'Hyperpolarisation' in magnetic resonance (NMR and MRI) is a way to dramatically increase the detectability of nuclei, in some cases generating signals that are 4-5 orders of magnitude stronger than conventional measurements. This technique allows the detection of trace or transient intermediates, decreases scanning time, enhances diagnostic tools in a clinical context, and unlocks greater versatility from benchtop NMR systems.
In this presentation, we will explore some of the chemical methods to generate, transfer, and store hyperpolarised states in a range of organic molecules of interest, focusing on the central role of organic synthesis and mechanism, molecular design, and catalysis.
To generate hyperpolarisation, the nuclear singlet spin isomer of dihydrogen known as para-hydrogen (p-H2) can be used as the 'source' of the enhanced NMR signal. The nuclear symmetry of p-H2 must be broken to unlock this latent signal, for instance through addition to a transition metal complex. The hyperpolarised state can subsequently be transferred to an unsaturated target compound (hydrogenation), to another molecule bound to the transition metal complex (ligand exchange), or through labile functional groups (proton exchange). Once delivered to the target molecule, the lifetime of the hyperpolarised state is limited by nuclear relaxation pathways, so use of longer-lived heteronuclei (13C, 15N), design of isolated 1H positions insulated from relaxation by 2H substitution, or molecules capable of producing 'long-lived singlet states' are all strategies to extend this lifetime, and can be accessed synthetically by selective incorporation of these stable isotopes. Interesting examples where p-H2 derived hyperpolarisation intersects with photochemistry and heterogeneous catalysis, the application of this technology, and prospects for enhancing benchtop NMR for reaction monitoring and portable spectroscopy, will be discussed.