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

Area of Science:

• Nuclear Magnetic Resonance Spectroscopy
• Chemical Kinetics
• Catalysis

Background:

• FlowNMR spectroscopy is limited for low-sensitivity nuclei (e.g., 31P, 13C) due to low pre-magnetisation from short sample residence times.
• Paramagnetic relaxation agents (PRAs) can enhance polarization and spin-lattice relaxation, potentially overcoming these limitations.

Purpose of the Study:

• To investigate the effectiveness of various transition metal complexes as PRAs in FlowNMR.
• To assess the chemical inertness of PRAs with catalytically active transition metal complexes.
• To demonstrate improved FlowNMR performance for reaction monitoring.

Main Methods:

• Screening of PRAs including [Co(acac)3], [Mn(acac)3], [Fe(acac)3], [Cr(acac)3], [Ni(acac)2]3, [Gd(tmhd)3], and [Cr(tmhd)3].
• Evaluation of PRA effectiveness in reducing 31P spin-lattice relaxation times (T1).
• Assessment of chemical stability and compatibility with transition metal catalysts.
• Application in Rh-catalysed hydroformylation for 1H and 31P{1H} FlowNMR improvement.

Main Results:

• High-spin Cr(III) acetylacetonates ([Cr(acac)3] and [Cr(tmhd)3]) were most effective, reducing 31P T1 values 4-5 fold at 10 mM.
• [Cr(acac)3] showed reactivity, while the bulkier [Cr(tmhd)3] remained stable and effective.
• Addition of [Cr(tmhd)3] significantly improved 1H and 31P{1H} FlowNMR data quality in hydroformylation.
• 13C relaxation times were reduced over six-fold, enabling quantitative 13C{1H} FlowNMR at natural abundance.

Conclusions:

• [Cr(tmhd)3] is a highly effective and chemically inert PRA for enhancing FlowNMR sensitivity.
• This approach enables quantitative reaction monitoring using 13C{1H} FlowNMR, even at natural abundance.
• PRAs offer a viable solution to overcome sensitivity limitations in FlowNMR for various nuclei.