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 times of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as H-1 and F-19, it significantly reduces the signal-to-noise ratio in P-31 and C-13 spectra, making FlowNMR impractical for low sensititvity nuclei at low 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. Herein, [Co(acac)(3)], [Mn(acac)(3)], [Fe(acac)(3)](,) [Cr(acac)(3)](,) [Ni(acac)(2)](3,) [Gd(tmhd)(3)] and [Cr(tmhd)(3)] are investigated 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 P-31 T-1 values four- to five-fold at PRA 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 degrees C, the bulkier [Cr(tmhd)(3)] was stable and equally effective as a PRA under these conditions. Compatibility with a range of representative transition metal complexes often used in homogeneous catalysis has been investigated, and application of [Cr(tmhd)(3)] in significantly improving H-1 and P-31{H-1} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, C-13 relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by C-13{H-1} FlowNMR spectroscopy at natural abundance.

Automated summary

Sensitivity in FlowNMR spectroscopy can be limited by low levels of pre-magnetisation, especially for low sensitivity nuclei at low concentrations. The use of paramagnetic relaxation agents (PRAs) can enhance polarisation and spin-lattice relaxation, mitigating the in-flow effect and improving the signal-to-noise ratio.