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A E S S S L T A E A C R C I yyyyN S M S E E H C C T N IO A April 2003 Vol. LXXXI, No. 8 yyyyC N • AMERI
Monthly Meeting Esselen Award to Bruce D. Roth: “The Discovery and Development of Lipitor® (Atorvastatin Calcium)”
Felice Frankel’s Imagery Technology Enables New Scientific Images to Emerge
ACS Short Course LC/MS Fundmentals and Applications, May 19-20, 2003
Interstellar Chemistry From a Faraday Lecture by William Klemperer Chair-Elect: J. Fuller-Stanley men- Standing Committees: Board of tioned the locales of the upcoming Bd. Of Publications: P. Gordon monthly meetings. She is negotiating reported that a professor from Tufts is with future meeting sites to obtain interested in becoming the new web- Directors favorable prices and she is also master. The Board is waiting for a pos- Notes of Meeting of January 9, addressing means to decrease program itive arrangement. J. Neumeyer asked expenses: purchase of an LCD projec- whether we should have the website 2003 tor to save on rental cost. operated by a professional. P. Gordon NOTE: Board Meetings are held on the Treasurer: J. Piper presented the responded that he thought there is monthly meeting day at 4:30 p.m. December 2002 financial report. He plenty of capability within the Section Section members are invited to attend. stated that there may be a temporary to maintain a website. A decision is to cash shortage until allocations from the be reached shortly. Officers’ Reports: trustees and the national ACS have Editor: The February issue will be Chair: J. Neumeyer thanked the sev- been received. 20 pages. Advertising is ahead of eral members of the Board, staff for Trustees: The Section’s investments budget. their efforts. He also thanked NESACS are performing well. Membership: M. Chen stated that one past chair, M. Hoffman for his able Archivist: M. Simon asked past chairs new member is expected for the dinner leadership and presented him with the who may have bound volumes of The at this meeting. ACS Past Chairman pin. He also wel- Nucleus to donate them to the archives. Budget: J. Piper distributed the draft comed J. Fuller-Stanley as incoming There was some discussion whether 2003 budget. Initial requests exceeded Chair-Elect. J. Neumeyer outlined past issues should be digitized and expected income by $50,000. The some of the plans for the current year: stored on CDs. A. Heyn countered that budget committee reduced this to a fundraising by the Medicinal Chem- with the rapid change of technologies, $15,000 deficit. The budget will be istry Group, improving the website. He CD’s may no longer be decipherable voted at the February Board meeting. also urged committees to stay within when software and hardware changes. Nominating: M. Hoffman asked those the Section’s budget. G. Weisman responded that, as new who wish to have one of the elected In order to help reduce meeting technologies become standard, previ- positions to let their willingness to costs to the Section, dinner prices will ous formats can be converted to remain stand for election be known soon. The be raised starting with March. usable. slate will be presented at the February continued on page 6 Join Us- Waters International GPC 2003 and ISPAC-16 Symposium
June 7-12, 2003 Baltimore Marriott Waterfront Hotel Baltimore, MD
For information and registration visit: www.waters.com/GPC2003
Sponsored by Waters Corporation and the International Symposium on Polymer Analysis and Characterization (ISPAC)
2 The Nucleus April 2003 The Northeastern Section of the American Chemical Society, Inc. Contents Office: Marilou Cashman, 23 Cottage St., Natick, MA 01760. 1-800-872-2054 (Voice or FAX) or 508-653-6329. Board of Directors ______2 e-mail: [email protected] Any Section business may be conducted Notes of the meeting of January 9, 2003 via the business office above. NESACS Homepage: http://www.NESACS.org Gustavus J. Esselen______4 Frank R. Gorga, Webmaster A brief biography of this illustrious past member and Section Chair Washington, D.C. ACS Hotline: 1-800-227-5558 Officers 2003 Monthly Meeting ______5 Chair: Esselen Award to Bruce D. Roth for the synthesis and development of Lipitor® John L. Neumeyer Harvard Medical School/McLean Hospital 115 Mill St., Belmont, MA 02478 Nominations Invited – Henry A. Hill Award ______5 617-855-3388; [email protected] Chair-Elect: Book Review ______6 Jean A. Fuller-Stanley Chemistry Department, Wellesley College “Hydrogen. The Essential Element” by J.S. Rigden, reviewed by L.J. Zompa Wellesley, MA 02481-8203 781-283-3224; [email protected] Felice Frankel’s Imagery ______7 Immediate Past Chair: Morton Z, Hoffman Reprint of the Nieman Report:“Technology Enables New Scientific Images to Chemistry Department, Boston University Emerge” by our March 2003 speaker Boston, MA 02215-2507 617-353-2494; [email protected] Secretary: ACS Short Course ______9 Michael Singer LC/MS:Fundamentals and Applications; May 19-20 at Northeastern University Sigma RBI 3 Strathmore Rd. Natick, MA 01760-2447 Interstellar Chemistry ______10 508-651-8151x291 From a Faraday Lecture at the Royal Institution, London, by William Klemperer [email protected] Treasurer: James Piper Cover: Dr. Bruce D. Roth, the 2003 Gustavus J. Esselen Awardee 19 Mill Rd., Harvard, MA 01451 978-456-3155 [email protected] Deadlines: Summer Issue: June 13, 2003 Auditor: September Issue: July 19, 2003 Anthony Rosner Archivist: Myron Simon 20 Somerset Rd. Newton, MA 02465; 617-332-5273 [email protected] Trustees: Joseph A. Lima, Esther A.H. Hopkins, Michael E. Strem, Councilors: Alternate Councilors: Term Ends 12/31/2003 Term Ends 12 /31/2003 The Nucleus is distributed to the members of the Northeastern Section of the American Chemical Catherine E. Costello Wallace Gleekman Society, to the secretaries of the Local Sections, and to editors of all local A.C.S. Section publications. William Klemperer Arno H.A. Heyn Forms close for advertising on the 1st of the month of the preceding issue. Text must be received by the Dorothy J. Phillips Howard R. Mayne editor six weeks before the date of issue. Barbara Wood Alfred Viola Editor: Arno Heyn, 21 Alexander Rd., Newton, MA 02461, Term Ends 12/31/2004 Term Ends 12/31/2004 Tel: 617-969-5712, FAX: 617-527-2032; e-mail: [email protected] Thomas R. Gilbert Timothy B. Frigo Patricia H. Hamm Donald O. Rickter Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273 Michael J. Hearn Lawrence T. Scott Mukund S. Chorghade, 14 Carlson Circle, Natick, MA 01760: Arlene W. Light Derk A. Wierda [email protected] Term Ends 12/31/2005 Term Ends 12/31/2005 Board of Publications: Marietta H. Schwartz (Chair), Patrick M. Gordon, vacant, E. Joseph Billo (Con- Mary T. Burgess Michaeline F. Chen sultant) Morton Z. Hoffman Patrick M. Gordon Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622 Doris I. Lewis Truman S. Light Amy E. Tapper Michael Singer Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050, Tel: 781-837-0424; FAX: 781-837-8792 All Chairs of standing Contributing Editors: Patricia Hamm, Features; Edward Atkinson, History of Chemistry; Dennis Committees, the editor Sardella, Book Reviews; Marietta H. Schwartz, Software Reviews. of THE NUCLEUS, and Calendar Coordinator: Donald O. Rickter, e-mail: [email protected] the Trustees of Section Proofreaders: E. Joseph Billo, Mukund S. Chorghade, Donald O. Rickter, M.S. Simon Funds are members of the Webpage: Webmaster: Samuel P. Kounaves, [email protected] Board of Directors. Any Asst. Webmasters: Terry Brush, [email protected] Councilor of the American Chemical Society Kurt Heinselman, [email protected] residing within the section area is an ex officio member of the Board of Directors. Copyright 2003, Northeastern Section of the American Chemical Society, Inc. The Nucleus April 2003 3 Gustavus Biography Corporate Patrons Astra Zeneca Pharmaceuticals John Dr. Roth was born in Philadelphia, PA Novartis Pharmaceutical Corp. He received a bachelors degree in Strem Chemicals, Inc. Chemistry from St. Joseph’s College in Esselen, Philadelphia, PA. During his under- Corporate Sponsors graduate career, he performed research Aerodyne Research, Inc. 1888-1952 under the direction of Dr. George L. Cambridge Isotope Laboratories Nelson. He then moved to Iowa State Consulting Resources Corp. An extensive biography was published University where he received a Ph.D. Houghton Chemical Corp. in the April 2000 issue of The in synthetic organic chemistry in 1984 New England Biolabs, Inc. NUCLEUS. under the direction of Dr. George A. Organix, Inc. Kraus, working on the total synthesis Gustavus John Esselen was one of the Polymedica Corp. of antifungal antibiotics, including the Sigma-RBI movers and shakers in the Northeast- total synthesis of the antifungal, antibi- ern Section, serving on numerous com- otic (±)-Kalafungin. Dr. Roth had mittees, Chairman twice (1922, 1923) postdoctoral training under the direc- and also a Director of the national tion of Dr. Andrew S. Kende at the ACS. He chaired the national meetings University of Rochester in Rochester, Red Sox of the ACS held in Boston in 1928 and N.Y. (1981 – 1982) during which he 1939. He was employed by General completed the total synthesis of the Tickets Electric Co. in Lynn, then Arthur D. insect antifeedant (±)-Ajugarin IV and Little, Inc. of Cambridge. In 1921 he the anticancer agent (±)-Quadrone. April 17, 2003 at 6:05 pm founded Gustavus J. Esselen, Inc., In 1982 Dr. Roth joined the Ather- Red Sox vs. Tampa Bay Devil which later became the Research Divi- osclerosis Chemistry Section of the Rays sion of the United States Testing Co., Chemistry Department of the Parke- Inc. and addressed problems submitted Davis Research Division, Warner- May 15, 2003 at 7:05 pm by commercial clients, especially in Lambert Company. As part of a Red Sox vs. Texas Rangers polymer chemistry and technology. He project aimed at discovering and was greatly interested in furthering the developing potent and specific Right field box seats (normally @$37) profession of chemistry, and it is in this inhibitors of the enzyme HMG-CoA available for $27. Call Marilou Cash- spirit that the funds donated by the reductase, the rate-limiting enzyme in man at 800-872-2054, then send a Esselen family to the Northeastern endogeneous cholesterol biosynthesis, check to her: Section were used for establishing the Dr. Roth synthesized the racemic ver- 23 Cottage St., Natick, MA 01760. award named in his honor, “…to rec- sion of atorvastatin (PD 123832) in For information, call: ognize and reward a chemist whose July of 1985. In subsequent develop- Wally Gleekman at 617-527-1192 scientific and technical work has con- ment, PD 123832 was separated into tributed to the public well-being and its two component enantiomers and a has thereby communicated positive chiral synthesis developed to prepare values of the chemical profession.” the active (+)-stereoisomer, which was for all of the decision-making with At this year’s 16th anniversary of then developed as atorvastatin and is regard to the preclinical development the award, the recipient Dr. Ronald now marketed in the United States of Lipitor®. Breslow amply fulfils these criteria. under the name Lipitor®. Dr. Roth Dr. Roth is the inventor or co- A full discussion of the criteria for the received the 1997 Warner-Lambert inventor of 42 issued U.S. patents and award were published in The Chairman’s Distinguished Scientific the author or co-author of 48 manu- NUCLEUS, Vol. 75(8), April 1997, Achievement Award for the discovery scripts, 35 published abstracts and 8 p.10. and development of Lipitor®. He also book chapters and review articles. He received the 1999 “Inventor of the is also an adjunct associate professor in Year Award” from the New York Intel- the Department of Medicinal Chem- lectual Property Law Association, Inc. istry in the School of Pharmacy of the In addition to being the inventor of University of Michigan. He is married Lipitor®, Dr. Roth led the chemistry with 4 children. His current position is team involved in the project, and was Vice President of Chemistry at the the co-chair of the Atherosclerosis Dis- Pfizer Global Research and Develop- covery Team which was responsible ment, Ann Arbor Laboratories.
4 The Nucleus April 2003 Nomination Monthly Meeting Henry A. Hill Award for The 842nd Meeting of the Northeastern Section of the Outstanding Service to the American Chemical Society Northeastern Section Esselen Award Meeting Nominations for the Henry A. Hill Award for Outstanding Service to the Thursday, April 10, 2003 Northeastern Section are invited. Harvard University, Cambridge, MA Nominations should be sent by Harvard Faculty Club, 20 Quincy St. August 1, 2003 to the Administrative Secretary, NESACS, Marilou Cash- 5:30 pm Social Hour man, 23 Cottage St., Natick, MA 6:30 pm Dinner 01760. A resume of professional activ- ities and description of the nominee’s 8:15 pm Award Meeting, Mallinckrodt Building, 12 Oxford St. service to the Northeastern Section Pfizer Lecture Hall (MB23), ground floor. should be included. The Award is to be Dr. John Neumeyer, NESACS Chair, presiding presented at the October meeting of The Esselen Award—Dr. Arno Heyn, Chair, Esselen Award Committee the Section. Michael J. Dube, Chair, Awards Introduction of the Award Recipient—Dr. James A. Bristol, Pfizer, Inc. Committee Presentation of the Award—Gustavus J, Esselen III The Discovery and Development of LIPITOR® (Atorvastatin Cal- cium)—Dr. Bruce D. Roth, Vice-President, Chemistry, Pfizer cally pure atorvastatin calcium were Global Research Development, Ann Arbor Laboratories accomplished through a close collabo- Dinner reservations should be made no later than noon, April 3. Please call or ration between discovery and develop- fax Marilou Cashman at (800) 872-2054 or e-mail at [email protected]. ment chemists. It was only with the Reservations not cancelled at least 24 hours in advance must be paid. Mem- development of a enantioselective syn- bers, $30.00; Non-members, $35.00; Retirees, $20.00; Students, $ 10.00. thesis with the potential for producing THE PUBLIC IS INVITED. bulk drug of sufficient purity and scale Anyone who needs special services or transportation, please call Marilou to support clinical trials that the deci- Cashman a few days in advance so that suitable arrangements can be made. sion was made to advance atorvastatin Free Parking in the Broadway Street Garage (3rd level or higher), enter from calcium into clinical trials. With the Cambridge St. via Felton St. initiation of clinical trials, it was found that atorvastatin calcium was more Next Meeting: May 8, 2003, Education Night, Boston University School of potent and efficacious than any of the Management Building, 595 Commonwealth Ave., Executive Dining Room, 4th available statins, producing a reduc- Floor. Social Hour and dinner 5:30 pm, evening meeting 7:45 pm. Dr. Guy A. tions in LDL-cholesterol ranging from Crosby, consultant, writer and lecturer on food and nutrition chemistry speaks 35% at the low dose to greater than on “Recent Developments in the Chemistry of Nutrition and Their Impact on 60% at the high dose of 80mg, a reduc- Human Health.” tion not attainable by any cholesterol lowering agent available at that time. mer. This inhibitor was designed This remarkable ability to lower LDL- Abstract based on molecular modeling compar- cholesterol has resulted in atorvastatin isons of the fungal metabolites and becoming the largest selling drug in The Discovery and other synthetically derived inhibitors. the history of the pharmaceutical Development of LIPITOR‚ In addition to development of the industry. (Atorvastatin Calcium) structure-activity relationships that led to atorvastatin calcium, another critical The NESACS website aspect of the development of this area Atorvastatin Calcium, currently mar- was the parallel improvement in the keted in the United States as LIPITOR‚ chemistry required to prepare com- WWW.NESACS.org was the first totally synthetic inhibitor pounds of the increased synthetic com- of HMG-CoA reductase, the rate-limit- plexity needed to potently inhibit this ing enzyme in cholesterol biosynthesis, enzyme. Ultimately, the development Have you looked at it? to be marketed as a single stereoiso- of several syntheses of enantiomeri-
The Nucleus April 2003 5 Board meeting. This year’s awardee is Board of Directors a chemist from industry and he will Book Review Continued from page 2 receive the award at the April 10 monthly meeting at Harvard. Hydrogen. The Essential meeting. Element Chemistry Education: R. Tanner Other Committees: stated that Norris/Richards Scholar Continuing Education: A. Viola by John S. Rigden applications, are available and will stated that efforts are under way to (Harvard University Press, 2002) soon be on the website. have one of the ACS Short Courses 280 pp, ISBN 0674007387, $28.00 Professional Relations: offered in the spring. Speakers’ Bureau: S. Buta thanked Reviewed by Leverett J. Zompa T. and A. Light reported on their Department of Chemistry attendance at an ACS mentoring work- Board members for their feedback. She is working on compiling a list for University of Massachusetts shop. The aims of the program are to Boston, MA 02125-3393 attract and retain younger members, announcing available speakers and especially women and minority mem- topics. bers, and to encourage participation by Younger Chemists: A. Tapper This book provides a view of the these groups in local section activities. announced that the February meeting development of modern physics based They mentioned that the NESACS will be co-sponsored with the YCC upon fundamental research on hydro- Board has a 41% female representa- and NOBChE. gen by experimental and theoretical th tion. Four of the females and one of The 5 annual Northeast Chem- physicists. John Rigden presents this the males are minority members. In the istry Research Conference is looking seminal research of twentieth century entire Section of 6052 members (as of for a locale physics in a clear and concise manner. December 31, 2000), 23.4% are Medicinal Chemistry: P. Gordon At the same time, he weaves in the female, 15.9% are minorities. stated that contact has been made with enticing historical events that began They suggested that efforts should the Swiss Consulate to inquire whether with early quantum theory and be made to recruit more high school it might co-sponsor a program to pro- advanced to recent validations of quan- teachers as Section Affiliates, and mote international science cooperation. tum electrodynamics, weighing the- materials to aid their teaching should New Business: J. Piper moved for the ory against extremely precise be made available by the national Budget Committee that Local Section measurements of hydrogen atomic ACS. Also, more student affiliate pro- Dues be set at 13% of national dues, spectral parameters. The centrality of grams should be established. i.e. $15 beginning with 2004. This hydrogen to the studies of Balmer, Means should be sought to attract motion is to be voted at the February Bohr, and Sommerfeld is carried more non-member chemists as ACS Board meeting. through to the modern day research on members, especially in industry. Cur- From the minutes of M. Singer Bose-Einstein condensates by Nobel rent programs for welcoming new Sec- Prize winners Cornell, Wieman, and tion members should be continued. All Ketterle. members should encourage non-mem- The early chapters of the book ber chemists of their acquaintance to will be quite familiar to chemists, as become members. the struggles are described of early Esselen Award: A. Heyn stated that twentieth century physicists attempting the 2003 awardee has been selected to understand the nature of the hydro- and will be announced at the February gen atom. The atomic structure of hydrogen provided by Niels Bohr and his idea of the quantized atom was grudgingly accepted by some because it could explain the data from the bright line spectrum of hydrogen. Some of the frustration felt by many physicists of the time is so aptly expressed by the quotation of Otto Stern (p. 39) who threatened to leave physics if “that crazy model of Bohr” turned out to be correct. Also described are the changes made to the Bohr model as more precise spectral data were obtained. This is exempli- Continued on page 18
6 The Nucleus April 2003 Felice Frankel’s Imagery Reprinted by permission from Nieman Reports, Fall 2002, 29-31. Technology Enables New Scientific Images to Emerge By Felice Frankel “This new process in science commu- nication will produce a different kind of journalistic thinking….“
A few months ago, a particularly Fig. 1 A microscopic image of a detail of a microrotor. The large blade measures breathtaking astronomical image about fifty microns cross. Research: A. Epstein, MIT. Photos by Felice Frankel appeared on the front pages of newspa- pers around the globe. These stun- ningly colored shapes captivated those who saw them. The picture, captured by the Hubble Space Telescope, was of the Cone Nebula, but the colors in the image were not actually seen by astronomers. They were, in fact, a construction from three separate sets of digital readings taken in blue, near- infrared, and hydrogen-alpha filters. Interestingly, that Cone Nebula image is fundamentally the same as the one of nanowires that I made with a scanning electron microscope. [See Fig. 2] Both of these pictures are visual displays of numbers; they are represen- tations of data. My nanowire image is a manifestation of the data made with image-processing algorithms that enable us to see structure. After col- lecting that data, I digitally colored Fig. 2 Nonowires, measuring 2-5 nanometers, span across electrodes. Image taken with a the image [not seen here]. By doing scanning electron microscope. Research C. Lieber, Harvard this, I was essentially changing the data, just as the astronomers did when niques, we are now able to “see” be- mity of this diminutive flash of time they balanced the values of their three yond what our unaided eyes allow. and begin to “see” molecules in motion data sets to create a readable image. Like Hubble, although on a completely and study how they operate. But in this case, the color choices I different scale, an atomic force micro- That such images can be “con- made had nothing to do with the mate- scope or a scanning electron micro- structed” does not diminish their value rial. Mine were purely aesthetic deci- scope can capture images and analyze in increasing our appreciation for and sions that provided representations to structures never before seen. Now they understanding of the scientific ad- help create a more engaging image can be measured in nanometers, 10-9 or vances they reveal. Scientific pictures than the original. a billionth of a meter. And with other previously made on film, for example, As scientific research becomes new instruments we are able to detect are just as much of a construction and more visual with the advancement of the femtosecond, 10-15 of second, a representation of reality, only made sophisticated image-capture tech- allowing us to comprehend the enor- Continued on page 8
The Nucleus April 2003 7 Felice Frankel Continued from page 7
with silver instead of pixels. The adjusted colors of the Cone Nebula are not simply imagined, rather they were created through the human interpreta- tion of technological data. Gaining this kind of extraordinary view offers us a remarkable window, but opening it requires adherence to the scientific integrity of this process. Certainly the misuse of this technology is possible, Fig. 4 A colony of yeast in a floral arrange- but so it was with film. It is just easier ment in a Petri dish. Research: T. Reynolds. to manipulate images in digital form. G. Fink, MIT’s Whithead Institute. Journalists should simply be more aware of this as images of all kinds Photos by Felice Frankel come into wider use. Even as these previously un- Fig. 3 Square drops of colored water in a fathomable concepts are clarified grid pattern. The surface on which each four through advancements in imaging and mm drop was placed is chemically patterned Fig. 5 A thin layer of gold buckling in pat- technology, we are still in desperate so that drops form squares. Research: G.M. terns on the surface of plastic. Photo taken need of new vocabularies to better Whitesides, Harvard University. under a microscope. Research: N. Bowden, communicate these ideas among our- G.M. Whitesides, Harvard University selves as scientists, and to the public. And in the years ahead, pictures will assume an increasingly prominent role in communicating scientific informa- tion. When published along with the drawings and illustrations currently made by graphic artists, images will become powerful tools in making diffi- cult concepts accessible and inspiring to the non-scientist. These technological tools will result in the emergence of an entirely new community of image-thinking writers and editors, illustrators, infor- mation architects, photographers and scientists, along with a fresh approach to science journalism. The creative process of telling scientific stories will become a collaboration among writers, editors and picture makers. Together they will develop a new and rigorous visual vocabulary of science as a com- pliment to the written word. This new process in science com- munication will produce a different kind of journalistic thinking by con- tributing richer and more informative visual tools not only to the public, but also to the research community as a whole. And with this new thinking will emerge a well deserved, if belated, respect for the power of the image.
8 The Nucleus April 2003 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 ACS Meetings. LC/MS: Fundamentals and Applications In this course you will receive an overview of applications for the environmental, biotechnology, pharmaceutical, and chemical industries, and for areas of forensics and toxicology. This Short Course is designed as a practical overview of LC/MS for researchers, practitioners, technicians and others who are currently using LC, LC/MS, or plan to do so in the future, and those dealing with data produced by LC/MS. Practition- ers just embarking on the technique will gain insight to select the appropriate instrument for different applications, and those currently using LC/MS and its data will develop an appreciation for, and an understanding of, the complexities of the data generated. Participants should bring a basic calculator to the course. DATES and TIME: Thursday, May 19, 2003; 8:00 a.m. – 5:00 p.m. and Friday, May 20, 2003; 8:30 a.m. – 5:00 p.m. PLACE: Egan Center, Room 340, Northeastern University, 360 Huntington Ave., Boston, MA PROGRAM AGENDA: • Solvent delivery systems, columns, interfaces, ioniza- • What changes may have to be made when porting LC tion methods, and mass analyzers; methods; data evalu- method to an LC/MS method ation • Types of mass analyzers, and which is most suitable for • What types of instruments are available for various a given analysis by LC/MS types of analyses • Steps in the interpretation of collisionally activated dis- • What are the latest developments in instrumentation sociation (CAD) data • How to get structural information from LC/MS • How ions are formed in an LC/MS analysis • How to deal with multiple-charge ions • Approaches to problem solving with LC/MS INSTRUCTORS: O. David Sparkman, Adjunct Professor of Chemistry at the University of the Pacific, Stockton, Cal., a consultant to the NIST Mass Spectrometry Data Center, teaches courses in mass spectrometry and analytical chemistry and man- ages 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 co-developer of the Mass Spectral Interpretation Quick Reference Guide. Frederick E. Klink, currently a consultant in LC, LC/MS, and other scientific instrumentation, has worked with a vari- ety of industrial clients. He has over 16 years of experience in a variety of technical and managerial positions in the analytical instrument industry. Starting as a life sciences applications chemist in HPLC, he has worked in product development, and product and marketing management for a major HPLC manufacturer. These are two of the most highly rated instructors in the ACS continuing education program. PRE-REGISTRATION REQUIRED – Registration Fees: ACS Members if received before May 2………… $500.00; after May 2 ……$575.00 Non-ACS Members if received before May 2….…$600.00; after May 2 ……$675.00 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: Organic Chemistry of Drug Design and Drug Action, Nov. 20-21, 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 April 2003 9 1 While optical astronomical observa- Interstellar Chemistry tions more than fifty years ago revealed the existence of molecules in By William Klemperer, the low density matter that exists Department of Chemistry and Chemical Biology, Harvard University2 between the stars, the subject has changed radically through radio astron- omyiv. Our knowledge of the universe is distributed in the universe, the distribu- Radioastronomical observation of steadily expanding. In large measure tion of matter is highly non-uniform. the galaxy has revealed a broad distri- this has been a result of radioastronom- Matter is found virtually entirely -7 bution of molecular species within the ical observations. Among the most within galaxies. Galaxies occupy 10 cool, low density regions between of the volume of the universe but con- important is that the majority of the stars. The density of matter that exists tain most of the known matter. The ori- radiation of the universe is almost uni- between stars, the interstellar medium, gin of this separation of radiation and form and follows the spectral distribu- is quite heterogeneous. The average tion of a thermal source at a matter is a topic of much current study interstellar density of 10-24 g cm-3 cor- temperature of 2.725 Ki as is the question of galaxy formation. . This cosmic responds to one hydrogen atom per background radiation is the remnant of While clearly fundamental to the ques- -3 cm . Molecules are observed in inter- tion of the chemistry that occurs, it is the initial event, the big bang. While stellar clouds, regions of higher than not our intent to discuss these most this radiation is essentially uniformly average density. Table I lists the mole- interesting questions.ii This sharp cules that have been observedv. The list 1 For an article which focuses on another aggregation of matter means that the is dominated by polar molecular forms aspect of interstellar chemistry, i.e. reac- chemistry we discuss is occurring in which exhibit very sharp spectral emis- tions on condensed phases, see Rebecca L. galaxies. It is sensible to discuss, there- sion frequencies through changes in Rawls (C&EN staff). Chem Eng. News, fore, the molecular abundances and the their rotational motions. There has 2002, 80(20), 31-37. iii chemistry occurring in the galaxy been a significant change in our 2 since observations are much easier in This Faraday Lecture which was pub- knowledge as a result of recent lished in Proceedings, The Royal Institu- view of the decrease of radiation inten- infrared spectroscopy as seen in Table tion, London, 1997, 209-244 is reprinted by sity as the inverse square of the dis- I. Our direct knowledge of abundances courtesy of the Royal Institution of Great tance. Thus most of the observations of the molecular components is still Britain. Emended and revised by Dr. Klem- we discuss here are of the galaxy. perer. somewhat limited. To gain a deeper insight into the likely molecular com- position of the interstellar medium models of chemical synthesis appropri- ate for the cold, low density conditions are extremely useful. Of primary importance is the composition of the cosmos. Table II is an abridged listing in which many minor elements are not included. It is clear from this table that there is a considerable difference between cosmic and terrestrial compo- sition. The hydrogen and helium com- prise 99% of the matter. Their chemistry will dominate the observed molecular abundances. There is a considerable variation in the total density in interstellar clouds as well as their optical opacity. In diffuse or translucent clouds the density is of the order of 102 – 103 mol- ecules per cubic centimeter with a kinetic temperature 50-100 K. In dense cold molecular clouds which are essen- tially opaque to the galactic radiation field, densities are between 104 – 106 cm-3, a factor of 1013 lower than continued on page 11
10 The Nucleus April 2003 Interstellar Chemistry 20K the equilibrium abundance ratio , [HNC] Central Mass. Continued from page 10 [HCN] atmospheric. Under these conditions predicted is 10-250. Further evidence collisions of a molecule with back- against using an equilibrium model for Section News ground gas are so infrequent , less than the prediction of the chemistry and -3 -1 Craig C. Mello, UMass Medical Cen- 10 sec , that virtually any species molecular abundances is found by con- ter, is to share the NAS Award in Mol- will be cooled by radiative emission if sideration of the reaction ecular Biology with Andrew Z. Fire of CO + 3H = CH + H O. it is prepared in a high energy 2 4 2 the Carnegie Institution of Washington metastable state. Thus a favorite At 20K the equilibrium constant, “for inventing methods to inactivate process of terrestrial photochemistry is [CH4][H2O] genes by RNA interference and help- preparation of long lived high energy K= 3 [CO][H2] ing to elucidate their underlying mech- triplet spin states of molecules with anism and biological function typical emission lifetimes of 0.1 sec. is readily calculated from stan- They will suffer many collisions in this Continued on page 12 time and are an extremely effective Table 1 Observed Interstellar and Circumstellar Moleculesa agent for energy storage allowing the (Number of Atoms) occurrence of reactions which nor- mally under thermal conditions have insufficient energy for reaction. In interstellar chemistry optically pre- pared electronically excited metastable species are unlikely to play a signifi- cant chemical role. We may note that vibrationally excited molecular hydro- gen has a lifetime of 105 sec. Thus it is a significant metastable species, which merits further discussion. The chem- istry of diffuse interstellar clouds is extremely interesting and presently somewhat unsettled. Since relatively few identified molecular species have been observed in these regions, we examine the general molecular clouds of considerably higher density. These clouds are effectively opaque to starlight and have temperatures near 10-20 K. In these interstellar regions the vast preponderance of molecules, especially polyatomic molecules, have been observed. In developing a scheme for the formation of the species listed in Table I, the standard method would be to first simply follow equilibrium arguments. The observed species of Table I shows clearly that equilibrium thermody- namic constraints are inappropriate, since in some instances high energy isomeric forms of species are quite abundant. Note that both HCN and its high energy isomer HNC are observed. The observed relative abundance [HNC] [HCN] a The species listed observed by rotational spectrum unless otherwise noted, c and l indicate cyclic and linear structure is near unity in cool molecular clouds. v Observed only by vibration rotation spectrum Using the canonical temperature of e Observed by electronic spectrum
The Nucleus April 2003 11 Interstellar Chemistry dard enthalpies to be 10490 molecules- 2cm6. For [H ] = 105 cm-3, a value typ- 2 Continued from page 11 ical of the molecular clouds the predicted ratio of CO/CH is 10-500 Table II Comparison of Cosmic Composition and Earth’s Crusta 4 such that given the volume of the observable universe is 1084 cm3 , there would be less than one molecule of CO present. This rules out arguments of chemical equilibrium for the useful prediction of the observed molecular abundances. CO is found to be the second most abundant interstellar molecule. It is used to map the molecular universe. Figure 1 shows a radio spectrum of CO. This was obtained by Pat Thad- deus upon my request. Note the high signal to noise level. It was obtained using a 4 foot diameter (1.3m) tele- scope on the roof of the Harvard Observatory in Cambridge, Massachu- setts. The integration time is 10 sec- onds. Carbon monoxide is a most important molecule. The lowest energy transition of the carbon monoxide mol- ecule occurs at 115,270 MHz, which has an equivalent temperature of 5.2K . The dipole moment of CO =0.1 D , a P.A. Cox The Elements Oxford 1997 ensuring a long radiative lifetime for the J=1 excited rotational level, quite cool regions at relatively low density emit this radiation. Furthermore, CO , with a dissociation energy greater than 11 electron volts, is perhaps the most strongly bonded molecule. Since all radiation with energy greater than the ionization potential of hydrogen , 13.6 ev. is essentially absent as a conse- quence of the vast amount of hydro- gen, CO is extremely stable. Virtually the entire molecular universe is mapped by the radio emission of CO. This is important in regions where matter, especially hydrogen, is molec- ular. Atomic hydrogen is readily detected by it characteristic magnetic hyperfine transition , the reorientation of its electron spin from parallel rela- tive to its nuclear spin to an anti paral- lel arrangement3. Mapping of the atomic hydrogen throughout the uni- continued on page 13
3 The atomic hydrogen transition was first observed astronomically by Professor Ed Purcell, who also invented (or discovered) nuclear magnetic resonance
12 The Nucleus April 2003 Radio frequency spectrum near 115. 270 Ghz of carbon monoxide in Orion a. The integra- tion time is 10 sec. The small displacement from the laboratory rest frequency is given as a velocity. The quality factor of the line, the frequency divided by the half width is seen to be near 106 which is representative of radioastronomical observations.
verse is accomplished by mean of this of major species on grain surfaces, ber density of the species B. The reac- unique transition at 1450MHz. Molec- with the strong exception of molecular tion rate constant k is expected to have ular hydrogen, with its electron spins hydrogen, which as a consequence of the Arrhenius form paired in an anti parallel arrangement its mobility and low surface binding ∆E by chemical bonding, is essentially energy, is quite unique. k = Aexp (-RT ) ∆ optically inactive under most interstel- The major species H2 and He play E is the activation energy for the lar conditionsvi. Its abundance is a major role in the chemical scheme reaction, R the gas constant T the tem- inferred from the CO abundance by we suggest. A kinetic scheme is needed perature. A is a constant. ≈ assuming the H2 since an equilibrium approach has For T 20K , any appreciable value CO been ruled out by the observed species. for ∆E (D1kcal/mole) will cause the ratio is either constant or known, ≈104. This scheme must be compatible with rate constant k to become vanishingly The mapping of CO is effectively the a very low temperature as well as a slow. Thus the usual reactions which mapping of molecular matter. very long time between collisions; the can occur with finite velocity at room The carbon monoxide/methane reaction scheme can only invoke two temperature, 300K, may be quenched system is indicative of what body collisions. Since the density in a under the conditions that concern us chemistries are required. The prepon- large interstellar cloud has a limit of here. derance of H would suggest, were about 106 molecules cm-3, three body The class of reactions known to 2 equilibrium thermochemistry applica- encounters, so important at atmos- occur with almost temperature inde- ble, that all carbon species be satu- pheric pressure , 1019 molecules cm-3, pendence are exothermic ion - mole- rated. Quite specific forms of relatively cannot occur in interstellar clouds. We cule reactions. These reactions in many large polyatomic species are observed, may parenthetically note that for instances are well studied. The colli- as shown in Table 1. In particular the regions surrounding stars which are sion frequency of an ion with a neutral larger organic species are very unsatu- losing mass the density and tempera- molecule occurs at the Langevin rate, rated rather than saturated as might be ture can be much higher. The chem- α istry of these stellar outflows will also k= 2e expected from the fact that hydrogen is µ by far the most abundant interstellar be different than that which obtains in molecular species. the large molecular clouds. Here e is the fundamental charge, the The chemistry of the interstellar The gas phase reactions that can polarizability of the neutral molecule, medium furthermore illustrates that occur are those that and µ the (reduced) mass. In general complex synthesis occurs under totally 1. Only involve binary collisions α vii abiotic conditions . This chemistry is 2. Only use species in their ground µ quite specific and the molecular abun- state dances are far from the obvious equi- is almost constant and k ≈ 2x10-9 sec-1 librium composition that would be 3. Have no activation energy. cm3. For many exothermic ion mole- expected were a universal catalyst The rate of the generic chemical reac- cule reactions the observed rate of present. The universal catalyst has fre- tion B + C = D +E is given as reaction is equal to the above collision d[D] viii quently been invoked in the past. There = k [B][C] frequency . For many of processes is little reason, except in hot relatively dt discussed presently the neutral mole- where [B] is the concentration or num- dense regions, to invoke the synthesis Continued on page 14
The Nucleus April 2003 13 essentially uniformly ionizing the vol- and occurs at the Langevin rate, Interstellar Chemistry -9 ume of the cloud. The degree of ion- namely with rate constant k= 2x10 . Continued from page 13 ization is of course exceedingly small, Since the density of a dense molecular cule is non-polar. For highly polar since the high energy cosmic ray flux cloud is near 105 molecules cm-3 the conversion of H + to H + occurs in molecules at very low temperatures the is low. Since the picture of cosmic rays 2 3 collision frequency can considerably is that they are uniform throughout the 5x103 sec, i.e. between one and two exceed the above Langevin rateix. galaxy measurements of high energy hours. Although viewed as a terrestrial The dense molecular clouds which flux in the solar neighborhood is process this appears quite slow, from are where the majority of interstellar assumed appropriate for the determina- an astronomical view it is essentially molecules are observed are massive tion of ionization in the dense cloudsxii. instantaneous. The reaction objects, as large as 106 times the mass H and He constitute 99 % of the H + H + = H + + H 2 2 2 3 + of the sun. The large amount of matter interstellar gas, requiring their ioniza- is highly exoergic. The structure of H3 makes these region opaque to starlight. tion and secondary reactions be first is an equilateral triangle. As such it These regions may be observed from examined. The primary processes are does not possess a dipole moment and + -17 -1 the countryside, where city light is H2 + crp = H2 + e + crp =10 sec does not have a radio frequency spec- absent from the sky, as the dark lanes molecules cm-3 trum. Oka first observed its vibrational in the Milky Wayx. Since the Milky He + crp = He+ + e + crp =10-17 sec-1 spectrum in the laboratoryxiii It is been Way is the plane of the galaxy it is reg- molecules cm-3 well studied in the laboratory and is ularly dense with stars. Thus the lack Here crp is a cosmic ray particle and prominent in the atmosphere of of stellar visibility is caused by the is the rate constant for this ionization Jupiterxiv. Recently it has been observed large regions of obscuring matter. This process. These are the dominant pri- in a number of interstellar regionsxv mary ionization processes. The disso- The reaction H + H + = H + + H shows lack of optical radiation means that a 2 2 3 ciative ionization of molecular that molecular hydrogen, H , has a different energy source must be sought 2 to drive the non-equilibrium kinetics. hydrogen greater proton affinity than does + The galaxy is bathed in cosmic H2 + crp = H + H + e + crp atomic hydrogen. That a substance has rays. These are high energy ions with occurs about five percent of the time. an affinity for H+ is a statement that the an elemental distribution following the The dominant secondary reaction of substance is a base, in the chemical xi + cosmic abundance of the elements . At H2 is with H2, namely sense. We have just noted that H2 is a H + H + =H+ + H stronger base than H. There are, how- energies of 100 Mev cosmic rays will 2 2 3 pass through a dense molecular cloud This reaction is extremely well studied ever, many substances that are stronger bases than H2. In fact any chemist will regard H2 as a very weak base. As a consequence many species will react + with H3 abstracting the proton. CO is the second most abundant molecule. The species HCO+ is extremely stable. The reaction H + + CO = HCO+ + H 3 is highly exothermic and occurs at the Langevin rate. This reaction essentially + + + converts H3 to HCO . HCO was discovered by Buhl and Snyderxvi in 1970. It is the most abundant ion in dense interstellar clouds. It is observed
in several very distant galaxiesxvii. As the most abundant ion it provides the most convenient measure of the ioniza- tion or ion production by cosmic rays. Transformation of ions such as H + + CO = HCO+ + H 3 does not change the number of ions. The destruction of ions is entirely by reaction with electrons, since negative ions are difficult to form. Thus for example: HCO+ + e = CO + H Continued on page 15
14 The Nucleus April 2003 Interstellar Chemistry hydrogen. The ionization of He by a heavy atom number. In forming larger high energy particle is substantially molecules from smaller several steps Continued from page 14 identical to that of hydrogen. It is the generally occur. This reaction is extremely rapid, with secondary processes that are so differ- CH , methane, has tetrahedral -7 4 rate constant kr≈ 3x10 since the long ent. The reaction symmetry and is non-polar. As such it He+ + H =H+ + He cannot be seen directly in dense inter- range interaction is Coulombic. 2 2 Under the simplifying assumption that =H+ + H + He stellar clouds by emission of radio fre- [ HCO+] = c[I+] = c[e] 1/2 < c ≤ 1 = He H+ + H quency radiation. It has been [I+]= the sum of positive ions is highly exothermic for each branch. frequently observed in the circumstel- d[I+] + It has been found by repeated labora- lar material of cool stars by its charac- = [H ] - k [I ][e] dt 2 r tory studies that the rate of this reac- teristic infrared absorption and is tion is at least 106 slower than the observed in the interstellar molecular + + 2 d[I ] [HCO ] Langevin rate. Thus our previous gen- clouds. It, as well as CH , are formed = [H ] - kr 2 3 DT 2 C eral statement that exothermic ion mol- by a series of hydrogenation steps after Since the abundance of ions is both ecule reactions proceed at the collision the initial reactions + + small and relatively time independent rate is not correct in this instance. The C + H2 =CH2 + h (slow radia- the standard steady state assumption of reason for this is due to the truly elec- tive association) tron structure nature of chemical reac- C + H +=CH+ + H chemical kinetics is likely to be appli- 3 2 xix + + cable tions . CH + H2 =CH2 + H + + + + d[I ] Since He does not react with the CH2 + H2 =CH3 + H =0 most abundant molecule, H , it then CH + + H =CH+ + h (slow radia- DT 2 3 2 5 reacts with the next most abundant tive association) + γ[H2] molecule CO. The reaction CH ++ e = CH + H, CH + H [ HCO ] = c + + 5 4 3 2 He + CO = C + O + He The reaction sequence using CH to kr 4 is well studied and proceeds at the produce larger hydrocarbons is 5 -3 + + for [H ] = 10 cm Langevin rate. This is important since CH4 + C =C2H2 + H2 +2 ≈ ≈ -3 -3 + + [ HCO ] [e] 2x10 cm it is C that is responsible for the vast =C2H3 + H + This estimate shows that the degree of array of organic molecules which dom- C2H2 + e = C2H + H + ionization in the molecular clouds is inate the list shown in Table I. Some C2H3 + e = C2H + H2 really quite low, details of this chemistry will follow. =C2H2 + H The importance of the two reac- The species C H is observed by radio [e] 2 = 2x10-8 tions where He+ + H = products astronomy and is widely distributed in [H ] 2 2 does not occur and interstellar molecular clouds as noted He++ CO = C++ O + He in Table I. C H , acetylene, is non We may further note that our previous 2 2 assumption that the essential primor- is rapid, is that the ionization of He is polar and as methane, has been fre- dial ion H + is essentially converted to quantitatively transferred into the pro- quently observed in the circumstellar 3 HCO+ rather than being destroyed by duction of C+. Since the ratio of He to gas of cool stars by its characteristic recombination with electrons. The ratio CO is 500 , the production of C+ infrared absorption. This sequence of of carbon monoxide to hydrogen in enhanced by that factor over produc- carbon ion insertion followed eventu- molecular clouds, tion by direct dissociative ionization ally by either dissociative electron CO + crp = C+ + O + e + crp. attachment or CO abstraction leads to [CO] ≈ -4 [H ] 10 The origin of the preponderance of the buildup of large organic molecules. 2 interstellar organic chemistry is a con- We note one further example of this. Thus destruction of H + by electrons is sequence of helium chemistry. The reaction sequence 3 + + a small fraction, 3%, of conversion by The chemistry we wish to explain C2H2 + C =C3H + H + + CO. The widespread abundance of is the abundance of compounds with C3H + H2 =C3H2 + H + + + HCO is direct evidence for the pri- several heavy atoms in them. Thus size C3H2 + H2 =C3H3 + H mary importance of ion molecule reac- is measured by the number of heavy leads to the production of the tions as the fundamental chemical atoms. The largest molecule in Table I extremely stable ion C H +, the first 3 3 process in the interstellar molecular is HC10CN, H-C C-C C-C C- aromatic. This species has the same xviii C C- C C -C N, a linear molecule. highly symmetrical shape as H + and is clouds . 3 The chemistry of He, the next Note the very high degree of unsatura- non-polar. Its presence, however, is most abundant species is now exam- tion. In Table I there are very few large readily inferred by the several species saturated species, such as H C-(CH ) - formed from it by dissociative electron ined. The ionization potential of 3 2 7 helium at 24 ev is almost twice that of CN, the saturated species of the same attachment. Continued on page 16
The Nucleus April 2003 15 Interstellar Chemistry (and unavailable) energy. The very the preponderance of organic poly- interesting radiative association reac- atomic species is due to the chemistry Continued from page 15 tion of helium. + + The species C H and C H are obvious C + H = CH + h We have not stressed sufficiently 3 2 3 2 2 products of the reaction Is quite slow, with rate constant 10-7 of the central role of radio astronomy in + collisional, and does not completely revealing the molecular universe. C3H3 + e = C3H2 + H deplete the carbon ion. Radio frequency radiation suffers =C3H + H2 Both C H and C H exist in two iso- The steps required to build up the approximately ten thousand times less 3 2 3 meric forms, cyclic and linear. All of larger species are more numerous but attenuation from the dark obscuring these have been observed by radio the picture that the larger species are interstellar matter than does optical astronomy in many molecular clouds. synthesized from the smaller species radiation. Thus the dark regions which It is again noteworthy that isomers does fit reasonably the observed size in a sense are molecule factories are with very different energies are distribution. If the carbon species came observed by the molecular emission. observed in these low temperature from the dissociation of large species The origin of the molecular emission is clouds showing molecular abundances which were desorbed from grain sur- caused by the changes in rotational are kinetically determined. The disso- faces by energetic particles a quite dif- quantum states of the species. In order ciative electron attachment of C H + ferent size distribution might be that radiation be emitted efficiently by 3 3 for the formation of both isomers of anticipated. Summarizing the origin of the changes in rotational quantum both species is then a simple high the preponderance of unsaturated states the species must possess an elec- energy process in which thermal equi- organic species as the large interstellar tric dipole moment. This requirement, librium behavior of product formation species is through a series of binary at first sight, would appear to eliminate would never be expected. reactions. The growth of the size of the the detectability of many interesting We must further point out that the molecule is effected by the insertion of species. Rotational spectroscopy is the carbon ion C+ is relatively stable in H . carbon ion. The high rate of production most developed area of molecular 2 of carbon ion is directly dependent spectroscopy. The rotational spectrum The direct reaction + C+ + H = CH+ + H upon the production of He by cosmic of a molecule is determined by the 2 does not occur in cold interstellar ray ionization. This indirect route geometric structure. It is therefore very molecular clouds since it is endother- results in a thousandfold enhancement closely connected to our understanding mic, therefore requiring considerable of organic chemistry. Thus we can say of molecular structure. This is also an exceptionally well developed area of physical science. There are many tech- niques for predicting the geometric structure of molecules, and concomi- tantly the rotational spectra. Radio astronomy is thus an excep- tionally powerful tool. It can penetrate dark regions and provide immediate molecular information, sometimes even for molecular species unobserved in terrestrial laboratories. The power of radioastronomy is further illustrated in Table III by the relatively long list of molecules seen in distant galaxies. It is noteworthy that the more abundant molecular species of our galaxy are seen everywhere. Since the list of Tables I and III have complete overlap, it is likely that the chemistry we have delineated is uni- versal. The formation of the species HCO+ by the reaction H + + CO = HCO+ + H 3 provides an insight into methods for determining the existence and abun- dance of non-polar molecules by radio Continued on page 17
16 The Nucleus April 2003 Table III Molecules Observed in Other Galaxies Interstellar Chemistry (Number of Atoms) Continued from page 16 23 456+ astronomy. Molecular nitrogen, N2, is extremely similar to carbon monoxide. CO HCN NH C H CH OH If N exists in the dense interstellar 3 3 2 3 2 clouds then the reaction CH HNC HNCO HCCCN CH3CN H + + N = HN + + H 3 2 2 + + will occur. The species HN is polar CN HCO H2CO CH3CCH 2 and thus has an observable rotational OH N H+ spectrum. It is readily observed by 2 radio telescopes. The species CO sim- 2 SO H2O ilarly has a linear symmetric non-polar structure. It is converted by reaction SiO OCS with H + to HCO + and becomes 3 2 6 observable. Note that both HCO + quality factors of the order of 10 . This chemistry of interstellar molecular 2 and HN + are listed in Table I. Proto- is high enough to insure uniqueness clouds. We have shown that the molec- 2 nation of non-polar molecules makes and reliability in the observations. The ular gas phase abundances, although them polar and observable. fact, furthermore, that a large number very far from the equilibrium composi- There are further evidences of the of spectral transitions can be deter- tion, can be understood in terms of reactions of H + with interstellar mole- mined in terms of a very small set of quite specific kinetic processes. These 3 cules. Both HCN and its high energy structural parameters of a molecular kinetic processes can be tested by isomer HNC are observed by their species allows the observer to readily direct laboratory measurements. There characteristic rotational spectra by confirm observations. Relatively few are many signatures for the cosmic ray radio astronomy. Since the energy dif- mistakes of the identification of induced ion molecule chemistries, such species have been made by radio as widespread high abundance of the ference of the species is extremely + large, approximately 1ev, the exis- astronomers. species HCO as well as the more recently observed H +. The preponder- tence of the high energy isomer in rela- It should be noted from the pres- 3 tively large amount indicates ent discussion that it is the gas phase ance of unsaturated organic molecules non-equilibrium behavior. In the past chemistry and gas phase composition as the dominant large polar polyatomic the species HCNH+ was inferred as an of interstellar molecular clouds that species is understood in terms of reac- has become relatively well understood tions of the carbon ion. The very high attractive candidate as the reactive + in recent years. The condensed phase rate of production of C is a direct con- intermediate. The reaction + HCNH+ +e = HCN +H remains much more uncertain. Infrared sequence of the non-reactivity of He , astronomy is developing at great produced by cosmic ray ionization, = HNC +H + is assumed to show about equal speed. The results from the Infrared with molecular hydrogen. Instead He Spectroscopic Observatory (ISO) are reacts with CO, an abundant molecule branching, in view of the large amount + of energy released in the electron stunningxx and are bringing new transferring the ionization to C pro- attachment reaction. The ion HCNH+ understanding. Vibrational spec- duction. In this sense the strongly non- has been observed, by its rotational troscopy especially of condensed phase equilibrium highly specific production spectrum, in interstellar molecular species generally has a lower quality of unsaturated carbon chains can be clouds. We may note that the proton factor, than the gas phase rotational fully understood in terms of a totally affinity of HCN is high compared to spectra discussed here. However, abiotic synthetic scheme. Whether this CO thus, HCNH+ is stable with respect molecular rotational spectroscopy of is a lesson of general significance to proton abstraction (which would condensed phase does not exist. The remains to be seen. simply form HCN) and indeed will be power of solid phase infrared observa- + References formed also from HCO reacting with tions is well illustrated by the observa- i For results from COBE (Cosmic Back- HCN. tion of (hydrogenated) diamonds in ground Explorer): http://space.gsfc. xxi Interstellar chemistry remains very space by their characteristic C-H nasa.gov/astro/cobe/cobe_home.html active today. We have stressed radio stretching vibration. These observa- ii P.J.E. Peebles. Principles of Physical astronomy as the observational tool. tions provide details of the size and Cosmology, Princeton University Press, The study of gas phase species by their formation of the spectral carrier. Princeton, N.J.USA, 1993. pure rotational spectra has many singu- The interstellar medium provides iii The galaxy = our galaxy like the earth, lar advantages. In particular the quality a unique laboratory of vast size, low the sun etc factor of the observation in high. Tak- density and low temperature. It is par- iv D.M. Rank; C.H. Townes; W.J. Welch. ing the quality factor to be the line fre- tially observable by radio astronomy. Science, 1971, 174, 1083. quency divided by line width, gives We have touched on one aspect of the Continued on page 18
The Nucleus April 2003 17 Interstellar Chemistry Book Review Continued from page 17 Continued from page 6 v An up to date listing of observed inter- xv B.J. McCall; T.R. Geballe; K.H. Hinkle; fied by the work of Arnold Sommer- stellar molecules may be found at T. Oka. Astrophys.J., 1999, 522,338; feld, who introduced elliptical orbits http://www.ph1.uni-koeln.de/vorher- Faraday Disc. 1998, 109, 267. for the hydrogen electron and by doing sagen/index.html xvi L.E. Snyder; D. Buhl. Nature,1970, so brought together relativity theory vi The Far Ultraviolet Spectroscopic 227, 862. and quantum mechanics. Although xvii Explorer, FUSE, has mapped H2 in P.M. Solomon; D. Downes; S. Radford. more satisfactory than the Bohr model many regions , Ap. J. Letters, 2000, 538 Astrophy. J. ,1992, 387, L55. in explaining the appearance of dou- (1). xviii Ref. 14 discusses this in considerable blets in the spectral lines it was clear vii Excellent reviews are E. Herbst. Annual detail using their observed H + abun- 3 that the Bohr-Sommerfeld theory of Reviews of Physical Chemistry, 1995, dance. atomic structure would soon be 46 , 27-53. xix B.H. Mahan. Accounts of Chem. Res., viii V.G. Anicich, W.T. Huntress,Jr. Astro- 1975, 8, 55. replaced by newer concepts. phys. J. 1986, 62, 553 (Suppl.) xx Many exciting results may be found at The author next turns to the ix D.C. Clary. J.Chem.Soc. Faraday http://isowww.estec.esa.nl/science/ importance of fundamental constants Trans., 1987 , 83, 139. xxi S.-Y. Sheu; I.-P. Lee; Y.T. Lee; H.-C. and their careful measurement. In x Very beautiful images may be found at Chang. Astrophys. J. 2002, 581, L55. chapter 6, a relatively short chapter, he http://antwrp.gsfc.nasa.gov/apod/dark_n emphasizes this point in relationship to ebulae.html the dimensionless fine-structure con- xi V. Trimble. Rev. Mod. Phys. 1975, 47, stant. At the end of the chapter is the 877. Have you looked story of Hans Bethe and the joke he xii E. Herbst; W. Klemperer. Astrophys. J., at the NEW and two accomplices played on the 1973, 185, 505. physics community by publishing a xiii T. Oka. Phys. Rev. Lett., 1980, 45, 531. NESACS website? paper in Naturwissenschaften concern- xiv T. Oka; T.R. Geballe. Astrophy. J., ing a fictitious value for this very con- 1990, 351, L53; stant. It is also interesting to note that J.P. Maillard; P. Drossart’ J.K.G. Wat- WWW.NESACS.org Bethe’s apparently playful and good son; S.J. Kim; J. Caldwell. Astrophy. J. sense of humor indirectly involved him 1990, 363, L37. as a “non-contributing” author in another paper referred to as the “Alpha Beta Gamma paper”, published in 1948 by George Gamow and a gradu- ate student Ralph Alpher (p. 213). The work of Pauli, Heisenberg, and Schrödinger and others who usher in the age of wave mechanics is then presented. One of the many interesting anecdotes included is a meeting between Bohr and Schrödinger as detailed by Werner Heisenberg (p. 83). It appears that Schrödinger visited the home of Bohr in Copenhagen during the Fall of 1926, to converse about quantum jumps and atomic structure. After many days and nights of discus- sion Schrödinger became ill and remained in bed, while Mrs. Bohr cared for him with food and tea. Niels Bohr on the other hand sat on the edge of the bed, continuing to argue. Chemists should be particularly interested to read about Harold Urey(Chapter 10). Not only is Urey cited for his work on the discovery of deuterium, but for his great generosity. Continued on page 19
18 The Nucleus April 2003 Book Review Continued from page 18 Trustees Report The discovery and development of Status as of December 31, 2002 NMR is described in chapters 12 through 14. The pioneering work of I.I. Consolidated Account* $ 1,225,333.78 Rabi, (the subject of another book by Esselen Trust 443,406.06 Rigden , Rabi: Scientist and Citizen, Richards Trust Income Acct. 43,938.79 Harvard University Press, 2000), of Edward M. Purcell, and of Felix Block Norris Trust Income Acct. 17,532.16 is presented with interesting details of Publications Trust Income Acct. 20,427.16 the earliest experiments. One is partic- ularly struck by the lack of funding Hill Trust Income Account 9,743.18 even at the great universities at that Levins Award Fund 10,589.37 time. For example, Purcell had to scrounge surplus magnets (p.143), and Total 1,770,970.50 Block had to use the majority of his research money to purchase an oscillo- The average interest earned on the principal was 4.73% scope worth $300. What a striking dif- The decrease in net worth for 2002 was $127,584 (6.5% compared with a decrease of ference this is to the cost of doing about 20% in the market) NMR research today! * The Consolidated Account consists of the principals of the Permanent Trust Fund, This section (chapters 15 and 16) Richards Trust Fund, Norris Trust Fund, Hill Trust Fund and the Publications Trust Fund. details the importance of the Lamb shift in the hydrogen atomic spectrum ing and, in the process, to under- atomic clock, and big bang cosmology and its interpretation by quantum elec- stand better the place of humankind are discussed, along with the people trodynamics. within the larger scheme of things.” and their personalities whose work The author does a particularly In the chapters that follow, experi- helped formulate the ideas that led to fine job in explaining the complicated the discoveries. Again the author theoretical discussion in lay terms. ments and concepts involving radio Perhaps chemists will not be familiar astronomy, galactic mapping, the Continued on page 20 with the events that unfolded after 1947 and the Shelter Island Confer- ence. The story is just as fascinating as those preceding. At the end of chapter 16 is a para- graph that I think best describes this book in the author’s own words: “In arriving at insights into nature’s bountiful imagination, we are fortunate that nature gave us the simple hydrogen atom. Its one electron with its nucleus of one pro- ton or one deuteron has stimulated the feeble imaginations of scientists to probe behind the common sense appearance of things and to soar to ever new heights of understanding. The concepts that have emerged from the laboratory have proven their power in synthesizing dis- parate realms of experience. At the same time, these concepts continue to challenge and boggle the best minds. As we look to the future, the hydrogen atom will continue to help us meet the challenge of embracing the natural world with understand-
The Nucleus April 2003 19 Bees and the War on Terrorism According to a report in The New York Times (May 13, 2002), scientists have been teaching honey bees to recognize certain explosive residues, working under Pentagon grants. Apparently bees are at least as sensitive to odors as dogs. Bees are also being considered for sniffing out drugs. Training consists in rewarding bees with sugar for sniffing out the wanted odors. Bees can be thus trained in just a few hours, much faster than dogs. This is NOT an April fool’s story!
Book Review Continued from page 19 focuses these stories through the hydrogen lens. Antimatter and particle physics, Bose-Einstein condensate, and exotic hydrogen-like atoms are all dis- GATEWAY CHEMICAL cussed in the closing chapters. This material introduces the reader to some TECHNOLOGY of the current research that fascinates today’s physicists: Why the absence of antimatter? How can the study of Ryd- CUSTOM SYNTHESIS berg atoms help unravel more myster- • Pharmaceuticals ies of atomic structure? Will • Agrichemicals Bose-Einstein condensates provide • Combinatorial Platforms insight to the domains between the • Competitor's Products microscopic quantum and macroscopic • Intermediates classical domains? • Analytical Standards John Rigden does an excellent job • Metabolites in putting the human quality into the technical material so that it is both PROCESS DEVELOPMENT entertaining and informative. I found • Process Evaluation this book good reading and highly rec- • New Route Development ommend it to anyone who wants to discover why hydrogen is the essential SPECTROSCOPIC SERVICES • LCMS (APCI and API-ES) element. • NMR (300 MHz) • GCMS (EI) Have you looked at the NEW 11810 Borman Dr • Saint Louis, Missouri 63146 NESACS website? 314.220.2691 (office) • 314.991.2834 (fax) www.gatewaychemical.com • [email protected] WWW.NESACS.org
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