Category Archives: SABRE

Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques #DNPNMR

Kovtunov, Kirill V., Ekaterina V. Pokochueva, Oleg G. Salnikov, Samuel F. Cousin, Dennis Kurzbach, Basile Vuichoud, Sami Jannin, et al. “Hyperpolarized NMR Spectroscopy: D-DNP, PHIP, and SABRE Techniques.” Chemistry – An Asian Journal 13, no. 15 (August 6, 2018): 1857–71.

https://doi.org/10.1002/asia.201800551.

The intensity of NMR signals can be enhanced by several orders of magnitude by using various techniques for the hyperpolarization of different molecules. Such approaches can overcome the main sensitivity challenges facing modern NMR/magnetic resonance imaging (MRI) techniques, whilst hyperpolarized fluids can also be used in a variety of applications in material science and biomedicine. This Focus Review considers the fundamentals of the preparation of hyperpolarized liquids and gases by using dissolution dynamic nuclear polarization (d-DNP) and parahydrogen- based techniques, such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP), in both heterogeneous and homogeneous processes. The various new aspects in the formation and utilization of hyperpolarized fluids, along with the possibility of observing NMR signal enhancement, are described.

Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC-SABRE

Pravdivtsev, Andrey N, Ivan Vladimirovich Skovpin, Alexandra I Svyatova, Nikita V Chukanov, Larisa M Kovtunova, Valerii I Bukhtiyarov, Eduard Y Chekmenev, Kirill V Kovtunov, Igor V Koptyug, and Jan-Bernd Hovener. “Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC-SABRE.” The Journal of Physical Chemistry, 2018, 9107–9114. 

https://doi.org/10.1021/acs.jpca.8b07163

Signal Amplification By Reversible Exchange (SABRE) is a new and rapidly developing hyperpolarization technique. The recent discovery of Spin-Lock Induced Crossing SABRE (SLIC-SABRE) showed that high field hyperpolarization transfer techniques developed so far were optimized for singlet spin order that does not coincide with the experimentally produced spin state. Here, we investigated the SLIC-SABRE approach and the most advanced quantitative theoretical SABRE model to date. Our goal is to achieve the highest possible polarization with SLIC-SABRE at high field using the standard SABRE system, IrIMes catalyst with pyridine. We demonstrated the accuracy of the SABRE model describing the effects of various physical parameters such as the amplitude and frequency of the radio frequency field, and the effects of chemical parameters such as the exchange rate constants. By fitting the model to the experimental data, the effective life time of the SABRE complex was estimated, as well as the entropy and enthalpy of the complex-dissociation reaction. We show, for the first time, that this SLIC-SABRE model can be useful for the evaluation of the chemical exchange parameters that are very important for the production of highly polarized contrast agents via SABRE.

Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization

Stewart, Neil J., Hiroyuki Kumeta, Mitsushi Tomohiro, Takuya Hashimoto, Noriyuki Hatae, and Shingo Matsumoto. “Long-Range Heteronuclear J-Coupling Constants in Esters: Implications for 13C Metabolic MRI by Side-Arm Parahydrogen-Induced Polarization.” Journal of Magnetic Resonance 296 (November 2018): 85–92.

https://doi.org/10.1016/j.jmr.2018.08.009

Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective method for hyperpolarization of 13C metabolites (e.g. acetate, pyruvate) for metabolic MRI. The timing and efficiency of typical spin order transfer methods including magnetic field cycling and tailored RF pulse sequences crucially depends on the heteronuclear J coupling network between nascent parahydrogen protons and 13C, post-parahydrogenation of the target compound. In this work, heteronuclear nJHC (1<n≤5) couplings of acetate and pyruvate esters pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC-based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond JHC ≲ 0.5 Hz were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT-simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for 13C hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type spin order transfer methods for PHIP-SAH were assessed, and the influence of direct nascent parahydrogen proton to 13C coupling when compared with indirect TOCSY-type transfer through intermediate (non-nascent parahydrogen) protons was studied by the density matrix approach.

Using hyperpolarised NMR and DFT to rationalise the unexpected hydrogenation of quinazoline to 3,4-dihydroquinazoline

Richards, Josh E., Alexander J. J. Hooper, Oliver W. Bayfield, Martin C. R. Cockett, Gordon J. Dear, A. Jonathon Holmes, Richard O. John, et al. “Using Hyperpolarised NMR and DFT to Rationalise the Unexpected Hydrogenation of Quinazoline to 3,4-Dihydroquinazoline.” Chemical Communications 54, no. 73 (2018): 10375–78.

https://doi.org/10.1039/C8CC04826F.

PHIP and SABRE hyperpolarized NMR methods are used to follow the unexpected metal-catalysed hydrogenation of quinazoline (Qu) to 3,4-dihydroquinazoline as the sole product. A solution of [IrCl(IMes)(COD)] in dichloromethane reacts with H2 and Qu to form [IrCl(H)2(IMes)(Qu)2] (2). The addition of methanol then results in its conversion to [Ir(H)2(IMes)(Qu)3]Cl (3) which catalyses the hydrogenation reaction. Density functional theory calculations are used to rationalise a proposed outer sphere mechanism in which (3) converts to [IrCl(H)2(H2)(IMes)(Qu)2]Cl (4) and neutral [Ir(H)3(IMes)(Qu)2](6), both of which are involved in the formation of 3,4-dihydroquinazoline via the stepwise transfer of H+ and H, withH2 identified as the reductant. Successive ligand exchange in 3 results in the production of thermodynamically stable [Ir(H)2(IMes)(3,4-dihydroquinazoline)3]Cl (5).

Perspective on the Hyperpolarisation Technique Signal Amplification by Reversible Exchange (SABRE) in NMR Spectroscopy and MR Imaging

Robertson, Thomas B.R., and Ryan E. Mewis. “Perspective on the Hyperpolarisation Technique Signal Amplification by Reversible Exchange (SABRE) in NMR Spectroscopy and MR Imaging.” In Annual Reports on NMR Spectroscopy, 93:145–212. Elsevier, 2018.

https://doi.org/10.1016/bs.arnmr.2017.08.001

Signal amplification by reversible exchange (SABRE) is a para-hydrogen-based technique that utilises a metal complex, normally centred on iridium, to propagate polarisation from para-hydrogen-derived hydride ligands to spin-½ nuclei located in a bound substrate. To date, substrates possessing 1H, 13C, 15N, 19F, 31P, 29Si, and 119Sn nuclei have been polarised by this technique. The exact positioning of these nuclei has a direct bearing on the enhancement observed and so substrates must be chosen or synthesised with care in order to maximise polarisation transfer, and hence the resulting enhancement. The chemical composition of the metal complex must be similarly appraised, as the exchange rate of substrates and para-hydrogen is implicated heavily in efficient polarisation transfer. The nature of the polarisation transfer, whether homogenous or heterogeneous, is another important facet to consider here, as is conducting SABRE in water-based systems. This review discusses the physical and theoretical aspects of the SABRE experiment, as well as the applications of the SABRE technique, namely, the detection of analytes at concentrations far below what would be possible with conventional NMR techniques and the collection of hyperpolarised magnetic resonance images. Advances relating to utilising singlet states for SABRE, pulse sequence design and the nature of the polarisation transfer mechanism are also discussed, and the implications for future SABRE-based discoveries highlighted.

Generating para-water from para-hydrogen: A Gedankenexperiment #DNPNMR

Ivanov, Konstantin L., and Geoffrey Bodenhausen. “Generating Para-Water from Para-Hydrogen: A Gedankenexperiment.” Journal of Magnetic Resonance 292 (July 1, 2018): 48–52.

https://doi.org/10.1016/j.jmr.2018.05.003.

A novel conceptual approach is described that is based on the transfer of hyperpolarization from para-hydrogen in view of generating a population imbalance between the two spin isomers of H2O. The approach is analogous to SABRE (Signal Amplification By Reversible Exchange) and makes use of the transfer of spin order from para-hydrogen to H2O in a hypothetical organometallic complex. The spin order transfer is expected to be most efficient at avoided level crossings. The highest achievable enrichment levels of para- and ortho-water are discussed.

Continuous hyperpolarization with parahydrogen in a membrane reactor #DNPNMR

Lehmkuhl, Sören, Martin Wiese, Lukas Schubert, Mathias Held, Markus Küppers, Matthias Wessling, and Bernhard Blümich. “Continuous Hyperpolarization with Parahydrogen in a Membrane Reactor.” Journal of Magnetic Resonance 291 (June 2018): 8–13. 

https://doi.org/10.1016/j.jmr.2018.03.012

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the ‘‘Signal Amplification by Reversible Exchange” (SABRE) approach uses para-enriched hydrogen, p-H2, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H2, supply and consecutive detection in a 1 T NMR spectrometer. Two SABRE substrates pyridine and nicotinamide were hyperpolarized, and more than 1000-fold signal enhancement was found. Our strategy combines low-field NMR spectrometry and a membrane flow reactor. This enables precise control of the experimental conditions such as liquid and gas pressures, and volume flow for ensuring repeatable maximum polarization.

Hyperpolarized NMR: d-DNP, PHIP, and SABRE

Kovtunov, Kirill Viktorovich, Ekaterina Pokochueva, Oleg Salnikov, Samuel Cousin, Dennis Kurzbach, Basile Vuichoud, Sami Jannin, et al. “Hyperpolarized NMR: D-DNP, PHIP, and SABRE.” Chemistry – An Asian Journal 0, no. ja (2018).

https://doi.org/10.1002/asia.201800551.

NMR signals intensities can be enhanced by several orders of magnitude via utilization of techniques for hyperpolarization of different molecules, and it allows one to overcome the main sensitivity challenge of modern NMR/MRI techniques. Hyperpolarized fluids can be successfully used in different applications of material science and biomedicine. This focus review covers the fundamentals of the preparation of hyperpolarized liquids and gases via dissolution dynamic nuclear polarization (d-DNP) and parahydrogen-based techniques such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP) in both heterogeneous and homogeneous processes. The different novel aspects of hyperpolarized fluids formation and utilization along with the possibility of NMR signal enhancement observation are described.

[NMR] Post-doc position in low-field SABRE hyperpolarisation

Post-doctoral position in low-field SABRE Hyperpolarisation

A fixed-term postdoctoral appointment in magnetic resonance is available to work with Dr Meghan Halse in the Centre for Hyperpolarisation in Magnetic Resonance (https://www.york.ac.uk/chym/) at the University of York to develop low-field NMR instrumentation and methods to study the signal amplification by reversible exchange (SABRE) hyperpolarisation method in situ – that is under the conditions of weak magnetic field where the polarisation transfer effect takes place.

Department

The Department of Chemistry is one of the largest and most successful academic departments at York. The Department was placed in the top ten UK universities for Research Power by the 2014 Research Excellence Framework exercise (REF). As a Department we strive to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel. We are proud of our Athena SWAN Gold Award. 

The University of York is a member of the Russell Group of research-intensive UK universities. The recent Research Excellence Framework (REF) confirmed the position of the University among the leading institutions in the UK for research. 

Role

You will join a team lead by Dr Meghan Halse (http://www.york.ac.uk/chemistry/staff/academic/h-n/mhalse/) and in addition to research responsibilities, you will be expected to assist with the supervision of more junior group members. 

You will design and construct NMR instrumentation for in situ SABRE detection in the micro-to-millitesla regime and implement methods for exploring and controlling the SABRE polarisation transfer process in these fields. You will use appropriate research techniques and methods for the acquisition and analysis of experimental data. You will write-up and disseminate research results, coordinate publications and further contribute to the identification of possible new areas of research. You will be expected to participate in seminar and conference presentations and support supervision of PhD and project students as well as outreach activities 

You are expected to have a first degree in Chemistry, Physics, Engineering or related subject and a PhD in Chemistry, Physics or Engineering or equivalent experience. You will have significant knowledge and experience of a range of research techniques and methodologies relating to magnetic resonance. You should have experience in magnetic resonance methodology and/or instrumentation development and application. Experience in low-field NMR and hyperpolarisation is desirable. You will have an understanding of the operation of a research laboratory and an awareness of health and safety issues.

You will also have:

Highly developed communication skills including competency to make presentations at conferences

Ability and experience of developing research projects and objectives, conducting research projects and working in a harmonious team

Highly developed self-motivation with good time management and IT skills

Ability to write up research work for publication in high profile journals and engage in public dissemination.

The post is fixed-term for a period of 24 months and will be available from 1 July 2018 or as soon as possible thereafter.

Salary from £31,604 – £35,550 a year on grade 6 of the University’s salary scales.

Informal enquiries may be made to Dr Meghan Halse (meghan.halse@york.ac.uk).

More information and application details can be found at: https://jobs.york.ac.uk/wd/plsql/wd_portal.show_job?p_web_site_id=3885&p_web_page_id=345282

Closing date: 29 April 2018

The Department of Chemistry values all employees for the qualities and skills they bring to the workplace and aims to be a diverse and egalitarian community in which all can thrive.

The University is committed to promoting a diverse and inclusive community – a place where we can all be ourselves and succeed on merit. We offer a range of family friendly, inclusive employment policies, flexible working arrangements, staff engagement forums, campus facilities and services to support staff from different backgrounds.

A place where we can ALL be ourselves #EqualityatYork– Dr Meghan E. Halse Lecturer Department of Chemistry University of York Heslington York YO10 5DD Email: meghan.halse@york.ac.ukTel: +44 (0)1904 322853 

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Re-polarization of nuclear spins using selective SABRE-INEPT

Knecht, S., et al., Re-polarization of nuclear spins using selective SABRE-INEPT. Journal of Magnetic Resonance, 2018. 287: p. 10-14.

https://doi.org/10.1016/j.jmr.2017.12.010

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes “re-polarization”, i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε. For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε≈260 for 15N nuclei, whereas SABRE-INEPT with re-polarization yields ε>2000. We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques.

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