Crystallography without the crystals: Porous for support

Porous for thought

Yasuhide Inokuma, Shota Yoshioka, Junko Ariyoshi, Tatsuhiko Arai, Makoto Fujita, Yuki Hitora, Kentaro Takada and Shigeki Matsunaga of The University of Tokyo, and Kari Rissanen of the University of Jyväskylä, Finland, have used a porous substrate to bring order to an otherwise uncrystallisable target molecule for X-ray diffraction studies. The approach precludes the need to develop a method for producing crystals of the material and may be applicable to a wide range of target compounds that are available in mere nanogram quantities that are not accessible to X-ray crystallography.

By virtue of its definition, if not its methodology, X-ray single-crystal diffraction is wholly limited to compounds that can be crystallised. Now, Fujita and Rissanen thrown out the received wisdom on crystallography to establish a novel protocol for such analyses that allows a target molecule to be studied by inducing X-ray diffracting order on the material using a porous complex that absorbs the molecule of interest from solution and supports them within its hollows. The approach thus requires just a tiny crystal of porous support and nanogram quantities of the target compound but can nevertheless generate a suitable diffraction pattern from which three-dimensional structural information can be extracted.

Breathtaking metaphor

Writing in a "News & Views" article to accompany the Fujita paper in Nature, Pierre Stallforth and Jon Clardy of Harvard Medical School, Boston, Massachusetts, point out how "Growing crystals remains more of an artisanal skill than an intellectual one, and is based on few general principles and lots of trial and error," and even then it is frequently limited by the small quantities of a compound that might be extracted from a sea slug or a rare herbal remedy for instance. They describe the new approach as circumventing this issue with a "breathtakingly simple" solution. They offer an aviation metaphor by way of explanation of the process, visualising the randomly moving throng of people at an airport and the few that are absorbed into a boarding aeroplane to become ordered by the seating within.

The Japanese and Finnish team was able to work with a crystal of host complex smaller than 0.1 x 0.1 x 0.1 mm in size with as little as 80 nanograms of target molecule adsorbed as a guest from solution. In a proof of principle, Fujita, Rissanen and their colleagues were able to carry out a structure determination on a scarce marine natural product - miyakosyne A - from a starting sample of just 5 micrograms. They suggest that there are many other natural and synthetic compounds for which chemists and crystallographers were not holding out any hope of ever obtaining X-ray data might now be characterised relatively quickly and easily.

Learning to fly

"The slow diffusion of guests into the solvent-filled voids of the crystalline sponges [based on cobalt or zinc complexes] is a particularly important process that renders the guests thermodynamically well equilibrated at the specific molecular-recognition sites of the hosts," Fujita and colleagues explain. "Accordingly, the guests are regularly ordered and made observable by crystallographic analysis," with the previously determined crystal structure of the host framework subtracted from the host-guest complex structure. The team suggests that their technique will be useful in the microanalysis of natural products, to food and perfume chemists, in drug discovery, forensic science and the daily research of synthetic organic chemists. "We are now expanding the scope of our 'crystalline sponge' method so as to analyse large and more scarce compounds," Inokuma told SpectroscopyNOW. "One of our final goals is to determine the protein structures with the method," he adds.

"It remains to be seen what percentage of molecules will be amenable to the authors' technique," Stallforth and Clardy point out, adding that the "sponges" used as the "aeroplane" hosts to bring order to the "passenger" guests will have to become widely and commercially available.