Quantitative Nuclear Magnetic Resonance Spectroscopy with Overhauser Dynamic Nuclear Polarization

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for process monitoring. However, the quantitative analysis of highly diluted components or of components in small sample volumes is difficult with this analytical method due to its inherent lack of sensitivity. The hyperpolarization technique Overhauser dynamic nuclear polarization (ODNP) holds promise to solve this problem because it can provide strong signal enhancements. Furthermore, ODNP operates on short time scales and can therefore be used on flowing samples. Despite these advantages, to our knowledge, ODNP has never been applied for quantitative analysis of mixtures-probably because NMR signal enhancements by ODNP can vary greatly for different molecules, making quantitative analysis of mixtures difficult. We demonstrated that this problem can be solved by a robust calibration: three binary mixtures were studied as test cases in a wide range of concentrations by ODNP-enhanced ${}^1$ H and ${}^{13}$ C NMR spectroscopy in continuous-flow experiments with a benchtop NMR spectrometer using a new tailored calibration procedure. We show that quantitative analysis with ODNP-enhanced NMR spectroscopy is possible even under these challenging conditions.