Parahydrogen-Induced Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation

Abstract

The feasibility of Carbon-13 Radiofrequency (RF) Amplification by Stimulated Emission of Radiation (C-13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1-¹³ C]acetate. Hyperpolarized ethyl [1-¹³ C]acetate was prepared via pairwise addition of parahydrogen to vinyl [1-¹³ C]acetate and polarization transfer from nascent parahydrogen-derived protons to the carbon-13 nucleus via magnetic field cycling yielding C-13 nuclear spin polarization of approximately 6 %. RASER signals were detected from samples with concentration ranging from 0.12 to 1 M concentration using a non-cryogenic 1.4T NMR spectrometer equipped with a radio-frequency detection coil with a quality factor (Q) of 32 without any modifications. C-13 RASER signals were observed for several minutes on a single bolus of hyperpolarized substrate to achieve 21 mHz NMR linewidths. The feasibility of creating long-lasting C-13 RASER on biomolecular carriers opens a wide range of new opportunities for the rapidly expanding field of C-13 magnetic resonance hyperpolarization.

Keywords: Carbon-13; Hyperpolarization; NMR Spectroscopy; Parahydrogen; RASER.

Figure 1.

(top) schematic of pairwise parahydrogen (p-H₂) addition to vinyl acetate (VA) precursor followed by polarization transfer from nascent p-H₂-derived protons to the ethyl acetate 1-¹³C nucleus via magnetic field cycling (note the optional ¹³C labeling shown with asterisk); (bottom) schematic of experimental setup for p-H₂ pairwise addition to unsaturated substrate, and polarization transfer to the ¹³C nucleus via magnetic field cycling (SI).

Figure 2.

Proton-decoupled ¹³C NMR RASER spectroscopy of solution-phase PHIP of ethyl [1-¹³C]acetate (P_13C~6%, 0.5 M in acetone-d₆) detected at 1.4 T using ¹³C resonator with Q of 32. (a-c) Time-domain ¹³C RASER signals and FT spectra recorded without a RF pulse but with ¹H decoupling for 1M, 0.5M, and 0.25M samples respectively (additional RASER acquisitions are shown in Figures S4–S7. (d) ¹³C spectrum of HP ethyl acetate with total magnetization well below the RASER threshold (recorded using a 10° RF pulse under otherwise similar detection conditions): FWHM = 0.23 Hz, and ¹³C T₂* ~ 1.4 seconds, Figure S2.