Realising the potential of cryogenic magic-angle spinning NMR

Progress in the development of new medicines and materials requires knowledge of molecular structures, i.e. the precise arrangment of atoms within molecules. For example, if one knows the precise shape of a malfunctioning protein molecule, one can try to design other molecules which bind to it, so as to prevent it from doing too much damage. 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 the current project we have designed and constructed 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 our project combines leading expertise in sample spinning, electronics and cryogenics, in order to overcome these difficulties. In the translation grant we will develop the equipment further so as to allow the samples to be exchanged rapidly and conveniently. We will also invite external users to run their samples on our equipment, in order to develop and strengthen scientific collaborations both within the UK and internationally. We will perform experiments on two different sets of biomolecules produced in Southampton and Leeds, in order to elucidate their molecular structure and functional mechanism. We will also study conducting materials of great technological importance, such as organic conductors, semiconductors and superconductors. The cryoMAS-NMR experiments will allow visualization of the electronic conduction properties with sub-molecular resolution. This will greatly assist the development of new materials with applications in computing, communications, solar energy, and fuel cells.