Category Archives: PHIP

Spatially resolved NMR spectroscopy of heterogeneous gas phase hydrogenation of 1,3-butadiene with para-hydrogen

Svyatova, Alexandra, Elizaveta S. Kononenko, Kirill V. Kovtunov, Dmitry Lebedev, Evgeniy Yu. Gerasimov, Andrey V. Bukhtiyarov, Igor P. Prosvirin, et al. “Spatially Resolved NMR Spectroscopy of Heterogeneous Gas Phase Hydrogenation of 1,3-Butadiene with Para-Hydrogen.” Catalysis Science & Technology 10, no. 1 (2020): 99–104.

https://doi.org/10.1039/C9CY02100K

Magnetic resonance-based methods such as nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are widely used to provide in situ/operando information of chemical reactions. However, the low spin density and magnetic field inhomogeneities associated with heterogeneous catalytic systems containing gaseous reactants complicate such studies. Hyperpolarization techniques, in particular parahydrogen-induced polarization (PHIP), increase significantly the NMR signal intensity. In this study, we test 16 glass tube reactors containing Pd, Pt, Rh or Ir nanoparticles dispersed on a thin layer of TiO2, CeO2, SiO2 or Al2O3 for the hydrogenation of 1,3-butadiene using parahydrogen. The catalytic coatings of Ir and Rh gave hydrogenation products with the highest nuclear spin polarization while the coatings of Pd are the most selective ones for the semihydrogenation of 1,3-butadiene to 1- and 2-butenes. Spatially resolved NMR spectroscopy of the reagent and the product distribution along the reactor axis provided further mechanistic insight into the catalytic function of these reactive coatings under operando conditions.

Lifetime of Para-hydrogen in Aqueous Solutions and Human Blood

Schmidt, Andreas B., Jakob Wörner, Andrey Pravdivtsev, Stephan Knecht, Harald Scherer, Stefan Weber, Jürgen Hennig, Dominik Elverfeldt, and Jan‐Bernd Hövener. “Lifetime of Para-Hydrogen in Aqueous Solutions and Human Blood.” ChemPhysChem 20, no. 19 (October 2, 2019): 2408–12.

https://doi.org/10.1002/cphc.201900670.

Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2), was instrumental in the early days of quantum mechanics and allows to boost the NMR signal by several orders of magnitude. pH2-induced polarization (PHIP) is based on the survival of pH2 spin order in solution, yet its lifetime has not been investigated in aqueous or biological media required for in vivo applications. Herein, we report longitudinal relaxation times (T1) and lifetimes of pH2 ( tPOC) in methanol and water, with or without O2, NaCl, rhodiumcatalyst or human blood. Furthermore, we present a relaxation model that uses T1 and tPOC for more precise theoretical predictions of the H2 spin state in PHIP experiments. All measured T1 values were in the range of 1.4–2 s and tPOC values were of the order of 10–300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP.

Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using 13C Metabolic Contrast Agents

Coffey, Aaron M., Roman V. Shchepin, Milton L. Truong, Ken Wilkens, Wellington Pham, and Eduard Y. Chekmenev. “Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using 13 C Metabolic Contrast Agents.” Analytical Chemistry 88, no. 16 (August 16, 2016): 8279–88.

https://doi.org/10.1021/acs.analchem.6b02130.

An open-source hyperpolarizer producing 13C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of opensource software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2−3 mL) of hyperpolarized 13C-succinate with %P13C ∼ 28% and 30 mM concentration and 13C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized 13C-phospholactate to 13C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice 13C MRI after tail vein injection of hyperpolarized 13C-phospholactate in mice.

Postdoctoral researcher, Parahydrogen biosensors for hypersensitive NMR analysis

See also the application link: https://rekry.saima.fi/certiahome/open_job_view.html?did=5600&jc=1&id=00007645&lang=en

Postdoctoral researcher, Parahydrogen biosensors for hypersensitive NMR analysis

The University of Oulu in Northern Finland, with approximately 15000 students and 3000 employees, is an international, multidisciplinary research university with a rich pool of creative and intellectual talent. The strengths of the University are broad, multidisciplinary research interests, a modern research and study environment, and wide cooperation with international research and educational institutes (http://www.oulu.fi/english).

The postdoctoral position is in the field of nuclear magnetic resonance (NMR), in the following specific topic: Development of metal-free catalytic systems for parahydrogen-based NMR hyperpolarization techniques.

The position is located at the NMR Research Unit (http://cc.oulu.fi/~nmrwww), in the Faculty of Science. We are an internationally established, combined experimental and theoretical team of about 20 people, of which 50% with a PhD degree. We develop experimental, theoretical and computational research methods based on magnetic resonance phenomena and apply those methods to topical problems in molecular and materials sciences. Our particular strength is in the tight connection between state-of-the-art measurements and calculations. We have an open and encouraging working atmosphere and have a substantial track record in successful funding applications both at the Academy of Finland and in EU programmes. We are a key user of the NMR laboratory facility of the University of Oulu, furnished with six spectrometers (300-600 MHz) suited for an unusually broad variety of studies (wide range of nuclei, gas/liquid/solid, different sample sizes, imaging capabilities, diffusion probe, micro CryoProbe, remote detection, spin-exchange optical pumping/parahydrogen-induced/SABRE hyperpolarization), two low-field, mobile NMR spectrometers as well as nuclear magneto-optic instrumentation. CPU-intensive computational research is carried out mainly using the facilities of the national supercomputer centre (2300 TFlop/s total capacity). Local linux clusters belonging to the Finnish Grid and Cloud Infrastructure are used for high-throughput production calculations.

Subject field and description of the position

The position is a part of Academy Project “Parahydrogen biosensors for hypersensitive NMR analysis” provided by the Academy of Finland.

The research direction of the position is briefly described in the following: The project aims at development of metal-free activators of H2 molecules capable of producing nuclear spin hyperpolarization upon activation of parahydrogen, increasing NMR sensitivity by orders of magnitude. Typically, metal-containing activators/catalysts are used in parahydrogen-based hyperpolarization techniques. We develop more biogenic metal-free catalytic systems that can be used to create hypersensitive NMR biosensors for biomolecular monitoring.

The length of the position is two years. The starting date of the position is September 16, 2019, or as soon as possible thereafter.

A six-month trial period will be effective in the beginning of the two-year contract.

Required Qualifications and assessment

The successful applicant must have a completed PhD in physics, chemistry, materials science, or a related field. The applicants must show a visible scientific profile. Significant experience in experimental NMR spectroscopy and other physical methods of analysis are to be documented for this position. Strong skills in synthetic and experimental organic chemistry are valuable to the project. Experience in the application of computational methods for studies of chemical reactivity is considered as an advantage. The project requires computer experience in data analysis (Excel, Origin, Matlab).

Fluent English, good communication skills and good teamwork skills are required. Further, demonstrated potential in acquiring supplementary (extramural) funding, and teaching experience will be taken as a merit when choosing the scientist. When assessing the applicant’s qualifications, issues to be considered will include scientific publications, thesis supervision, activity in the scientific community, practical familiarity with the field in question, scientific work abroad, and other international activities.

As part of the NMR Research Unit, the duties also include supervising scientific research of BSc, MSc and PhD students as well participation in important research activities of the group. Participation in teaching within the physics curriculum and acquiring research funding are naturally expected.

Salary

The salary will be based on the levels 5-6 of the demand level chart for university–level teaching and research staff of Finnish universities. In addition, a salary component based on personal work performance will be paid (maximum of 50 % of the job-specific component). The salary is thus in practice roughly 3400–4000 € per month, depending on the appointee’s qualifications, experience and the progress in the research.

Application Procedure

The following documents must be attached to the application:

1) Brief curriculum vitae in English

2) List of publications in international peer-reviewed journals

3) Brief description of research merits

4) Brief (1-2 pages) research and action plan in English

5) Contact information of two persons whom may be asked to give a statement of the candidate

Applications, together with all relevant enclosures, should be submitted using electronic application form by September 1, 2019 23:59 (Finnish local time).

Interview

The top candidates for the posts may be interviewed and asked to present their plans for running the post successfully.

For further information regarding the filling of this post:

Dr. Vladimir Zhivonitko, NMR Research Unit, University of Oulu, tel. +358-41-495 7904, email: vladimir.zhivonitko(at)oulu.fi

====================================

This is the AMPERE MAGNETIC RESONANCE mailing list:

http://www.drorlist.com/nmrlist.html

NMR web database:

http://www.drorlist.com/nmr.html

Combination of OPSY and PhD-PHIP results in enhanced sensitivity in PHIP

Bussandri, S., L. Buljubasich, and R.H. Acosta. “Combination of OPSY and PhD-PHIP Results in Enhanced Sensitivity in PHIP.” Journal of Magnetic Resonance 299 (February 2019): 28–32. 

https://doi.org/10.1016/j.jmr.2018.12.006.

Despite the large degree of polarization in PHIP experiments compared to the Boltzmann factor, the presence of a large amount of non-reacted molecules with thermal polarization is an important obstacle when dealing with very diluted samples. The feasibility of enhancing both sensitivity and resolution in a single experiment by combining two well established pulse sequences, OPSY and PHD-PHIP is presented. OPSY is used as a block for filtering the signals originated from thermally polarized protons. PhD-PHIP, on the other hand, is used as an acquisition block, increasing the resolution and further improving the sensitivity by preventing signal canceling in the presence of magnetic field inhomogeneities. Experiments in a complex sample with very low hyperpolarization levels are presented showing the excellent performance of the method.

[NMR] Postdoc position at NYU #PHIP

alexej.jerschow@nyu.edu via listes.univ-paris-diderot.fr 

Postdoctoral position at New York University

(NMR, MRI, magnetometry, battery research)

Department of Chemistry

Applications are solicited for an individual to be appointed as an postdoctoral associate in the group of Alexej Jerschow. The research will focus on one or both of these research areas:

• In-situ and in operando NMR/MRI and magnetometry of batteries and

electrochemical devices.

• Study of nuclear spin singlet state life times and singlet relaxation

mechanisms, the development of efficient singlet/triplet conversion pulse

sequences and methodology, as well as para-hydrogen induced polarization

(PHIP)

Successful applicants must hold a Ph.D. degree in a related field. The ideal candidate will have strong experience in two or more of these areas:

• MRI, NMR

• Machine learning and image processing

• Hardware/microcontroller/FPGA/data acquisition set up / programming /

operation

• Magnetometry

• Electrochemistry

• MD or ab initio simulations

Some relevant publications:

• Nat Comm 9:1776, 2018, http://dx.doi.org/10.1038/s41467-018-04192-x

• J. Phys. Chem. C. in press 2018,

https://pubs.acs.org/doi/10.1021/acs.jpcc.8b01958

• PNAS, 2016, 113, 10779-84,

http://www.pnas.org/content/early/2016/09/06/1607903113.abstract

• Chem. Phys. Chem. 2016, in press,

http://dx.doi.org/10.1002/cphc.201600663

• J. Magn. Reson. 2017, 284, 1-7

https://doi.org/10.1016/j.jmr.2017.09.005; free access link:

https://authors.elsevier.com/a/1Vkv~_OpItj~0r

• PCCP17, 2015, 24370 – 24375, http://dx.doi.org/10.1039/c5cp03716f

There is also an opportunity to be involved in other ongoing projects in the laboratory.

The lab is located in newly renovated facilities of the Molecular Nanoscience Center at NYU’s Washington Square Campus in the heart of Manhattan.

The terms of employment which would be a year, with a possibility of renewal, include a competitive salary and other benefits. Applications will be reviewed on a rolling basis, and candidates will be considered until the position is filled.

To be considered, all applicants must submit a cover letter summarizing research experience and specifying the interests in this position; a curriculum vitae (including a full list of publications); a statement of research interests; and two letters of reference. The application can be submitted through this link: http://apply.interfolio.com/62897.

====================================

This is the AMPERE MAGNETIC RESONANCE mailing list:

http://www.drorlist.com/nmrlist.html

NMR web database:

http://www.drorlist.com/nmr.html

Ultrafast Single‐Scan 2D NMR Spectroscopic Detection of a PHIP‐Hyperpolarized Protease Inhibitor #PHIP

Kiryutin, Alexey S., Grit Sauer, Daniel Tietze, Martin Brodrecht, Stephan Knecht, Alexandra V. Yurkovskaya, Konstantin L. Ivanov, Olga Avrutina, Harald Kolmar, and Gerd Buntkowsky. “Ultrafast Single‐Scan 2D NMR Spectroscopic Detection of a PHIP‐Hyperpolarized Protease Inhibitor.” Chemistry – A European Journal 25, no. 16 (March 15, 2019): 4025–30.

https://doi.org/10.1002/chem.201900079

Two-dimensional (2D) NMR is one of the most important spectroscopic tools for the investigation of biological macromolecules. However, owing to the low sensitivity of NMR it takes usually from several minutes to many hours to record such a spectrum. Here we show that a bioactive derivative of the sunflower trypsin inhibitor-1 (SFTI-1), a tetradecapeptide, can be detected by the combination of parahydrogen-induced polarization (PHIP) and ultrafast 2D-NMR spectroscopy (in the following abbreviated as 2D-NMR). The PHIP activity of the inhibitor was achieved by labeling with O-propargyl-Ltyrosine. In 1D-PHIP experiments an enhancement of approximately 1200 compared to normal NMR was found. This enhancement permits measurement of 2D-NMR correlation spectra of low concentrated SFTI-1 in less than 10 seconds, employing ultrafast single-scan 2D-NMR detection. As experimental examples PHIP assisted ultrafast single-scan TOCSY spectra of SFTI-1 are shown.

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.

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).

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.

Have a question?

If you have questions about our instrumentation or how we can help you, please contact us.