Molecules Tip Their Hands

16.01.2014

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  (l-r) Profs. Zeev Vager and Dirk Schwalm and Dr. Oded Heber
     

 

 
 
To understand the new finding arising from a recent collaboration between scientists at the Weizmann Institute and researchers in Germany, one must go back in time. First, one needs to go back to 1847, the year Louis Pasteur discovered that tartaric acid crystals come in two different forms – mirror images that, like hands, appear in “left” and “right” versions that cannot be superimposed on one another. Those molecules – known as chiral molecules – presaged a headache for drug manufacturers and the chemical industry in general, who soon found that the right- and left-handed forms could react very differently, especially in drug compounds. While researchers working in the field of stereochemistry, which deals specifically with the chemistry of chiral molecules, have made some progress in purifying compounds to contain just one form or the other, separating the two remains a problem in many cases.

Next, one needs to look back some 30 years, to the work being done in a Weizmann Institute lab. That’s when Prof. Zeev Vager of the then Nuclear Physics Department, together with the Institute’s Prof. Ron Naaman and researchers from the Argonne National Laboratory, Illinois, developed an innovative method of imaging molecules. Called Coulomb explosion imaging, it consists of accelerating molecular ions to a significant fraction of the velocity of light and shooting them onto a very thin sheet of carbon. As the molecules speed through this foil, their electrons are stripped away while the positively charged nuclei spread out in formation as they race toward a detector. The detector not only records the landing points of the nuclei but also times their touchdown, presenting a magnified, accurate, three-dimensional image of the molecule.

Vager continued to work on the Coulomb explosion technique for many years; he and Prof. Daniel Zajfman introduced it to the Max Planck Institute for Nuclear Physics in Heidelberg, Germany, while Vager was on a sabbatical in the mid-1990s. While the method proved most effective for imaging very small molecules, Vager at some point thought it could also be used for identifying left- and right-handed chiral molecules, even though they tend to be larger and more complex. As he was searching for a feasible chiral species, another Weizmann Institute scientist, the late Prof. Emanuel Gil-Av, whose research dealt with various aspects of chirality, suggested a molecule called oxirane as a test object. Vager discussed this proposal with Prof. Volker Schurig (a former postdoc of Gil-Av’s) and with one of Schurig’s students, Oliver Trapp, at the Institute for Organic Chemistry of the University of Tübingen. Though the molecule was borderline as far as the Coulomb explosion technique was concerned, a more serious obstacle was the difficulty in producing the relatively large amounts of chiral oxirane (up to a gram) needed for these experiments. Thus the intriguing prospect of being the first to determine the spatial structure of a chiral molecule in its gas phase had to be put on ice.  
 
Coulomb explosion method
 
 
Fast forward to this past year: A group of physicists and chemists from the Weizmann Institute and Germany finally managed to systematically overcome the various hurdles to imaging chiral oxirane molecules with the Coulomb explosion method. Oliver Trapp, now a professor at the Institute of Organic Chemistry at Heidelberg University, together with his PhD student Kersten Zawatzky and his former mentor Schurig, devised and succeeded in carrying out a sophisticated, multi-step process to synthesize grams of isotope-labeled oxirane with a well-defined chirality. Dr. Holger Kreckel of the Max Planck Institute for Nuclear Physics and his PhD student Philipp Herwig, together with his institute colleagues Prof. Dr. Dirk Schwalm (see below) and Prof. Dr. Andreas Wolf, as well as Vager and Dr. Oded Heber of the Weizmann institute, rejuvenated and modified the Coulomb explosion imaging setup at the Max Planck Institute to cope with the special requirements imposed on the detection system by the atomic break-up products of oxirane. After several test runs with non-chiral oxirane molecules, the team could finally perform the imaging measurements with chiral oxirane; its handedness was kept secret by the chemists until the final analyses of the experiment had been performed by the physicists. “Fortunately,” jokes Vager, “we got the right answer.”
 
The results appeared recently in Science. This was the first time that the spatial structure of isolated chiral molecules could be directly imaged. The method could prove highly useful to researchers and drug developers who need to unambiguously determine the handedness of their compounds.
 

Back to his roots

 
 
Prof. Dirk Schwalm
 
“I agreed to come to the Weizmann Institute for a year,” says Prof. Dirk Schwalm, “and I have already been here for seven.” Schwalm is a former director of the Max Planck Institute for Nuclear Physics in Heidelberg, Germany, where he worked on the ion storage ring – an evacuated tube about 56 m in circumference used for physics experiments. Among other things, this ring enables scientists to mimic atomic and molecular processes that occur in the emptiest stretches of outer space. That facility is what drew the Weizmann Institute’s Prof. Daniel Zajfman, a physicist who researches these processes, to frequently visit the Max Planck Institute.
 
In 2005, when Schwalm retired, Zajfman took over the directorship, spending part of his time in Heidelberg and part in his Weizmann Institute lab. But the next year, when Zajfman was appointed President of the Weizmann Institute, he resigned his position at the Max Planck Institute. He did not, however, give up his friendship with Schwalm and, indeed asked Schwalm to join the Weizmann Institute as a visiting scientist. Schwalm now spends more than half of each year helping lead Zajfman’s research group, thus enabling Prof. Zajfman to invest more time and energy in his presidential duties.
 
Schwalm says that he is very happy to be at the Weizmann Institute. He especially enjoys the fact that the experimental tools and the research groups are comparatively small, which enables him to get involved again in hands-on physics. “I have the chance to know every screw in the equipment,” he says. “This is a fantastic opportunity to go back to my ‘physics roots.’”
 

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