Dynamic Structural Science at the RC@H

All chemical reactions and biological processes involve the movement of atoms, molecules or electrons and the speed at which these events occur may range from the very fast (femtoseconds, 10^-15 s) to the rather slow (hours or days). If we are to be able to improve our understanding of all these processes it would be very helpful if we could actually watch the atoms move and make molecular movies showing the progress of a chemical reaction. However, this is not straightforward because of the size of the atoms and molecules involved, which are too small to be seen through a conventional microscope. The techniques that have been available up to now include time resolved spectroscopy, which gives information on how some atoms within a molecule may move, or NMR spectroscopy which provides valuable information about molecular conformations in solution and allows some relatively slow processes to be followed. Ideally, a three dimensional picture of a molecule as it transforms is required. In the solid state it has been possible to obtain a three dimensional picture of a molecule or a biological macromolecule using X-ray or neutron diffraction for about the last 100 years, but both these techniques require minutes, and more often hours or, in the case of neutron diffraction, even days to obtain enough data to obtain this three dimensional picture. Thus, X-ray and neutron diffraction techniques have only been useful for obtaining the structures of molecules before they react or after the reaction is complete. The aim of this proposal is to develop a new technique called time resolved, or dynamic, structural science, which will bring the dimension of time into the crystallographic experiment and allow us to determine the structures of short-lived intermediates, with lifetimes of microseconds or less, or, by taking snapshots of a chemical process as it occurs at 100 picosecond intervals, make a molecular movie and watch the process occur. In order to achieve this aim we propose to assemble a range of experts from the leading structural and time resolved science groups in the UK and centre them at the new Research Complex at Harwell. This multidisciplinary team consisting of chemists, biologists and physicists will use the unique facilities on the Harwell site to develop the dynamic structural methods necessary to make molecular movies and to compare the results obtained by these methods in the solid state with the results obtained by time resolved spectroscopic methods. The Research Complex provides a unique working environment that will facilitate interactions with other physical and life scientists. Occupancy of the Complex also provides easy access to the Diamond Light Source, which generates very high intensity X-rays suitable for the crystallographic studies, the ISIS neutron source, which provides high intensity neutrons that are particularly useful for looking at materials that contain light atoms such as hydrogen, and the Lasers for Science Facility, which has high power lasers, whose very intense and tuneable light beams can be used for photoactivating the molecules to be studied and where the time resolved spectroscopy will be carried out.Once the new methodologies have been developed they will be used to study a range of important chemical and biological processes, that will include catalytic processes, light activated biological processes and reactions involving the movement of hydrogen atoms which are very important in both chemical and biological processes. The information gained will provide a better understanding of the reaction mechanisms and will point the way to the design of new, energy efficient catalysts, smarter sensor materials, new, more effective pharmaceuticals and other new materials. We will also work with scientists outside our consortium to allow our project to do an even wider range of exciting science and watch still more chemistry happen.

The main impact that will result from this project is the discovery of new knowledge and the development of new experimental techniques that will lead to scientific advances in the physical and life sciences. The ability to view molecular movies of molecules reacting or macromolecules undergoing conformational changes will have a wide appeal since it is an inherent pictorial approach that will help to resolve complex processes. The new methodologies developed will certainly have an impact on the way that chemical and biological processes are thought about and will open up pathways for new types of experiment to be designed and performed. Obvious applications of this work will be in (i) the area of catalysis, where it will be possible to follow a catalytic process as it occurs by identifying reaction intermediates, (ii) in the area of molecular sensors and opto-electronic materials, where it will be possible to measure the bond parameters and establish the configuration of a photoactivated molecule with a lifetime of less than a microsecond, and (iii) in the structural dynamics of biological macromolecules where the ability to visualise intermediates will direct the design of novel therapeutic agents. These three examples show that while the initial impact will be in the academic area the knowledge gained will drive applications development. The development of new sensors and energy efficient devices will, in due course, have a benefit for the wider society, and will enable the development of environmentally clean catalysts. The drive for energy efficient and environmentally friendly processes is a major societal target. Similarly, the better understanding of biologically important molecules will have a major impact in the area of healthcare. For the same reasons, this project will lead to the development of new products and procedures that will be beneficial to the economy and assist in wealth creation for UK plc. A key component of the project is the training of young scientists in the area of time resolved structural science. The initial beneficiaries will be the PDRAs and the visiting students who will be given unique multidisciplinary training in this developing area of science. These skills will provide them with the expertise that will allow them to have a significant impact in either the academic or industrial communities and enhance their career prospects. Through the annual workshops to be set up during the project the skill set will be spread to a wider audience of academics and industrialists and this will have an immediate impact on the development of new products and processes and on the development of new science. In this way a people pipeline will be set up that will involve worldwide participation.