Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy

Sensitivity in FlowNMR spectroscopy for reaction monitoring often suffers from low levels of pre-magnetisation due to limited residence time of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as 1H and 19F, it significantly reduces the signal-to-noise ratio in 31P and 13C spectra, making FlowNMR impractical especially at low analyte concentrations. Paramagnetic relaxation agents (PRAs), which enhance polarisation and spin-lattice relaxation, could eliminate the adverse in-flow effect and improve the signal-to-noise ratio. Here, we investigate [Co(acac)3], [Mn(acac)3], [Fe(acac)3], [Cr(acac)3], [Ni(acac)2]3, [Gd(tmhd)3] and [Cr(tmhd)3] for their effectiveness in improving signal intensity per unit time in FlowNMR applications under the additional constraint of chemical inertness towards catalytically active transition metal complexes. High-spin Cr(III)acetylacetonates emerged as the most effective compounds successfully reducing 31P T1 values four- to five-fold at concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac)3] showed signs of chemical reactivity with a mixture of triphenylphosphine, triphenylphosphine oxide and triphenylphosphate over the course of several hours at 80° C, the bulkier [Cr(tmhd)3] was stable and equally effective as a PRA under these conditions.