Name: coulomb explosion imaging as a tool to distinguish between stereoisomers
Uploaded: 2017-08-18T15:00:00
Description: Watch this Scientific Journal Video about Coulomb Explosion Imaging as a Tool to Distinguish Between Stereoisomers at JoVE.com

We thank Robert Berger (Philipps-Universit&#228;t Marburg, Germany) for inspiring discussions about the interpretation of our data and molecular chirality in general. We are grateful to Julia Kiedrowski, Alexander Schie&#223;er and Michael Reggelin from TU Darmstadt (Germany), as well as Benjamin Spenger, Manuel Mazenauer and J&#252;rgen Stohner from ZHAW W&#228;denswil (Switzerland) for providing the sample.
The project was supported by the Hessen State Initiative for Scientific and Economic Excellence under the focus ELCH (Electron dynamics of chiral systems) and the Federal Ministry of Education and Research (BMBF). MS acknowledges financial support by the Adolf Messer foundation.

Caution: Make sure to be familiar with all possible hazards connected with the experiment and in the laboratory. The procedure below includes class-IV lasers, high voltage and vacuum. Consult the material safety data sheet (MSDS) for the species to be investigated.

1. Preparation
<ol>
	<li>Preparatory considerations 
	NOTE: Before the actual experiment starts, two main choices have to be made; the first regarding the possible species under investigations...

<ol>
	<li>G&#252;bitz, G., Schmid, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chiral+Separation+by+Chromatographic+and+Electromigration+Techniques.+A+Review.">Chiral Separation by Chromatographic and Electromigration Techniques. A Review.</a> Biopharm. Drug Disposition. 22, 291-336 (2001).</li><li>Berova, N., Polaravapu, P. L., Nakanishi, K., Woody, R. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Comprehensive Chiroptical Spectroscopy. , (2012).</li><li>Bijvoet, J. M., Peerdeman, A. F., van Bommel, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+the+Absolute+Configuration+of+Optically+Active+Compounds+by+means+of+X-rays.">Determination of the Absolute Configuration of Optically Active Compounds by means of X-rays.</a> Nature. 168 (4268), 271-272 (1951).</li><li>Pitzer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+Determination+of+Absolute+Molecular+Stereochemistry+in+Gas+Phase+by+Coulomb+Explosion+Imaging.">Direct Determination of Absolute Molecular Stereochemistry in Gas Phase by Coulomb Explosion Imaging.</a> Science. 341 (6150), 1096-1100 (2013).</li><li>Pitzer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Absolute+Configuration+from+Different+Multifragmentation+Pathways+in+Light-Induced+Coulomb+Explosion+Imaging.">Absolute Configuration from Different Multifragmentation Pathways in Light-Induced Coulomb Explosion Imaging.</a> Chem Phys Chem. 17 (16), 2465-2472 (2016).</li><li>Vager, Z., Naaman, R., Kanter, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coulomb+Explosion+Imaging+of+small+molecules.">Coulomb Explosion Imaging of small molecules.</a> Science. 244 (4903), 426-431 (1989).</li><li>Herwig, P. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+the+Absolute+Configuration+of+a+Chiral+Epoxide+in+the+Gas+Phase.">Imaging the Absolute Configuration of a Chiral Epoxide in the Gas Phase.</a> Science. 342 (6162), 1084-1186 (2013).</li><li>D&#246;rner, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cold+Target+Recoil+Ion+Momentum+Spectroscopy:+a+'momentum+microscope'+to+view+atomic+collision+dynamics.">Cold Target Recoil Ion Momentum Spectroscopy: a 'momentum microscope' to view atomic collision dynamics.</a> Physics Reports. 330, 95-192 (2000).</li><li>Ullrich, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recoil-ion+and+electron+momentum+spectroscopy:+reaction-microscopes.">Recoil-ion and electron momentum spectroscopy: reaction-microscopes.</a> Rep. Prog. Phys. 66 (9), 1463-1545 (2003).</li><li>Jagutzki, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+Hit+Readout+of+a+Microchannel+Plate+Detector+With+a+Three-Layer+Delay-Line+Anode.">Multiple Hit Readout of a Microchannel Plate Detector With a Three-Layer Delay-Line Anode.</a> IEEE Trans Nucl Sci. 49 (5), 2477-2483 (2002).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> RoentDek GmbH MCP Delay Line Detector Manual. , (2017).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> RoentDek GmbH The RoentDek Constant Fraction Discriminators CFD8c, CFD7x, CFD4c, CFD1c and CFD1x. , (2017).</li><li>Zeller, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+the+He2+quantum+halo+state+using+a+free+electron+laser.">Imaging the He2 quantum halo state using a free electron laser.</a> PNAS. 113 (51), 14651-14655 (2016).</li><li>Pitzer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereochemical+configuration+and+selective+excitation+of+the+chiral+molecule+halothane.">Stereochemical configuration and selective excitation of the chiral molecule halothane.</a> J. Phys. B.: At. Mol. Opt. Phys. 49 (23), 234001 (2016).</li><li>Hine, J., Dowell, A. M., Singley, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carbon+Dihalides+as+Intermediates+in+the+Basic+Hydrolysis+of+Haloforms:+IV+Relative+Reactivities+of+Haloforms.">Carbon Dihalides as Intermediates in the Basic Hydrolysis of Haloforms: IV Relative Reactivities of Haloforms.</a> J. Am. Soc. Chem. 78, 479-482 (1956).</li><li>Wales, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+coincidence+detection+algorithm+for+improving+detection+rates+in+coulomb+explosion+imaging.">A coincidence detection algorithm for improving detection rates in coulomb explosion imaging.</a> Nucl. Instr. Meth. in Phys. Res. A. 667, 11-15 (2012).</li><li>Kastirke, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Konstruktion und Aufbau einer UHV-tauglichen COLTRIMS-Kammer. , (2014).</li><li>Calegari, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Charge+migration+induced+by+attosecond+pulses+in+bio-relevant+molecules.">Charge migration induced by attosecond pulses in bio-relevant molecules.</a> J. Phys. B.: At. Mol. Opt. Phys. 49 (14), 142001 (2016).</li><li>Gaie-Levrel, F., Garcia, G. A., Schwell, M., Nahon, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=VUV+state-selected+photoionization+of+thermally-desorbed+biomolecules+by+coupling+an+aerosol+source+to+an+imaging+photoelectron/photoion+coincidence+spectrometer:+case+of+the+amino+acids+tryptophan+and+phenylalanine.">VUV state-selected photoionization of thermally-desorbed biomolecules by coupling an aerosol source to an imaging photoelectron/photoion coincidence spectrometer: case of the amino acids tryptophan and phenylalanine.</a> Phys. Chem. Chem. Phys. 13, 7024-7036 (2010).</li><li>Ablikim, U., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+absolute+geometries+of+cis+and+trans+molecular+isomers+by+Coulomb+Explosion+Imaging.">Identification of absolute geometries of cis and trans molecular isomers by Coulomb Explosion Imaging.</a> Sci. Rep. 6, 38202 (2016).</li></ol>

Due to the variety of components, a COLTRIMS setup requires a rather high level of technical expertise, especially in the areas of vacuum technique, particle detection, fast electronics and data analysis. Before turning to the investigation of complex species, it should thus be thoroughly checked if the setup is running properly, e.g. by performing and analyzing a measurement on a diatomic or triatomic species.
Optimizing the intensity and duration of the laser pulses and the overlap ...

Chirality is a feature of our nature that has been fascinating researchers for more than 150 years. In the 19th century, Pasteur, van&#39;t Hoff and others discovered that molecules can occur in two mirror image structures that are not super-imposable - like our left and right hands. This property was termed &#39;chiral&#39;, from the Greek word for &#39;hand&#39;.
So far, no difference in thermodynamic properties or in energy levels of left- and right-handed forms (the two &#39;enantiomers&#39;) has been found. In order to analyze the handedness of a given sample and to separate the enantiomers, interaction with other chiral molecules can be used, as is for example done in various chromatographical approaches.1 Chiroptical methods such as (vibrational) circular dichroism, (V)CD, and optical rotatory dispersion, ORD, are routinely employed to distinguish between enantiomers.2
When it comes to the determination of the microscopic structure, these techniques require additional information, e.g. from quantum-chemical calculations. The only technique that is widely accepted to directly determine the absolute configuration is anomalous X-ray diffraction.3
It has recently been shown that the absolute configuration of simple chiral species can be determined by Coulomb Explosion Imaging.4,5 In this approach, molecules in the gas phase are multiply ionized so that the remaining cores strongly repel each other. This repulsion leads to fast fragmentation (&#39;explosion&#39;) of the molecules. The direction and the magnitude of the fragment momenta correlate to the structure of the molecule &#8211; for small molecules, the momentum directions correspond surprisingly well to the bond axes. Coulomb Explosion for molecular structure determination has been pioneered using molecular ion beams from an accelerator.6 This beam foil technique has recently also been applied for chiral recognition.7
Contrary to anomalous X-ray diffraction, the sample must not be crystalline but provided in the gas phase. This makes the Coulomb Explosion approach ideal for volatile species and thus complementary to X-ray diffraction. In certain cases, the handedness can even be determined for individual molecules.
In practice, the exact reconstruction of the molecular structure has proven difficult even for methane derivatives, e.g. molecules with a central carbon and different substituents. This is attributed to the fact that the interaction between the fragments is not exactly Coulombic and that not all bonds break simultaneously. In order to obtain stereochemical information, especially to distinguish between enantiomers, this reconstruction is fortunately not necessary. Instead, the momentum vectors of different fragments can be correlated to yield a quantity that is distinct for the left- and right-handed molecules. To get reliable results, at least four fragment momenta have to be recorded.
In order to measure this momentum information, the fragments from one &#8211; and only one &#8211; molecular break-up have to be detected in a single measurement step. This condition is usually referred to as &#39;coincident detection&#39;. In addition, the emission directions have to be analyzed, which amounts in practice to record the time and the position of the fragment impact in a list-mode data format.
In atomic and molecular physics, techniques have been developed that implement this approach of measurement by employing electrostatic spectrometers for mass separation and time- and position-sensitive multi-hit detectors. The most prominent example is the COLTRIMS (Cold Target Recoil Ion Momentum Spectroscopy) setup &#8211; also known as Reaction Microscope.8,9 A sketch for this kind of experiment is given in Figure 1. Contrary to a standard COLTRIMS that can record electrons as well, Coulomb Explosion Imaging requires only the ion detector.
Spectrometer and detector are mounted under ultra-high vacuum (&#60;1 x 10-9 hPa) to avoid creation of ions from residual gas. Single molecules of the sample are provided via a gaseous free molecular jet created by supersonic expansion: By virtue of the vapor pressure, the molecules expand through a small nozzle (around 50 &#181;m diameter) into the vacuum. This part of the experiment, the source chamber, is separated from the interaction region by usually two skimmers and differentially pumped stages. An additional differentially pumped section is located behind the interaction region to dump the gas jet and thus avoid background gas in the interaction region.
The ionizing radiation intersects with the molecular jet under 90&#176;. Most laboratories nowadays use femtosecond laser pulses, although synchrotron radiation, fast ions or electron impact are possible &#39;projectiles&#39; to induce Coulomb Explosion.
The following protocol makes the assumption that a running setup for coincident imaging of ions and a femtosecond laser are available in the lab. The peak intensity needed to induce Coulomb Explosion into four or even five fragments must be on the order of 6 x 1014 W/cm2. To avoid exceedingly long measurements, the repetition rate of the laser should be 10 kHz or more. This is crucial because, on the one hand, coincident detection can only be ascertained if the probability for fragmentation in the laser focus is significantly below 1 per laser pulse (ideally not more than 10%). The total fragmentation rate, on the other hand, should not be lower than a few kHz because the share of relevant multifragmentation pathways is usually less than 10-4. As encouraging fact, it should be mentioned that in principle already a single fragmentation event is sufficient to identify the configuration of an enantiopure sample, and that detection of a few hundred allows to determine the abundance of the enantiomers in a sample of unknown enantiomeric composition.

<table border="0" cellpadding="0" cellspacing="0" width="599">
	<tbody>
		<tr height="31">
			<td height="31" style="height:31px;width:179px;">CHBrCl2</td>
			<td style="width:93px;">SigmaAldrich</td>
			<td style="width:147px;">139181-10G</td>
			<td style="width:180px;">or other suitable sample</td>
		</tr>
		<tr height="31">
			<td height="31" style="height:31px;width:179px;">femtosecond laser system</td>
			<td>KMLabs</td>
			<td style="width:147px;">Wyvern500</td>
			<td style="width:180px;"></td>
		</tr>
		<tr height="31">
			<td height="31" style="height:31px;width:179px;">High-reflective mirrors</td>
			<td>EKSMA</td>
			<td style="width:147px;">042-0800</td>
			<td style="width:180px;"></td>
		</tr>
		<tr height="31">
			<td height="31" style="height:31px;width:179px;">mirror mounts</td>
			<td>Newport</td>
			<td style="width:147px;">U100-A-LH-2K&#160;&#160;</td>
			<td style="width:180px;"></td>
		</tr>
		<tr height="35">
			<td height="35" style="height:35px;width:179px;">focusing mirror (protected silver, f = 75 mm)</td>
			<td>Thorlabs&#160;</td>
			<td style="width:147px;">CM254-075-P01</td>
			<td style="width:180px;">(if available: f = 60 mm)</td>
		</tr>
		<tr height="51">
			<td height="51" style="height:51px;width:179px;">COLTRIMS spectrometer, including electronics and data acquisition system</td>
			<td>RoentDek</td>
			<td style="width:147px;">custom</td>
			<td style="width:180px;">contrary to the standard COLTRIMS, only one detector is needed</td>
		</tr>
	</tbody>
</table>

coulomb explosion imaging as a tool to distinguish between stereoisomers

This article shows how the COLTRIMS (Cold Target Recoil Ion Momentum Spectroscopy) or the "reaction microscope" technique can be used to distinguish between enantiomers (stereoisomers) of simple chiral species on the level of individual molecules. In this approach, a gaseous molecular jet of the sample expands into a vacuum chamber and intersects with femtosecond (fs) laser pulses. The high intensity of the pulses leads to fast multiple ionization, igniting a so-called Coulomb Explosion that produces several cationic (positively charged) fragments. An electrostatic field guides these cations onto time- and position-sensitive detectors. Similar to a time-of-flight mass spectrometer, the arrival time of each ion yields information on its mass. As a surplus, the electrostatic field is adjusted in a way that the emission direction and the kinetic energy after fragmentation lead to variations in the time-of-flight and in the impact position on the detector.
Each ion impact creates an electronic signal in the detector; this signal is treated by high-frequency electronics and recorded event by event by a computer. The registered data correspond to the impact times and positions. With these data, the energy and the emission direction of each fragment can be calculated. These values are related to structural properties of the molecule under investigation, i.e. to the bond lengths and relative positions of the atoms, allowing to determine molecule by molecule the handedness of simple chiral species and other isomeric features.

In this part, we show results obtained for halomethanes. These species are ideal for proof-of-principle experiments due to their simplicity and high vapor pressure. In the meantime, the more complex species halothane has been investigated using single soft-x-ray photons from a synchrotron source to induce multiple ionization.14
CHBrClF
Bromochlo...

Watch this Scientific Journal Video about Coulomb Explosion Imaging as a Tool to Distinguish Between Stereoisomers at JoVE.com

Coulomb Explosion Imaging as a Tool to Distinguish Between Stereoisomers

For small chiral species, Coulomb Explosion Imaging provides a new approach to determine the handedness of individual molecules.

This article shows how the COLTRIMS (Cold Target Recoil Ion Momentum Spectroscopy) or the "reaction microscope" technique can be used to distinguish ...

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Transition Metals and Coordination Complexes

Stereoisomerism

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