Quantitative Analysis in Continuous-Flow \(^1\)H Benchtop NMR Spectroscopy by Paramagnetic Relaxation Enhancement

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is an excellent tool for reaction and process monitoring. Process monitoring is often carried out online, where the analytic device is operated in flow mode. Benchtop NMR spectrometers are especially well-suited for these applications because they can be installed close to the studied process. However, quantitative analysis of a fast-flowing liquid with NMR spectroscopy is challenging because short residence times in the magnetic field of the spectrometer result in inefficient polarization buildup and thus poor signal intensity. This is particularly problematic for benchtop NMR spectrometers, where it severely limits the flow velocity in quantitative measurements. One method for increasing polarization in continuous-flow NMR spectroscopy is paramagnetic relaxation enhancement (PRE). Here, the interaction of the studied liquid with a PRE agent significantly accelerates the buildup of nuclear polarization prior to NMR detection, which enables quantitative measurements at high flow velocities. For process monitoring applications, the synthesis of robust and chemically inert immobilized PRE agents is mandatory. This was accomplished in the present work, where a new PRE agent is tested on 12 common solvents including water, acetonitrile, 1,4-dioxane, and binary mixtures with quantitative benchtop \(^1\)H NMR spectroscopy at 1 Tesla. The results show that the flow regime for quantitative measurements can be greatly extended by the use of the synthesized PRE agent.