Towards large‐scale steady‐state enhanced nuclear magnetization with in situ detection

Abstract

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 2 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.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 = 1,3bis-(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.

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.…”

Spin Hyperpolarization in Modern Magnetic Resonance

“…This holds great promise for applications in chemistry, biomedicine, and fundamental physics. 824 Currently investigated applications of in situ SABRE-ZULF include the NMR study of systems undergoing chemical exchange 395 as well as biomolecular analysis. 825 The polarization method used in SABRE-ZULF experiments is essentially the SABRE-SHEATH approach described above.…”

Instrumentation for Hydrogenative Parahydrogen-Based Hyperpolarization Techniques

“…While dedicated setups to produce diagnostically relevant contrast agent have not yet emerged, some interesting setups were described that allow exploiting the unique properties at these fields. Among these are (a) the distribution of the polarization across an entire molecule and different coherences, (b) the unique sensors to detect signals in the Hz–kHz range, − and (c) the identification of molecules by their J -couplings rather than their chemical shift. − …”

“…The detection sensitivity for conventional RF coils, as used for high field MR experiments, decreases with frequency . Therefore, at ultralow fields, different magnetic field detectors such as atomic magnetometers (Figure a) ,,,,, or superconducting quantum interference devices (SQUIDs) (Figure b) , may be more sensitive than inductive detection. Such sensors are even sensitive enough to perform magnetoencephalography but can also be used to detect nuclear spins.…”