Category Archives: Hyperpolarization

XeUS: A second-generation automated open-source batch-mode clinical-scale hyperpolarizer

Birchall, Jonathan R., Robert K. Irwin, Panayiotis Nikolaou, Aaron M. Coffey, Bryce E. Kidd, Megan Murphy, Michael Molway, et al. “XeUS: A Second-Generation Automated Open-Source Batch-Mode Clinical-Scale Hyperpolarizer.” Journal of Magnetic Resonance 319 (October 2020): 106813.

https://doi.org/10.1016/j.jmr.2020.106813.

We present a second-generation open-source automated batch-mode 129Xe hyperpolarizer (XeUS GEN2), designed for clinical-scale hyperpolarized (HP) 129Xe production via spin-exchange optical pumping (SEOP) in the regimes of high Xe density (0.66–2.5 atm partial pressure) and resonant photon flux (~170 W, Dk = 0.154 nm FWHM), without the need for cryo-collection typically employed by continuous-flow hyperpolarizers. An Arduino micro-controller was used for hyperpolarizer operation. Processing open-source software was employed to program a custom graphical user interface (GUI), capable of remote automation. The Arduino Integrated Development Environment (IDE) was used to design a variety of customized automation sequences such as temperature ramping, NMR signal acquisition, and SEOP cell refilling for increased reliability. A polycarbonate 3D-printed oven equipped with a thermoelectric cooler/heater provides thermal stability for SEOP for both binary (Xe/N2) and ternary (4He-containing) SEOP cell gas mixtures. Quantitative studies of the 129Xe hyperpolarization process demonstrate that near-unity polarization can be achieved in a 0.5 L SEOP cell. For example, %PXe of 93.2 ± 2.9% is achieved at 0.66 atm Xe pressure with polarization build-up rate constant cSEOP = 0.040 ± 0.005 minÀ1, giving a max dose equivalent % 0.11 L/h 100% hyperpolarized, 100% enriched 129Xe; %PXe of 72.6 ± 1.4% is achieved at 1.75 atm Xe pressure with cSEOP of 0.041 ± 0.001 minÀ1, yielding a corresponding max dose equivalent of 0.27 L/h. Quality assurance studies on this device have demonstrated the potential to refill SEOP cells hundreds of times without significant losses in performance, with average %PXe = 71.7%, (standard deviation rP = 1.52%) and mean polarization lifetime T1 = 90.5 min, (standard deviation rT = 10.3 min) over the first ~200 gas mixture refills, with sufficient performance maintained across a further ~700 refills. These findings highlight numerous technological developments and have significant translational relevance for efficient production of gaseous HP 129Xe contrast agents for use in clinical imaging and bio-sensing techniques.

Materials chemistry of triplet dynamic nuclear polarization #DNPNMR

Nishimura, Koki, Hironori Kouno, Yusuke Kawashima, Kana Orihashi, Saiya Fujiwara, Kenichiro Tateishi, Tomohiro Uesaka, Nobuo Kimizuka, and Nobuhiro Yanai. “Materials Chemistry of Triplet Dynamic Nuclear Polarization.” Chemical Communications 56, no. 53 (2020): 7217–32.

https://doi.org/10.1039/D0CC02258F

This Feature Article overviews the recently-emerged materials chemistry of triplet dynamic nuclear polarization (triplet-DNP) towards biological and medical applications.

Dynamic nuclear polarization with photo-excited triplet electrons (triplet-DNP) has the potential to enhance the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) at a moderate temperature. While many efforts have been devoted to achieving a large nuclear polarization based on triplet-DNP, the application of triplet-DNP has been limited to nuclear physics experiments. The recent introduction of materials chemistry into the field of triplet-DNP has achieved air-stable and water-soluble polarizing agents as well as the hyperpolarization of nanomaterials with a large surface area such as nanoporous metal–organic frameworks (MOFs) and nanocrystal dispersion in water. This Feature Article overviews the recently-emerged materials chemistry of triplet-DNP that paves new paths towards unprecedented biological and medical applications.

Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange

Kim, Sarah, Sein Min, Heelim Chae, Hye Jin Jeong, Sung Keon Namgoong, Sangwon Oh, and Keunhong Jeong. “Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange.” Molecules 25, no. 15 (July 23, 2020): 3347.

https://doi.org/10.3390/molecules25153347.

Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 µL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.

Analysis of 1-aminoisoquinoline using the signal amplification by reversible exchange hyperpolarization technique #SABRE

Jeong, Hye Jin, Sein Min, and Keunhong Jeong. “Analysis of 1-Aminoisoquinoline Using the Signal Amplification by Reversible Exchange Hyperpolarization Technique.” The Analyst, 2020, 10.1039.D0AN00967A.

https://doi.org/10.1039/D0AN00967A

Signal amplification by reversible exchange (SABRE), a parahydrogen-based hyperpolarization technique, is valuable in detecting low concentrations of chemical compounds, which facilitates the understanding of their functions at molecular level as well as their applicability in nuclear magnetic resonance (NMR) and magentic resource maging (MRI). SABRE of 1- aminoisoquinoline (1-AIQ) is significant because isoquinoline derivatives are the fundamental structures in compounds with notable biological activity and are basic organic building blocks. Through this study, we explain how SABRE is applied to hyperpolarize 1-AIQ for diverse solvent systems such as deuterium and non-deuterium solvents. We observed the amplification of individual protons of 1-AIQ at various magnetic fields. Further, we describe the polarization transfer mechanism of 1-AIQ compared to pyridine using density functional theory (DFT) calculations. These hyperpolarization techniques, including the polarization transfer mechanism investigation on 1-AIQ, will provide a firm basis for the future application of the hyperpolarization study on various bio-friendly materials.

Geminal parahydrogen-induced polarization: accumulating long-lived singlet order on methylene proton pairs #DNPNMR #SABRE

Dagys, Laurynas, Barbara Ripka, Markus Leutzsch, Gamal A. I. Moustafa, James Eills, Johannes F. P. Colell, and Malcolm H. Levitt. “Geminal Parahydrogen-Induced Polarization: Accumulating Long-Lived Singlet Order on Methylene Proton Pairs.” Magnetic Resonance 1, no. 2 (August 7, 2020): 175–86.

https://doi.org/10.5194/mr-1-175-2020

In the majority of hydrogenative parahydrogen-induced polarization (PHIP) experiments, the hydrogen molecule undergoes pairwise cis addition to an unsaturated precursor to occupy vicinal positions on the product molecule. However, some ruthenium-based hydrogenation catalysts induce geminal hydrogenation, leading to a reaction product in which the two hydrogen atoms are transferred to the same carbon centre, forming a methylene (CH2) group. The singlet order of parahydrogen is substantially retained over the geminal hydrogenation reaction, giving rise to a singlet-hyperpolarized CH2 group. Although the T1 relaxation times of the methylene protons are often short, the singlet order has a long lifetime, provided that singlet–triplet mixing is suppressed, either by chemical equivalence of the protons or by applying a resonant radiofrequency field. The long lifetime of the singlet order enables the accumulation of hyperpolarization during the slow hydrogenation reaction. We introduce a kinetic model for the behaviour of the observed hyperpolarized signals, including both the chemical kinetics and the spin dynamics of the reacting molecules. Our work demonstrates the feasibility of producing singlet-hyperpolarized methylene moieties by parahydrogen-induced polarization. This potentially extends the range of molecular agents which may be generated in a hyperpolarized state by chemical reactions of parahydrogen.

Helium-rich mixtures for improved batch-mode clinical-scale spin-exchange optical pumping of Xenon-129

Birchall, Jonathan R., Panayiotis Nikolaou, Robert K. Irwin, Michael J. Barlow, Kaili Ranta, Aaron M. Coffey, Boyd M. Goodson, et al. “Helium-Rich Mixtures for Improved Batch-Mode Clinical-Scale Spin-Exchange Optical Pumping of Xenon-129.” Journal of Magnetic Resonance 315 (June 2020): 106739.

https://doi.org/10.1016/j.jmr.2020.106739

We present studies of spin-exchange optical pumping (SEOP) using ternary xenon-nitrogen-helium gas mixtures at high xenon partial pressures (up to 1330 Torr partial pressure at loading, out of 2660 Torr total pressure) in a 500-mL volume SEOP cell, using two automated batch-mode clinical-scale 129Xe hyperpolarizers operating under continuous high-power (~170 W) pump laser irradiation. In this pilot study, we explore SEOP in gas mixtures with up to 45% 4He content under a wide range of experimental conditions. When an aluminum jacket cooling/heating design was employed (GEN-3 hyperpolarizer), 129Xe polarization (%PXe) of 55.9 ± 0.9% was observed with mono-exponential build-up rate cSEOP of 0.049 ± 0.001 minÀ1 for the 4He-rich mixture (1000 Torr Xe/900 Torr He, 100 Torr N2), compared to % PXe of 49.3 ± 3.3% at cSEOP of 0.035 ± 0.004 minÀ1 for the N2-rich gas mixture (1000 Torr Xe/100 Torr He, 900 Torr N2). When forced-air cooling/heating was used (GEN-2 hyperpolarizer), %PXe of 83.9 ± 2.7% was observed at cSEOP of 0.045 ± 0.005 minÀ1 for the 4He-rich mixture (1000 Torr Xe/900 Torr He, 100 Torr N2), compared to %PXe of 73.5 ± 1.3% at cSEOP of 0.028 ± 0.001 minÀ1 for the N2-rich gas mixture (1000 Torr Xe and 1000 Torr N2). Additionally, %PXe of 72.6 ± 1.4% was observed at a build-up rate cSEOP of 0.041 ± 0.003 minÀ1 for a super-high-density 4He-rich mixture (1330 Torr Xe/1200 Torr 4He/130 Torr N2), compared to %PXe = 56.6 ± 1.3% at a build-up rate of cSEOP of 0.034 ± 0. 002 minÀ1 for an N2-rich mixture (1330 Torr Xe/1330 Torr N2) using forced air cooling/heating. The observed SEOP hyperpolarization performance under these conditions corresponds to %PXe improvement by a factor of 1.14 ± 0.04 at 1000 Torr Xe density and by up to a factor of 1.28 ± 0.04 at 1330 Torr Xe density at improved SEOP build-up rates by factors of 1.61 ± 0.18 and 1.21 ± 0.11 respectively. Record %PXe levels have been obtained here: 83.9 ± 2.7% at 1000 Torr Xe partial pressure and 72.6 ± 1.4% at 1330 Torr Xe partial pressure. In addition to improved thermal stability for SEOP, the use of 4He-rich gas mixtures also reduces the overall density of produced inhalable HP contrast agents; this property may be desirable for HP 129Xe inhalation by human subjects in clinical settings—especially in populations with heavily impaired lung function. The described approach should enjoy ready application in the production of inhalable 129Xe contrast agent with near-unity 129Xe nuclear spin polarization.

Optimisation of pyruvate hyperpolarisation using SABRE by tuning the active magnetisation transfer catalyst

Tickner, Ben. J., Olga Semenova, Wissam Iali, Peter J. Rayner, Adrian C. Whitwood, and Simon B. Duckett. “Optimisation of Pyruvate Hyperpolarisation Using SABRE by Tuning the Active Magnetisation Transfer Catalyst.” Catalysis Science & Technology 10, no. 5 (2020): 1343–55.

https://doi.org/10.1039/C9CY02498K

Hyperpolarisation techniques such as signal amplification by reversible exchange (SABRE) can deliver NMR signals several orders of magnitude larger than those derived under Boltzmann conditions. SABRE is able to catalytically transfer latent magnetisation from para-hydrogen to a substrate in reversible exchange via temporary associations with an iridium complex. SABRE has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many in vivo MRI studies. In this work, we seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst. We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [Ir(H)2(η2-pyruvate)(sulfoxide)(NHC)] catalyst to produce a rationale for achieving high pyruvate signal gains in a cheap and refreshable manner. This optimisation approach allows us to achieve signal enhancements of 2140 and 2125-fold for the 1-13C and 2-13C sites respectively of sodium pyruvate-1,2-[13C2].

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.

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

Glass tube reactors with Pd, Pt, Rh or Ir nanoparticles dispersed on a thin layer of TiO2, CeO2, SiO2 or Al2O3 provided mechanistic insight into the hydrogenation of 1,3-butadiene using para hydrogen. 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 para-hydrogen-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 para-hydrogen. 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.

Enhanced Intersystem Crossing and Transient Electron Spin Polarization in a Photoexcited Pentacene-Trityl Radical

Avalos, Claudia E., Sabine Richert, Etienne Socie, Ganesan Karthikeyan, Gilles Casano, Gabriele Stevanato, Dominik J. Kubicki, et al. “Enhanced Intersystem Crossing and Transient Electron Spin Polarization in a Photoexcited Pentacene-Trityl Radical.” The Journal of Physical Chemistry A, June 25, 2020, acs.jpca.0c03498.

https://doi.org/10.1021/acs.jpca.0c03498

Identifying and characterizing systems that generate well-defined states with large electron spin polarization is of high interest for applications in molecular spintronics, high-energy physics and magnetic resonance spectroscopy. The generation of electron spin polarization on free-radical substituents tethered to pentacene derivatives has recently gained a great deal of interest for its applications in molecular electronics. After photoexcitation of the chromophore, pentacene-radical derivatives can rapidly form spin-polarized triplet excited states through enhanced intersystem crossing. Under the right conditions, the triplet spin polarization, arising from mS-selective intersystem crossing rates, can be transferred to the tethered stable radical. The efficiency of this spin polarization transfer depends on many factors: local magnetic and electric fields, excited state energetics, molecular geometry, and spin-spin coupling. Here we present transient electron paramagnetic resonance (EPR) measurements on three pentacene derivatives tethered to Finland trityl, BDPA or TEMPO radicals to explore the influence of the nature of the radical on the spin polarization transfer. We observe efficient polarization transfer between the pentacene excited triplet and the trityl radical, but do not observe the same for the BDPA and TEMPO derivatives. The polarization transfer behavior in the pentacene-trityl system is also investigated in different glassy matrices and is found to depend markedly on the solvent used. The EPR results are rationalized with the help of femtosecond and nanosecond transient absorption measurements, yielding complementary information on the excited-state dynamics of the three pentacene derivatives. Notably, we observe a two orders of magnitude difference in the timescale of triplet formation between the pentacene-trityl system and the pentacene systems tethered with the BDPA and TEMPO radicals.

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