Chair, Awards Committee them. Acknowledgement. The author is greatly indebted to the coworkers whose names appear in the references, and to the al., which encompasses 19 papers, see: Hart, H.; Rappoport, National Science Foundation, the Air Force Office of Scien- Z.; Biali, S.E. in The Chemistry of Enols; Rappoport, Z., Ed.; tific Research and the donors of the Petroleum Research Wiley: Chichester, 1990; p 502. Fund of the American Chemical Society for support of the 15 Lindner, P.E.; Lemal, D.M. J. Am. Chem. Soc. 1997, 119, work carried out in our laboratory. 3259. See also Lindner, P.E.; Lemal, D.M. J. Org. Chem. References 1996, 61, 5109; Lindner, P.E.; Correa, R.A.; Gino, J.; Lemal, D.M. J. Am. Chem. Soc. 1996, 118, 2556; Correa, R.A.; Lind- 1 Chemistry of Organic Fluorine Compounds II: A Critical ner, P.E.; Lemal, D.M. J. Am. Chem. Soc. 1994, 116, 10795. Review; Hudlicky, M.; Pavlath, A.E., Eds.; American Chemi- cal Society: Washington, D.C., 1995. Fluorine at the Millen- 16 Keeffe, J.R.; Kresge, A.J.; Schepp, N.P. J. Am. Chem. Soc. nium. Fascinated by Fluorine; Banks, R.E., Ed.; Elsevier: 1990, 112, 4862. Oxford, 2000. Organofluorine Chemistry, Principles and 17 Zeiger, D.N.; Liebman, J.F. J. Mol. Struct. 2000, 556, 83. Commercial Applications; Banks, R.E.; Smart, B.E.; Tatlow, 18 Bent, H.A. Chem. Rev. 1961, 61, 275. J.C., Eds.; Plenum: New York, 1994. 19 Frey, H.M. J. Chem. Soc. 1964, 365. 2 Curran, D.P. Pure Appl. Chem. 2000, 72, 1649. Horvath, I.T. 20 Dailey, W.P.; Lemal, D.M. J. Am. Chem. Soc. 1984, 106, Acc. Chem. Res. 1998, 31, 641. 1169. 3 Paprott, G.; Lentz, D.; Seppelt, K. Chem. Ber. 1984, 117, 21 Emsley, J.W.; Feeney, J.; Sutcliffe, L.H. High Resolution 1153. Paprott, G.; Seppelt, K. J. Am. Chem. Soc. 1984, 106, Nuclear Magnetic Resonance Spectroscopy; Pergamon: 4060. Oxford, 1966; Vol. 2, Chap. 11. The range of 19F chemical 4 Streitwieser, A., Jr.; Nelson, L.L. J. Am. Chem. Soc. 1976, 98, shifts is ~300 ppm for organofluorine compounds and ~1000 2188. ppm overall. 5 Laganis, E.D.; Lemal, D.M. J. Am. Chem. Soc. 1980, 102, 22 Joshi, R.M.; Zwolinski, B.J. in Ham, G.E., Ed.; Vinyl Poly- 6633. merization; Marcel Dekker: New York, 1967; Vol. 1. 6 Blint, R.J.; McMahon, T.B.; Beauchamp, J.L. J. Am. Chem. 23 Correa, R.A.; Jing, N.; Lemal, D.M. J. Org. Chem. 1993, 58, Soc. 1974, 96, 1269. 6406. 7 Brundle, C.R.; Robin, M.B.; Kuebler, N.A.; Basch, H. J. Am. 24 Srinivasan, R.; Levi, A.A. J. Am. Chem. Soc. 1963, 85, 3363. Chem. Soc. 1972, 94, 1451. Brundle, C.R.; Robin, M.B.; 25 Jing, N.; Lemal, D.M. J. Am. Chem. Soc. 1993, 115, 8481. Kuebler, N.A. J. Am. Chem. Soc. 1972, 94, 1466. 26 Houk, K.N.; Gustafson, S.M.; Black, K.A. J. Am. Chem. Soc. 8 Yim, M.B.; Wood, D.E. J. Am. Chem. Soc. 1976, 98, 2053. 1992, 114, 8565. Dupuis, M.; Murray, C.; Davidson, E.R. J. 9 Lemal, D.M.; Dunlap, L.H., Jr. J. Am. Chem. Soc. 1972, 94, Am. Chem. Soc. 1991, 113, 9756. 6562. 27 Liebman, J.; Dolbier, W.R., Jr.; Greenberg, A. J. Phys. Chem. 10 Rendall, W.A.; Clement, A.; Torres, M.; Strausz, O.P. J. Am. 1986, 90, 394. Bauld, N.L.; Cessac, J.; Holloway, R.L. J. Am. Chem. Soc. 1986, 108, 1691. Rendall, W.A.; Torres, M.; Chem. Soc. 1977, 99, 8140. Strausz, O.P. J. Am. Chem. Soc. 1986, 107, 723. 28 Junk, C.P., Ph.D. Dissertation, Dartmouth College, 2000. 11 Kobayashi, Y.; Kumadaki, I.; Ohsawa, A.; Sekine, Y. Tetrahe- 29 Wiberg, K.B.; Matturro, M.G.; Okarma, P.J.; Jason, M.E. J. dron Lett. 1975, 1639. Am. Chem. Soc. 1984, 106, 2194. Wiberg, K.B.; Matturro, 12 Oth, J.F.M. Angew. Chem. Int. Ed. Engl. 1968, 7, 646. Adam, M.G.; Okarma, P.J.; Jason, M.E.; Dailey, W.P.; Burgmaier, W.; Chang, J.C. Internat. J. Chem. Kinetics 1969, 1, 487. G.J.; Bailey, W.F.; Warner, P. Tetrahedron 1986, 42, 1895. 13 Dabbagh, A.-M.; Flowers, W.T.; Haszeldine, R.N.; Robinson, 30 Zhang, Y.; Smith, J.R.; Lemal, D.M. J. Am. Chem. Soc. 1996, P.J. J. Chem. Soc., Chem. Commun. 1975, 323. Clifton, E.D.; 118, 9454. Flowers, W.T.; Haszeldine, R.N. J. Chem. Soc., Chem. Com- 31 Eaton, P.E.; Temme, G.E., III J. Am. Chem. Soc. 1973, 95, mun. 1969, 1216. 7508. 14 For a concise summary of this w ork of Bekker, Knunyants et 32 Smith, J.R., Ph.D. Dissertation, Dartmouth College, 1999
The Nucleus March 2002 11 raphy) of their summer projects to the NESACS Education Applications Invited Committee by November 8, 2002 for publication in The Nucleus. They are also required to participate in the North- The James Flack Norris and Theodore east Student Chemistry Research Conference (NSCRC) in William Richards Undergraduate Summer April 2003. Research Scholarships Eligibility: Applications will be accepted from student/f ac- ulty teams at colleges and universities within the Northeast- The Northeastern Section of the American Chemical Society ern Section. The undergraduate student must be a (NESACS) established the James Flack Norris and chemistry, biochemistry, chemical engineering, or molecular Theodore William Richards Undergraduate Summer Schol- biology major in good standing, and have completed at least arships to honor the memories of Professors Norris and two full years of college-level chemistry by summer, 2002. Richards by promoting research interactions between under- graduate students and faculty. Application: Application forms are available on the Research awards of $3250 will be given for the summer NESACS web site at http://www.nesacs.org. Completed of 2002. The student stipend is $2750 for a minimum com- applications are to be submitted no later than March 22, mitment of ten weeks of full-time research work. The 2002 to the Chair of the Selection Committee: remaining $500 of the award can be spent on supplies, Professor Edwin Jahngen, travel, and other items relevant to the student project. University of Massachusetts Lowell Institutions whose student/faculty team receives a Nor- ris/Richards Undergraduate Summer Research Scholarship Chemistry Department, Room 520 are expected to contribute toward the support of the faculty 265 Riverside Street, Olney Hall members and to waive any student fees for summer Lowell, MA 01854-5047 research. Academic credit may be granted to the students at the discretion of the institutions. Notification: Applicants will be notified of the results by e-mail on April 26, 2002. Written confirmation will follow. Award winners are required to submit a report (~5-7 double-spaced pages including figures, tables, and bibliog- We Got All Your GPC/SEC Needs
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12 The Nucleus March 2002 ACS SHORT COURSE Designed to improve the skills and marketability of practicing B.S., M.S., and Ph.D. chemists. The NESACS Committee on Continuing Education is pleased to sponsor this newly updated National ACS Two-Day Short Course, at a registration fee less than half of that charged at National and Regional ACS Meetings. INTERPRETATION OF MASS SPECTRA This Short Course is designed for chemical scientists who require the knowledge and skill of mass spectral interpretation. The course does not require expertise in advanced mathematics, physics, or theoretical chemistry. Registrants should have a basic knowledge of chemistry, and course work in organic chemistry is desirable. Participants should bring a basic calcula- tor to the course. DATES and TIME: Thursday, May 2, 2002; 8:00 a.m. – 5:00 p.m. and Friday, May 3, 2002; 8:30 a.m. – 5:00 p.m. PLACE: Snell Library, Room 90, Northeastern University, 360 Huntington Ave., Boston, MA PROGRAM AGENDA: Introduction to Chemical Bonding in Organic Mole- Mass Spectra of High Molecular Weight Compounds. cules as it Pertains to Mass Spectrometry MS/MS Mass Spectra – What Are They and How Do How the EI Mass Spectrum is Formed – Rules and We Deal With Them? Principles. Fragmentation of Specific Compound Types – Naturally Occurring Stable Isotope Abundances and Aliphatic and Aromatic Hydrocarbons, Alcohols, Their Role in Peak Intensity Amines, Acids, Aldehydes, and Ketones. The Molecular Ion Library Searches and Mixed Spectral Data Odd-electron ions; the nitrogen rule; logical losses. Chemical Ionization and Electron Ionization Spectra Fragmentation as it Relates to Structure, Elemental Used Together to Determine the Identity and Struc- Composition, and Compound Type. ture of an Unknown. COURSE BONUS! Bring your own mass spectra to the course for analysis. The instructor will help you to interpret your spectra and use them as examples for class discussion if appropriate. INSTRUCTOR: O. David Sparkman is an Adjunct Professor of Chemistry at the University of the Pacific in Stockton, Cal., and a con- sultant to the National Institute of Standards and Technology Mass Spectrometry Data Center. At the University of the Pacific he teaches courses in mass spectrometry and analytical chemistry and manages the mass spectrometry facility. He is on the Editorial Advisory Boards of the Journal of the American Society for Mass Spectrometry and the HD Science GC/MS Update – Part B. He is the author of Mass Spectrometry Desk Reference, and with J. Throck Watson developed the Mass Spectral Interpretation Quick Reference Guide. Professor Sparkman is one of the highest rated instructors in the ACS Short Course program.. PRE-REGISTRATION REQUIRED – Registration Fees: ACS Members if received before Apr 17………… $450.00; after April 17 ……$525.00 Non-ACS Members if received before April 17 ..…$550.00; after April 17 ……$625.00 There will be a limited number of scholarships for unemployed ACS Members on a space-available basis. Parking Fee: about $14.00/day University cafeterias will be available for lunches. For further information contact: Prof. Alfred Viola at (617) 373 2809 Registration form for Short Course: Interpretation of Mass Spectra. May 2-3, 2002 Name: ______Business Affiliation:______Mailing ______Telephone:______Address______Mail with remittance to: Prof. Alfred Viola, Chair (Please make checks payable to NESACS. NESACS Committee on Cont. Ed. Sorry, we cannot accept credit cards or Department of Chemistry purchase orders.) Northeastern University Boston, MA 02115
The Nucleus March 2002 13 Candidates for 2003 Board of
Chair-Elect: Director-at-Large: Directors Howard R. Mayne Ernest V. Groman Jean Fuller Stanley Chu W. Jung Notes of Meeting of December 6, 2001 Treasurer: Julia H. Miwa James U. Piper Carmela C. Amato-Wierda NOTE: Board Meetings are held on the monthly meeting day at 4:30 p.m. Sec- Auditor: Nominating Committee: tion members are invited to attend. Anthony L. Rosner Timothy B. Frigo Michael J. Hearn Officers’ Reports: Trustee: Chair: T. Frigo announced that Donald O. Rickter Michael E. Strem NESACS has received a mini-grant of Derk A. Wierda Councilor/ Alternate Councilor: $500 from the ACS Office of Diversity for the February 2002 joint meeting Mary Burgess Norris Award Committee: with NOBCChE. Michaeline Chen James A. Golen Howard R. Mayne T. Frigo relayed Dr. Shakhashiri’s Mukund S. Chorghade appreciation for having been awarded Marietta Schwartz Patrick M. Gordon lifetime membership to NESACS. He J. Donald Smith Morton Z. Hoffman also sent a video-tape of the Holiday Doris I. Lewis Timothy B. Frigo, Chair, Nominating Lecture, to be kept by D. Lewis and to Truman S. Light Committee be made available on loan. Donald O. Rickter A meeting with officials of the Boston Lawrence T. Scott Note: Candidates my be nominated by Museum of Science is to be held for Michael Singer petition, accompanied by signatures of planning for NCW 2002. 130 members, to be submitted to the He reminded board members that Amy Tapper David Warr NESACS office by March 24, 2002. annual reports are due. Chair-Elect: M. Hoffman stated that for the February 14 Meeting (Valen- tine’s Day), in honor of the occasion, members’“Special Valentines” are to be invited to the reception and dinner as guests of the Section. Treasurer: J. Piper presented the November 2001 Treasurer’s Report. After some discussion, it was MOVED and VOTED to accept the report. Standing Committees: Bd. Of Publications: MIT is starting a Program in Science Writing which may offer an opportunity for coopera- tion. The reader survey has been com- pleted and results are being tabulated for later presentation. A revised budget has been pre- sented to the Budget Committee. Help from YCC is sought for help- ing improving the website appearance. Editor: The January issue is to be 24 pages, with the first summer scholar report to be in the issue. Membership: M. Chen stated that two new members will be at tonight’s din- ner. continued on page 15
14 The Nucleus March 2002 Chemistry Education: R. Tanner stated several issues for next year’s At the NESACS Meeting “Connections to Chemistry” meeting: How to accommodate the increased MIT Faculty Clup on December 6, 2001 number of applicants, how to maintain current costs per person, whether there can be industrial sponsorship. Also, Chemmatters has been sent to all attendees of the 2001 “Connec- tions” with a label stating “compli- ments of NESACS.” Norris Richards Scholar papers have been submitted to the NUCLEUS. Only one of the Scholars has asked for support to attend the Orlando ACS Spring Meeting. The other three expect to present papers at the Boston ACS Fall Meeting. (l-r) Tim Frigo, Chair of the Northeastern Section; Mark Sands (Washington University School The issue of section and personal of Medicine); Seng Cheng (Genzyme Corp.); Dennis Vaccaro (Symbiontics, Inc.); Ernest Groman, liability was raised. Clarification of Program Chair of the Medicinal Chemistry Section. (photo by Morton Hoffman) Section responsibility, such as for Sec- needed for the April Research Sympo- recipients on both the national and tion-supported travel to ACS Meetings sium Organizing Committee. local level. is to be sought by the Chair with help Government Affairs: M. Hearn stated New Business: A. Heyn stated that it from M. Strem. that the National OLGA is planning is time to activate a National Meeting Esselen Award: J. Koob reported the 2002 State House Day. The State’s Committee for the August 2002 ACS (written report) that four nominations newest Congressman is to be con- Meeting in Boston. M. Hof fman have been received and a committee tacted. The ACS Chemistry and Public agreed to chair this committee. meeting has been scheduled for Affairs Committee is modifying the From the minutes of M. Singer December 18, 2001 to make a final Grass Roots Awards to recognize selection. Six or seven members are expected to be present, one of them by speakerphone from California. Ways are to be sought for trimming the costs of the award meeting. Other Committees: Natl. Chemistry Week: D. Lewis MOVED as the sense of the Board for making a $2000 donation to the Bas- sam Shakhashiri Science Foundation in Eastern Scientific lieu of giving Dr. Shakhashiri an hono- rarium. So VOTED unanimously. Summerthing: D. Lewis stated that 1/2 page Ad Appears here Summerthing 2002 will again be at the Boston Red Sox, with the date to be determined after the game schedule is Ad # EAST 584N available. If it is possible to schedule this event during the August 25-29, Strip Repro supplied 2002 National ACS Meeting in Boston, 1000 tickets will be ordered, otherwise 200 if the game is in June or July. Younger Chemists: A. Tapper reported that the February 14, 2002 Career event is all set with 5 speakers from 3:00-5:30 pm, preceding the reg- ular monthly NESACS meeting. She stated that volunteers are
The Nucleus March 2002 15 CID’s have been useful in many bio- Summer Research Report logical processes, this approach has not been extended to the post-translational Toward a Small-Molecule Activated Protein Splicing System modification of protein levels. In this Ravi V. Shah† , Joshua M. Finkelstein, and Gregory L. Verdine, Department of research, we aim to construct a ligand- Chemistry and Chemical Biology Harvard University activated intein that allows small mol- ecule-dependent induction of protein levels using CID technology. The ability to perturb the activity close proximity to one other. This Protein splicing involves the exci- of intracellular proteins in a specific, approach has proven fruitful in the sion of non-coding peptides called dose-dependent fashion with small modulation of various important cat- inteins that interrupt the coding extein molecules represents a significant boon alytic and signaling events, namely sequences of a given polypeptide. to clinical and basic medical research. Fas-mediated apoptosis, eukaryotic This autocatalytic activity has sparked One general approach, chemical induc- gene transcriptional regulation, and several structural and mechanistic tion of dimerization (CID), uses small activation of receptor tyrosine kinases studies (for review, see Perler, 1998). molecules to dimerize two different (Belshaw et al., 1996, Amara et al. The intein structure is modular, with proteins, bringing these proteins in 1997, Rivera et al. 1996). Although conserved N- and C-terminal regions and nucleophilic residues at splice junctions are respon- sible for the ac yl transfer reactions leading to extein lig- ation (Fig.1 Mills et al., 1998). Recent work in protein splicing has focused Figure 1, Mechanism of trans splicing. on the use of trans InteinN and InteinC associate with one splicing elements, another. Intein byproducts are shaded. with each e xtein fused to either the N- or C-terminal half of the minimal intein. Splicing acti vity is then dependent on association between the two intein termini to form the active site (Mills et al., 1998; Evans et al., 2000). Recently, Ozawa et al. have engi- neered a trans splicing system of the VDE intein from S. cerevisciae that is dependent on protein-protein interac- tions (Figure 2A; Ozawa et al. 2000). The authors split the VDE intein and an EGFP reporter in half (VDE N, VDEC; EGFPN, EGFPC) and coex- pressed protein fusions of EGFPN- VDEN-calmodulin and M13 peptide-VDEC-EGFPC in E. coli. Splic- ing was shown to be dependent on the interaction between calmodulin and M13 peptide in E. coli, as constructs lacking these binding partners did not splice in trans to produce an EGFP sig- nal.
† 2001 Norris/Richards Summer Scholar Boston, MA 02115 16 The Nucleus March 2002 ligated via mutually-primed PCR with external primers containing BamHI and XhoI sites, and cloned into the BamHI XhoI sites of the galactose- inducible yeast expression vector pESC-Leu (Clontech). FKBP (FKBP1- 107) amplified from plasmids available in the laboratory (Nyanguile et al. 1997) was cloned into the XhoI-NheI sites of pESC-Leu (Clontech). (The full construct is referred to as pESC- Leu-NTERM.) Similar techniques (mutually primed PCR followed by cloning) were used to clone VDEC (VMA1389-454) and EGFPC (EGFP129- 239) into the SalI-XhoI sites of the galactose-inducible yeast expression vector pESC-His (Clontech). FRB* was amplified from plasmids already available in the laboratory (Liberles et al. 1997) was cloned into the BamHI- SalI sites of pESC-His. (The full con- struct is referred to as pESC-His-CTERM.) The “Linker” Figure 2, Experimental paradigm. (A) Ozawa approach: Dimerization of calmodulin and residues were derived from Ozawa et M13 peptide initiates protein splicing. (B) CID approach: Rapamycin induces dimerization al. (2000) and incorporated into PCR of FKBP and FRB to initiate splicing. cloning primers to confer flexibility to These results suggest that the using the QiaGEN genomic DN A the signal tripartite fusion protein. The reconstitution of the intein active site is extraction kit (Qiagen, Inc., Valencia, amino acid sequence of the N-terminal a proximity-driven process, wherein CA). These two PCR products were linker was ASNLENGRNG; the the association of the N- and C-termi- continued on page 18 nal intein fragments leads to trans splicing. In this research, we sought to apply the CID system to protein splic- ing,by replacing the calmodulin and M13 peptide with FKBP (FK-506- binding protein) and FRB* (FKBP- rapamycin bonding domain), tw o proteins that interact in the presence pf the macrolide rapamycin (Figure 2B, Liberles et al. 1997). Chemo Dynamics LP Experimental Plasmid construction. Standard PCR 1/3 page Ad Appears here cloning methods were used to construct the fusions EGFPN-VDEN- Linker-FKBP and FRB-Linker-VDEC- Ad # CHEM 681N EGFPC. The mutant EGFP “m125” (E125I, I129C) used by Ozawa et al. Strip Repro Supplied (2000) was used in this research. EGFPN (EGFP1-128) was amplified from the pCI-EGFP plasmid (Clon- tech, Palo Alto, CA) and VDEN (VMAI1-184) was amplified from genomic DNA extracted from strain BY4741 (MATa, his3D1 leu2D0, met15D0, ura3D0, fpr1::kanMX4; Research Genetics, Huntsville, AL) The Nucleus March 2002 17 Summer Research thiogalactopyranoside (IPTG, final 50 mL aliquot of the stationary phase concentration 1 mM; control was unin- overnight culture was reinoculated into Continued from page 17 duced), and allowing expression for 4 fresh 1 L kanamycin-supplemented sequence of the C-terminal linker was h. A 1 mL aliquot of induced and unin- LB, grown to OD 600 0.4-0.7, and GNNCDNNDV. For in vitro studies, duced cells were pelleted; the super- induced at the optimal temperature the full N-terminal intein construct was natant was removed; the cell pellet was (25°C for C-terminal, 30°C for N-ter- subcloned from pESC-Leu-NTERM resuspended and lysed by boiling at minal) for 24 hr and 4 hr, respectively. into the BamHI-EcoRI sites of bacter- 100°C for 10 min in SDS loading Cells were pelleted, resuspended in 20 ial expression vector pET-28b (called buffer (2% SDS, 0.25% bromophenol mL Lysis Buffer, and mechanically pET-28-NTERM; Novagen, Madison, blue, 10% ß-mercaptoethanol). The lyzed via French press. Lysates were WI); the C-terminal construct was sub- resulting lysates were subjected to centrifuged at 15,000g for 20 min. The cloned from pESC-His-CTERM into SDS-PAGE on a NuPAGE 4-12% Bis- pET28b vector encodes hexahistidine the BamHI-XhoI sites of pET-28b Tris gradient gel in MES electrophore- tags at the N- and C-terminal ends of (called pET-28-CTERM). Sequence sis buffer (Invitrogen, Carlsbad, CA). the recombinant proteins, and these Experiments to assay the solubility of His tags were used to purify the pro- confirmation of all constructs was per- 2+ formed by Seqwright, Inc. (Houston, the expressed proteins were run in a teins via Ni affinity chromatography. TX). similar manner, lysing cells via sonica- As such, the resulting supernatant was tion in Lysis Buffer (500 mM NaCl, 50 loaded onto an affinity column charged Expression and solubility testing. 2+ Each pET-28b construct (pET-28b- mM Tris-HCl pH 8.0) and pelleting the with 2 mL Ni TALON resin (Clon- CTERM and pET28b-NTERM) were lysates. Both the supernatant (soluble) tech) and pre-equilibrated with 20 mL transformed into BL21(DE3) lysogen and pelleted cell debris (insoluble) Lysis Buffer. The supernatant-contain- competent cells (Novagen). The levels fraction were boiled in SDS loading ing column was incubated for 1 hr at of expression at 25, 30, and 37°C for buffer and subjected to SDSPAGE as 4°C under gentle shaking. Supernatant both constructs were assessed by grow- above. was allowed to flow through the col- ing one colony from each BL21(DE3) Protein overexpression. One colony of umn (“flow through”), and the column transformation in kanamycin (30 the appropriate BL21(DE3) transfor- was subsequently washed 4 x 10 mL of µg/mL)-supplemented Luria-Bertani mant was inoculated into a 1 L culture Lysis Buffer (“wash”). The bound pro- medium (LB) to an optical density of kanamycin-supplemented LB, and teins were eluted from the column by grown at 37°C (pET-28b-NTERM) or addition of Elution Buffer (500 mM (OD600) of 0.4-0.7, inducing transcrip- tion via addition of isopropyl-ß-D- 25°C (pET-28b-CTERM) overnight. A NaCl, 50 mM Tris-HCl pH 8.0, 100 mM imidazole) in 1 mL aliquots. Frac- tions were collected and assayed for protein using the Bradford assay (Bio- Rad, Hercules, CA), and protein- containing fractions were pooled (“eluant”). Construction of yeast strain. In yeast cells, the FKBP ortholog Fprlp binds rapamycin to form a complex that binds Torlp, ultimately leading to growth arrest in G1 (Zheng et al., 1995). In order to overcome the prob- lem of rapamycin cytotoxicity in yeast cells, an fprl knock-out yeast strain mutant for Torlp had to be constructed. It is known that a mutation in the non- essential tor1 allele (S1972R) renders yeast rapamycin-resistant (Zheng et al. 1995). The Tor1 wild-type allele was cloned from yeast genomic DNA, appropriately mutated, and gel puri- fied. We first transformed the FKBP- containing pESC-Leu-NTERM into the BY4741 strain and selected on Leu-deficient, geneticin (30 µg/mL)- containing agar (Leu- gen) with glu-
18 The Nucleus March 2002 cose as a carbon source. Although the (EGFP and VDE) that may not fold may increase soluble expression) and yeast fpr1 had been deleted, the FKBP correctly outside the context of the full more extensive purification for yield- from our transformed pESCLeu- peptide, it is possible that the peptides ing a target free of contaminants for in NTERM construct will participate in a co-purifying with our target may be vitro studies. deleterious FKBP-rapamycin-TOR molecular chaperones responsible for Future goals. The difficulties inherent interaction. A colony from the first re-folding proteins in E. coli. in soluble expression and purification transformation (BY4741 with pESC- The C-terminal intein construct of the C-terminal intein fragment have Leu-NTERM) was grown in Leu - posed more difficulties with respect to led us to pursue in vivo studies in yeast media supplemented with galactose to soluble expression and purification. and mammalian cells. We are currently induce the expression of the N-termi- Again, the C-terminal intein express at attempting the Torlp recombination nal intein construct containing FKBP. high levels at both 30°C and 37°C and yeast transformations as discussed Homologous recombination of our (Figure 3), but solubility experiments (Zheng et al. 1995), and will select for mutant tor1 allele into the genome of showed that a significantly higher frac- recombinants resistant to rapamycin. these cells is currently being con- tion of the C-terminal fusion protein After transforming the rapamycin- ducted, and selection will be per- was solubly expressed at 37°C than at resistant strain containing the N-termi- formed on Leu-, gen agar plates 30°C (Figure 4). However, attempted nal intein construct with our supplemented with galactose and 1 purification of large-scale preparations C-terminal construct, we will induce µg/mL rapamcyin. Transformations of the fusion protein at 37°C failed were completed as described by the (Figure 5). In order to increase solubil- S.C. EasyComp Transformation Kit ity, we attempted overexpression at a (Invitrogen). lower temperature, with favorable Results and Discussion. expression results (data not shown). Protein expression. High levels of pro- Although we did not attempt a solubil- tein expression of the N-terminal con- ity test at this temperature, the large- struct were obtained at both 30°C and scale preparation of the fusion protein 37°C (Figure 3). The absence of a at 25°C was partially successful, yield- strong band in the soluble fraction at ing small amounts of the impure pro- 37°C for the N-terminal construct (Fig- tein (Figure 6). Interestingly, a similar ure 4) indicates that the overexpressed pattern of bands co-eluted with the C- N-terminal intein product is not solu- terminal intein as with the N-terminal ble and well-folded at 37°C: We there- intein. This may be a further indication fore conducted a large-scale expression of a cellular unfolded protein chaper- and purifiction of the pET -28b- one response or simply that we are NTERM at 30°C to yield the ~50kD eluting constitutively expressed ubiqui- product in reasonable purity (Figure 5). tous proteins that have affinity for the Figure 5. Purification of N- and C-inteins. Since our Ni column. We are currently looking FT = flow of lysate through column; WA into other expression systems (for = wash; EL = elution. Boiled induced cells NTERM and CTERM constructs 2+ consist of several segments of proteins example, different bacterial cell lines and Ni resin also included.
Figure 3. N and C-terminal intein fusion Figure 4. Solubility test of N- and C-terminal Figure 6. Purification of C-intein. expression. The arrows indicate the band inteins. (Note: lane for “37 uninduced” not Legend as in Figure 5. corresponding to the overexpressed prod- loaded in N-terminal constructs) uct (~50 kD for N; ~30 kD for C). continued on page 21 The Nucleus March 2002 19 TION
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Create your own success in this opportunity at our headquarters in Cambridge, Massachusetts: Scientist, Computational Chemistry Contribute to our vision by joining the Computational Chemistry Department, where you will be responsible for providing ongoing support of medicinal chemical activities. Located at our headquarters in Cambridge, Massachusetts, your primary functions will be to support structure-based design using docking methods augmented by diversity assessment of virtual libraries. You will also be encouraged to engage in methods research in these areas. A PhD in Computational Chemistry (post doctoral fellowship preferred) is required, along with 2-5 years of industrial experience in several areas of computa- tional chemistry, including library design, diversity evaluation, and especially structure-based design. Experience with sev- eral standard software packages, particularly MOE, Flo and Dockit, is preferred, and programming experience in Perl, SVL, C, C++ or Java is desirable. You will be working in an environment that requires your close communication with the teams
ALIZA COMMERCI you will support.
Help us drive our products through commercialization to market by emailing only one resume to [email protected]. When applying, please use the Source Code NUC0302. We are an equal opportunity employer committed to discovering the individual in everyone.
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20 The Nucleus March 2002 Summer Research subsequent dose-dependent activation Mycobacterium tuberculosis RecA by a ligand allow reversible, temporal intein. PNAS USA 1998 95(7), 3542- Continued from page 19 control of protein levels appropriate to 3548. expression of both N- and C-terminal the patient. In total, CID protein modi- Nyanguile, O., Uesugi, M, Austin, D., fragments with galactose and assay for fication allows the construction of a Verdine, G. A nonnatural transcrip- in vivo splicing activity upon addition ligand-activated intein with the ability tional coactivator. PNAS USA 1997 of rapamycin. We are also in the to titrate intracellular protein levels in a 94, 13402-13406. process of subcloning the N- and C- dose- and time-dependent manner, giv- Ozawa, T., Nogami, S., Sato, M., terminal intein fusions into pCMV- ing access to a wide range of novel Ohya, Y., Umezawa, Y. A fluorescent Script mammalian expression vector applications in genetics and medicine. indicator for detecting protein-pro- (Stratagene, La Jolla, CA). Instead of References tein interactions in vivo based on relying on FKBP and FRB dimeriza- Amara, J., Clackson, T., Rivera, V.M., protein splicing. Anal. Chem. 2000 tion with rapamycin, our new system Guo, T., Keenan, T., Natesan, S., 72(21): 5151-5157. involves a small molecule-dimerizer Pollock, R, Yang, W., Courage, N., Ozawa, T., Kaihara, A, Sato, M., Tachi- that is more orthogonal to cellular Holt, D., Gilman, M. A versatile hara, K., Umeza wa, Y. Split function. We are constructing fusion synthetic dimerizer for the regulation luciferase as an optical probe for proteins of the form EGFPN-VDEN- of protein-protein interactions. PNAS detecting protein-protein interactions in mammalian cells based on protein Linker-FKBP3* and FKBP3*-Linker- USA 1997 20, 10618-10623. C C splicing. Anal. Chem. 2001. 73(21), VDE -EGFP , where FKBP 3* Belshaw, P.J., Ho, S.N., Crabtree, G.R, represents three copies of an engi- Schreiber, S.L. Controlling protein 2516-2521. neered variant of FKBP that selectively association and subcellular localiza- Ozawa, T., Umezawa, Y. Detection of binds to the small molecule homod- tion with a synthetic ligand that protein-protein interactions in vivo imerizer AP1903 (Clackson et al. induces heterodimerization of pro- based on protein splicing. Curr. 1998). AP1903 can selectively dimer- teins. PNAS USA 1996 93, 4604- Opinion in Chem. Biol.2001 5, 578- ize FKBP* that is present on both the 4607. 583. N- and C-terminal intein fusions in the Chan, T., Carvalho, J., Riles, L., Perler, F. Protein splicing of inteins presence of endogenous FKBP. Pre- Zheng, X. A chemical genomics and hedgehog autoproteolysis: struc- sumably, an increased number of approach toward understanding the ture, function, and evolution. Cell copies of FKBP* will force a dimeriza- global functions of the target of 1998 92, 1-4. tion event via cooperative effects. We rapamycin protein. PNAS USA 2000 Rivera, V., Clackson, T., Natesan, S., will very shortly complete the cloning 97(24):13227-13232. Pollock, R, Amara, J., Keenan, T., and assay of this system in mammalian Clackson, T., Yang, W., Rozamus, L., Magar, S., Phillips, T., Courage, N., cells. Hatada, M., Amara, J., Rollins, C., Cerasoli, F., Holt, D., Gilman, M. A Implications. The development of this Stevenson, L., Magari, S., Wood, S.., humanized system for pharmaco- technology could make a very large Courage, N., Lu, X., Cerasoli, F., logic control of gene expression. impact on expression profiling using Gilman, M., Holt, D. Redesigning an Nature Medicine 1996 2, 1028-1032. DNA microarrays. The ability to con- FKBP-ligand interface to generate Zheng, X.-F., Fiorentino, D., Chen, J., trol protein levels in a temporal and chemical dimerizer with novel speci- Crabtree, GR., Schrieber, S. TOR dose-dependent fashion would allow ficity. Kinase domains are required for tw o us to monitor genome-wide responses Evans, T.C. Jr., Martin, D., Kolly, R, distinct functions, only one of which is inhibited by rapamycin. Cell 1995 to the increased expression of a partic- Panne, D., Sun, L., Ghosh, I., Chen, ular gene. Current profiling studies L., Benner, J., Liu, X.Q., Xu, M. 82, 121-130. rely on “knocking out” or overexpress- Protein trans-splicing and cycliza- Feb. Puzzle Solution ing genes of interest, which has limita- tion by a naturally split intein from tions because gene overexpression is the dnaE gene of Synechocystis nonconditional; transfection perma- species PCC6803. J. Biol. Chem. nently alters the expression profile of a 2000 275(13): 9091-9094. cell. Development of a ligand-activated Liberles, S.D., Diver, S.T., Austin, intein would allow rapid, ligand D.J., Schrieber, S.L. Inducible gene dependent increases in protein expres- expression and protein translocation sion, facilitating the study of biological using nontoxic ligands identified by events that occur quickly. Therapeuti- a mammalian three-hybrid screen. cally, viral-mediated delivery of med- PNAS USA 1997 94, 7825-7830. ically relevant proteins (for example, Mills, K., Lew, B., Jiang, S., Paulus, H. tumor suppressor gene products) in Protein splicing in trans by purified their “inactive-intein fused” form and N- and C-terminal fragments of the
The Nucleus March 2002 21 an obvious choice for a review in a tal observations in the laboratory of her Book Review periodical aimed at chemical profes- pregnant body. sionals. Certainly, I would not have In the very early stages of her Having Faith. An Ecologist’s expected to be interested in reviewing pregnancy, during the time when, to Journey To Motherhood it. When it came across my desk (unso- quote Psalm 139, “when I was growing licited), my initial reaction was “Here’s in secret in my mother’s womb”, there by Sandra Steingraber (Perseus Books, one that was clearly misdirected,” is not much that Steingraber can actu- 2001 288 pp., ISBN 0738204676; rather like my reaction when my wife ally observe. She nonetheless imagines $26.00 hardcover} and I are trolling the aisles of the local the changes taking place, such as the Reviewed by Dennis J. Sardella, video store and she picks up a film proliferation of blood vessels, in imag- Department of Chemistry, Merkert whose jacket blurb describes it as inative parallels between external Chemistry Center, Boston College, “heartwarming”. For some reason, observations as a naturalist with the Chestnut Hill, MA 02467 however, I glanced through the first processes taking place within her: few pages of “Having Faith” and was Phil Cousineau, in his book The Art of “Plant physiologists still can ’t drawn into it, so here I am, recom- Pilgrimage, says, that “The difference explain why maple sap runs in the mending that you read a book which is between pilgrim and tourist is the spring. It’s a mystery that secretly not about chemists, or the chemical intention of attention, the quality of the pleases me. All trees stockpile sugar profession, but which illustrates beauti- curiosity.” From this perspective, San- during the winter, and in most fully what can happen when an artist dra Steingraber’s book, Having Faith. species simple capillary action can and a scientist inhabit the same body. An Ecologist’s Journey To account for its ascent from roots to Sandra Steingraber, who currently Motherhood, qualifies as a pilgrimage branches in the early spring, This is teaches at Cornell, can flat out write. through pregnancy, with Steingraber the same adhesive force that draws Someone, during her scientific appren- serving up an enjoyable blend of expe- a drop of water through a paper ticeship, obviously forgot to tell her rience, scientific reflection, and writing napkin. But this principle cannot about the importance of writing in the that verges on the poetic. account for the ten to twelve gallons third person and/or the passive voice. Now a book chronicling the ten of 4 percent sucrose solution that The result is a style that is a kind of months of a pregnancy and the first your average sugar maple can pull extended meditation on her experimen- year of infancy may not, admittedly, be up its trunk and pour into a bucket
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22 The Nucleus March 2002 Puzzle Column Book Review By permission from the The INDICATOR of the New York/North Jersey Sections, Continued from page 22 December 2001 Transuranium Elements by Colleen M. Parriott during the month of March. Injure any other tree and sap will merely ooze from the wound. But the com- plex hydraulics of maples somehow generates an interior force that exceeds the outside air pressure. Sap spurts from every gash and bro- ken branch.” (p. 30) “My botanical reverie soon turns obstetrical. In fact, the internal anatomy of a human placenta resembles a maple grove: the long columns of cells sent out by the embryo into the uterine lining dur- ing the first few weeks of pregnancy quickly branch and branch again until, by the third month of preg- nancy, the treetops of an entire for- est press up against the deepest layers of the womb. Meanwhile, the open taps of the uterus’s spiral arteries send jets of blood spurting between these arboreal structures.” (p. 31) Across 55. Element 99, named after 18. ___’I-hijjah As the book advances along with 1. Not germ a famous scientist (12th Muslim month) 63. Stocking problem 22. Type sizes her pregnancy, Steingraber’s attention 5. Ancient Egyptian creator deity 64. Garden tool 25. Lie moves beyond the confines of her body 65. ____ Domini 29. Baby goat to the interactions linking the mother, 9. Look for sales 13. Once ____ a time . . . 66. Melody 30. Slap the developing fetus and the environ- 14. Tree snake 68. Hindu honorific title 31. A long time ment. Along the way, she discusses the 15. Rate 69. Stand in line 32. First transuranium ele- effects of teratogens such as diethyl- 16. Nothing more 70. Paul formerly ment discovered stilbestrol (DES), mercury and lead, 17. Reversed 71. Predecessor of KGB 34. 151 to Caesar exploring and challenging some time- 19. Singing voice 72. Grafted: heraldry 35. ___ Arbor, Michigan honored ideas such as the notions of 20. Ancient Syria 73. Shade trees 36. ___ Dawn Chong threshold toxicity limits and the pla- 21. Grow incisors 74. Oxhide strap 37. Element named after the 75. Fishing pole part school It was discovered cental barrier that supposedly protects 23. Bog 24. Element named after at the unborn child from exogenous con- Down 39. Biblical judge taminants (both now known to be state it was discovered in 26. Leukotrines alias 1. It may be poison 40. Group incorrect). She provides information on 27. Department in France 2. Verdi work 42. Black or Red the various ways in which data on birth 28. Go downhill fast? 3. Upright and honest 47. Type of whale defects is (and often is not) catalogued 30. Female fowl 4. Condition resulting from 50. After taxes throughout the United States. She 33. Baking soda, informally low iron levels 52. Rodent, sometimes employs data from the Toxics Release 38. As I was going to 5. Element Important In 53. Rub out Inventory to describe the release of St. _____ nuclear weapons and 54. Large painting toxins into the environment as a result 41. Wraths nuclear energy 56. A taxing gp. 57. “It’s ___ __ never” of both natural processes and human 43. Forearm bones 6. Copier supply 44. To delete 7. Cosmetician Elizabeth 58. Metal-working tool activity, highlighting the ways in which 59. Allegro and adagio government and business have often 45. Masking or scotch 8. Port-au-Prince’s city 46. Ore diggers 9. Mineral spring 60. Stupid and trivial chosen to ignore data far decades. Her 48. Make a lap 10. 163 days for curium, 433 61. Join together discussion of lead contamination 49. Summer color years for americium 62. Hotel alternative ranges widely, covering 51. Beer container 11. Set of eight 67. Capone and Hirt continued on page 24 53. Flightless bird 12. Menial workers
The Nucleus March 2002 23 Pictures of T.W. Richards from Harvard University Archives
T.W.R. in 1888
T.W.R. in 1907
Asst. Prof. T.W.R. with his Harvard Chem 4 Class in 1892 (back row, center)
Book Review the single greatest emitters of lead graber’s narrative; while informative into the biosphere, were until rela- thought provoking and sobering, never Continued from page 23 tively recently exempt from environ- became hysterical. There are even • the known toxicity of lead com- mental regulations governing lead laughs along the way, such as when pounds, the introduction of emission, she speaks of feeling herself isolated, organolead compounds as antiknock eventually connecting again with her in transit between two worlds: additives in gasolines and their con- personal story linking lead pollution in “Being pregnant is like walking tinued use for decades in the f ace of the starting point of her and her hus- over a plank-and-cable bridge. incontrovertible evidence of lead band’s journey from a leave in her Behind me, on one bank, is the tribe toxicity, arguably because the alter- home state of Illinois (one of the major of women who are not mothers. native, ethanol, was nonpatentable, US areas of combustion-based lead They drink wine, stay up late, skip and therefore less profitable, release) to Somerville, her husband’s meals, change lovers, study San- home city, where she and her husband skrit, and write grant proposals for a • the promotion of lead-based pig- then resided. five-year study of tropical cloud ments by the paint industry, the con- In all the back and forth move- forests. In front of me, on the other sequence being that their banning in ment between the intricate process tak- bank, is the tribe of mothers. They the United States trailed that in ing place within her and the potential arrive at meetings late, leave parties Europe by decades, environmental assaults that could early, are badly in need of haircuts, • the fact that coal-based power plants, derail or terminate it, though, Stein- know way too much about the care
24 The Nucleus March 2002 T.W.R. in 1920 (age 52)
T.W.R. in Manchester, England with H.B. Dixon in 1911
Harvard Research Group of T.W.R. in 1905 Front row: (L to R): H.H. Willard, F.G. Jackson, T.W.R., Burgess, Grinnel Jones; Back row: Delbrück, Carrol-Thomas, Matthews, Coffin, Frevert, J.H. Wilson, Rowe, Mabes (the names are in indistinct handwriting! Corrections invited)
and feeding of guinea pigs, and (a process which she links to conserva- there is simply a lot to learn about the have to hang up now.” (p. 94) tion of mass as one moves up the food interlocking nature of biological and chain) concentrates toxins in mother’s The well-established correlation biochemical processes and the way in milk, making it among the most con- between brain size and gestational which they are inextricably intertwined period suggests that human pregnan- taminated of foods. with the world in which we live and cies should last about twenty-two This, in a way, brings me back to move. Finally, because the demo- months. However, the size of the where I began - to the question of why graphic shift in the profession in recent human pelvis makes this impossible, a middle-aged male chemist should be decades makes it extremely likely that the result being that the first year of enthusiastically recommending a book in the near future (if it has not already on the pregnancy of an ecologist, and life can be regarded as the last twelve happened) you, or someone in your why I think you should consider read- months of pregnancy. This provides a laboratory or department, will be expe- ing it. There are, in fact, quite a few rationale for Steingraber’s devoting the riencing these remarkable changes, or last third of her book to her first year reasons, beginning with the quality and be married to someone experiencing of motherhood, and in particular to an vitality of Sandra Steingraber’s writing extensive discussion of nursing and , which many scientists could benefit them, or working with or supervising mother’s milk. Steingraber provides a from imitating at some level. Next is someone negotiating them, the ability vivid contrast between the extensive her ability to integrate the personal and to appreciate the magnitude and the benefits provided by mother’s milk and professional perspectives in a way that majesty of what is happening could the alarming fact that biomagnification respects the integrity of both. Thirdly, prove very useful.
The Nucleus March 2002 25 BUSINESS DIRECTORY
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The Nucleus March 2002 27 Harvard, MA 01451 19 Mill Road
March 5 March 18 Prof. John A. Gerlt (Univ. of Illinois, Urbana- Prof. Bill Tolman (Univ. of Minnesota) Champaign) "Using Synthetic Chemistry to Understand "Does Sequence or Structure Determine Enzyme Copper and Iron Active Sites in Proteins" Function? Different Reactions Catalyzed by the Boston Univ., 590 Commonwealth Ave., 'Same' Active Site" Science Center Auditorium, SCI 107, 4:00 pm Tufts Univ., Pearson Chem. Building, Jennifer Stone, Stern Group (MIT) 62 Talbot Ave., Medford, Room 106, 4:30 pm Biochemistry Seminar Series March 6 "Molecular Mechanisms of T cell Triggering" MIT, Room 6-120, 4pm Prof. Richard Eisenberg (Rochester Univ.) Harvard/MIT Inorganic Chemistry Seminar @ March 19 Harvard Prof. Erick M. Carreira (ETH, Zurich) Harvard Univ., MB-23 Pfizer Lecture Hall, Novartis Lecture in Synthetic Organic Chemistry 4:15 pm MIT, Room 6-120, 4 pm March 7 March 20 Prof. Bryan Coughlin (U Mass Amherst) Prof. Dev Arya (Clemson Univ.) TBA "Neomycin-Nucleic Acid Interactions" Dartmouth College, room 101 Fairchild, Boston College, Merkert Chemistry Center, 10:30 am Room 130, 2609 Beacon St. 4:00 pm
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