Parahydrogen induced polarization in face of keto–enol tautomerism: proof of concept with hyperpolarized ethanol

Abstract

Hyperpolarization (HP) techniques are increasingly important in magnetic resonance imaging (MRI) and spectroscopy (MRS). HP methods have the potential to overcome the fundamentally low sensitivity of magnetic resonance (MR). A breakthrough of HP-MR in life sciences and medical applications is still limited by the small number of accessible, physiologically relevant substrates. Our study presents a new approach to extend PHIP to substrates that primarily cannot be hyperpolarized due to a steady intramolecular re-arrangement, the so-called keto-enol tautomerism. To overcome this obstacle we exploited the fact that instead of the instable enol form the corresponding stable ester can be used as a precursor molecule. This strategy now enables the hydrogenation which is required to apply the standard PHIP procedure. As the final step a hydrolysis is necessary to release the hyperpolarized target molecule. Using this new approach ethanol was successfully hyperpolarized for the first time. It may therefore be assumed that the outlined multi-step procedure can be used for other keto-enol tautomerized substances thereby opening the application of PHIP to a multitude of molecules relevant to analyzing metabolic pathways.

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

“…Parahydrogenation of vinyl acetate (1) and hydrolysis have been previously reported 34 for obtaining hyperpolarized ethanol. Here it is shown that polarization transfer to the 13 C carboxylate signal is possible by means of magnetic field cycling.…”

NMR Hyperpolarization Techniques for Biomedicine

“…Despite the synthetic challenges, new concepts of using –OH protection in -C=C-O-R motifs have significantly expanded the reach of molecular targets for PHIP, [54, 57] because the protecting group can be removed after PHIP either metabolically [52, 54, 58] or synthetically. [57] …”

Pulsed Magnetic Resonance to Signal‐Enhance Metabolites within Seconds by utilizing para‐Hydrogen

“…Finally, the sidearm is cleaved off, yielding the hyperpolarized metabolite . A similar approach has been investigated for hyperpolarizing ethanol and has recently been shown to be applicable in gas‐phase reactions . Polarization transfer in PHIP‐SAH has been achieved so far by a field‐cycling procedure, in which a sample is shuttled into a magnetic field below the earth's field, followed by re‐magnetization to transfer proton polarization to 13 C‐labeled nuclei .…”