New paradigms for NMR of organic solids

Nuclear Magnetic Resonance (NMR) spectroscopy is a vital analytical tool across science. NMR is most usually applied to substances dissolved in solution since this considerably simplifies the interpretation of the results (spectra) that are obtained; molecular motion averages out interactions, such as the dipolar (through space magnetic) interaction between the magnetic nuclei. However, in many applications, particularly in materials chemistry and biology, it is impossible or inappropriate to apply NMR to samples in solutions and it is necessary to work with solid samples. This creates particular difficulties for studies using hydrogen (1H) NMR which is otherwise the most widely used form of NMR (including in medical imaging applications). Typical organic (carbon-containing) molecules contain high densities of hydrogen nuclei. Although an advantage in terms of the strength of the NMR signal, the multiple magnetic (dipolar) interactions between the hydrogen nuclei cause the NMR signal to decay quickly and broaden the NMR lines into uninformative broad features. This problem has traditionally been tackled in a couple of ways. Firstly by spinning the sample (magic-angle spinning), but unfeasibly high spinning rates would be required to completely remove the dipolar interactions. Secondly using radio-frequency irradiation to average out the dipolar interactions, but this can be technically complex and the results are very susceptible to experimental deficiencies. Since the line-broadening involves the interactions of multiple nuclear spins it has been difficult to model computationally and to investigate mathematically. As a result, progress in improving 1H NMR spectra in solids has been rather fitful.This project will tackle this bottle-neck for the development of solid-state NMR. Firstly by putting together a consortium of international research groups with complementary expertise (experimental, computational and theoretical) and equipment (including NMR spectrometers operating at some of the highest magnetic fields available worldwide) we will be able to tackle the problem simultaneously and systematically from different directions. Secondly, recent advances in spectrometer hardware, simulation and NMR theory mean that the individual tools are in place to make concerted progress. Finally we will be focussing on one parameter, the decay rate of the magnetisation, which is the key limiting factor. Previous work has addressed final NMR spectra, but since these are affected by a number of additional factors, this has tended to confuse the underlying issues. The large discrepancies between simulations and current experiments suggest that potentially major improvements are possible.Finding routes to producing high-quality NMR spectra of hydrogen-containing organic solids in a routine fashion will have a major impact on the practice of solid-state NMR. Some experiments which are currently impractical due to the length of time they would take will become practical and narrowing the NMR lines will allow new, finer spectral detail to be measured, such as weak interactions across hydrogen bonds connecting different components of crystal structures. As a result this proposal is being supported by a wide range of scientists, varying from users of solid-state NMR to manufacturers of pharmaceutics to suppliers of NMR equipment.

The principal direct short-term non-academic beneficiaries of the research described in this proposal are within the commercial private sector: 1. Users of solid-state NMR, most notably the pharmaceutical industry which has made major recent investments in the analytical provision of solid-state NMR infrastructure, 2. Suppliers of commercial solid-state NMR analytical services, 3. Instrument manufacturers. The research project plan also identifies beneficiaries in the fields of energy storage materials and biophysics, where the impact is more likely to be felt in the medium/long term. The benefits to users of solid-state NMR spectra and suppliers of commercial solid-state NMR services are derived from the major improvements in experimental methodology that should emerge from this research. Solid-state NMR is a powerful tool for the characterisation of organic solids, and is widely used in the pharmaceutical industry for example, but performance is limited directly and indirectly by the poor resolution of 1H NMR spectra in the solid state. Bringing 1H resolution and coherence lifetimes for 1H, 13C and 15N NMR towards their theoretical limits would transform the viability of many solid-state NMR experiments, and greatly increase the attractiveness of solid-state NMR as an analytical tool. Similarly, step changes in the utility of a technique are of obvious benefit to the instrument manufacturers. Moreover, a primary goal is to identify the key hardware features that determine experimental performance. This will provide the manufacturers with a roadmap for hardware development and guide internal R&D. In both cases, the impact of progress will feed through swiftly to the target audiences i.e. within a few years. Beyond these immediate target areas, the benefits will diffuse out to all users applying NMR to organic solids e.g. research scientists developing new materials for energy storage, or determining structures of difficult but important biological materials such as amyloid plaques and membrane proteins. Hence the longer term benefits will reach well beyond the area of the project itself to a wide range of materials chemistry and biophysical applications, with evident societal and economic impact. The most important asset for maximising the impact of this research is the composition of the proposed consortium which consists of academics with complementary research interests across solid-state NMR, instrument manufacturers and pharmaceutical companies (who are the UK industrial users with by far the largest investments in solid-state NMR). The project is designed to include validation of the results on important applications such as pharmaceutical and energy storage materials. Together with the composition of the consortium, this ensures that the work will impact on wider applications and not just be limited to the circle of academic researchers working in solid-state NMR methodology. In addition to the normal dissemination mechanisms for scientific research via publications and conference presentations, a project website will aggregate results and provide a valuable resource beyond the lifetime of the project. The PDRA will finish the project with a very strong skills set that would make him/her very employable: 2 recent EPSRC-funded PDRAs at Durham and Warwick now have positions as specialist solid-state NMR spectroscopists in the pharmaceutical industry and with a spectrometer manufacturer.