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

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 mins)-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 "re-hyperpolarize" 15N spins in subsequent attempts, as well as by 1H NMR and ICP-MS. Record-high 15N nuclear polarization of up to ~34% was achieved, corresponding to >100,000-fold enhancement at 9.4 T, and approximately 5/6th of the 15N hyperpolarization is retained after ~20-second-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.