High-field Dynamic Nuclear Polarization Magic Angle Spinning NMR for Chemistry, Physics, Materials, Pharmaceuticals and Biomolecular Science

Lead Research Organisation: University of Nottingham
Department Name: Sch of Physics & Astronomy

Abstract

Solid-state nuclear magnetic resonance (NMR) is a spectroscopic technique which is used to study the molecular structure and dynamics of systems from the advanced materials used for hydrogen storage, drug delivery and catalysis to biological molecules, such as proteins and RNA. However, compared to other approaches, solid-state NMR suffers from a lack of sensitivity and long acquisition times for signal accumulation or large sample volumes are required. The amount of signal acquired in a NMR experiment depends on the nuclear spin polarization which arises in the presence of a magnetic field, and since the magnetic moments of nuclei are relatively weak, a superconducting magnet is required. However, even with the strongest superconducting magnets available today, NMR studies of dilute species, such as molecules adsorbed on surfaces, proteins in whole cells or isotopes with low natural abundance, are impossible.

However, the electronic magnetic moment is about three orders of magnitude stronger than that for the hydrogen nucleus and consequently unpaired electrons in radicals carry a much larger spin polarization. Hence, the NMR signal can be enhanced by so-called dynamic nuclear polarization (DNP) which involves the transfer of the large electronic polarization from radicals implanted in the sample onto neighbouring nuclei via their mutual dipolar coupling. The DNP process requires the saturation of particular frequencies in the electron spin resonance spectrum using a strong microwave source. The principles of DNP have been known since the early days of NMR, but the technique was limited to magnetic fields much smaller than those used in modern NMR spectrometers with severe implications for the resolution of chemical sites. However, the development of gyrotrons as high-power microwave sources has made robust DNP instrumentation operating at high frequencies possible. Signal enhancements of up to 300-fold can now be achieved, corresponding to a reduction of a factor of 100000 in the required measuring time. The recent commercialization of DNP hardware makes it possible to focus on applications in a wide range of scientific disciplines rather than having to worry about the complex instrumental requirements.

This proposal aims to provide access to DNP solid-state NMR for a broad section of the UK science community by installing a DNP Facility at the University of Nottingham based on a commercial instrument.

Planned Impact

Without novel developments in techniques for structure characterization such as solid-state NMR the molecular sciences would not be able to achieve their potential impact on the wealth and health of the UK. Over the last decades the impact of solid-state NMR measurements on diverse areas of science, technology and industry has been considerable. For example, the method has provided crucial insight into the role of defects in electrode materials in cycling of rechargeable batteries, into the effect of polymorphism on pharmaceutical formulations and into the structure of ion channels in cell membranes targeted by new drugs. However, lack of sensitivity means that solid-state NMR is often unfeasible for real systems where the active component is present in small concentrations, such as catalysts supported on surfaces, drug molecules in pharmaceutical formulations or particular proteins in whole cells. Nevertheless, the atomic-level structural characterization even for amorphous or heterogeneous systems provided by solid-state NMR is a pre-requisite for intelligent molecular design of new materials or understanding the structural biology behind new therapeutic treatments. The new DNP MAS NMR technology has the potential to overcome the sensitivity issue in many NMR application by providing signal enhancements by a factor ~100 and more, corresponding to a 10,000-fold decrease in the required experiment time. This represents a paradigm shift in the capability of solid-state NMR which opens up significant possibilities for new applications. Thus, the impact of DNP on the broad range of science already underpinned by solid-state NMR will be substantial.

At Nottingham we envisage that the DNP MAS NMR instrument will provide a unique and novel measurement technology to add value to research in a range of RCUK-funded high-impact priority areas, including advanced manufacturing, sustainable processing, energy, drug discovery and biomedical imaging, as indicated by the specific projects described in the Case for Support. Potential developments in these areas extend beyond the underlying science and encompass the economic well-being of the UK, the quality of life of its citizens or solutions to global problems, such as climate change. For example, insight from DNP will help design novel catalysts which support new processing technologies, improved porous materials for CO2 sequestration or H2 storage or new antimicrobial therapies.
Some 40 researchers from 15 institutions have expressed interest in using the DNP MAS NMR Facility which will provide access to the only instrument of its kind in the UK. The many novel applications and interesting projects proposed in their Letters of Support reflect the unique versatility of solid-state NMR in the UK and the potential impact of DNP on this portfolio. Many of the advances envisaged through the application of DNP are aimed exactly at the big questions behind the EPSRC's research themes and grand challenges or the BBSRC's strategic priorities.

Solid-state NMR is already recognized as a powerful analysis tool by several leading companies in the food, healthcare, pharmaceutical and speciality chemicals sectors, including AstraZeneca, GlaxoSmithKline, Unilever and Johnson Matthey. However, the combination with DNP has only recently emerged as a robust experimental technique through the availability of commercial hardware and has yet to be adopted by researchers based in industry. The proposed DNP MAS NMR Facility will allow UK-based industry to evaluate the potential impact of this technique on their business through pilot studies.

DNP MAS NMR will provide new insight about molecular structure in real systems which will trigger advances in high-impact areas of science and industry. It is critical that DNP MAS NMR instrumentation is a part of the UK's infrastructure.

Publications

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Hope MA (2017) Surface-selective direct 17O DNP NMR of CeO2 nanoparticles. in Chemical communications (Cambridge, England)

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Shimon D (2019) DNP-NMR of surface hydrogen on silicon microparticles. in Solid state nuclear magnetic resonance

 
Description With this grant we established a unique facility in the UK which is now used also by a number of externals groups (e.g. Cambridge, Southampton, Liverpool, Oxford)
Exploitation Route We have secured a follow up grant (EP/R042853/1) that we are using to further offer access to this unique facility.
Our user commuinty has also submitted in Oct 2019 a statement of community need in response to an EPSRC call for new nation research facilities. This statement of need was prioritised in Feb 2020 but then despite contacting EPSRC we have not heard anyhting since February 2021. Do to financial constraints we are currently not able to keep the facility open during the COVId19 lockldown.
Sectors Chemicals,Energy

URL https://www.nottingham.ac.uk/dnpnmr/home.aspx
 
Description This grant has been used to fund access of external users to a unique DNP MAS NMR spectrometer which we host in our lab (It is the only commercial instrument of its kind in the UK). some of the projects using the new method have potential impact on UK economy. For instance, work done by the external group of Prof Clare Grey's group at the University of Cambridge who have used our facility at several occasions has potential impact to the commercial energy storage sector. We have also provided access to the instrument (against payment of an access charge) for confidentai collaborations with the industrial sector (e.g. Johnson Matthey, GSK). NMR spectroscopy underpins many chemical, biological, and physical studies and is critical to the chemical and pharmaceuticals industries. The method is capable of characterising crystalline, amorphous, organic and inorganic materials with atomic resolution. However, the intrinsic sensitivity limitations of the conventional method generally precluded its use for surfaces, interfaces, and elucidating small components of large complex systems or environments of nuclei with low isotopic abundance (such as 13C, 15N, and 17O). Therefore, the sensitivity gains associated with DNP MAS NMR offered by our facility make it a key enabling technology. It allows structure analysis, where conventional methods fail. The breadth of the research currently supported by DNP MAS NMR is evidenced by the access statistics for our spectrometer since its installation in 2016. The 42 research projects carried out so far from 18 different institutions have covered 14 separate EPSRC research areas as well as some of the key themes and priorities of BBSRC and MRC. Consequently,our facilityl enables research aligned to the EPSRC Prosperity Outcomes of Productivity (e.g. rational design of innovative materials), Resilience (e.g. sustainable and selective catalysis), and Health (e.g. designer pharmaceutical formulations) and will impact the Themes of Energy, Engineering, Healthcare technologies, Manufacturing the future, Physical sciences, and Research infrastructure. Based on the success of this facility, we have been successful in 2021 to attract further funding for the next 5 years to keep our facility open to the UK science community.
Sector Chemicals,Energy,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Maximising the sharing of the Nottingham DNP MAS NMR Facility
Amount £161,949 (GBP)
Funding ID EP/R042853/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2018 
End 09/2020