Inversion of Hyperpolarized ¹³C NMR Signals through Cross-Correlated Cross-Relaxation in Dissolution DNP Experiments

Abstract

Dissolution dynamic nuclear polarization (DDNP) is a versatile tool to boost signal amplitudes in solution-state nuclear magnetic resonance (NMR) spectroscopy. For DDNP, nuclei are spin-hyperpolarized “ ex situ ” in a dedicated DNP device and then transferred to an NMR spectrometer for detection. Dramatic signal enhancements can be achieved, enabling shorter acquisition times, real-time monitoring of fast reactions, and reduced sample concentrations. Here, we show how the sample transfer in DDNP experiments can affect NMR spectra through cross-correlated cross-relaxation (CCR), especially in the case of low-field passages. Such processes can selectively invert signals of 13 C spins in proton-carrying moieties. For their investigations, we use schemes for simultaneous or “parallel” detection of hyperpolarized 1 H and 13 C nuclei. We find that 1 H → 13 C CCR can invert signals of 13 C spins if the proton polarization is close to 100%. We deduce that low-field passage in a DDNP experiment, a common occurrence due to the introduction of so-called “ultra-shielded” magnets, accelerates these effects due to field-dependent paramagnetic relaxation enhancements that can influence CCR. The reported effects are demonstrated for various molecules, laboratory layouts, and DDNP systems. As coupled 13 C– 1 H spin systems are ubiquitous, we expect similar effects to be observed in various DDNP experiments. This might be exploited for selective spectroscopic labeling of hydrocarbons.

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

“…A significant fraction of the polarization was lost during sample dissolution and transfer due to fast relaxation during rapid low-field passage. 61 It should be noted, though, that solution-state enhancements depend critically on the layout of the laboratory where the DDNP system is situated and the effective magnetic fields during sample transfer. 62 The 3-to 4-fold prolonged relaxation times enable a similarly extended detection time window.…”

“…The solution-state enhancements were on the order of 10 000 for 13 C and 100 for 1 H nuclei. A significant fraction of the polarization was lost during sample dissolution and transfer due to fast relaxation during rapid low-field passage . It should be noted, though, that solution-state enhancements depend critically on the layout of the laboratory where the DDNP system is situated and the effective magnetic fields during sample transfer …”

“…(b) Proton longitudinal relaxation times with (blue) and without (purple) neutralization of FS. (c) The same as in panel b, but for carbon-13 longitudinal relaxation times (asterisks indicate signals that might be affected by cross-relaxation effects) 56.…”

Rapid and Simple 13C-Hyperpolarization by 1H Dissolution Dynamic Nuclear Polarization Followed by an Inline Magnetic Field Inversion

“…1 H spins in methyl groups hyperpolarized by either dDNP 28,40 or quantum rotor-induced polarization (QRIP) 41 have been shown to cross-relax to the methyl 13 C. Negroni et al gave a detailed account of the polarization transfer pathways between equivalent 1 H spins and a single 13 C spin, mediated by dipolar 1 H− 13 C interactions during the transfer of a hyperpolarized solution between the dDNP polarizer and the liquid-state spectrometer. 28 For all molecules in which the liquid-state T 1,app could be reliably fitted to the polarization decay, we found that the value was longer for the experiment without field inversion. This might be explained by the presence of RASER effects in all experiments with field inversion.…”

“…In the past years, spin dynamics in the liquid state at zero to ultralow field (ZULF) have been abundantly used to transfer spin order from 1 H to 13 C in parahydrogen-induced polarization experiments (PHIP). ,− In the context of dDNP experiments, the consequences of spin dynamics at low field have been attested during the transfer of a hyperpolarized solution from the polarizer to the liquid-state spectrometer, but, to date, they have not been exploited actively to transfer polarization from 1 H to 13 C spins. , Here, we propose to prepare 13 C-hyperpolarized metabolites using 1 H DNPwhich can readily be performed within minutes on any existing dDNP devicefollowed by dissolution and an inline flow through an adiabatic magnetic field inversion chamber to transfer the 1 H Zeeman order to the 13 C spins through the J -coupling. This inversion chamber might have the potential to become a broadly compatible add-on to any existing dDNP device.…”