Emanuel Gil-Av (1916-1996): A man with a legacy

CHIRALITY 10:373–374 (1998)

Emanuel Gil-Av (1916–1996): A Man With a Legacy NELU GRINBERG, Guest Editor

In 1983 I emigrated from Romania to Israel. In my quest for a job, I was advised to investigate possibilities for a postdoctoral fellowship at the Weizmann Institute in Rehovot, Israel. Thus, on a sunny morning, I went to The Weizmann Institute and began to inquire about people dealing with my field of expertise of chromatographic separation. A friend of mine introduced me to Professor Emanuel Gil-Av. I knocked on his office door and a voice answered ‘‘come in.’’ A gentle man, in his late sixties, with a wide warm smile greeted me. I asked if he had five minutes to listen to me. I sat down and next I knew I was speaking with him about my previous work for over an hour. I understood later that I did not receive any special treatment, but rather this was his customary manner in dealing with his postdocs and his collaborators—always with patience, generously giving his well-qualified opinions and advice. This was Professor Emanuel Gil-Av. When I joined his group, though small, it was still a melting pot of scientists from all over the world, Japan, Germany, Italy, the United States, and myself freshly out of Romania, all coming to learn from his experience. An electric exchange of ideas always characterized his group, and he was a central figure with his scientific intuition and expert opinions. Emanuel Gil-Av was born Emanuel Zimkin (in 1952 he changed his name to Emanuel Gil-Av) in Penza, Russia, in 1916. His family immigrated to what was then Palestine when he was 12 years old. There, he attended the high school at the Gymnasium Herzelia in Tel Aviv. To continue his education, Gil-Av went to France, where he studied petroleum chemistry at the Chemistry Institute of Strasbourg. After his graduation, he accepted a fellowship at the E´cole Nationale Supe´rieure du Pe´trole in Strasbourg. With the second World War and the Nazi German invasion of France in 1940, Gil-Av moved again, to England. Here he worked in London in the laboratory of Chaim Weizmann (who later became the first President of Israel), working under the direction of both Weizmann and Ernst David Bergmann; and in Manchester for Petrochemical Ltd. His work concerned the development of processes for the conversion of non-aromatic and hydroaromatic materials into a wide range of aromatics. All these compounds were regarded as key raw materials, building blocks for the synthesis of strategic materials such as artificial rubber, polymers, drugs, and explosives needed by the Allies during the War. The time spent in Weizmann’s Laboratories and the contacts with these marvelous scientists laid the foundation for his future scientific career. With the end of World War II and the revival of the infrastructure and the economy in Palestine (which was at that time under British mandate), he decided to return © 1998 Wiley-Liss, Inc.

home. With a research grant from Petrochemical Ltd. and an invitation from Dr. Chaim Weizmann and Professor Ernst David Bergmann, (the Daniel Sieff Research Institute’s first Director), he settled in Rehovot at the Institute (which was the core for the later Weizmann Institute of Science). His research at that time focused on the utilization of Reppe chemistry for carboxylation of alkynols (nickel carbonyl as catalyst). Gil-Av finished his research project just before the outbreak of the Israel War of Independence in 1948. Thus, a nation was born and with it an economic and scientific revival. In the midst of these events, Gil-Av decided to pursue an academic career and began to work for his Ph.D. degree under Prof. E. D. Bergmann, undertaking the synthesis of oxazolidines, compounds of great interest in the medicinal field. Together with S. Pinkas, he promoted infrared spectroscopy as a versatile tool for the characterization of heterocycles containing CO and N, and of hydrogen bond patterns. Gil-Av received his Ph.D. degree in 1951. At that time Israel did not have any source of domestic fuel. This led him to pursue a new research direction together with one of his former students, J. Shabtai, an exploration of Israel’s oil shale deposits. Together with Heller and Steckel, he fostered the use of mass spectrometry and gas chromatography for the characterization, separation, qualitative and quantitative analyses of oil shale and for products of aromatization of paraffinic hydrocarbons. His work in argentation gas chromatography (in collaboration with J. Shabtai) constituted a milestone in the development of complexation chromatography. Gil-Av was a visionary in science and was always looking to solve the impossible. One of these impossible tasks was the separation of enantiomers. The existence of an internationally acclaimed center for peptide chemistry at the Weizmann Institute, along with his experience in gas chromatographic separation, stimulated him to approach the field of chiral discrimination. His previous work with David Nurok on the separation of diastereomers set the foundation for what was to be the epochal discovery of enantiomeric separation using gas chromatography. ‘‘When we started this work in 1964,’’ Gil-Av mentioned in one of his papers, ‘‘this topic was in a ‘state of frustration.’ Nobody believed it could be done. In fact, people were convinced that there could not possibly be a large enough difference in the interaction between D- and L-solute with an asymmetric solvent. This was the feeling people had, even those known as unorthodox thinkers. This view had also some experimental basis, because a number of communications had been published, in which it was claimed that such resolutions could be effected, but nobody was able to re-

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produce these results and some of them were shown to be definitely wrong.’’ Thus, when Beni Feibush, who at that time started his Ph.D. work under Gil-Av’s supervision, defended his proposal for his Ph.D. thesis entitled ‘‘The Separation of Optical Enantiomers by GC on Optical Active Stationary Phases,’’ the experienced committee advised him, in a fatherly manner, to choose another subject. In fact, the group established a model for chiral discrimination that is valid to date: ‘‘There should be a special correlation between the solvent and the solute in order to establish a difference in the behavior of the enantiomers and to separate them in the GC column: (a) strong interactions such as p-p interactions, [coordinate-covalent] bonds, hydrogen bonds, etc., to yield short-lived diastereomers; (b) close proximity of the bonds to the respective asymmetric carbons; (c) more than a single bond to prevent free rotation and to increase the interaction between the adjacent solvent-solute molecules, while the two respective asymmetric carbons are brought to proximity; (d) minimize the non-contributing associative forms which do not bring the respective asymmetric centers to proximity.’’ Despite the quite elaborate model, the first trials were unsuccessful. However, the scientific stubbornness that was characteristic of Gil-Av’s group led to the seminal paper authored in 1966 by E. Gil-Av, B. Feibush, and Rosita Charles reporting the first successful direct enantiomeric separation. The astonishment in the scientific community was quite high. In fact, the difficulty of this task was immediately inferred by A.J.P. Martin (in a letter to Gil-Av) who, upon learning of the first direct gas chromatographic separation of enantiomers performed by Gil-Av’s group wrote: ‘‘As you no doubt know, I had not expected such attempts to lead to much success, believing that the substrate-solvent association would normally be too loose to distinguish between enantiomers.’’ This topic, which for many was an untouchable problem, a prohibited field, was now a new technique, capable of resolving an enormous number of unanswered questions. In fact this discovery laid the foundation for significant advances in many fields, particularly in the life sciences and the pharmaceutical industry. The emerging focus on the separation of enantiomers attracted many scientists from abroad to learn and collaborate with Gil-Av. Thus, Wolker Schurig from Tubingen University (Germany) and Frank Mikes (Czechoslovakia) did extensive work in Gil-Av’s group on chiral organometallic complexes and their implications for enantiomeric separa-

tion. The developments in the field of HPLC led Frank Mikes, who got his Ph.D. degree under Gil-Av’s supervision, to report, in 1973, the first separation using a charge transfer mechanism. Many major contributions in the field of separation of enantiomers have Gil-Av’s name linked to them. Thus, separation of helicene enantiomers by HPLC on TAPA (with F. Mikes and G. Boshart) and riboflavin (with Y.H. Kim), recognition of the principle of reciprocity in enantiomeric separation, the use of chiral eluants in HPLC (with P.E. Hare and S. Weinstein), the discovery of a temperature-dependent reversal of enantioselectivity via enthalpy-entropy compensation (with K. Watabe and R. Charles), and the observation of enantiomer enrichment by self-amplification of optical activity during chromatography on achiral stationary phases (with R. Charles) are just a few of his remarkable contributions. In recognition of his pioneering work he received the Bergmann Prize in Chemistry in 1977 and the Tswett Medal of the USSR Academy of Science in 1980. For his contribution to the field of chiral separation he was the first recipient of the Gold Chirality Medal awarded to him in 1991 at the Third International Symposium on Chiral Discrimination. Besides being a distinguished scientist, Emanuel Gil-Av was a humanist. Along with chemistry, he could discuss music, painting, and the other arts with the same confidence and knowledge. When I arrived in his group he had already retired, being a Professor Emeritus at the Weizmann Institute. In fact he never retired. He worked up until the last days of his life, when he was hampered by a difficult illness that claimed his life on March 24, 1996. In fact his last paper, which appeared post-mortem and was published in the Journal of Physical Chemistry, was accepted without changes and questions from reviewers. This issue of Chirality tries to bring homage to Professor Gil-Av through all the contributors, each of whom is at the forefront in the field of chiral recognition. Their contributions are a testament to his legacy, which will live forever through his former students, postdocs, and colleagues, who will value and remember the life of Emanuel Gil-Av (Zichrono L’vrecha—may his memory be for a blessing). Nelu Grinberg, Ph.D. Research Fellow Merck Research Laboratories Rahway, NJ 07065-0914