Relayed hyperpolarization for zero-field nuclear magnetic resonance

Abstract

Zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) is a rapidly developing form of spectroscopy that provides rich spectroscopic information in the absence of large magnetic fields. However, signal acquisition still requires a mechanism for generating a bulk magnetic moment for detection, and the currently used methods only apply to a limited pool of chemicals or come at prohibitively high cost. We demonstrate that the parahydrogen-based SABRE (signal amplification by reversible exchange)-Relay method can be used as a more general means of generating hyperpolarized analytes for ZULF NMR by observing zero-field J-spectra of [¹³C]-methanol, [1-¹³C]-ethanol, and [2-¹³C]-ethanol in both ¹³C-isotopically enriched and natural abundance samples. We explore the magnetic field dependence of the SABRE-Relay efficiency and show the existence of a second maximum at 19.0 ± 0.3 mT. Despite presence of water, SABRE-Relay is used to hyperpolarize ethanol extracted from a store-bought sample of vodka (%P_H ~ 0.1%).

Fig. 1.. SABRE-Relay optimization and ZULF NMR measurements of methanol.

(A) Molecular diagram of the SABRE-Relay process: Parahydrogen (pH₂) coordinates with the Ir catalyst to form [Ir(IMes)(BnNH₂)₃H₂] (denoted [Ir] below), allowing the transfer of spin order onto the bound substrate, benzylamine (BnNH₂), and to a second substrate via proton exchange. (B) Schematic of the experiment showing two possible detection modes: (left) inductive detection used in this work using a benchtop NMR spectrometer (40 or 60 MHz); (right) detection of NMR with an OPM in the ZULF regime. (C) ¹H NMR spectrum (1.4 T) of methanol and benzylamine (both 230 mM) in DCM (top) at thermal equilibrium polarization and (bottom) a SABRE-Relay hyperpolarized (B_T ~ 7 mT, 10-s bubbling, 60 SCCM pH₂ at 5 bar) spectrum of the same sample. (D) Magnetic field dependence of SABRE-Relay–derived hyperpolarization of methanol detected via ¹³C DEPT at 1.4 T showing two clear maxima. a.u., arbitrary units. (E) Methanol molar polarization as a function of methanol and benzylamine concentrations. Both chemicals were increased in tandem by adding concentrated stock solution to the activated [Ir] catalyst. (F) ZULF NMR event sequence: bubbling of pH₂ into the sample at 6.5 mT for 10 s followed by a drop in field induced by sample insertion into magnetic shield through the solenoid (22 μT) before reaching the 40-μT Helmholtz coil field. This was nonadiabatically switched off immediately before acquisition of the NMR signal. (G) ZULF NMR spectrum (64 scans) of SABRE-Relay–polarized methanol-¹³C (230 mM methanol, 230 mM benzylamine, 12 mM [Ir]) showing peaks at J and 2J, where J is the heteronuclear ¹J_CH coupling. (H) Full ZULF NMR spectrum (64 scans) showing 50-Hz noise peak and overtones from transmission-line noise (*) and noise arising from the laser of the OPM sensor and the temperature-stabilization circuit (^o).

Fig. 2.. SABRE-Relay of ¹³C-labeled ethanol with detection in the ZULF regime.

(A and B) Simulated and experimental zero-field J-spectra (64 scans) of [1-¹³C]-ethanol and [2-¹³C]-ethanol (230 mM) hyperpolarized by SABRE-Relay separately using the carrier amine benzylamine. Red dots represent the positions of the [¹³C] nucleus. (C) Relaxometry of [1-¹³C]- and [2-¹³C]-ethanol at zero field obtained by integrating peaks at 210 and 128 Hz, respectively, and then fitting the results with a monoexponential decay function with the stated time constant. Each data point represents the sum of four scans.

Fig. 3.. Hyperpolarization and detection of a methanol/ethanol mixture at natural isotopic abundance.

(A) High-field (1 T) ¹H NMR spectra of a thermally polarized (top) and SABRE-Relay–polarized (bottom) sample containing ethanol (750 mM) extracted from vodka and methanol (750 mM) at natural isotopic abundance with benzylamine (250 mM) and Ir catalyst (12 mM). The SABRE spectrum was observed after 10 s of bubbling with parahydrogen in a field of 19 mT at 5 bar and 60 SCCM. (B) ZULF NMR spectrum of the same sample following 1500 scans and similar SABRE parameters as in (A). The peaks of methanol at 140 and 280 Hz represent J_CH and 2J_CH, and the cluster of peaks surrounding 210 Hz arise from the AX₂ spin system of [1-¹³C]-ethanol (3/2*J_CH, J = 140 Hz). Peaks for [2-¹³C]-ethanol are visible around 255 Hz, although markedly less clear than those of the other ethanol isotopomer; (*) denotes peak from an unknown source.