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

Abstract

1H 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 1H 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.

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

“…Whereas SABRE at about 6 mT field has been shown to be very efficient for substrates such as Py [more than 1% nuclear spin polarization achieved corresponding to a sensitivity enhancement (ε) of 5 × 10 5 and 6 × 10 4 at 5.75 and 47.5 mT, respectively], [11a, 12] hyperpolarization at 47.5 mT largely relies on the high-field SABRE effect, which significantly enhances not only proton polarization of Py but also the proton nuclear spin polarization of Ir–dihydride and o -H 2 . [16] As a result, an in situ proton NMR spectrum acquired during p -H 2 bubbling at 47.5 mT has two distinctive NMR resonances detected at 47.5 mT (Figure 2 a). On the basis of the previous high-field SABRE in situ NMR spectroscopy studies at 9.4 T, [16] these two resonances are assigned to HP Py and Ir–dihydride due to their chemical shift difference of 31.5 ppm, which corresponds to a frequency separation of 64 Hz at 47.5 mT (2.02 MHz 1 H frequency).…”

“…[16] As a result, an in situ proton NMR spectrum acquired during p -H 2 bubbling at 47.5 mT has two distinctive NMR resonances detected at 47.5 mT (Figure 2 a). On the basis of the previous high-field SABRE in situ NMR spectroscopy studies at 9.4 T, [16] these two resonances are assigned to HP Py and Ir–dihydride due to their chemical shift difference of 31.5 ppm, which corresponds to a frequency separation of 64 Hz at 47.5 mT (2.02 MHz 1 H frequency). Notably, HP signals from the Py protons (δ ≈ 8–8.5 ppm) and HP o -H 2 (δ ≈ 4.5 ppm) cannot be distinguished due to a relatively broad NMR line with a full width at half height (FWHH) of about 20 Hz and a chemical shift difference of only 9–10 Hz.…”

“…[15] However, SABRE was recently shown to be feasible at high magnetic fields, consistent with an incoherent mechanism of polarization transfer. [16] High-field in situ SABRE (although relatively inefficient for substrate hyperpolarization if compared to conventional low-field SABRE) at 9.4 T revealed several additional HP species including orthohydrogen ( o -H 2 ) and a Ir–dihydride complex; the presence of the Ir complex has to be accounted for in low-field NMR where chemical shift dispersion is limited.…”

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

“…To get around these technical problems, recently several methods for generation of high-field SABRE polarization have been proposed [12,14,16,33]. The easiest method for generating SABRE polarization at a high magnetic field is based on using cross-relaxation; such a method can be implemented by bubbling pH 2 through the solution during a long period of time.…”

“…The easiest method for generating SABRE polarization at a high magnetic field is based on using cross-relaxation; such a method can be implemented by bubbling pH 2 through the solution during a long period of time. For common SABRE complexes and substrates cross-relaxation-derived NMR enhancements have been observed for 1 H [33] and 15 N [12] before. We have demonstrated that by using this straightforward approach at a high field (specifically, at B 0 = 9.4 T) one can easily hyperpolarize the spins of the stabilized Ir-complex with a signal enhancement up to 800 (see spectrum 1 in Figure 3B and the corresponding 1 H SABRE spectra in SM).…”