Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange.

The present work investigates the potential for enhancing the NMR signals of DNA nucleobases by parahydrogen-based hyperpolarization. Signal amplification by reversible exchange (SABRE) and SABRE in Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) of selected DNA nucleobases is demonstrated with the enhancement (ε) of 1H, 15N, and/or 13C spins in 3-methyladenine, cytosine, and 6-O-guanine. Solutions of the standard SABRE homogenous catalyst Ir(1,5-cyclooctadeine)(1,3-bis(2,4,6-trimethylphenyl)imidazolium)Cl ("IrIMes") and a given nucleobase in deuterated ethanol/water solutions yielded low 1H ε values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of 15N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. 1H and 15N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements (ε~240) of both 15N atoms for doubly labelled cytosine reveal the preferential binding of specific tautomer(s), thus giving insight into the matching of polarization-transfer and tautomerization time scales. 13C enhancements of up to nearly 50-fold were also obtained for this cytosine isotopomer. These efforts may enable the future investigation of processes underlying cellular function and/or dysfunction, including how DNA nucleobase tautomerization influences mismatching in base-pairing.

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

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.