Terahertz electron paramagnetic resonance: A window on biological exploitation of quantum mechanics

Everyone who reads a newspaper or watches the news on television will know that we are facing an energy crisis. The world's fossil-fuel energy reserves are dwindling and yet our thirst for energy is accelerating at an ever increasing rate. Scientists and engineers dream of solving this problem by harvesting the vast power of our Sun, storing its energy by breaking apart water and forming hydrogen gas. If only we could find an efficient and economical way of performing this chemical conversion the dream could become a reality. Our greatest hope today lies in harnessing the power of nature's own biological catalysts, enzymes, to promote desired chemical reactions. Enzymes are extremely efficient catalysts that allow chemical reactions to take place billions of times faster than normal. Unfortunately, enzymes are limited to the specific set of chemical reactions that they evolved to catalyse. Attempts to tailor enzymes to our needs have so far been disappointing. This is not surprising given our poor understanding of how they work. Conventional theory is unable to account for the incredible increases by which a reaction is speeded up by enzymes. A new emerging theory of enzyme catalysis suggests that if we had a window on this world we would see enzymes manipulating a phenomenon called quantum mechanical tunnelling to their advantage. We envisage chemical reactions overcoming the energy barrier that slows their progress, not by climbing over it, but by tunnelling directly through it. Even more strange, we think that enzymes might use their subtle vibrations to squeeze the energy barrier, reducing its thickness, to promote tunnelling and speed up the reaction.

This project seeks to determine whether enzymes have indeed evolved to manipulate quantum mechanics, by using their movements to accelerate chemical reactions. In order to do this a novel instrument will be constructed to provide a unique window on this world. This instrument is based on a technique called Electron Paramagnetic Resonance (EPR), a cousin of the more familiar Magnetic Resonance Imaging (MRI) technology seen in hospitals. While existing instruments use microwave radiation, which limits their ability to distinguish features, this new instrument will use radiation that lies between the microwave and infra-red parts of the spectrum, so-called terahertz radiation. This will result in structural information being revealed in exquisite detail. In addition, flashes of terahertz radiation will be generated using pulses of laser light lasting less than one millionth of a millionth of a second enabling snap-shots to be taken of enzymes in action. The ability to watch these fast tunnelling processes is essential to our understanding of enzyme function and is far beyond the reach of existing instruments. Producing these action-packed enzyme movies with such high-definition structural information will rely on the precise timing between multiple bursts of terahertz radiation. To achieve these ambitious goals this project brings together a combination of industrial and academic collaborators with expertise in laser development, advanced EPR measurements and apparatus, and enzyme catalysis. Under my leadership, this project will provide knowledge crucially important to the successful exploitation of these remarkable biological catalysts.

The diverse array of new materials and science that can be studied with a compact laboratory-based terahertz-frequency electron paramagnetic resonance (EPR) spectrometer will certainly result in a significant worldwide market for the technology. The potential of this novel instrument will be explored in collaboration with Bruker, a leading international manufacturer of EPR spectrometers, starting with a workshop hosted at their research facility (see Statement of Support). The spectrometers optical synchronisation scheme is anticipated to have a more immediate commercial impact, which will be exploited in collaboration with Spectra-Physics (see Statement of Support). In addition to the technological outputs from this project, the knowledge gained in enzyme catalysis will ultimately benefit the whole of society. It will contribute to the global energy challenge, through the engineering of biological catalysts for improved energy utilisation in a wide range of industrial processes. An understanding of the fundamental mechanisms for proton (hydrogen) transfer in enzymes will also have major biomedical impacts, such as in controlling drug metabolism. Furthermore, the insights afforded by this ultrafast THz-EPR spectrometer into the fundamental mechanisms at the heart of a range of biological organisms offers potential benefits in bio-energy production, bio-remediation (converting waste to energy), carbon management, and are expected to provide new strategies for developing artificial solar cells that could operate efficiently in low-light environments such as northern Europe. The dissemination of knowledge from this project to Members of Parliament and the general public will also help inform the choices society faces in tackling the energy challenge.

The post-doctoral research associate employed on this grant will benefit from thorough training in all aspects of the commissioning and utilisation of a cutting-edge spectrometer. Furthermore, the chance to work in collaboration with internationally-leading academics and a global manufacturer of advanced laser technology will provide a wealth of training opportunities, ranging from advanced experimental techniques to business awareness. This will greatly benefit their future career, be it in industry or academia.