Frémy’s Salt as a Low-Persistence Hyperpolarization Agent: Efficient Dynamic Nuclear Polarization Plus Rapid Radical Scavenging

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is a key technique for molecular structure determination in solution. However, due to its low sensitivity, many efforts have been made to improve signal strengths and reduce the required substrate amounts. In this regard, dissolution dynamic nuclear polarization (DDNP) is a versatile approach as signal enhancements of over 10 000-fold are achievable. Samples are signal-enhanced ex situ by transferring electronic polarization from radicals to nuclear spins before dissolving and shuttling the boosted sample to an NMR spectrometer for detection. However, the applicability of DDNP suffers from one major drawback, namely, paramagnetic relaxation enhancements (PREs) that critically reduce relaxation times due to the codissolved radicals. PREs are the primary source of polarization losses canceling the signal improvements obtained by DNP. We solve this problem by using potassium nitrosodisulfonate (Freḿy's salt) as polarization agent (PA), which provides high nuclear spin polarization and allows for rapid scavenging under mild reducing conditions. We demonstrate the potential of Freḿy's salt, (i) showing that both 1 H and 13 C polarization of ∼30% can be achieved and (ii) describing a hybrid sample shuttling system (HySSS) that can be used with any DDNP/NMR combination to remove the PA before NMR detection. This gadget mixes the hyperpolarized solution with a radical scavenger and injects it into an NMR tube, providing, within a few seconds, quantitatively radical-free, highly polarized solutions. The cost efficiency and broad availability of Freḿy's salt might facilitate the use of DDNP in many fields of research.

Missing Pieces in Structure Puzzles: How Hyperpolarized NMR Spectroscopy Can Complement Structural Biology and Biochemistry

“…To record high‐field solution‐state NMR spectra subsequent to DNP at low temperatures (often denoted as the “signal build‐up”), the sample is rapidly dissolved with a burst of hot solvent and transferred to a conventional NMR spectrometer for detection. Various implementations of how to dissolve and transfer the sample have been reported for a variety of applications [69–73] . Prototypically though, D 2 O pressurized to >1 MPa is used for dissolution.…”

“…Recently, another solution has been developed, where two solutions can be mixed ex situ in a dedicated “mixing chamber” prior to transfer to the NMR tube [73] . The system is described in Figure 2.…”

Paramagnetic relaxivity of delocalized long-lived states of protons in chains of CH2 groups

“…Scavenging by sodium ascorbate may be accelerated ca. 100 times if one uses Frémy's salt instead of TEMPOL (Negroni et al, 2022). Several alternative approaches have been developed to remove radicals once DNP has been achieved.…”

Real-Time Polarimetry of Hyperpolarized 13C Nuclear Spins Using an Atomic Magnetometer

“…The observation that the 13 C T 1 is unchanged across 3 orders of magnitude in field is not so surprising for such a small molecule, given that paramagnetic relaxivities in aqueous solution are generally found to be constant below 1 mT . We expect that the use of nonpersistent-radical polarizing agents, − filtration, or other strategies to remove paramagnetic dopants from the solution should prolong the decay time at both the storage and detection fields.…”