Progress in the development of new medicines and materials requires knowledge of molecular structures, i.e. the precise arrangment of atoms within molecules. Scientists only have a few methods available for finding out about the structures of large molecules like proteins.
The most successful method is X-ray crystallography. However, this powerful method requires crystals, which are difficult to produce for many very important biomolecules, especially the type of receptor proteins which sit inside cell membranes ("membrane proteins").
Another promising method is called solid-state NMR (nuclear magnetic resonance), which uses the fact that many of the nuclei at the centres of hydrogen, carbon and nitrogen atoms are weakly magnetic, and behave as small bar magnets. In NMR, radiowaves are used together with a strong magnetic field to probe the interactions between these magnets, allowing one to build up a picture of the molecular structure. Solid-state NMR has been used to obtain structural information from large biomolecules such as membrane proteins, without the need to form crystals. Unfortunately, the NMR signals are very weak. Rather large amounts of sample are often required. This greatly limits the application of this method, since many of the most interesting and important molecules are only available in very small quantities.
In this project we are designing equipment to perform solid-state NMR at very low temperatures, approaching the boiling point of liquid Helium (4.2 Kelvin, or -269 degrees C). The NMR signal is much stronger at these temperatures. This will allow biologists and chemists to obtain the vital molecular structural information using at least 10 times less sample than was possible before.
The project is technically demanding because one must not only keep the sample very cold, but also rotate it very rapidly at a certain angle to the applied magnetic field (this is called magic-angle-spinning, or MAS). This rapid sample rotation is necessary to obtain the most informative NMR signals. Cryogenic magic-angle-spinning NMR is a major technical challenge, and the project combines leading expertise in sample spinning, electronics and cryogenics, in order to overcome these difficulties.
A further difficulty is that the NMR signal often takes a long time to build up at cryogenic temperatures. This is because molecular motion is needed to magnetize the atomic nuclei, and this molecular motion slows down a lot when the material is very cold. Another part of the project addresses this problem by designing molecules which have very fast molecular motion, even at cryogenic temperatures. These molecules (called cryorelaxors) are able to speed up the build-up of the NMR signal on neighbouring molecules. One molecular system that is under study involves a closed, symmetrical, cage of sixty carbon atoms is known as a fullerene. Chemical synthesis processes have been developed that allow one to insert hydrogen molecules (H2) into fullerene cages, where they behave as perfectly free rotors, able to move according to the laws of quantum mechanics. We are studying the behaviour of these quantum rotors by nuclear magnetic resonance, neutron scattering, and infrared spectroscopy.
Hydrogen molecule (yellow) trapped inside a fullerene cage (black).
References:
M. Carravetta, Y. Murata, M. Murata, I. Heinmaa, R. Stern, A. Tontcheva, A. Samoson, Y. Rubin, K. Komatsu and M. H. Levitt, "Solid state NMR of molecular hydrogen trapped inside an open-cage fullerene". J. Am. Chem. Soc., 126, 4092-4093 (2004).
M. Carravetta, O. G. Johannessen, M. H. Levitt, I. Heinmaa, R. Stern, A. Samoson, A. J. Horsewill, Y. Murata and K. Komatsu, "Cryogenic NMR Spectroscopy of Endohedral Hydrogen-Fullerene Complexes", J. Chem. Phys., 124, 104507 (2006).
S. Mamone, A. Dorsch, O. G. Johannessen, M. V. Naik, P. K. Madhu and M. H. Levitt, "A Hall effect angle detector for solid-state NMR", J. Magn. Reson., 190, 135-141 (2008).