Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods

Abstract

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of (13)C, (13)C{(1)H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1H NMR spectroscopy

“…Hence, selective excitation of the overlapping signals at δ 8.70 for the H-5 ring protons of the pyridyl unit of 4f in conjunction with 1D COSY or NOE methods enabled the observation of a resolved connection to the distinguished benzylic protons. It is worth noting that similar 1D COSY methods have been used by Tessari et al to establish the magnitude of hydride substrate couplings in the catalyst, 52 whilst use of the NOE approach has been described by some of us 5 . The ratio of these peaks is proportional to the amount of material in solution.…”

“…Magnetic resonance imaging (MRI) is a widely used clinical imaging technique that shares the same principles of NMR, and presents the same inherent problem of low sensitivity, which limits its application in many fields 3 . Recently, several hyperpolarization techniques have been developed to overcome the sensitivity issue of NMR and MRI, allowing detection of trace amounts of a certain compound in a complex mixture,4, 5 detection of a metabolite in cells 6 or real-time imaging in small rodents 7 . The most used hyperpolarisation techniques are dynamic nuclear polarization (DNP),8, 9 spin-exchange optical pumping (SEOP), metastability exchange optical pumping (MEOP), 10 parahydrogen induced polarization (PHIP) 11 and spontaneous amplification by reversible exchange (SABRE),11, 12, 13 which recently emerged as a promising modality for in vivo pre-clinical and clinical MRI 14, 15…”

Quantitative In Situ Monitoring of Parahydrogen Fraction Using Raman Spectroscopy

“…Between intervals, the PB held the gas pressure constant at 5 bar in the FT. The polariser box has previously been used to automate SABRE NMR experiments, 19,20,28,29 but in this case it was simply used to control the flow of gas out of the pH 2 generator.…”

Multidimensional NMR approaches towards highly resolved, sensitive and high-throughput quantitative metabolomics

“…It should be noted that the short lifetime of the enhanced signals resulting from SABRE makes the use of multidimensional NMR difficult. Nevertheless, this drawback can be efficiently circumvented by combining UF 2D NMR with SABRE [34]. This was nicely illustrated by Daniele et al, who recorded singlescan COSY spectra of complex mixtures in the submillimolar range (Figure 4a) [35 ].…”