In Situ Hyperpolarization Enables ¹⁵N and ¹³C Benchtop NMR at Natural Isotopic Abundance

Without employing isotopic labeling, we demonstrate the generation of ¹⁵N and ¹³C NMR signals for molecules containing -NH₂ motifs using benchtop NMR spectrometers (1-1.4 T). Specifically, high-SNR (>50) detection of ammonia, 4-aminopyridine, benzylamine, and phenethylamine dissolved in methanol or dichloromethane is demonstrated after only 10 s of parahydrogen bubbling using signal amplification by reversible exchange and applying a pulse sequence based on spin-lock-induced crossing. Optimization of the sequence parameters allows us to achieve up to 12% ¹⁵N and 0.4% ¹³C polarization in situ without the need for the sample transfer typically employed in other hyperpolarization methods. Moreover, hyperpolarization is generated continuously without having to stop the parahydrogen bubbling to reset magnetization, paving the way toward fast 2D spectroscopic methods and relaxometry. The provided methodology may find application for the identification of diluted chemicals relevant to industry and research with the aid of affordable benchtop NMR spectrometers.