Category Archives: SABRE

In Situ and Ex Situ Low-Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

Barskiy, D.A., et al., In Situ and Ex Situ Low-Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization. ChemPhysChem, 2014. 15(18): p. 4100-7.

http://www.ncbi.nlm.nih.gov/pubmed/25367202

By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 10(5) -fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high-resolution low-field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real-time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low-field (milli-Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen-enhanced NMR and MRI, which are free from the limitations of high-field magnetic resonance (including susceptibility-induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields.

LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization

Theis, T., et al., LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization. J Magn Reson, 2014. 248C(0): p. 23-26.

http://www.ncbi.nlm.nih.gov/pubmed/25299767

Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate \”Low-Irradiation Generation of High Tesla-SABRE\” (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules.

Evaluation of Activation Energies for Pairwise and Non-Pairwise Hydrogen Addition to Propyne Over Pd/Aluminosilicate Fiberglass Catalyst by Parahydrogen-Induced Polarization (PHIP)

Salnikov, O.G., et al., Evaluation of Activation Energies for Pairwise and Non-Pairwise Hydrogen Addition to Propyne Over Pd/Aluminosilicate Fiberglass Catalyst by Parahydrogen-Induced Polarization (PHIP). Appl. Magn. Reson., 2014. 45(10): p. 1051-1061.

http://dx.doi.org/10.1007/s00723-014-0586-7

Hydrogenation of propyne to propene over Pd/aluminosilicate fiberglass catalyst in the temperature range 175–350 °C was investigated with the use of parahydrogen-induced polarization (PHIP) technique. Activation energies for both pairwise and non-pairwise H2 addition routes were estimated. It was found that at 175–275 °C the activation energies for hydrogen addition to the triple bond of propyne have similar values (about 60–70 kJ/mol) for both routes of hydrogen addition. At higher temperatures (275–350 °C), the rate constant for pairwise hydrogen addition reaches a maximum value while the rate constant for non-pairwise hydrogen addition continues to increase with increasing temperature.

Achieving 1% NMR polarization in water in less than 1min using SABRE

Zeng, H., et al., Achieving 1% NMR polarization in water in less than 1min using SABRE. J Magn Reson, 2014. 246C(0): p. 119-121.

http://www.ncbi.nlm.nih.gov/pubmed/25123540

The development of biocompatible hyperpolarized media is a crucial step towards application of hyperpolarization in vivo. This article describes the achievement of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the parahydrogen induced polarization technique based on signal amplification by reversible exchange (SABRE). Polarization was achieved in less than 1min.

The role of level anti-crossings in nuclear spin hyperpolarization

Ivanov, K.L., et al., The role of level anti-crossings in nuclear spin hyperpolarization. Prog. NMR. Spec., 2014. 81(0): p. 1-36.

http://www.sciencedirect.com/science/article/pii/S0079656514000454

Nuclear spin hyperpolarization is an important resource for increasing the sensitivity of NMR spectroscopy and MRI. Signal enhancements can be as large as 3–4 orders of magnitude. In hyperpolarization experiments, it is often desirable to transfer the initial polarization to other nuclei of choice, either protons or insensitive nuclei such as 13C and 15N. This situation arises primarily in Chemically Induced Dynamic Nuclear Polarization (CIDNP), Para-Hydrogen Induced Polarization (PHIP), and the related Signal Amplification By Reversible Exchange (SABRE). Here we review the recent literature on polarization transfer mechanisms, in particular focusing on the role of Level Anti-Crossings (LACs) therein. So-called “spontaneous” polarization transfer may occur both at low and high magnetic fields. In addition, transfer of spin polarization can be accomplished by using especially designed pulse sequences. It is now clear that at low field spontaneous polarization transfer is primarily due to coherent spin-state mixing under strong coupling conditions. However, thus far the important role of LACs in this process has not received much attention. At high magnetic field, polarization may be transferred by cross-relaxation effects. Another promising high-field technique is to generate the strong coupling condition by spin locking using strong radio-frequency fields. Here, an analysis of polarization transfer in terms of LACs in the rotating frame is very useful to predict which spin orders are transferred depending on the strength and frequency of the B1 field. Finally, we will examine the role of strong coupling and LACs in magnetic-field dependent nuclear spin relaxation and the related topic of long-lived spin-states.

The Feasibility of Formation and Kinetics of NMR Signal Amplification by Reversible Exchange (SABRE) at High Magnetic Field (9.4 T)

Barskiy, D.A., et al., The feasibility of formation and kinetics of NMR signal amplification by reversible exchange (SABRE) at high magnetic field (9.4 T). J Am Chem Soc, 2014. 136(9): p. 3322-5.

http://www.ncbi.nlm.nih.gov/pubmed/24528143

(1)H NMR signal amplification by reversible exchange (SABRE) was observed for pyridine and pyridine-d5 at 9.4 T, a field that is orders of magnitude higher than what is typically utilized to achieve the conventional low-field SABRE effect. In addition to emissive peaks for the hydrogen spins at the ortho positions of the pyridine substrate (both free and bound to the metal center), absorptive signals are observed from hyperpolarized orthohydrogen and Ir-complex dihydride. Real-time kinetics studies show that the polarization build-up rates for these three species are in close agreement with their respective (1)H T1 relaxation rates at 9.4 T. The results suggest that the mechanism of the substrate polarization involves cross-relaxation with hyperpolarized species in a manner similar to the spin-polarization induced nuclear Overhauser effect. Experiments utilizing pyridine-d5 as the substrate exhibited larger enhancements as well as partial H/D exchange for the hydrogen atom in the ortho position of pyridine and concomitant formation of HD molecules. While the mechanism of polarization enhancement does not explicitly require chemical exchange of hydrogen atoms of parahydrogen and the substrate, the partial chemical modification of the substrate via hydrogen exchange means that SABRE under these conditions cannot rigorously be referred to as a non-hydrogenative parahydrogen induced polarization process.

Toward nanomolar detection by NMR through SABRE hyperpolarization

Eshuis, N., et al., Toward nanomolar detection by NMR through SABRE hyperpolarization. J Am Chem Soc, 2014. 136(7): p. 2695-8.

http://www.ncbi.nlm.nih.gov/pubmed/24475903

SABRE is a nuclear spin hyperpolarization technique based on the reversible association of a substrate molecule and para-hydrogen (p-H2) to a metal complex. During the lifetime of such a complex, generally fractions of a second, the spin order of p-H2 is transferred to the nuclear spins of the substrate molecule via a transient scalar coupling network, resulting in strongly enhanced NMR signals. This technique is generally applied at relatively high concentrations (mM), in large excess of substrate with respect to metal complex. Dilution of substrate ligands below stoichiometry results in progressive decrease of signal enhancement, which precludes the direct application of SABRE to the NMR analysis of low concentration (muM) solutions. Here, we show that the efficiency of SABRE at low substrate concentrations can be restored by addition of a suitable coordinating ligand to the solution. The proposed method allowed NMR detection below 1 muM in a single scan.

Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods

Lloyd, L.S., et al., Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods. J. Am. Chem. Soc., 2012. 134(31): p. 12904-12907.

http://dx.doi.org/10.1021/ja3051052

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of 13C, 13C{1H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods

Lloyd, L.S., et al., Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods. J. Am. Chem. Soc., 2012. 134(31): p. 12904-12907.

http://dx.doi.org/10.1021/ja3051052

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of 13C, 13C{1H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

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