Hyperpolarizing Concentrated Metronidazole ¹⁵ NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime.

The NMR hyperpolarization of uniformly ¹⁵ N-labeled [¹⁵ N₃ ]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the ¹⁵ NO₂ group is hyperpolarized through spin relays created by ¹⁵ N spins in [¹⁵ N₃ ]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_15N ) of around 16 % is achieved on all three ¹⁵ N sites. This product of ¹⁵ N polarization and concentration of ¹⁵ N spins is around six-fold better than any previous value determined for ¹⁵ N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T₁ ≈10 min). A novel synthesis of uniformly ¹⁵ 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.

Duke Scholars

Author Warren S. Warren Chemistry