SABRE-Relay: A Versatile Route to Hyperpolarization

Abstract

Signal Amplification by Reversible Exchange (SABRE) is used to switch on the latent singlet spin order of para-hydrogen (p-H2) so that it can hyperpolarize a substrate (sub = nicotinamide, nicotinate, niacin, pyrimidine, and pyrazine). The substrate then reacts reversibly with [Pt(OTf)2(bis-diphenylphosphinopropane)] by displacing OTf– to form [Pt(OTf)(sub)(bis-diphenylphosphinopropane)]OTf. The 31P NMR signals of these metal complexes prove to be enhanced when the substrate possesses an accessible singlet state or long-lived Zeeman polarization. In the case of pyrazine, the corresponding 31P signal was 105 ± 8 times larger than expected, which equated to an 8 h reduction in total scan time for an equivalent signal-to-noise ratio under normal acquisition conditions. Hence, p-H2 derived spin order is successfully relayed into a second metal complex via a suitable polarization carrier (sub). When fully developed, we expect this route involving a second catalyst to successfully hyperpolarize many classes of substrates that are not amenable to the original SABRE method.

“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

“…We also note that while no 13 C signal was detected that could be assigned to catalyst‐bound acetate (under either HP or thermally‐polarized conditions; see also the variable temperature experiment in Figure S7), a small shift in the “free” 13 C acetate signal is observed in the presence of the catalyst (Figure S1 in SI). Taken together with the presence of the new hydride 1 H resonances upon acetate addition (Figure C), these results are consistent with “direct” transfer of spin order from hydride 1 H spins to transiently bound 13 C acetate spins under SABRE‐SHEATH conditions—as opposed to a SABRE‐RELAY‐type mechanism involving HP ligand 1 H spins, and/or a mechanism that does not involve direct acetate binding to the catalyst.…”

Hyperpolarization of Pyridyl Fentalogues by Signal Amplification By Reversible Exchange (SABRE)

“…However, this approach failed to yield any detectable signal enhancement for either analyte following polarization transfer in earth's magnetic field and subsequent detection in a 1.4 T field. This was again, perhaps, expected, given that polarization of amines by SABRE‐Relay has only been exemplified for primary and secondary amines . To the best of our knowledge, polarization of tertiary amines has not been reported.…”

“…However, the lack of suitable ligation groups/atoms to the SABRE catalyst meant that conventional SABRE could not be employed, although it was attempted to validate the change in approach (no enhancement observed). Instead a combined SABRE‐Relay CASH (catalyst separated hyperpolarization)‐SABRE approach was utilized (see SI for details). However, this approach failed to yield any detectable signal enhancement for either analyte following polarization transfer in earth's magnetic field and subsequent detection in a 1.4 T field.…”

“…An iridium centred catalyst is typically employed to propagate polarisation, via J‐coupling, between the para hydrogen derived hydrides and the spin‐ nuclei of the analyte molecule being polarised . The pre‐catalyst, [Ir(IMes)(COD)Cl] (IMes=1,3‐ bis (2,4,6‐trimethylphenyl)imidazole‐2‐ylidene, COD=cyclooctadiene) has been shown to be an excellent catalyst, following activation, in this regard for a number of substrates such as nicotinamide, quinazoline, and niacin . Manipulation of the spin‐reservoir of the substrate, such as deuteration, has been shown to be an effective route by which polarization can be maximized.…”

A role for low concentration reaction intermediates in the signal amplification by reversible exchange process revealed by theory and experiment

“…20 Specially created longer-lived states have been harnessed to alleviate these relaxation issues, often in conjunction with rationally designed substrates and catalysts. 14,[21][22][23][24][25][26] The role of the catalyst in SABRE has recently been reviewed. 27 Because of the catalytic nature of SABRE, hard to detect reaction intermediates might be expected to play a role in this process and we show here that their effect is currently underestimated.…”