Meeting the Sensitivity Grand Challenges in Pulsed Electron Magnetic Resonance

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Summary This instrument development project seeks to substantially and dramatically increase the sensitivity and time resolution and capability of electron paramagnetic resonance (EPR) spectrometers and to demonstrate a major impact across biology, chemistry, physics and materials science. One of the fundamental quantum mechanical rules governing the basic structure and organisation of matter, is that electrons like to pair up. However, in many materials there are unpaired electrons left over from this pairing process. Such systems are known as paramagnetic and examples include radicals, many types of metal atoms, and defects in crystals. The reactivity of any given unpaired electron strongly depends on its local atomic environment. Some radicals are so reactive that they are able to tear electrons from any nearby molecules and initiate a destructive cascade of reactions. Indeed, it is the accumulated damage from such free radicals within the body that is believed to underlie our aging process, despite the body evolving many defense mechanisms. Measurements of free radicals in the blood can be health indicators. Other paramagnets can be relatively stable and highly beneficial. Transient paramagnetic species are involved in closely regulated reactions in huge numbers of biological processes. Much of the UK's chemical industry depends on the use of radicals and transition metals to initiate and promote catalytic reactions. Paramagnetic defects in crystals, thin films or at interfaces can determine or strongly affect a material's electronic, magnetic, optical, chemical and mechanical properties and are hugely important in the UK's material science and electronics industries. The sensitivity of NMR or MRI experiments can be dramatically increased by making electron spins interact with local nuclei.Even in systems where there are no naturally occurring unpaired electrons, molecular biologists have developed ways to routinely add free radical (electron) spin labels at specific sites within biomolecules, which can be used as "molecular spies" to understand reactions, interactions, large-scale structure and fast dynamics with a precision not possible with other techniques. Characterisation of such structures and processes can underpin the understanding of the mechanisms behind disease and the development of new drugs. The most important tool in studying and understanding these systems is pulsed electron paramagnetic resonance. This technique involves placing a paramagnetic sample in a large magnetic field and illuminating it with a carefully controlled sequence of rapid high power microwave pulses and monitoring the response of the sample. Until relatively recently, it was widely believed there was little scope to significantly improve the sensitivity of pulsed EPR instruments. Yet ten years ago we demonstrated a significant increase by a factor of between 15 and 30 in concentration sensitivity for common measurements. Today, commercial instruments have nearly but still not caught up. This project now seeks to further increase sensitivity, by another factor of 30. This increase will be achieved by taking advantage of recent advances in fast electronics and by modifying an existing state-of-the-art system using techniques that we have already demonstrated in many proof-of-principle experiments. This would be a major advance, particularly for molecular biology, as for the first time it would allow spin-labeled protein systems to be investigated at natural (in-cell) protein concentrations using electron magnetic resonance. There are also many important electronic, materials and catalytic systems, which involve paramagnetic centres in thin films or at interfaces where sensitivity is paramount.To maximise the impact of the instrument development, the project is linked to a large number of applications and methodology development programmes, with a wide range of local collaborators and co-investigators.