Quasi-Resonance Fluorine-19 Signal Amplification by Reversible Exchange

Abstract

We report on an extension of the quasiresonance (QUASR) pulse sequence used for signal amplification by reversible exchange (SABRE), showing that we may target distantly J-coupled 19 F-spins. Polarization transfer from the parahydrogen-derived hydrides to the 19 F nucleus is accomplished via weak five-bond J-couplings using a shaped QUASR radio frequency pulse at a 0.05 T magnetic field. The net result is the direct generation of hyperpolarized 19 F z-magnetization, derived from the parahydrogen singlet order. An accumulation of 19 F polarization on the free ligand is achieved with subsequent repetition of this pulse sequence. The hyperpolarized 19 F signal exhibits clear dependence on the pulse length, irradiation frequency, and delay time in a manner similar to that reported for 15 N QUASR-SABRE. Moreover, the hyperpolarized 19 F signals of 3-19 F-14 N-pyridine and 3-19 F-15 Npyridine isotopologues are similar, suggesting that (i) polarization transfer via QUASR-SABRE is irrespective of the nitrogen isotopologue and (ii) the presence or absence of the spin-1/2 15 N nucleus has no impact on the efficiency of QUASR-SABRE polarization transfer. Although optimization of polarization transfer efficiency to 19 F (P 19 F ≈ 0.1%) was not the goal of this study, we show that high-field SABRE can be efficient and broadly applicable for direct hyperpolarization of 19 F spins.

“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

“…While strong 1 H SABRE of py is observed following addition of acetate (Figure C), no enhancement is observed for 1 H spins of acetate (methyl protons at 2.1 ppm)—indicating that SABRE was not sufficient to observe acetate signal enhancement in the 1 H spectrum under the tested conditions. However, the presence of a pair of new dispersive 1 H resonances in the hydride region are consistent with (at least) weak but direct binding of the additional ligand—acetate—to the catalyst in a manner that reduces local symmetry …”

“…While strong 1 HSABRE of py is observed following addition of acetate ( Figure 2C), no enhancement is observed for 1 Hs pins of acetate (methyl protons at 2.1 ppm)-indicating that SABRE was not sufficient to observe acetate signal enhancement in the 1 H spectrum under the tested conditions.However,the presence of ap air of new dispersive 1 Hr esonances in the hydride region are consistent with (at least) weak but direct binding of the additional ligand-acetate-to the catalyst in am anner that reduces local symmetry. [31] Thep otential for SABRE-SHEATH enhancement of 1-13 C-acetate was then investigated by bubbling p-H 2 into the sample within amu-metal magnetic shield prior to the sample being rapidly transported to the spectrometers9.4 Tmagnet for detection;for this experiment, p-H 2 was bubbled for 30 s at 75 psi pressure and as ample temperature of % 23 8 8C (slightly above room temperature), the sodium 1-13 C-acetate concentration was 30 mm,t he magnetic field strength in the sample region of the shield was estimated to be % 0.7 mT, and the manual transport time was % 5s .F igure 3A shows as ingle-scan hyperpolarized 13 Cs pectrum following SA- Figure 1. Scheme summarizing the experimental approach:F ollowing catalyst activation, 1 HS ABRE is first observed on an auxiliary ligand (pyridine, "Py");following addition of sodium 1-13 C-acetate, SABRE-SHEATH is performed to yield HP 1-13 C-acetate, which likely exchanges with other ligands on the complex with weak, transient binding to Ir.…”

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

“…In this context, SABRE does not require harsh conditions, and substrates can be constantly hyperpolarized without any structural changes during the polarization transfer. Furthermore, in this method, the polarization can be real-time transferred from protons to other isotopes such as 13 C 19 , 15 N 20 – 23 , 31 P 24 , 19 F 25 , 119 Sn 26 , and 29 Si 27 without chemical changes.…”

Infinite-order perturbative treatment for quantum evolution with exchange

“…On the forefront of magnetic resonance techniques are hyperpolarization methods (11)(12)(13)(14)(15), which overcome the intrinsically low signal-to-noise limits by distilling spin order from an external source. Of particular interest over the past decade is signal amplification by reversible exchange (SABRE) (5,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), in which the singlet order of parahydrogen is converted into observable magnetization or more complex spin states on target ligands during transient interactions with an iridium catalyst ( Fig. 1A).…”