Towards Large-Scale Steady-State Enhanced Nuclear Magnetization with In Situ Detection

Abstract

<div>Signal Amplification By Reversible Exchange (SABRE) boosts NMR signals of various nuclei enabling new applications spanning from magnetic resonance imaging to analytical chemistry and fundamental physics. SABRE is especially well positioned for continuous generation of enhanced magnetization on a large scale, however, several challenges need to be addressed for accomplishing this goal. Specifically, SABRE requires (i) a specialized catalyst capable of reversible H<sub>2</sub> activation and (ii) physical transfer of the sample from the point of magnetization generation to the point of detection (e.g., a high-field or a benchtop NMR spectrometer). Moreover, (iii) continuous parahydrogen bubbling accelerates solvent (e.g., methanol) evaporation, thereby limiting the experimental window to tens of minutes per sample.</div><div>In this work, we demonstrate a strategy to rapidly generate the best-to-date precatalyst (a compound that is chemically modified in the course of the reaction to yield the catalyst) for SABRE, [Ir(IMes)(COD)Cl] (IMes = 1,3-bis-(2,4,6-trimethylphenyl)-imidazol-2-ylidene, COD = cyclooctadiene) via a highly accessible synthesis. Second, we measure hyperpolarized samples using a home-built zero-field NMR spectrometer and study the field dependence of hyperpolarization directly in the detection apparatus, eliminating the need to physically move the sample during the experiment. Finally, we prolong the measurement time and reduce evaporation by presaturating parahydrogen with the solvent vapor before bubbling into the sample. These advancements extend opportunities for exploring SABRE hyperpolarization by researchers from various fields and pave the way to producing large quantities of hyperpolarized material for long-lasting detection of SABRE-derived nuclear magnetization.</div>

Relayed hyperpolarization for zero-field nuclear magnetic resonance

“…Collection of J -spectra of nonisotopically labeled methanol and ethanol samples was aided by the addition of a presaturating chamber containing a small volume of solvent with substrate through which the parahydrogen was directed before bubbling through the sample chamber. This is necessary because both the solvent (DCM) and substrate (methanol and, to a lesser extent, ethanol) evaporate quickly during p H 2 bubbling without presaturation ( 26 ). The addition of the presaturator more than doubled the possible acquisition time, allowing hundreds of acquisitions to be taken per sample before significant loss of signal.…”

Relayed Hyperpolarization for Zero-Field Nuclear Magnetic Resonance

“…Furthermore, this method is mostly limited to concentrated samples and/or large magnetic fields, so alternative avenues for generating substantial NMR signals are required. Hyperpolarization techniques present an alternative to the brute-force approach, and techniques such as PHIP (parahydrogen-induced polarization) (21), SABRE (Signal Amplification By Reversible Exchange) (22)(23)(24), and dDNP (dissolution Dynamic Nuclear Polarization) (25), have already been shown to produce sufficient signal for detection in the ZULF regime (26)(27)(28)(29). SABRE is especially well suited for this, since: (i) it is based on chemical interactions of parahydrogen (pH2) which can be quickly and inexpensively produced (23); (ii) hyperpolarization can be generated multiple times in the same sample, allowing multiple experiments signal averaging; (iii) transfer of polarization from pH2 to heteronuclei such as 15 N and 13 C typically occurs at fields in the µT regime (0.1 -1.0 µT for 15 N and 13 C), which is synergistically compatible with ZULF NMR detection requirements such as shielding from the Earth's magnetic field (30,31).…”