Single-Scan Multidimensional NMR Analysis of Mixtures at Sub-Millimolar Concentrations by using SABRE Hyperpolarization

Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE‐enhanced 1H NMR signals are short lived, and SABRE is often used to record 1D NMR spectra only. When the sample of interest is a complex mixture, this results in severe overlaps for 1H spectra. In addition, the use of a co‐substrate, whose signals may obscure the 1H spectra, is currently the most efficient way to lower the detection limit of SABRE experiments. Here, we describe an approach to obtain clean, SABRE‐hyperpolarized 2D 1H NMR spectra of mixtures of small molecules at sub‐millimolar concentrations in a single scan. The method relies on the use of para‐hydrogen together with a deuterated co‐substrate for hyperpolarization and ultrafast 2D NMR for acquisition. It is applicable to all substrates that can be polarized with SABRE. Amplified success: An approach to obtain clean, SABRE‐hyperpolarized, 1D and 2D NMR spectra of mixtures of small molecules in a single scan is described. By relying on a deuterated co‐substrate, together with ultrafast 2D NMR sequences, the discrimination of molecules at sub‐millimolar concentrations can be achieved.