TY - JOUR

T1 - Facile Removal of Homogeneous SABRE Catalysts for Purifying Hyperpolarized Metronidazole, a Potential Hypoxia Sensor

AU - Kidd, Bryce E.

AU - Gesiorski, Jonathan L.

AU - Gemeinhardt, Max E.

AU - Shchepin, Roman V.

AU - Kovtunov, Kirill V.

AU - Koptyug, Igor V.

AU - Chekmenev, Eduard Y.

AU - Goodson, Boyd M.

N1 - Publisher Copyright: Copyright © 2018 American Chemical Society.

PY - 2018/7/26

Y1 - 2018/7/26

N2 - Here, we report a simple and effective method to remove IrIMes homogeneous polarization transfer catalysts from solutions where NMR signal amplification by reversible exchange (SABRE) has been performed, while leaving intact the substrate's hyperpolarized state. Following microtesla SABRE hyperpolarization of 15N spins in metronidazole, addition of SiO2 microparticles functionalized with 3-mercaptopropyl or 2-mercaptoethyl ethyl sulfide moieties provides removal of the catalyst from solution well within the hyperpolarization decay time at 0.3 T (T1 > 3 min) and enabling transfer to 9.4 T for detection of enhanced 15N signals in the absence of catalyst within the NMR detection region. Successful catalyst removal from solution is supported by the inability to "rehyperpolarize" 15N spins in subsequent attempts, as well as by 1H NMR and inductively coupled plasma mass spectrometry. Record-high 15N nuclear polarization of up to ∼34% was achieved, corresponding to >100 000-fold enhancement at 9.4 T (or >320,000-fold enhancement at 3.0 T), and approximately 5/6th of the 15N hyperpolarization is retained after ∼20 s long purification procedure. Taken together, these results help pave the way for future studies, involving in vivo molecular imaging using agents hyperpolarized via rapid and inexpensive parahydrogen-based methods.

AB - Here, we report a simple and effective method to remove IrIMes homogeneous polarization transfer catalysts from solutions where NMR signal amplification by reversible exchange (SABRE) has been performed, while leaving intact the substrate's hyperpolarized state. Following microtesla SABRE hyperpolarization of 15N spins in metronidazole, addition of SiO2 microparticles functionalized with 3-mercaptopropyl or 2-mercaptoethyl ethyl sulfide moieties provides removal of the catalyst from solution well within the hyperpolarization decay time at 0.3 T (T1 > 3 min) and enabling transfer to 9.4 T for detection of enhanced 15N signals in the absence of catalyst within the NMR detection region. Successful catalyst removal from solution is supported by the inability to "rehyperpolarize" 15N spins in subsequent attempts, as well as by 1H NMR and inductively coupled plasma mass spectrometry. Record-high 15N nuclear polarization of up to ∼34% was achieved, corresponding to >100 000-fold enhancement at 9.4 T (or >320,000-fold enhancement at 3.0 T), and approximately 5/6th of the 15N hyperpolarization is retained after ∼20 s long purification procedure. Taken together, these results help pave the way for future studies, involving in vivo molecular imaging using agents hyperpolarized via rapid and inexpensive parahydrogen-based methods.

KW - ENHANCEMENT

KW - MAGNETIC-RESONANCE

KW - N-15 HYPERPOLARIZATION

KW - NITROIMIDAZOLE

KW - NMR SIGNAL AMPLIFICATION

KW - PARA-HYDROGEN

KW - PARAHYDROGEN

KW - REVERSIBLE EXCHANGE

KW - SENSITIVITY

KW - SPECTROSCOPY

UR - http://www.scopus.com/inward/record.url?scp=85049154409&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcc.8b05758

DO - 10.1021/acs.jpcc.8b05758

M3 - Article

C2 - 30559921

AN - SCOPUS:85049154409

VL - 122

SP - 16848

EP - 16852

JO - Journal of Physical Chemistry C

JF - Journal of Physical Chemistry C

SN - 1932-7447

IS - 29

ER -