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

Abstract

Herein, we demonstrate “direct” 13C hyperpolarization of 13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to 13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism.

15N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields

“…Thus, temperature optimization is crucial for efficient SABRE‐SHEATH hyperpolarization of [ 15 N 3 ]nimorazole. This observation is different from the optimal temperature of nearly all other SABRE‐SHEATH substrates studied to date with optimal % P 15N achieved at room temperature of ≈20 °C [25, 27, 38, 40] with the exception of [ 15 N 2 ]imidazole [57] (t OPT >75 °C)–this is likely explained by the different kinetics of nimorazole dissociation from Ir complex.…”

“…Subsequent dissociation of the complex liberates HP biomolecule to the solution. SABRE technique underwent a rapid development over the past few years, [19, 24] and the list of amenable biomolecules has been rapidly expanding [25–30] . Although [1‐ 13 C]pyruvate and other 13 C‐containing biomolecules are biomedically interesting, their primary limitation is a relatively short lifetime of HP state with exponential decay time constant T 1 on the order of 1 min in most favorable cases [4, 5, 12] .…”

15N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields

“…[55] The temperature dependence of [ 15 N 3 ]nimorazole polarization exhibits ac lear maximum at % 54 8 8C-with %P 15N being an order of magnitude greater than that at % 20 8 8C. Thus, temperature optimization is crucial for efficient SABRE-SHEATH hyperpolarization of [ 15 N 3 ]nimorazole.T his observation is different from the optimal temperature of nearly all other SABRE-SHEATH substrates studied to date with optimal %P 15N achieved at room temperature of % 20 8 8C [25,27,38,40] with the exception of [ 15 N 2 ]imidazole [57] (t OPT > 75 8 8C)-this is likely explained by the different kinetics of nimorazole dissociation from Ir complex.…”

“…SABRE technique underwent arapid development over the past few years, [19,24] and the list of amenable biomolecules has been rapidly expanding. [25][26][27][28][29][30] Although [1-13 C]pyruvate and other 13 C-containing biomolecules are biomedically interesting,t heir primary limitation is ar elatively short lifetime of HP state with exponential decay time constant T 1 on the order of 1min in most favorable cases. [4,5,12] HP 15 Nsites have garnered alot of attention recently because their T 1 can be on the order of 10 min or longer [28,[31][32][33] -as aresult, the detection window of HP injectable biomolecules can be significantly expanded.…”

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).…”