Albin's sequential transfer, how it works

Coulomb Explosion Imaging as a tool to distinguish between stereoisomers

Summary

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

Abstract

This article shows how the COLTRIMS (Cold Target Recoil Ion Momentum Spectroscopy) or the "Reaction Microscope" technique can be used to distinguish enantiomers (stereoisomers) of simple chiral species at the individual molecule level. In this approach, a gaseous molecular jet expands the sample into a vacuum chamber and cuts femtoseconds (fs) with laser pulses. The high intensity of the pulses leads to multiple ionizations too quickly, igniting a so-called Coulomb explosion that produces multiple cationic (positively charged) fragments. An electrostatic field carries these cations to time-critical and position detectors. Similar to a time-of-flight mass spectrometer, the arrival time of each ion provides information about its mass. An excess of the electrostatic field is set in such a way that the radiation direction and the kinetic energy after fragmentation lead to variations in the time-of-flight and effects on the detector.

Each ion impact creates an electronic signal in the detector; This signal is handled by high-frequency electronics and recorded by a computer through an event. The stored data correspond to the impact times and positions. With this data, the energy and the direction of radiation of each fragment can be calculated. These values ​​relate to the structural properties of the molecule determined; H. on the bond lengths and relative positions of atoms, molecule by molecule, determine the handedness of simple chiral species and allow other isomeric functions.

Introduction

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Chirality is a part of our nature that has been fascinating researchers for more than 150 years. In the 19thth Century, Pasteur and van't Hoff discovered that molecules can appear in two mirror-image structures that are not super-integrative - like our left and right hands. This property was called "chiral", from the Greek word for "hand".

So far, no difference in thermodynamic properties or energy levels of the left and right-handed forms (the two "enantiomers") has been found. To analyze the handedness of a sample and separate the enantiomers, interaction with other chiral molecules can be used, such as in various chromatographical approaches. 1 Chiroptical methods such as (vibrational) circular dichroism, (V) CD, and optic rotatory dispersion, ORD, are routinely used to distinguish enantiomers. 2

When it comes to determining the microscopic structure, these techniques require additional information, e.g. B. of quantum physical calculations. The only technique that is generally accepted to directly determine the absolute configuration is anomalous X-ray diffraction. 3

Recently it has been shown that the absolute configuration can be determined easily by chiral species by Coulomb explosion imaging. 4,5 In this approach molecules in the gas phase are multiplying ionized so that the remaining nuclei strongly repel one another. This repulsion leads to rapid fragmentation ("explosion") of the molecules. The direction and extent of the momenta fragment correlate to the structure of the molecule - for small molecules, the dynamics directions correspond surprisingly well to the bond axes. Coulomb explosion for molecular structure determination has been pioneered with molecular ion beams from an access key. 6 this beam-slide technique has also recently applied for chiral recognition. 7

Contrary to the anomalous X-ray diffractometry, the sample does not have to be crystalline but 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 also be determined for individual molecules.

In practice, the exact reconstruction of the molecular structure even for methane derivatives, z. B. Molecules with a central carbon and different substituents proved difficult. This is due to the fact that the interaction between the fragments is not exactly Coulomb and at the same time does not break all bonds. Fortunately, this reconstruction is not necessary in order to provide stereochemical information, especially to differentiate between enantiomers. Instead, the dynamics vectors can be correlated from different fragments to deliver an amount that differs for the left and right-handed molecules. To obtain reliable results, at least four fragment momenta must be recorded.

In order to measure this dynamic information, the fragments from one - and only - molecular decay must be recognized in a single measurement step. This condition is usually referred to as "coincident detection". In addition, the emission directions have to be analyzed, the amounts in practice affecting the recording of the time and position of the fragment in a list-mode data format.

Atomic and molecular physics have developed techniques implementing this approach of measurement through the use of electrostatic spectrometers for mass separation and time-sensitive and position multi-hit detectors. The most prominent example is the COLTRIMS (Cold Target Recoil Ion Momentum Spectroscopy) setup - also known as the reaction microscope. 8,9 a sketch for such an experiment is in illustration 1listed. Unlike a standard COLTRIMS, which can record electrons as well, the Coulomb Explosion Imaging only requires the ion detector.

Spectrometer and detector are mounted in an ultra-high vacuum (<1 x 10-9 hPa) to avoid the creation of ions from residual gas. Individual molecules of the sample are provided via a gaseous molecular free jet created by supersonic expansion: due to the vapor pressure, the molecules expand through a small nozzle (around 50 µm in diameter) into the vacuum. This part of the experiment, the source chamber, is separated from the interaction region by typically two skimmers and differentially pumped phases. An additional differentially pumped section is located behind the interaction region to dump the gas jet and thus avoid background gas in the interaction area.

The ionizing radiation overlaps with the molecular jet under 90 °. Most laboratories nowadays use femtosecond laser pulses, although synchrotron radiation, fast ion or electron effects are possible to induce "projectiles" Coulomb explosions.

The following protocol makes the assumption that an ongoing setup for the congruent imaging of ions and a femtosecond laser are available in the laboratory. The peak intensity required to induce Coulomb explosion in four or even five fragments must be on the order of 6 x 1014 W / cm2. To avoid extremely 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 determined if the probability that fragmentation in the laser focus is well 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 proportion of relevant multifragmentation paths is usually less than 10-4. So encouraging fact, it should be mentioned that in principle a single fragmentation event is sufficient to identify the configuration of an enantiopure sample, and the detection of a few hundred allows to determine the abundance of enantiomers in a sample of enantiomers unknown composition.

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Protocol

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Caution: Be sure to be familiar with all possible hazards associated with the experiment and in the laboratory. The following procedure includes Class IV lasers, high voltage, and vacuum. Consult the Material Safety Data Sheet (MSDS) for the species being examined.

1. Preparation

  1. preparatory considerations
    Note: before the actual experiment begins, two important decisions must be made; the first about the possible types under examinations and the second the electric field in the spectrometer. It is assumed that the setup has previously been used for other experiments and that the spectrometer itself will not be modified.
      1. Sample Choice of a sample where fragmentation ways can be expected, the signature of the handedness or the structural feature to be examined. Remember that hydrogen atoms are often released as neutral fragments; functional groups that differ only by the number of hydrogen atoms probably cannot be distinguished. Start with simple (maybe achiral) types like trihalomethanes or haloethanes.
      2. Check that there is at least 0.02 moles of the sample, as this is the minimum amount used in successful experiments so far
      3. Check whether sufficient vapor pressure can be achieved with the sample. Depending on the design of the device, steam pressure> 5 hPa are necessary for a sufficient density of the jet for laser experiments. If the vapor pressure is significantly lower, check whether the required vapor pressure can be achieved by heating the sample material. This can be done for liquid and solid samples by sublimation for the latter. If heating is needed, it is necessary to have a positive temperature gradient along the path of the gas in the system (with the nozzle being the hottest part) to avoid condensation. Advanced preparation of sampling plans such as collection by a carrier gas may be considered.
    1. Choice of electric field strength in the spectrometer
      Note: a value of 50 to 100 V / cm has proven to be reasonable since Coulomb Explosion Imaging. The optimal value, however, depends on the geometry of the spectrometer. The following steps show how to optimize the electric field strength.
      1. Estimation of the flight time of the expected cationic fragments. The spectrometer consists only of a homogeneous field region with length s and electric field strength E., Mean time-of-flight of a particle with mass m and charge Q just go through
        < img="" alt="formula 1" src="/ Files/ftp_upload/56062/56062eq1.jpg">
      2. appreciate the spread X from the fragment cations with mass m on the detector with the time-of-flightt calculated above and the formula
        < img="" alt="Equation 2" src="/files/ ftp_upload/56062/56062eq2.jpg">
        Ions gain momentum pX of up to 400 atomic units of dynamics (protons up to 150 atomic units).
      3. When the spatial spread X of the lightest ion species larger than the detector radius increase the electric field strength in the calculation until the spread is a few millimeters smaller than the detector size. The electric field strength should not be much higher, this leads to a lower resolution for heavier fragments that are less distributed on the detector.
  2. Review of the experimental setup
    Note: before starting the actual measurement, it must be checked that the experimental setup is well prepared.
    1. Check that the vacuum in the interaction chamber is <1 x 10 -9 hPa. If this is not the case, the residual gas leads to a high rate. If in doubt about the vacuum conditions, go to step 2.2.1 where the ionization of the residual gas is determined. If the pressure is too high, do a leak check. If there is no leak, bake the chamber for a couple of days.
    2. Check the connections for the power supply and the detector signals according to the instructions or description to experiment.
    3. Check that the data acquisition software on the measurement computer is able to acquire and analyze at least four ions. Make sure that the dead time of electronic assemblies and the pulse width of the signal are below 30 ns.
  3. Prepare sample delivery
    1. Check that the delivery sample tubes are clean and tightened. If the sample is corrosive (z. B. Sauer) ensure that all components in the system and the roughing pumps of the vacuum chamber are compatible with the selected sample. Pump the sample delivery system with a vacuum pump, open valves and make sure that the pressure in the experimental chamber does not increase.
    2. Clean and prepare the sample receiver. Ultrasonic bath with acetone or a standard laboratory glassware washer are sufficient.
    3. Prepare the heating of the reservoir and sample delivery system when the sample needs to be heated (see 1.1.1.3). The most convenient way is with adjustable heating circuits, each consisting of a heating wire, a temperature sensor and a temperature controller.
    4. Using the sample has a very low vapor pressure, whether it tends to form clusters (e.g. Acids), different approaches for collection or copropagation with inert gases. Modify the design of the gas pipes depending on these requirements.
    5. Check that the molecular jet is well aligned. For this purpose a noble gas sample (e.g. Argon) so that a tight jet can be achieved (about 1 bar absolute pressure should be sufficient for a 50 µm nozzle). Maximize the pressure in the Jet Dump section by moving the manipulator mounted on the nozzle.
  4. Offer femtosecond laser pulses
    Note: the ionizing pulses are provided by a femtosecond laser system. Describing such lasers and their uses in detail is beyond the scope of this protocol. If a commercial laser system is used, see the manual.
    1. Turn on the laser and check the laser beam profile on the output.
    2. Check and correct (if necessary) the beam path, the entrance window of the experiment by adjusting the respective mirror.
    3. If necessary, align the focusing mirror in the experimental chamber using the respective manipulator. Center the reflection of the focusing mirror in relation to the incoming beam.
    4. Insert filter or a rotatable polarizer in the beam path a peak intensity of about 6 x 10 14 W / cm 2 to reach. Use linear polarization for normal coulomb explosion imaging. If dichroism effects are to be studied, change the polarization of a quarter-wave plate just before the entrance window.
    5. Insert a photodiode in a place where there is a reliable replica of the laser pulse (z. B. a mirror image or the transmission through an axis mirror). Connect the output of the photodiode on an oscilloscope and make sure the diode produces clean pulses at the repetition rate of the laser.
    6. Always block the beam when not in use.

2. Switch on the spectrometer and detectors

Note: this part of the protocol slightly depends on the actual implementation of the spectrometer and detector. The description here is valid for a standard COLTRIMS setup with a hexagonal delay line detector (HEX75). 10 In this implementation a detector has 7 output channels: one for the microchannels plates (MCPs) and two for each of the three layers of the anode.

  1. Switch power supplies.
    1. Turn off vacuum pressure gauges in the interaction chamber as they could generate ions that can be seen by the detector.
    2. Connect the amplified signal output (with a fast amplifier with gain ≈ 100) of the MCP to a fast (preferably analog) oscilloscope. Set the oscilloscope to 5 or 10 ns per division on the time scale and 100 mV per division on the signal scale. Make sure the electronic noise is below 30 mV.
    3. Switch on the high voltage power supply for the detector. For a typical ion detector, the voltage is -2,000 V for the front and 300 V for the anode side. The voltage depends on the age of the MCPs and should be set so that the analog signals are maximal but do not saturate. Check the current one. It depends on the resistance of the MCPs in the detector but should not exceed 50 µA. On the oscilloscope track, a few signals per second with a signal level of several hundred mV should be visible ('dark graph').
    4. Tune the power supply for the spectrometer to the value established in step 1.1.2.
  2. Check detector signals by ionizing the residual gas
    Note: a detailed description of the start-up detector can also be found in the respective manuals. 11, 12
    1. attenuate the laser power to an estimated value below 10 14 W / cm 2 in focus. Unlock the laser and watch the oscilloscope trace. This leads to a rate of more than 5% of the laser repetition rate, the amount of residual gas in the chamber is too high or the laser beam is touching the spectrometer. Fix this problem before proceeding.When the count rate is significantly lower than 5% of the laser repetition rate, gradually increase the laser intensity.
    2. Have a closer look at the signals. They should only show a peak of several hundred mV and no 'ringing' (vibrations after the actual pulse). The width of the MCP signal should not exceed 10 ns (FWHM).
    3. Check out the oscilloscope trace of all six anode signals. The signals are wider here (20-30 ns) and usually a bit lower voltage. Check again that there is no signal interference. If all anode signals are below 100 mV, increase the voltage (step 2.1.3) in steps of 50 V. Tuning the gain factor can help to get the same pulse height for all channels.
    4. These analog signals convert NIM standard signals (Nuclear Metrology Module) of -0.8 V through a constant fraction discriminator (CFD). Check the settings of the CFD before every single attempt. You will find a detailed description of the instructions available on the Internet. flow 12 the NIM pulses into a time-to-digital converter (TDC), which records the arrival time of the pulses with high resolution (usually 25 Ps). These time signals are the input for the data acquisition and analysis software.
    5. Turn on the data acquisition software and start data recording. Look at the successful distribution for each channel - the histograms should be similar for all channels. If not for some channels, check the CFD settings (step 2.2.4) for those channels. Check the settings by additionally checking the sum of the signal lead times for each of the detector layers as described in the detector manual. If necessary, correct the settings of CFDs.
    6. Show a detector image in the data acquisition software. The detector should appear as a circle with a diffuse spot (image of the laser focus) in the middle. The expansion of the spot is mainly due to the thermal velocity of the residual gas that is ionized.
    7. The signal of the laser diode (step 1.5.5) in the data acquisition, preferably in the same way as the detector signals. A time-of-flight spectrum is displayed in the software. If the observed peaks relate to residual gas species (H. 2, H 2 O, possibly N. 2, O 2, CO 2) by calculating their expected time of flights from the spectrometer geometry (step 1.1.2.1).
    8. Try to minimize the laser pulse duration by maximizing the count rate, via the dispersion correction of the laser system. A shorter pulse (and thus a higher peak intensity) leads to a significant increase in the interest rate.
    9. If the background pressure is so low that the rate is not high enough to carry out the above steps activate the gas jet (see point 2.3) and carry out steps 2.2.1 to 2.2.8. The time-of-flight spectrum in step 2.2.7 should then of course be dominated by the types in the jet.
    10. Find the absolute orientation of the detector. To do this, move the focusing mirror, the image of the laser focus shifts visible in the detector image in the software. Note the direction of movement (used in step 5.1.1). This step is important for the measurement of the absolute configuration, because it allows to avoid the inversion of the measured moments in relation to the real laboratory area.
  3. Find overlap of gas jet and laser.
    1. Switch the gas jet as described in step 1.3.5.
    2. When the speed increases, and a very narrow point ('Jet Place') is visible on the detector image in the data acquisition program ensure that the molecular jet and laser beam at least partially overlap. In this case, carefully tune the manipulator for the focusing mirror to maximize the count in the jet spot. If they overlap optimally, they should exceed the number of graphs from the residual gas (step 2.2) by orders of magnitude. It may be necessary to reduce the laser power as the MCP count rate should not exceed 30 kHz. If the background is too high compared to the signal from the gas beam due to the ionization of the residual gas, consider extending the laser beam outside of the chamber to achieve a narrower focus.
    3. If no jet spot is visible on the detector image, adjust the manipulator for the focusing mirror in larger steps to find the overlap, and then proceed to step 2.3.2.

3. Try delivery

  1. Prepare as well as all tools, receiver seals and other items needed as the exposure of the sample to the environment should be minimized.
  2. Fill the sample in the receiver to which the experiment is to be connected. If the sample has a high vapor pressure, cool the receiver and try beforehand to reduce evaporation losses in this step.
  3. Connect the trial cylinder to the jet system and tighten the connection vacuum-tight. Cool down the cylinder (e.g. to avoid losses) and pump for a few seconds to remove air.
  4. Open the valve on the nozzle. The pressure in the source chamber should be at least several 10 -5 increase hPa.
  5. Check if a jet spot is visible (step 2.3.2) and identify the most prominent peaks in the spectrum of the flight time.
  6. Optimization of the experimental conditions (temperature, laser intensity, pressure of copropagating gas ...) to maximize the ionization rate from the sample. Remember, the heater leads to thermal expansion of the components, so if necessary adjust the jet manipulator (step 1.4.5).

4. Measurement

Note: the following steps are done in the data acquisition software.

  1. Check mass spectrum and random spectrum.
    1. A time-of-flight spectrum of the property and assign the various peaks to masses that can occur in the fragmentation (superordinate mass, abundant fragments).
    2. The plot of the time of flight of the first ion on the x-axis and the time of flight of the second ion on the y-axis. Regions with many counts show two fragments in unit of act emitted. Sharp diagonal lines indicate a break-up into two charged fragments.
    3. Plot a similar histogram for more particles, z. B. the sum of the time-of-flights for the first two ions on the x-axis and the sum of the time-of-flights for the third and fourth ions on the y-axis. An example of such a multicoincidence spectrum is in Figure 2.
    4. Try to identify the different breaks in the four-particle or five-particle spectrum and check whether there is a break-up that could reveal the structural information under investigation.
  2. Estimate measurement time.
    1. Let the experiment run for about 1 h and check the number of for the selected channel. Be careful not to count background events.
    2. Multiply that number by the expected time it takes for the experiment. The total number of counts in the corresponding channel should be at least a few thousand.
    3. If the number of graphs in the selected channel is well below this value, increase the laser intensity and repeat steps 4.2.1 and 4.2.2. Make sure that the price is still low enough for congruent detection (see introduction).

5. Analysis of the data

Note: Data analysis in a Coulomb Explosion Imaging experiment is a complex but worthwhile task because many parameters can be tuned after the experiment and a variety of correlations between the measured momenta can be explored. All of the following steps are usually carried out in the data analysis software after the experiment.

  1. Calibrate test parameters
    Note: As a first step, ensure that the position and time information reconstructed by the detector is correct. Similar to the tuning of the electronics (step 2.2), the exact procedure depends on the implementation in this case on the data analysis software. Thus, only general information can be given.
    1. Plot images of the detector. Check that for all three anode layer detector image size corresponds to the actual size of the MCP and that the detector image is centered at 0. Make sure that all combinations of the three layers produce the same detector image. If necessary, rotate or tilt the detector so that the coordinate system of the image detector corresponds to the laboratory frame (use the measurements from step 2.2.10).
    2. Identify different masses in the time-of-flight spectrum and use the spectrometer function (step 1.1.2.1) to match these values. The important parameter in this step is the time-of-flight balancing t0All time-of-flight values ​​are corrected for
    3. Have a look at the random spectra (see step 4.1.4) and identify promising breakup channels. It is recommended to score the time-of-flight values ​​of a few 100 ns around interesting patterns and select only the events in these windows for further steps. Otherwise the number of unnecessary events is too large and slows down the analysis.
    4. Save the corrected values ​​for X, y, t for further analysis.
  2. Calculate ion momenta and energies.
    1. Using the experimental parameters and the assumed mass-to-charge ratios, the dynamics components pX, py and pZ to calculate. Use this to calculate the kinetic energies of the fragments and their sum, the kinetic energy release (KER).
    2. Use the random spectrum (step 4.1.4) to optimize the electric field strength E. and the spectrometer length s and determine a plot of impact position vs. time-of-flight the position offsets X0 and y 0 and the speed V. jet of the gas jet. When precise calibration is required, Usage calculates N 2 and O 2 Fragmentation in two separate types with very closely and well characterized vibrational progressions in kinetic energy version (see Ref. 13 and notes therein).
      1. P.X Vs py etc. of the property and set the parameters so that the momenta are centered on a sphere in the dynamic space (e.g. on a circle in the two-dimensional parcels) and centered on 0. This is because the kinetic energy should not depend on the direction of emission of the fragment ion.
      2. Plot the sum dynamics of all fragments from a molecular break-up. For a complete break-up, the distribution should be narrow (usually <10 atomic unit dynamics) and centered around 0.
  3. Choose relevant events and properties of the molecular system to study.
    1. Separate the actual decay events from the background by setting constraints on the sum dynamics around the observed peaks (typically less than 20 atomic units in each direction).
    2. For these events, vectors use arithmetic to construct sets that contain structural information to be studied. An example of the differentiation between left and right handed stereoisomers is given in the following section.

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Representative Results

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In this part we show results for trihalomethanes. These types are ideal for proof of principle experiments because of their simplicity and high vapor pressure. In the meantime, the more complex types of halothane have been investigated using single soft X-ray photons from a synchrotron source to induce multiple ionizations. 14

CHBrClF

Bromochlorofluoromethane (CHBrClF) is a prime example of chiral molecules with a stereogenic carbon atom. It is also the ideal candidate for Coulomb Imaging Explosion due to its simple structure and high vapor pressure (around 600 hPa at room temperature). Unfortunately, the species is not commercially available; For the experiment presented here, a racemic mixture of reacting CHBr2Cl with HgF2 according to reference15synthesized. Enantio-enriched samples are difficult to come by in the quantities needed, so only results for resolution have so far been obtained.

For the results presented here, the sample was cooled to around 240 K to a corresponding target density with the given nozzle (10% of the ionization probability per pulse). The peak intensity of the laser was estimated to be 6 x 1014 W / cm2. Measurement at 100 kHz laser repetition rate took 11 h.

To distinguish from R. and S.- Enantiomers, a normalized triple product calculated from the momentum vectors of three halogens fluorine, chlorine and bromine. This amount can be interpreted geometrically as the cosine of the angle between the fluorine dynamics and the plane to the chlorine and bromine momenta.

Figure 3 shows cosθ for the isotope CH79Br35ClF, along with the geometric definition. Two clear peaks are visible, indicating the enantiomers. The position of the peaks is consistent with the classic molecular dynamics simulation. Since there is almost no background, the assignment of handedness works on a single molecule level.

CHBrCl2

The chirality of CHBrCl2 occurs only when the isotopes 35Cl and 37Cl are present in the same molecule. A sample with natural abundance of isotopes thus contains achiral and chiral molecules. Two additional complications arise here: Firstly, the time-of-flight distributions of the chlorine and bromine isotopes overlap or due to the small mass difference. This is particularly relevant for chlorine, since the determination of the handedness depends on the correct assignment of the isotopes. Second, the chiral species has CH79Br35Cl37Cl (within the facility accuracy) of the same total mass as genus achiral CH81Br35Cl2. The investigation of this kind can thus be seen as a benchmark test for the method.

Used with the spectrometer (spectrometer length s = 60.5 mm, electric field strength E. = 57.1 V / cm), the data for the chiral isotope CH79Br35Cl37Cl over the entire dynamics could be selected using an algorithm suggested by reference16 assign which of the hits belongs to which isotope.

Geometric considerations lead to the conclusion that there may be orientations of the molecule in space where the two isotopes of chlorine have the same time of flight; in this case they cannot be distinguished as fundamental. A method to clarify these events was included in the Supplementary Materials reference4described. As a result, the configuration of isotopic chiral molecules can also be determined with high reliability.


illustration 1: Look into a COLTRIMS setup. Molecules call the setup through the nozzle and a couple of skimmers go through. In the interaction chamber, the laser pulses cross with the molecular jet under 90 °. Ions are guided through the electric field of the spectrometer with the detector (above). For better visibility, not all spectrometer plates are displayed. The remaining molecules are thrown into a differentially pumped section (jet dump) in order to keep the background pressure in the large-area interaction as low as possible. Illustration by reference17 modified with the kind permission of G. Kastirke. Please click here for a larger version of this figure.


Figure 2: Four-particle random spectrum. This histogram is an extension of the time-of-flight mass spectrum to four particles: the sum of the time-of-flights for the first and second hits on the detector are plotted on the X-Axis, the total for the third and fourth hit on the y-Axis. The center of the summit makes it possible to identify the masses of the four fragments found. The shape of the structures contains additional information: if the momenta of the fragments add up to zero, the events are contained in a narrow line (H, CF, Cl, Br). If an undetected fragment carries momentum, the zero-total dynamics of the measured particles lead to an expansion of the functions. For illustration, data from synchrotron, not laser, measurements by higher statistics are used. Illustration by reference5 reproduced with permission from Wiley-VCH. Please click here for a larger version of this figure.


Figure 3: Differentiation of the enantiomers in the five-particle decay of CHBrClF via the chirality parameter cosΘas defined in the text. The peak with positive values ​​corresponds to the R-enantiomer, the peak with negative values ​​for the S-enantiomer. The inset shows cos θ geometric. The low background enables the handedness to be assigned for individual molecules. Illustration by reference4 Reproduced with permission from AAAS. Please click here for a larger version of this figure.

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Discussion

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Due to the large number of components, a COLTRIMS setup requires a fairly high level of professional competence, especially in the areas of vacuum technology, particle detectors, fast electronics and data analysis.Before embarking on the investigation of complex species, it should therefore be thoroughly checked that the setup is correct, z. B. is carried out by making and analyzing a measurement in a diatomic or triatomic manner.

Optimizing the intensity and duration of the laser pulses and the overlap with the molecular jet is important to achieve as many multiple ionization events as possible. Since the dynamic distribution could be expanded by sequential ionization during the different cycles of the laser pulse, the pulse duration should ideally not exceed 40 fs. It is important to obtain sufficient statistics during the measurement. On the positive side, the determination of the absolute configuration requires a particularly high precision compared to other random experiments, d. H. the method is fairly robust to fluctuations in laser or jet intensity and electric field distortions in the spectrometer.

The most fundamental limitation of the technique concerns its applicability to larger molecules. Note that the results of the momenta fragments do not represent the structure of the molecules in real space one has to keep. For complex biomolecules, the relationship between measured momenta and molecular structure should not be as simple as the molecules presented here. In addition, complex molecules that break apart to produce many that contain no information about the configuration can potentially reduce the yield of the relevant channels. Theoretical modeling of fragmentation, control of decay patterns and more sophisticated analytical methods will be required if the technique is to be extended to molecules with at least three carbon atoms. At this point in time it does not seem possible to study the configuration of proteins or molecules of similar complexity, but the actual constraints have yet to be determined.

Another limitation of the current setup is the relatively high sample consumption due to the molecular jet. It can be done by implementing a recycling mechanism (z. B. Cold traps in the vacuum foreline) can be reduced. Still, it would be beneficial for other sample preparation methods such as profuse nozzles, thermal desorption18 to test or laser desorption techniques19 who were successfully applied to studying bio-molecules in the gas phase.

Coulomb Explosion Imaging is a destructive method i.e. Molecules that have been fragmented to determine the configuration can no longer be used. However, only a fraction is actually ionized (this is one of the reasons for the high sample consumption mentioned in the previous paragraph). This would make it possible to use recycled molecules for subsequent applications.

As the measurement of the momenta allows me to create an "aligned" database of the molecules and to choose certain spatial directions, the random technique opens up new perspectives for the study of the effects of asymmetry in chiral molecules, this is especially the case when the momenta of electrons in unit of action, which can be achieved with a full COLTRIMS setup. Pump-probe techniques also allow to study the structural dynamics of chiral species.

Recently, Coulomb Explosion Imaging has also been used to determine the absolute geometries of Cis and TransIsomers,20 Add a new class of possible types and questions to be addressed. As the study of stereochemistry with random spectroscopy is still in its infancy, the authors hope that this article will help inspire new experiments in the directions given in the preceding paragraphs.

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Disclosures

The authors do not declare any conflict of interest.

Acknowledgments

We thank Robert Berger (Philipps-Universität Marburg, Germany) for stimulating discussions about the interpretation of the data and molecular chirality in general. We are grateful to Julia Kiedrowski, Alexander Schießer and Michael Reggelin from TU Darmstadt (Germany), as well as Benjamin Spenger, Manuel Mazenauer and Jürgen Stohner from ZHAW Wädenswil (Switzerland) for providing the sample.

The project was supported by the state initiative Hessen for scientific and economic excellence under the focus ELCH (electron dynamics chiral systems) and the Federal Ministry of Education and Research (BMBF). MS recognizes financial support from the Adolf Messer Foundation.

Materials

SurnameCompanyCatalog NumberComments
CHBrCl2Sigma Aldrich139181-10Gor other suitable sample
femtosecond laser systemKMLabsWyvern500
High-reflective mirrorsEKSMA042-0800
mirror mountsNewportU100-A-LH-2K
focusing mirror (protected silver, f = 75 mm)ThorlabsCM254-075-P01(if available: f = 60 mm)
COLTRIMS spectrometer, including electronics and data acquisition systemRoentDekcustomcontrary to the standard COLTRIMS, only one detector is needed

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