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

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 N-15 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 (T-1 > 3 min) and enabling transfer to 9.4 T for detection of enhanced N-15 signals in the absence of catalyst within the NMR detection region. Successful catalyst removal from solution is supported by the inability to rehyperpolarize N-15 spins in subsequent attempts, as well as by( 1)H NMR and inductively coupled plasma mass spectrometry. Record-high N-15 nuclear polarization of up to similar 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 N-15 hyperpolarization is retained after similar to 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.