SABRE polarized low field rare-spin spectroscopy

Abstract

High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR instruments operating at low magnetic fields are emerging as a compact, inexpensive, and highly accessible alternative but suffer from low thermal polarization at a low field strength and consequently a low signal. However, certain hyperpolarization techniques create high polarization levels on target molecules independent of magnetic fields, giving low-field NMR a significant sensitivity boost. In this study, SABRE (Signal Amplification By Reversible Exchange) was combined with high homogeneity electromagnets operating at mT fields, enabling high resolution ¹H, ¹³C, ¹⁵N, and ¹⁹F spectra to be detected with a single scan at magnetic fields between 1 mT and 10 mT. Chemical specificity is attained at mT magnetic fields with complex, highly resolved spectra. Most spectra are in the strong coupling regime where J-couplings are on the order of chemical shift differences. The spectra and the hyperpolarization spin dynamics are simulated with SPINACH. The simulations start from the parahydrogen singlet in the bound complex and include both chemical exchange and spin evolution at these mT fields. The simulations qualitatively match the experimental spectra and are used to identify the spin order terms formed during mT SABRE. The combination of low field NMR instruments with SABRE polarization results in sensitive measurements, even for rare spins with low gyromagnetic ratios at low magnetic fields.

FIG. 1.

Setup of the spectroscopy electromagnet [(a)–(c)] and the 6.5 mT ultra-low field (ULF) MRI scanner [(d)–(g)]: (a) electromagnet with an EHQE resonator, (b) 41.7 kHz detection coil, (c) parahydrogen bubbling through the SABRE active solution using a pipette tip and a small glass vial, (d) imaging magnet with the detection coil in the middle, (e) coil for 28 kHz (¹H) detection at 6.5 mT, (f) coil for 276 kHz (¹⁵N) detection at 6.5 mT, and (g) parahydrogen bubbling through a SABRE active solution with Teflon tubing in a high-pressure NMR tube.

FIG. 2.

¹³C-labeled acetonitrile: (a) ¹H spectrum of acetonitrile at 41.7 kHz labeled with ¹³C at the nitrile carbon, (b) corresponding ¹³C spectrum at 41.7 kHz, (c) “quick” simulation of the proton spectrum starting from I_z(1)S_z(4) + I_z(2)S_z(4) + I_z(3)S_z(4) − 2I_z(1)I_z(2)I_z(3)S_z(4), and (d) “quick” simulation of the carbon spectrum with starting state S_z(4) after suggested cross relaxation/NOE. ²J_CH = 10.3 Hz. The spin order for the ¹H spectrum simulated with the “quick” approach is chosen as is for consistency with the ¹⁵N labeled acetonitrile experiments, even though all the individual terms yield the same spectrum (see the ¹H spectrum of ¹⁵N acetonitrile in the supplementary material). The “complete” simulations are provided in the supplementary material as well.

FIG. 3.

¹⁵N-labeled acetonitrile with J_NH = 1.74 Hz: (a) ¹H spectrum at 41.7 kHz, (b) corresponding ¹⁵N spectrum at 41.7 kHz, and (c) ¹⁵N SABRE-SHEATH experiment: shuttling from the 2 µT field for polarization into 10 mT for detection. [(d)–(f)] “Quick” simulations with the initial state for (d) and (e) I_z(1)S_z(4) + I_z(2)S_z(4) + I_z(3)S_z(4) − 2I_z(1)I_z(2)I_z(3)S_z(4), only single spin order S_z(4) for (f) (“complete” simulations provided in the supplementary material).

FIG. 4.

¹H and ¹⁵N low-field spectra of ¹⁵N-pyridine: [(a) and (b)] single-scan SABRE spectra recorded at 41.7 kHz on the solenoid electromagnet (EHQE NMR), [(c) and (d)] corresponding “complete” simulations accounting for the spin evolution and the chemical dynamics, [(e) and (f)] ¹H and ¹⁵N spectra of ¹⁵N-pyridine recorded in the ULF MRI magnet at 6.5 mT, and [(g) and (h)] corresponding “complete” simulations accounting for the spin evolution and the chemical dynamics (“quick” simulations provided in the supplementary material).

FIG. 5.

Low-field SABRE spectra of 3-fluoropyridine at 41.7 kHz: [(a) and (b)] scan ¹H and ¹⁹F spectra recorded on the solenoid electromagnet and [(c) and (d)] corresponding “complete” simulations accounting for the spin evolution and the chemical dynamics (“quick” simulations provided in the supplementary material).