A 700 MHz broadband cryoprobe and NMR spectrometer at UCL Chemistry

Lead Research Organisation: University College London
Department Name: Chemistry

Abstract

There are different types of scientific equipment in each university. But one type which is most widely used by hundreds, from undergraduate students to emeritus staff, is nuclear magnetic resonance (NMR) spectroscopy. The advantage of NMR relies on its versatility and applicability to nearly any kind of material. The NMR of a liquid, mainly a solution of a material in a solvent, is particularly widespread due to the ease of use and the rich information content provided by well-resolved signals. The major problem in NMR, however, is sensitivity: we usually need milligrams of a sample to collect an NMR signal. Sensitivity is measured as a signal-to-noise ratio on a standard sample. One way to improve it is to increase the magnetic field strength. After about 25 years of magnet developments, a saturated state was approached. A breakthrough came in 1999 when the temperature of the probe coil and other parts was dropped drastically giving a >4-fold increase in sensitivity. This translates into a >16-fold reduction in time. The introduction of cryoprobes in NMR can be compared to the implementation of fast processors in computers. The increase in sensitivity means that we can now measure not only 1H or 31P with nearly 100% natural abundance but also 13C or 15N of small amounts of sample.

The main objective of this proposal is to introduce the first broadband cryoprobe at the highest 1H frequency of 700 MHz into a daily research of a diverse range of materials and drugs in Physical and Life sciences. To give a few examples, the new equipment will be used in such studies as the origin of life, drug discovery, cancer research, metabonomics, batteries, polymers and catalysis. The equipment will be installed in UCL, which has a £385M total EPSRC support. It will become part of the existing NMR facility in UCL Chemistry, with 4 solution and 1 solid-state NMRs. The 700 MHz instrument will be the highest field instrument at UCL Chemistry and will underpin both chemical biologyand materials research.

In recent years, several new appointments have been made, many of which actively use NMR, including Prof Battaglia - the chemistry of biological polymers, Dr Powner - origins of life via chemical pathways leading to biological form and function, multicomponent reactions, sulphur and phosphorus chemistry, Dr Chudasama (named by Forbes magazine as one of the world's top scientists under the age of 30) - novel biotechnology drugs for selective delivery of chemotherapy to tumour cells via combinations with antibodies, Dr Bronstein - conjugated fused aromatic small molecules and polymers for use in optoelectronics. Within a short time, Dr Powner has become our leading NMR user, running >35% of the total number of NMR spectra. His research will gain considerably from the multinuclear and improved signal dispersion capabilities of the new instrument.

In addition to addressing the increased demand within UCL Chemistry, the new equipment will be used by >15 other UCL departments, which have joint EPSRC supported research projects with Chemistry, including Biochemical Engineering, Chemical Engineering, Eastman Dental Institute, School of Pharmacy, Wolfson Institute and others.

As this is a unique facility with the first helium-cooled broadband cryoprobe in the UK, the use of the new equipment will be extended to include other UK universities and research institutions in order to address their need in NMR of less studied nuclei. The operation of the facility will be fully automated to provide high throughput. Remote access will also be enabled for users from outside UCL Chemistry.

It is expected that the new facility will provide more comprehensive structural information by expanding NMR to nearly all atoms present in a molecule, not just 1H and 13C. This will enable drawing detailed structure-property relationships, which in turn will enhance our ability to design new advanced materials and drugs with desired properties and functions.

Planned Impact

Development of new materials and drugs with desired properties relies on our knowledge of their structure and dynamics. The most versatile technique in this regard is NMR spectroscopy. Applied separately on each type of nucleus present in a material NMR provides much-needed selectivity for structure and dynamics studies, which in turn advances our ability to design new materials and drugs.

The major problem of NMR, however, is its sensitivity, requiring larger quantities of samples than other methods. The objective of this proposal is to establish a 700 MHz NMR facility with a helium-cooled broadband cryoprobe. The proposed facility will be unique in the sense that it will combine multiple cutting-edge NMR technologies into a single all-in-one instrument dedicated to comprehensive studies of materials at the atomistic level. It will provide record levels of sensitivity for NMR measurements enabling experiments considered as unfeasible until recently, such as 19F NMR detections at micromolar concentrations or natural abundance NMR of 15N in the absence of nearby protons.

To our knowledge, there is no such facility in the world, making this instrument unique as multinuclear NMR equipment at the internationally leading level. Therefore, the requested equipment meets national needs by establishing a unique world-leading research activity. As such, it will be available to students and staff from UK academia and industry.

The immediate beneficiaries will include the EPSRC funded projects. Researchers from London and other UK universities will be provided with the full walk-up access to the new facility. In UCL Chemistry alone, the facility will have a direct impact on the research of >20 groups. The highest sensitivity of multinuclear NMR facility combined with fully automated and remote operation will satisfy requests from hundreds of users promptly, expediting wide impact of the facility.

The impact of the proposed facility on fundamental and applied sciences spans Chemistry, Materials Science, Biology, Physics, Medicine, Healthcare, Engineering, Geology and others. The research enabled by the new equipment is relevant to the strategic EPSRC themes:

1. Energy (EP/K014714 £3.7M, EP/N009533 £1.3M, EP/L017091 £840K)
2. Healthcare Technologies (EP/K031953 £11M, EP/M01732X £564K)
3. Manufacturing the Future (EP/L017709 £2.3M, EP/K014897 £1.9M, EP/N01572X £778K)
4. Physical Sciences (EP/K004980 £970K, EP/M02220X £345K)
5. Research Infrastructure (CRUK&EPSRC Cancer Imaging Centre at KCL&UCL)

The new equipment will benefit research falling within the four Grand Challenges of Chemical Sciences and Engineering:

(i) Dial-a-Molecule - 100% efficient synthesis
(ii) Directed Assembly of Extended Structures with Targeted Properties
(iii) Systems Chemistry: Exploring the Chemical Roots of Biological Organisation
(iv) Utilising CO2 in Synthesis and Transforming the Chemicals Industry

The research benefiting from the new facility is also relevant to 2 out of 4 Grand Challenges in Physics:

(i) Nanoscale Design of Functional Materials and
(ii) Understanding the Physics of Life,

as well as in Healthcare Technologies:

(i) Developing Future Therapies and
(ii) Optimising Treatment.

Thus, the new equipment will contribute towards addressing long-term public expectations and industrial needs identified by EPSRC. For example, the amidation reaction by Dr Sheppard will be crucial for direct amide synthesis, the most commonly used reaction in the pharmaceutical industry, which is a sector of huge importance to the UK economy.

The principal and substantial impacts will come from the work done by many groups using the new facility, which will affect lives of broader social groups through developments of, e.g., new batteries, solar panels, drugs and healthcare products. The new facility will also impact research into diagnostics and therapy of such diseases as cancer, liver cirrhosis and multiple sclerosis.

Publications

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Fernández-García C (2018) Selective aqueous acetylation controls the photoanomerization of a-cytidine-5'-phosphate. in Chemical communications (Cambridge, England)

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Gibson SM (2018) Dihalohydration of Alkynols: A Versatile Approach to Diverse Halogenated Molecules. in European journal of organic chemistry

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Janicki MJ (2018) Photostability of oxazoline RNA-precursors in UV-rich prebiotic environments. in Chemical communications (Cambridge, England)

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Motherwell WB (2018) Noncovalent Interactions of p Systems with Sulfur: The Atomic Chameleon of Molecular Recognition. in Angewandte Chemie (International ed. in English)

 
Description Currently, the 700 MHz instrument operates without the broadband cryoprobe the delivery of which is expected on 26th March. Nevertheless, the instrument is available for use with a room temperature broadband probe both to academic and non-academic users. As an example, over 70 NMR spectra were run for Abcam Plc (Cambridge) between November 2017 and March 2018. Since July 2017, the facility has also been used by users from the UCL Dementia Research Centre, which focuses on the clinical research into various forms of dementia. The research group led by Prof David Selwood, which develops drugs for multiple sclerosis and other diseases, has also started using the facility since its installation.
First Year Of Impact 2018
Sector Chemicals,Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic,Policy & public services

 
Description NMR Metabonomics for the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Researchers from UCL Centre of Rheumatology and New Zealand
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Title NMR Chemical shift anisotropy measurements 
Description Using 300 MHz and 700 MHz NMR instruments, it has been shown that static lineshape measurements are better suited for accurate measurements of the chemical shift anisotropy than those based on magic-angle spinning. 
Type Of Material Data analysis technique 
Year Produced 2017 
Provided To Others? Yes  
Impact Accurate measurements of chemical shift anisotropy is important for materials, chemistry and biological sciences. 
URL https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub
 
Description Noncovalent Interactions of p Systems with Sulfur 
Organisation University of Southampton
Department Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution The relative strength of noncovalent interactions between a thioether sulfur atom and various p systems in designed top pan molecular balances was determined by NMR spectroscopy. Compared to its oxygen counterpart, the sulfur atom displays a remarkable ability to interact with almost equal facility over the entire range of p systems studied, with the simple alkene emerging as the most powerful partner. With the exception of the O···heteroarene interaction, all noncovalent interactions of sulfur with p systems are favoured over oxygen.
Collaborator Contribution Experimental structure determinations in the solid state were carried by our partners Dr. G.J.Tizzard and Prof. S. J. Coles from School of Chemistry, University of Southampton.
Impact Publication at http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201708485/abstract
Start Year 2015
 
Description Tin chemical shift anisotropy in tin dioxide 
Organisation Rutherford Appleton Laboratory
Department Scientific Computing Department
Country United Kingdom 
Sector Public 
PI Contribution Experimental NMR measurements of 119Sn and 31P NMR powder lineshapes using 300 MHz and 700 MHz NMR facilities.
Collaborator Contribution Computational predictions of NMR chemical shift anisotropy
Impact Publication at https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub#!
Start Year 2017
 
Description Tin chemical shift anisotropy in tin dioxide 
Organisation University of Oxford
Department Department of Materials
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental NMR measurements of 119Sn and 31P NMR powder lineshapes using 300 MHz and 700 MHz NMR facilities.
Collaborator Contribution Computational predictions of NMR chemical shift anisotropy
Impact Publication at https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub#!
Start Year 2017
 
Description A visit and spectra for The King Fahad Academy Bromyard Avenue London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A visit took place on 31 October 2017, during which the NMR equipment including the new 700 MHz NMR was demonstrated. This was followed by measurements of NMR spectra for the student projects (Extended Essay in Chemistry).
Year(s) Of Engagement Activity 2017
 
Description NMR visits for schools 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The new equipment was demonstrated to school pupils visiting UCL Chemistry on the Spectroscopy Day on 13 September 2017.
Year(s) Of Engagement Activity 2017
 
Description Provision of NMR service to users from Industry and Academia 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Users from other UCL departments and other UK universities visited the facility. Spectra were recorded on the new facility for users from other universities, as well as from industrial companies.
Year(s) Of Engagement Activity 2017,2018