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

J Am Chem Soc. 2016 Jul 6;138(26):8080-3. doi: 10.1021/jacs.6b04784. Epub 2016 Jun 23.

Abstract

Direct NMR hyperpolarization of naturally abundant (15)N 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 P(15)N of up to ∼24% is achieved using parahydrogen with 80% para fraction corresponding to P(15)N ≈ 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 (15)N site (using J(2)H-(15)N), we also hyperpolarized more distant (15)N sites in metronidazole using longer-range spin-spin couplings (J(4)H-(15)N and J(5)H-(15)N). 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Metronidazole / chemistry*
  • Metronidazole / metabolism
  • Molecular Probes / chemistry*
  • Molecular Probes / metabolism
  • Tumor Hypoxia*

Substances

  • Anti-Bacterial Agents
  • Molecular Probes
  • Metronidazole