From Crystallography to Light!

As the International Year of Crystallography gives way to the International Year of Light, we end the #Crystallography365 series with a retrospective of how research in optics has advanced crystallography, and a prospective on how it will do so in the future.

There was crystallography before x-rays, but since 1912 the field has been intimately connected to x-ray optics [1]. In 1895, just after Maxwell had shown that light was a transverse electromagnetic wave, Rontgen discovered x-rays while conducting experiments of the optical properties of cathode rays. Rontgen’s mysterious x-rays captured worldwide attention; but particularly that of Arnold Sommerfeld’s. Although a theoretician himself, he had assembled an impressive group of experimentalists in his research group. Sommerfeld had surmised that that x-rays were transverse EM waves with a wavelength on the order of 1 angstrom, and furthermore that diffraction through a suitably sized slit would prove this fact.

In 1912 Max Von Laue, then an experimentalist in Sommerfeld’s group, showed that crystalline materials diffract x-rays, thus in just one single experiment demonstrating the wave nature of x-rays and the lattice structure of crystals [2]. Then using mathematical arguments from wave optics W.L Bragg (the son) developed his groundbreaking formulas relating the intensity of spots and structure. Later, using optics and engineering, W.H. Bragg (the father) constructed the first x-ray spectrometer, and Weissenberg invented the x-ray camera named after him [3].

The invention of synchrotron light sources and advances in x-ray optics have boosted crystallography to new heights. Synchrotrons were first built for particle physics applications. X-ray radiation production in synchrotrons is an energy-sapping nuisance, and literally holes needed to be drilled in the particle pipe to let the x-rays out. Of course scientists soon realized that this ‘waste radiation’ might be useful after all [4]. Today with many exotic x-ray optical designs, large synchrotron machines give crystallographers more and more brilliant monochromatic x-rays, and with the ability to get higher and higher resolutions in both space and time. This has been particularly useful in powder and macromolecular applications.

In the coming years research in optics holds many exciting opportunities for crystallographers. Advances in plasma photonics are reducing the size of x-ray sources such that light with characteristics previously only available at large synchrotron user facilities becomes available from machines small enough for individual labs [5-7].

Free electron lasers (FELs) provide peak brilliance 8 orders of magnitudes larger than synchrotron light sources, and pulses on the order of 10s of femtoseconds [8]. FELs are enabling ultra-short, but still ultra-bright light pulses that allow reliable structure determination from much smaller crystals. This is extremely important for protein crystallographers, shaving possibly years off the current process and opening the door to bigger and more membrane bound complexes [9]. The ultra-short pulse length and high repetition rates mean that chemical dynamics will routinely be studied crystallographically [10].

At the end of this celebration of 100 years of x-ray crystallography, crystallographers are in a sense where they’ve been all along, at the forefront of optics research. So the International Year of Light is a perfect successor to the International Year of Crystallography.

[1] Nave, C. (1999), Matching X-ray source, optics and detectors to protein crystallography requirements, Acta Cryst. D55, 1663-1668, doi:10.1107/S0907444999008380

[2] Von Laue, M. (1915), Nobel Lecture: Concerning the Detection of X-ray Interferences”. Nobel Media AB 2014. Web. 31 Dec 2014.

[3] Weissenberg K., Ein neues Röntgengoniometer. Z. Physik, 23 (1924),229-238, doi: 10.1007/BF01327586

[4] Phillips, J. C., Wlodawer, A., Yevitz, M. M., & Hodgson, K. O. (1976). Applications of synchrotron radiation to protein crystallography: preliminary results. Proceedings of the National Academy of Sciences of the United States of America, 73(1), 128–132, PMCID: PMC335853

[5] Corde, S., Phuoc, K. T., Lambert, G., Fitour, R., Malka, V., Rousse, A., … & Lefebvre, E. (2013). Femtosecond x rays from laser-plasma accelerators. Reviews of Modern Physics, 85(1), 1, doi: 10.1103/RevModPhys.85.1

[6] Schlenvoigt, H-P., K. Haupt, A. Debus, F. Budde, O. Jäckel, S. Pfotenhauer, H. Schwoerer et al. (2007). A compact synchrotron radiation source driven by a laser-plasma wakefield accelerator. Nature Physics, 4(2), 130-133, doi:10.1038/nphys811

[7] Lyncean Technologies,

[8] Margaritondo, G., & Rebernik Ribic, P. (2011). A simplified description of X-ray free-electron lasers. Journal of synchrotron radiation, 18(2), 101-108, doi: 10.1107/S090904951004896X

[9] Spence, J. C., & Chapman, H. N. (2014). The birth of a new field. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1647), 20130309, doi: 10.1098/rstb.2013.0309

[10] Minitti, Michael P., James M. Budarz, Adam Kirrander, Joseph Robinson, Thomas J. Lane, Daniel Ratner, Kenichiro Saita et al. Toward structural femtosecond chemical dynamics: imaging chemistry in space and time. Faraday discussions 171 (2014): 81-91, doi: 10.1039/C4FD00030G


Sodium hydride, simple yet historic.

What is it?

Though it looks pretty simple, this structure has a special place in history as it was one of the first structures to be discovered with neutron diffraction.  Though the positions of the sodium atoms in sodium hydride were known for some time (from x-ray diffraction), there was still debate if the hydrogen atoms were at the ½, ½, ½ point in the unit cell (a zinc blende structure) or at the ½, 0, 0 point in the unit cell (a rock salt structure).

In the 1940’s a number of researchers realised that instead of using x-rays to diffract off a material, they could use some different radiation – a beam of neutrons.  This was only possible with the development of nuclear reactors, which could provide a steady source of neutrons.

Neutrons interact with matter in a very different way to x-rays.  With  x-rays, the amount they scatter from an atom is proportional to the number of electrons they have in their outer shell – for instance sodium atoms (with 11 electrons each) scatters much better than hydrogen atoms (with only one electron for each atom).  Instead of interacting with the ‘cloud’ of electrons, neutrons diffract by interacting with the nucleus of the atom itself, and are not affected by it’s size, and so have a much more complex trend as you move through the elements of the periodic table.    For instance heavy hydrogen (deuterium) has a scattering cross length from neutrons that is twice that of sodium.

The effect that is to x-rays the structure of sodium hydride looks like this:

The structure of sodium hydride showing the relative scattering of the sodium (yellow) and hydrogen (pink) atoms.

The structure of sodium hydride showing the relative scattering of the sodium (yellow) and hydrogen (pink) atoms.

and to neutrons it looks like this!

And this shows the relative scattering of the heavy hydrogen (pink) and sodium atoms (yellow) to neutron diffraction.

And this shows the relative scattering of the heavy hydrogen (pink) and sodium atoms (yellow) to neutron diffraction.

This meant that the first researchers using neutron diffraction could work out that the structure of sodium hydride was, in fact, the rock salt structure.  This paved the way for many other structures to be solved with neutron diffraction, locating atoms that would be difficult to see with x-rays.
Shull, one of the authors of this work on sodium hydride, was later to share the Nobel Prize in Physics for his development of neutron diffraction.

A bit of a mouthful – hexamethylenetetramine

What does it look like?

Here the brown atoms are carbon, and the light blue atoms are nitrogen atoms.  Image generated by the VESTA (Visualisation for Electronic and STructual Analysis) software

Here the brown atoms are carbon, and the light blue atoms are nitrogen atoms. Image generated by the VESTA (Visualisation for Electronic and STructual Analysis) software

What it is?

Though it’s name is a bit of a mouthful, this is a relatively simple molecular compound.  It is made up of six carbon atoms and four nitrogen atoms which bond together to form a little cluster.

The structure of hexamethylenetetramine is significant to crystallography.  It was determined in 1923 and was arguably the first molecular structure to be found.  It was chosen for the investigation beacuse it was known to form a cubic crystal structure, one of very few molecular materials to do so.  Materials with cubic symmetry are more straight forward to solve, as there’s less parameters to find.  This work really proved that molecules would arrange into crystals, and paved the way for Kathleen Lonsdale’s work on benzene ring. This, in turn, lead to the field of molecular crystallography which is still very active today.

Where did the structure come from?

This structure comes from the 1923 Journal of the American Chemical Society paper by Dickinson and Raymond.  There’s no crystallographic information file for this one in the Crystallographic Open Database, so the coordinates were taken from the paper itself.

A mineral of history – Fluorite

William Henry Bragg's portrait on winning the Nobel Prize, image from the Noble Foundation

William Henry Bragg’s portrait on winning the Nobel Prize, image from the Noble Foundation

Today would have been the 152nd birthday of one of the founders of crystallography, William Henry Bragg. Together with his son WL Bragg, he won the 1915 Nobel Prize in physics. Between this work and the work of the previous year’s Nobel Prize won by Max von Laue, these researchers put down the rules for us to discover how atoms are arranged in solids.

After finishing his PhD with J.J. Thomson (the man who discovered the electron) W.H. Bragg journeyed to Australia, where at the age of 23 he became a professor of physics at Adelaide University. Here he also married Gwendoline Todd the daughter of Charles and Alice Todd (who Alice Springs is named after), and their first son William Lawrence was born.

The family moved to the UK in 1909, W.H. Bragg to take up a position at the university of Leeds, and W.L. Bragg to continue his university studies at Cambridge. It was during this time that the both worked on the equation that was to bear there name, and the research that would earn them a Noble Prize.

We’ve already covered the mineral, Braggite, named after WH and WL Bragg – then instead today we thought we’d cover one of the first crystal structures they worked out, Fluorite.

What does it look like?

So far this year we come across many ways to represent crystal structures. This may be the most original yet!

What is it?

Calcium Floruride, CaF2 or Flourite, is a colourful mineral that is found all over the world. It comes in a large range of colours, from green through to dark purple, all dependent on the small amount of element impurities contained within it.  Given the right impurities, it will also fluorescence under UV light – the name of this property actually takes its name from fluorite.

In working out the structure of fluorite, the Bragg’s noted the similarity of its diffraction to that of diamond. From this they could work out that the atoms would be similarly arranged but with gaps as there isn’t a 1 to 1 ratio of fluorine atoms to calcium atoms.

Where did the structure come from?

Like the rock salt structure, you can read about how this structure was discovered straight from the book ‘X-rays and crystal structure’ by W.H. and W.L. Bragg.

A ring of progress – Benzene

What does it look like?

Image generated by the Mercury crystal structure visualisation software

Image generated by the Mercury crystal structure visualisation software

What is it?

Benzene is the simplest aromatic hydrocarbon and also quite the crystallographic puzzle for many years. Though it had been known for a long time that benzene was made up of a ring of carbon atoms, in the early years of the crystallography one question that was sought by a number of researchers was to determine the shape of the ring of benzene. There was a lot of debate, for instance WL Bragg (one of the founders of the field of crystallography) thought the molecule itself was bent.

The work of Cox in 1932 that showed that the molecule within solid benzene was not bent and in fact a flat ring. However, it was Kathleen Lonsdale who had paved the way for the understanding of the shape of the benzene molecule, with her structure of hexamethylbenzene in 1929. Together this work paved the way for the wide field of molecular crystallography that has many impacts on our way of life.

Where did the structure come from?

Cox first published the structure of benzene in the Proceedings of the Royal Society A in 1932, but refined his structure with a number of other investigations at different temperatures.


Dorothy Crowfoot Hodgkin and the structure of Vitamin B12

Today is the birthday of Dorothy Crowfoot Hodgkin O.M. FRS who was awarded the 1964 Nobel Prize for her determinations by X-ray techniques of the structures of important biochemical substances


What does it look like?

A space filling model of Vitamin B12 (cyano-cobalamin) (top)  - and a “capped stick representation of the same molecular structure (red= oxygen, grey= carbon, white = hydrogen, blue = cobalt, mauve = nitrogen, orange = phosphorus)  both structures depict the molecule in the same orientation – note the ease of access to the CN group bound at the top of the corrin ring – the reactive position of the molecule.  Isolated red crosses or spheres are water of crystallization. (coordinates used from DOI: 10.1039/c003378b)

A space filling model of Vitamin B12 (cyano-cobalamin) (top) – and a “capped stick representation of the same molecular structure (red= oxygen, grey= carbon, white = hydrogen, blue = cobalt, mauve = nitrogen, orange = phosphorus) both structures depict the molecule in the same orientation – note the ease of access to the CN group bound at the top of the corrin ring – the reactive position of the molecule. Isolated red crosses or spheres are water of crystallization. (coordinates used from DOI: 10.1039/c003378b)

What is it and how was the structure found?

This is Vitamin B-12.

A vitamin is an organic compound vital to the nutrition of an organism. For any particular organism if the substance cannot be synthesized in sufficient (but very small) amounts, the vitamin must then be obtained from the diet.  For instance, Vitamin D is a vitamin in humans because in certain circumstances, particularly low exposure to UV radiation, the normal synthesis of the substance does not occur and it must be consumed from dietary sources to meet metabolic requirements.

Vitamin B12 is chemically the most complex vitamin with a group of closely related substances functioning in the organism to provide the necessary source of cobalamin to vital enzymatic pathways of the metabolism.   The recommended dietary intake in humans varies but is in the range of 1-3 micrograms (millionths of a gram) per day. Vitamin B12 deficiency can result either from an inadequate dietary intake, or from conditions in which the ability to absorb the nutrient is diminished. Biosynthesis of vitamin B12 only occurs in bacteria and archaea and passes into the food chain via due to bacterial symbiosis.

The common features of the Vitamin B12 group of compounds are (i) the corrin ring (similar to the porphyrin ring which binds to the metals present in haem, chlorophyll and cytochrome) which has (ii) a cobalt atom bound in its centre. (iii) One of the carbon atoms on the “outside” of the corrin ring carries to a long chain of atoms ending in a dimethylbenzimidazole group which joins on to the cobalt through one of its nitrogen atoms on one side of the corrin ring and on the other side of the corrin, a sixth substituent bonds to the cobalt atom – this is the site of the biological reactivity of Vitamin B12 and can be occupied by hydroxyl (-OH), methyl (-CH3), cyano (-CN) or 5’-deoxyadenosyl (via its C5’ atom). All of these compounds form crystals which are deep red in colour.

The complete structure of vitamin B12 was determined by Dorothy Hodgkin and her collaborators by means of X-ray crystallographic methods. Using structures from fragments and combining knowledge of the chemistry and with access to early computer based fourier methods, the structure was fully revealed. It is interesting to note the sharing of information which went on between the crystallographic groups and the chemists who were engaged in studying the structure. The documents demonstrate that the two different approaches were to be published simultaneously and Dorothy maintained an inclusive and generous approach to publication of this important structure. Dorothy learned that Alexander Todd (Nobel Prize for Chemistry 1957) had agreed to present a talk about “some new nitrogen-containing compounds” at a meeting of the Chemical Society which he had not mentioned to Dorothy when he was in Oxford a day or two prior to this for the purpose of discussing the publication of the structure. When Dorothy got wind of this talk, she attended and finding that he was announcing the structure, at the end of the talk Dorothy stood up and explained how it had been done. After this occurrence, Dorothy insisted that members of her crystallographic group went wherever Todd was speaking so that they could give a comment at the end.

A study designed to isolate the substance in liver which cured anaemia in dogs (iron), along the way revealed the presence of a different substance which cured pernicious anaemia in humans. For several years sufferers of pernicious anaemia were required to consume large amounts of raw liver or drink “liver juice” to treat their condition. The 1934 Nobel Prize in Physiology or medicine was awarded to Whipple, Minot and Murphy for their work in pointing the way to a treatment for this condition. In 1928 Edwin Cohn prepared an extract that was 50-100 times more effective in the treatment of the disease than raw liver products and together these discoveries led to the identification of the group of compounds known as Vitamin B12


JD Bernal and the structure of water

Can we understand the structure of a liquid?  Dr Alison Edwards’ celebrates one of the pioneers of X-ray crystallography and how he thought about the structure of the most fundamental of liquids, water.

What does it look like?

JD Burnal and his model of water.  Image re-produced from 'Burnal and the structure of water' by J.L. Finney

JD Burnal and his model of water. Image re-produced from ‘Burnal and the structure of water’ by J.L. Finney

J.D. Bernal is shown building a water (liquid) model in which randomness was introduced by using a number of different sized connecting rods to separate the spheres which depict the water molecules. This later work stemmed from Bernal’s insight that further work was required was due to his conviction that the proposed 1933 model was “too crystalline”.

What is it and where did the structure come from?

The structure of water was determined by the application of Bernal’s crystallographic understandings to a liquid system. This occurred in two bouts: the seminal work in 1933 with R.H. Fowler: A Theory of Water and Ionic Solution with Particular Reference to Hydrogen and Hydroxyl Ions, appears in the First volume of The Journal of Chemical Physics (p. 515-548). It has citations numbering in the thousands and was highly influential in the formation of the thinking about the role played by water in biological systems. Later work in the sixties refined and improved the fit of his more randomised proposed model to available data. An excellent account of the original and later work can be accessed here.

On the 113th anniversary of the birth of J.D. Bernal, we should celebrate the application of careful thought to the solution of interesting problems!

Bernal was a thinker and scholar of such high renown that he was known to his friends as “Sage” – there are well-documented stories of the breadth and depth of his knowledge both within science and more broadly in the human condition. His scholarly output was prodigious and eminently readable and the biographies and articles about him are entertaining. The Biographical Memoir of the Fellows of the Royal Society (DOI: 10.1098/rsbm.1980.0002 is freely accessible at ) and was written by one of his early students: Dorothy M.C. Hodgkin O.M. F.R.S. it opens:

“John Desmond Bernal lived his life to the full. He liked to say that his biography ought to be written in four colours, on interleaved pages, to show his different activities, fitted together. Oral tradition differs as to the colours of the pages; black and white, certainly for science, red for politics, blue for arts, purple or yellow for his personal life”

In a science where “big data” is now a dominant feature it is instructive to remember that very significant insights into matter can be achieved by thinking clearly about the limited data which were available.