15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH

N-15 nuclear spins of imidazole-N-15(2) were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A N-15 NMR signal enhancement of similar to 2000-fold at 9.4 T is reported using parahydrogen gas (similar to 50% para-) and similar to 0.1 M imidazole-N-15(2) in methanol:aqueous buffer (similar to 1:1). Proton binding to a N-15 site of imidazole occurs at physiological pH (pK(a) similar to 7.0), and the binding event changes the N-15 isotropic chemical shift by similar to 30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. N-15-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.