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

• Published in: Chemistry : a European journal 2018-06, Vol.24 (42), p.10641-10645
• Main Authors: Kidd, Bryce E., Mashni, Jamil A., Limbach, Miranda N., Shi, Fan, Chekmenev, Eduard Y., Hou, Yuqing, Goodson, Boyd M.
• Format: Article
• Language: English
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201802622

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 N 2 -acetylimidazole. Through 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 ( T 1 ~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 T 1 of ~14 s at 0.3 T. Straight-forward 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 13 C spin is polarized via “spin relay” from a 15 N spin closer to the catalyst, exploiting scalar coupling. Hydrolytic cleavage yields two separate hyperpolarized agents-— 13 C-acetate/acetic acid and 15 N 2 -imidazole-—whose enhanced NMR signals can report on metabolism and local pH, respectively.