Toward Cleavable Metabolic/pH Sensing “Double Agents” Hyperpolarized by NMR Signal Amplification by Reversible Exchange

We show the simultaneous generation of hyperpolarized 13C‐labeled acetate and 15N‐labeled imidazole following spin‐relay of hyperpolarization and hydrolysis of the acetyl moiety on 1–13C‐15N2‐acetylimidazole. Using SABRE‐SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), transfer of spin order occurs from parahydrogen to acetylimidazole 15N atoms and the acetyl 13C site (≈263‐fold enhancement), giving rise to relatively long hyperpolarization lifetimes at 0.3 T (T1≈52 s and ≈149 s for 13C and 15N, respectively). Immediately following polarization transfer, the 13C‐labeled acetyl group is hydrolytically cleaved to produce hyperpolarized 13C‐acetate/acetic acid (≈140‐fold enhancement) and 15N‐imidazole (≈180‐fold enhancement), the former with a 13C T1 of ≈14 s at 0.3 T. Straightforward synthetic routes, efficient spin‐relay of SABRE hyperpolarization, and facile bond cleavage open a door to the cheap and rapid generation of long‐lived hyperpolarized states within a wide range of molecular targets, including biologically relevant carboxylic acid derivatives, for metabolic and pH imaging. A “spin‐spy” with two masters: While bound to a catalyst, a molecular “double agent” borrows nuclear spin order from parahydrogen. The molecule's more‐distant 13C spin is polarized via “spin relay” from a 15N spin closer to the catalyst, exploiting scalar coupling. Hydrolytic cleavage yields two separate hyperpolarized agents—13C‐acetate/acetic acid and 15N2‐imidazole—the enhanced NMR signals of which can report on metabolism and local pH, respectively.