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

Abstract

Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE-enhanced (1)H 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 (1)H spectra. In addition, the use of a co-substrate, whose signals may obscure the (1) H 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 (1)H 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.

Iridium α‐Carboxyimine Complexes Hyperpolarized with para‐Hydrogen Exist in Nuclear Singlet States before Conversion into Iridium Carbonates

“…Furthermore, while the required polarization transfer conditions are readily met at low field, high‐field transfer through radio frequency excitation is also feasible . Hence, p ‐H 2 now reflects a truly versatile hyperpolarization platform and it is not surprising that high sensitivity analytical approaches have been demonstrated ,. The necessary progress into aqueous media has also been significant and is expected to lead to successful in vivo study in the future ,…”

SABRE Hyperpolarization of Bipyridine Stabilized Ir-Complex at High, Low and Ultralow Magnetic Fields

“…Traditionally SABRE was a low-field method that was used to hyperpolarize various Ir-complexes and substrates [8,9,11,[28][29][30][31]. For this reason, first of all we would like to see whether the stabilized complex can be used for generating hyperpolarization in conventional low-field SABRE experiments (LF-SABRE).…”

2D NMR Trace Analysis by Continuous Hyperpolarization at High Magnetic Field

“…[2e,3a, 14,16] Thep reviously demonstrated linearity of SABRE signals with concentration [3c] applies also to the present 2D approach, and provides an accurate concentration determination in the nanomolar regime.…”

“…[13] Here,the spin-order of the hydrides is used to enhance the NMR signals of substrate protons in the metal complex by long-range scalar couplings.Being performed at high field, no sample transfer is required, which allows for rapid acquisition of multiple scans of continuously hyperpolarized spectra. This is illustrated by the 2D NMR spectrum in Figure [2e, 14] Theconventional 1 Hspectrum in Figure 2B illustrates the sensitivity gain offered by our high field hyperpolarization approach. This spectrum was acquired on the same substrate mixture employed for the 2D experiment.…”