Perspective pubs.acs.org/crystal
Peggy Etter: A Personal Recollection Published as part of the Crystal Growth & Design Margaret C. (Peggy) Etter Memorial virtual special issue Joel Bernstein*,‡ Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel 84120 Faculty of Science, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates Faculty of Science, New York University Shanghai, Pudong New Area, Shanghai 200122 China ABSTRACT: In a tragically shortened career Margaret C. (Peggy) Etter (1943−1992) not only made pioneering scientific contributions to the budding field of organic solid state chemistry. She also was a devoted and motivating mentor, resolute colleague, and inspiriting advocate to many practitioners in the developing discipline. The breadth of current activity in the field is very much a tribute to her scientific legacy. Little has been written about Peggy Etter the person. I was fortunate to be a colleague and collaborator for nearly 15 years during which time I got to know her as both remarkable scientist and a very special individual. This personal contribution, introducing the virtual memorial issue, tries to portray some of the highlights of that relationship.
thought that the first time I met Peggy was in late May of 1978. How that happened is one of those personal/ professional contacts that makes doing science such a wonderful experience. I was completing my first sabbatical at the University of Illinois with David Curtin and Iain Paul, and in March had attended the annual American Crystallographic Association meeting at the University of Oklahoma. (As I recall that was the first ACA meeting at which posters were presented in addition to oral talks.) At lunchtime on the first or second day of the meeting I ran into Carol Brock, a contemporary and long time friend, who was at the start of what turned out to be a distinguished career at the University of Kentucky. She said there was someone I absolutely had to meet and introduced me to Bill Gleason, then a faculty member at the College of St. Catherine in St. Paul. Bill and I hit it off immediately and spent much of the rest of the meeting excitedly discussing the science, people, and places of organic solid state chemistry. Upon parting, Bill said, “You’ve got to come to Minnesota and meet Peggy Ettereven though it is late in the academic year I’ll try to arrange a seminar.” And he did. Late in May I flew up to Minneapolis midday on a Sunday. Bill picked me up at the airport and took me out to his home in suburban Minneapolis. For hours we continued our animated discussions, before and after dinner finishing off a bottle of Jack Daniels and a couple of cigars. Monday was the physical chemistry seminar day at “the U”. I don’t recall much of the morningI was probably still working off the excesses of the previous daybut I vividly recall meeting Peggy just before the seminar and could place her precisely in the room even today. For my entire talk she exhibited that characteristic shining smile of enjoyment and enthusiasm that so many who got to know her still fondly remember. I recall that for me as the speaker it was almost disconcerting. After the seminar (one of my first on Conformational Polymorphism),1,2 Peggy had to run off, but we had already
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arranged for one of her typical days on the morrow. She would pick me up at my hotel at 0730 for breakfast in “Dinkytown”, the Twin Cities version of the potpourri of student oriented shops and eateries that borders every American university. Starting the day with an early breakfast was part of the Etter ritual for visitors. It was a sort of “get to know each other in a more private, less formal atmosphere before the exposure to the organization”. We then drove 20 or so minutes out to her office. Peggy was working in the Central Research Laboratories at the mile square 3M campus in St. Paul, a fascinatingly diverse company, at the time dealing with about 60,000 products from Scotch Tape to sandpaper, dental materials to underwater cable connectors, road signs to magnetic media, and more (but not Post-Its that had not yet been marketed, or Velcro that had not been purchased from its inventor). Although it was a unique institution, it was my first real exposure to the chemical industry. She took me through what seemed like a maze of endless corridors to her office where we had more exciting chemistry to discuss. Then to lunch, a visit to the, enthralling for me at least, “Hall of Products”, and the first of my many pilgrimages to the 3M company store. I was like a kid in a toy store: all kinds of sticky stuff (Scotch tape, masking tape, surgical tape, etc.) and Scotch Guard, auto waxes, silver polish, tape cassettes, label maker at dirt cheap prices (and limited quantities), along with things I didn’t really need but couldn’t resist. As I recall during the rest of the day I got a review of Peggy’s activities at 3M, along with some background about her career till then. I had been familiar with her Ph.D. research, carried out at the University of Minnesota under the direction of Jack Received: September 7, 2015 Revised: December 7, 2015 Published: February 2, 2016 1135
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I spent another intermittent summer or two at 3M and continued as a consultant there until the middle 1980s. Peggy’s fortunes slowly improved, and reached a zenith during one of my summer visits, when she and Bill Gleason came to my desk (next to the entrance to her office) ecstatically grinning almost beyond control. They had just come from a meeting with their managers where they had been informed that 3M was going to embark on a major push in solid state chemistry; as part of that effort Peggy was expected to play a leading role and should go to Israel to visit with many of the major players in the field, especially the group at the Weizmann Institute (Mendel Cohen, Meir Lahav, Leslie Leiserowitz et al.). I don’t know if it is endemic to industrial basic research (if one can use that term), but my experience at 3M, with my visits every few months, was such that every time I arrived it seemed like the research priorities had changed. It was very difficult to focus on the long-term. It was very difficult to sense continuity in individual projects or in the overall program in which I personally was involved. Peggy’s proposed visit was a testimony to that lack of a longterm research program. I went back to Israel and enthusiastically started helping Peggy to organize her visit. But true to the culture of changing priorities the visit envisioned at that time never materialized. After a few months the enthusiasm had vanished, and the focused program went into essentially perpetual hibernation. During those consultation visits I got to know Peggy better and better as a scientist and as a person. Her middle initial “C” was for her maiden name, Cairns, for she was the second child of Theodore (Ted) Cairns who spent most of his distinguished career as a research chemist at DuPont, serving eight years as the director of its then renowned Central Research Department. He was a member of the U.S. National Academy of Sciences, but for the solid state chemistry community he is probably best known for his synthesis of the classic electron acceptor tetracyanoethylene.5 Her father had been a Ph.D. student of the fabled Roger Adams at the University of Illinois, and he counted as close friends many of the leading organic chemists of the middle of the 20th century. As an example of the kind of company her parents kept she once said to me, “I grew up at the knees of J. D. Roberts.” So, literally and figuratively, good chemistry was in her blood. In the opening sentence I said I thought that the first time I met Peggy was during that May 1978 visit to Minnesota. Not so. One of those summer afternoons at 3M we were chatting about nothing special over coffee, so we wandered off into a little about our personal pasts. I recalled that Peggy’s CV indicated that she had attained her B.Sc. at the University of Pennsylvania and her M.Sc. from the University of Delaware. We got to discussing our undergraduate days so I naturally mentioned my alma mater Cornell, at which she perked up and told me that she had been a freshman at Cornell in the fall of 1960. That jogged my memory and I mentioned that I had been a counselor for freshman orientation week that fall, noting that each group had the name of a defunct U.S. political party. With that infectious Etter enthusiasm and distinguished laugh she recalled that she was in the Mugwump groupthe very group for which I was part of the staff. So we had obviously met more than 20 years before. But it didn’t end there. Somehow we got on the subject of birthdays, and it turned out that she and I share the same birth dateSeptember 12with a two year difference (she was the
Gougoutas. It turned out to be a classic study of topotactic reactions3 and even today provides a model of how these systems can and should be studied. I returned to Urbana the next day to finish the sabbatical year before returning to Beer Sheva, but the connections with David Curtin, Iain Paul, Bill Gleason, and Peggy Etter had been established. In those days they were still maintained by snail mail. Peggy worked assiduously and enthusiastically at 3M to develop a research program in organic solid state chemistry, often dealing with an administration that was less enthusiastic than she was, if not, at times even a bit hostile. In 1980 Gleason moved to 3M, although he was not initially working in the same department as Peggy. The crystallographic facilities at 3M consisted essentially of a vintage powder diffractometer. Around the beginning of 1980, Peggy succeeded in convincing the 3M authorities to purchase a single crystal diffractometer. Her elegant thesis work had been carried out on X-ray cameras, for the most part on a Weissenberg camera. She had no experience operating a single crystal instrument or with any of the programs (e.g., SHELX, vintage 1976) that were being developed and used for single crystal structure solution. Curtin suggested to Peggy that she hire me as a consultant for a couple of months to show her the ropes on her new Nonius diffractometer and get her off and running in the new era of single crystal structure solution. So Peggy called me in Beer Sheva late in the spring of 1980 and invited me to 3M for a couple of months that summer. It was my first consulting offer, and I was honored and excited by the prospect, although it took me away from the family for most of the summer. They joined me for a couple of weeks in August. I brought SHELX with me to Minnesota (as I recall on a 9track magnetic tape) and got it installed. What were we going to work on? At the time 3M had a photographic subsidiary with a research lab in the UK. Derek Cash from that lab had been working with two photographic dyes, a cationic cyanine dye and an anionic oxonol dye, that when combined formed what seemed an endless number of polymorphs as well as solvated and unsolvated salts. Peggy was collaborating with Derek in characterizing many of those materials, but had been frustrated in attempts to obtain any single crystal structure determinations. So that’s what she gave me to do. Within a couple of weeks we had installed all the programs, measured the data, and had the structures of the red and green polymorphs of the (unsolvated) salt. That turned into a 1984 J. Am. Chem. Soc. paper, my first with Peggy, in which we reported on the preparation of no fewer than 14 salts of these two ions (including solvates). Peggy’s 3M research program was beginning to develop, although the administration was quite slow in recognizing and encouraging it. One of her supporters was Sam Smith, a warm and personable industrial chemist of “the old school”, who was the inventor of ScotchGuard. Every now and then Peggy would point out some other inventor that we passed in the hall or somewhere on campus. One day she showed up with a little yellow pad and explained that this was one of the newest “little sticky things” that 3M had come up with. It was being tested among 3M employees. I was immediately enthralled, so she took me across campus to meet the inventors. 3M had what I thought was an unusual, but it turned out to be very successful,and often cited by management gurus,4 attitude toward inventors. An inventor would “captain” an idea from conception right through market launch. This created and maintained great loyalty to the product and to the company. 1136
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Figure 1. A facsimile of the Organic Solid State Family Tree that appeared ad hoc on the Etter Group blackboard. The blue lines indicate connections between Ph.D. mentors and their students; the red lines connect postdoctoral associations.
younger). So we are precisely matched Virgos, which may explain our personal and scientific consonance. Peggy’s office at 3M was arbitrarily divided into two sections “decorated” with 3” × 5” cards, each of which had a hand drawn hydrogen-bonded motif and the literature reference from which it was taken. As I recall it the ones immediately around her desk surrounded a sign saying “YES!!”, and those (less numerous) relegated to more distant parts of the room were associated with a “NO!” sign. She was already collecting examples of what we would call today hydrogen-bond synthons. The frustrations of developing a serious program in solid state organic chemistry at 3M continued to mount during 1981 and 1982, and Peggy decided to change course. She undertook a belated postdoc in solid state NMR with Bob Bryant at the University of Minnesota. It was familiar territory from her predoctoral days. (We stayed in touch, especially when I got to the Twin Cities on 3M business.) In 1984 she applied for a faculty opening in chemistry at Minnesota. These were turbulent times in the Department of Chemistry. It was the subject of a major lawsuit (the Regender case) for gender discrimination that resulted in a decision to require the Department of Chemistry to hire a specific number of women and report regularly for 10 years to the court on their status and progress toward tenure. Peggy did not fall into that category of required hires, but she certainly was affected by the general tensions that pervaded the department. In 1984 she was appointed an assistant professor of chemistry and started building an academic research group. Toward the end of the 1980s, I was approaching my third sabbatical and Peggy was directing her experience of solid state NMR at the analysis of polymorphs. Spending a year in the familiar territory of Minnesota working on the solid state NMR of polymorphs with Peggy seemed like the perfect combination. We made arrangements for the academic year 1988−1989. June 1988 coincided with David (DY as he was affectionately referred to by colleagues and students) Curtin’s retirement from teaching at the University of Illinois. Iain Paul, who had collaborated so successfully with Curtin in establishing the organic solid state chemistry program there, joined with Steve Byrn, one of Curtin’s early graduate students in that program, and Peggy to organize a weekend retirement symposium for Curtin. They invited key players in the field from all over the world and asked me to present the opening Friday afternoon talk recounting DY’s career.
Since I was going to spend the following academic year in Minneapolis, I thought it would be a good idea to spend 2−3 days there looking for housing for the family. I coordinated that visit with Peggy who met me at the airport following a morning flight, with a typical Peggy surprise. She informed me that I was going to present the pizza luncheon seminar to her group now about 10 peopleand dictated the subject. All of her students were going to be piling into a van for the drive down to Urbana and the Curtin Symposium that coming weekend. The names of many of the speakers were of course familiar to them, but from the literature. Then, as now, the organic solidstate community is very much an extended research family, with many interconnections. Those connections stem from the fact that in the early 1960s, when organic solid-state chemistry was undergoing a renaissance, there were few centers of activity, and many of the early workers in the field could trace their professional roots to one of those centers. Peggy’s charge to me was to go through the speaker list and trace the professional “nepotism” in our small scientific family. It was a totally ad libbed performance. Over the course of an hour the blackboard (a true slate black board that required real chalk, I might add) filled with a family tree connecting mentors, postdocs, sabbatical visitors, etc. as recreated in Figure 1. The students noted almost every detail, and then, armed with these “program notes” piled into the van for the 10−12 h ride to Urbana for the first Midwest Conference on Organic Solid State Chemistry, honoring D. Y. Curtin. The announcement for the meeting and the program is shown in Figure 2. The program contains very much a “Who’s Who” of the persona and their areas activity in organic solid state chemistry of those days (Figure 3). Peggy, Steve, and Iain envisioned this meeting not only as forum to honor DY, but as the first of an annual gathering of groups from Midwest academic institutions to facilitate interactions between groups that were often isolated in their own institutions and to cultivate and perpetuate the activities in organic solid state chemistry in those institutions. The governing principles were, and still are, that the meeting would be of minimal cost and the presentations in whatever form would be mainly, if not exclusively, by students and postdocs. There would be plenty of time for social mingling to foster the esprit de corps and build lasting relationships and a lasting scientific community. Since the first one in June 1988 1137
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Figure 2. Announcement for the First Midwest Organic Solid State Chemistry Symposium, honoring D. Y. Curtin. Figure 3. Program for the First Midwest Organic Solid State Chemistry Symposium, honoring D. Y. Curtin.
almost all of Midwest Symposia have been held during the first 2 weeks of June and have adhered to that tradition. Then, in the course of the Friday and Saturday lectures the students constantly referred to the solid-state family tree. As the program shows, Friday afternoon was devoted to the lecture I was invited to give summarizing Curtin’s career and contributions. It was a heady and challenging task, but one that I was extremely honored by. Given the challenge, and the desire to get it just right, I wrote out the entire talk to be delivered from the text, the only time in my entire career that I gave a talk in this way. But I didn’t want it to come across as being read, so I practiced it aloud seemingly an endless number of times before actually giving it, and in fact most people in the audience thought it was extemporaneous.6 During the following year in Peggy’s lab she had the printed copy run off and distributed to her students as well as a number of participants in the symposium. It may be obtained from the author on request.
papers in the 1920s,7 and she was putting together a manuscript for submission to Accounts of Chemical Research. In order to help clarify and organize her thoughts she gave a series of weekly seminars at her group meeting. Following every one of those seminars she would seek my reaction. After four or five weeks she remarked on my unabashed lack of enthusiasm for the graph set approach. At one point she simply asked what she had to do to prove to me that this could be a useful tool for defining and comparing hydrogen bonding patterns, as opposed to the usual practice among crystallographers of listing the metrics of individual hydrogen bonds. I remembered that about a decade earlier as part of investigating conformational polymorphs I had published a paper describing the three polymorphs of a fairly simple molecule, iminodiacetic acid.8 I recalled poring over packing diagrams for hours trying to decipher how to distinguish among the three polymorphs. In the end they were described as various sized (all greater than 20 atoms) rings, in accord with the description given by the authors of one of the earlier published structures.9 In the usual fashion I also provided tables full of hydrogen bond metrics that I imagine nobody really read or used, although they were de rigeur for that kind of crystallographic paper. My continuing frustration with that paper (and others) was that there was no “take home” message.
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GRAPH SETS We arrived back in Minneapolis at the end of the summer of 1988. By then Peggy had made considerable progress on deciphering the patterns of hydrogen bonding and especially the application of graph sets to the description and characterization of hydrogen bond patterns. She had read and digested the early literature on hydrogen bonds, starting from the initial 1138
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and I had worked many hours on the iminodiacetic acid problem and through that self-teaching experience had developed a protocol for examining structures, identifying graph sets, and comparing them. Part of that experience had been included in Peggy’s original manuscript. There were many other technical and “procedural” aspects of the use of the graph sets that she had included, and there appeared to be a natural distinction between the philosophy behind the application of graph sets to hydrogen bonding patterns and the actual technical details in doing it, and Peggy decided to separate the two. She edited and rewrote the Accounts manuscript, and John and I worked on adopting the technical parts that had been removed from there into a separate manuscript for submission to Acta Crystallographica. The Accounts paper12 is by far her most cited paper, with well over 2500 citations, while the Acta Crystallographica paper13 comes in second with about half that number.
The reader might think that the existence and characterization of three polymorphs was interesting, but if you asked her a week later about how to distinguish among the structures, that message had not been conveyed in the paper. I showed the paper to Peggy and expressed my long-standing frustration. She looked it over and immediately suggested that we spend a couple of hours the following afternoon together deriving the graph sets for the three polymorphs. At that point in time, both our understanding of some of the ramifications of the graph sets and the technical means for rapidly producing packing diagrams with the appropriate views and number of molecules for complete definition of the first and second level graph sets made this considerably more than a trivial task. We didn’t have access to a graphics terminal with appropriate software for plotting, rotating, and interpreting packing diagrams. There was a lot of plotting structures on paper, generating the patterns, counting the number of atoms in each pattern, deciding if there were rings, chains, etc. How do we define the first level, the second level? What role does symmetry play? Peggy had developed some good ideas about how to deal with these questions, but they still led to a good bit of head scratching. Nevertheless, after about 4 h we had worked out the first and second level graph sets for the three polymorphs, and I must admit that the result was almost an epiphany for me. Here is the table that we derived from that analysis (taken from the paper that we subsequently published in the Journal of the Chemical Society).10
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REALIZATION OF A DREAM: THE PILGRIMAGE Peggy was on a roll. She had an active and productive research group. She was invited to be a plenary lecturer at the 1990 Bordeaux Congress of the International Union of Crystallography. She was included in the teaching staff of the 1991 International Crystallography School on Crystallography held annually on different topics in Erice, Sicily. The Accounts paper had been published along with a number of pioneering studies on the preparation and characterization of co-crystals, and a variety of other studies in solid-state organic chemistry. In December of 1990, I received an urgent email from Bill Gleason to call him as soon as possible, which I did. He informed me that after a few months of dealing with increasingly intense back pain, Peggy had been diagnosed with Stage IV kidney cancer and a growth (as she described it to me) “the size of a tennis ball” was removed. She began the regimen of chemotherapy and radiation treatment that would last for months, but alas would not save her. Many in the community were devastated, but Peggy continued to work to the fullest extent and to make arrangements to ensure that every graduate student would have a mentor who could direct research until completion of their degrees, and every postdoc would find a suitable position. And so it was.14 Peggy canceled her planned trip to Erice, but John MacDonald and a postdoc Mark Whitener did attend. Following the meeting, the three of us did a delightful weeklong tour of Sicily, and of course Peggy was a constant thought and frequent subject of conversation. Back in Beer Sheva, I received a call from Prof. Efrat Lifshitz at the Technion in Haifa. She was responsible for organizing the annual meeting of the Israel Chemical Society. In those days the meeting was essentially a “family affair” of Israeli chemists, but the normal practice was to invite one or two speakers from abroad for plenary lectures. Efrat was casting about for a suitable candidate and had consulted with Dorit Arad who had met Peggy at a meeting in 1988, leading to a very close friendship. Dorit had recommended Peggy to Efrat and suggested that she get my opinion. I told her that if Peggy could make it she would give a wonderful talk and that she would not be disappointed. Efrat sent out the invitation. Peggy was thrilled. For most of her career she had wanted to visit Israel and its concentration of organic solid-state chemists, with the center of gravity, of course at the Weizmann Institute. The timing of the Israel Chemical Society Annual Meeting, scheduled for February 1992, was also propitious. It was to
Table 1. Summary of First- and Second-Order Graph-Set Assignments for IMDA Polymorphs Polymorph (1) Polymorph (2) Polymorph (3)
N1 = C(5)R22(10)C(8) N1 = C(5)R22(10)C(8) N1 = C(5)C(5)C(8)
N2 = R22(14) N2 = R22(8)
Now it was a simple matter to see that Polymorph 3 could be distinguished from Polymorphs 1 and 2 at the first level graph set, while the latter two could be distinguished at the second level. Moreover, the distinctions could be rather easily summarized and recalled. I became an immediate convert, and we decided to write that up as an example of the potential uses of graph sets. As I recall the next day, Peggy asked one of her graduate students, John MacDonald, to work with me on putting the whole thing together. That was the beginning of a delightful working relationship.11 Peggy continued to work on her Accounts manuscript. When she thought she had a final version for submission she gave it to me for a critical reading. I thought it was greatI still maintain an abiding admiration for her ability to write, but I told her that there was no way that it would be accepted. Since its founding in 1968 the journal has had an implacable limit of 8 printed pages for any paper. I am not aware of any exceptions. Peggy was unmoved. She insisted that she couldn’t get the message over in that limitation and went ahead and submitted. After something on the order of a week to 10 days I returned from lunch 1 day to find Peggy almost in tears. Her “magnum opus” had been returned without even being sent to referees, with the instructions to shorten it to the required length if she wanted it considered for publicationno compromises in this instance either. So we immediately had a brainstorming session to figure out how to rescue the paper and get the job done. By this time John 1139
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them. Shortly after arriving in Minneapolis she entered a hospice where she remained until her death on June 9, 1992. She had collected all her strength for that final pilgrimage to the mecca of solid state chemistry and left an unforgettable mark on all who met, heard ,and were inspired by a supremely talented and totally undaunted woman.
follow a planned Italian−Israeli binational meeting on organic solid-state chemistry that I had organized with my counterparts in Italy. We immediately included Peggy in the program. Another of her long time wishes was to give a seminar at the Weizmann Institute. This was duly arranged as well. The planning and coordination for Peggy’s visit went on in earnest. By the time February rolled around she was essentially bound to a wheelchair, although she could move a bit on her feet and half sit supported by a stool. To facilitate her visit she drafted her sister Betsy Reveal to accompany her and provide the locomotion for her wheelchair. There were some memorable moments of that visit. Peggy and Betsy were flying from Minneapolis to Tel Aviv on Swissair via Zurich. Angelo Gavezzotti, who was coming in for the Italo−Israeli meeting got word of their itinerary, and in his inimitable manner silently volunteered his assistance. Instead of flying to Tel Aviv from Milan he took the train to Zurich and joined Peggy and Betsy on the last leg to Tel Aviv. Having another pair of hands along was most appreciated by the two “Cairns women”. Peggy wanted to see as much as possible of Israel. A couple of days in and around Beer Sheva included the Dead Sea, Masada, Ben-Gurion’s house, and the spectacular site of his grave in Sde Boqer and some other desert landscapes. The Italo−Israeli meeting was held at a seaside hotel in Herzliya, and Peggy presented one of her sparkling talks without incident. A day or two later she was scheduled to speak in the Gerhardt Schmidt Lecture Hall at the Weizmann Institute. I had left her in the charge of my able colleagues there a day or two before and showed up a couple of hours before her talk. When she had finished her last appointment prior to her talk, we met outside the lecture room a quarter of an hour before her talk and she called me aside with a whispered something like, “Joel, I’m not sure I can go through with the talk”. She went off to “freshen up”, while in half panic I contemplated what we might do to alleviate the situation. She returned indicating that she would be able to start lecture but was uncertain for how long she could continue. She entered the lecture room, and after being introduced took her place on the stage, half leaning on a stool that had been provided for her. I remember that the talk was of the usual Etter perfection, but all I could think about was how she was managing physically. She was managing just fine, and from subsequent developments that apparently was a false alarm, but nevertheless very disconcerting under the circumstances. Peggy’s final “appearance”and indeed, it turned out to be just thatwas the Israel Chemical Society plenary lecture to a few hundred participants in the Churchill Auditorium at the Technion. It was a late afternoon time slot, after a coffee break. Once again the solitary stool awaited her on the stage. I don’t recall who chaired that session, but Peggy appeared in a bright red blazer showing no signs of her affliction. She half sat on the stool and proceeded to present an absolutely brilliant lecture. At the close, Efrat came up to me, literally in tears, and said, “She made my meeting”. There followed a lovely dinner with about 15 friends and colleagues at a local Haifa restaurant. I remember it being a particularly joyous celebration of Peggy’s visit and her successes. The next morning Peggy and Betsy headed for the airport for the flights to Zurich and Minneapolis. Even by the time she got on the plane for Zurich, Peggy’s condition had significantly deteriorated, so the flights back were very difficult for both of
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THE LEGACY Rewind to April 1990, and another retirement symposium. This time it was Jack Dunitz’s, held in the Auditorium Magnum at the ETH, and I was invited to be one of the eight speakers. Still fresh from my sabbatical transformation in the Etter lab I decided to talk about hydrogen bonding and the graph sets. I wanted to tell this rather distinguished audience about this way of defining and comparing hydrogen bond patterns and thought that telling the iminodiacetic acid story pretty much as it happened would be appropriate. It seemed that the best way to do that would be for them to be able to simultaneously see what they were meant to compare, the difficulty in doing it without the graph sets, and the simplicity of the process and the results with the aid of the graph sets. Those were still the days that preceded Powerpoint and computer graphic presentations; we were in the heyday of overhead transparencies. Since the iminodiacetic acid system was trimorphic, in order for the audience to be able to compare structures and hydrogen bond patterns I needed to be able to show three crystal structures simultaneously. So I prepared a presentation that employed three simultaneous overhead projectors. I suppose the lecture appeared to be a bit frenetic as I moved from projector to projector using overlays on the transparencies to first define then characterize the hydrogen bond patterns. However, it went over very well, even though to this day I suspect that Jack is a bit skeptical of the utility of the graph sets. Almost immediately following the lecture I was approached by Olga Kennard, the founder and director of the Cambridge Crystallographic Data Centre (CCDC) and a long time friend of Dunitz. She had heard about the graph sets earlier from Peggy, but was now convinced that the method of analysis should be incorporated into the software of the Cambridge Structural Database (CSD). She invited me to spend a summer in Cambridge to try to get that job done. It turned out that my first summer available was in 1992, so we agreed to arrange it for then. In the interim, there were some other contributing developments. Upon my return to Beer Sheva following the year in Peggy’s lab, I was approached by Liat Shimoni to be her advisor for her master’s degree. I agreed and suggested that she search the CSD for additional hydrogen bonded polymorphic systems to which we could apply the graph set analysis. Also, Steve Byrn invited Peggy and me to speak at one of his three-day “short courses” on polymorphs and solvates in pharmaceuticals that he was organizing at Purdue. Almost simultaneously Ray Davis at the University of Texas contacted me with a question about graph sets. Ray and I had been graduate students together at Yale and had maintained contact on and off over the years.15 I suggested to Ray that he hop on a plane to Purdue to discuss the matters with us, and indeed he showed up. I recall a couple of long, stimulating evening sessions over beers at one of the West Lafayette watering holes as Peggy went through the basics of the graph sets, and we described our experiences of the previous year. Ray became a convert and went back to Austin to convince a fresh Ph.D. 1140
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student to work on developing the graph set approach. The frequency of our correspondence increased significantly, and we bounced ideas, problems, and solutions back and forth. The notice of Peggy’s illness late in 1990 put a serious damper on some of that activity, but Ray and I continued to be in touch quite regularly. We applied for and received a grant from the U.S.-Israel Binational Science Foundation to support our work on the subject. The summer of 1992 finally arrived and I set off for Cambridge armed with two more years of experience with the graph sets and the results of Liat’s master’s thesis research. I arrived in Cambridge on the first Sunday in July with an outline of how to proceed with the software development to incorporate the definition and presentation of the graph sets into the CSD software. At around 10 on Monday morning I was called to a meeting with Olga and two of her senior scientific collaborators (as I recall it was Frank Allen and Robin Taylor). All looked rather serious, and after the usual formalities Olga informed me that they were quite far behind schedule in preparing the forthcoming October release of the database. As a result she could not assign to me the two promised programmers, and as far as the CCDC was concerned, implementation of the graph sets would be set on a back burner. Olga told me I was free to spend the summer at the CCDC and I could do whatever I wished. I was crestfallen by the change in plans, and walked out to wander those special streets of Cambridge while I tried to gather my thoughts. Peggy had died just 3 weeks before, and I had hoped that incorporating the graph set analysis into the CSD would be a tribute to her contribution, but that clearly was going to be delayedif it ever came to pass. As the hours passed I realized that even though Peggy and Ray and I (and our students) had made considerable progress in the 2−3 years of working on these problems, there was no overview of the progress that had been made since Peggy’s seminal Accounts paper and the problems that still remained to be solved. It occurred to me that a review summarizing the situation would be appropriate and could serve as a testimonial to Peggy. I suggested that to Ray, and in light of the time and resources I now had on my hands volunteered to spend the summer preparing the first draft of the manuscript. We would provide the overview and incorporate the still unpublished results of our two graduate studentsboth of whom had completed their theses. So that became my activity for the summer. Ray conveniently arranged a week of theater and touring in London with his wife, Sharon, during that stay, and we had a couple of brainstorming sessions both at the CCDC and, not to miss out on an opportunity to enjoy some good English brew at the famous Eagle Pub, where Watson and Crick announced their cracking of the DNA puzzle. In fact it took almost two years to complete the review, which of course was dedicated to Peggy’s memory and submitted to Angewandte Chemie.16,17 It has turned out to be by far my most cited publication and hopefully a tribute to Peggy’s contribution. That summer of 1992 did not see the incorporation of graph set definition and representation into the CSD software. That was accomplished a few years later when Greg Shields signed on as a Ph.D student with Sam Motherwell at the CCDC; he did a superb job of implementing the graph sets into the Cambridge Structural Database software, so that the analysis and graph set assignment is now readily accessible to all users on pressing a single key.18
Perspective
CLOSING REMARKS
There has been remarkable progress in organic solid-state chemistry in the more than two decades since Peggy’s death. Much of that progress grew from the seeds of her work. In the middle and late 1980s many members of her group were routinely making co-crystals by grinding, which at the time seemed almost daft. Clearly, it is now a common technique that has been modified in many ways. The whole field of co-crystals has expanded exponentially, with latter-day practitioners often unaware of her early and pioneering contributions. The approach of looking at the patterns of hydrogen bonding (and other intermolecular interactions) and defining those patterns in terms of a graph set notation followed on the earlier ideas of Wells19 as well as Hamilton and Ibers,20 but she simplified it and turned it into the vocabulary of structural chemists. That vocabulary can be used to define and describe the synthons21 and tectons22 used in supramolecular chemistry. She combined insatiable curiosity and acute observation with an almost childlike enthusiasm and fascination with unusual chemical phenomena. Her observation of and investigation of jumping crystals23 in the course of a routine investigation of a crystal structure of an organometallic compound for a 3M colleague is still a classic in a field now known as mechanochemistry.24 She very early recognized the value of solid state NMR in characterizing polymorphs and following solid state phenomena of molecular crystals and demonstrated that potential in a number of early papers.25 She had an almost uncanny ability to project the potential of a discovery into chemical use. For instance, the realization that triphenylphosphine oxide would be an excellent hydrogen bond acceptor led to a photo-filled communication in J. Am. Chem. Soc. demonstrating how poorly crystallizing molecules with hydrogen bond donors could be induced to form exquisite crystals through hydrogen bond complexing with triphenylphosphine oxide.26 On a more personal plane she was deeply concerned with and constantly involved in improving the opportunities for women in science. She regularly lectured on the subject to high school and college students, and consciously tried to serve as a role model for both her female undergraduate and graduate students.27 In the course of a scientific careeror perhaps any career for that matterone is blessed with meeting and working with relatively few truly inspirational people who are both friends and colleagues in the practice of science. For me, and I think for many fortunate others, Peggy Etter was one of those people.
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THE SCIENTIFIC LEGACY OF PEGGY’S PUBLICATIONS Michael Ward and Mark Hollingsworth edited a memorial issue of Chemistry of Materials that appeared two years following her death, and included an excellent description of her career.28 The text was followed by a list of her 86 publications. As of April 2015 those publications have been cited more that 9300 times, and a number of them continue to be regularly cited. With the perspective of more than two decades it is illuminating to examine the scope and impact of Peggy’s work. In the paper that follows this one, Bill Ojala, who was one of the last group of Peggy’s students, describes her mentoring style, the culture of the Etter group, and the research during the 1141
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course of her career.29 The areas covered range from solid state NMR to hydrogen bonding motifs, design motifs utilizing hydrogen bonding interactions, polymorphism, phase transitions and reactions, crystal growth, topotaxy and structure− property relations, host−guest chemistry and brief ventures into chemical microscopy and medicinal chemistry. Much of it is truly interdisciplinary, so it is difficult to make clear distinctions among the list of publications. With that caveat, the publications roughly can be divided as follows. The greatest number of publications (26) deal with various aspects of hydrogen bonding, including the development and application of the graph sets and the recognition and utilization of hydrogen bonding patterns to create structural motifs in crystals. Those structural motifs were employed in attempts to obtain co-crystals (a term she essentially defined for the community), often with the goal of achieving polar crystals (11 papers). There were many enlightening studies (13 papers) of phase transitions and reactions in crystals, a significant number of these resulting from the keen observations of unexpected phenomena that prompted thorough and revealing investigations and insights into fundamental chemical phenomena. Peggy was fascinated by the whole phenomenon of crystal growth and published four papers devoted to that subject, although it is an important component of many of her other papers. She was no less intrigued by polymorphism, and there are five papers in which the emphasis is on the structure and comparison of polymorphic structures. Throughout her career she was a great believer in the use of solid state NMR in the study of the organic solid state as demonstrated by the 10 papers distributed at regular intervals in her list of publications. The paper resulting from her Ph.D thesis, of course, contains one of the classic studies of the detailed structural study of a topotactic reaction. There were occasional forays into host− guest chemistry (3 papers), packing and structure/property relations (2 papers), medicinal chemistry (2 papers), and even chemical microscopy (1 paper). Her desire and ability to interact with colleagues are demonstrated by the 11 (mainly structural) papers on a variety of compounds published with colleagues at 3M and the University of Minnesota. Rather than being simple structure reports, many of these are distinguished by the unique chemical and structural insights that Peggy could provide. In all, Peggy’s was a remarkable career both for its tragic brevity and for its continuing impact, even 23 years following her death.
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Perspective
REFERENCES
(1) Bernstein, J.; Hagler, A. T. J. Am. Chem. Soc. 1978, 100, 673−681. (2) Cruz-Cabeza, A. J.; Bernstein, J. Chem. Rev. 2014, 114, 2170− 2191. (3) Gougoutas, J. Z.; Chang, K. H.; Etter, M. C. J. Solid State Chem. 1976, 16, 283−291. (4) For example, Peters, T. J.; Waterman, R. H. Jr. In Search of Excellence; Harper Collins: New York, 2004. (5) Cairns, T. L.; Carboni, R. A.; Coffman, D. D.; Engelhardt, V. A.; Heckert, R. E.; Little, E. L.; McGeer, E. G.; McKusick, B. V.; Middleton, W. J.; Scribner, R. M.; Theobald, C. W.; Winberg, H. E. J. Am. Chem. Soc. 1958, 80, 2775−2778. (6) Historical footnote: A referee recalled a few memorable lines of a poem that Peggy read in honor of DY after the banquet during this celebration: “And what he thought was P two one/Was P two one on c”. The same referee pointed out additional historical details related to the family tree in Figure 1. They were not in the original on Peggy’s seminar room blackboard, but they are included here for completeness. Howard Zimmerman, who was John Scheffer’s Ph.D. mentor, was a postdoc with R. B. Woodward and also did research with Harry Wasserman. This is yet another connection to Peggy, since she was an academic granddaughter of Woodward. (7) For example, Latimer, W. M.; Rodebush, W. H. J. Am. Chem. Soc. 1920, 42, 1419−1433. Pauling, L. J. Am. Chem. Soc. 1931, 53, 1367− 1400. (8) Bernstein, J. Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. 1979, 35, 360−366. (9) Historical footnote: On the face of it this seems today like a trivial exercise. Fpr the enlightenment of future generations and the nostalgia of mine here is how we did it then (and we thought we were operating at or near the forefront of technology). The instructions for the ORTEP drawings were prepared on punched cards, one instruction per card (clearly, any mistake in punching the card [discovered before or after submission of the job] required discarding the card with the improper and uncorrectable holes). The deck of cards was submitted at the computer center (remote terminals to the central computer were still a rare luxury). If the job ran successfully, at best within a few hours, then a stereo plot was requested, usually on a strip chart rather than a single sheet. In 1978 the version of ORTEP that we had did not include the hidden line removal, so that was done by hand with Tippex. The resulting plots were much too large for stereo viewing. Thus, in order to view the figures in stereo they were rolled out on the floor, and we stood on a chair with a specially designed stereo viewer (with front surface mirrors) manufactured by General Electric for viewing stereo X-ray photographs (prior to the invention of CAT). The diagrams could then be read and interpreted, or if (as generally) requiring modification, be regenerated by repeating the whole process until a satisfactory result was obtained. That would then be photographed in glossy black and white for submission to the journal with the provision that the printed version must have the left and right eye images separated by approximately 6.0 cm to enable viewing in stereo. Many laboratories were equipped with stereo glasses originally produced for the U.S. Air Force for stereo viewing of air reconnaissance photographs; these would then be used for viewing the published figures in stereo. With some practice one could learn to get the stereo effect without the glasses. (10) Bernstein, J.; Etter, M. C.; MacDonald, J. C. J. Chem. Soc., Perkin Trans. 2 1990, 695−698. (11) John was also my teaching assistant in a graduate course on organic solid-state chemistry that I gave at the University of Minnesota during one semester that year. (12) Etter, M. C. Acc. Chem. Res. 1990, 23, 120−126. (13) Etter, M. C.; MacDonald, J. D.; Bernstein, J. Acta Crystallogr., Sect. B: Struct. Sci. 1990, 46, 256−262. (14) Historical footnote. I saw Peggy a number of times in the course of her illness, and in one of those meetings, she discussed her illness. She had the suspicion that it could be attributed to her doctoral thesis experimental work which had involved many hours of working with a Weissenberg camera. Those were quite “open” systems. And although
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest. ‡ Emeritus, Department of Chemistry, Ben-Gurion University of the Negev.
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ACKNOWLEDGMENTS Although, as titled, this is a personal recollection, I have benefitted greatly from the critical reading and suggestions of a number of Peggy’s former students, colleagues, and an astute referee with a memory better than mine. They know who they are and I wish to thank them here. 1142
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Crowell: New York, 1980) from Peggy’s office, and I henceforth became very careful with the use of pronouns in my language. (28) Hollingsworth, M. D.; Ward, M. D. Chem. Mater. 1994, 6, 1087−1089 (covering biographical notes and a list of Peggy’s publications). (29) Ojala, W. H. Cryst. Growth Des. 2016, 16, DOI: 10.1021/ acs.cgd.5b01482.
there were beam stops and lead shielding around a camera, the chances of radiation exposure were considerable. I often have thought that she and Rosalind Franklin suffered a similar tragic fate for similar reasonsof course without any way to prove it. (15) Historical footnote. In those days the Yale Chemistry Department fielded an excellent softball team from among its graduate students. For my first two years we rarely lost a game, and I think that we may even have won the summer intramural league championship once or twice. Ray was the left fielder who would chase down a fly ball with the grace of an antelope. Other noted players, who became distinguished chemists were Mait Jones (Princeton, third base), Jack Gilbert (University of Texas Austin, shortstop), John D’Auria (Simon Fraser University, pitcher and outfield), Robert Rando (Harvard, outfield), and Al Fratini (University of Dayton, pitcher). I played a number of infield positions, including catcher. In the course of writing this I was informed of Ray’s untimely passing on May 29, 2013. He was a distinguished teacher of thousands of University of Texas freshmen chemistry students over 40 years, and the author of one of the best selling freshman textbooks. His acumen for precision in chemical thinking and writing contributed greatly to the successes of our joint efforts. To help bring home lessons on separate occasions he presented me with two memorable books on writing: John R. Trimble’s “Writing with Style” (Prentice Hall, 2000) and Lynne Truss’s “Eats, Shoots and Leaves” (Gotham, 2003). I sorely miss his wise counsel and scientific comradeship. (16) Historical footnote: The paper contains prefatory and closing quotations from the Maimonides’ classic philosophical treatise “Guide for the Perplexed”. It was the title of the work and the purpose of the review that led me to that source. Upon arrival at the CCDC I mentioned this to Sam Motherwell who had returned to the CCDC after spending a number of years involved in the effort to computerize the Cambridge University Libraries. He told me that his friend, Prof. Stefan Reif, who was in charge of cataloging the Cairo Geniza collection in the Cambridge Library was an expert in Maimonides writings and could help me find the appropriate quotations. Sure enough, a few weeks later Sam brought me precisely what I was looking for. I later met Reif in the library for a private showing of some of the remarkable documents in the Geniza collection. (17) Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N. L. Angew. Chem., Int. Ed. Engl. 1995, 34, 1555−1575. (18) Motherwell, W. D. S.; Shields, G. P.; Allen, F. H. Acta Crystallogr., Sect. B: Struct. Sci. 1999, 55, 1044−1056. Motherwell, W. D. S.; Shields, G. P.; Allen, F. H. Acta Crystallogr., Sect. B: Struct. Sci. 2000, 56, 466−473. (19) Wells, A. F. Structural Inorganic Chemistry, 5th ed.; Clarendon Press: Oxford, 1989; pp 294−315. (20) Hamilton, W. C.; Ibers, J. A. Hydrogen Bonding in Solids; W.A. Benjamin: New York, 1968; pp 19−21. (21) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311− 2327. (22) Wuest, J. D. Chem. Commun. 2005, 5830−5837. (23) Etter, M. C.; Siedle, A. R. Mol. Cryst. Liq. Cryst. 1983, 96, 35− 38. (24) James, S. L.; Frišcǐ c, T. Chem. Soc. Rev. 2013, 42, 7494−7498. (25) Etter, M. C.; Hoye, R. C. Trans. Am. Crystallogr. Assoc 1986, 22, 31−48. (26) Etter, M. C.; Baures, P. W. J. Am. Chem. Soc. 1988, 110, 639−40. (27) Historical footnote. At one point I was a personal “target” of this campaign. Early in that 1988−1989 sabbatical, I was describing some of our work on organic conductors at an Etter group meeting. I was asked a number of times if we had tried something or done some experiment or calculation. At some point out of sheer frustration I pointed out that we did not have enough manpower. “You don’t have enough what?” “Manpower”, I responded innocently. That exchange was repeated three or four times until I finally got the message, and responded with something like “Enough people to do the work”. I was immediately rewarded with one of the dozen or so copies of “The Manual of Non-Sexist Writing” (C. Miller and K. Swift, Lippincott & 1143
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