Hyperpolarizing Concentrated Metronidazole NO Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime.

The NMR hyperpolarization of uniformly N-labeled [ N ]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the NO group is hyperpolarized through spin relays created by N spins in [ N ]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P ) of around 16 % is achieved on all three N sites. This product of N polarization and concentration of N spins is around six-fold better than any previous value determined for N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T ≈10 min). A novel synthesis of uniformly N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.