Development of a Dynamic Nuclear Polarisation based NMR techniques for the rapid detection and characterisation of reaction intermediates.
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
Project SummarySummary Catalysis mediated by compounds of the transition metal elements is an extremely important area of inorganic chemistry and is the corner stone of virtually the entire chemicals industry. Central to the ability to refine and optimise any catalytic system is a detailed knowledge of the pathways by which the reaction proceeds. One technique commonly used in the study of these types of reaction and for the observation of catalytic intermediates is nuclear magnetic resonance (NMR) spectroscopy. This technique utilises the phenomenon of nuclear magnetism to detect molecules containing atoms with magnetically active nuclei. Nuclei of isotopes such as 1H, 13C, 15N and 31P can therefore be thought of as tiny bar magnets. When placed in the field of a strong magnet, such as that found inside an NMR spectrometer, the bar magnets can either align to reinforce or oppose the main field with the result that states of differing energies are produced. Transitions between these states can be achieved by the absorption of radio frequency signals. These frequencies are a characteristic feature of the chemical environment of the nuclei and ultimately can be used to identify the contributing compound. The sensitivity of this technique is however greatly limited.In this project we will utilise a new technique called dynamic nuclear polarisation (DNP) to increase the sensitivity of the NMR method by a factor that will approach 10,000 and allow the detection and characterisation of low concentration reactive compounds that would otherwise not be observable. Our aim is to established procedures and methodologies that will allow us to sensitise by DNP a suitable precursor substrate compound that subsequently undergoes chemical reactions, using the NDP derived signals as a probe to detect that passage of the substrate through transient intermediates involved in the reaction mechanism. This will enable us follow their reactivity and gain an understanding of the sequence of fundamental reaction steps involved in the catalytic cycle.In order to achieve this however, new NMR experiments must be designed in order to efficiently utilise the signal generated by the DNP method involving the implementation of state-of-the-art rapid scan (in collaboration with Prof Frydman of the Weizmann Institute, Israel) and selective observation methods. We will also need to design and build a sampling handling system that mixes the DNP sensitised materials with other compounds involved in the reaction of study and delivers the reaction mixture in a controlled manner into the region of the NMR spectrometer where measurements will be taken.We will first target simple reactions involving metal containing compounds that yield stable products as a testing ground for these new techniques and will then follow onto to study catalytic reactions. Our initial choice of system is the widely used alkene metathesis reaction catalysed by Grubb's catalyst (Nobel prize 2005) using DNP sensitised alkenes to probe the metallic compounds involved in the catalytic reaction mechanism. Some of the intermediates have already been observed an identified but much work can still be achieved. Therefore this system acts as an ideal proving ground for these methods. Later will be extend our study to another high value reaction, the Heck reaction and focus on the system catalysed by palladium containing P,C-palladcyclic complexes. Here, very little is known about the exact mechanism of operation or the route by which the catalyst is activated.This work will have significant impact, not only on the immediate catalytic chemistry community, but the techniques developed will also have spin-off applications in other fields such as biological NMR research and other areas of analytical chemistry where limited sample size is a major problem.
People |
ORCID iD |
S Duckett (Principal Investigator) |
Publications
Adams RW
(2009)
Reversible interactions with para-hydrogen enhance NMR sensitivity by polarization transfer.
in Science (New York, N.Y.)
Adams RW
(2009)
A theoretical basis for spontaneous polarization transfer in non-hydrogenative parahydrogen-induced polarization.
in The Journal of chemical physics
Description | We worked to hyperpolarise a range of molecules by the DNP effect. We subsequently examined the reactivity of these molecules in order to probe a number of reaction mechanisms. |
Exploitation Route | Our findings revealed that this method was harder to employ than we originally envisaged. We recently re-installed the equipment in a new location and are now finalising two further papers. |
Sectors | Healthcare,Other |
URL | http://www.york.ac.uk/chym/ |
Description | We worked to understand the DNP effect and harness it for the examination of chemical reactions. |
First Year Of Impact | 2010 |
Sector | Chemicals,Healthcare |
Impact Types | Societal,Economic |
Description | GlaxoSmithKline (GSK) |
Amount | £65,000 (GBP) |
Funding ID | STU029361 |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 10/2010 |
End | 09/2013 |
Description | GlaxoSmithKline (GSK) |
Amount | £65,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 10/2013 |
End | 09/2017 |
Description | Wellcome Trust Capital Awards Scheme |
Amount | £4,360,000 (GBP) |
Funding ID | 092506/B/10/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2011 |
End | 11/2016 |
Description | Wellcome Trust Strategic Awards Scheme |
Amount | £3,500,000 (GBP) |
Funding ID | 098335/Z/12/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2012 |
End | 11/2017 |
Description | Bruker BioSpin |
Organisation | Bruker Corporation |
Department | Bruker BioSpin |
Country | Germany |
Sector | Private |
PI Contribution | We have worked with Bruker to produce a parahydrogen generator, a device for the preparation of hyperpolarised samples and a flow probe for the detection of hyperpolarised signals |
Collaborator Contribution | Bruker have provided access to equipment and engineering. They have provided legal support for patents |
Impact | Bruker now sell a parahydrogen generator. A beta test version of the polariser in on test with 5 international research groups. |
Start Year | 2009 |
Description | Developing DNP as a molecular probe |
Organisation | Oxford Instruments |
Country | United Kingdom |
Sector | Private |
PI Contribution | We worked to develop methods to study reactions by DNP |
Collaborator Contribution | Knowledge, equipment and materials |
Impact | Publications |
Start Year | 2007 |
Title | Field cycling method for magnetic resonance |
Description | An NMR experiment on hyperpolarizable magnetic nuclei of substrate molecules in a living human or animal body, involves polarizing the substrate molecules by non-hydrogenating para-hydrogen induced polarization (=NH-PHIP) into a singlet/pseudo singlet state in low magnetic field and injecting the substrate molecules into the living body, the body or a part thereof being previously located inside a magnet at low magnetic field. The magnet is switched on to high magnetic field, and in at least part of the substrate molecules, the singlet state/pseudo singlet state is converted into observable magnetisation. An MRI or MRS measurement is carried out with the living body or the part thereof, collecting data from the substrate molecules. The NMR experiment is well applicable on hyperpolarized nuclei within a patient, with reduced losses of magnetization due to relaxation processes. |
IP Reference | US2014012129 |
Protection | Patent granted |
Year Protection Granted | 2014 |
Licensed | Yes |
Impact | We hope that this patent will be used by Bruker BioSpin. |
Title | HYPERPOLARITZATION OF COMPOUNDS FOR NMR, IN PARTICULAR BY MEANS OF PHIP |
Description | An NMR method is presented having enhanced sensitivity on a compound comprising hyperpolarizable nuclei, in particular applying enhanced PHIP. Polarization is thereby transferred from a prepared fluid, which is enriched with symmetric molecules of a particular spin state (e.g. para-hydrogen enriched), directly to the hyperpolarizable nuclei of a compound, without altering the chemical identity of the compound in this process. Spin transfer is achieved using a template having sites of ordered environment, and the fluid and the compound are brought together in the presence of the template. Polarization transfer to the hyperpolarizable nuclei of the compound is thereby easier to perform and can be applied to a broader scope of compounds. |
IP Reference | US2010219826 |
Protection | Patent granted |
Year Protection Granted | 2010 |
Licensed | Yes |
Impact | This product has been licensed to Bruker BioSpin |
Title | NMR MEASUREMENT APPARATUS WITH FLOW-THROUGH PROBEHEAD |
Description | The invention relates to a device (1, 21, 31, 41, 64) for the preparation and measurement of a nuclear spin reso nance (NMR) measurement sample (10), including-a flow-through NMR probehead (2), with a first tube (3) and a second tube (14) each for the supply and removal of a liquid NMR measurement sample (10),-at least one chamber (4, 22, 32) which is connected to one of the tubes (3, 14),-a sample inlet (5) for introducing the liquid measurement sample (10) into the device (1, 21, 31, 41, 64), wherein at least one chamber (4, 22, 32) has at least one connection for increasing (9, 24, 25, 42, 43, 46, 47) and releasing (8, 23, 27, 48a, 48b) the gas pressure, and in which at least one chamber (4, 22, 32) comprises means for mixing the liquid measurement sample (10) contained in the chamber (4, 22, 32) with a gas With the inventive device it is possible to reduce the measurement sample consumption when doing an NMR spectroscopic measurement on liquid measurement samples to which spin order can be catalytically transferred. |
IP Reference | US2011285396 |
Protection | Patent granted |
Year Protection Granted | 2011 |
Licensed | Yes |
Impact | This has been licensed to Bruker BioSpin |
Title | PULSE SEQUENCING WITH HYPERPOLARISABLE NUCLEI |
Description | There is described a method of selective observation of non-hydrogenative para- hydrogen induced polarisation (NH-PHIP) as enhanced magnetic resonance signals which comprises separating the thermal and longitudinal spin order states. There is also described a template comprising [Ir(COD)(NHC)(Py)]+, and analogues thereof, for use in a PHIP magnetic resonance technique and a method for its preparation. |
IP Reference | WO2010067076 |
Protection | Patent application published |
Year Protection Granted | 2010 |
Licensed | Yes |
Impact | We are working with Bruker BipSpin on the application. |
Title | Parahydrogen Generator |
Description | We worked with Bruker BioSpin to produce a device to make parahydrogen |
Type Of Technology | New/Improved Technique/Technology |
Year Produced | 2013 |
Impact | The device is being used by a number of researchers to help support hyperpolarisation studies aligned to clinical MRI. |
URL | http://www.bruker.com/products/mr/nmr/accessories/hyperpolarization/parahydrogen-generator/overview.... |
Company Name | HYPERNETICS IMAGING LIMITED |
Description | Currently company holds the patents associated with SABRE and seeks to develop their use. |
Year Established | 2013 |
Impact | Currently seeking investment |
Description | 5th Australian Organometallics Meeting (Sydney) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | 70 academics, postdocs and research students attended a research presentation, which sparked questions and discssion afterwards Subsequent joint ARC grant with B Messerle (Sydney) |
Year(s) Of Engagement Activity | 2010 |
Description | 7th Conference on Field Cycling NMR Relaxometry |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | People attended a presentation which sparked questions and discussion afterwards Other researchers now use our methods |
Year(s) Of Engagement Activity | 2011 |
URL | http://www.ffcrelax.com/ffcrelax/ffc2011/mainpage.php?folder=program&page=index.php |
Description | BioNMR workshop Weizmann Institute. |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Over 50 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.weizmann.ac.il/weizsites/bionmr/ |
Description | Chemistry Meets Imaging: Molecular Routes to Enhance Contrast |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at international meeting at Duke, USA |
Year(s) Of Engagement Activity | 2015 |
URL | http://cmbi.duke.edu/conferences/ |
Description | Euromar, Florence, Italy. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Over 100 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.euromar.org/about.html |
Description | Experimental Nuclear Magnetic Resonance Conference (ENC), Daytona Beach USA. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Over 100 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.enc-conference.org/ |
Description | German-UK MR Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited key-note talk at international meeting. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.chemie.tu-darmstadt.de/gdch-fgmr2015/fgmr_2015/index.en.jsp |
Description | Gordon Conference, In Vivo Magnetic Resonance |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Over 100 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.grc.org/programs.aspx?year=2014&program=invivo |
Description | Huddersfield Hyperpolarisation Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Series of presentations detailing aspects of hyperpolarisation |
Year(s) Of Engagement Activity | 2016 |
Description | Imaging in 2020 VII, Bridging Molecular Imaging and Therapy, Jackson Hole USA. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | people attended a presentation which sparked questions and discussion afterwards 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2011 |
Description | Intermediary Metabolism in Cancer meeting, Dallas USA. |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Over 100 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods. This includes groups at Johns Hopkins, UT Southwestern Medical Centre, and the University Medical Center Freiburg |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.utsouthwestern.edu/edumedia/edufiles/departments_centers/airc/annual-symposium-202010.pdf |
Description | Invited Speaker, Euromar, Dublin, Eire. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Over 100 people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2012 |
Description | New national centre to transform medical imaging |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Detail new funding stream A new £6.8 million research centre based across two Yorkshire universities will aim to transform diagnosis and treatment of patients suffering from cancer, heart disease and musculoskeletal diseases with the help of new medical imaging facilities to be created at Leeds Teaching Hospitals and the University of York. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.york.ac.uk/news-and-events/news/2014/medical-imaging-centre/ |
Description | New scanning technology aims to achieve quicker diagnosis of disease |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | New scanning technology aims to achieve quicker diagnosis of disease. Groundbreaking research taking place at the University of York could lead to Alzheimer's disease being diagnosed in minutes using a simple brain scan. Scientists are working on new technology that could revolutionise the way in which Magnetic Resonance Imaging (MRI) scans are used to view the molecular events behind diseases like Alzheimer's, without invasive procedure, by increasing the sensitivity of an average hospital scanner by 200,000 times. The technology underpinning this project, SABRE (Signal Amplification by Reversible Exchange), has received a £3.6m Strategic Award from the Wellcome Trust to fund a team of seven post-doctoral researchers from this month. on-going |
Year(s) Of Engagement Activity | 2012 |
URL | http://www.york.ac.uk/chym/news/2012/scanning/ |
Description | Opening National Centre of Hyperpolarised MRI |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Scientific talk on developments in SABRE hyperpolarisation. |
Year(s) Of Engagement Activity | 2016 |
Description | Rank Prize Symposium |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I contributed to a workshop aimed at driving forward change in chemical detection Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2011 |
URL | http://www.rankprize.org/index.php/symposia/general |
Description | Talk, ISMAR, Rio de Janerio, Brazil |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | people attended a presentation which sparked questions and discussion afterwards Over 15 research groups worldwide have adopted our methods |
Year(s) Of Engagement Activity | 2013 |
Description | Using SABRE to improve NMR and MRI |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk given in Paris |
Year(s) Of Engagement Activity | 2016 |
Description | Wellcome Trust Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | To inform on progress towards the clinical uptake of SABRE |
Year(s) Of Engagement Activity | 2016 |
Description | Wellcome Trust, Next Generation Brain Imaging Technologies, London, UK. |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | people attended a presentation which sparked questions and discussion afterwards Funding awarded to take methods forward. |
Year(s) Of Engagement Activity | 2011 |
Description | York Hyperpolarisation Symposium (2 Day) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Series of 20 talks over 2 days |
Year(s) Of Engagement Activity | 2016 |
Description | iMR CDT Research Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at CDT workshop to inform on hyperpolarisation with parahydrogen |
Year(s) Of Engagement Activity | 2015 |
URL | https://www2.warwick.ac.uk/fac/sci/physics/research/condensedmatt/imr_cdt/news_events/ |
Description | press release |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | A press release written to share a research success Over 30 reports in the national and international media picked up this press release. Interviews resulted on local radio. |
Year(s) Of Engagement Activity | 2009 |
URL | http://www.york.ac.uk/news-and-events/news/2009/medical-diagnosis/ |
Description | press release |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Information shared with public Research progresses towards clinical use |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.york.ac.uk/news-and-events/news/2010/research/hyperpolarisation/ |