Over20 15N Hyperpolarization in UnderOne Minute for Metronidazole an Antibiotic and Hypoxia Probe

摘要

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.