Special Issue: Chiral Separation, in Dedication to Professor Emanuel Gil‐Av
2016-09-29

Distinguished chemistry Professor Emanuel Gil-Av (1916–1996) was a pioneer of chiral chromatographic analysis. His seminal research in the emerging area of supramolecular chiral recognition between chiral selectands and chiral selectors was performed in Israel at the Weizmann Institute of Science (Figure 1). The year 1966 marks the fiftieth anniversary of the first quantitative, and fully reproducible, separation of enantiomers on a non-racemic chiral stationary phase (CSP) by gas chromatography (GC) reported by Emanuel Gil-Av, Binyamin Feibush and Rosita Charles-Sigler. Gil-Av's group later extended their work to chiral liquid chromatography (LC) and chiral thin-layer chromatography (TLC). Contemporaries initially considered their research as a challenging academic curiosity, but soon it became an essential enantioseparation technique to determine enantiomeric compositions. Industry, as well as the academic world, soon realized the importance of chiral analytical methods in a number of different areas, including stereochemistry, asymmetric synthesis, agricultural and medicinal chemistry, and in pharmaceutical R&D and manufacturing. Adina, Rona and Volker Schurig, Emanuel Gil-Av, Nelu Grinberg at the Weizmann Institute of Science in 1983. The awareness of different pharmacokinetic and pharmacodynamic properties of enantiomeric pharmaceuticals prompted health organizations and drug regulatory organizations around the world to specify the marketing of only the beneficial single-handed drug molecule (the eutomer). Racemic drugs of the past then underwent a ‘racemic switch' to redevelop a single enantiomeric species. Concurrently with manufacturing progress to produce drugs of only one handedness, reliable and sensitive enantioselective analytical techniques (of which Gil-Av's methods were the first) had to be developed for their identification, detection and quantification, while treating the undesirable enantiomer (the distomer) as an impurity. The global market of chiral technology is above 1 billion in 2016. Following Gil-Av's invention in 1966, the ChirBase data bank reported more than 200,000 enantiomeric separations on over 1,800 CSPs by chiral LC in 2016. 8,000 enantioseparations of chiral analytes by GC were described in 3,000 publications until 1996. The above mentioned triple dates of 1916, 1966 and 1996 prompted us to honor this eminent scientist at the centenary of his birth by dedicating a special issue of the Israel Journal of Chemistry to his memory. Motivated by his legacy, eighteen international scholars participated in a comprehensive effort that encompasses various aspects of chirality. The scope of the subjects in this special issue is quite broad. Many are the direct outcome of inspiration by Emanuel Gil-Av's pioneering work. Others are farther afield and were contributed by scientists who wanted to honor his memory. The special issue devoted to Emanuel Gil-Av contains reviews on the enantiomeric analysis of chiral flavors, fragrances and of atropisomeric polychlorinated biphenyls (PCBs) by enantioselective GC, as well as the trace analysis of d-amino acids by enantioselective LC. Miniaturization of enantiomeric analysis by chiral microfluidic techniques employing capillary electrophoresis (CE), capillary electrochromatography (CEC) and capillary/nano-liquid chromatography (CLC/nano-LC) is described. The chromatographic elution profiles of interconverting enantiomers featuring plateau formation and affording kinetic data of enantiomerization are treated in this issue. The use of chiral metal coordination compounds for the separation of enantiomers by complexation chromatography, started by Gil-Av as an alternative tool for the use of amino acid derived CSPs, is reviewed. Emanuel Gil-Av and Rosita Charles belong to the first researchers who observed enantiomeric fractionation of non-racemic mixtures in an achiral chromatographic environment. Two contributions in this issue deal with the phenomenon of chromatographic self-discrimination of enantiomers (SDE). The heterodipeptide formation from l-amino acids is studied by scanning electron spectroscopy (SEM). The universality of symmetry, the antithesis of chirality, and how it is differently emphasized in many branches of science is reviewed. The temperature effect upon the distortion of highly symmetrical molecules has been studied by continuous symmetry measures (CSM) and is explained. In contrast, symmetry-breaking as the signature and precondition of life on Earth and the consequent search for non-racemic molecules in extraterrestrial environments (Meteorites, Rosetta-mission, Exo-Mars) by enantioselective GC is discussed. These endeavors follow up first trials in this area by Gil-Av et al. in the 1970s at NASA. The origin of terrestrial homochirality by super-high-velocity meteorite impact is hypothesized. The adsorption of achiral and chiral sulfur-containing molecules upon a gold icosahedral nanocluster is accompanied by a loss of inversion symmetry. The continuous symmetry measure (CSM) was employed to quantify the resulting distortion from centro-symmetry of the cluster-molecule complex and its magnitude was correlated to hyperpolarizability, a phenomenon of potential relevance to non-linear optics. Interestingly, dwelling on the evolution of chirality science over the last 50 years, one reviewer remarked, “It started with chiral GC and LC chromatography, followed by chiral bioorganic chemistry, chirality in lower organisms and their means of communication by chiral pheromones, chiral pharmacology and medicine, asymmetric synthesis and solid state chirality. Next great steps will be Chiral Physics: chirality of atoms, electronic systems and primary particles, chiral combinations of physical fields and their interaction with molecules and then with living matter, chirality of spin isomers of molecules by starting with water, chirality of star ensembles, chirality in information storage and communication and many others.” A contribution emerging from the Department of Chemical Physics of the Weizmann Institute of Science touches novel challenges in Chiral Physics. The direct determination of absolute configuration by Coulomb-explosion-imaging, first conceived by Emanuel Gil-Av and Zeev Vager at the Weizmann Institute, is also reported. The comprehensive list of references in all contributions of this special issue devoted to Emanuel Gil-Av provides an invaluable source of information for experts in the field and for newcomers entering the fascinating topic of stereochemistry alike. The present compendium contains a summary of established results compiled by experts in the area. But also new ideas opening new horizons and unexpected findings are treated in the hope that this will stir discussion and stimulate further endeavors in the spirit of Gil-Av's approach to innovative science. Volker Schurig Robert Glaser University of Tübingen Ben-Gurion University of the Negev Guest Editor Guest Editor