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

Abstract

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 1 H and 19 F, it significantly reduces the signal-tonoise ratio in 31 P and 13 C 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 31 P 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°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 1 H and 31 P{ 1 H} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, 13 C relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by 13 C{ 1 H} FlowNMR spectroscopy at natural abundance.

Improved Detection and Quantification of Cyclopropane Fatty Acids via Homonuclear Decoupling Double Irradiation NMR Methods

“…Thus, the need for additional specialized and expensive equipment may restrict the widespread application or adoption of these techniques, particularly in the field of food analysis. Other strategies to increase SNR, which include the use of paramagnetic agents to shorten the spin–lattice ( T 1 ) relaxation time of the nucleus of interest, have been described. , …”

“…Other strategies to increase SNR, which include the use of paramagnetic agents to shorten the spin−lattice (T 1 ) relaxation time of the nucleus of interest, have been described. 16,17 Here, we explore one of the most important (but surprisingly understudied) aspects of decoupling in NMR spectroscopy. Although signal decoupling can improve the resolution of overcrowded spectra due to the collapse of multiplet into singlet, the former has the important benefit of increasing SNR.…”

“…Other strategies to increase SNR, which include the use of paramagnetic agents to shorten the spin–lattice ( T 1 ) relaxation time of the nucleus of interest, have been described. 16 , 17 …”