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Abstract Metronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of15N nuclei in these compounds using SABRE‐SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol‐d4is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE‐SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average15N polarization of up to 7.2–7.4 % for both substrates. The highest15N polarizations were observed in methanol‐d4for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors.
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Terminal Diazirines Enable Reverse Polarization Transfer from 15 N 2 Singlets
Abstract Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The15N2labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (‐CH15N2) moiety to1H, thus combining the advantages of long lifetimes of15N polarization with superior sensitivity of1H detection. Despite the proximity of1H to15N nuclei in the diazirine moiety,15NT1times of up to (4.6±0.4) min and singlet lifetimesTsof up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized1H2singlet states in CH2groups of chiral molecules. The singlet lifetime of1H singlets is up to (9.2±1.8) min, thus exceeding1HT1relaxation time (at 8.45 T) by a factor of ≈100.
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- Award ID(s):
- 1665090
- PAR ID:
- 10117078
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 58
- Issue:
- 32
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 11118-11124
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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