Indirect Zero-Field Nuclear Magnetic Resonance Spectroscopy

Abstract

This study develops the two-field correlation spectroscopy (COSY) in zero to ultralow field (ZULF) liquid state nuclear magnetic resonance (NMR). We demonstrated the successful integration of signal amplification by reversible exchange (SABRE) hyperpolarization with two-dimensional (2D) NMR spectroscopy, enabling the detection of ZULF COSY spectra with increased sensitivity. Field cycling allowed the acquisition of two-field COSY spectra at varying magnetic field strengths, including zero-field conditions. This enabled insight into both J-coupling and Zeeman-dominated regimes, benefiting from ultralow field observation sensitivity and mitigating the low-frequency noise by conducting readout at higher fields (>5 μT). Our study explores the effects of polarization transfer, apodization techniques, and the potential for further application of ZULF NMR in chemical analysis exemplified for three X-nuclei and three corresponding molecules: [1-¹³C]pyruvate, [¹⁵N]acetonitrile, and [3-¹⁹F]pyridine. These findings pave the way for more sensitive and cost-effective NMR spectroscopy in low-field regimes.

1

Experimental overview of SABRE at ZULF.¹³C phase-corrected NMR spectrum of [1-¹³C]­pyruvate at B _acq = 6.8 μT (a) and B _acq < 2 nT (b). Experimental ZULF NMR and SABRE setup (described in the Methods section) containing the pH₂ cylinder, the mass flow controller (MFC), sample container, the reservoir, and the back-pressure regulator (BPR) (c). SABRE schematic, where pH₂ and [1-¹³C]­pyruvate exchange with an iridium complex (d). At appropriate conditions (exposed to specific static magnetic fields or radiofrequency magnetic fields B _hyp), polarization transfer from pH₂ to ¹³C occurs. , For example, the target heteronuclei can be polarized when the Larmor frequency difference between the pH₂-derived hydride ligands and the heteronuclei is of similar order to the combination of J-coupling interactions: this experiment is referred to as SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). Schematics of 1D ZULF (e) and ZULF COSY (f) sequences. The 1D ZULF sequence allows the measurement of the 1D spectrum at the field B _acq, which can be in the ZULF regime. ZULF COSY enables the measurement of 2D correlation spectra with an evolution field of B _evo and the readout at B _acq; B _evo can be in the ZULF regime.

2

Two-field COSY spectra of [1-¹³C]­pyruvate at B _evo< 2 nT and B _acq = 6.8 μT. Experimental (a) and simulated (b) absolute spectra of the ¹³C signal (left) and ¹H signal (right) are shown together with projections in direct and indirect dimensions. We see peaks at the typical quartet positions of ¹³C and doublet positions of ¹H in the direct frequency dimension projection and at 0, ±J, and ±2J frequencies in the indirect frequency dimension projection.

3

Two-field COSY spectra of [1-¹³C]­pyruvate at B _evo = 25 nT and B _acq = 6.8 μT. Experimental (a) and simulated (b) absolute spectra of the ¹³C signal (left) and ¹H signal (right) are shown together with projections in direct and indirect dimensions. We see peaks at the typical quartet positions of ¹³C and doublet positions of ¹H in the direct dimension. At the same time, no clear pattern can be deduced in the intermediate coupling regime in the indirect frequency dimension projection.

4

Two-field COSY spectra of [1-¹³C]­pyruvate at B _evo = 494 nT and B _acq = 6.8 μT. Experimental (a) and simulated (b) absolute spectra of the ¹³C signal (left) and ¹H signal (right) are shown together with projections in direct and indirect dimensions. We see peaks at the typical quartet positions of ¹³C and doublet positions of ¹H in the direct and indirect dimensions. Indirect projections additionally comprise ¹H–¹³C and ¹³C–¹H cross-peaks. The order of nuclei in cross-peak assignment reflects the order of indirect and direct encoding.