Improving the Hyperpolarization of ³¹P Nuclei by Synthetic Design

Traditional ³¹P NMR or MRI measurements suffer from low sensitivity relative to ¹H detection and consequently require longer scan times. We show here that hyperpolarization of ³¹P nuclei through reversible interactions with <i>para</i>hydrogen can deliver substantial signal enhancements in a range of regioisomeric phosphonate esters containing a heteroaromatic motif which were synthesized in order to identify the optimum molecular scaffold for polarization transfer. A 3588-fold ³¹P signal enhancement (2.34% polarization) was returned for a partially deuterated pyridyl substituted phosphonate ester. This hyperpolarization level is sufficient to allow single scan ³¹P MR images of a phantom to be recorded at a 9.4 T observation field in seconds that have signal-to-noise ratios of up to 94.4 when the analyte concentration is 10 mM. In contrast, a 12 h 2048 scan measurement under standard conditions yields a signal-to-noise ratio of just 11.4. ³¹P-hyperpolarized images are also reported from a 7 T preclinical scanner