Hyperpolarised 1H–13C Benchtop NMR Spectroscopy

Abstract

Benchtop NMR spectrometers with sub-ppm spectral resolution have opened up new opportunities for performing NMR outside of the standard laboratory environment. However, the relatively weak magnetic fields of these devices (1–2 T) results in low sensitivity and significant peak overlap in 1H NMR spectra. Here, we use hyperpolarised 13C{1H} NMR to overcome these challenges. Specifically, we demonstrate the use of the signal amplification by reversible exchange (SABRE) parahydrogen-based hyperpolarisation technique to enhance the sensitivity of natural abundance 1D and 2D 13C{1H} benchtop NMR spectra. We compare two detection methods for SABRE-enhanced 13C NMR and observe an optimal 13C{1H} signal-to-noise ratio (SNR) for a refocused INEPT approach, where hyperpolarisation is transferred from 1H to 13C. In addition, we exemplify SABRE-enhanced 2D 13C benchtop NMR through the acquisition of a 2D HETCOR spectrum of 260 mM of 4-methylpyridine at natural isotopic abundance in a total experiment time of 69 min. In theory, signal averaging for over 300 days would be required to achieve a comparable SNR for a thermally polarised benchtop NMR spectrum acquired of a sample of the same concentration at natural abundance.

Low‐field benchtop NMR spectroscopy: status and prospects in natural product analysis†

“…Research is on‐going to increase the sensitivity 10000‐fold or more through hyperpolarisation. This would accomplish a 13 C spectrum in one scan, 70–74 or enable metabolite analysis in sec 75 . SABRE (signal amplification by reversible exchange) is such a promising technique but it is not universal for all analytes, requires additional chemicals and logistically it is rather complicated 70–72 .…”

Recent Applications of Benchtop Nuclear Magnetic Resonance Spectroscopy

“…Solvent suppression based on gradient pulse sequence [97,107] Homo-decoupling method using different pure-shift methods [108] Addition of salts as chemical shift agents to peptide sample [109] Hyperpolarization methods (SABRE) [110][111][112][113][114] Figure 11 shows that spectral resolution can be increased using various pulse sequences and the homo-decoupling method, which is another technique commonly used in high-field NMR spectroscopy. Moreover, benchtop NMR spectrometers with gradient coils can be used to increase signal sensitivity through the programming of various pulse sequences [108].…”

“…In this study, improved resolution resulted in more accurate quantitative analysis, which allowed the researchers to better understand peptide reaction kinetics. Although they are not universally applicable to all samples, hyperpolarization methods can be used for the enhancement of low-field NMR signals [110][111][112][113][114]. Hyperpolarization generates a population distribution that is significantly larger than that dictated by the Boltzmann distribution at thermal equilibrium.…”

“…Among the hyperpolarization methods such as dynamic nuclear polarization, spin-exchange optical pumping, and parahydrogen-induced polarization (PHIP), PHIP is the one most commonly used to enhance the sensitivity of benchtop NMR spectroscopy. In particular, the reversible exchange (SABRE) method, a non-hydrogenation PHIP technique, has been exclusively used, as it does not Although they are not universally applicable to all samples, hyperpolarization methods can be used for the enhancement of low-field NMR signals [110][111][112][113][114]. Hyperpolarization generates a population distribution that is significantly larger than that dictated by the Boltzmann distribution at thermal equilibrium.…”

Rapid13C NMR hyperpolarization delivered frompara-hydrogen enables the low concentration detection and quantification of sugars

“…41,48 Since the polarization is produced ex situ it is also independent of detection eld, which means detection can occur on signicantly cheaper benchtop devices. [49][50][51] The applicability of SABRE is not limited to 1 H NMR and can be applied to many different nuclei such as 13 C, 52-54 19 F, 55,56 and 15 N, [57][58][59] among others. 60,61 In the case of 13 C and 15 N, the resonance condition for SABRE occurs at much lower magnetic elds, so PTFs of around 5 mG are required for the direct transfer of polarization from the catalysts hydride ligands.…”