Hyperpolarization of "Neat" Liquids by NMR Signal Amplification by Reversible Exchange

We report NMR Signal Amplification by Reversible Exchange (SABRE) hyperpolarization of the rare isotopes in "neat" liquids, each composed only of an otherwise pure target compound with isotopic natural abundance (n.a.) and millimolar concentrations of dissolved catalyst. Pyridine (Py) or Py derivatives are studied at 0.4% isotopic natural abundance ¹⁵N, deuterated, ¹⁵N enriched, and in various combinations using the SABRE-SHEATH variant (microTesla magnetic fields to permit direct ¹⁵N polarization from parahydrogen via reversible binding and exchange with an Ir catalyst). We find that the dilute n.a. ¹⁵N spin bath in Py still channels spin order from parahydrogen to dilute ¹⁵N spins, without polarization losses due to the presence of ¹⁴N or ²H. We demonstrate P(15N) ≈ 1% (a gain of 2900 fold relative to thermal polarization at 9.4 T) at high substrate concentrations. This fundamental finding has a significant practical benefit for screening potentially hyperpolarizable contrast agents without labeling. The capability of screening at n.a. level of ¹⁵N is demonstrated on examples of mono- and dimethyl-substituted Py (picolines and lutidines previously identified as promising pH sensors), showing that the presence of a methyl group in the ortho position significantly decreases SABRE hyperpolarization.