Recent advances in nuclear magnetic resonance spectroscopy detection compatible with on-flow operational regimes: New uses of NMR detectors hyphenated to LCs and other separation techniques and in reaction monitoring

Flow NMR, where samples are continuously loaded (on-flow) into the probe, provides rich structural information of purified fractions when the NMR spectrometer is coupled (hyphenated) to liquid chromatography (LC) or another separation technique, or in reaction monitoring, where no previous separation takes place. The main features of NMR spectrometers as detectors in separation instruments working in continuous, on-flow mode are briefed. Emphasis is made on alternative modes of operation of these so-constituted LC-NMR platforms, and on newer, improved instrumental designs, all of them aiming to overcome, or at least ameliorate, those weaknesses intrinsic of on-flow LC-NMR setups when conventional NMR experiments are used. These shortcomings are the limited time for detection (NMR acquisition) in continuous flow regimes and the comparatively small amount of sample entering the NMR detection probe (low sensitivity). This work is structured in three parts. First, some modes of operation, alternative to on-flow regimes, are revised. In the second part, some improvements in hardware design that boost the sensitivity of the detector, notably miniaturized NMR probes amenable to be coupled to separation techniques, are presented. In the third part, novel NMR methodologies aimed at reducing experiment time and suitable for on-flow work are considered. Representative examples are given for each scenario. Finally, future prospects of flow NMR protocols, either hyphenated to a separation technique or not, are discussed.