Over 20% (15)N Hyperpolarization in Under One Minute for Metronidazole, an Antibiotic and Hypoxia Probe.
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.
Department of Radiology, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Danila A
DA
Barskiy
Department of Radiology, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Roman V
RV
Shchepin
Department of Radiology, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Aaron M
AM
Coffey
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Thomas
T
Theis
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Warren S
WS
Warren
Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University , Carbondale, Illinois 62901, United States.
Boyd M
BM
Goodson
Department of Radiology, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.|Department of Biomedical Engineering, Vanderbilt-Ingram Cancer Center, Vanderbilt University , Nashville, Tennessee 37232, United States.|Russian Academy of Sciences , Leninskiy Prospekt 14, Moscow 119991, Russia.
Eduard Y
EY
Chekmenev
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008795:Metronidazole / Q000737:chemistry* / Q000378:metabolism; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D000072258:Tumor Hypoxia
D000900:Anti-Bacterial Agents; D015335:Molecular Probes; D008795:Metronidazole