Toward Cleavable Metabolic/pH Sensing "Double Agents" Hyperpolarized by NMR Signal Amplification by Reversible...

We show the simultaneous generation of hyperpolarized ¹³ C-labeled acetate and ¹⁵ N-labeled imidazole following spin-relay of hyperpolarization and hydrolysis of the acetyl moiety on 1-¹³ C-¹⁵ N₂ -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 ¹⁵ N atoms and the acetyl ¹³ C site (≈263-fold enhancement), giving rise to relatively long hyperpolarization lifetimes at 0.3 T (T₁ ≈52 s and ≈149 s for ¹³ C and ¹⁵ N, respectively). Immediately following polarization transfer, the ¹³ C-labeled acetyl group is hydrolytically cleaved to produce hyperpolarized ¹³ C-acetate/acetic acid (≈140-fold enhancement) and ¹⁵ N-imidazole (≈180-fold enhancement), the former with a ¹³ C 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.