Requiem for gas-phase electron diffraction

The technique of gas-phase electron diffraction for the determination of molecular structure was a great invention. By 1930, the time of the first experiment [1], all necessary ingredients had come together for bringing it about. It had been established that electrons have dual particle/wave nature, thus capable of interference. A few years before the first gas-phase electron diffraction experiment, the first solid-phase electron diffraction experiments had been performed. It was also known that a sample of arbitrarily oriented gaseous molecules could yield a diffraction pattern as it had been shown for X-rays [2].

Gas-phase electron diffraction offered major benefits as compared with other means of structure determination. The intensity of irradiation/matter interaction was million times higher in case of electrons versus X-rays. Hence, much shorter exposures would suffice for recording electron diffraction as compared with X-ray diffraction. The diffraction of electrons depended primarily on the nuclear charges of the atoms rather than on the electrons exclusively, as in X-ray diffraction. Hence, a more accurate determination of hydrogen positions could be expected from electron diffraction than from X-ray diffraction. A beautiful gas-phase electron diffraction pattern is presented in Fig. 1. It was taken of gaseous adamantane, C₁₀H₁₆, a highly symmetrical molecule, in Ken Hedberg’s laboratory at Oregon State University in Corvallis, in 1969 [3].

Fig. 1

A beautiful electron diffraction pattern of a gaseous adamantane sample (cf. [3])

A drawback for gas-phase electron diffraction versus X-ray crystallography is the limitation in size and complexity of the targets. However, this drawback was not in the forefront while there was a crucial necessity of accurate information on the structure of small and medium-size molecules. On the contrary, the information on gaseous molecules determined by solely intramolecular interactions, that is, free of intermolecular interactions present in crystals, was much welcome in the quest for understanding the architecture of molecules. Such information helped Linus Pauling (1901–1994, Fig. 2) build up his extensive edifice of what we know about the nature of chemical bonding.

Fig. 2

Linus Pauling (courtesy of Linus Pauling)

Pauling himself contributed considerably to the development of gas-phase electron diffraction. He learned about the new technique during his visit at Herman Mark’s (1895–1992, [4]) Ludwigshafen laboratory in Germany in the early 1930s. There, Mark and his younger associate, Raymund Wierl, had performed the first ever electron diffraction experiments on gaseous samples, consisting of simple molecules, such as carbon tetrachloride [1]. In their pioneering publication, the authors gave credit to Walther Bothe who, in a comment during a recent meeting, raised the possibility of electron diffraction of gases. Mark’s laboratory in Ludwigshafen was an industrial laboratory of the German giant chemical company I. G. Farbenindustrie. This company would years later acquire infamy for its complicity in the Holocaust. For the time being though, it was a workplace that allowed experimentation not directly needed or benefitting its primary tasks. There were no plans to continue with gas-phase electron diffraction at Ludwigshafen and Mark was happy to oblige when Pauling expressed his desire to take the technique back with him to the California Institute of Technology in Pasadena. It was not long after the invention of gas electron diffraction that the officials of I. G. Farbenindustrie advised Mark to depart from the company. The reason was Mark’s Jewish roots although this happened well before Hitler and the Nazis came to power in Germany and introduced the anti-Jewish laws. Subsequently, Mark had a distinguished career in polymer science in the USA [4].

To estimate internuclear distances, Mark and Wierl had to mark the vaguely expressed maxima and minima on the diffraction pattern of steeply falling intensity. It was a tremendous progress when the Norwegian group introduced a technical trick, which produced a more even intensity distribution and Linus Pauling Fourier-transformed it, yielding a probability density distribution of internuclear distances, which was named the radial distribution—obviously, a misnomer. For a rigorously rigid molecule, the radial distribution consists of a series of lines, one for each atomic pair. The height of such a line is proportional to the number of such atomic pairs in the molecule and the nuclear charges of the two participating atoms. Due to molecular vibrations, those lines broaden to the extent determined by the amplitudes of the respective vibrations. The analysis of the radial distribution expanded the possibilities of the technique. In addition, it had unique didactic value in that it was possible to read off internuclear distances, among them bond distances, directly from it. Linus Pauling in his classic, The Nature of the Chemical Bond, quoted numerous structural characteristics from gaseous electron diffraction analyses [5].

During World War II, only limited progress was made in developing and utilizing gas-phase electron diffraction. An exception was a pivotal discovery by Odd Hassel (Fig. 3) in the Oslo laboratory. He established the presence of conformational equilibria for systems in which the relatively large barriers to internal rotation made the coexistence of different conformers possible, especially in cyclohexane derivatives. Under German occupation, Hassel refused publishing his discoveries in German and he had no access to publishing in English. His studies appeared in Norwegian in obscure periodicals. After the war, he communicated an extended summary of his discoveries in English [6]. Hassel was awarded the Nobel Prize in Chemistry in 1969. He received half of that year’s prize; the other half went for related discoveries to Derek H. R. Barton. Their joint motivation was “for their contributions to the development of the concept of conformation and its application in chemistry.” Hassel’s Nobel Prize was the only Nobel recognition for unambiguously gas electron diffraction work. Previously, the motivation of Peter Debye’s (1884–1966) 1936 Nobel Prize in Chemistry mentioned this technique: “[for his work on] molecular structure through his investigations on dipole moments and the diffraction of X-rays and electrons in gases.” In his Nobel lecture, among other topics, Debye discussed some early results from electron diffraction, but conspicuously downplayed the Mark-Wierl invention of the new technique.

Fig. 3

Odd Hassel (left, courtesy of Otto Bastiansen) and Otto Bastiansen (right, photograph by Istvan Hargittai)

The Norwegian group did much to further develop the technique and to help establish other laboratories setting up gas-phase electron diffraction experiments. Otto Bastiansen’s (1918–1995, Fig. 3) dissertational work in 1948 used electron diffraction for analyzing structures in which various conditions hindered free rotation about single bonds [7]. He was a senior member of the Oslo group for decades and the mentor to others outside his home country. Bastiansen suggested that from time to time, the structure of the most fundamental molecules should be reinvestigated to ensure that for them such information remained available at the highest level of accuracy.

After World War II, Jerome Karle (1918–2013, Fig. 4) and Isabella Karle (1921–2017, Fig. 4) elevated the level of accuracy in the determination of molecular geometry by quantitatively considering the impact of molecular vibrations [8,9,10]. For the linear carbon dioxide molecule, they found the distance between the two oxygen atoms somewhat shorter than twice the length of the carbon-to-oxygen bond. The discrepancy was a consequence of the bending vibrations. This observation had serious impact on the electron diffraction studies as the impact of molecular vibrations had to be considered to fulfill the ever-increasing accuracy requirements. This was also necessary to bring the results of electron diffraction studies to a common denominator with those originating from other physical techniques and, eventually, from computations. In 1985, Jerome Karle and Herbert A. Hauptman shared the chemistry Nobel Prize for their direct methods for X-ray crystallography. In his contribution to their joint discoveries, Karle utilized his experience with gas-phase electron diffraction.

Fig. 4

From left to right: Istvan Hargittai, Magdolna Hargittai, Isabella Karle, and Jerome Karle, 1978, Pécs, Hungary (by an unknown photographer)

Both precision and accuracy had always been in the forefront of the aspirations of the leading researchers in the application of gas-phase electron diffraction [11]. Precision pertained to the reproducibility of structural information and, significantly, not only within the same laboratory, but also among the laboratories employing this technique. The accuracy pertaining to the true values of structural parameters meant a great deal also for the possibility of combining diffraction data and spectroscopic data. Such combined analyses held the promise of elucidating structures that could not be obtained by a single technique and of achieving their higher accuracy. Thriving for ever higher accuracy produced some attempts that bordered esoteric proportions, such as detecting bond length differences in carbon-to-carbon bonds upon substitution of a hydrogen by a deuterium. Such exercises, however, demonstrated the high level of understanding the interrelationship of geometry and intramolecular motion.

A telling example was the comparison of the bond lengths in CH₄ and CD₄ molecules. There was a difference between the bond lengths in them as determined by electron diffraction and as determined by rotational spectroscopy. Electron diffraction yielded thermal average lengths between the nuclear positions and the rotational transitions yielded distances between average nuclear positions. Once, most of the impact of molecular vibrations were eliminated the two techniques yielded consistent results though the difference between C–H and C–D persisted. Further reduction of the data taking care of the impact of all vibrations led to the equilibrium distances and there the two techniques provided the same lengths within experimental error [12]. On the long run, the chemically meaningful information come from analyzing large amounts of structural information—data mining—and from information of series of related molecules rather than the intricacies of, for example, bond length changes upon isotopic substitution.

A brilliant example of one of the many advantages of the gas-phase electron diffraction technique was the determination of the PF₅ molecular geometry. This molecule has a trigonal bipyramidal shape with the axial P − F bonds longer than the equatorial P − F bonds. The difference is 0.05 angströms, much larger than the experimental error in which the systematic error could be ignored as two distances were compared from the same experiment [13]. In this case, the extremely short interaction time between the molecules in the target of the diffraction experiment and the electron beam played a pivotal role. The rearrangement of the axial and equatorial P–F bonds, like a pseudorotation [14], is a faster process than the interaction time of some other physical techniques. However, the interaction time in the electron diffraction experiment is still orders of magnitude faster. It depends on the accelerating voltage used in the experiment, staying in the region of 10⁻¹⁸–10⁻²⁰ s.

By the mid-1970s, all the methodological tools of gas electron diffraction had been in place. At its height, gas electron diffraction laboratories operated in Norway, Britain, the USA, Germany, the Soviet Union, Japan, Hungary, Belgium, the Netherlands, and elsewhere. Great strides were made in employing special experimental setups to investigate substances that could be brought into the gas phase only at high temperatures. In determining the structure of unstable species, even reaction intermediates, a combined experiment of electron diffraction and quadrupole mass spectrometry was constructed and operated with success (Fig. 5). From the 1970s on, a systematic collection of gas-phase molecular structure data was developed due to Barbara Starck’s (1924–2001, [16]) initiative and dedicated activities.

Fig. 5

Combined electron diffraction/quadrupole mass spectrometry experiment of the Budapest group [15]. The electron diffraction apparatus was a product of a plant in Sumy, a city in north-eastern Ukraine (then, in the Soviet Union) and the quadrupole mass spectrometer of the Institute for Nuclear Research in Debrecen, Hungary

At the rate quantum chemical calculations were becoming available and could be utilized in a combined analysis with electron diffraction, they were. We have monitored this interaction over the years (see, e.g., [17, 18]). The initially hesitant joint application of data gave way to ever expanding combined analyses. A useful approach was when parameter differences from quantum chemical calculation were assumed and not varied in the analysis of electron diffraction data. This took into effect the possible differences in the physical meaning of the thermal average parameters from the diffraction experiment and the equilibrium parameters from computation. With further improvement of the computational possibilities, the diffraction data were playing a diminishing role in the combined analysis. It was increasingly realized that for many tasks, computation alone sufficed.

A good summary of both the technique and a set of structural findings were presented in a two-volume treatise (Fig. 6 [19]). With time, the weakness in the competitiveness of gas-phase electron diffraction was manifested in three aspects. One was the ever-increasing possibilities of quantum chemical computation. Another, the possibilities of data mining of data banks of ever-increasing riches of structural information. The third was the disadvantage of the laborious experimentation and the not quite automated analysis in using this technique. All this explains the diminishing interest of the potential graduate students in doing gas-phase electron diffraction work. Nonetheless, these comments are not meant as if burying the technique. There are still a few laboratories using it with success. Gas-phase electron diffraction has greatly contributed to modern structural chemistry. Its contributors, of whom only a few are mentioned in this Editorial, deserve respect and remembrance.

Fig. 6

The covers of the two-volume treatise about the techniques and applications of gas-phase electron diffraction

The utilization of electron scattering in structural chemistry does not end with the demise of the gas-phase electron diffraction technique. In conclusion, we mention two Nobel Prizes that signify its continuing pivotal role. In 2011, Dan Shechtman’s discovery of quasicrystals was recognized. His electron diffraction experiments made possible the first observation of regular but non-periodic structures leading to the extension of the concept of what a crystal is and to the further broadening of what generalized crystallography means. In 2017, Jacques Dubochet, Joachim Frank, and Richard Henderson received the chemistry Nobel Prize for developing cryogenic electron microscopy. The structure of even a single biological molecule embedded in vitreous (amorphous) ice can be determined by this technique. The use of electron scattering in structural chemistry is meeting heretofore unimaginable challenges.