Over 20% (15)N Hyperpolarization in Under One Minute for Metronidazole, an Antibiotic and Hypoxia Probe.

Abstract

Direct NMR hyperpolarization of naturally abundant 15N sites in metronidazole is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In only a few tens of seconds, nuclear spin polarization P15N of up to ∼24% is achieved using parahydrogen with 80% para fraction corresponding to P15N ≈ 32% if ∼100% parahydrogen were employed (which would translate to a signal enhancement of ∼0.1-million-fold at 9.4 T). In addition to this demonstration on the directly binding 15N site (using J2H-15N), we also hyperpolarized more distant 15N sites in metronidazole using longer-range spin–spin couplings (J4H-15N and J5H-15N). Taken together, these results significantly expand the range of molecular structures and sites amenable to hyperpolarization via low-cost parahydrogen-based methods. In particular, hyperpolarized nitroimidazole and its derivatives have powerful potential applications such as direct in vivo imaging of mechanisms of action or hypoxia sensing.