Nuclear spin hyperpolarization of the solvent using signal amplification by reversible exchange (SABRE)

Abstract

Here we report the polarization of the solvent OH protons by SABRE using standard iridium-based catalysts under slightly acidic conditions. Solvent polarization was observed in the presence of a variety of structurally similar N-donor substrates while no solvent enhancement was observed in the absence of substrate or para-hydrogen (p-H2). Solvent polarization was sensitive to the polarizing field and catalyst:substrate ratio in a manner similar to that of substrate protons. SABRE experiments with pyridine-d5 suggest a mechanism where hyperpolarization is transferred from the free substrate to the solvent by chemical exchange while measured hyperpolaization decay times suggest a complimentary mechanism which occurs by direct coordination of the solvent to the catalytic complex. We found the solvent hyperpolarization to decay nearly 3 times more slowly than its characteristic spin-lattice relaxation time suggesting that the hyperpolarized state of the solvent may be sufficiently long lived (~20 s) to hyperpolarize biomolecules having exchangeable protons. This route may offer future opportunities for SABRE to impact metabolic imaging.

Harnessing polarisation transfer to indazole and imidazole through signal amplification by reversible exchange to improve their NMR detectability

“…These measurements were made in an automated flow apparatus that has been described previously [10a] . This device, the Polariser, is represented in Fig.…”

“…using the first generation of phosphine‐based SABRE catalysts4 were observed to produce a 2‐fold NMR signal enhancement [6a] . A study on imidazole by Moreno et al [10d] . using the second generation of carbene‐based SABRE catalysts [6b] produced an improved response.…”

“…As the original substrate molecule is reformed after ligand dissociation, there is no change in its chemical identity during this process, but it has now become a hyperpolarised (HP) species. SABRE catalysts based on N ‐heterocyclic carbene (NHC) iridium complexes that contain 1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene (IMes) or 1,3‐bis(2,4,6‐trimethylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene (SIMes) ligands are used in this study,8, 9 although studies on other templates and a range of substrates have been described in the literature 6, 9, 10. A number of theoretical approaches have been used to model the SABRE effect, of which the level‐anti‐crossing approach provides a readily understandable solution 11.…”

“…One of the drivers for the development of hyperpolarisation methods is the potential to collect in vivo data on a hyperpolarised agent that may ultimately prove to be diagnostic of health [10b] . Another is the use of high‐sensitivity methods in analytical chemistry.…”

“…[ 10 , 13 ] Other routes to hyperpolarisation include dynamic nuclear polarisation,2 parahydrogen‐induced polarisation[ 6 , 14 ] with substrate functionalisation and spin‐exchange optical pumping. [ 10 , 15 ]…”