Herein, we demonstrate “direct”13C hyperpolarization of13C‐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 the13C 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 to13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the13C 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.
We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction with benchtop (1.1 T) and high field (9.4 T) NMR magnets, highlighting the versatility of this system to operate with any NMR or MRI system. The STAR uses semipermeable membranes to efficiently deliver parahydrogen into solutions at nano to milli Tesla fields, which enables1H,13C, and15N hyperpolarization on a large range of substrates including drugs and metabolites. The unique features of the STAR are leveraged for important applications, including continuous hyperpolarization of metabolites, desirable for examining steady‐state metabolism in vivo, as well as for continuous RASER signals suitable for the investigation of new physics.
more » « less- NSF-PAR ID:
- 10306806
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ChemPhysChem
- Volume:
- 22
- Issue:
- 24
- ISSN:
- 1439-4235
- Page Range / eLocation ID:
- p. 2526-2534
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
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Abstract Herein, we demonstrate “direct”13C hyperpolarization of13C‐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 the13C 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 to13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the13C 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.
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Abstract Parahydrogen-induced polarization of13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C]acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for1H to13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in13C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for1H to13C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively). Nevertheless, a significant13C NMR signal enhancement with respect to thermal polarization allowed us to perform13C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.
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Abstract Hyperpolarization techniques are key to extending the capabilities of MRI for the investigation of structural, functional and metabolic processes in vivo. Recent heterogeneous catalyst development has produced high polarization in water using parahydrogen with biologically relevant contrast agents. A heterogeneous ligand‐stabilized Rh catalyst is introduced that is capable of achieving15N polarization of 12.2±2.7 % by hydrogenation of neurine into a choline derivative. This is the highest15N polarization of any parahydrogen method in water to date. Notably, this was performed using a deuterated quaternary amine with an exceptionally long spin‐lattice relaxation time (
T 1) of 21.0±0.4 min. These results open the door to the possibility of15N in vivo imaging using nontoxic similar model systems because of the biocompatibility of the production media and the stability of the heterogeneous catalyst using parahydrogen‐induced polarization (PHIP) as the hyperpolarization method. -
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Abstract Hyperpolarization techniques are key to extending the capabilities of MRI for the investigation of structural, functional and metabolic processes in vivo. Recent heterogeneous catalyst development has produced high polarization in water using parahydrogen with biologically relevant contrast agents. A heterogeneous ligand‐stabilized Rh catalyst is introduced that is capable of achieving15N polarization of 12.2±2.7 % by hydrogenation of neurine into a choline derivative. This is the highest15N polarization of any parahydrogen method in water to date. Notably, this was performed using a deuterated quaternary amine with an exceptionally long spin‐lattice relaxation time (
T 1) of 21.0±0.4 min. These results open the door to the possibility of15N in vivo imaging using nontoxic similar model systems because of the biocompatibility of the production media and the stability of the heterogeneous catalyst using parahydrogen‐induced polarization (PHIP) as the hyperpolarization method.
